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Patients with compensated cirrhosis and chronic genotype 1 hepatitis C virus infections were significantly more likely to clear their infections and had fewer adverse effects when treated with simeprevir and sofosbuvir instead of peginterferon, ribavirin, and sofosbuvir, investigators reported in the April issue of Gastroenterology. “Patients given the interferon-containing regimen had a significantly greater rate of virologic relapse than patients given simeprevir and sofosbuvir ... and reported worse outcomes and more side effects,” said Dr. Brian L. Pearlman and his associates of Atlanta Medical Center and Emory University, Atlanta.

Liver disease associated with chronic hepatitis C virus (HCV) infection causes at least 350,000 deaths per year worldwide. Genotype 1 (GT-1) HCV is the most common HCV strain and the hardest to treat, especially when patients have cirrhosis. Treatments for chronic GT-1 HCV infections historically included interferon, but achieved only moderate rates of sustained virologic response (SVR) and caused adverse somatic and psychiatric effects. All-oral, interferon-free regimens are now in widespread use, but many of the pivotal trials were industry sponsored and had strict enrollment criteria, potentially limiting their generalizability in community settings, the researchers reported (Gastroenterology 2015 April [doi:10.1053/j.gastro.2014.12.027]).Their open-label trial included 82 patients with HCV GT-1a infection and Child’s grade A cirrhosis recruited from two clinical practices in Atlanta. Thirty-two of the patients were treatment naive, while 50 had previously not responded to peginterferon and ribavirin treatment. Patients were randomized to either 12 weeks of all-oral simeprevir (150 mg/day) and sofosbuvir (400 mg/day), or peginterferon alfa 2b (1.5 mcg/kg per week), ribavirin (1000-1200 mg/day), and sofosbuvir (400 mg/day).Fully 54 of 58 (93%) patients given the simeprevir-sofosbuvir regimen had undetectable levels of HCV RNA at 12 weeks (SVR12), compared with 18 of 24 (75%) patients who received the interferon-containing regimen (P = .02), the researchers reported. Rates of SVR12 among prior nonresponders were 92% and 64%, and were 95% and 80% for treatment-naive patients, although P-values did not reach statistical significance. The interferon group also had a higher rate of virologic relapse than did patients given simeprevir and sofosbuvir (P = .009), and had worse self-reported outcomes and more side effects, the researchers said. Patients in both groups who achieved SVR12 had higher quality-of-life scores than those who did not. Notably, almost half of patients were African American, a group that has historically had lower cure rates compared with other racial groups, said the investigators.

“Given that several new regimens for genotype 1 infection, including the sofosbuvir-ledipasvir combination pill, already have been approved, we believe that this study is very timely,” Dr. Pearlman and his associates said. “Although these are not head-to-head comparisons, the 12-week simeprevir and sofosbuvir regimen in this trial may compare favorably with the SVR rates for 12 weeks of sofosbuvir/ledipasvir and 12 weeks of the regimen, paritaprevir/ritonavir, ombitasvir and dasabuvir plus ribavirin for patients with cirrhosis, particularly for prior nonresponders to older therapies, with the caveat that many more patients were studied in the registration trials.”While industry-sponsored trials have had psychiatric exclusion criteria, several patients in the open-label trial had serious psychiatric conditions, said the researchers. A patient with stable bipolar disorder received the interferon-containing regimen, and two patients with stable schizophrenia received the all-oral regimen. None reported worsening psychiatric symptoms on treatment.

Dr. Pearlman reported having contracted research for Johnson & Johnson, Gilead, Abbvie, Bristol-Myers Squibb, Boehringer Ingelheim, and Merck; and having served on speaker and advisory boards for Johnson & Johnson, Gilead, and Abbvie. He also was an investigator and author in the COSMOS trial of simeprevir and sofosbuvir in patients with HCV/HIV coinfection. The other authors reported no conflicts of interest.

Patients with compensated cirrhosis and chronic genotype 1 hepatitis C virus infections were significantly more likely to clear their infections and had fewer adverse effects when treated with simeprevir and sofosbuvir instead of peginterferon, ribavirin, and sofosbuvir, investigators reported in the April issue of Gastroenterology. “Patients given the interferon-containing regimen had a significantly greater rate of virologic relapse than patients given simeprevir and sofosbuvir ... and reported worse outcomes and more side effects,” said Dr. Brian L. Pearlman and his associates of Atlanta Medical Center and Emory University, Atlanta.

Liver disease associated with chronic hepatitis C virus (HCV) infection causes at least 350,000 deaths per year worldwide. Genotype 1 (GT-1) HCV is the most common HCV strain and the hardest to treat, especially when patients have cirrhosis. Treatments for chronic GT-1 HCV infections historically included interferon, but achieved only moderate rates of sustained virologic response (SVR) and caused adverse somatic and psychiatric effects. All-oral, interferon-free regimens are now in widespread use, but many of the pivotal trials were industry sponsored and had strict enrollment criteria, potentially limiting their generalizability in community settings, the researchers reported (Gastroenterology 2015 April [doi:10.1053/j.gastro.2014.12.027]).Their open-label trial included 82 patients with HCV GT-1a infection and Child’s grade A cirrhosis recruited from two clinical practices in Atlanta. Thirty-two of the patients were treatment naive, while 50 had previously not responded to peginterferon and ribavirin treatment. Patients were randomized to either 12 weeks of all-oral simeprevir (150 mg/day) and sofosbuvir (400 mg/day), or peginterferon alfa 2b (1.5 mcg/kg per week), ribavirin (1000-1200 mg/day), and sofosbuvir (400 mg/day).Fully 54 of 58 (93%) patients given the simeprevir-sofosbuvir regimen had undetectable levels of HCV RNA at 12 weeks (SVR12), compared with 18 of 24 (75%) patients who received the interferon-containing regimen (P = .02), the researchers reported. Rates of SVR12 among prior nonresponders were 92% and 64%, and were 95% and 80% for treatment-naive patients, although P-values did not reach statistical significance. The interferon group also had a higher rate of virologic relapse than did patients given simeprevir and sofosbuvir (P = .009), and had worse self-reported outcomes and more side effects, the researchers said. Patients in both groups who achieved SVR12 had higher quality-of-life scores than those who did not. Notably, almost half of patients were African American, a group that has historically had lower cure rates compared with other racial groups, said the investigators.

“Given that several new regimens for genotype 1 infection, including the sofosbuvir-ledipasvir combination pill, already have been approved, we believe that this study is very timely,” Dr. Pearlman and his associates said. “Although these are not head-to-head comparisons, the 12-week simeprevir and sofosbuvir regimen in this trial may compare favorably with the SVR rates for 12 weeks of sofosbuvir/ledipasvir and 12 weeks of the regimen, paritaprevir/ritonavir, ombitasvir and dasabuvir plus ribavirin for patients with cirrhosis, particularly for prior nonresponders to older therapies, with the caveat that many more patients were studied in the registration trials.”While industry-sponsored trials have had psychiatric exclusion criteria, several patients in the open-label trial had serious psychiatric conditions, said the researchers. A patient with stable bipolar disorder received the interferon-containing regimen, and two patients with stable schizophrenia received the all-oral regimen. None reported worsening psychiatric symptoms on treatment.

Dr. Pearlman reported having contracted research for Johnson & Johnson, Gilead, Abbvie, Bristol-Myers Squibb, Boehringer Ingelheim, and Merck; and having served on speaker and advisory boards for Johnson & Johnson, Gilead, and Abbvie. He also was an investigator and author in the COSMOS trial of simeprevir and sofosbuvir in patients with HCV/HIV coinfection. The other authors reported no conflicts of interest.

Patients with compensated cirrhosis and chronic genotype 1 hepatitis C virus infections were significantly more likely to clear their infections and had fewer adverse effects when treated with simeprevir and sofosbuvir instead of peginterferon, ribavirin, and sofosbuvir, investigators reported in the April issue of Gastroenterology. “Patients given the interferon-containing regimen had a significantly greater rate of virologic relapse than patients given simeprevir and sofosbuvir ... and reported worse outcomes and more side effects,” said Dr. Brian L. Pearlman and his associates of Atlanta Medical Center and Emory University, Atlanta.

Liver disease associated with chronic hepatitis C virus (HCV) infection causes at least 350,000 deaths per year worldwide. Genotype 1 (GT-1) HCV is the most common HCV strain and the hardest to treat, especially when patients have cirrhosis. Treatments for chronic GT-1 HCV infections historically included interferon, but achieved only moderate rates of sustained virologic response (SVR) and caused adverse somatic and psychiatric effects. All-oral, interferon-free regimens are now in widespread use, but many of the pivotal trials were industry sponsored and had strict enrollment criteria, potentially limiting their generalizability in community settings, the researchers reported (Gastroenterology 2015 April [doi:10.1053/j.gastro.2014.12.027]).Their open-label trial included 82 patients with HCV GT-1a infection and Child’s grade A cirrhosis recruited from two clinical practices in Atlanta. Thirty-two of the patients were treatment naive, while 50 had previously not responded to peginterferon and ribavirin treatment. Patients were randomized to either 12 weeks of all-oral simeprevir (150 mg/day) and sofosbuvir (400 mg/day), or peginterferon alfa 2b (1.5 mcg/kg per week), ribavirin (1000-1200 mg/day), and sofosbuvir (400 mg/day).Fully 54 of 58 (93%) patients given the simeprevir-sofosbuvir regimen had undetectable levels of HCV RNA at 12 weeks (SVR12), compared with 18 of 24 (75%) patients who received the interferon-containing regimen (P = .02), the researchers reported. Rates of SVR12 among prior nonresponders were 92% and 64%, and were 95% and 80% for treatment-naive patients, although P-values did not reach statistical significance. The interferon group also had a higher rate of virologic relapse than did patients given simeprevir and sofosbuvir (P = .009), and had worse self-reported outcomes and more side effects, the researchers said. Patients in both groups who achieved SVR12 had higher quality-of-life scores than those who did not. Notably, almost half of patients were African American, a group that has historically had lower cure rates compared with other racial groups, said the investigators.

“Given that several new regimens for genotype 1 infection, including the sofosbuvir-ledipasvir combination pill, already have been approved, we believe that this study is very timely,” Dr. Pearlman and his associates said. “Although these are not head-to-head comparisons, the 12-week simeprevir and sofosbuvir regimen in this trial may compare favorably with the SVR rates for 12 weeks of sofosbuvir/ledipasvir and 12 weeks of the regimen, paritaprevir/ritonavir, ombitasvir and dasabuvir plus ribavirin for patients with cirrhosis, particularly for prior nonresponders to older therapies, with the caveat that many more patients were studied in the registration trials.”While industry-sponsored trials have had psychiatric exclusion criteria, several patients in the open-label trial had serious psychiatric conditions, said the researchers. A patient with stable bipolar disorder received the interferon-containing regimen, and two patients with stable schizophrenia received the all-oral regimen. None reported worsening psychiatric symptoms on treatment.

Dr. Pearlman reported having contracted research for Johnson & Johnson, Gilead, Abbvie, Bristol-Myers Squibb, Boehringer Ingelheim, and Merck; and having served on speaker and advisory boards for Johnson & Johnson, Gilead, and Abbvie. He also was an investigator and author in the COSMOS trial of simeprevir and sofosbuvir in patients with HCV/HIV coinfection. The other authors reported no conflicts of interest.

For individuals infected with hepatitis C virus (HCV), new regimens are highly effective, but also very expensive, at approximately $28,000 for 4 weeks of treatment. However, the treatment is cost effective for HCV patients with cirrhosis and for those without cirrhosis who have failed other treatments, according to a new study.

©Mathier/thinkstockphotos.com

In an analysis of the cost effectiveness of sofosbuvir-based treatments for patients with HCV genotypes 2 and 3, Dr. Benjamin Linas of Boston Medical Center reported that when compared with pegylated interferon and ribavirin therapy, treatment regimens based on the new direct-acting antiviral are only cost effective for select groups (Ann. Intern Med, [doi:10.7326/M15-0674]).

Cure rates with sofosbuvir are higher than are rates with the previous standard of care, and sustained virologic response (SVR) “is associated with a greatly reduced lifetime risk for liver-related morbidity and mortality,” noted Dr. Linas and his colleagues.

Using sophisticated statistical modeling to compare HCV treatment with pegylated interferon and ribavirin – the previous standard of care – to the newly Food and Drug Administration–approved sofosbuvir-ribavirin regimen, Dr. Linas explored clinical outcomes and costs for several different patient groups, including treatment-naive and treatment-experienced HCV genotype 2 and 3 patients with and without cirrhosis.

Clinical outcomes, modeled from clinical trial and observational cohort data, were expressed as life expectancy in quality-adjusted life-years (QALYs) and lifetime medical costs. Investigators then calculated the incremental cost-effectiveness ratio (ICER) for each treatment strategy, dividing any additional cost for a more expensive treatment by the QALYs gained from this regimen.

Using the commonly accepted ICER threshold of $100,000 per QALY, Dr. Linas and colleagues concluded that sofosbuvir-based HCV therapy for treatment-naive patients without cirrhosis was not cost effective, with ICERs of $238,000-$266,000. Interferon-based treatments, they noted, still achieve an approximately 80% rate of cure in this population.

In the constrained resources of the real world, Dr. Linas and his associates noted that this analysis is important. “Treatment strategies that do not use limited resources where they are likely to have the greatest impact may result in unequal access to interferon-free regimens, thereby limiting the population-level benefits of new HCV treatments,” they said.

For individuals infected with hepatitis C virus (HCV), new regimens are highly effective, but also very expensive, at approximately $28,000 for 4 weeks of treatment. However, the treatment is cost effective for HCV patients with cirrhosis and for those without cirrhosis who have failed other treatments, according to a new study.

©Mathier/thinkstockphotos.com

In an analysis of the cost effectiveness of sofosbuvir-based treatments for patients with HCV genotypes 2 and 3, Dr. Benjamin Linas of Boston Medical Center reported that when compared with pegylated interferon and ribavirin therapy, treatment regimens based on the new direct-acting antiviral are only cost effective for select groups (Ann. Intern Med, [doi:10.7326/M15-0674]).

Cure rates with sofosbuvir are higher than are rates with the previous standard of care, and sustained virologic response (SVR) “is associated with a greatly reduced lifetime risk for liver-related morbidity and mortality,” noted Dr. Linas and his colleagues.

Using sophisticated statistical modeling to compare HCV treatment with pegylated interferon and ribavirin – the previous standard of care – to the newly Food and Drug Administration–approved sofosbuvir-ribavirin regimen, Dr. Linas explored clinical outcomes and costs for several different patient groups, including treatment-naive and treatment-experienced HCV genotype 2 and 3 patients with and without cirrhosis.

Clinical outcomes, modeled from clinical trial and observational cohort data, were expressed as life expectancy in quality-adjusted life-years (QALYs) and lifetime medical costs. Investigators then calculated the incremental cost-effectiveness ratio (ICER) for each treatment strategy, dividing any additional cost for a more expensive treatment by the QALYs gained from this regimen.

Using the commonly accepted ICER threshold of $100,000 per QALY, Dr. Linas and colleagues concluded that sofosbuvir-based HCV therapy for treatment-naive patients without cirrhosis was not cost effective, with ICERs of $238,000-$266,000. Interferon-based treatments, they noted, still achieve an approximately 80% rate of cure in this population.

In the constrained resources of the real world, Dr. Linas and his associates noted that this analysis is important. “Treatment strategies that do not use limited resources where they are likely to have the greatest impact may result in unequal access to interferon-free regimens, thereby limiting the population-level benefits of new HCV treatments,” they said.

For individuals infected with hepatitis C virus (HCV), new regimens are highly effective, but also very expensive, at approximately $28,000 for 4 weeks of treatment. However, the treatment is cost effective for HCV patients with cirrhosis and for those without cirrhosis who have failed other treatments, according to a new study.

©Mathier/thinkstockphotos.com

In an analysis of the cost effectiveness of sofosbuvir-based treatments for patients with HCV genotypes 2 and 3, Dr. Benjamin Linas of Boston Medical Center reported that when compared with pegylated interferon and ribavirin therapy, treatment regimens based on the new direct-acting antiviral are only cost effective for select groups (Ann. Intern Med, [doi:10.7326/M15-0674]).

Cure rates with sofosbuvir are higher than are rates with the previous standard of care, and sustained virologic response (SVR) “is associated with a greatly reduced lifetime risk for liver-related morbidity and mortality,” noted Dr. Linas and his colleagues.

Using sophisticated statistical modeling to compare HCV treatment with pegylated interferon and ribavirin – the previous standard of care – to the newly Food and Drug Administration–approved sofosbuvir-ribavirin regimen, Dr. Linas explored clinical outcomes and costs for several different patient groups, including treatment-naive and treatment-experienced HCV genotype 2 and 3 patients with and without cirrhosis.

Clinical outcomes, modeled from clinical trial and observational cohort data, were expressed as life expectancy in quality-adjusted life-years (QALYs) and lifetime medical costs. Investigators then calculated the incremental cost-effectiveness ratio (ICER) for each treatment strategy, dividing any additional cost for a more expensive treatment by the QALYs gained from this regimen.

Using the commonly accepted ICER threshold of $100,000 per QALY, Dr. Linas and colleagues concluded that sofosbuvir-based HCV therapy for treatment-naive patients without cirrhosis was not cost effective, with ICERs of $238,000-$266,000. Interferon-based treatments, they noted, still achieve an approximately 80% rate of cure in this population.

In the constrained resources of the real world, Dr. Linas and his associates noted that this analysis is important. “Treatment strategies that do not use limited resources where they are likely to have the greatest impact may result in unequal access to interferon-free regimens, thereby limiting the population-level benefits of new HCV treatments,” they said.

Taking the antiarrythmic drug amiodarone with the hepatitis C antiviral drugs ledipasvir and sofosbuvir, or with sofosbuvir plus another direct-acting antiviral drug, has been associated with cases of symptomatic bradycardia – including a fatal cardiac arrest – according to the Food and Drug Administration.

Because of the reports, the antiviral drugs’ labels now recommend against using amiodarone with those hepatitis C drugs.

An FDA statement issued March 24 described the bradycardia cases as “serious and life-threatening.” Gilead Sciences markets the ledipasvir and sofosbuvir combination as Harvoni and markets sofosbuvir as Sovaldi to treat chronic hepatitis C virus (HCV) infection.

Gilead issued a “Dear Health Care Provider” letter that provides further details of the cases. There have been nine postmarketing reports of symptomatic bradycardia in patients who were taking amiodarone with Harvoni; amiodarone with Sovaldi plus another hepatitis C antiviral drug, simeprevir (Olysio); or amiodarone with an investigational hepatitis C antiviral drug, daclatasvir.

Of those cases, six occurred with in the first 24 hours of starting treatment with the antivirals, and three cases occurred within the first 2-12 days after antiviral therapy was started. A pacemaker was needed in three cases, and one case was a fatal cardiac arrest.

In three cases, a “rechallenge with HCV treatment in the setting of continued amiodarone therapy resulted in recurrence of symptomatic bradycardia,” according to the Gilead letter.

The effect of coadministration on the blood levels of the antiviral drugs is not known, nor is the mechanism behind the cardiac effect.

The labeling of the fixed-dose combination of ledipasvir and sofosbuvir (Harvoni) now includes a section on “serious symptomatic bradycardia” when coadministered with amiodarone, and says that coadministration is not recommended. The label adds that if a patient on amiodarone or Harvoni has no other alternative than to take that combination, patients should be counseled about the bradycardia risk.

Cardiac monitoring is recommended for inpatients during the first 48 hours the patient is taking the drugs, “after which outpatient or self-monitoring of the heart rate should occur on a daily basis through at least the first 2 weeks of treatment.”

The label notes that amiodarone has a long half-life, so cardiac monitoring is still necessary if the patient discontinues amiodarone just before starting treatment with Harvoni. Similar labeling changes have been made to the Sovaldi label.

Adverse events associated with Harvoni or Sovaldi should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/Safety/MedWatch/.

emechcatie@frontlinemedcom.com

Taking the antiarrythmic drug amiodarone with the hepatitis C antiviral drugs ledipasvir and sofosbuvir, or with sofosbuvir plus another direct-acting antiviral drug, has been associated with cases of symptomatic bradycardia – including a fatal cardiac arrest – according to the Food and Drug Administration.

Because of the reports, the antiviral drugs’ labels now recommend against using amiodarone with those hepatitis C drugs.

An FDA statement issued March 24 described the bradycardia cases as “serious and life-threatening.” Gilead Sciences markets the ledipasvir and sofosbuvir combination as Harvoni and markets sofosbuvir as Sovaldi to treat chronic hepatitis C virus (HCV) infection.

Gilead issued a “Dear Health Care Provider” letter that provides further details of the cases. There have been nine postmarketing reports of symptomatic bradycardia in patients who were taking amiodarone with Harvoni; amiodarone with Sovaldi plus another hepatitis C antiviral drug, simeprevir (Olysio); or amiodarone with an investigational hepatitis C antiviral drug, daclatasvir.

Of those cases, six occurred with in the first 24 hours of starting treatment with the antivirals, and three cases occurred within the first 2-12 days after antiviral therapy was started. A pacemaker was needed in three cases, and one case was a fatal cardiac arrest.

In three cases, a “rechallenge with HCV treatment in the setting of continued amiodarone therapy resulted in recurrence of symptomatic bradycardia,” according to the Gilead letter.

The effect of coadministration on the blood levels of the antiviral drugs is not known, nor is the mechanism behind the cardiac effect.

The labeling of the fixed-dose combination of ledipasvir and sofosbuvir (Harvoni) now includes a section on “serious symptomatic bradycardia” when coadministered with amiodarone, and says that coadministration is not recommended. The label adds that if a patient on amiodarone or Harvoni has no other alternative than to take that combination, patients should be counseled about the bradycardia risk.

Cardiac monitoring is recommended for inpatients during the first 48 hours the patient is taking the drugs, “after which outpatient or self-monitoring of the heart rate should occur on a daily basis through at least the first 2 weeks of treatment.”

The label notes that amiodarone has a long half-life, so cardiac monitoring is still necessary if the patient discontinues amiodarone just before starting treatment with Harvoni. Similar labeling changes have been made to the Sovaldi label.

Adverse events associated with Harvoni or Sovaldi should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/Safety/MedWatch/.

emechcatie@frontlinemedcom.com

Taking the antiarrythmic drug amiodarone with the hepatitis C antiviral drugs ledipasvir and sofosbuvir, or with sofosbuvir plus another direct-acting antiviral drug, has been associated with cases of symptomatic bradycardia – including a fatal cardiac arrest – according to the Food and Drug Administration.

Because of the reports, the antiviral drugs’ labels now recommend against using amiodarone with those hepatitis C drugs.

An FDA statement issued March 24 described the bradycardia cases as “serious and life-threatening.” Gilead Sciences markets the ledipasvir and sofosbuvir combination as Harvoni and markets sofosbuvir as Sovaldi to treat chronic hepatitis C virus (HCV) infection.

Gilead issued a “Dear Health Care Provider” letter that provides further details of the cases. There have been nine postmarketing reports of symptomatic bradycardia in patients who were taking amiodarone with Harvoni; amiodarone with Sovaldi plus another hepatitis C antiviral drug, simeprevir (Olysio); or amiodarone with an investigational hepatitis C antiviral drug, daclatasvir.

Of those cases, six occurred with in the first 24 hours of starting treatment with the antivirals, and three cases occurred within the first 2-12 days after antiviral therapy was started. A pacemaker was needed in three cases, and one case was a fatal cardiac arrest.

In three cases, a “rechallenge with HCV treatment in the setting of continued amiodarone therapy resulted in recurrence of symptomatic bradycardia,” according to the Gilead letter.

The effect of coadministration on the blood levels of the antiviral drugs is not known, nor is the mechanism behind the cardiac effect.

The labeling of the fixed-dose combination of ledipasvir and sofosbuvir (Harvoni) now includes a section on “serious symptomatic bradycardia” when coadministered with amiodarone, and says that coadministration is not recommended. The label adds that if a patient on amiodarone or Harvoni has no other alternative than to take that combination, patients should be counseled about the bradycardia risk.

Cardiac monitoring is recommended for inpatients during the first 48 hours the patient is taking the drugs, “after which outpatient or self-monitoring of the heart rate should occur on a daily basis through at least the first 2 weeks of treatment.”

The label notes that amiodarone has a long half-life, so cardiac monitoring is still necessary if the patient discontinues amiodarone just before starting treatment with Harvoni. Similar labeling changes have been made to the Sovaldi label.

Adverse events associated with Harvoni or Sovaldi should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/Safety/MedWatch/.

emechcatie@frontlinemedcom.com

Two different statistical models found that novel therapies for chronic HCV infection, particularly the combination of sofosbuvir and ledipasvir, are cost effective in most patients, according to separate reports published online March 17 in Annals of Internal Medicine.

However, both groups of researchers cautioned that if these expensive agents are made available to the millions of eligible patients across the country, it would have an immense impact on health care costs for both public and private payers.

Courtesy NIH

The novel therapies, which typically contain sofosbuvir in combination with ledipasvir, simeprevir, or daclatasvir, substantially reduce the length of treatment, achieve much higher rates of sustained viral response (SVR), and offer interferon-free alternatives for patients who can’t tolerate or don’t respond to standard interferon-based treatments. But it is unclear whether these benefits justify their profound expense, compared with current care. Both statistical models were developed to examine this issue, but from different perspectives.

In one study, funded primarily by the National Institutes of Health, investigators constructed a model that simulated 120 possible clinical courses of HCV-infected adults based on different ages and sexes, treatment histories, HCV genotypes, fibrosis scores, and interferon tolerances. For each of these patient profiles, they ran simulations in which patients received either “the old standard of care” (peginterferon and ribavirin, either with or without boceprevir and telaprevir) or sofosbuvir plus ledipasvir.

The average per-patient cost of standard care ranged from $15,000 to $71,000, depending on the patient profile, while that of sofosbuvir-ledipasvir ranged from $66,000 to $154,000, said Jagpreet Chhatwal, Ph.D., of the University of Texas MD Anderson Cancer Center, Houston, and his associates.

Compared with standard care, treating 10,000 patients with sofosbuvir-ledipasvir was projected to prevent 600 cases of decompensated cirrhosis, 310 cases of hepatocellular carcinoma (HCC), 60 liver transplantations, and 550 liver-related deaths, which would result in substantial cost savings. Also, compared with standard care, the incremental cost-effectiveness ratio of sofosbuvir-ledipasvir was $55,400 per additional quality-of-life-year (QALY) gained, which falls well within the accepted range for therapies for other medical conditions. Thus, the new therapy proved to be cost-effective for most HCV patients (Ann. Intern. Med. 2015 March 17 [doi:10.7326/M14-1336]). But there was an important caveat: Many more patients would be eligible for the novel therapies than for the standard care, because the novel therapies are much more easily tolerated. With the addition of so many eligible patients, the resources needed to treat them “could be immense and unsustainable.” Compared with standard care, giving these novel HCV therapies to all eligible patients “would cost an additional $65 billion in the next 5 years,” which would not be counterbalanced by the estimated $16 billion saved by preventing cirrhosis, HCC, and transplantations.

Therefore, “despite the cost-effectiveness of [novel] HCV treatments, our analysis shows that it is unaffordable at the current price,” Dr. Chhatwal and his associates said.

In the other study, funded primarily by CVS Health, researchers developed a discrete-event simulation model of the natural history and progression of liver disease in treatment-naive patients, categorized by whether they were infected with HCV genotype 1, 2, or 3. Several possible treatment regimens were considered for each genotype, and the SVR rates they were projected to attain were derived from those reported in clinical trials, said Mehdi Najafzadeh, Ph.D., of the division of pharmacoepidemiology and pharmacoeconomics, Brigham and Women’s Hospital and Harvard Medical School, Boston, and his associates.

“From a societal perspective, the newly approved PEG-free regimen of sofosbuvir-ledipasvir for 12 weeks could be very cost-effective relative to usual care (costing $12,825/QALY gained) for patients with HCV genotype 1.” This treatment proved to be the optimal strategy in the greatest number of simulations involving genotype 1.

Similarly, for genotype 3 the combination of sofosbuvir plus ledipasvir plus ribavirin for 12 weeks cost $73,000/QALY gained, compared with usual care. This also represents “relatively good value.” However, for genotype 2 the most cost-effective novel therapy, sofosbuvir-ribavirin, was $110,168/QALY gained, which is not considered cost-effective, Dr. Najafzadeh and his associates said (Ann. Intern. Med. 2015 March 17 [doi:10.7326;M14-1152]). Again, an important caveat to these findings was that, at their current prices, the cost of these drugs were not outweighed by the savings that accrued from preventing the complications of HCV. And “regardless of the cost-effectiveness of novel HCV treatments, there is considerable concern that their very high prices could substantially increase short-term overall drug spending for many public and private payers,” the investigators noted.

However, the fact that these regimens don’t reduce health care costs “is an exceptionally high bar” to hold them to – one that “is generally not expected when evaluating whether a new strategy represents good value for the money,” they added.

ginews@gastro.org

Two different statistical models found that novel therapies for chronic HCV infection, particularly the combination of sofosbuvir and ledipasvir, are cost effective in most patients, according to separate reports published online March 17 in Annals of Internal Medicine.

However, both groups of researchers cautioned that if these expensive agents are made available to the millions of eligible patients across the country, it would have an immense impact on health care costs for both public and private payers.

Courtesy NIH

The novel therapies, which typically contain sofosbuvir in combination with ledipasvir, simeprevir, or daclatasvir, substantially reduce the length of treatment, achieve much higher rates of sustained viral response (SVR), and offer interferon-free alternatives for patients who can’t tolerate or don’t respond to standard interferon-based treatments. But it is unclear whether these benefits justify their profound expense, compared with current care. Both statistical models were developed to examine this issue, but from different perspectives.

In one study, funded primarily by the National Institutes of Health, investigators constructed a model that simulated 120 possible clinical courses of HCV-infected adults based on different ages and sexes, treatment histories, HCV genotypes, fibrosis scores, and interferon tolerances. For each of these patient profiles, they ran simulations in which patients received either “the old standard of care” (peginterferon and ribavirin, either with or without boceprevir and telaprevir) or sofosbuvir plus ledipasvir.

The average per-patient cost of standard care ranged from $15,000 to $71,000, depending on the patient profile, while that of sofosbuvir-ledipasvir ranged from $66,000 to $154,000, said Jagpreet Chhatwal, Ph.D., of the University of Texas MD Anderson Cancer Center, Houston, and his associates.

Compared with standard care, treating 10,000 patients with sofosbuvir-ledipasvir was projected to prevent 600 cases of decompensated cirrhosis, 310 cases of hepatocellular carcinoma (HCC), 60 liver transplantations, and 550 liver-related deaths, which would result in substantial cost savings. Also, compared with standard care, the incremental cost-effectiveness ratio of sofosbuvir-ledipasvir was $55,400 per additional quality-of-life-year (QALY) gained, which falls well within the accepted range for therapies for other medical conditions. Thus, the new therapy proved to be cost-effective for most HCV patients (Ann. Intern. Med. 2015 March 17 [doi:10.7326/M14-1336]). But there was an important caveat: Many more patients would be eligible for the novel therapies than for the standard care, because the novel therapies are much more easily tolerated. With the addition of so many eligible patients, the resources needed to treat them “could be immense and unsustainable.” Compared with standard care, giving these novel HCV therapies to all eligible patients “would cost an additional $65 billion in the next 5 years,” which would not be counterbalanced by the estimated $16 billion saved by preventing cirrhosis, HCC, and transplantations.

Therefore, “despite the cost-effectiveness of [novel] HCV treatments, our analysis shows that it is unaffordable at the current price,” Dr. Chhatwal and his associates said.

In the other study, funded primarily by CVS Health, researchers developed a discrete-event simulation model of the natural history and progression of liver disease in treatment-naive patients, categorized by whether they were infected with HCV genotype 1, 2, or 3. Several possible treatment regimens were considered for each genotype, and the SVR rates they were projected to attain were derived from those reported in clinical trials, said Mehdi Najafzadeh, Ph.D., of the division of pharmacoepidemiology and pharmacoeconomics, Brigham and Women’s Hospital and Harvard Medical School, Boston, and his associates.

“From a societal perspective, the newly approved PEG-free regimen of sofosbuvir-ledipasvir for 12 weeks could be very cost-effective relative to usual care (costing $12,825/QALY gained) for patients with HCV genotype 1.” This treatment proved to be the optimal strategy in the greatest number of simulations involving genotype 1.

Similarly, for genotype 3 the combination of sofosbuvir plus ledipasvir plus ribavirin for 12 weeks cost $73,000/QALY gained, compared with usual care. This also represents “relatively good value.” However, for genotype 2 the most cost-effective novel therapy, sofosbuvir-ribavirin, was $110,168/QALY gained, which is not considered cost-effective, Dr. Najafzadeh and his associates said (Ann. Intern. Med. 2015 March 17 [doi:10.7326;M14-1152]). Again, an important caveat to these findings was that, at their current prices, the cost of these drugs were not outweighed by the savings that accrued from preventing the complications of HCV. And “regardless of the cost-effectiveness of novel HCV treatments, there is considerable concern that their very high prices could substantially increase short-term overall drug spending for many public and private payers,” the investigators noted.

However, the fact that these regimens don’t reduce health care costs “is an exceptionally high bar” to hold them to – one that “is generally not expected when evaluating whether a new strategy represents good value for the money,” they added.

ginews@gastro.org

Two different statistical models found that novel therapies for chronic HCV infection, particularly the combination of sofosbuvir and ledipasvir, are cost effective in most patients, according to separate reports published online March 17 in Annals of Internal Medicine.

However, both groups of researchers cautioned that if these expensive agents are made available to the millions of eligible patients across the country, it would have an immense impact on health care costs for both public and private payers.

Courtesy NIH

The novel therapies, which typically contain sofosbuvir in combination with ledipasvir, simeprevir, or daclatasvir, substantially reduce the length of treatment, achieve much higher rates of sustained viral response (SVR), and offer interferon-free alternatives for patients who can’t tolerate or don’t respond to standard interferon-based treatments. But it is unclear whether these benefits justify their profound expense, compared with current care. Both statistical models were developed to examine this issue, but from different perspectives.

In one study, funded primarily by the National Institutes of Health, investigators constructed a model that simulated 120 possible clinical courses of HCV-infected adults based on different ages and sexes, treatment histories, HCV genotypes, fibrosis scores, and interferon tolerances. For each of these patient profiles, they ran simulations in which patients received either “the old standard of care” (peginterferon and ribavirin, either with or without boceprevir and telaprevir) or sofosbuvir plus ledipasvir.

The average per-patient cost of standard care ranged from $15,000 to $71,000, depending on the patient profile, while that of sofosbuvir-ledipasvir ranged from $66,000 to $154,000, said Jagpreet Chhatwal, Ph.D., of the University of Texas MD Anderson Cancer Center, Houston, and his associates.

Compared with standard care, treating 10,000 patients with sofosbuvir-ledipasvir was projected to prevent 600 cases of decompensated cirrhosis, 310 cases of hepatocellular carcinoma (HCC), 60 liver transplantations, and 550 liver-related deaths, which would result in substantial cost savings. Also, compared with standard care, the incremental cost-effectiveness ratio of sofosbuvir-ledipasvir was $55,400 per additional quality-of-life-year (QALY) gained, which falls well within the accepted range for therapies for other medical conditions. Thus, the new therapy proved to be cost-effective for most HCV patients (Ann. Intern. Med. 2015 March 17 [doi:10.7326/M14-1336]). But there was an important caveat: Many more patients would be eligible for the novel therapies than for the standard care, because the novel therapies are much more easily tolerated. With the addition of so many eligible patients, the resources needed to treat them “could be immense and unsustainable.” Compared with standard care, giving these novel HCV therapies to all eligible patients “would cost an additional $65 billion in the next 5 years,” which would not be counterbalanced by the estimated $16 billion saved by preventing cirrhosis, HCC, and transplantations.

Therefore, “despite the cost-effectiveness of [novel] HCV treatments, our analysis shows that it is unaffordable at the current price,” Dr. Chhatwal and his associates said.

In the other study, funded primarily by CVS Health, researchers developed a discrete-event simulation model of the natural history and progression of liver disease in treatment-naive patients, categorized by whether they were infected with HCV genotype 1, 2, or 3. Several possible treatment regimens were considered for each genotype, and the SVR rates they were projected to attain were derived from those reported in clinical trials, said Mehdi Najafzadeh, Ph.D., of the division of pharmacoepidemiology and pharmacoeconomics, Brigham and Women’s Hospital and Harvard Medical School, Boston, and his associates.

“From a societal perspective, the newly approved PEG-free regimen of sofosbuvir-ledipasvir for 12 weeks could be very cost-effective relative to usual care (costing $12,825/QALY gained) for patients with HCV genotype 1.” This treatment proved to be the optimal strategy in the greatest number of simulations involving genotype 1.

Similarly, for genotype 3 the combination of sofosbuvir plus ledipasvir plus ribavirin for 12 weeks cost $73,000/QALY gained, compared with usual care. This also represents “relatively good value.” However, for genotype 2 the most cost-effective novel therapy, sofosbuvir-ribavirin, was $110,168/QALY gained, which is not considered cost-effective, Dr. Najafzadeh and his associates said (Ann. Intern. Med. 2015 March 17 [doi:10.7326;M14-1152]). Again, an important caveat to these findings was that, at their current prices, the cost of these drugs were not outweighed by the savings that accrued from preventing the complications of HCV. And “regardless of the cost-effectiveness of novel HCV treatments, there is considerable concern that their very high prices could substantially increase short-term overall drug spending for many public and private payers,” the investigators noted.

However, the fact that these regimens don’t reduce health care costs “is an exceptionally high bar” to hold them to – one that “is generally not expected when evaluating whether a new strategy represents good value for the money,” they added.

ginews@gastro.org

The new ASCEND trial will examine whether primary care physicians can use a new antiviral therapy to treat hepatitis C virus as effectively as specialists do, according to a press release from the National Institutes of Health.

While past treatments for HCV were long-term, complex, and generally required a specialist physician, new drug developments may not require such in-depth treatment and could be handled by a primary care physician. The ASCEND study will involve 600 patients in the Washington, D.C. area, with 350 patients continuing their normal treatment with a specialist, and 250 patients receiving their treatment at a primary care location. Both groups will receive the same medication.

“The recent advent of direct-acting antiviral medications has offered promising new treatment options for people who are chronically infected with hepatitis C,” Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Disease, said. “The ASCEND study will help determine whether these medications are similarly effective when administered in an urban, community-based setting.”

Find the full press release on the NIH website.

The new ASCEND trial will examine whether primary care physicians can use a new antiviral therapy to treat hepatitis C virus as effectively as specialists do, according to a press release from the National Institutes of Health.

While past treatments for HCV were long-term, complex, and generally required a specialist physician, new drug developments may not require such in-depth treatment and could be handled by a primary care physician. The ASCEND study will involve 600 patients in the Washington, D.C. area, with 350 patients continuing their normal treatment with a specialist, and 250 patients receiving their treatment at a primary care location. Both groups will receive the same medication.

“The recent advent of direct-acting antiviral medications has offered promising new treatment options for people who are chronically infected with hepatitis C,” Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Disease, said. “The ASCEND study will help determine whether these medications are similarly effective when administered in an urban, community-based setting.”

Find the full press release on the NIH website.

The new ASCEND trial will examine whether primary care physicians can use a new antiviral therapy to treat hepatitis C virus as effectively as specialists do, according to a press release from the National Institutes of Health.

While past treatments for HCV were long-term, complex, and generally required a specialist physician, new drug developments may not require such in-depth treatment and could be handled by a primary care physician. The ASCEND study will involve 600 patients in the Washington, D.C. area, with 350 patients continuing their normal treatment with a specialist, and 250 patients receiving their treatment at a primary care location. Both groups will receive the same medication.

“The recent advent of direct-acting antiviral medications has offered promising new treatment options for people who are chronically infected with hepatitis C,” Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Disease, said. “The ASCEND study will help determine whether these medications are similarly effective when administered in an urban, community-based setting.”

Find the full press release on the NIH website.

Hospitals should carefully monitor equipment for hepatitis C virus contamination and the possibility of health care transmission, according to a Feb. 27 report from the Centers for Disease Control and Prevention.

Jezperklauzen/ThinkStock.com

The CDC report focuses on two specific cases of health care–transmitted HCV. In 2010, a patient without HCV in a New Jersey hospital was treated by an anesthesiologist who had immediately beforehand treated someone with HCV. Despite the single commonality between the two patients, patient A contracted HCV.

In 2011, a patient in Wisconsin with a history of diabetes and chronic renal disease was diagnosed with HCV-4, a subtype of the disease that is rare in that part of the world. The infection occurred in 2009, when this patient had a kidney transplant at the same time as a patient with HCV-4 also was having a kidney transplant. The two transplants shared a surgeon, but the source of infection was likely a perfusion machine where an HCV-positive kidney and an HCV-negative kidney were both stored without cleaning the machine.

“These cases illustrate the importance of partnerships and communication between public health and health care professionals to ensure that basic infection control and injection safety practices are optimized wherever health care is delivered,” the CDC investigators concluded.

Read the full report in the MMWR (2015;64:165-70).

Hospitals should carefully monitor equipment for hepatitis C virus contamination and the possibility of health care transmission, according to a Feb. 27 report from the Centers for Disease Control and Prevention.

Jezperklauzen/ThinkStock.com

The CDC report focuses on two specific cases of health care–transmitted HCV. In 2010, a patient without HCV in a New Jersey hospital was treated by an anesthesiologist who had immediately beforehand treated someone with HCV. Despite the single commonality between the two patients, patient A contracted HCV.

In 2011, a patient in Wisconsin with a history of diabetes and chronic renal disease was diagnosed with HCV-4, a subtype of the disease that is rare in that part of the world. The infection occurred in 2009, when this patient had a kidney transplant at the same time as a patient with HCV-4 also was having a kidney transplant. The two transplants shared a surgeon, but the source of infection was likely a perfusion machine where an HCV-positive kidney and an HCV-negative kidney were both stored without cleaning the machine.

“These cases illustrate the importance of partnerships and communication between public health and health care professionals to ensure that basic infection control and injection safety practices are optimized wherever health care is delivered,” the CDC investigators concluded.

Read the full report in the MMWR (2015;64:165-70).

Hospitals should carefully monitor equipment for hepatitis C virus contamination and the possibility of health care transmission, according to a Feb. 27 report from the Centers for Disease Control and Prevention.

Jezperklauzen/ThinkStock.com

The CDC report focuses on two specific cases of health care–transmitted HCV. In 2010, a patient without HCV in a New Jersey hospital was treated by an anesthesiologist who had immediately beforehand treated someone with HCV. Despite the single commonality between the two patients, patient A contracted HCV.

In 2011, a patient in Wisconsin with a history of diabetes and chronic renal disease was diagnosed with HCV-4, a subtype of the disease that is rare in that part of the world. The infection occurred in 2009, when this patient had a kidney transplant at the same time as a patient with HCV-4 also was having a kidney transplant. The two transplants shared a surgeon, but the source of infection was likely a perfusion machine where an HCV-positive kidney and an HCV-negative kidney were both stored without cleaning the machine.

“These cases illustrate the importance of partnerships and communication between public health and health care professionals to ensure that basic infection control and injection safety practices are optimized wherever health care is delivered,” the CDC investigators concluded.

Read the full report in the MMWR (2015;64:165-70).

Death rates for liver cancer have been rising for some time among both men and women, while rates of colon and rectal cancer continue to decline from historic highs in the 1940s, the American Cancer Society reported.

In 2011, the death rate for liver cancer was 10/100,000 population (age-adjusted to the 2000 U.S. standard population) for men and 4.7/100,000 for women. The death rate for men reached its all-time low in 1980, when it was 5.8; for women, the low was 4.1 in 1987-1988. From 2007 to 2011, the overall death rate rose by 2.5% per year, according to the ACS.

“Screening for liver cancer has not been shown to reduce mortality,” the report said. “Nonetheless, many doctors in the U.S. screen individuals at high risk for the disease (e.g., those with cirrhosis) with ultrasound or blood tests.”

Death rates for colorectal cancer went the opposite way over that recent 4-year period – dropping by 2.5% a year overall from 2007 to 2011. The longer-term trend has seen rates for women declining since reaching a high of 35.2/100,000 in 1947, while the rate for men has been dropping since 1980, when it was 34.2. In 2011, the death rates for colorectal cancer were 13.1 in women and 18.5 in men, the ACS reported.

“This trend reflects declining incidence rates and improvements in early detection and treatment,” the ACS said in its report, which used data from the National Center for Health Statistics.

rfranki@frontlinemedcom.com

Death rates for liver cancer have been rising for some time among both men and women, while rates of colon and rectal cancer continue to decline from historic highs in the 1940s, the American Cancer Society reported.

In 2011, the death rate for liver cancer was 10/100,000 population (age-adjusted to the 2000 U.S. standard population) for men and 4.7/100,000 for women. The death rate for men reached its all-time low in 1980, when it was 5.8; for women, the low was 4.1 in 1987-1988. From 2007 to 2011, the overall death rate rose by 2.5% per year, according to the ACS.

“Screening for liver cancer has not been shown to reduce mortality,” the report said. “Nonetheless, many doctors in the U.S. screen individuals at high risk for the disease (e.g., those with cirrhosis) with ultrasound or blood tests.”

Death rates for colorectal cancer went the opposite way over that recent 4-year period – dropping by 2.5% a year overall from 2007 to 2011. The longer-term trend has seen rates for women declining since reaching a high of 35.2/100,000 in 1947, while the rate for men has been dropping since 1980, when it was 34.2. In 2011, the death rates for colorectal cancer were 13.1 in women and 18.5 in men, the ACS reported.

“This trend reflects declining incidence rates and improvements in early detection and treatment,” the ACS said in its report, which used data from the National Center for Health Statistics.

rfranki@frontlinemedcom.com

Death rates for liver cancer have been rising for some time among both men and women, while rates of colon and rectal cancer continue to decline from historic highs in the 1940s, the American Cancer Society reported.

In 2011, the death rate for liver cancer was 10/100,000 population (age-adjusted to the 2000 U.S. standard population) for men and 4.7/100,000 for women. The death rate for men reached its all-time low in 1980, when it was 5.8; for women, the low was 4.1 in 1987-1988. From 2007 to 2011, the overall death rate rose by 2.5% per year, according to the ACS.

“Screening for liver cancer has not been shown to reduce mortality,” the report said. “Nonetheless, many doctors in the U.S. screen individuals at high risk for the disease (e.g., those with cirrhosis) with ultrasound or blood tests.”

Death rates for colorectal cancer went the opposite way over that recent 4-year period – dropping by 2.5% a year overall from 2007 to 2011. The longer-term trend has seen rates for women declining since reaching a high of 35.2/100,000 in 1947, while the rate for men has been dropping since 1980, when it was 34.2. In 2011, the death rates for colorectal cancer were 13.1 in women and 18.5 in men, the ACS reported.

“This trend reflects declining incidence rates and improvements in early detection and treatment,” the ACS said in its report, which used data from the National Center for Health Statistics.

rfranki@frontlinemedcom.com

Patients coinfected with HIV and hepatitis C genotype 1 show high response rates to a three-drug regimen of ombitasvir, paritaprevir codosed with ritonavir, and dasabuvir, plus ribavirin, according to an open-label, uncontrolled pilot study published in JAMA.

Among the 63 patients – who were either HCV treatment-naive or had previously experienced treatment failure with peginteferon plus ribavirin – treated with the all-oral ombitasvir, paritaprevir codosed with ritonavir, and dasabuvir (known as 3D) plus ribavirin regimen, 94% of those treated for 12 weeks and 91% of those treated for 24 weeks achieved a sustained virologic response 12 weeks (SVR12) after treatment.

There were no confirmed HIV breakthroughs or serious adverse events – even though the study group included some patients with compensated cirrhosis – although around half of patients experienced treatment-related fatigue, 19% experienced insomnia, 18% experienced nausea, and 16% experienced headache (JAMA 2015 Feb. 23 [doi:10.1001/jama.2015.1328]).

“The efficacy and safety of the 3D-plus-ribavirin regimen for patients co-infected with HCV/HIV-1 need to be further investigated in larger studies; however, response rates reported here are similar to those in studies of HCV-monoinfected patients, which suggest that difficult-to-cure patients, such as prior [pegylated interferon] null responders with cirrhosis and HCV genotype 1a, may benefit from longer treatment duration,” wrote Dr. Mark S. Sulkowski, director of the viral hepatitis center and professor of medicine at Johns Hopkins University, Baltimore, and his colleagues.

In another study, researchers found that a 12-week course of a fixed-dose combination of ledipasvir and sofosbuvir in treatment-naive patients with hepatitis C genotype 1 and HIV coinfection achieved sustained virologic response rates of 98% at 12 weeks after treatment.

The open-label, phase 2b study in 50 patients recorded one case of relapse at week 4, which may have been linked to resistance-associated mutation, but no discontinuations or serious adverse events attributable to the study drug (JAMA 2015 Feb. 23 [doi:10.1001/jama.2015.1373]).

The study excluded individuals with cirrhosis, but many participants had poor prognostic factors, including African American race, male sex, IL28B non-CC genotype, and genotype 1a infection.

“These results show for the first time, to our knowledge, that an interferon- and ribavirin-free therapy is associated with high SVR rates in patients co-infected with HCV and HIV,” wrote Dr. Anu Osinusi of the University of Maryland, Baltimore, and her colleagues.

Dr. Sulkowski’s study was funded by AbbVie. Some of his coauthors declared a range of funding and consultancies from pharmaceutical companies including AbbVie and several coauthors are employees of AbbVie.

Dr. Osinusi’s study was funded by the National Institutes of Health, the German Research Foundation, and Gilead Sciences. Four coauthors reported speaking engagements, consultancies, fees, grants, stocks and other support from pharmaceutical companies including Gilead.

Patients coinfected with HIV and hepatitis C genotype 1 show high response rates to a three-drug regimen of ombitasvir, paritaprevir codosed with ritonavir, and dasabuvir, plus ribavirin, according to an open-label, uncontrolled pilot study published in JAMA.

Among the 63 patients – who were either HCV treatment-naive or had previously experienced treatment failure with peginteferon plus ribavirin – treated with the all-oral ombitasvir, paritaprevir codosed with ritonavir, and dasabuvir (known as 3D) plus ribavirin regimen, 94% of those treated for 12 weeks and 91% of those treated for 24 weeks achieved a sustained virologic response 12 weeks (SVR12) after treatment.

There were no confirmed HIV breakthroughs or serious adverse events – even though the study group included some patients with compensated cirrhosis – although around half of patients experienced treatment-related fatigue, 19% experienced insomnia, 18% experienced nausea, and 16% experienced headache (JAMA 2015 Feb. 23 [doi:10.1001/jama.2015.1328]).

“The efficacy and safety of the 3D-plus-ribavirin regimen for patients co-infected with HCV/HIV-1 need to be further investigated in larger studies; however, response rates reported here are similar to those in studies of HCV-monoinfected patients, which suggest that difficult-to-cure patients, such as prior [pegylated interferon] null responders with cirrhosis and HCV genotype 1a, may benefit from longer treatment duration,” wrote Dr. Mark S. Sulkowski, director of the viral hepatitis center and professor of medicine at Johns Hopkins University, Baltimore, and his colleagues.

In another study, researchers found that a 12-week course of a fixed-dose combination of ledipasvir and sofosbuvir in treatment-naive patients with hepatitis C genotype 1 and HIV coinfection achieved sustained virologic response rates of 98% at 12 weeks after treatment.

The open-label, phase 2b study in 50 patients recorded one case of relapse at week 4, which may have been linked to resistance-associated mutation, but no discontinuations or serious adverse events attributable to the study drug (JAMA 2015 Feb. 23 [doi:10.1001/jama.2015.1373]).

The study excluded individuals with cirrhosis, but many participants had poor prognostic factors, including African American race, male sex, IL28B non-CC genotype, and genotype 1a infection.

“These results show for the first time, to our knowledge, that an interferon- and ribavirin-free therapy is associated with high SVR rates in patients co-infected with HCV and HIV,” wrote Dr. Anu Osinusi of the University of Maryland, Baltimore, and her colleagues.

Dr. Sulkowski’s study was funded by AbbVie. Some of his coauthors declared a range of funding and consultancies from pharmaceutical companies including AbbVie and several coauthors are employees of AbbVie.

Dr. Osinusi’s study was funded by the National Institutes of Health, the German Research Foundation, and Gilead Sciences. Four coauthors reported speaking engagements, consultancies, fees, grants, stocks and other support from pharmaceutical companies including Gilead.

Patients coinfected with HIV and hepatitis C genotype 1 show high response rates to a three-drug regimen of ombitasvir, paritaprevir codosed with ritonavir, and dasabuvir, plus ribavirin, according to an open-label, uncontrolled pilot study published in JAMA.

Among the 63 patients – who were either HCV treatment-naive or had previously experienced treatment failure with peginteferon plus ribavirin – treated with the all-oral ombitasvir, paritaprevir codosed with ritonavir, and dasabuvir (known as 3D) plus ribavirin regimen, 94% of those treated for 12 weeks and 91% of those treated for 24 weeks achieved a sustained virologic response 12 weeks (SVR12) after treatment.

There were no confirmed HIV breakthroughs or serious adverse events – even though the study group included some patients with compensated cirrhosis – although around half of patients experienced treatment-related fatigue, 19% experienced insomnia, 18% experienced nausea, and 16% experienced headache (JAMA 2015 Feb. 23 [doi:10.1001/jama.2015.1328]).

“The efficacy and safety of the 3D-plus-ribavirin regimen for patients co-infected with HCV/HIV-1 need to be further investigated in larger studies; however, response rates reported here are similar to those in studies of HCV-monoinfected patients, which suggest that difficult-to-cure patients, such as prior [pegylated interferon] null responders with cirrhosis and HCV genotype 1a, may benefit from longer treatment duration,” wrote Dr. Mark S. Sulkowski, director of the viral hepatitis center and professor of medicine at Johns Hopkins University, Baltimore, and his colleagues.

In another study, researchers found that a 12-week course of a fixed-dose combination of ledipasvir and sofosbuvir in treatment-naive patients with hepatitis C genotype 1 and HIV coinfection achieved sustained virologic response rates of 98% at 12 weeks after treatment.

The open-label, phase 2b study in 50 patients recorded one case of relapse at week 4, which may have been linked to resistance-associated mutation, but no discontinuations or serious adverse events attributable to the study drug (JAMA 2015 Feb. 23 [doi:10.1001/jama.2015.1373]).

The study excluded individuals with cirrhosis, but many participants had poor prognostic factors, including African American race, male sex, IL28B non-CC genotype, and genotype 1a infection.

“These results show for the first time, to our knowledge, that an interferon- and ribavirin-free therapy is associated with high SVR rates in patients co-infected with HCV and HIV,” wrote Dr. Anu Osinusi of the University of Maryland, Baltimore, and her colleagues.

Dr. Sulkowski’s study was funded by AbbVie. Some of his coauthors declared a range of funding and consultancies from pharmaceutical companies including AbbVie and several coauthors are employees of AbbVie.

Dr. Osinusi’s study was funded by the National Institutes of Health, the German Research Foundation, and Gilead Sciences. Four coauthors reported speaking engagements, consultancies, fees, grants, stocks and other support from pharmaceutical companies including Gilead.

Individuals with hepatitis C infection are three times more likely to develop cirrhosis than are those who are hepatitis C negative, and fibrosis progression is pronounced within the first 5 years after infection, a retrospective cohort study has found.

Analysis of 10-year follow-up data from 1,840 individuals in a national database of hepatitis C (HCV) infected veterans, and 1,840 uninfected controls, found 18.4% of HCV+ individuals developed cirrhosis, compared with 6.1% of uninfected individuals, and they had a significantly higher rate of hepatic decompensation events (1.79% vs. 0.33%).

Increasing age, white race, hypertension, anemia, and a history of alcohol abuse were associated with a higher risk of cirrhosis among HCV+ individuals, but baseline or recent history of alcohol abuse or dependence did not significantly impact risk, according to a paper published online in JAMA Internal Medicine (2015;175:178-85 [doi:10.1001/jamainternmed.2014.6502]).

Courtesy NIH

“Our study shows that fibrosis progression after HCV infection starts early and that a substantial proportion of HCV-infected persons develop significant fibrosis or cirrhosis within the first 5-10 years of infection [but] on the other hand, progression of cirrhosis to hepatic decompensation is uncommon in the first 9 years after cirrhosis,” wrote Dr. Adeel A. Butt of the University of Pittsburgh, and colleagues.

The National Institutes of Health and the VA Pittsburgh Healthcare System supported the study. Two authors declared receiving grants and fees from private industry.

Individuals with hepatitis C infection are three times more likely to develop cirrhosis than are those who are hepatitis C negative, and fibrosis progression is pronounced within the first 5 years after infection, a retrospective cohort study has found.

Analysis of 10-year follow-up data from 1,840 individuals in a national database of hepatitis C (HCV) infected veterans, and 1,840 uninfected controls, found 18.4% of HCV+ individuals developed cirrhosis, compared with 6.1% of uninfected individuals, and they had a significantly higher rate of hepatic decompensation events (1.79% vs. 0.33%).

Increasing age, white race, hypertension, anemia, and a history of alcohol abuse were associated with a higher risk of cirrhosis among HCV+ individuals, but baseline or recent history of alcohol abuse or dependence did not significantly impact risk, according to a paper published online in JAMA Internal Medicine (2015;175:178-85 [doi:10.1001/jamainternmed.2014.6502]).

Courtesy NIH

“Our study shows that fibrosis progression after HCV infection starts early and that a substantial proportion of HCV-infected persons develop significant fibrosis or cirrhosis within the first 5-10 years of infection [but] on the other hand, progression of cirrhosis to hepatic decompensation is uncommon in the first 9 years after cirrhosis,” wrote Dr. Adeel A. Butt of the University of Pittsburgh, and colleagues.

The National Institutes of Health and the VA Pittsburgh Healthcare System supported the study. Two authors declared receiving grants and fees from private industry.

Individuals with hepatitis C infection are three times more likely to develop cirrhosis than are those who are hepatitis C negative, and fibrosis progression is pronounced within the first 5 years after infection, a retrospective cohort study has found.

Analysis of 10-year follow-up data from 1,840 individuals in a national database of hepatitis C (HCV) infected veterans, and 1,840 uninfected controls, found 18.4% of HCV+ individuals developed cirrhosis, compared with 6.1% of uninfected individuals, and they had a significantly higher rate of hepatic decompensation events (1.79% vs. 0.33%).

Increasing age, white race, hypertension, anemia, and a history of alcohol abuse were associated with a higher risk of cirrhosis among HCV+ individuals, but baseline or recent history of alcohol abuse or dependence did not significantly impact risk, according to a paper published online in JAMA Internal Medicine (2015;175:178-85 [doi:10.1001/jamainternmed.2014.6502]).

Courtesy NIH

“Our study shows that fibrosis progression after HCV infection starts early and that a substantial proportion of HCV-infected persons develop significant fibrosis or cirrhosis within the first 5-10 years of infection [but] on the other hand, progression of cirrhosis to hepatic decompensation is uncommon in the first 9 years after cirrhosis,” wrote Dr. Adeel A. Butt of the University of Pittsburgh, and colleagues.

The National Institutes of Health and the VA Pittsburgh Healthcare System supported the study. Two authors declared receiving grants and fees from private industry.

Immunity against the hepatitis C virus can be induced by cultured primary human liver sinusoidal endothelial cells, according to a study published in the February issue of Gastroenterology (doi:10.1053/j.gastro.2014.10.040).

“We found HLSECs [primary human LSECs] express many of the receptors implicated in HCV [hepatitis C virus] attachment and entry and HLSEC-to-hepatocyte contact was dispensable for uptake,” wrote lead author Dr. Silvia M. Giugliano of the University of Colorado, Denver, and her associates.

© Wavebreakmedia Ltd / ThinkStockPhotos.com

In a cohort study, investigators exposed HLSECs and immortalized liver endothelial cells (TMNK-1) to several variants of HCV: full-length transmitted/founder virus, sucrose-purified Japanese fulminant hepatitis–1 (JFH-1), a virus encoding a luciferase reporter, and the HCV-specific pathogen-associated molecular pattern molecules (PAMP, substrate for RIG-I). Cells were analyzed by using polymerase chain reaction (PCR), immunofluorescence, and immunohistochemical assays.

Results showed that HLSECs, regardless of contact between cells, were able to internalize HCV when exposed to it and replicate, though not translate HCV RNA. The HCV RNA “induced consistent and broad transcription of multiple interferons (IFNs) [via] pattern recognition receptors (TLR7 and retinoic acid-inducible gene 1).” Furthermore, supernatants from primary HLSECs transfected with HCV-specific PAMP molecules had larger inductions of IFNs and IFN-stimulated genes in HLSECs.

“Conditioned media from IFN-stimulated HLSECs induced expression of antiviral genes by uninfected primary human hepatocytes,” wrote Dr. Giugliano and her coauthors. “Exosomes, derived from HLSECs following stimulation with either type I or type III IFNs, controlled HCV replication in a dose-dependent manner.”

However, the investigators say that more study is required to understand why HCV is able to present so persistently if the means to combat the virus are so apparent in the immune system.

“These results raise a number of intriguing questions, for example, how the use of exogenous IFN to treat viral hepatitis could be expected to induce additional, previously unrecognized antiviral mechanisms involving HLSECs,” says the study. “Further work is warranted to understand why despite these innate immune responses, HCV is able to establish persistence and fail eradication with IFN-based antiviral therapy.”

The study supported by grants R21-AI103361 and U19 AI 1066328; Dr. Rosen received a Merit Review grant and Dr. Shaw received grant R21-AI 106000. The authors reported no financial conflicts of interest.

dchitnis@frontlinemedcom.com

Immunity against the hepatitis C virus can be induced by cultured primary human liver sinusoidal endothelial cells, according to a study published in the February issue of Gastroenterology (doi:10.1053/j.gastro.2014.10.040).

“We found HLSECs [primary human LSECs] express many of the receptors implicated in HCV [hepatitis C virus] attachment and entry and HLSEC-to-hepatocyte contact was dispensable for uptake,” wrote lead author Dr. Silvia M. Giugliano of the University of Colorado, Denver, and her associates.

© Wavebreakmedia Ltd / ThinkStockPhotos.com

In a cohort study, investigators exposed HLSECs and immortalized liver endothelial cells (TMNK-1) to several variants of HCV: full-length transmitted/founder virus, sucrose-purified Japanese fulminant hepatitis–1 (JFH-1), a virus encoding a luciferase reporter, and the HCV-specific pathogen-associated molecular pattern molecules (PAMP, substrate for RIG-I). Cells were analyzed by using polymerase chain reaction (PCR), immunofluorescence, and immunohistochemical assays.

Results showed that HLSECs, regardless of contact between cells, were able to internalize HCV when exposed to it and replicate, though not translate HCV RNA. The HCV RNA “induced consistent and broad transcription of multiple interferons (IFNs) [via] pattern recognition receptors (TLR7 and retinoic acid-inducible gene 1).” Furthermore, supernatants from primary HLSECs transfected with HCV-specific PAMP molecules had larger inductions of IFNs and IFN-stimulated genes in HLSECs.

“Conditioned media from IFN-stimulated HLSECs induced expression of antiviral genes by uninfected primary human hepatocytes,” wrote Dr. Giugliano and her coauthors. “Exosomes, derived from HLSECs following stimulation with either type I or type III IFNs, controlled HCV replication in a dose-dependent manner.”

However, the investigators say that more study is required to understand why HCV is able to present so persistently if the means to combat the virus are so apparent in the immune system.

“These results raise a number of intriguing questions, for example, how the use of exogenous IFN to treat viral hepatitis could be expected to induce additional, previously unrecognized antiviral mechanisms involving HLSECs,” says the study. “Further work is warranted to understand why despite these innate immune responses, HCV is able to establish persistence and fail eradication with IFN-based antiviral therapy.”

The study supported by grants R21-AI103361 and U19 AI 1066328; Dr. Rosen received a Merit Review grant and Dr. Shaw received grant R21-AI 106000. The authors reported no financial conflicts of interest.

dchitnis@frontlinemedcom.com

Immunity against the hepatitis C virus can be induced by cultured primary human liver sinusoidal endothelial cells, according to a study published in the February issue of Gastroenterology (doi:10.1053/j.gastro.2014.10.040).

“We found HLSECs [primary human LSECs] express many of the receptors implicated in HCV [hepatitis C virus] attachment and entry and HLSEC-to-hepatocyte contact was dispensable for uptake,” wrote lead author Dr. Silvia M. Giugliano of the University of Colorado, Denver, and her associates.

© Wavebreakmedia Ltd / ThinkStockPhotos.com

In a cohort study, investigators exposed HLSECs and immortalized liver endothelial cells (TMNK-1) to several variants of HCV: full-length transmitted/founder virus, sucrose-purified Japanese fulminant hepatitis–1 (JFH-1), a virus encoding a luciferase reporter, and the HCV-specific pathogen-associated molecular pattern molecules (PAMP, substrate for RIG-I). Cells were analyzed by using polymerase chain reaction (PCR), immunofluorescence, and immunohistochemical assays.

Results showed that HLSECs, regardless of contact between cells, were able to internalize HCV when exposed to it and replicate, though not translate HCV RNA. The HCV RNA “induced consistent and broad transcription of multiple interferons (IFNs) [via] pattern recognition receptors (TLR7 and retinoic acid-inducible gene 1).” Furthermore, supernatants from primary HLSECs transfected with HCV-specific PAMP molecules had larger inductions of IFNs and IFN-stimulated genes in HLSECs.

“Conditioned media from IFN-stimulated HLSECs induced expression of antiviral genes by uninfected primary human hepatocytes,” wrote Dr. Giugliano and her coauthors. “Exosomes, derived from HLSECs following stimulation with either type I or type III IFNs, controlled HCV replication in a dose-dependent manner.”

However, the investigators say that more study is required to understand why HCV is able to present so persistently if the means to combat the virus are so apparent in the immune system.

“These results raise a number of intriguing questions, for example, how the use of exogenous IFN to treat viral hepatitis could be expected to induce additional, previously unrecognized antiviral mechanisms involving HLSECs,” says the study. “Further work is warranted to understand why despite these innate immune responses, HCV is able to establish persistence and fail eradication with IFN-based antiviral therapy.”

The study supported by grants R21-AI103361 and U19 AI 1066328; Dr. Rosen received a Merit Review grant and Dr. Shaw received grant R21-AI 106000. The authors reported no financial conflicts of interest.

dchitnis@frontlinemedcom.com