LIVER MEETING 2011

SAN FRANCISCO – Patients with primary sclerosing cholangitis may not benefit from cholecystectomy for small gallbladder polyps, based on a Mayo Clinic study.

Polyps smaller than 0.8 cm on ultrasound were benign in all cases studied, and surgical complications were common when 57 primary sclerosing cholangitis (PSC) patients had cholecystectomies at the Mayo Clinic in Rochester, Minn.

A baseline Child-Pugh score of 7 or greater was linked to increased risk of early postoperative complications.

"We have to be careful who we send for cholecystectomy for these very small lesions, given the morbidity associated with the procedure," said lead investigator Dr. John Eaton, chief medical resident in internal medicine at the Mayo Clinic.

"If you are looking at a [small] lesion and see something that’s concerning" – for instance, adjacent-wall thickening or arterial blood flow – "then it’s a case-by-case decision, [but it] needs to be made with this information in the background," he said at the annual meeting of the American Association for the Study of Liver Diseases.

Cholecystectomies are currently recommended to remove gallbladder lesions – whatever the size – in PSC patients because they are at greater risk for gallbladder cancer. It hasn’t been clear, though, whether the surgery is necessary for small polyps, or whether patients encounter complications after cholecystectomy, Dr. Eaton said.

Almost 70% percent (39) of the subjects were men. The PSC was histologic stage I or II in about half (54%) of the total cohort (31 of 57 patients). Gallbladder lesions on ultrasound were the most common indications for surgery. People with prior liver transplants or history of cholangiocarcinoma were excluded from the study.

For the cholecystectomies, about half of the patients had a laparoscopic procedure. Seventeen patients (30%) had additional surgeries when their gallbladders were removed.

Only seven polyps were smaller than 0.8 cm on preoperative ultrasounds; all of these proved to be benign, most often granulomas or normal tissue. The smallest polyp with low-grade dysplasia was 0.8 cm, and the smallest adenocarcinoma was 1.2 cm. As expected, larger growths were more likely to be cancerous.

The 0.8-cm cut-off was 100% sensitive and 70% specific for gallbladder neoplasia; the area under the receiver operating characteristic curve (AUC) was 0.90. "It’s pretty strong" as a predictor, Dr. Eaton said.

A 1.20-cm cut-off was 100% sensitive and 79% specific for gallbladder cancer, with an AUC of 0.93.

Twenty-three patients (40%) had a complication within 6 weeks after surgery, some with more than one. Bile leaks were most common. One patient required a liver transplant. A baseline Child-Pugh score of 7 was 41% sensitive and 88% specific for early postoperative complications.

Regarding longer-term follow-up, 53 patients were followed for a total of 259 patient-years. The only baseline characteristic associated with death or transplant was a PSC stage of IV (hazard ratio, 8.10; 95% confidence interval, 1.27-161.18; P = .02).

The researchers concluded that "gallbladder polyps less than 0.8 cm [on ultrasound] can be observed in patients with PSC given the low probability of malignancy and [the] high morbidity associated with a cholecystectomy."

However, the study "in no way comments on the natural history or progression [of gallbladder polyps]. If we detect one of these small lesions, well then what happens? We really can’t comment on what we should do after that," for example, whether it should be frequent ultrasounds and watchful waiting or some other approach, Dr. Eaton said.

Dr. Eaton said he has no disclosures.

SAN FRANCISCO – Patients with primary sclerosing cholangitis may not benefit from cholecystectomy for small gallbladder polyps, based on a Mayo Clinic study.

Polyps smaller than 0.8 cm on ultrasound were benign in all cases studied, and surgical complications were common when 57 primary sclerosing cholangitis (PSC) patients had cholecystectomies at the Mayo Clinic in Rochester, Minn.

A baseline Child-Pugh score of 7 or greater was linked to increased risk of early postoperative complications.

"We have to be careful who we send for cholecystectomy for these very small lesions, given the morbidity associated with the procedure," said lead investigator Dr. John Eaton, chief medical resident in internal medicine at the Mayo Clinic.

"If you are looking at a [small] lesion and see something that’s concerning" – for instance, adjacent-wall thickening or arterial blood flow – "then it’s a case-by-case decision, [but it] needs to be made with this information in the background," he said at the annual meeting of the American Association for the Study of Liver Diseases.

Cholecystectomies are currently recommended to remove gallbladder lesions – whatever the size – in PSC patients because they are at greater risk for gallbladder cancer. It hasn’t been clear, though, whether the surgery is necessary for small polyps, or whether patients encounter complications after cholecystectomy, Dr. Eaton said.

Almost 70% percent (39) of the subjects were men. The PSC was histologic stage I or II in about half (54%) of the total cohort (31 of 57 patients). Gallbladder lesions on ultrasound were the most common indications for surgery. People with prior liver transplants or history of cholangiocarcinoma were excluded from the study.

For the cholecystectomies, about half of the patients had a laparoscopic procedure. Seventeen patients (30%) had additional surgeries when their gallbladders were removed.

Only seven polyps were smaller than 0.8 cm on preoperative ultrasounds; all of these proved to be benign, most often granulomas or normal tissue. The smallest polyp with low-grade dysplasia was 0.8 cm, and the smallest adenocarcinoma was 1.2 cm. As expected, larger growths were more likely to be cancerous.

The 0.8-cm cut-off was 100% sensitive and 70% specific for gallbladder neoplasia; the area under the receiver operating characteristic curve (AUC) was 0.90. "It’s pretty strong" as a predictor, Dr. Eaton said.

A 1.20-cm cut-off was 100% sensitive and 79% specific for gallbladder cancer, with an AUC of 0.93.

Twenty-three patients (40%) had a complication within 6 weeks after surgery, some with more than one. Bile leaks were most common. One patient required a liver transplant. A baseline Child-Pugh score of 7 was 41% sensitive and 88% specific for early postoperative complications.

Regarding longer-term follow-up, 53 patients were followed for a total of 259 patient-years. The only baseline characteristic associated with death or transplant was a PSC stage of IV (hazard ratio, 8.10; 95% confidence interval, 1.27-161.18; P = .02).

The researchers concluded that "gallbladder polyps less than 0.8 cm [on ultrasound] can be observed in patients with PSC given the low probability of malignancy and [the] high morbidity associated with a cholecystectomy."

However, the study "in no way comments on the natural history or progression [of gallbladder polyps]. If we detect one of these small lesions, well then what happens? We really can’t comment on what we should do after that," for example, whether it should be frequent ultrasounds and watchful waiting or some other approach, Dr. Eaton said.

Dr. Eaton said he has no disclosures.

SAN FRANCISCO – Patients with primary sclerosing cholangitis may not benefit from cholecystectomy for small gallbladder polyps, based on a Mayo Clinic study.

Polyps smaller than 0.8 cm on ultrasound were benign in all cases studied, and surgical complications were common when 57 primary sclerosing cholangitis (PSC) patients had cholecystectomies at the Mayo Clinic in Rochester, Minn.

A baseline Child-Pugh score of 7 or greater was linked to increased risk of early postoperative complications.

"We have to be careful who we send for cholecystectomy for these very small lesions, given the morbidity associated with the procedure," said lead investigator Dr. John Eaton, chief medical resident in internal medicine at the Mayo Clinic.

"If you are looking at a [small] lesion and see something that’s concerning" – for instance, adjacent-wall thickening or arterial blood flow – "then it’s a case-by-case decision, [but it] needs to be made with this information in the background," he said at the annual meeting of the American Association for the Study of Liver Diseases.

Cholecystectomies are currently recommended to remove gallbladder lesions – whatever the size – in PSC patients because they are at greater risk for gallbladder cancer. It hasn’t been clear, though, whether the surgery is necessary for small polyps, or whether patients encounter complications after cholecystectomy, Dr. Eaton said.

Almost 70% percent (39) of the subjects were men. The PSC was histologic stage I or II in about half (54%) of the total cohort (31 of 57 patients). Gallbladder lesions on ultrasound were the most common indications for surgery. People with prior liver transplants or history of cholangiocarcinoma were excluded from the study.

For the cholecystectomies, about half of the patients had a laparoscopic procedure. Seventeen patients (30%) had additional surgeries when their gallbladders were removed.

Only seven polyps were smaller than 0.8 cm on preoperative ultrasounds; all of these proved to be benign, most often granulomas or normal tissue. The smallest polyp with low-grade dysplasia was 0.8 cm, and the smallest adenocarcinoma was 1.2 cm. As expected, larger growths were more likely to be cancerous.

The 0.8-cm cut-off was 100% sensitive and 70% specific for gallbladder neoplasia; the area under the receiver operating characteristic curve (AUC) was 0.90. "It’s pretty strong" as a predictor, Dr. Eaton said.

A 1.20-cm cut-off was 100% sensitive and 79% specific for gallbladder cancer, with an AUC of 0.93.

Twenty-three patients (40%) had a complication within 6 weeks after surgery, some with more than one. Bile leaks were most common. One patient required a liver transplant. A baseline Child-Pugh score of 7 was 41% sensitive and 88% specific for early postoperative complications.

Regarding longer-term follow-up, 53 patients were followed for a total of 259 patient-years. The only baseline characteristic associated with death or transplant was a PSC stage of IV (hazard ratio, 8.10; 95% confidence interval, 1.27-161.18; P = .02).

The researchers concluded that "gallbladder polyps less than 0.8 cm [on ultrasound] can be observed in patients with PSC given the low probability of malignancy and [the] high morbidity associated with a cholecystectomy."

However, the study "in no way comments on the natural history or progression [of gallbladder polyps]. If we detect one of these small lesions, well then what happens? We really can’t comment on what we should do after that," for example, whether it should be frequent ultrasounds and watchful waiting or some other approach, Dr. Eaton said.

Dr. Eaton said he has no disclosures.

SAN FRANCISCO – Outcomes after liver transplantation for acute liver failure steadily improved during a recent period spanning about 2 decades, researchers reported at the annual meeting of the American Association for the Study of Liver Diseases.

An analysis of data from nearly 5,000 European patients found that rates of both graft survival and patient survival increased over time, even as the mean age of donors and recipients was rising.

However, rates of graft loss and death remained high during the first year after surgery, driven mainly by infection, rejection, and primary delayed function or nonfunction of the graft.

"A progressive and constant improvement in the survival rate after liver transplantation for acute liver failure has been achieved in the last 20 years despite an increase in donor and recipient age," commented lead investigator Dr. Giacomo Germani. "High mortality and graft loss still persist, especially within the first year posttransplant."

Importantly, deaths and graft losses due to social causes – mainly nonadherence to therapy and suicide – were much more common among patients who underwent transplantation because of paracetamol (known as acetaminophen in the United States) toxicity than among other patients. And more than half of these events occurred in the first year, suggesting that early psychiatric and related intervention for this group of recipients could be beneficial, according to Dr. Germani.

For the study, the investigators analyzed data from the European Liver Transplant Registry, which captures data on liver transplants done in 23 countries. The authors identified 4,903 patients older than 16 years who underwent isolated liver transplantation for fulminant or subfulminant acute liver failure between 1988 and 2009.

Temporal trends showed that the annual number of transplantations for acute liver failure increased until approximately 1994 and then remained essentially stable thereafter, reported Dr. Germani, who is a research fellow with the Royal Free Hospital and University College London, and a physician with the Padova (Italy) University Hospital.

On average, recipients were 39 years old and donors were 41 years old, but the age of both groups increased during the study period.

"The most important change [over time] was the increase in the donor age," Dr. Germani maintained. For example, donors older than 60 years made up merely 2% of all donors in 1988-1993 but 21% in 2004-2009.

There was a shift in the etiology of the acute liver failure leading to transplantation during the study period that most likely reflected more effective diagnosis, he said. The proportion of cases recorded as having an unknown etiology fell from 60% in 1988-1993 to just 33% in 2004-2009. Meanwhile, there were increases in the proportions attributed to paracetamol toxicity, other drug toxicity, and other known causes (for example, traumatic or operative liver injury).

For the entire study period, the cumulative 10-year rates of graft and patient survival were 50% and 63%, respectively, "almost comparable with [those for] transplantation for other etiology," Dr. Germani observed.

Both outcomes improved significantly during the study period. For example, the cumulative 5-year rate of graft survival improved steadily from about 50% in 1988-1993 to about 70% in 2004-2009 (P less than .001).

Social causes accounted for just 1% of all deaths and graft losses for the entire cohort. But they accounted for nearly 8% of those among patients who underwent transplantation because of paracetamol toxicity.

Temporal trends in the causes of death or graft loss showed increases in the proportions that were due to cardiovascular causes (likely related to increasing recipient age) and to primary delayed function or nonfunction of the graft (likely related to increasing use of livers from donors having less favorable characteristics), according to Dr. Germani.

After determining that mortality and graft loss were most common in the first year after transplantation and particularly in the first 3 months, the investigators identified independent risk factors for these outcomes and incorporated them into predictive models.

There was generally good correspondence between observed and model-predicted mortality and graft loss, according to Dr. Germani.

When applied to older adults, the models identified those at especially high risk for poor outcome. For example, among the cohort of patients older than 50 years of age, the risk of graft loss or death in the first year after transplantation was 44% to 61% if the patient was older than 60 years, was male, or had an incompatible ABO match with the donor, depending on the factor. With all three factors combined, the risk jumped to 80%.

"It is therefore important to reevaluate the selection of older patients with acute liver failure as potential recipients for liver transplantation in order to avoid futile transplants," Dr. Germani recommended.

Dr. Germani reported that he had no relevant conflicts of interest.

SAN FRANCISCO – Outcomes after liver transplantation for acute liver failure steadily improved during a recent period spanning about 2 decades, researchers reported at the annual meeting of the American Association for the Study of Liver Diseases.

An analysis of data from nearly 5,000 European patients found that rates of both graft survival and patient survival increased over time, even as the mean age of donors and recipients was rising.

However, rates of graft loss and death remained high during the first year after surgery, driven mainly by infection, rejection, and primary delayed function or nonfunction of the graft.

"A progressive and constant improvement in the survival rate after liver transplantation for acute liver failure has been achieved in the last 20 years despite an increase in donor and recipient age," commented lead investigator Dr. Giacomo Germani. "High mortality and graft loss still persist, especially within the first year posttransplant."

Importantly, deaths and graft losses due to social causes – mainly nonadherence to therapy and suicide – were much more common among patients who underwent transplantation because of paracetamol (known as acetaminophen in the United States) toxicity than among other patients. And more than half of these events occurred in the first year, suggesting that early psychiatric and related intervention for this group of recipients could be beneficial, according to Dr. Germani.

For the study, the investigators analyzed data from the European Liver Transplant Registry, which captures data on liver transplants done in 23 countries. The authors identified 4,903 patients older than 16 years who underwent isolated liver transplantation for fulminant or subfulminant acute liver failure between 1988 and 2009.

Temporal trends showed that the annual number of transplantations for acute liver failure increased until approximately 1994 and then remained essentially stable thereafter, reported Dr. Germani, who is a research fellow with the Royal Free Hospital and University College London, and a physician with the Padova (Italy) University Hospital.

On average, recipients were 39 years old and donors were 41 years old, but the age of both groups increased during the study period.

"The most important change [over time] was the increase in the donor age," Dr. Germani maintained. For example, donors older than 60 years made up merely 2% of all donors in 1988-1993 but 21% in 2004-2009.

There was a shift in the etiology of the acute liver failure leading to transplantation during the study period that most likely reflected more effective diagnosis, he said. The proportion of cases recorded as having an unknown etiology fell from 60% in 1988-1993 to just 33% in 2004-2009. Meanwhile, there were increases in the proportions attributed to paracetamol toxicity, other drug toxicity, and other known causes (for example, traumatic or operative liver injury).

For the entire study period, the cumulative 10-year rates of graft and patient survival were 50% and 63%, respectively, "almost comparable with [those for] transplantation for other etiology," Dr. Germani observed.

Both outcomes improved significantly during the study period. For example, the cumulative 5-year rate of graft survival improved steadily from about 50% in 1988-1993 to about 70% in 2004-2009 (P less than .001).

Social causes accounted for just 1% of all deaths and graft losses for the entire cohort. But they accounted for nearly 8% of those among patients who underwent transplantation because of paracetamol toxicity.

Temporal trends in the causes of death or graft loss showed increases in the proportions that were due to cardiovascular causes (likely related to increasing recipient age) and to primary delayed function or nonfunction of the graft (likely related to increasing use of livers from donors having less favorable characteristics), according to Dr. Germani.

After determining that mortality and graft loss were most common in the first year after transplantation and particularly in the first 3 months, the investigators identified independent risk factors for these outcomes and incorporated them into predictive models.

There was generally good correspondence between observed and model-predicted mortality and graft loss, according to Dr. Germani.

When applied to older adults, the models identified those at especially high risk for poor outcome. For example, among the cohort of patients older than 50 years of age, the risk of graft loss or death in the first year after transplantation was 44% to 61% if the patient was older than 60 years, was male, or had an incompatible ABO match with the donor, depending on the factor. With all three factors combined, the risk jumped to 80%.

"It is therefore important to reevaluate the selection of older patients with acute liver failure as potential recipients for liver transplantation in order to avoid futile transplants," Dr. Germani recommended.

Dr. Germani reported that he had no relevant conflicts of interest.

SAN FRANCISCO – Outcomes after liver transplantation for acute liver failure steadily improved during a recent period spanning about 2 decades, researchers reported at the annual meeting of the American Association for the Study of Liver Diseases.

An analysis of data from nearly 5,000 European patients found that rates of both graft survival and patient survival increased over time, even as the mean age of donors and recipients was rising.

However, rates of graft loss and death remained high during the first year after surgery, driven mainly by infection, rejection, and primary delayed function or nonfunction of the graft.

"A progressive and constant improvement in the survival rate after liver transplantation for acute liver failure has been achieved in the last 20 years despite an increase in donor and recipient age," commented lead investigator Dr. Giacomo Germani. "High mortality and graft loss still persist, especially within the first year posttransplant."

Importantly, deaths and graft losses due to social causes – mainly nonadherence to therapy and suicide – were much more common among patients who underwent transplantation because of paracetamol (known as acetaminophen in the United States) toxicity than among other patients. And more than half of these events occurred in the first year, suggesting that early psychiatric and related intervention for this group of recipients could be beneficial, according to Dr. Germani.

For the study, the investigators analyzed data from the European Liver Transplant Registry, which captures data on liver transplants done in 23 countries. The authors identified 4,903 patients older than 16 years who underwent isolated liver transplantation for fulminant or subfulminant acute liver failure between 1988 and 2009.

Temporal trends showed that the annual number of transplantations for acute liver failure increased until approximately 1994 and then remained essentially stable thereafter, reported Dr. Germani, who is a research fellow with the Royal Free Hospital and University College London, and a physician with the Padova (Italy) University Hospital.

On average, recipients were 39 years old and donors were 41 years old, but the age of both groups increased during the study period.

"The most important change [over time] was the increase in the donor age," Dr. Germani maintained. For example, donors older than 60 years made up merely 2% of all donors in 1988-1993 but 21% in 2004-2009.

There was a shift in the etiology of the acute liver failure leading to transplantation during the study period that most likely reflected more effective diagnosis, he said. The proportion of cases recorded as having an unknown etiology fell from 60% in 1988-1993 to just 33% in 2004-2009. Meanwhile, there were increases in the proportions attributed to paracetamol toxicity, other drug toxicity, and other known causes (for example, traumatic or operative liver injury).

For the entire study period, the cumulative 10-year rates of graft and patient survival were 50% and 63%, respectively, "almost comparable with [those for] transplantation for other etiology," Dr. Germani observed.

Both outcomes improved significantly during the study period. For example, the cumulative 5-year rate of graft survival improved steadily from about 50% in 1988-1993 to about 70% in 2004-2009 (P less than .001).

Social causes accounted for just 1% of all deaths and graft losses for the entire cohort. But they accounted for nearly 8% of those among patients who underwent transplantation because of paracetamol toxicity.

Temporal trends in the causes of death or graft loss showed increases in the proportions that were due to cardiovascular causes (likely related to increasing recipient age) and to primary delayed function or nonfunction of the graft (likely related to increasing use of livers from donors having less favorable characteristics), according to Dr. Germani.

After determining that mortality and graft loss were most common in the first year after transplantation and particularly in the first 3 months, the investigators identified independent risk factors for these outcomes and incorporated them into predictive models.

There was generally good correspondence between observed and model-predicted mortality and graft loss, according to Dr. Germani.

When applied to older adults, the models identified those at especially high risk for poor outcome. For example, among the cohort of patients older than 50 years of age, the risk of graft loss or death in the first year after transplantation was 44% to 61% if the patient was older than 60 years, was male, or had an incompatible ABO match with the donor, depending on the factor. With all three factors combined, the risk jumped to 80%.

"It is therefore important to reevaluate the selection of older patients with acute liver failure as potential recipients for liver transplantation in order to avoid futile transplants," Dr. Germani recommended.

Dr. Germani reported that he had no relevant conflicts of interest.

SAN FRANCISCO – Transesophageal echocardiogram does not cause bleeding in cirrhotic patients with small varices or with large varices that have been previously treated, according to Australian researchers at the annual meeting of the American Association for the Study of Liver Diseases.

In a retrospective case series, 75 patients with varices had undergone 78 transesophageal echocardiograms (TEEs), most of which were done to rule out endocarditis or to monitor hemodynamic stability during liver transplantation. A total of 62 patients (83%) had esophageal varices, and 19 (25%) had gastric varices.

About half of the esophageal varices were larger than 5 mm, sometimes with red whale marks, spurting, or other endoscopic stigmata. In a few cases, the varices filled up more than half of the esophageal lumen. Large varices were treated before TEE, usually by banding or transjugular intrahepatic portosystemic shunt.

Twenty-two percent (14) of the esophageal varices and 33% (6) of the gastric varices were treated before TEE. The rest were deemed too small to need treatment.

None of the patients bled from the TEE procedure, which was done in one case just a week after banding, but in most cases was done several months later, said investigator and gastroenterologist Lucy Lim.

It’s an important finding because the theoretical bleeding risk means that "there’s still a lot of controversy" about whether TEEs are safe in patients with varices. Cardiologists – who most often do the procedure – sometimes "outright refuse if there are even small varices. They are the ones we need to convince," said Dr. Lim of the gastroenterology and liver transplant unit at the Austin Hospital in Melbourne.

Almost 70% (52) of the patients were men (average age, 54 years). The majority had Childs-Pugh A cirrhosis; the rest had Childs-Pugh B. The cirrhosis was attributed to hepatitis C or alcohol consumption in most cases. Varices are a common complication of cirrhosis-induced portal vein hypertension.

A smaller 2009 case series also found that TEEs were safe in patients with varices (J. Am. Soc. Echocardiogr. 2009;22:396-400). A comprehensive review of the issue was published in 2010 (J. Am. Soc. Echocardiogr. 2010;23:1115-27).

Dr. Lim said she had no relevant financial disclosures.

SAN FRANCISCO – Transesophageal echocardiogram does not cause bleeding in cirrhotic patients with small varices or with large varices that have been previously treated, according to Australian researchers at the annual meeting of the American Association for the Study of Liver Diseases.

In a retrospective case series, 75 patients with varices had undergone 78 transesophageal echocardiograms (TEEs), most of which were done to rule out endocarditis or to monitor hemodynamic stability during liver transplantation. A total of 62 patients (83%) had esophageal varices, and 19 (25%) had gastric varices.

About half of the esophageal varices were larger than 5 mm, sometimes with red whale marks, spurting, or other endoscopic stigmata. In a few cases, the varices filled up more than half of the esophageal lumen. Large varices were treated before TEE, usually by banding or transjugular intrahepatic portosystemic shunt.

Twenty-two percent (14) of the esophageal varices and 33% (6) of the gastric varices were treated before TEE. The rest were deemed too small to need treatment.

None of the patients bled from the TEE procedure, which was done in one case just a week after banding, but in most cases was done several months later, said investigator and gastroenterologist Lucy Lim.

It’s an important finding because the theoretical bleeding risk means that "there’s still a lot of controversy" about whether TEEs are safe in patients with varices. Cardiologists – who most often do the procedure – sometimes "outright refuse if there are even small varices. They are the ones we need to convince," said Dr. Lim of the gastroenterology and liver transplant unit at the Austin Hospital in Melbourne.

Almost 70% (52) of the patients were men (average age, 54 years). The majority had Childs-Pugh A cirrhosis; the rest had Childs-Pugh B. The cirrhosis was attributed to hepatitis C or alcohol consumption in most cases. Varices are a common complication of cirrhosis-induced portal vein hypertension.

A smaller 2009 case series also found that TEEs were safe in patients with varices (J. Am. Soc. Echocardiogr. 2009;22:396-400). A comprehensive review of the issue was published in 2010 (J. Am. Soc. Echocardiogr. 2010;23:1115-27).

Dr. Lim said she had no relevant financial disclosures.

SAN FRANCISCO – Transesophageal echocardiogram does not cause bleeding in cirrhotic patients with small varices or with large varices that have been previously treated, according to Australian researchers at the annual meeting of the American Association for the Study of Liver Diseases.

In a retrospective case series, 75 patients with varices had undergone 78 transesophageal echocardiograms (TEEs), most of which were done to rule out endocarditis or to monitor hemodynamic stability during liver transplantation. A total of 62 patients (83%) had esophageal varices, and 19 (25%) had gastric varices.

About half of the esophageal varices were larger than 5 mm, sometimes with red whale marks, spurting, or other endoscopic stigmata. In a few cases, the varices filled up more than half of the esophageal lumen. Large varices were treated before TEE, usually by banding or transjugular intrahepatic portosystemic shunt.

Twenty-two percent (14) of the esophageal varices and 33% (6) of the gastric varices were treated before TEE. The rest were deemed too small to need treatment.

None of the patients bled from the TEE procedure, which was done in one case just a week after banding, but in most cases was done several months later, said investigator and gastroenterologist Lucy Lim.

It’s an important finding because the theoretical bleeding risk means that "there’s still a lot of controversy" about whether TEEs are safe in patients with varices. Cardiologists – who most often do the procedure – sometimes "outright refuse if there are even small varices. They are the ones we need to convince," said Dr. Lim of the gastroenterology and liver transplant unit at the Austin Hospital in Melbourne.

Almost 70% (52) of the patients were men (average age, 54 years). The majority had Childs-Pugh A cirrhosis; the rest had Childs-Pugh B. The cirrhosis was attributed to hepatitis C or alcohol consumption in most cases. Varices are a common complication of cirrhosis-induced portal vein hypertension.

A smaller 2009 case series also found that TEEs were safe in patients with varices (J. Am. Soc. Echocardiogr. 2009;22:396-400). A comprehensive review of the issue was published in 2010 (J. Am. Soc. Echocardiogr. 2010;23:1115-27).

Dr. Lim said she had no relevant financial disclosures.

SAN FRANCISCO – The Mediterranean diet is superior to the low-fat diet for decreasing hepatic fat and increasing insulin sensitivity in patients with nonalcoholic fatty liver disease, based on a randomized crossover study conducted in Australia.

After just 6 weeks on the Mediterranean diet, the 12 patients studied had significant improvements in a range of metabolic measures, such as a greater than one-third decrease in hepatic triglyceride content. In contrast, they had no such improvements after 6 weeks on the low-fat diet.

©Dušan Zidar/Fotolia.com

"The Mediterranean diet treats the underlying pathophysiology of NAFLD; this diet shows promise as a dietary recommendation for NAFLD," first author Dr. Marno C. Ryan said in her presentation of the results at the annual meeting of the American Association for the Study of Liver Diseases. "However, this is a small, highly controlled study, and larger, longer-term studies are needed to confirm these findings."

Importantly, the Mediterranean diet was also well received. "All of our patients enjoyed it, a lot more than the low-fat diet. Our dietitian actually was personally involved in preparing a lot of the meals, and she followed certain techniques that are required to do the slow cooking, etc., so the food was very tasty," she explained, noting that a larger trial would require more patient training in food preparation.

Also, cost might be a barrier for some patients in following the Mediterranean diet, acknowledged Dr. Ryan, a physician with St. Vincent’s Hospital in Melbourne. "Olive oil was a concern, and fish was as well. We did provide patients with money, approximately $80 a week, for that."

The investigators are now planning a similar but larger, less well controlled study in which patients will be followed for 2 years and will have liver biopsy at the beginning and end, she said.

Dr. T. Jake Liang, president of the AASLD and chief of the liver diseases branch at the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Md., pointed out that roughly 2%-3% of the U.S. population has NAFLD. That number is likely to increase, he said, given that two-thirds of the population is now overweight.

These new findings are "interesting; further long-term study is warranted," he said in a press conference. "Obviously, if we can prevent and treat a disease with a diet, that’s probably better than any drugs we can develop."

Insulin resistance is implicated in the pathogenesis of NAFLD as well as the other components of metabolic syndrome, such as abdominal obesity and dyslipidemia, Dr. Ryan said, giving some background for the study. "Therefore, any therapeutic strategies directed toward NAFLD should also encompass potential benefits for these associated features." To be eligible for the study, patients needed to be nondiabetic, with biopsy-proven NAFLD with fibrosis classified as less than F3 in extent, and to consume fewer than two servings of alcohol daily. The cohort had an equal sex distribution, a mean body mass index of 32 kg/m², and a mean hepatic triglyceride content of 11%.

The patients were randomized to start the study with either the Mediterranean diet or the low-fat, high-carbohydrate diet currently recommended for patients with NAFLD. They ate one diet for 6 weeks, returned to their own diet for 6 weeks as a washout, and then went on the alternate diet for 6 weeks. The aim was to change diet without inducing weight loss, since that can be a confounding factor, Dr. Ryan noted.

All patients received dietary instructions, weekly rotating menus, and approximately 70% of the meals needed for the study diets. They underwent testing – lab assays of fasting blood samples, a 3-hour euglycemic clamp study, and liver imaging and spectroscopy – before and at the end of each 6-week study period.

"This diet shows promise as a dietary recommendation for NAFLD."

Patients lost only small amounts of weight on the two diets, an average of 1 kg on the Mediterranean diet and 2.4 kg on the low-fat diet, a nonsignificant difference, Dr. Ryan reported.

The main results showed that the Mediterranean diet was associated with a 39% reduction from baseline in hepatic triglyceride content. This was determined via magnetic resonance spectroscopy after adjustment for weight loss (P = .001). There was a similar reduction in hepatic fat fraction measured by volumetric magnetic resonance imaging (P = .006).

The Mediterranean diet was also associated with improvements in insulin sensitivity as determined from reductions in homeostasis model assessment–insulin resistance, or HOMA-IR (P = .008) and fasting insulin levels (P = .003), and an increase in the glucose infusion rate on the euglycemic clamp study (P = .09).

In contrast, the low-fat diet was not associated with significant changes from baseline in any of these measures. "Interestingly, the serum insulin concentration actually increased across the 6-week period of the low-fat diet, presumably in response to the higher carbohydrate intake," she noted.

The sequence of the diets did not influence the study’s overall findings, according to Dr. Ryan. Neither diet significantly improved serum levels of liver enzymes, which were elevated at baseline.

When the two diets were directly compared with each other, the Mediterranean diet bested the low-fat diet in terms of changes in hepatic triglyceride content (P = .03), insulin levels (P = .008), and glucose infusion rate for the euglycemic clamp study (P = .03).

Dr. Ryan and Dr. Liang reported that they had no relevant conflicts of interest.

SAN FRANCISCO – The Mediterranean diet is superior to the low-fat diet for decreasing hepatic fat and increasing insulin sensitivity in patients with nonalcoholic fatty liver disease, based on a randomized crossover study conducted in Australia.

After just 6 weeks on the Mediterranean diet, the 12 patients studied had significant improvements in a range of metabolic measures, such as a greater than one-third decrease in hepatic triglyceride content. In contrast, they had no such improvements after 6 weeks on the low-fat diet.

©Dušan Zidar/Fotolia.com

"The Mediterranean diet treats the underlying pathophysiology of NAFLD; this diet shows promise as a dietary recommendation for NAFLD," first author Dr. Marno C. Ryan said in her presentation of the results at the annual meeting of the American Association for the Study of Liver Diseases. "However, this is a small, highly controlled study, and larger, longer-term studies are needed to confirm these findings."

Importantly, the Mediterranean diet was also well received. "All of our patients enjoyed it, a lot more than the low-fat diet. Our dietitian actually was personally involved in preparing a lot of the meals, and she followed certain techniques that are required to do the slow cooking, etc., so the food was very tasty," she explained, noting that a larger trial would require more patient training in food preparation.

Also, cost might be a barrier for some patients in following the Mediterranean diet, acknowledged Dr. Ryan, a physician with St. Vincent’s Hospital in Melbourne. "Olive oil was a concern, and fish was as well. We did provide patients with money, approximately $80 a week, for that."

The investigators are now planning a similar but larger, less well controlled study in which patients will be followed for 2 years and will have liver biopsy at the beginning and end, she said.

Dr. T. Jake Liang, president of the AASLD and chief of the liver diseases branch at the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Md., pointed out that roughly 2%-3% of the U.S. population has NAFLD. That number is likely to increase, he said, given that two-thirds of the population is now overweight.

These new findings are "interesting; further long-term study is warranted," he said in a press conference. "Obviously, if we can prevent and treat a disease with a diet, that’s probably better than any drugs we can develop."

Insulin resistance is implicated in the pathogenesis of NAFLD as well as the other components of metabolic syndrome, such as abdominal obesity and dyslipidemia, Dr. Ryan said, giving some background for the study. "Therefore, any therapeutic strategies directed toward NAFLD should also encompass potential benefits for these associated features." To be eligible for the study, patients needed to be nondiabetic, with biopsy-proven NAFLD with fibrosis classified as less than F3 in extent, and to consume fewer than two servings of alcohol daily. The cohort had an equal sex distribution, a mean body mass index of 32 kg/m², and a mean hepatic triglyceride content of 11%.

The patients were randomized to start the study with either the Mediterranean diet or the low-fat, high-carbohydrate diet currently recommended for patients with NAFLD. They ate one diet for 6 weeks, returned to their own diet for 6 weeks as a washout, and then went on the alternate diet for 6 weeks. The aim was to change diet without inducing weight loss, since that can be a confounding factor, Dr. Ryan noted.

All patients received dietary instructions, weekly rotating menus, and approximately 70% of the meals needed for the study diets. They underwent testing – lab assays of fasting blood samples, a 3-hour euglycemic clamp study, and liver imaging and spectroscopy – before and at the end of each 6-week study period.

"This diet shows promise as a dietary recommendation for NAFLD."

Patients lost only small amounts of weight on the two diets, an average of 1 kg on the Mediterranean diet and 2.4 kg on the low-fat diet, a nonsignificant difference, Dr. Ryan reported.

The main results showed that the Mediterranean diet was associated with a 39% reduction from baseline in hepatic triglyceride content. This was determined via magnetic resonance spectroscopy after adjustment for weight loss (P = .001). There was a similar reduction in hepatic fat fraction measured by volumetric magnetic resonance imaging (P = .006).

The Mediterranean diet was also associated with improvements in insulin sensitivity as determined from reductions in homeostasis model assessment–insulin resistance, or HOMA-IR (P = .008) and fasting insulin levels (P = .003), and an increase in the glucose infusion rate on the euglycemic clamp study (P = .09).

In contrast, the low-fat diet was not associated with significant changes from baseline in any of these measures. "Interestingly, the serum insulin concentration actually increased across the 6-week period of the low-fat diet, presumably in response to the higher carbohydrate intake," she noted.

The sequence of the diets did not influence the study’s overall findings, according to Dr. Ryan. Neither diet significantly improved serum levels of liver enzymes, which were elevated at baseline.

When the two diets were directly compared with each other, the Mediterranean diet bested the low-fat diet in terms of changes in hepatic triglyceride content (P = .03), insulin levels (P = .008), and glucose infusion rate for the euglycemic clamp study (P = .03).

Dr. Ryan and Dr. Liang reported that they had no relevant conflicts of interest.

SAN FRANCISCO – The Mediterranean diet is superior to the low-fat diet for decreasing hepatic fat and increasing insulin sensitivity in patients with nonalcoholic fatty liver disease, based on a randomized crossover study conducted in Australia.

After just 6 weeks on the Mediterranean diet, the 12 patients studied had significant improvements in a range of metabolic measures, such as a greater than one-third decrease in hepatic triglyceride content. In contrast, they had no such improvements after 6 weeks on the low-fat diet.

©Dušan Zidar/Fotolia.com

"The Mediterranean diet treats the underlying pathophysiology of NAFLD; this diet shows promise as a dietary recommendation for NAFLD," first author Dr. Marno C. Ryan said in her presentation of the results at the annual meeting of the American Association for the Study of Liver Diseases. "However, this is a small, highly controlled study, and larger, longer-term studies are needed to confirm these findings."

Importantly, the Mediterranean diet was also well received. "All of our patients enjoyed it, a lot more than the low-fat diet. Our dietitian actually was personally involved in preparing a lot of the meals, and she followed certain techniques that are required to do the slow cooking, etc., so the food was very tasty," she explained, noting that a larger trial would require more patient training in food preparation.

Also, cost might be a barrier for some patients in following the Mediterranean diet, acknowledged Dr. Ryan, a physician with St. Vincent’s Hospital in Melbourne. "Olive oil was a concern, and fish was as well. We did provide patients with money, approximately $80 a week, for that."

The investigators are now planning a similar but larger, less well controlled study in which patients will be followed for 2 years and will have liver biopsy at the beginning and end, she said.

Dr. T. Jake Liang, president of the AASLD and chief of the liver diseases branch at the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Md., pointed out that roughly 2%-3% of the U.S. population has NAFLD. That number is likely to increase, he said, given that two-thirds of the population is now overweight.

These new findings are "interesting; further long-term study is warranted," he said in a press conference. "Obviously, if we can prevent and treat a disease with a diet, that’s probably better than any drugs we can develop."

Insulin resistance is implicated in the pathogenesis of NAFLD as well as the other components of metabolic syndrome, such as abdominal obesity and dyslipidemia, Dr. Ryan said, giving some background for the study. "Therefore, any therapeutic strategies directed toward NAFLD should also encompass potential benefits for these associated features." To be eligible for the study, patients needed to be nondiabetic, with biopsy-proven NAFLD with fibrosis classified as less than F3 in extent, and to consume fewer than two servings of alcohol daily. The cohort had an equal sex distribution, a mean body mass index of 32 kg/m², and a mean hepatic triglyceride content of 11%.

The patients were randomized to start the study with either the Mediterranean diet or the low-fat, high-carbohydrate diet currently recommended for patients with NAFLD. They ate one diet for 6 weeks, returned to their own diet for 6 weeks as a washout, and then went on the alternate diet for 6 weeks. The aim was to change diet without inducing weight loss, since that can be a confounding factor, Dr. Ryan noted.

All patients received dietary instructions, weekly rotating menus, and approximately 70% of the meals needed for the study diets. They underwent testing – lab assays of fasting blood samples, a 3-hour euglycemic clamp study, and liver imaging and spectroscopy – before and at the end of each 6-week study period.

"This diet shows promise as a dietary recommendation for NAFLD."

Patients lost only small amounts of weight on the two diets, an average of 1 kg on the Mediterranean diet and 2.4 kg on the low-fat diet, a nonsignificant difference, Dr. Ryan reported.

The main results showed that the Mediterranean diet was associated with a 39% reduction from baseline in hepatic triglyceride content. This was determined via magnetic resonance spectroscopy after adjustment for weight loss (P = .001). There was a similar reduction in hepatic fat fraction measured by volumetric magnetic resonance imaging (P = .006).

The Mediterranean diet was also associated with improvements in insulin sensitivity as determined from reductions in homeostasis model assessment–insulin resistance, or HOMA-IR (P = .008) and fasting insulin levels (P = .003), and an increase in the glucose infusion rate on the euglycemic clamp study (P = .09).

In contrast, the low-fat diet was not associated with significant changes from baseline in any of these measures. "Interestingly, the serum insulin concentration actually increased across the 6-week period of the low-fat diet, presumably in response to the higher carbohydrate intake," she noted.

The sequence of the diets did not influence the study’s overall findings, according to Dr. Ryan. Neither diet significantly improved serum levels of liver enzymes, which were elevated at baseline.

When the two diets were directly compared with each other, the Mediterranean diet bested the low-fat diet in terms of changes in hepatic triglyceride content (P = .03), insulin levels (P = .008), and glucose infusion rate for the euglycemic clamp study (P = .03).

Dr. Ryan and Dr. Liang reported that they had no relevant conflicts of interest.

SAN FRANCISCO – Radiofrequency ablation appears to work as well as surgical resection for treating early-stage hepatocellular carcinomas, based on a randomized trial of 168 patients.

Researchers at Southwest Hospital in Chongqing, China, compared radiofrequency ablation (RFA) with surgical resection; there were 84 patients in each group. Each patient had either one or two tumors that were less than 4 cm in diameter.

In the surgical resection group, 81 patients (96%) were alive at 1 year, 74 (88%) at 2 years, and 63 (75%) at 3 years. In the RFA group, 78 (93%) were alive at 1 year, 70 (83%) at 2 years, and 57 (68%) at 3 years. The differences between groups were not statistically significant (P = .3).

Results for tumor recurrence were similar: 27 (32%) of the surgery patients had tumor recurrence within 3 years, compared with 35 (42%) of the RFA patients. Again, this difference was not statistically significant.

For treatment of one or two liver tumors less than 4 cm, "RFA provided the same overall and recurrence-free survival rates as surgical resection [and] has the advantages of minimal invasiveness and a low occurrence of complications," said lead investigator Dr. Ma Kuansheng of the hospital’s hepatobiliary surgery department. Also, costs are lower with RFA, he added.

The study findings could help settle the debate about which technique is better for treating early liver cancer. "There are always arguments [about whether] you should just cut it out, [or] try [RFA]. I think this study basically shows that there is no difference, so you should decide what’s the most economic way of dealing with this," said Dr. Jake Liang, president of the American Association for the Study of Liver Diseases, at the association’s annual meeting.

In the United States, both treatment approaches are available. However, surgery can be especially difficult in patients with cirrhosis. "Because their livers are all scarred, it’s very difficult to resect them," said Dr. Liang, also chief of the Liver Diseases Branch of the National Institute of Diabetes and Digestive and Kidney Diseases.

Almost 10% of the RFA patients developed complications during the procedure, including two patients with hemorrhage. In contrast, complications occurred in over 20% of surgery patients, including two with hemorrhage that required emergency laparotomy, and one with a liver abscess.

RFA took an average of 41 minutes, and had a mean blood loss of 21 mL. Surgery took 141 minutes on average, and blood loss was a mean of 375 mL; many patients needed transfusions. Length of hospital stay was about 1 week for RFA patients vs. just over 2 weeks for surgery patients.

Eight RFA patients had residual tumor that was missed during the procedure: six with tumor under the liver capsule, one with tumor next to the gallbladder, and one with tumor adjacent to the portal vein trunk. Analysis both with and without those patients did not significantly affect 3-year survival outcomes.

Most of the patients in both arms were men, with a mean age of about 50 years. A total of 85% had blood markers of hepatitis, most often hepatitis B surface antigen. There were no statistically significant baseline differences in alanine aminotransferase; alpha-fetoprotein; tumor size, number, or grade; or other characteristics.

The findings come at a time when liver cancer is on the rise, "mostly because of viral hepatitis," Dr. Liang noted. "The best treatment for liver cancer is liver transplantation. You get a very high cure rate if you transplant early enough, but, obviously, not everybody can be transplanted. There are resource issues," he said.

Dr. Kuansheng and Dr. Liang said they have no financial disclosures.

SAN FRANCISCO – Radiofrequency ablation appears to work as well as surgical resection for treating early-stage hepatocellular carcinomas, based on a randomized trial of 168 patients.

Researchers at Southwest Hospital in Chongqing, China, compared radiofrequency ablation (RFA) with surgical resection; there were 84 patients in each group. Each patient had either one or two tumors that were less than 4 cm in diameter.

In the surgical resection group, 81 patients (96%) were alive at 1 year, 74 (88%) at 2 years, and 63 (75%) at 3 years. In the RFA group, 78 (93%) were alive at 1 year, 70 (83%) at 2 years, and 57 (68%) at 3 years. The differences between groups were not statistically significant (P = .3).

Results for tumor recurrence were similar: 27 (32%) of the surgery patients had tumor recurrence within 3 years, compared with 35 (42%) of the RFA patients. Again, this difference was not statistically significant.

For treatment of one or two liver tumors less than 4 cm, "RFA provided the same overall and recurrence-free survival rates as surgical resection [and] has the advantages of minimal invasiveness and a low occurrence of complications," said lead investigator Dr. Ma Kuansheng of the hospital’s hepatobiliary surgery department. Also, costs are lower with RFA, he added.

The study findings could help settle the debate about which technique is better for treating early liver cancer. "There are always arguments [about whether] you should just cut it out, [or] try [RFA]. I think this study basically shows that there is no difference, so you should decide what’s the most economic way of dealing with this," said Dr. Jake Liang, president of the American Association for the Study of Liver Diseases, at the association’s annual meeting.

In the United States, both treatment approaches are available. However, surgery can be especially difficult in patients with cirrhosis. "Because their livers are all scarred, it’s very difficult to resect them," said Dr. Liang, also chief of the Liver Diseases Branch of the National Institute of Diabetes and Digestive and Kidney Diseases.

Almost 10% of the RFA patients developed complications during the procedure, including two patients with hemorrhage. In contrast, complications occurred in over 20% of surgery patients, including two with hemorrhage that required emergency laparotomy, and one with a liver abscess.

RFA took an average of 41 minutes, and had a mean blood loss of 21 mL. Surgery took 141 minutes on average, and blood loss was a mean of 375 mL; many patients needed transfusions. Length of hospital stay was about 1 week for RFA patients vs. just over 2 weeks for surgery patients.

Eight RFA patients had residual tumor that was missed during the procedure: six with tumor under the liver capsule, one with tumor next to the gallbladder, and one with tumor adjacent to the portal vein trunk. Analysis both with and without those patients did not significantly affect 3-year survival outcomes.

Most of the patients in both arms were men, with a mean age of about 50 years. A total of 85% had blood markers of hepatitis, most often hepatitis B surface antigen. There were no statistically significant baseline differences in alanine aminotransferase; alpha-fetoprotein; tumor size, number, or grade; or other characteristics.

The findings come at a time when liver cancer is on the rise, "mostly because of viral hepatitis," Dr. Liang noted. "The best treatment for liver cancer is liver transplantation. You get a very high cure rate if you transplant early enough, but, obviously, not everybody can be transplanted. There are resource issues," he said.

Dr. Kuansheng and Dr. Liang said they have no financial disclosures.

SAN FRANCISCO – Radiofrequency ablation appears to work as well as surgical resection for treating early-stage hepatocellular carcinomas, based on a randomized trial of 168 patients.

Researchers at Southwest Hospital in Chongqing, China, compared radiofrequency ablation (RFA) with surgical resection; there were 84 patients in each group. Each patient had either one or two tumors that were less than 4 cm in diameter.

In the surgical resection group, 81 patients (96%) were alive at 1 year, 74 (88%) at 2 years, and 63 (75%) at 3 years. In the RFA group, 78 (93%) were alive at 1 year, 70 (83%) at 2 years, and 57 (68%) at 3 years. The differences between groups were not statistically significant (P = .3).

Results for tumor recurrence were similar: 27 (32%) of the surgery patients had tumor recurrence within 3 years, compared with 35 (42%) of the RFA patients. Again, this difference was not statistically significant.

For treatment of one or two liver tumors less than 4 cm, "RFA provided the same overall and recurrence-free survival rates as surgical resection [and] has the advantages of minimal invasiveness and a low occurrence of complications," said lead investigator Dr. Ma Kuansheng of the hospital’s hepatobiliary surgery department. Also, costs are lower with RFA, he added.

The study findings could help settle the debate about which technique is better for treating early liver cancer. "There are always arguments [about whether] you should just cut it out, [or] try [RFA]. I think this study basically shows that there is no difference, so you should decide what’s the most economic way of dealing with this," said Dr. Jake Liang, president of the American Association for the Study of Liver Diseases, at the association’s annual meeting.

In the United States, both treatment approaches are available. However, surgery can be especially difficult in patients with cirrhosis. "Because their livers are all scarred, it’s very difficult to resect them," said Dr. Liang, also chief of the Liver Diseases Branch of the National Institute of Diabetes and Digestive and Kidney Diseases.

Almost 10% of the RFA patients developed complications during the procedure, including two patients with hemorrhage. In contrast, complications occurred in over 20% of surgery patients, including two with hemorrhage that required emergency laparotomy, and one with a liver abscess.

RFA took an average of 41 minutes, and had a mean blood loss of 21 mL. Surgery took 141 minutes on average, and blood loss was a mean of 375 mL; many patients needed transfusions. Length of hospital stay was about 1 week for RFA patients vs. just over 2 weeks for surgery patients.

Eight RFA patients had residual tumor that was missed during the procedure: six with tumor under the liver capsule, one with tumor next to the gallbladder, and one with tumor adjacent to the portal vein trunk. Analysis both with and without those patients did not significantly affect 3-year survival outcomes.

Most of the patients in both arms were men, with a mean age of about 50 years. A total of 85% had blood markers of hepatitis, most often hepatitis B surface antigen. There were no statistically significant baseline differences in alanine aminotransferase; alpha-fetoprotein; tumor size, number, or grade; or other characteristics.

The findings come at a time when liver cancer is on the rise, "mostly because of viral hepatitis," Dr. Liang noted. "The best treatment for liver cancer is liver transplantation. You get a very high cure rate if you transplant early enough, but, obviously, not everybody can be transplanted. There are resource issues," he said.

Dr. Kuansheng and Dr. Liang said they have no financial disclosures.

SAN FRANCISCO – The anticoagulant enoxaparin appears to prevent portal vein thrombosis in patients with advanced cirrhosis, based on a small Italian study presented at the annual meeting of the American Association for the Study of Liver Diseases.

In this trial, 6 of 36 patients (17%) randomized to placebo developed partial or complete portal vein thrombosis (PVT) within a year, whereas none of the 34 patients (0%) randomized to 4,000 IU daily of the low-molecular-weight heparin developed PVT.

The analysis indicated that enoxaparin had a significant protective effect (HR 0.218; 95% CI, 0.048-0.994, P = .049) in these patients with advanced cirrhosis.

At enrollment, none of the patients had PVT. The treatment and placebo groups had no significant differences in terms of biochemical or demographic factors at the outset of the trial, which was the first to prospectively investigate whether anticoagulation prevents PVT.

At the meeting, lead investigator Dr. Erica Villa, professor of gastroenterology at the University of Modena and Reggio Emilia in Modena, Italy, said that the results need to be confirmed in larger studies.

All of the subjects had cirrhosis classified as Child-Pugh B7 to C10. The mean age in both groups was 57 years, and the mean MELD (Model for End-Stage Liver Disease) score was approximately 14. Men made up more than 60% of both arms.

Enoxaparin appeared to provide significant protection against decompensation – defined as new-onset ascites, hepatic encephalopathy, or variceal bleeding – and death. Four enoxaparin patients (12%) decompensated during treatment, whereas 22 (61%) in the placebo arm decompensated. The difference persisted even after treatment with enoxaparin ended at 12 months.

Similarly, although 10 patients died in the enoxaparin group – 4 from sepsis, 2 from progressive liver failure, 3 from hepatocellular carcinoma, and 1 from variceal bleeding – 16 died in the placebo group. These deaths were due to sepsis in seven patients, progressive liver failure in another seven, hepatocellular carcinoma in one, and variceal bleeding in one.

There were no hemorrhagic or other treatment-related adverse events in the enoxaparin group, although asymptomatic thrombocytopenia led to the withdrawal of one patient 3 months into the trial. Three enoxaparin patients had liver transplants while on the drug, and Dr. Villa noted that they did not need extra blood transfusions.

Dr. Villa said she had no disclosures. She said the study was funded internally, and not by a company that makes enoxaparin.

SAN FRANCISCO – The anticoagulant enoxaparin appears to prevent portal vein thrombosis in patients with advanced cirrhosis, based on a small Italian study presented at the annual meeting of the American Association for the Study of Liver Diseases.

In this trial, 6 of 36 patients (17%) randomized to placebo developed partial or complete portal vein thrombosis (PVT) within a year, whereas none of the 34 patients (0%) randomized to 4,000 IU daily of the low-molecular-weight heparin developed PVT.

The analysis indicated that enoxaparin had a significant protective effect (HR 0.218; 95% CI, 0.048-0.994, P = .049) in these patients with advanced cirrhosis.

At enrollment, none of the patients had PVT. The treatment and placebo groups had no significant differences in terms of biochemical or demographic factors at the outset of the trial, which was the first to prospectively investigate whether anticoagulation prevents PVT.

At the meeting, lead investigator Dr. Erica Villa, professor of gastroenterology at the University of Modena and Reggio Emilia in Modena, Italy, said that the results need to be confirmed in larger studies.

All of the subjects had cirrhosis classified as Child-Pugh B7 to C10. The mean age in both groups was 57 years, and the mean MELD (Model for End-Stage Liver Disease) score was approximately 14. Men made up more than 60% of both arms.

Enoxaparin appeared to provide significant protection against decompensation – defined as new-onset ascites, hepatic encephalopathy, or variceal bleeding – and death. Four enoxaparin patients (12%) decompensated during treatment, whereas 22 (61%) in the placebo arm decompensated. The difference persisted even after treatment with enoxaparin ended at 12 months.

Similarly, although 10 patients died in the enoxaparin group – 4 from sepsis, 2 from progressive liver failure, 3 from hepatocellular carcinoma, and 1 from variceal bleeding – 16 died in the placebo group. These deaths were due to sepsis in seven patients, progressive liver failure in another seven, hepatocellular carcinoma in one, and variceal bleeding in one.

There were no hemorrhagic or other treatment-related adverse events in the enoxaparin group, although asymptomatic thrombocytopenia led to the withdrawal of one patient 3 months into the trial. Three enoxaparin patients had liver transplants while on the drug, and Dr. Villa noted that they did not need extra blood transfusions.

Dr. Villa said she had no disclosures. She said the study was funded internally, and not by a company that makes enoxaparin.

SAN FRANCISCO – The anticoagulant enoxaparin appears to prevent portal vein thrombosis in patients with advanced cirrhosis, based on a small Italian study presented at the annual meeting of the American Association for the Study of Liver Diseases.

In this trial, 6 of 36 patients (17%) randomized to placebo developed partial or complete portal vein thrombosis (PVT) within a year, whereas none of the 34 patients (0%) randomized to 4,000 IU daily of the low-molecular-weight heparin developed PVT.

The analysis indicated that enoxaparin had a significant protective effect (HR 0.218; 95% CI, 0.048-0.994, P = .049) in these patients with advanced cirrhosis.

At enrollment, none of the patients had PVT. The treatment and placebo groups had no significant differences in terms of biochemical or demographic factors at the outset of the trial, which was the first to prospectively investigate whether anticoagulation prevents PVT.

At the meeting, lead investigator Dr. Erica Villa, professor of gastroenterology at the University of Modena and Reggio Emilia in Modena, Italy, said that the results need to be confirmed in larger studies.

All of the subjects had cirrhosis classified as Child-Pugh B7 to C10. The mean age in both groups was 57 years, and the mean MELD (Model for End-Stage Liver Disease) score was approximately 14. Men made up more than 60% of both arms.

Enoxaparin appeared to provide significant protection against decompensation – defined as new-onset ascites, hepatic encephalopathy, or variceal bleeding – and death. Four enoxaparin patients (12%) decompensated during treatment, whereas 22 (61%) in the placebo arm decompensated. The difference persisted even after treatment with enoxaparin ended at 12 months.

Similarly, although 10 patients died in the enoxaparin group – 4 from sepsis, 2 from progressive liver failure, 3 from hepatocellular carcinoma, and 1 from variceal bleeding – 16 died in the placebo group. These deaths were due to sepsis in seven patients, progressive liver failure in another seven, hepatocellular carcinoma in one, and variceal bleeding in one.

There were no hemorrhagic or other treatment-related adverse events in the enoxaparin group, although asymptomatic thrombocytopenia led to the withdrawal of one patient 3 months into the trial. Three enoxaparin patients had liver transplants while on the drug, and Dr. Villa noted that they did not need extra blood transfusions.

Dr. Villa said she had no disclosures. She said the study was funded internally, and not by a company that makes enoxaparin.

SAN FRANCISCO – Telaprevir is unlikely to be cost-effective as a first-line agent in treatment-naive genotype 1 hepatitis C patients with the CC interleukin 28B polymorphism, according to economic modeling of previously published data.

That’s because most of them don’t need telaprevir; about two-thirds will have a sustained virologic response (SVR) – essentially a cure – with standard pegylated interferon alfa/ribavirin therapy. It makes more economic sense to try that approach first, keeping telaprevir (Incivek) in reserve for patients who relapse or fail to respond, said lead investigator Dr. Ziad Gellad of Duke University, Durham, N.C.

SVR rates with that approach are about 90%, the same as if telaprevir was used right from the start. "The same proportion of the population will be cured whether you use telaprevir upfront or whether you use it as rescue. Maybe it’s worth reconsidering whether everyone needs these expensive drugs," Dr. Gellad said.

Of course, patients might not want to endure a 48-week or longer interferon/ribavirin regimen when adding telaprevir from the start may shorten treatment to 24 weeks, and it’s unclear at this point if insurers would ask them to do so. "Everybody is still working through those [payment] issues" following telaprevir’s May 2011 Food and Drug Administration approval, Dr. Gellad said.

Current labeling indicates that the drug can be used combination with interferon and ribavirin for both HCV treatment-naive patients and those who’ve failed initial dual therapy, suggesting a role as either a first- or second-line agent. Labeling also notes that the CC IL28B genotype – as opposed to the CT or TT genotypes – strongly predicts response to dual therapy.

There are commercially available screening blood tests for the polymorphism. The patent on the technology is shared by Duke, Merck, and Duke scientists who discovered it. It’s mostly academic hepatologists who screen for the polymorphism at present, said Dr. Jake Liang, president of the American Association for the Study of Liver Diseases.

"With dwindling resources, we need to figure out whether a particular treatment is more cost effective than others," said Dr. Jake Liang, president of the American Association for the Study of Liver Diseases.

Although the study results support the test’s utility, Dr. Gellad, who has no ownership rights to the patent, cautioned that the "use of IL28 screening is still unclear. It may be that there are other pretreatment predictors that will also be helpful, or it may be, as many have argued, that on-treatment response is the best predictor [of outcome], rendering IL28 testing obsolete. This is still a matter of debate."

Dr. Gellad and his colleagues compared previously published SVR rates, and their associated costs, for three regimens. The first, standard 48 weeks of interferon and ribavirin, cost $54,931 and gave patients an estimated 19.38 quality-adjusted life years (QALYS). Interferon/ribavirin for 24 weeks – in individuals with rapid virologic responses – cost $46,785 and gave patients 19.26 QALYS. Modeling included re-treating nonresponders and relapsers with a 48-week telaprevir-inclusive regimen.

In the third strategy, individuals got 12 weeks of telaprevir in combination with either 24 or 48 weeks of interferon and ribavirin, again based on their virologic responses. The approach cost $68,788 and gave people 19.34 QALYS.

With all three approaches leading to SVRs in about 90% of patients and just over 19 QALYS, paying more for the same ultimate result makes little economic sense, the researchers concluded.

The study "is very important," said Dr. Liang, also chief of the liver diseases branch of the National Institute of Diabetes and Digestive and Kidney Diseases.

"With dwindling resources, we need to figure out whether a particular treatment is more cost effective than others. We are all very excited about the approval of [direct-acting antivirals like telaprevir] that clearly enhance treatment response, but perhaps not one size fits all. Maybe this could be a way for us to save some money," he said.

Dr. Gellad and his colleagues will continue to study the issue, and plan to include boceprevir (Victrelis) – another direct-acting HCV antiviral approved in May – to their modeling. "The story will get more interesting," he said.

Dr. Gellad is a consultant to and gets grant support from Merck, maker of boceprevir. He said that the company was not involved in the study.

SAN FRANCISCO – Telaprevir is unlikely to be cost-effective as a first-line agent in treatment-naive genotype 1 hepatitis C patients with the CC interleukin 28B polymorphism, according to economic modeling of previously published data.

That’s because most of them don’t need telaprevir; about two-thirds will have a sustained virologic response (SVR) – essentially a cure – with standard pegylated interferon alfa/ribavirin therapy. It makes more economic sense to try that approach first, keeping telaprevir (Incivek) in reserve for patients who relapse or fail to respond, said lead investigator Dr. Ziad Gellad of Duke University, Durham, N.C.

SVR rates with that approach are about 90%, the same as if telaprevir was used right from the start. "The same proportion of the population will be cured whether you use telaprevir upfront or whether you use it as rescue. Maybe it’s worth reconsidering whether everyone needs these expensive drugs," Dr. Gellad said.

Of course, patients might not want to endure a 48-week or longer interferon/ribavirin regimen when adding telaprevir from the start may shorten treatment to 24 weeks, and it’s unclear at this point if insurers would ask them to do so. "Everybody is still working through those [payment] issues" following telaprevir’s May 2011 Food and Drug Administration approval, Dr. Gellad said.

Current labeling indicates that the drug can be used combination with interferon and ribavirin for both HCV treatment-naive patients and those who’ve failed initial dual therapy, suggesting a role as either a first- or second-line agent. Labeling also notes that the CC IL28B genotype – as opposed to the CT or TT genotypes – strongly predicts response to dual therapy.

There are commercially available screening blood tests for the polymorphism. The patent on the technology is shared by Duke, Merck, and Duke scientists who discovered it. It’s mostly academic hepatologists who screen for the polymorphism at present, said Dr. Jake Liang, president of the American Association for the Study of Liver Diseases.

"With dwindling resources, we need to figure out whether a particular treatment is more cost effective than others," said Dr. Jake Liang, president of the American Association for the Study of Liver Diseases.

Although the study results support the test’s utility, Dr. Gellad, who has no ownership rights to the patent, cautioned that the "use of IL28 screening is still unclear. It may be that there are other pretreatment predictors that will also be helpful, or it may be, as many have argued, that on-treatment response is the best predictor [of outcome], rendering IL28 testing obsolete. This is still a matter of debate."

Dr. Gellad and his colleagues compared previously published SVR rates, and their associated costs, for three regimens. The first, standard 48 weeks of interferon and ribavirin, cost $54,931 and gave patients an estimated 19.38 quality-adjusted life years (QALYS). Interferon/ribavirin for 24 weeks – in individuals with rapid virologic responses – cost $46,785 and gave patients 19.26 QALYS. Modeling included re-treating nonresponders and relapsers with a 48-week telaprevir-inclusive regimen.

In the third strategy, individuals got 12 weeks of telaprevir in combination with either 24 or 48 weeks of interferon and ribavirin, again based on their virologic responses. The approach cost $68,788 and gave people 19.34 QALYS.

With all three approaches leading to SVRs in about 90% of patients and just over 19 QALYS, paying more for the same ultimate result makes little economic sense, the researchers concluded.

The study "is very important," said Dr. Liang, also chief of the liver diseases branch of the National Institute of Diabetes and Digestive and Kidney Diseases.

"With dwindling resources, we need to figure out whether a particular treatment is more cost effective than others. We are all very excited about the approval of [direct-acting antivirals like telaprevir] that clearly enhance treatment response, but perhaps not one size fits all. Maybe this could be a way for us to save some money," he said.

Dr. Gellad and his colleagues will continue to study the issue, and plan to include boceprevir (Victrelis) – another direct-acting HCV antiviral approved in May – to their modeling. "The story will get more interesting," he said.

Dr. Gellad is a consultant to and gets grant support from Merck, maker of boceprevir. He said that the company was not involved in the study.

SAN FRANCISCO – Telaprevir is unlikely to be cost-effective as a first-line agent in treatment-naive genotype 1 hepatitis C patients with the CC interleukin 28B polymorphism, according to economic modeling of previously published data.

That’s because most of them don’t need telaprevir; about two-thirds will have a sustained virologic response (SVR) – essentially a cure – with standard pegylated interferon alfa/ribavirin therapy. It makes more economic sense to try that approach first, keeping telaprevir (Incivek) in reserve for patients who relapse or fail to respond, said lead investigator Dr. Ziad Gellad of Duke University, Durham, N.C.

SVR rates with that approach are about 90%, the same as if telaprevir was used right from the start. "The same proportion of the population will be cured whether you use telaprevir upfront or whether you use it as rescue. Maybe it’s worth reconsidering whether everyone needs these expensive drugs," Dr. Gellad said.

Of course, patients might not want to endure a 48-week or longer interferon/ribavirin regimen when adding telaprevir from the start may shorten treatment to 24 weeks, and it’s unclear at this point if insurers would ask them to do so. "Everybody is still working through those [payment] issues" following telaprevir’s May 2011 Food and Drug Administration approval, Dr. Gellad said.

Current labeling indicates that the drug can be used combination with interferon and ribavirin for both HCV treatment-naive patients and those who’ve failed initial dual therapy, suggesting a role as either a first- or second-line agent. Labeling also notes that the CC IL28B genotype – as opposed to the CT or TT genotypes – strongly predicts response to dual therapy.

There are commercially available screening blood tests for the polymorphism. The patent on the technology is shared by Duke, Merck, and Duke scientists who discovered it. It’s mostly academic hepatologists who screen for the polymorphism at present, said Dr. Jake Liang, president of the American Association for the Study of Liver Diseases.

"With dwindling resources, we need to figure out whether a particular treatment is more cost effective than others," said Dr. Jake Liang, president of the American Association for the Study of Liver Diseases.

Although the study results support the test’s utility, Dr. Gellad, who has no ownership rights to the patent, cautioned that the "use of IL28 screening is still unclear. It may be that there are other pretreatment predictors that will also be helpful, or it may be, as many have argued, that on-treatment response is the best predictor [of outcome], rendering IL28 testing obsolete. This is still a matter of debate."

Dr. Gellad and his colleagues compared previously published SVR rates, and their associated costs, for three regimens. The first, standard 48 weeks of interferon and ribavirin, cost $54,931 and gave patients an estimated 19.38 quality-adjusted life years (QALYS). Interferon/ribavirin for 24 weeks – in individuals with rapid virologic responses – cost $46,785 and gave patients 19.26 QALYS. Modeling included re-treating nonresponders and relapsers with a 48-week telaprevir-inclusive regimen.

In the third strategy, individuals got 12 weeks of telaprevir in combination with either 24 or 48 weeks of interferon and ribavirin, again based on their virologic responses. The approach cost $68,788 and gave people 19.34 QALYS.

With all three approaches leading to SVRs in about 90% of patients and just over 19 QALYS, paying more for the same ultimate result makes little economic sense, the researchers concluded.

The study "is very important," said Dr. Liang, also chief of the liver diseases branch of the National Institute of Diabetes and Digestive and Kidney Diseases.

"With dwindling resources, we need to figure out whether a particular treatment is more cost effective than others. We are all very excited about the approval of [direct-acting antivirals like telaprevir] that clearly enhance treatment response, but perhaps not one size fits all. Maybe this could be a way for us to save some money," he said.

Dr. Gellad and his colleagues will continue to study the issue, and plan to include boceprevir (Victrelis) – another direct-acting HCV antiviral approved in May – to their modeling. "The story will get more interesting," he said.

Dr. Gellad is a consultant to and gets grant support from Merck, maker of boceprevir. He said that the company was not involved in the study.

SAN FRANCISCO – Physicians in the United States should not be too quick to cross hepatitis E off their lists of possible diagnoses for patients who have not traveled abroad, researchers with the Centers for Disease Control and Prevention advise.

They performed serologic and molecular testing in 123 patients with acute hepatitis-like illness that was not hepatitis A, B, or C, and found that 22% had hepatitis E, according to results reported at the annual meeting of the American Association for the Study of Liver Diseases.

Nearly two-thirds of these patients had no history of recent international travel. Slightly more than a quarter had undergone organ transplantation.

"This work is very important to build awareness about hepatitis E in the U.S., where this disease is not reportable and [its] epidemiology ... is unknown," lead investigator Dr. Jan Drobeniuc said in an interview. "Our work shows that this disease is more common in the U.S. than previously thought."

Although physicians have usually relied on a travel history to tip them off to the presence of hepatitis E, these surveillance data suggest that infection in the United States may in fact be more common among nontravelers.

"I think that hepatitis E should enter into the differential diagnosis of hepatitis even for people who did not travel abroad," Dr. Drobeniuc said. "Previously, this prerequisite was kind of biasing the physicians – their first question would be, ‘Did you travel?’ If you didn’t travel, they just dismissed the case. So I think this travel-nontravel situation has to be removed to prevent bias for the physicians, and [they should] just do laboratory testing to determine the disease."

Research suggests that about one in five people in the United States has antibodies to hepatitis E (J. Infect. Dis. 2009;200:48-56). "So the obvious question would be, why is there no acute disease, why don’t we see the actual cases?" noted Dr. Drobeniuc, senior service fellow and microbiologist with the CDC. "Probably the reason is it’s not reportable."

To get a better handle on its epidemiology, the CDC established a passive surveillance system for physicians who had patients with hepatitis that did not have a readily identifiable cause.

The investigators tested specimens from 123 patients who had acute hepatitis-like illness with jaundice and/or elevated liver function test results, were referred to the surveillance system between 2005 and 2011, and were serologically confirmed not to have hepatitis A, B, or C.

According to study results reported in a poster session at the meeting, 27 (22%) of the patients had hepatitis E, based on the presence of antiviral IgM antibodies in serum or viral RNA in serum or stool.

The patients had been referred from 14 states; the states accounting for the largest shares were Texas and Illinois. The median age was 42 years, and the majority of patients were male (59%) and white (52%).

Viral genotyping in a subset of patients showed that three-fourths had genotype 3. And phylogenetic analysis showed that these strains were genetically similar to those seen previously in indigenous cases of hepatitis E and in swine in the United States.

"Our work shows that this disease is more common in the U.S. than previously thought."

Twenty-six percent of the patients were organ transplant recipients, a population that seems to be at high risk for developing persistent disease. "This most likely is related to the fact that they are immunosuppressed and they do not develop a proper immune response to the infection," Dr. Drobeniuc explained. All of the recipients who had viral genotyping were found to have genotype 3.

Fully 63% of the patients had not traveled outside the United States in the previous 2 months. Compared with travelers, nontravelers were significantly older, less likely to be of South Asian race/ethnicity, and more likely to be organ transplant recipients. All of the cases of genotype 3 occurred among nontravelers.

It was not clear how the patients studied became infected with hepatitis E. Their clinical course attested to the fact that this infection can sometimes be severe, as two patients experienced fulminant hepatic failure, and one of them died.

Because the surveillance system was passive and relied on the discretion of referring physicians, the rate of hepatitis E seen "most likely does not reflect the incidence of hepatitis E in the United States," he commented. Additionally, it was not possible to accurately assess temporal trends.

"Now we are expanding this passive surveillance to a more active approach," with testing in cases referred by laboratories, Dr. Drobeniuc noted. Given that viremia is usually short-lived in infected patients, a particular aim is to identify more cases in the acute phase, so that the virus can be isolated and genotyped. "An active approach will probably give a much better picture of hepatitis E in the United States," he concluded.

Dr. Drobeniuc reported having no conflicts of interest.

SAN FRANCISCO – Physicians in the United States should not be too quick to cross hepatitis E off their lists of possible diagnoses for patients who have not traveled abroad, researchers with the Centers for Disease Control and Prevention advise.

They performed serologic and molecular testing in 123 patients with acute hepatitis-like illness that was not hepatitis A, B, or C, and found that 22% had hepatitis E, according to results reported at the annual meeting of the American Association for the Study of Liver Diseases.

Nearly two-thirds of these patients had no history of recent international travel. Slightly more than a quarter had undergone organ transplantation.

"This work is very important to build awareness about hepatitis E in the U.S., where this disease is not reportable and [its] epidemiology ... is unknown," lead investigator Dr. Jan Drobeniuc said in an interview. "Our work shows that this disease is more common in the U.S. than previously thought."

Although physicians have usually relied on a travel history to tip them off to the presence of hepatitis E, these surveillance data suggest that infection in the United States may in fact be more common among nontravelers.

"I think that hepatitis E should enter into the differential diagnosis of hepatitis even for people who did not travel abroad," Dr. Drobeniuc said. "Previously, this prerequisite was kind of biasing the physicians – their first question would be, ‘Did you travel?’ If you didn’t travel, they just dismissed the case. So I think this travel-nontravel situation has to be removed to prevent bias for the physicians, and [they should] just do laboratory testing to determine the disease."

Research suggests that about one in five people in the United States has antibodies to hepatitis E (J. Infect. Dis. 2009;200:48-56). "So the obvious question would be, why is there no acute disease, why don’t we see the actual cases?" noted Dr. Drobeniuc, senior service fellow and microbiologist with the CDC. "Probably the reason is it’s not reportable."

To get a better handle on its epidemiology, the CDC established a passive surveillance system for physicians who had patients with hepatitis that did not have a readily identifiable cause.

The investigators tested specimens from 123 patients who had acute hepatitis-like illness with jaundice and/or elevated liver function test results, were referred to the surveillance system between 2005 and 2011, and were serologically confirmed not to have hepatitis A, B, or C.

According to study results reported in a poster session at the meeting, 27 (22%) of the patients had hepatitis E, based on the presence of antiviral IgM antibodies in serum or viral RNA in serum or stool.

The patients had been referred from 14 states; the states accounting for the largest shares were Texas and Illinois. The median age was 42 years, and the majority of patients were male (59%) and white (52%).

Viral genotyping in a subset of patients showed that three-fourths had genotype 3. And phylogenetic analysis showed that these strains were genetically similar to those seen previously in indigenous cases of hepatitis E and in swine in the United States.

"Our work shows that this disease is more common in the U.S. than previously thought."

Twenty-six percent of the patients were organ transplant recipients, a population that seems to be at high risk for developing persistent disease. "This most likely is related to the fact that they are immunosuppressed and they do not develop a proper immune response to the infection," Dr. Drobeniuc explained. All of the recipients who had viral genotyping were found to have genotype 3.

Fully 63% of the patients had not traveled outside the United States in the previous 2 months. Compared with travelers, nontravelers were significantly older, less likely to be of South Asian race/ethnicity, and more likely to be organ transplant recipients. All of the cases of genotype 3 occurred among nontravelers.

It was not clear how the patients studied became infected with hepatitis E. Their clinical course attested to the fact that this infection can sometimes be severe, as two patients experienced fulminant hepatic failure, and one of them died.

Because the surveillance system was passive and relied on the discretion of referring physicians, the rate of hepatitis E seen "most likely does not reflect the incidence of hepatitis E in the United States," he commented. Additionally, it was not possible to accurately assess temporal trends.

"Now we are expanding this passive surveillance to a more active approach," with testing in cases referred by laboratories, Dr. Drobeniuc noted. Given that viremia is usually short-lived in infected patients, a particular aim is to identify more cases in the acute phase, so that the virus can be isolated and genotyped. "An active approach will probably give a much better picture of hepatitis E in the United States," he concluded.

Dr. Drobeniuc reported having no conflicts of interest.

SAN FRANCISCO – Physicians in the United States should not be too quick to cross hepatitis E off their lists of possible diagnoses for patients who have not traveled abroad, researchers with the Centers for Disease Control and Prevention advise.

They performed serologic and molecular testing in 123 patients with acute hepatitis-like illness that was not hepatitis A, B, or C, and found that 22% had hepatitis E, according to results reported at the annual meeting of the American Association for the Study of Liver Diseases.

Nearly two-thirds of these patients had no history of recent international travel. Slightly more than a quarter had undergone organ transplantation.

"This work is very important to build awareness about hepatitis E in the U.S., where this disease is not reportable and [its] epidemiology ... is unknown," lead investigator Dr. Jan Drobeniuc said in an interview. "Our work shows that this disease is more common in the U.S. than previously thought."

Although physicians have usually relied on a travel history to tip them off to the presence of hepatitis E, these surveillance data suggest that infection in the United States may in fact be more common among nontravelers.

"I think that hepatitis E should enter into the differential diagnosis of hepatitis even for people who did not travel abroad," Dr. Drobeniuc said. "Previously, this prerequisite was kind of biasing the physicians – their first question would be, ‘Did you travel?’ If you didn’t travel, they just dismissed the case. So I think this travel-nontravel situation has to be removed to prevent bias for the physicians, and [they should] just do laboratory testing to determine the disease."

Research suggests that about one in five people in the United States has antibodies to hepatitis E (J. Infect. Dis. 2009;200:48-56). "So the obvious question would be, why is there no acute disease, why don’t we see the actual cases?" noted Dr. Drobeniuc, senior service fellow and microbiologist with the CDC. "Probably the reason is it’s not reportable."

To get a better handle on its epidemiology, the CDC established a passive surveillance system for physicians who had patients with hepatitis that did not have a readily identifiable cause.

The investigators tested specimens from 123 patients who had acute hepatitis-like illness with jaundice and/or elevated liver function test results, were referred to the surveillance system between 2005 and 2011, and were serologically confirmed not to have hepatitis A, B, or C.

According to study results reported in a poster session at the meeting, 27 (22%) of the patients had hepatitis E, based on the presence of antiviral IgM antibodies in serum or viral RNA in serum or stool.

The patients had been referred from 14 states; the states accounting for the largest shares were Texas and Illinois. The median age was 42 years, and the majority of patients were male (59%) and white (52%).

Viral genotyping in a subset of patients showed that three-fourths had genotype 3. And phylogenetic analysis showed that these strains were genetically similar to those seen previously in indigenous cases of hepatitis E and in swine in the United States.

"Our work shows that this disease is more common in the U.S. than previously thought."

Twenty-six percent of the patients were organ transplant recipients, a population that seems to be at high risk for developing persistent disease. "This most likely is related to the fact that they are immunosuppressed and they do not develop a proper immune response to the infection," Dr. Drobeniuc explained. All of the recipients who had viral genotyping were found to have genotype 3.

Fully 63% of the patients had not traveled outside the United States in the previous 2 months. Compared with travelers, nontravelers were significantly older, less likely to be of South Asian race/ethnicity, and more likely to be organ transplant recipients. All of the cases of genotype 3 occurred among nontravelers.

It was not clear how the patients studied became infected with hepatitis E. Their clinical course attested to the fact that this infection can sometimes be severe, as two patients experienced fulminant hepatic failure, and one of them died.

Because the surveillance system was passive and relied on the discretion of referring physicians, the rate of hepatitis E seen "most likely does not reflect the incidence of hepatitis E in the United States," he commented. Additionally, it was not possible to accurately assess temporal trends.

"Now we are expanding this passive surveillance to a more active approach," with testing in cases referred by laboratories, Dr. Drobeniuc noted. Given that viremia is usually short-lived in infected patients, a particular aim is to identify more cases in the acute phase, so that the virus can be isolated and genotyped. "An active approach will probably give a much better picture of hepatitis E in the United States," he concluded.

Dr. Drobeniuc reported having no conflicts of interest.

SAN FRANCISCO – When cancer patients have hepatitis B virus, prophylaxis to prevent its reactivation during chemotherapy lowers their mortality, but screening for the virus remains uncommon, said researchers from M.D. Anderson Cancer Center in Houston.

Just 17% (1,787) of 10,729 patients who started chemotherapy there during a 3-year study were screened beforehand for hepatitis B virus (HBV), despite recommendations to do so from the Centers for Disease Control and Prevention and other groups.

Of those screened, 151 (8%) proved to be positive for hepatitis B surface antigen (HBsAg) and/or antibody to hepatitis B core antigen (anti-HBc). In all, 34 of them (23%) reactivated during chemotherapy. Most were being treated for hematologic malignancies.

Among the nine patients whose hepatitis B reactivated despite prophylaxis – in most cases with lamivudine (Epivir) – two patients (22%) died. Among the 11 who were treated with antivirals only after reactivation, 8 (72%) died. And of the 14 who were not treated with antivirals for their reactivation, 10 (71%) died.

M.D. Anderson probably isn’t the only institution failing to follow the HBV screening and prophylaxis recommendations, and physicians may be unaware of the guidelines, said lead investigator Dr. Jessica Hwang at the annual meeting of the American Association for the Study of Liver Diseases.

There’s also been – at least until now – a lack of large studies supporting the practice of screening and prophylaxis for HBV before chemotherapy. The evidence gap has led to debate about the merits of the approach, said Dr. Hwang, assistant professor in the department of general internal medicine at M.D. Anderson.

Now the study findings address this gap, showing that "preventable reactivation does occur. Prophylactic antivirals [can] dramatically reduce mortality in cancer patients with hepatitis B infection. You need to prophylax them before chemotherapy," Dr. Hwang said.

At least one observer agreed. It’s "a very simple solution to prevent potentially life-threatening complications" from the virus, said Dr. T. Jake Liang, president of the American Association for the Study of Liver Diseases and chief of the Liver Diseases Branch of the National Institute of Diabetes and Digestive and Kidney Diseases.

Patients in the study were more likely to be screened if they were male, treated with rituximab (Rituxan), had hematologic cancers, or had at least one HBV risk factor. The risk factors include injection drug use, living with a person who has chronic hepatitis B, and hemodialysis, among others.

Patients were more likely to screen positive for HBV if they had a risk factor, or if they were male, Asian, or black.

The study also found that reactivators tended to be slightly younger – 47 years on average – than HBV-positive patients who did not reactivate; their mean age was 54.

Dr. Liang said he has no disclosures. Dr. Hwang disclosed grant support form Bristol-Myers Squibb, maker of the anti-HBV drug entecavir (Baraclude). The company funded the study, together with the National Cancer Institute and the American Cancer Society.

SAN FRANCISCO – When cancer patients have hepatitis B virus, prophylaxis to prevent its reactivation during chemotherapy lowers their mortality, but screening for the virus remains uncommon, said researchers from M.D. Anderson Cancer Center in Houston.

Just 17% (1,787) of 10,729 patients who started chemotherapy there during a 3-year study were screened beforehand for hepatitis B virus (HBV), despite recommendations to do so from the Centers for Disease Control and Prevention and other groups.

Of those screened, 151 (8%) proved to be positive for hepatitis B surface antigen (HBsAg) and/or antibody to hepatitis B core antigen (anti-HBc). In all, 34 of them (23%) reactivated during chemotherapy. Most were being treated for hematologic malignancies.

Among the nine patients whose hepatitis B reactivated despite prophylaxis – in most cases with lamivudine (Epivir) – two patients (22%) died. Among the 11 who were treated with antivirals only after reactivation, 8 (72%) died. And of the 14 who were not treated with antivirals for their reactivation, 10 (71%) died.

M.D. Anderson probably isn’t the only institution failing to follow the HBV screening and prophylaxis recommendations, and physicians may be unaware of the guidelines, said lead investigator Dr. Jessica Hwang at the annual meeting of the American Association for the Study of Liver Diseases.

There’s also been – at least until now – a lack of large studies supporting the practice of screening and prophylaxis for HBV before chemotherapy. The evidence gap has led to debate about the merits of the approach, said Dr. Hwang, assistant professor in the department of general internal medicine at M.D. Anderson.

Now the study findings address this gap, showing that "preventable reactivation does occur. Prophylactic antivirals [can] dramatically reduce mortality in cancer patients with hepatitis B infection. You need to prophylax them before chemotherapy," Dr. Hwang said.

At least one observer agreed. It’s "a very simple solution to prevent potentially life-threatening complications" from the virus, said Dr. T. Jake Liang, president of the American Association for the Study of Liver Diseases and chief of the Liver Diseases Branch of the National Institute of Diabetes and Digestive and Kidney Diseases.

Patients in the study were more likely to be screened if they were male, treated with rituximab (Rituxan), had hematologic cancers, or had at least one HBV risk factor. The risk factors include injection drug use, living with a person who has chronic hepatitis B, and hemodialysis, among others.

Patients were more likely to screen positive for HBV if they had a risk factor, or if they were male, Asian, or black.

The study also found that reactivators tended to be slightly younger – 47 years on average – than HBV-positive patients who did not reactivate; their mean age was 54.

Dr. Liang said he has no disclosures. Dr. Hwang disclosed grant support form Bristol-Myers Squibb, maker of the anti-HBV drug entecavir (Baraclude). The company funded the study, together with the National Cancer Institute and the American Cancer Society.

SAN FRANCISCO – When cancer patients have hepatitis B virus, prophylaxis to prevent its reactivation during chemotherapy lowers their mortality, but screening for the virus remains uncommon, said researchers from M.D. Anderson Cancer Center in Houston.

Just 17% (1,787) of 10,729 patients who started chemotherapy there during a 3-year study were screened beforehand for hepatitis B virus (HBV), despite recommendations to do so from the Centers for Disease Control and Prevention and other groups.

Of those screened, 151 (8%) proved to be positive for hepatitis B surface antigen (HBsAg) and/or antibody to hepatitis B core antigen (anti-HBc). In all, 34 of them (23%) reactivated during chemotherapy. Most were being treated for hematologic malignancies.

Among the nine patients whose hepatitis B reactivated despite prophylaxis – in most cases with lamivudine (Epivir) – two patients (22%) died. Among the 11 who were treated with antivirals only after reactivation, 8 (72%) died. And of the 14 who were not treated with antivirals for their reactivation, 10 (71%) died.

M.D. Anderson probably isn’t the only institution failing to follow the HBV screening and prophylaxis recommendations, and physicians may be unaware of the guidelines, said lead investigator Dr. Jessica Hwang at the annual meeting of the American Association for the Study of Liver Diseases.

There’s also been – at least until now – a lack of large studies supporting the practice of screening and prophylaxis for HBV before chemotherapy. The evidence gap has led to debate about the merits of the approach, said Dr. Hwang, assistant professor in the department of general internal medicine at M.D. Anderson.

Now the study findings address this gap, showing that "preventable reactivation does occur. Prophylactic antivirals [can] dramatically reduce mortality in cancer patients with hepatitis B infection. You need to prophylax them before chemotherapy," Dr. Hwang said.

At least one observer agreed. It’s "a very simple solution to prevent potentially life-threatening complications" from the virus, said Dr. T. Jake Liang, president of the American Association for the Study of Liver Diseases and chief of the Liver Diseases Branch of the National Institute of Diabetes and Digestive and Kidney Diseases.

Patients in the study were more likely to be screened if they were male, treated with rituximab (Rituxan), had hematologic cancers, or had at least one HBV risk factor. The risk factors include injection drug use, living with a person who has chronic hepatitis B, and hemodialysis, among others.

Patients were more likely to screen positive for HBV if they had a risk factor, or if they were male, Asian, or black.

The study also found that reactivators tended to be slightly younger – 47 years on average – than HBV-positive patients who did not reactivate; their mean age was 54.

Dr. Liang said he has no disclosures. Dr. Hwang disclosed grant support form Bristol-Myers Squibb, maker of the anti-HBV drug entecavir (Baraclude). The company funded the study, together with the National Cancer Institute and the American Cancer Society.

SAN FRANCISCO – Nonalcoholic steatohepatitis patients may need a more thorough cardiovascular workup before liver transplantation, according to a study presented at the annual meeting of the American Association for Liver Diseases.

Standard pretransplant cardiac screening results were similar for 115 nonalcoholic steatohepatitis (NASH) and 127 alcohol-induced cirrhosis patients. Most patients had received transthoracic echocardiograms, and many had had other tests, including dobutamine stress echocardiograms, cardiac catheterizations, and ECGs.

The Revised Cardiac Risk Index, a common heart screen for noncardiac surgeries that focuses mostly on ischemia, predicted cardiac events in 6.6% of both groups.

The rate of cardiac events was higher in the NASH group; 26% had significant cardiac events within a year of surgery, two-thirds of those within a month. Cardiac arrests and arrhythmias – some fatal – were the most common events in the NASH group. Meanwhile, about 8% of the alcoholic-cirrhosis patients had cardiac events during their first postop year.

The inaccuracy of the screening of NASH patients illustrates the need for better methods of identifying cardiac risks prior to liver transplants, said investigator Dr. Lisa VanWagner, a first-year fellow in gastroenterology and hepatology at Northwestern University, Chicago.

"Current algorithms are designed to predict MI and plaque rupture. We tend to overutilize dobutamine stress echoes and other noninvasive stress tests to look for ischemic heart disease," she said.

In addition to atherosclerosis, NASH patients may have low systemic resistance, chronotropic incompetence, and other problems that a too-narrow focus on ischemia might miss. The cardiac arrests and arrhythmias noted in the study may not have been "related to plaque rupture. We really need to better risk-stratify these patients," said Dr. VanWagner, who noted she hopes to develop a liver-transplant specific cardiac risk index.

Tricuspid regurgitation might have predictive value, she said, as well as pulmonary hypertension and prolonged QTc interval, although the latter two did not differ significantly between the two groups before transplant.

Indeed, there were just two statistical differences; left ventricular hypertrophy was slightly more common in alcoholic-cirrhosis patients (20% vs. 15%), and that group was more likely than the NASH group to have clean coronary arteries on left heart catheterization (20% vs. 14%).

The mean age in the NASH group was 58 years, and 45% of NASH patients were women. The mean age in the alcoholic-cirrhosis group was 53 years, and 18% of patients were women. Mean MELD (Model for End-Stage Liver Disease) scores were about 25 for members of both groups.

NASH patients were more likely to be obese, dyslipidemic, and hypertensive. But even after controlling for those factors, as well as for smoking and prior history of coronary artery disease, NASH patients were still more likely to have an adverse cardiovascular event within a year of transplant (odds ratio, 2.69; 95% confidence interval, 1.32-6.34).

Most patients in both groups were alive at 1 year, but only 4% were alive in the NASH group at 10 years, compared with 18% in the alcoholic-cirrhosis group.

Before surgery, about 50% of NASH patients were on a beta-blocker, and 10% on a statin, although more than half had statin indications.

Dr. VanWagner said she has no disclosures.

SAN FRANCISCO – Nonalcoholic steatohepatitis patients may need a more thorough cardiovascular workup before liver transplantation, according to a study presented at the annual meeting of the American Association for Liver Diseases.

Standard pretransplant cardiac screening results were similar for 115 nonalcoholic steatohepatitis (NASH) and 127 alcohol-induced cirrhosis patients. Most patients had received transthoracic echocardiograms, and many had had other tests, including dobutamine stress echocardiograms, cardiac catheterizations, and ECGs.

The Revised Cardiac Risk Index, a common heart screen for noncardiac surgeries that focuses mostly on ischemia, predicted cardiac events in 6.6% of both groups.

The rate of cardiac events was higher in the NASH group; 26% had significant cardiac events within a year of surgery, two-thirds of those within a month. Cardiac arrests and arrhythmias – some fatal – were the most common events in the NASH group. Meanwhile, about 8% of the alcoholic-cirrhosis patients had cardiac events during their first postop year.

The inaccuracy of the screening of NASH patients illustrates the need for better methods of identifying cardiac risks prior to liver transplants, said investigator Dr. Lisa VanWagner, a first-year fellow in gastroenterology and hepatology at Northwestern University, Chicago.

"Current algorithms are designed to predict MI and plaque rupture. We tend to overutilize dobutamine stress echoes and other noninvasive stress tests to look for ischemic heart disease," she said.

In addition to atherosclerosis, NASH patients may have low systemic resistance, chronotropic incompetence, and other problems that a too-narrow focus on ischemia might miss. The cardiac arrests and arrhythmias noted in the study may not have been "related to plaque rupture. We really need to better risk-stratify these patients," said Dr. VanWagner, who noted she hopes to develop a liver-transplant specific cardiac risk index.

Tricuspid regurgitation might have predictive value, she said, as well as pulmonary hypertension and prolonged QTc interval, although the latter two did not differ significantly between the two groups before transplant.

Indeed, there were just two statistical differences; left ventricular hypertrophy was slightly more common in alcoholic-cirrhosis patients (20% vs. 15%), and that group was more likely than the NASH group to have clean coronary arteries on left heart catheterization (20% vs. 14%).

The mean age in the NASH group was 58 years, and 45% of NASH patients were women. The mean age in the alcoholic-cirrhosis group was 53 years, and 18% of patients were women. Mean MELD (Model for End-Stage Liver Disease) scores were about 25 for members of both groups.

NASH patients were more likely to be obese, dyslipidemic, and hypertensive. But even after controlling for those factors, as well as for smoking and prior history of coronary artery disease, NASH patients were still more likely to have an adverse cardiovascular event within a year of transplant (odds ratio, 2.69; 95% confidence interval, 1.32-6.34).

Most patients in both groups were alive at 1 year, but only 4% were alive in the NASH group at 10 years, compared with 18% in the alcoholic-cirrhosis group.

Before surgery, about 50% of NASH patients were on a beta-blocker, and 10% on a statin, although more than half had statin indications.

Dr. VanWagner said she has no disclosures.

SAN FRANCISCO – Nonalcoholic steatohepatitis patients may need a more thorough cardiovascular workup before liver transplantation, according to a study presented at the annual meeting of the American Association for Liver Diseases.

Standard pretransplant cardiac screening results were similar for 115 nonalcoholic steatohepatitis (NASH) and 127 alcohol-induced cirrhosis patients. Most patients had received transthoracic echocardiograms, and many had had other tests, including dobutamine stress echocardiograms, cardiac catheterizations, and ECGs.

The Revised Cardiac Risk Index, a common heart screen for noncardiac surgeries that focuses mostly on ischemia, predicted cardiac events in 6.6% of both groups.

The rate of cardiac events was higher in the NASH group; 26% had significant cardiac events within a year of surgery, two-thirds of those within a month. Cardiac arrests and arrhythmias – some fatal – were the most common events in the NASH group. Meanwhile, about 8% of the alcoholic-cirrhosis patients had cardiac events during their first postop year.

The inaccuracy of the screening of NASH patients illustrates the need for better methods of identifying cardiac risks prior to liver transplants, said investigator Dr. Lisa VanWagner, a first-year fellow in gastroenterology and hepatology at Northwestern University, Chicago.

"Current algorithms are designed to predict MI and plaque rupture. We tend to overutilize dobutamine stress echoes and other noninvasive stress tests to look for ischemic heart disease," she said.

In addition to atherosclerosis, NASH patients may have low systemic resistance, chronotropic incompetence, and other problems that a too-narrow focus on ischemia might miss. The cardiac arrests and arrhythmias noted in the study may not have been "related to plaque rupture. We really need to better risk-stratify these patients," said Dr. VanWagner, who noted she hopes to develop a liver-transplant specific cardiac risk index.

Tricuspid regurgitation might have predictive value, she said, as well as pulmonary hypertension and prolonged QTc interval, although the latter two did not differ significantly between the two groups before transplant.

Indeed, there were just two statistical differences; left ventricular hypertrophy was slightly more common in alcoholic-cirrhosis patients (20% vs. 15%), and that group was more likely than the NASH group to have clean coronary arteries on left heart catheterization (20% vs. 14%).

The mean age in the NASH group was 58 years, and 45% of NASH patients were women. The mean age in the alcoholic-cirrhosis group was 53 years, and 18% of patients were women. Mean MELD (Model for End-Stage Liver Disease) scores were about 25 for members of both groups.

NASH patients were more likely to be obese, dyslipidemic, and hypertensive. But even after controlling for those factors, as well as for smoking and prior history of coronary artery disease, NASH patients were still more likely to have an adverse cardiovascular event within a year of transplant (odds ratio, 2.69; 95% confidence interval, 1.32-6.34).

Most patients in both groups were alive at 1 year, but only 4% were alive in the NASH group at 10 years, compared with 18% in the alcoholic-cirrhosis group.

Before surgery, about 50% of NASH patients were on a beta-blocker, and 10% on a statin, although more than half had statin indications.

Dr. VanWagner said she has no disclosures.