HCV Hub

VIENNA – More than 75% of patients with decompensated cirrhosis due to chronic hepatitis C virus (HCV) infection achieved a sustained virologic response at 12 weeks (SVR12) with all-oral HCV therapy in a routine clinical practice setting.

SVR12 was achieved in 74%-81% of patients treated with various regimens containing the direct antiviral agents sofosbuvir (Sovaldi) and simeprevir (Olysio), with or without ribavirin, based on interim data from the ongoing HCV-Target study. “All-oral DAA therapy has been readily used to treat HCV cirrhosis with MELD (Model for End-Stage Liver Disease) score greater than or equal to 10,” study investigator Dr. Rajender Reddy reported at the meeting sponsored by the European Association for the Study of the Liver.

Sara Freeman/Frontline Medical News

“There is limited experience with all-oral DAA [direct antiviral agent] therapy in patients who have advanced HCV liver disease,” said Dr. Reddy, who is director of hepatology and medical director of liver transplantation at the Hospital of the University of Pennsylvania in Philadelphia. “HCV therapy in decompensated cirrhosis in the era of interferon-based therapy has been associated with suboptimal response and poor tolerability.”

Alternatively, these early findings from HCV-Target suggest that all-oral DAA therapy is not only effective in patients with advanced liver disease, but also that such treatment is well tolerated, he said.

HCV-Target is a longitudinal, observational study involving an international consortium of academic and community medical centers in the U.S., Canada, and Europe. HCV treatment is administered according to the local standard of care and the regimen selected by the patient’s health care provider.

As of October 2014, 2,204 patients were enrolled and 253 had a baseline MELD score of 10 or higher; 216 had completed treatment and had 12 weeks’ follow-up data available for analysis. Of these, 76 received a combination of sofosbuvir and ribavirin, 108 had been treated with sofosbuvir and simeprevir, and 32 had received all three drugs.

The mean age of patients was 59 years, but ranged from 38 to 80 years. The majority (59%) of patients had failed prior treatment, and around 73% had a history of prior hepatic decompensation, suggesting advancement of their liver disease.

“Sustained virologic response varied by genotype and regimen,” Dr. Reddy observed. SVR12 rates ranged from 52% to 74% in patients with genotype 1 (GT1). Most (63%) of these patients had received a combination of sofosbuvir and simeprevir, which yielded the highest SVR12 rates (72% in treatment-experienced and 78% in previously untreated GT1 patients).

SVR12 was 81% in patients with GT2, the majority (97%) had been treated with sofosbuvir plus ribavirin, with just 3% receiving all three drugs in combination.

SVR12 was the lowest, at 39%, in patients with GT3, all of whom had received sofosbuvir plus ribavirin.

Relapse rates were highest in GT3 patients, at 46% versus 26% in GT1 and 7% in GT2 patients.

SVR12 rates were also evaluated in relation to the MELD score. Of interest, said Dr. Reddy, was that patients with a MELD score of 10-15 (n=187) and those with a MELD score of 16-21 (n=21) had comparable SVR12 rates that ranged from 55% to 73%, with the lowest response rates being seen in patients treated with sofosbuvir plus ribavirin. Although there were only eight patients with a MELD score greater than 21, SVR12 was 100%.

Multivariate analysis to look at predictors of response was performed exclusively in GT1 patients and showed that being GT1a and having elevated bilirubin levels were negative predictors of response, with respective odds ratios of 0.39 (P = .069) and 0.46 (P = .002). Higher albumin levels, however, were associated with better outcomes (OR = 2.52, P = .026).

In terms of safety, 86% of 234 patients experienced any adverse event. Dr. Reddy highlighted anemia, which was more common (seen in about 30% of patients) with the ribavirin regimens, and photosensitivity, which was only seen in patients treated with simeprevir.

There were 44 serious adverse events; 16 were due to hepatic decompensation, 10 resulted from infections, 3 were deaths (one of which was due to liver failure), and 12 were liver transplants.

“Long-term follow-up is needed to assess the impact of SVR on the reversibility of liver disease,” he said.

The study is sponsored by the University of Florida and the University of Carolina at Chapel Hill and funded in part by AbbVie, Gilead, Janssen, Kadmon, Merck, Bristol-Myers Squibb, and GlaxoSmithKline. Dr. Reddy has acted as an ad-hoc advisory board member for and received research support from Gilead, Bristol-Myers Squibb, Merck, AbbVie, and Janssen.

VIENNA – More than 75% of patients with decompensated cirrhosis due to chronic hepatitis C virus (HCV) infection achieved a sustained virologic response at 12 weeks (SVR12) with all-oral HCV therapy in a routine clinical practice setting.

SVR12 was achieved in 74%-81% of patients treated with various regimens containing the direct antiviral agents sofosbuvir (Sovaldi) and simeprevir (Olysio), with or without ribavirin, based on interim data from the ongoing HCV-Target study. “All-oral DAA therapy has been readily used to treat HCV cirrhosis with MELD (Model for End-Stage Liver Disease) score greater than or equal to 10,” study investigator Dr. Rajender Reddy reported at the meeting sponsored by the European Association for the Study of the Liver.

Sara Freeman/Frontline Medical News

“There is limited experience with all-oral DAA [direct antiviral agent] therapy in patients who have advanced HCV liver disease,” said Dr. Reddy, who is director of hepatology and medical director of liver transplantation at the Hospital of the University of Pennsylvania in Philadelphia. “HCV therapy in decompensated cirrhosis in the era of interferon-based therapy has been associated with suboptimal response and poor tolerability.”

Alternatively, these early findings from HCV-Target suggest that all-oral DAA therapy is not only effective in patients with advanced liver disease, but also that such treatment is well tolerated, he said.

HCV-Target is a longitudinal, observational study involving an international consortium of academic and community medical centers in the U.S., Canada, and Europe. HCV treatment is administered according to the local standard of care and the regimen selected by the patient’s health care provider.

As of October 2014, 2,204 patients were enrolled and 253 had a baseline MELD score of 10 or higher; 216 had completed treatment and had 12 weeks’ follow-up data available for analysis. Of these, 76 received a combination of sofosbuvir and ribavirin, 108 had been treated with sofosbuvir and simeprevir, and 32 had received all three drugs.

The mean age of patients was 59 years, but ranged from 38 to 80 years. The majority (59%) of patients had failed prior treatment, and around 73% had a history of prior hepatic decompensation, suggesting advancement of their liver disease.

“Sustained virologic response varied by genotype and regimen,” Dr. Reddy observed. SVR12 rates ranged from 52% to 74% in patients with genotype 1 (GT1). Most (63%) of these patients had received a combination of sofosbuvir and simeprevir, which yielded the highest SVR12 rates (72% in treatment-experienced and 78% in previously untreated GT1 patients).

SVR12 was 81% in patients with GT2, the majority (97%) had been treated with sofosbuvir plus ribavirin, with just 3% receiving all three drugs in combination.

SVR12 was the lowest, at 39%, in patients with GT3, all of whom had received sofosbuvir plus ribavirin.

Relapse rates were highest in GT3 patients, at 46% versus 26% in GT1 and 7% in GT2 patients.

SVR12 rates were also evaluated in relation to the MELD score. Of interest, said Dr. Reddy, was that patients with a MELD score of 10-15 (n=187) and those with a MELD score of 16-21 (n=21) had comparable SVR12 rates that ranged from 55% to 73%, with the lowest response rates being seen in patients treated with sofosbuvir plus ribavirin. Although there were only eight patients with a MELD score greater than 21, SVR12 was 100%.

Multivariate analysis to look at predictors of response was performed exclusively in GT1 patients and showed that being GT1a and having elevated bilirubin levels were negative predictors of response, with respective odds ratios of 0.39 (P = .069) and 0.46 (P = .002). Higher albumin levels, however, were associated with better outcomes (OR = 2.52, P = .026).

In terms of safety, 86% of 234 patients experienced any adverse event. Dr. Reddy highlighted anemia, which was more common (seen in about 30% of patients) with the ribavirin regimens, and photosensitivity, which was only seen in patients treated with simeprevir.

There were 44 serious adverse events; 16 were due to hepatic decompensation, 10 resulted from infections, 3 were deaths (one of which was due to liver failure), and 12 were liver transplants.

“Long-term follow-up is needed to assess the impact of SVR on the reversibility of liver disease,” he said.

The study is sponsored by the University of Florida and the University of Carolina at Chapel Hill and funded in part by AbbVie, Gilead, Janssen, Kadmon, Merck, Bristol-Myers Squibb, and GlaxoSmithKline. Dr. Reddy has acted as an ad-hoc advisory board member for and received research support from Gilead, Bristol-Myers Squibb, Merck, AbbVie, and Janssen.

VIENNA – More than 75% of patients with decompensated cirrhosis due to chronic hepatitis C virus (HCV) infection achieved a sustained virologic response at 12 weeks (SVR12) with all-oral HCV therapy in a routine clinical practice setting.

SVR12 was achieved in 74%-81% of patients treated with various regimens containing the direct antiviral agents sofosbuvir (Sovaldi) and simeprevir (Olysio), with or without ribavirin, based on interim data from the ongoing HCV-Target study. “All-oral DAA therapy has been readily used to treat HCV cirrhosis with MELD (Model for End-Stage Liver Disease) score greater than or equal to 10,” study investigator Dr. Rajender Reddy reported at the meeting sponsored by the European Association for the Study of the Liver.

Sara Freeman/Frontline Medical News

“There is limited experience with all-oral DAA [direct antiviral agent] therapy in patients who have advanced HCV liver disease,” said Dr. Reddy, who is director of hepatology and medical director of liver transplantation at the Hospital of the University of Pennsylvania in Philadelphia. “HCV therapy in decompensated cirrhosis in the era of interferon-based therapy has been associated with suboptimal response and poor tolerability.”

Alternatively, these early findings from HCV-Target suggest that all-oral DAA therapy is not only effective in patients with advanced liver disease, but also that such treatment is well tolerated, he said.

HCV-Target is a longitudinal, observational study involving an international consortium of academic and community medical centers in the U.S., Canada, and Europe. HCV treatment is administered according to the local standard of care and the regimen selected by the patient’s health care provider.

As of October 2014, 2,204 patients were enrolled and 253 had a baseline MELD score of 10 or higher; 216 had completed treatment and had 12 weeks’ follow-up data available for analysis. Of these, 76 received a combination of sofosbuvir and ribavirin, 108 had been treated with sofosbuvir and simeprevir, and 32 had received all three drugs.

The mean age of patients was 59 years, but ranged from 38 to 80 years. The majority (59%) of patients had failed prior treatment, and around 73% had a history of prior hepatic decompensation, suggesting advancement of their liver disease.

“Sustained virologic response varied by genotype and regimen,” Dr. Reddy observed. SVR12 rates ranged from 52% to 74% in patients with genotype 1 (GT1). Most (63%) of these patients had received a combination of sofosbuvir and simeprevir, which yielded the highest SVR12 rates (72% in treatment-experienced and 78% in previously untreated GT1 patients).

SVR12 was 81% in patients with GT2, the majority (97%) had been treated with sofosbuvir plus ribavirin, with just 3% receiving all three drugs in combination.

SVR12 was the lowest, at 39%, in patients with GT3, all of whom had received sofosbuvir plus ribavirin.

Relapse rates were highest in GT3 patients, at 46% versus 26% in GT1 and 7% in GT2 patients.

SVR12 rates were also evaluated in relation to the MELD score. Of interest, said Dr. Reddy, was that patients with a MELD score of 10-15 (n=187) and those with a MELD score of 16-21 (n=21) had comparable SVR12 rates that ranged from 55% to 73%, with the lowest response rates being seen in patients treated with sofosbuvir plus ribavirin. Although there were only eight patients with a MELD score greater than 21, SVR12 was 100%.

Multivariate analysis to look at predictors of response was performed exclusively in GT1 patients and showed that being GT1a and having elevated bilirubin levels were negative predictors of response, with respective odds ratios of 0.39 (P = .069) and 0.46 (P = .002). Higher albumin levels, however, were associated with better outcomes (OR = 2.52, P = .026).

In terms of safety, 86% of 234 patients experienced any adverse event. Dr. Reddy highlighted anemia, which was more common (seen in about 30% of patients) with the ribavirin regimens, and photosensitivity, which was only seen in patients treated with simeprevir.

There were 44 serious adverse events; 16 were due to hepatic decompensation, 10 resulted from infections, 3 were deaths (one of which was due to liver failure), and 12 were liver transplants.

“Long-term follow-up is needed to assess the impact of SVR on the reversibility of liver disease,” he said.

The study is sponsored by the University of Florida and the University of Carolina at Chapel Hill and funded in part by AbbVie, Gilead, Janssen, Kadmon, Merck, Bristol-Myers Squibb, and GlaxoSmithKline. Dr. Reddy has acted as an ad-hoc advisory board member for and received research support from Gilead, Bristol-Myers Squibb, Merck, AbbVie, and Janssen.

VIENNA – Major cardiovascular (CV) events are significantly increased in hospital patients who are infected with the hepatitis C virus (HCV) versus those who are not, according to data presented at the meeting sponsored by the European Association for the Study of the Liver.

A retrospective analysis of more than 200,000 inpatients with and without HCV infection at discharge showed that those with HCV were 29% more likely to have had an acute MI, 98% more likely to have had a cerebral vascular accident (CVA), and 88% times more likely to have coronary artery disease (CAD). There was also an 8% increased risk for heart failure (HF).

“HCV infection is strongly linked to an increase in cardiovascular outcome, length of hospital stay, and cost of care,” Dr. Firew Wubiee and Dr. Charles Howell of Howard University, Washington, D.C., reported in an ePoster at the meeting.

For their retrospective analysis, data were obtained from the 2011 Nationwide Inpatient Sample, which is a large all-payer inpatient care database in the United States that contains information on more than 7 million hospital stays.

ICD-9 codes were used to identify all inpatient cases with and without HCV infection at discharge and those with major CV events, excluding those with liver cirrhosis, hepatocellular carcinoma, and cases of liver transplantation. Dr. Wubiee and Dr. Howell found that inpatients with HCV infection were significantly (P < .001) younger than were those without HCV (mean age 52.8 vs. 57.9 years). They were significantly more likely (P < .001) to be male (62.2% vs. 40%), have a smoking history (45.5% vs. 22.7%), be from ethnic or racial minorities (26.4% vs. 5.1%), and have a household income of less than $39,000 (41% vs. 29.1%).

While inpatients with HCV were also significantly (P < .001) more likely than were those without HCV to have diabetes mellitus (2.1% vs. 1.8%), they were significantly less likely (P < .001) to have other known CV risk factors such as obesity (8.7% vs. 11.8%), dyslipidemia (13.2% vs. 28.1%), and hypertension (49.7% vs. 51%).

Odds ratios for CV outcomes were adjusted for multiple confounding factors, including age, race, obesity, diabetes, dyslipidemia, smoking, alcohol use, hypertension, and hepatitis B infection. The adjusted odds ratios for major CV outcomes were 2.29 for AMI, 1.98 for CVA, 1.88 for CAD, and 1.08 for HF (all P < .001).

The duration of in-hospital treatment was longer for patients with HCV than for those without, with adjusted differences of 1.3 days for AMI (P < .001), 2.02 days for CVA (P < .003), 0.52 days for CAD (P < .001), and 0.37 days for HF (P < .001).

The adjusted cost of inpatient care was also higher for HCV-infected versus noninfected individuals with a mean cost difference of $10,126 for AMI, (P < .001), $10,105 for CVA (P < .002), $2,703 for CAD (P < .001), and $1,895 for HF (P < .001).

“We hypothesized that the inflammation and insulin resistance related to HCV increases the prevalence of cardiovascular diseases compared to patients without HCV,” Dr. Wubiee and Dr. Howell observed.

“The results are consistent with mounting evidence for [a] biological and epidemiological association between HCV infection and cardiovascular morbidity,” they said and suggested “HCV needs to be considered a cardiovascular risk factor.”

VIENNA – Major cardiovascular (CV) events are significantly increased in hospital patients who are infected with the hepatitis C virus (HCV) versus those who are not, according to data presented at the meeting sponsored by the European Association for the Study of the Liver.

A retrospective analysis of more than 200,000 inpatients with and without HCV infection at discharge showed that those with HCV were 29% more likely to have had an acute MI, 98% more likely to have had a cerebral vascular accident (CVA), and 88% times more likely to have coronary artery disease (CAD). There was also an 8% increased risk for heart failure (HF).

“HCV infection is strongly linked to an increase in cardiovascular outcome, length of hospital stay, and cost of care,” Dr. Firew Wubiee and Dr. Charles Howell of Howard University, Washington, D.C., reported in an ePoster at the meeting.

For their retrospective analysis, data were obtained from the 2011 Nationwide Inpatient Sample, which is a large all-payer inpatient care database in the United States that contains information on more than 7 million hospital stays.

ICD-9 codes were used to identify all inpatient cases with and without HCV infection at discharge and those with major CV events, excluding those with liver cirrhosis, hepatocellular carcinoma, and cases of liver transplantation. Dr. Wubiee and Dr. Howell found that inpatients with HCV infection were significantly (P < .001) younger than were those without HCV (mean age 52.8 vs. 57.9 years). They were significantly more likely (P < .001) to be male (62.2% vs. 40%), have a smoking history (45.5% vs. 22.7%), be from ethnic or racial minorities (26.4% vs. 5.1%), and have a household income of less than $39,000 (41% vs. 29.1%).

While inpatients with HCV were also significantly (P < .001) more likely than were those without HCV to have diabetes mellitus (2.1% vs. 1.8%), they were significantly less likely (P < .001) to have other known CV risk factors such as obesity (8.7% vs. 11.8%), dyslipidemia (13.2% vs. 28.1%), and hypertension (49.7% vs. 51%).

Odds ratios for CV outcomes were adjusted for multiple confounding factors, including age, race, obesity, diabetes, dyslipidemia, smoking, alcohol use, hypertension, and hepatitis B infection. The adjusted odds ratios for major CV outcomes were 2.29 for AMI, 1.98 for CVA, 1.88 for CAD, and 1.08 for HF (all P < .001).

The duration of in-hospital treatment was longer for patients with HCV than for those without, with adjusted differences of 1.3 days for AMI (P < .001), 2.02 days for CVA (P < .003), 0.52 days for CAD (P < .001), and 0.37 days for HF (P < .001).

The adjusted cost of inpatient care was also higher for HCV-infected versus noninfected individuals with a mean cost difference of $10,126 for AMI, (P < .001), $10,105 for CVA (P < .002), $2,703 for CAD (P < .001), and $1,895 for HF (P < .001).

“We hypothesized that the inflammation and insulin resistance related to HCV increases the prevalence of cardiovascular diseases compared to patients without HCV,” Dr. Wubiee and Dr. Howell observed.

“The results are consistent with mounting evidence for [a] biological and epidemiological association between HCV infection and cardiovascular morbidity,” they said and suggested “HCV needs to be considered a cardiovascular risk factor.”

VIENNA – Major cardiovascular (CV) events are significantly increased in hospital patients who are infected with the hepatitis C virus (HCV) versus those who are not, according to data presented at the meeting sponsored by the European Association for the Study of the Liver.

A retrospective analysis of more than 200,000 inpatients with and without HCV infection at discharge showed that those with HCV were 29% more likely to have had an acute MI, 98% more likely to have had a cerebral vascular accident (CVA), and 88% times more likely to have coronary artery disease (CAD). There was also an 8% increased risk for heart failure (HF).

“HCV infection is strongly linked to an increase in cardiovascular outcome, length of hospital stay, and cost of care,” Dr. Firew Wubiee and Dr. Charles Howell of Howard University, Washington, D.C., reported in an ePoster at the meeting.

For their retrospective analysis, data were obtained from the 2011 Nationwide Inpatient Sample, which is a large all-payer inpatient care database in the United States that contains information on more than 7 million hospital stays.

ICD-9 codes were used to identify all inpatient cases with and without HCV infection at discharge and those with major CV events, excluding those with liver cirrhosis, hepatocellular carcinoma, and cases of liver transplantation. Dr. Wubiee and Dr. Howell found that inpatients with HCV infection were significantly (P < .001) younger than were those without HCV (mean age 52.8 vs. 57.9 years). They were significantly more likely (P < .001) to be male (62.2% vs. 40%), have a smoking history (45.5% vs. 22.7%), be from ethnic or racial minorities (26.4% vs. 5.1%), and have a household income of less than $39,000 (41% vs. 29.1%).

While inpatients with HCV were also significantly (P < .001) more likely than were those without HCV to have diabetes mellitus (2.1% vs. 1.8%), they were significantly less likely (P < .001) to have other known CV risk factors such as obesity (8.7% vs. 11.8%), dyslipidemia (13.2% vs. 28.1%), and hypertension (49.7% vs. 51%).

Odds ratios for CV outcomes were adjusted for multiple confounding factors, including age, race, obesity, diabetes, dyslipidemia, smoking, alcohol use, hypertension, and hepatitis B infection. The adjusted odds ratios for major CV outcomes were 2.29 for AMI, 1.98 for CVA, 1.88 for CAD, and 1.08 for HF (all P < .001).

The duration of in-hospital treatment was longer for patients with HCV than for those without, with adjusted differences of 1.3 days for AMI (P < .001), 2.02 days for CVA (P < .003), 0.52 days for CAD (P < .001), and 0.37 days for HF (P < .001).

The adjusted cost of inpatient care was also higher for HCV-infected versus noninfected individuals with a mean cost difference of $10,126 for AMI, (P < .001), $10,105 for CVA (P < .002), $2,703 for CAD (P < .001), and $1,895 for HF (P < .001).

“We hypothesized that the inflammation and insulin resistance related to HCV increases the prevalence of cardiovascular diseases compared to patients without HCV,” Dr. Wubiee and Dr. Howell observed.

“The results are consistent with mounting evidence for [a] biological and epidemiological association between HCV infection and cardiovascular morbidity,” they said and suggested “HCV needs to be considered a cardiovascular risk factor.”

A 12-week course of oral daclatasvir, asunaprevir, and beclabuvir, with or without ribavirin, achieved a sustained virologic response (SVR) in patients with hepatitis C, judging from the findings of two studies.

In the first open-label study (UNITY-1), 312 treatment-naive and 103 treatment-experienced cirrhosis-free patients with chronic infection with hepatitis C virus (HCV) genotype 1 were treated with an oral fixed-dose regimen of daclatasvir, asunaprevir, and beclabuvir for 12 weeks, reported Dr. Andrew J. Muir of Duke Clinical Research Institute, Durham, N.C., and his associates.

Overall, 91.3% of patients achieved an SVR at 12 weeks (HCV-RNA < 25 IU/mL) after treatment cessation, with a slightly greater response among treatment-naive patients, compared with treatment-experienced patients (92% vs. 89.3%), according to a paper published May 5 in JAMA.

HCV treatment regimens are evolving rapidly away from interferon-based regimens toward all-oral antiviral regimens, such as the one used in this study, according to the investigators.

Daclatasvir inhibits the HCV NS5A protein, asunaprevir is an NS3 protease inhibitor with activity against genotypes 1 and 4.5, and beclabuvir is a nonnucleoside NS5B inhibitor.

Patients with genotype 1b showed higher response rates than those with genotype 1a in both the treatment-experienced and treatment-naive cohorts (JAMA 2015;313:1728-35 [doi:10.1001/jama.2015.3860]).

The second study (UNITY-2) involved 112 treatment-naive and 90 treatment-experienced patients with HCV and compensated cirrhosis, also treated with daclatasvir, asunaprevir, and beclabuvir.

However in this study, published in the same edition of JAMA, the patients were also randomized to double-blinded, weight-based ribavirin (1000-1200 mg/day) or placebo (JAMA 2015;313:1736-44 [doi:10.1001/jama.2015.3868]).

Among the treatment-naive group, 98% of patients also treated with ribavirin achieved an SVR at 12 weeks, while the response rate for treatment alone was 93%.

The response rate was 93% among treatment-experienced patients also given ribavirin and 87% among those given treatment alone.

The authors of the UNITY-2 study said patients with cirrhosis often experienced problems with peginterferon-based treatment regimens because of reduced response rates and more frequent and severe adverse events, hence the interest in interferon-free treatment options.

Both studies observed treatment-emergent alanine aminotransferase elevations – two cases in UNITY-1 and four cases in UNITY-2 – but only UNITY-2 recorded treatment-related adverse events, including anemia, aminotransferase and bilirubin elevations, and ribavirin overdose.

The UNITY-2 study also recorded grade 3 or 4 hemoglobin abnormalities in 5% of patients taking ribavirin but none in the treatment-only group.

Researchers on UNITY-1 said the response rates they observed in their study group were comparable to those seen in other phase III studies of all-oral direct-acting antiviral regimens, such as the fixed-dose combinations of sofosbuvir and ledipasvir and ABT-450/ritonavir, ombitasvir, dasabuvir, and ribavirin.

“Furthermore, SVR12 rates in this study were consistently high across baseline subgroups of patients, including sex, age, HCV-RNA level, and IL28B genotype, suggesting that this regimen has the potential to be broadly effective across genotype 1 patient populations,” wrote Dr. Fred Poordad of the University of Texas Health Science Center at San Antonio and his associates in the UNITY-1 study.

They qualified this by pointing out that the study included relatively few patients of black race – as did UNITY-2 – although the response rates were still high among this group.

Both studies were funded by Bristol-Myers Squibb. Many authors reported personal fees, grants, and speaking engagements from the pharmaceutical industry, including Bristol-Myers Squibb, and several authors were employees of Bristol-Myers Squibb.

A 12-week course of oral daclatasvir, asunaprevir, and beclabuvir, with or without ribavirin, achieved a sustained virologic response (SVR) in patients with hepatitis C, judging from the findings of two studies.

In the first open-label study (UNITY-1), 312 treatment-naive and 103 treatment-experienced cirrhosis-free patients with chronic infection with hepatitis C virus (HCV) genotype 1 were treated with an oral fixed-dose regimen of daclatasvir, asunaprevir, and beclabuvir for 12 weeks, reported Dr. Andrew J. Muir of Duke Clinical Research Institute, Durham, N.C., and his associates.

Overall, 91.3% of patients achieved an SVR at 12 weeks (HCV-RNA < 25 IU/mL) after treatment cessation, with a slightly greater response among treatment-naive patients, compared with treatment-experienced patients (92% vs. 89.3%), according to a paper published May 5 in JAMA.

HCV treatment regimens are evolving rapidly away from interferon-based regimens toward all-oral antiviral regimens, such as the one used in this study, according to the investigators.

Daclatasvir inhibits the HCV NS5A protein, asunaprevir is an NS3 protease inhibitor with activity against genotypes 1 and 4.5, and beclabuvir is a nonnucleoside NS5B inhibitor.

Patients with genotype 1b showed higher response rates than those with genotype 1a in both the treatment-experienced and treatment-naive cohorts (JAMA 2015;313:1728-35 [doi:10.1001/jama.2015.3860]).

The second study (UNITY-2) involved 112 treatment-naive and 90 treatment-experienced patients with HCV and compensated cirrhosis, also treated with daclatasvir, asunaprevir, and beclabuvir.

However in this study, published in the same edition of JAMA, the patients were also randomized to double-blinded, weight-based ribavirin (1000-1200 mg/day) or placebo (JAMA 2015;313:1736-44 [doi:10.1001/jama.2015.3868]).

Among the treatment-naive group, 98% of patients also treated with ribavirin achieved an SVR at 12 weeks, while the response rate for treatment alone was 93%.

The response rate was 93% among treatment-experienced patients also given ribavirin and 87% among those given treatment alone.

The authors of the UNITY-2 study said patients with cirrhosis often experienced problems with peginterferon-based treatment regimens because of reduced response rates and more frequent and severe adverse events, hence the interest in interferon-free treatment options.

Both studies observed treatment-emergent alanine aminotransferase elevations – two cases in UNITY-1 and four cases in UNITY-2 – but only UNITY-2 recorded treatment-related adverse events, including anemia, aminotransferase and bilirubin elevations, and ribavirin overdose.

The UNITY-2 study also recorded grade 3 or 4 hemoglobin abnormalities in 5% of patients taking ribavirin but none in the treatment-only group.

Researchers on UNITY-1 said the response rates they observed in their study group were comparable to those seen in other phase III studies of all-oral direct-acting antiviral regimens, such as the fixed-dose combinations of sofosbuvir and ledipasvir and ABT-450/ritonavir, ombitasvir, dasabuvir, and ribavirin.

“Furthermore, SVR12 rates in this study were consistently high across baseline subgroups of patients, including sex, age, HCV-RNA level, and IL28B genotype, suggesting that this regimen has the potential to be broadly effective across genotype 1 patient populations,” wrote Dr. Fred Poordad of the University of Texas Health Science Center at San Antonio and his associates in the UNITY-1 study.

They qualified this by pointing out that the study included relatively few patients of black race – as did UNITY-2 – although the response rates were still high among this group.

Both studies were funded by Bristol-Myers Squibb. Many authors reported personal fees, grants, and speaking engagements from the pharmaceutical industry, including Bristol-Myers Squibb, and several authors were employees of Bristol-Myers Squibb.

A 12-week course of oral daclatasvir, asunaprevir, and beclabuvir, with or without ribavirin, achieved a sustained virologic response (SVR) in patients with hepatitis C, judging from the findings of two studies.

In the first open-label study (UNITY-1), 312 treatment-naive and 103 treatment-experienced cirrhosis-free patients with chronic infection with hepatitis C virus (HCV) genotype 1 were treated with an oral fixed-dose regimen of daclatasvir, asunaprevir, and beclabuvir for 12 weeks, reported Dr. Andrew J. Muir of Duke Clinical Research Institute, Durham, N.C., and his associates.

Overall, 91.3% of patients achieved an SVR at 12 weeks (HCV-RNA < 25 IU/mL) after treatment cessation, with a slightly greater response among treatment-naive patients, compared with treatment-experienced patients (92% vs. 89.3%), according to a paper published May 5 in JAMA.

HCV treatment regimens are evolving rapidly away from interferon-based regimens toward all-oral antiviral regimens, such as the one used in this study, according to the investigators.

Daclatasvir inhibits the HCV NS5A protein, asunaprevir is an NS3 protease inhibitor with activity against genotypes 1 and 4.5, and beclabuvir is a nonnucleoside NS5B inhibitor.

Patients with genotype 1b showed higher response rates than those with genotype 1a in both the treatment-experienced and treatment-naive cohorts (JAMA 2015;313:1728-35 [doi:10.1001/jama.2015.3860]).

The second study (UNITY-2) involved 112 treatment-naive and 90 treatment-experienced patients with HCV and compensated cirrhosis, also treated with daclatasvir, asunaprevir, and beclabuvir.

However in this study, published in the same edition of JAMA, the patients were also randomized to double-blinded, weight-based ribavirin (1000-1200 mg/day) or placebo (JAMA 2015;313:1736-44 [doi:10.1001/jama.2015.3868]).

Among the treatment-naive group, 98% of patients also treated with ribavirin achieved an SVR at 12 weeks, while the response rate for treatment alone was 93%.

The response rate was 93% among treatment-experienced patients also given ribavirin and 87% among those given treatment alone.

The authors of the UNITY-2 study said patients with cirrhosis often experienced problems with peginterferon-based treatment regimens because of reduced response rates and more frequent and severe adverse events, hence the interest in interferon-free treatment options.

Both studies observed treatment-emergent alanine aminotransferase elevations – two cases in UNITY-1 and four cases in UNITY-2 – but only UNITY-2 recorded treatment-related adverse events, including anemia, aminotransferase and bilirubin elevations, and ribavirin overdose.

The UNITY-2 study also recorded grade 3 or 4 hemoglobin abnormalities in 5% of patients taking ribavirin but none in the treatment-only group.

Researchers on UNITY-1 said the response rates they observed in their study group were comparable to those seen in other phase III studies of all-oral direct-acting antiviral regimens, such as the fixed-dose combinations of sofosbuvir and ledipasvir and ABT-450/ritonavir, ombitasvir, dasabuvir, and ribavirin.

“Furthermore, SVR12 rates in this study were consistently high across baseline subgroups of patients, including sex, age, HCV-RNA level, and IL28B genotype, suggesting that this regimen has the potential to be broadly effective across genotype 1 patient populations,” wrote Dr. Fred Poordad of the University of Texas Health Science Center at San Antonio and his associates in the UNITY-1 study.

They qualified this by pointing out that the study included relatively few patients of black race – as did UNITY-2 – although the response rates were still high among this group.

Both studies were funded by Bristol-Myers Squibb. Many authors reported personal fees, grants, and speaking engagements from the pharmaceutical industry, including Bristol-Myers Squibb, and several authors were employees of Bristol-Myers Squibb.

VIENNA – Patients infected with hepatitis C virus who developed cirrhosis and received statin treatment had significantly lower rates of both death and cirrhosis decompensation, compared with cirrhosis patients who did not receive a statin in a confounder-adjusted analysis of data from more than 2,700 patients in a U.S. Department of Veterans Affairs database.

While this suggestive evidence is not strong enough to warrant routinely prescribing statins to cirrhosis patients, it does highlight the need to prescribe a statin to any cirrhosis patient who qualifies for the drug by standard criteria because of established cardiovascular disease or as part of primary prevention when there is elevated cardiovascular risk, Dr. Arpan Mohanty said at the meeting sponsored by the European Association for the Study of the Liver.

Conventional wisdom has often led to withholding statins from patients with liver disease out of concern for risk of statin-induced hepatotoxicity, said Dr. Mohanty, a gastroenterology researcher at Yale University in New Haven, Conn. But the new findings suggesting such overwhelming benefit from statin treatment in these patients indicates that “statin use should not be avoided” when patients with liver disease would otherwise qualify for statin treatment. “Statins should be prescribed when required for atherosclerosis,” she said, adding that in New Haven her program has run sessions to educate primary care physicians on this.

The study used data collected during 1996-2009 by the Hepatitis C Virus Clinical Case Registry of the U.S. Department of Veterans Affairs, which includes more than 340,000 veterans, of whom more than 45,000 had been diagnosed with cirrhosis. Further analysis identified 1,323 eligible veterans from this group on statin treatment, and 12,522 not on statin treatment. Propensity score matching narrowed the study group down to 685 hepatitis C virus–infected veterans with cirrhosis who were on statin treatment, and 2,062 closely matched veterans infected with HCV and with cirrhosis but not receiving statin therapy.

©Sebastian Kaulitzki/thinkstockphotos.com

The patients averaged 56 years old, 98% were men, and comorbidities were common; a third had a history of coronary artery disease, more than 80% had hypertension, more than half had diabetes, and more than half had alcohol dependency. Among patients with a serum cholesterol level greater than 200 mg/dL, 57% were not on a statin; among those with a serum low-density cholesterol level of about 160 mg/dL, 35% were not receiving a statin. “Statin use is low in patients with cirrhosis, even in those with high cardiovascular risk,” Dr. Mohanty said.

She and her associates tracked the incidence of death for a median of more than 2 years in these patients, and they followed new episodes of cirrhosis decompensation for nearly 2 years. With adjustment for age, body mass index, serum albumin, and fibrosis-4 and MELD (Model for End-Stage Liver Disease) scores, the rates of both death and cirrhosis decompensation were each a statistically significant 45% lower among the patients on statins, compared with those not on a statin, they reported.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

VIENNA – Patients infected with hepatitis C virus who developed cirrhosis and received statin treatment had significantly lower rates of both death and cirrhosis decompensation, compared with cirrhosis patients who did not receive a statin in a confounder-adjusted analysis of data from more than 2,700 patients in a U.S. Department of Veterans Affairs database.

While this suggestive evidence is not strong enough to warrant routinely prescribing statins to cirrhosis patients, it does highlight the need to prescribe a statin to any cirrhosis patient who qualifies for the drug by standard criteria because of established cardiovascular disease or as part of primary prevention when there is elevated cardiovascular risk, Dr. Arpan Mohanty said at the meeting sponsored by the European Association for the Study of the Liver.

Conventional wisdom has often led to withholding statins from patients with liver disease out of concern for risk of statin-induced hepatotoxicity, said Dr. Mohanty, a gastroenterology researcher at Yale University in New Haven, Conn. But the new findings suggesting such overwhelming benefit from statin treatment in these patients indicates that “statin use should not be avoided” when patients with liver disease would otherwise qualify for statin treatment. “Statins should be prescribed when required for atherosclerosis,” she said, adding that in New Haven her program has run sessions to educate primary care physicians on this.

The study used data collected during 1996-2009 by the Hepatitis C Virus Clinical Case Registry of the U.S. Department of Veterans Affairs, which includes more than 340,000 veterans, of whom more than 45,000 had been diagnosed with cirrhosis. Further analysis identified 1,323 eligible veterans from this group on statin treatment, and 12,522 not on statin treatment. Propensity score matching narrowed the study group down to 685 hepatitis C virus–infected veterans with cirrhosis who were on statin treatment, and 2,062 closely matched veterans infected with HCV and with cirrhosis but not receiving statin therapy.

©Sebastian Kaulitzki/thinkstockphotos.com

The patients averaged 56 years old, 98% were men, and comorbidities were common; a third had a history of coronary artery disease, more than 80% had hypertension, more than half had diabetes, and more than half had alcohol dependency. Among patients with a serum cholesterol level greater than 200 mg/dL, 57% were not on a statin; among those with a serum low-density cholesterol level of about 160 mg/dL, 35% were not receiving a statin. “Statin use is low in patients with cirrhosis, even in those with high cardiovascular risk,” Dr. Mohanty said.

She and her associates tracked the incidence of death for a median of more than 2 years in these patients, and they followed new episodes of cirrhosis decompensation for nearly 2 years. With adjustment for age, body mass index, serum albumin, and fibrosis-4 and MELD (Model for End-Stage Liver Disease) scores, the rates of both death and cirrhosis decompensation were each a statistically significant 45% lower among the patients on statins, compared with those not on a statin, they reported.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

VIENNA – Patients infected with hepatitis C virus who developed cirrhosis and received statin treatment had significantly lower rates of both death and cirrhosis decompensation, compared with cirrhosis patients who did not receive a statin in a confounder-adjusted analysis of data from more than 2,700 patients in a U.S. Department of Veterans Affairs database.

While this suggestive evidence is not strong enough to warrant routinely prescribing statins to cirrhosis patients, it does highlight the need to prescribe a statin to any cirrhosis patient who qualifies for the drug by standard criteria because of established cardiovascular disease or as part of primary prevention when there is elevated cardiovascular risk, Dr. Arpan Mohanty said at the meeting sponsored by the European Association for the Study of the Liver.

Conventional wisdom has often led to withholding statins from patients with liver disease out of concern for risk of statin-induced hepatotoxicity, said Dr. Mohanty, a gastroenterology researcher at Yale University in New Haven, Conn. But the new findings suggesting such overwhelming benefit from statin treatment in these patients indicates that “statin use should not be avoided” when patients with liver disease would otherwise qualify for statin treatment. “Statins should be prescribed when required for atherosclerosis,” she said, adding that in New Haven her program has run sessions to educate primary care physicians on this.

The study used data collected during 1996-2009 by the Hepatitis C Virus Clinical Case Registry of the U.S. Department of Veterans Affairs, which includes more than 340,000 veterans, of whom more than 45,000 had been diagnosed with cirrhosis. Further analysis identified 1,323 eligible veterans from this group on statin treatment, and 12,522 not on statin treatment. Propensity score matching narrowed the study group down to 685 hepatitis C virus–infected veterans with cirrhosis who were on statin treatment, and 2,062 closely matched veterans infected with HCV and with cirrhosis but not receiving statin therapy.

©Sebastian Kaulitzki/thinkstockphotos.com

The patients averaged 56 years old, 98% were men, and comorbidities were common; a third had a history of coronary artery disease, more than 80% had hypertension, more than half had diabetes, and more than half had alcohol dependency. Among patients with a serum cholesterol level greater than 200 mg/dL, 57% were not on a statin; among those with a serum low-density cholesterol level of about 160 mg/dL, 35% were not receiving a statin. “Statin use is low in patients with cirrhosis, even in those with high cardiovascular risk,” Dr. Mohanty said.

She and her associates tracked the incidence of death for a median of more than 2 years in these patients, and they followed new episodes of cirrhosis decompensation for nearly 2 years. With adjustment for age, body mass index, serum albumin, and fibrosis-4 and MELD (Model for End-Stage Liver Disease) scores, the rates of both death and cirrhosis decompensation were each a statistically significant 45% lower among the patients on statins, compared with those not on a statin, they reported.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

VIENNA– In addition to dramatically increasing the risk of liver cancer more than 68-fold, chronic hepatitis C virus (HCV) infection more than doubled or tripled the risk of a host of other solid tumors and hematologic malignancies in a large retrospective, cross-sectional study.

Data from the Kaiser Permanente Southern California HMO accounting for more than 145,000 patient-years of follow-up for HCV-infected individuals and 14,000,000 patient-years of follow-up for non–HCV-infected individuals showed the crude rate ratio for the development of all cancers including hepatocellular carcinoma (HCC) was 2.33 (P < .0001), and excluding HCC, was 1.84.

The crude rate ratios for individual cancers in HCV-infected, compared with non–HCV-infected individuals were 68.67 for hepatocellular carcinoma (HCC); 3.59 for non-Hodgkin’s lymphoma (NHL); 3.41 for multiple myeloma; 3.05 for renal cancer; 3.03 for stomach cancer; 2.79 for pancreatic cancer; 2.56 for head and neck cancer; 2.51 for esophageal cancer; 2.44 for lung cancer; 2.05 for prostate cancer; and 1.88 for colorectal cancer.

Courtesy ILC 2015

“We need to interpret these results cautiously,” Dr. Anders Nyberg, a hepatologist at Kaiser Permanente Southern California in San Diego, acknowledged at the International Liver Congress sponsored by the European Association for the Study of the Liver.

“The strength of the study is that it is a large database in a ‘real-world’ population,” but one limitation is that it cannot establish causality and how chronic HCV infection might be linked to the increased risk of these cancers.

The link between chronic HCV infection and liver cancer is well established, and Swedish researchers have also previously reported a link with NHL and multiple myeloma (Hepatology 2005;13:652-9; doi:10.1002/hep.20608). Dr. Nyberg noted, however, that there are sporadic data on HCV and other cancer types.

The objective of the present study was therefore to look further at the possible association between HCV infection and cancer in a large population by linking the Kaiser Permanente Southern California data to the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database. Patients were included if they had HCV diagnosed between 2008 and 2012 and were aged 18 years or older but excluded if they had HIV coinfection or a history of solid organ or bone marrow transplantation.

The study population consisted of 1,831 patients with a mean age of 62 years who had chronic HCV and a cancer diagnosis, 33,881 patients aged a mean of 59 years who had HCV but no cancer diagnosis, and 5,297,191 individuals aged 72 years without HCV. Dr. Nyberg noted that study subjects were predominantly male (around 50%-60%) and from white or Hispanic backgrounds.

Baseline comorbidities were more common in patients with HCV and cancer, with a Charlson Comorbidity Index of 2.1, than in those with HCV but no cancer (Charlson index of 1.5) or those in the non–HCV-infected cohort (Charlson index 0.5). There was a higher percentage of patients who smoked tobacco or with alcohol abuse in the HCV vs. non–HCV-infected cohort groups, and HCV patients were more likely to have diabetes mellitus and cirrhosis, but a lower body mass index.

When HCV and non–HCV-infected cohorts were stratified according to tobacco use, alcohol abuse, diabetes mellitus, and body weight, the increase in the cancer rate ratio for all cancer sites remained significant, as did the increase in rate of HCC and NHL.

“In the absence of alcohol abuse, tobacco use, and diabetes mellitus, there was an increase in the rate of many cancer types among those with HCV,” Dr. Nyberg said. However, when those variables were present, HCV had a more moderate effect on the cancer rates than the variables themselves, but rates were still increased.

“I interpret these data that the increased overall cancer rate is multifactorial. It may be related to hepatitis C, but it is also related to alcohol abuse, tobacco use, and diabetes mellitus,” Dr. Nyberg said at a press conference. “In the short term, my take-home message is that we can take HCV out of the equation.”

He qualified this further in an interview saying, “It is important not to just address the hepatitis C but also to address the other risk factors like stopping smoking, cutting down on drinking, reducing weight, and trying to prevent diabetes.”

This is a descriptive study, Dr. Nyberg added, and more research will be needed to further evaluate the findings.

The study was supported by a grant from Gilead Sciences paid to Kaiser Permanente Southern California. Dr. Anders Nyberg and Dr. Lisa Nyberg are employees of Kaiser Permanente Southern California but had no personal financial conflicts of interest.

VIENNA– In addition to dramatically increasing the risk of liver cancer more than 68-fold, chronic hepatitis C virus (HCV) infection more than doubled or tripled the risk of a host of other solid tumors and hematologic malignancies in a large retrospective, cross-sectional study.

Data from the Kaiser Permanente Southern California HMO accounting for more than 145,000 patient-years of follow-up for HCV-infected individuals and 14,000,000 patient-years of follow-up for non–HCV-infected individuals showed the crude rate ratio for the development of all cancers including hepatocellular carcinoma (HCC) was 2.33 (P < .0001), and excluding HCC, was 1.84.

The crude rate ratios for individual cancers in HCV-infected, compared with non–HCV-infected individuals were 68.67 for hepatocellular carcinoma (HCC); 3.59 for non-Hodgkin’s lymphoma (NHL); 3.41 for multiple myeloma; 3.05 for renal cancer; 3.03 for stomach cancer; 2.79 for pancreatic cancer; 2.56 for head and neck cancer; 2.51 for esophageal cancer; 2.44 for lung cancer; 2.05 for prostate cancer; and 1.88 for colorectal cancer.

Courtesy ILC 2015

“We need to interpret these results cautiously,” Dr. Anders Nyberg, a hepatologist at Kaiser Permanente Southern California in San Diego, acknowledged at the International Liver Congress sponsored by the European Association for the Study of the Liver.

“The strength of the study is that it is a large database in a ‘real-world’ population,” but one limitation is that it cannot establish causality and how chronic HCV infection might be linked to the increased risk of these cancers.

The link between chronic HCV infection and liver cancer is well established, and Swedish researchers have also previously reported a link with NHL and multiple myeloma (Hepatology 2005;13:652-9; doi:10.1002/hep.20608). Dr. Nyberg noted, however, that there are sporadic data on HCV and other cancer types.

The objective of the present study was therefore to look further at the possible association between HCV infection and cancer in a large population by linking the Kaiser Permanente Southern California data to the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database. Patients were included if they had HCV diagnosed between 2008 and 2012 and were aged 18 years or older but excluded if they had HIV coinfection or a history of solid organ or bone marrow transplantation.

The study population consisted of 1,831 patients with a mean age of 62 years who had chronic HCV and a cancer diagnosis, 33,881 patients aged a mean of 59 years who had HCV but no cancer diagnosis, and 5,297,191 individuals aged 72 years without HCV. Dr. Nyberg noted that study subjects were predominantly male (around 50%-60%) and from white or Hispanic backgrounds.

Baseline comorbidities were more common in patients with HCV and cancer, with a Charlson Comorbidity Index of 2.1, than in those with HCV but no cancer (Charlson index of 1.5) or those in the non–HCV-infected cohort (Charlson index 0.5). There was a higher percentage of patients who smoked tobacco or with alcohol abuse in the HCV vs. non–HCV-infected cohort groups, and HCV patients were more likely to have diabetes mellitus and cirrhosis, but a lower body mass index.

When HCV and non–HCV-infected cohorts were stratified according to tobacco use, alcohol abuse, diabetes mellitus, and body weight, the increase in the cancer rate ratio for all cancer sites remained significant, as did the increase in rate of HCC and NHL.

“In the absence of alcohol abuse, tobacco use, and diabetes mellitus, there was an increase in the rate of many cancer types among those with HCV,” Dr. Nyberg said. However, when those variables were present, HCV had a more moderate effect on the cancer rates than the variables themselves, but rates were still increased.

“I interpret these data that the increased overall cancer rate is multifactorial. It may be related to hepatitis C, but it is also related to alcohol abuse, tobacco use, and diabetes mellitus,” Dr. Nyberg said at a press conference. “In the short term, my take-home message is that we can take HCV out of the equation.”

He qualified this further in an interview saying, “It is important not to just address the hepatitis C but also to address the other risk factors like stopping smoking, cutting down on drinking, reducing weight, and trying to prevent diabetes.”

This is a descriptive study, Dr. Nyberg added, and more research will be needed to further evaluate the findings.

The study was supported by a grant from Gilead Sciences paid to Kaiser Permanente Southern California. Dr. Anders Nyberg and Dr. Lisa Nyberg are employees of Kaiser Permanente Southern California but had no personal financial conflicts of interest.

VIENNA– In addition to dramatically increasing the risk of liver cancer more than 68-fold, chronic hepatitis C virus (HCV) infection more than doubled or tripled the risk of a host of other solid tumors and hematologic malignancies in a large retrospective, cross-sectional study.

Data from the Kaiser Permanente Southern California HMO accounting for more than 145,000 patient-years of follow-up for HCV-infected individuals and 14,000,000 patient-years of follow-up for non–HCV-infected individuals showed the crude rate ratio for the development of all cancers including hepatocellular carcinoma (HCC) was 2.33 (P < .0001), and excluding HCC, was 1.84.

The crude rate ratios for individual cancers in HCV-infected, compared with non–HCV-infected individuals were 68.67 for hepatocellular carcinoma (HCC); 3.59 for non-Hodgkin’s lymphoma (NHL); 3.41 for multiple myeloma; 3.05 for renal cancer; 3.03 for stomach cancer; 2.79 for pancreatic cancer; 2.56 for head and neck cancer; 2.51 for esophageal cancer; 2.44 for lung cancer; 2.05 for prostate cancer; and 1.88 for colorectal cancer.

Courtesy ILC 2015

“We need to interpret these results cautiously,” Dr. Anders Nyberg, a hepatologist at Kaiser Permanente Southern California in San Diego, acknowledged at the International Liver Congress sponsored by the European Association for the Study of the Liver.

“The strength of the study is that it is a large database in a ‘real-world’ population,” but one limitation is that it cannot establish causality and how chronic HCV infection might be linked to the increased risk of these cancers.

The link between chronic HCV infection and liver cancer is well established, and Swedish researchers have also previously reported a link with NHL and multiple myeloma (Hepatology 2005;13:652-9; doi:10.1002/hep.20608). Dr. Nyberg noted, however, that there are sporadic data on HCV and other cancer types.

The objective of the present study was therefore to look further at the possible association between HCV infection and cancer in a large population by linking the Kaiser Permanente Southern California data to the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database. Patients were included if they had HCV diagnosed between 2008 and 2012 and were aged 18 years or older but excluded if they had HIV coinfection or a history of solid organ or bone marrow transplantation.

The study population consisted of 1,831 patients with a mean age of 62 years who had chronic HCV and a cancer diagnosis, 33,881 patients aged a mean of 59 years who had HCV but no cancer diagnosis, and 5,297,191 individuals aged 72 years without HCV. Dr. Nyberg noted that study subjects were predominantly male (around 50%-60%) and from white or Hispanic backgrounds.

Baseline comorbidities were more common in patients with HCV and cancer, with a Charlson Comorbidity Index of 2.1, than in those with HCV but no cancer (Charlson index of 1.5) or those in the non–HCV-infected cohort (Charlson index 0.5). There was a higher percentage of patients who smoked tobacco or with alcohol abuse in the HCV vs. non–HCV-infected cohort groups, and HCV patients were more likely to have diabetes mellitus and cirrhosis, but a lower body mass index.

When HCV and non–HCV-infected cohorts were stratified according to tobacco use, alcohol abuse, diabetes mellitus, and body weight, the increase in the cancer rate ratio for all cancer sites remained significant, as did the increase in rate of HCC and NHL.

“In the absence of alcohol abuse, tobacco use, and diabetes mellitus, there was an increase in the rate of many cancer types among those with HCV,” Dr. Nyberg said. However, when those variables were present, HCV had a more moderate effect on the cancer rates than the variables themselves, but rates were still increased.

“I interpret these data that the increased overall cancer rate is multifactorial. It may be related to hepatitis C, but it is also related to alcohol abuse, tobacco use, and diabetes mellitus,” Dr. Nyberg said at a press conference. “In the short term, my take-home message is that we can take HCV out of the equation.”

He qualified this further in an interview saying, “It is important not to just address the hepatitis C but also to address the other risk factors like stopping smoking, cutting down on drinking, reducing weight, and trying to prevent diabetes.”

This is a descriptive study, Dr. Nyberg added, and more research will be needed to further evaluate the findings.

The study was supported by a grant from Gilead Sciences paid to Kaiser Permanente Southern California. Dr. Anders Nyberg and Dr. Lisa Nyberg are employees of Kaiser Permanente Southern California but had no personal financial conflicts of interest.

VIENNA – Roughly half of American adults with chronic hepatitis C infection are unaware of their infection, and about one-fifth of these people with unsuspected infection likely have advanced liver fibrosis, according to a new analysis of U.S. data.

These findings “strengthen the recommendation for hepatitis C virus (HCV) screening in asymptomatic individuals,” Dr. Prowpanga Udompap said at the meeting sponsored by the European Association for the Study of the Liver.

Courtesy US. Dept of Veterans Affairs

People infected by HCV with advanced liver fibrosis have top priority for receiving curative drug treatment, according to recommendations by the American Association for the Study of the Liver and the Infectious Diseases Society of America.

People who have HCV-associated liver fibrosis that goes untreated also risk having their infection become more refractory to cure over time, they risk progressive hepatic deterioration that will eventually become symptomatic, and they face increasing risk for developing liver cancer, noted Dr. W. Ray Kim, senior author of the study and professor of medicine and chief of gastroenterology and hepatology at Stanford (Calif.) University.

Mitchel L. Zoler/Frontline Medical News

Dr. Kim said he was surprised that such a large percentage of Americans who have unrecognized HCV infection also probably have substantial hepatic damage.

“To me it’s alarming that 20% of people who are not aware of their HCV infection are treatment candidates. These people are out there, but not getting treated,” he said in an interview.

Current U.S. HCV screening recommendations from the Centers for Disease Control and Prevention call for screening all Americans born during 1945-1965, “but there is no incentive to screen” and many U.S. primary care physicians don’t have HCV screening on their radar, he said.

The analysis conducted by Dr. Udompap and Dr. Kim used data collected by the National Health and Nutrition Examination Survey during 2001-2012, when the National Center for Health Statistics administered HCV testing to 45,000 of the 62,000 individuals who participated in the survey during this period.

Of the 45,000 people tested, 420 (0.9%) screened antibody positive and had infection confirmed by a second, RNA-based test. The HCV positive patients then received a survey that included a question of whether they were aware of their HCV status before their current test result notification. One hundred sixty-three people (39%) completed and returned the survey: Eighty-three said they had previously been unaware they were HCV positive, and 80 said that they had known about their infection. The 50% rate of awareness of HCV chronic infection is consistent with a previously reported rate (Hepatology 2012;55:1652-61), said Dr. Udompap, a gastroenterology researcher at Stanford.

Mitchel L. Zoler/Frontline Medical News

Individuals who were aware of their infection and those who were not had very similar demographic and clinical parameters. The average age was 53 years, and about two-thirds were men.

Dr. Udompap ran estimates of each respondent’s liver fibrosis and cirrhosis severity using the FIB-4 score and APRI score and data collected during the survey on age, liver enzyme levels, and platelet counts. These calculations showed that 22% of those ignorant of their HCV-positive status had a high probability of having advanced fibrosis, and 11% had a high probability of having cirrhosis, Dr. Udompap reported.

These rates tracked close to those of the people who knew about their HCV-positive status, of whom 15% had a high probability of having advanced liver fibrosis and 11% were highly likely to have cirrhosis.

Dr. Udompap reported having no financial disclosures. Dr. Kim has been a consultant to several drug companies that market, or are developing drugs, used to eradicate hepatitis C infections.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

VIENNA – Roughly half of American adults with chronic hepatitis C infection are unaware of their infection, and about one-fifth of these people with unsuspected infection likely have advanced liver fibrosis, according to a new analysis of U.S. data.

These findings “strengthen the recommendation for hepatitis C virus (HCV) screening in asymptomatic individuals,” Dr. Prowpanga Udompap said at the meeting sponsored by the European Association for the Study of the Liver.

Courtesy US. Dept of Veterans Affairs

People infected by HCV with advanced liver fibrosis have top priority for receiving curative drug treatment, according to recommendations by the American Association for the Study of the Liver and the Infectious Diseases Society of America.

People who have HCV-associated liver fibrosis that goes untreated also risk having their infection become more refractory to cure over time, they risk progressive hepatic deterioration that will eventually become symptomatic, and they face increasing risk for developing liver cancer, noted Dr. W. Ray Kim, senior author of the study and professor of medicine and chief of gastroenterology and hepatology at Stanford (Calif.) University.

Mitchel L. Zoler/Frontline Medical News

Dr. Kim said he was surprised that such a large percentage of Americans who have unrecognized HCV infection also probably have substantial hepatic damage.

“To me it’s alarming that 20% of people who are not aware of their HCV infection are treatment candidates. These people are out there, but not getting treated,” he said in an interview.

Current U.S. HCV screening recommendations from the Centers for Disease Control and Prevention call for screening all Americans born during 1945-1965, “but there is no incentive to screen” and many U.S. primary care physicians don’t have HCV screening on their radar, he said.

The analysis conducted by Dr. Udompap and Dr. Kim used data collected by the National Health and Nutrition Examination Survey during 2001-2012, when the National Center for Health Statistics administered HCV testing to 45,000 of the 62,000 individuals who participated in the survey during this period.

Of the 45,000 people tested, 420 (0.9%) screened antibody positive and had infection confirmed by a second, RNA-based test. The HCV positive patients then received a survey that included a question of whether they were aware of their HCV status before their current test result notification. One hundred sixty-three people (39%) completed and returned the survey: Eighty-three said they had previously been unaware they were HCV positive, and 80 said that they had known about their infection. The 50% rate of awareness of HCV chronic infection is consistent with a previously reported rate (Hepatology 2012;55:1652-61), said Dr. Udompap, a gastroenterology researcher at Stanford.

Mitchel L. Zoler/Frontline Medical News

Individuals who were aware of their infection and those who were not had very similar demographic and clinical parameters. The average age was 53 years, and about two-thirds were men.

Dr. Udompap ran estimates of each respondent’s liver fibrosis and cirrhosis severity using the FIB-4 score and APRI score and data collected during the survey on age, liver enzyme levels, and platelet counts. These calculations showed that 22% of those ignorant of their HCV-positive status had a high probability of having advanced fibrosis, and 11% had a high probability of having cirrhosis, Dr. Udompap reported.

These rates tracked close to those of the people who knew about their HCV-positive status, of whom 15% had a high probability of having advanced liver fibrosis and 11% were highly likely to have cirrhosis.

Dr. Udompap reported having no financial disclosures. Dr. Kim has been a consultant to several drug companies that market, or are developing drugs, used to eradicate hepatitis C infections.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

VIENNA – Roughly half of American adults with chronic hepatitis C infection are unaware of their infection, and about one-fifth of these people with unsuspected infection likely have advanced liver fibrosis, according to a new analysis of U.S. data.

These findings “strengthen the recommendation for hepatitis C virus (HCV) screening in asymptomatic individuals,” Dr. Prowpanga Udompap said at the meeting sponsored by the European Association for the Study of the Liver.

Courtesy US. Dept of Veterans Affairs

People infected by HCV with advanced liver fibrosis have top priority for receiving curative drug treatment, according to recommendations by the American Association for the Study of the Liver and the Infectious Diseases Society of America.

People who have HCV-associated liver fibrosis that goes untreated also risk having their infection become more refractory to cure over time, they risk progressive hepatic deterioration that will eventually become symptomatic, and they face increasing risk for developing liver cancer, noted Dr. W. Ray Kim, senior author of the study and professor of medicine and chief of gastroenterology and hepatology at Stanford (Calif.) University.

Mitchel L. Zoler/Frontline Medical News

Dr. Kim said he was surprised that such a large percentage of Americans who have unrecognized HCV infection also probably have substantial hepatic damage.

“To me it’s alarming that 20% of people who are not aware of their HCV infection are treatment candidates. These people are out there, but not getting treated,” he said in an interview.

Current U.S. HCV screening recommendations from the Centers for Disease Control and Prevention call for screening all Americans born during 1945-1965, “but there is no incentive to screen” and many U.S. primary care physicians don’t have HCV screening on their radar, he said.

The analysis conducted by Dr. Udompap and Dr. Kim used data collected by the National Health and Nutrition Examination Survey during 2001-2012, when the National Center for Health Statistics administered HCV testing to 45,000 of the 62,000 individuals who participated in the survey during this period.

Of the 45,000 people tested, 420 (0.9%) screened antibody positive and had infection confirmed by a second, RNA-based test. The HCV positive patients then received a survey that included a question of whether they were aware of their HCV status before their current test result notification. One hundred sixty-three people (39%) completed and returned the survey: Eighty-three said they had previously been unaware they were HCV positive, and 80 said that they had known about their infection. The 50% rate of awareness of HCV chronic infection is consistent with a previously reported rate (Hepatology 2012;55:1652-61), said Dr. Udompap, a gastroenterology researcher at Stanford.

Mitchel L. Zoler/Frontline Medical News

Individuals who were aware of their infection and those who were not had very similar demographic and clinical parameters. The average age was 53 years, and about two-thirds were men.

Dr. Udompap ran estimates of each respondent’s liver fibrosis and cirrhosis severity using the FIB-4 score and APRI score and data collected during the survey on age, liver enzyme levels, and platelet counts. These calculations showed that 22% of those ignorant of their HCV-positive status had a high probability of having advanced fibrosis, and 11% had a high probability of having cirrhosis, Dr. Udompap reported.

These rates tracked close to those of the people who knew about their HCV-positive status, of whom 15% had a high probability of having advanced liver fibrosis and 11% were highly likely to have cirrhosis.

Dr. Udompap reported having no financial disclosures. Dr. Kim has been a consultant to several drug companies that market, or are developing drugs, used to eradicate hepatitis C infections.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

VIENNA – A new, once-daily, single-pill regimen for treating chronic hepatitis C infection without interferon or ribavirin showed 95% eradication efficacy after 12 weeks of safe treatment in a pivotal trial with 421 treatment-naive patients.

The study results also showed that the combination of grazoprevir and elbasvir, drugs that target two different hepatitis C proteins, was equally effective in noncirrhotic and compensated cirrhotic patents. Although more than 90% of the enrolled patients were infected by genotype 1 hepatitis C, the new combination also showed efficacy in the small number of patients enrolled who were infected by either genotype 4 or genotype 6 virus.

Mitchel L. Zoler/Frontline Medical News

Perhaps the most important consequence of the new study, the C-EDGE trial, is that it put the grazoprevir-elbasvir combination on track for near-term approval as another simple, effective, interferon- and ribavirin-free regimen to cure patients of chronic hepatitis C infection, a step that would sharpen competition in this niche and could lead to price reductions among the currently available, high-cost treatments.

“I love competition,” said Dr. Stefan Zeuzem as he reported the results at the meeting, which was sponsored by the European Association for the Study of the Liver. “We should have many regimens that produce excellent sustained virologic response because we see in the data that certain drug combinations fit better for special indications,” said Dr. Zeuzem, professor and chief of medicine at J.W. Goethe University Hospital in Frankfurt, Germany.

“This provides an excellent option, and we need more options” for treating chronic hepatitis C, said Dr. K. Rajender Reddy, a coauthor with Dr. Zeuzem on the study and professor and director of hepatology at the University of Pennsylvania in Philadelphia.

“It’s one pill, it works in more than 90% of patients, the side effect profile is good,” and the grazoprevir-elbasvir combination can be used in patients with severe renal impairment and a glomerular filtration rate below 30 mL/min per 1.73 m², something not recommended with one of the major drugs now available for treating hepatitis C, sofosbuvir (Sovaldi and Harvoni), Dr. Reddy said in an interview.

Mitchel L. Zoler/Frontline Medical News

And it’s a “huge step” toward simpler hepatitis C–treatment regimens that are applicable to a broader range of patients, commented Dr. Donald M. Jensen, a hepatologist in Oak Park, Ill. who helped develop hepatitis C–treatment recommendations for the American Association for the Study of Liver Diseases.

“It offers the ability to treat multiple genotypes and had a high success rate, but it still relies on a protease inhibitor so it will still have issues of drug-drug interactions,” Dr. Jensen said in an interview. “Hopefully, as more regimens come out, companies will have to price their regimens competitively.”

The C-EDGE trial randomized 316 patients to immediate treatment with the grazoprevir-elbasvir combination and 105 patients to 4 weeks of placebo treatment as controls for adverse-effect monitoring, after which they also began active treatment. The trial enrolled patients during June 2014-March 2015 at 60 centers in nine countries. The rate of sustained virologic response after 12 weeks, the study’s primary endpoint, occurred in 92% of patients infected with genotype 1a, 99% of those infected by 1b, 100% of the 18 patients infected by genotype 4, and in 8 of the 10 patients infected by genotype 6, Dr. Zeuzem reported.

Concurrent with his talk at the meeting on April 24, the results were published online (Ann. Int. Med. 2015 [doi:10.7326/M15-0785]).

Mitchel L. Zoler/Frontline Medical News

“You can use this regimen comfortably for genotype 4. Whether you want to take the data seriously for genotype 6 is a question,” noted Dr. Reddy, who acknowledged that the 10-patient experience for genotype 6 is too preliminary to provide firm guidance on efficacy. The apparent efficacy of the grazoprevir-elbasvir combination beyond genotype 1 reflects the fact that both drugs are “second generation” agents, particularly designed to have pan-genotype efficacy, Dr. Reddy said.

The safety profile of the two drugs was encouraging, with adverse events occurring at rates no different than in the placebo arm. No patient had a serious adverse event on active treatment, and two patients in the active arm discontinued because of an adverse event.

The data also showed that the regimen was effective regardless of age, sex, race, or the presence of compensated cirrhosis. All of the virologic failures occurred in patients with high viral loads – greater than 800,000 IU/mL – when they started treatment, a finding consistent with prior reports, Dr. Zeuzem said. The patients who had virologic failure carried resistance-associated variant strains of hepatitis C.

The C-EDGE trial was sponsored by Merck, which is developing the drugs used in the study. Dr. Zeuzem has been a consultant for and speaker on behalf of Merck and for AbbVie, Bristol-Myers Squibb, Gilead, and Janssen. Dr. Reddy has been a consultant to and received research support from Merck and Bristol-Myers Squibb, AbbVie, Janssen, and Gilead, Dr. Jensen had no disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

VIENNA – A new, once-daily, single-pill regimen for treating chronic hepatitis C infection without interferon or ribavirin showed 95% eradication efficacy after 12 weeks of safe treatment in a pivotal trial with 421 treatment-naive patients.

The study results also showed that the combination of grazoprevir and elbasvir, drugs that target two different hepatitis C proteins, was equally effective in noncirrhotic and compensated cirrhotic patents. Although more than 90% of the enrolled patients were infected by genotype 1 hepatitis C, the new combination also showed efficacy in the small number of patients enrolled who were infected by either genotype 4 or genotype 6 virus.

Mitchel L. Zoler/Frontline Medical News

Perhaps the most important consequence of the new study, the C-EDGE trial, is that it put the grazoprevir-elbasvir combination on track for near-term approval as another simple, effective, interferon- and ribavirin-free regimen to cure patients of chronic hepatitis C infection, a step that would sharpen competition in this niche and could lead to price reductions among the currently available, high-cost treatments.

“I love competition,” said Dr. Stefan Zeuzem as he reported the results at the meeting, which was sponsored by the European Association for the Study of the Liver. “We should have many regimens that produce excellent sustained virologic response because we see in the data that certain drug combinations fit better for special indications,” said Dr. Zeuzem, professor and chief of medicine at J.W. Goethe University Hospital in Frankfurt, Germany.

“This provides an excellent option, and we need more options” for treating chronic hepatitis C, said Dr. K. Rajender Reddy, a coauthor with Dr. Zeuzem on the study and professor and director of hepatology at the University of Pennsylvania in Philadelphia.

“It’s one pill, it works in more than 90% of patients, the side effect profile is good,” and the grazoprevir-elbasvir combination can be used in patients with severe renal impairment and a glomerular filtration rate below 30 mL/min per 1.73 m², something not recommended with one of the major drugs now available for treating hepatitis C, sofosbuvir (Sovaldi and Harvoni), Dr. Reddy said in an interview.

Mitchel L. Zoler/Frontline Medical News

And it’s a “huge step” toward simpler hepatitis C–treatment regimens that are applicable to a broader range of patients, commented Dr. Donald M. Jensen, a hepatologist in Oak Park, Ill. who helped develop hepatitis C–treatment recommendations for the American Association for the Study of Liver Diseases.

“It offers the ability to treat multiple genotypes and had a high success rate, but it still relies on a protease inhibitor so it will still have issues of drug-drug interactions,” Dr. Jensen said in an interview. “Hopefully, as more regimens come out, companies will have to price their regimens competitively.”

The C-EDGE trial randomized 316 patients to immediate treatment with the grazoprevir-elbasvir combination and 105 patients to 4 weeks of placebo treatment as controls for adverse-effect monitoring, after which they also began active treatment. The trial enrolled patients during June 2014-March 2015 at 60 centers in nine countries. The rate of sustained virologic response after 12 weeks, the study’s primary endpoint, occurred in 92% of patients infected with genotype 1a, 99% of those infected by 1b, 100% of the 18 patients infected by genotype 4, and in 8 of the 10 patients infected by genotype 6, Dr. Zeuzem reported.

Concurrent with his talk at the meeting on April 24, the results were published online (Ann. Int. Med. 2015 [doi:10.7326/M15-0785]).

Mitchel L. Zoler/Frontline Medical News

“You can use this regimen comfortably for genotype 4. Whether you want to take the data seriously for genotype 6 is a question,” noted Dr. Reddy, who acknowledged that the 10-patient experience for genotype 6 is too preliminary to provide firm guidance on efficacy. The apparent efficacy of the grazoprevir-elbasvir combination beyond genotype 1 reflects the fact that both drugs are “second generation” agents, particularly designed to have pan-genotype efficacy, Dr. Reddy said.

The safety profile of the two drugs was encouraging, with adverse events occurring at rates no different than in the placebo arm. No patient had a serious adverse event on active treatment, and two patients in the active arm discontinued because of an adverse event.

The data also showed that the regimen was effective regardless of age, sex, race, or the presence of compensated cirrhosis. All of the virologic failures occurred in patients with high viral loads – greater than 800,000 IU/mL – when they started treatment, a finding consistent with prior reports, Dr. Zeuzem said. The patients who had virologic failure carried resistance-associated variant strains of hepatitis C.

The C-EDGE trial was sponsored by Merck, which is developing the drugs used in the study. Dr. Zeuzem has been a consultant for and speaker on behalf of Merck and for AbbVie, Bristol-Myers Squibb, Gilead, and Janssen. Dr. Reddy has been a consultant to and received research support from Merck and Bristol-Myers Squibb, AbbVie, Janssen, and Gilead, Dr. Jensen had no disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

VIENNA – A new, once-daily, single-pill regimen for treating chronic hepatitis C infection without interferon or ribavirin showed 95% eradication efficacy after 12 weeks of safe treatment in a pivotal trial with 421 treatment-naive patients.

The study results also showed that the combination of grazoprevir and elbasvir, drugs that target two different hepatitis C proteins, was equally effective in noncirrhotic and compensated cirrhotic patents. Although more than 90% of the enrolled patients were infected by genotype 1 hepatitis C, the new combination also showed efficacy in the small number of patients enrolled who were infected by either genotype 4 or genotype 6 virus.

Mitchel L. Zoler/Frontline Medical News

Perhaps the most important consequence of the new study, the C-EDGE trial, is that it put the grazoprevir-elbasvir combination on track for near-term approval as another simple, effective, interferon- and ribavirin-free regimen to cure patients of chronic hepatitis C infection, a step that would sharpen competition in this niche and could lead to price reductions among the currently available, high-cost treatments.

“I love competition,” said Dr. Stefan Zeuzem as he reported the results at the meeting, which was sponsored by the European Association for the Study of the Liver. “We should have many regimens that produce excellent sustained virologic response because we see in the data that certain drug combinations fit better for special indications,” said Dr. Zeuzem, professor and chief of medicine at J.W. Goethe University Hospital in Frankfurt, Germany.

“This provides an excellent option, and we need more options” for treating chronic hepatitis C, said Dr. K. Rajender Reddy, a coauthor with Dr. Zeuzem on the study and professor and director of hepatology at the University of Pennsylvania in Philadelphia.

“It’s one pill, it works in more than 90% of patients, the side effect profile is good,” and the grazoprevir-elbasvir combination can be used in patients with severe renal impairment and a glomerular filtration rate below 30 mL/min per 1.73 m², something not recommended with one of the major drugs now available for treating hepatitis C, sofosbuvir (Sovaldi and Harvoni), Dr. Reddy said in an interview.

Mitchel L. Zoler/Frontline Medical News

And it’s a “huge step” toward simpler hepatitis C–treatment regimens that are applicable to a broader range of patients, commented Dr. Donald M. Jensen, a hepatologist in Oak Park, Ill. who helped develop hepatitis C–treatment recommendations for the American Association for the Study of Liver Diseases.

“It offers the ability to treat multiple genotypes and had a high success rate, but it still relies on a protease inhibitor so it will still have issues of drug-drug interactions,” Dr. Jensen said in an interview. “Hopefully, as more regimens come out, companies will have to price their regimens competitively.”

The C-EDGE trial randomized 316 patients to immediate treatment with the grazoprevir-elbasvir combination and 105 patients to 4 weeks of placebo treatment as controls for adverse-effect monitoring, after which they also began active treatment. The trial enrolled patients during June 2014-March 2015 at 60 centers in nine countries. The rate of sustained virologic response after 12 weeks, the study’s primary endpoint, occurred in 92% of patients infected with genotype 1a, 99% of those infected by 1b, 100% of the 18 patients infected by genotype 4, and in 8 of the 10 patients infected by genotype 6, Dr. Zeuzem reported.

Concurrent with his talk at the meeting on April 24, the results were published online (Ann. Int. Med. 2015 [doi:10.7326/M15-0785]).

Mitchel L. Zoler/Frontline Medical News

“You can use this regimen comfortably for genotype 4. Whether you want to take the data seriously for genotype 6 is a question,” noted Dr. Reddy, who acknowledged that the 10-patient experience for genotype 6 is too preliminary to provide firm guidance on efficacy. The apparent efficacy of the grazoprevir-elbasvir combination beyond genotype 1 reflects the fact that both drugs are “second generation” agents, particularly designed to have pan-genotype efficacy, Dr. Reddy said.

The safety profile of the two drugs was encouraging, with adverse events occurring at rates no different than in the placebo arm. No patient had a serious adverse event on active treatment, and two patients in the active arm discontinued because of an adverse event.

The data also showed that the regimen was effective regardless of age, sex, race, or the presence of compensated cirrhosis. All of the virologic failures occurred in patients with high viral loads – greater than 800,000 IU/mL – when they started treatment, a finding consistent with prior reports, Dr. Zeuzem said. The patients who had virologic failure carried resistance-associated variant strains of hepatitis C.

The C-EDGE trial was sponsored by Merck, which is developing the drugs used in the study. Dr. Zeuzem has been a consultant for and speaker on behalf of Merck and for AbbVie, Bristol-Myers Squibb, Gilead, and Janssen. Dr. Reddy has been a consultant to and received research support from Merck and Bristol-Myers Squibb, AbbVie, Janssen, and Gilead, Dr. Jensen had no disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

As health officials continue to battle an intravenous drug use–related HIV outbreak in a rural county in Indiana, the Centers for Disease Control and Prevention has issued an official health advisory stressing the need for vigilance at the state and local levels with respect to detecting and controlling similar outbreaks in other communities across the United States.

The Indiana outbreak began in November, with 11 new HIV infections diagnosed by January in Scott County, where fewer than 5 infections per year had been identified previously; since January, an unprecedented 135 infections have been confirmed, and 6 others are under investigation, according to Dr. Jerome M. Adams, Indiana State Health Commissioner.

“To put this in further perspective, from 2009 through 2013, the county only reported three new cases of HIV,” Dr. Adams said in a joint Indiana State Department of Health/CDC teleconference.

New cases are being reported every day on an hourly basis, he added.

The affected community includes only 4,200 people, and 84% of those diagnosed with HIV also tested positive for hepatitis C virus (HCV) infection, Dr. Joan Duwve, chief medical consultant, Indiana State Department of Health, said during the teleconference.

According to the CDC advisory, 96% of 108 infected individuals who were interviewed reported injecting dissolved prescription-type oxymorphone, as well as sharing syringes. The advisory states that “urgent action is needed to prevent further HIV and HCV transmission in this area and to investigate and control any similar outbreaks in other communities.”

Although the national incidence of HIV infections has declined markedly – by about 90% – since peaking in the 1990s, about 50,000 new infections occur each year in the United States, and about 8% of those are associated with intravenous drug use.

“The United States is facing an epidemic of prescription opioid abuse that must be addressed. Opioid poisoning deaths have nearly quadrupled from 1999 through 2011. This epidemic of opioid abuse has already contributed to a severe and growing epidemic of viral hepatitis among people who inject drugs,” said Dr. Jonathan Mermin, director of the National Center for HIV/AIDS Viral Hepatitis, STD, and TB Prevention, who also participated in the teleconference.

New CDC data on HCV show a 150% increase in reports of acute HCV infections nationwide between 2010 to 2013, he said.

“The majority of these infections are believed to be attributable to injection drug use, so we must act now to reverse this trend and to prevent this from undoing progress in HIV prevention to date,” he said.

To identify and control outbreaks quickly, the CDC made several recommendations for both health departments and healthcare providers.

Health departments should review the most recent sources of data on HIV and HCV diagnoses, overdose deaths, admissions for drug treatment, and drug arrests, looking specifically for recent increases in the number of HIV infections attributed to intravenous drug use, and the number of HCV infections among those aged 35 years and younger.

These, as well as high rates of prescription-type opioid abuse and overdose, drug treatment admissions, or drug arrests, are attributes of communities at risk for unrecognized clusters of infections, according to the advisory.

Other recommendations for health departments include ensuring complete contact tracing for new diagnoses and testing of all contacts, ensuring that people who inject drugs and those at high risk of drug injection have access to integrated prevention services, and reminding venues such as emergency departments and community-based clinical practices of the importance of routine opt-out of HIV testing as well as HCV testing per current recommendations.

Additionally, local health department should notify state health departments and the CDC of any suspected clusters of HIV or HCV infection.

Likewise, health care professionals should report suspected clusters to their local or state health department, ensure that HCV-infected patients are also tested for HIV and vice versa, and ensure that those receiving treatment for either HIV or HCV are adhering to prescribed therapy and are engaged in ongoing care.

Syringe-sharing and sexual partners of those diagnosed with HIV or HCV should be encouraged to undergo testing, and providers should report all newly diagnosed infections to the health department, and should refer all persons with substance abuse problems for medication-assisted treatment and counseling. Effective treatments should be used as appropriately indicated.

The risks and benefits of all pain treatment options, and the fact that long-term opioid therapy is not associated with reduced chronic pain, should be discussed with any person for whom opioids are under consideration for pain management, according to the advisory.

In Indiana, where a public health emergency was declared on March 26 and has been extended until May 24, the only local health care provider in the county where all the cases occurred, along with local health officials, law enforcement, community partners, regional health care providers, and the CDC, provided a comprehensive response, including a public education campaign, establishment of an incident command center and community outreach center, short-term authorization of syringe exchange, and support for comprehensive medical care. The care includes HIV and HCV treatment, as well as substance abuse counseling and treatment, according to a “Notes From the Field Report” in the Morbidity and Mortality Weekly Report (MMWR 2015 April 24;64 [early release]:1-2).

“State and local health departments and academic partners, with the assistance of CDC, are working to implement and improve the community outreach programs supported by the executive order and to interrupt injection drug use-related HIV and hepatitis C virus transmission. Contact tracing by state and CDC disease intervention specialists continues to identify those potentially exposed,” the report states.

During the teleconference, Dr. Duwve described the response in detail, noting that the HIV treatment clinic is staffed by Indiana University infectious disease physicians and is supported by the Indiana State Department of Health and local partners.

Testing and treatment services are also provided at the county jail, she said.

“The outbreak highlights the vulnerability of many rural, resource poor populations to drug use, misuse, and addiction. This outbreak also demonstrates the importance of timely HIV surveillance activity and rapid response to interrupt disease transmission,” she said, noting that it also points to the need for expanded mental health and substance use treatment programs in medically under-served rural areas.

Dr. Mermin of the CDC added that “the situation in Indiana should serve as a warning that we cannot let down our guard against these deadly infections.”

sworcester@frontlinemedcom.com

As health officials continue to battle an intravenous drug use–related HIV outbreak in a rural county in Indiana, the Centers for Disease Control and Prevention has issued an official health advisory stressing the need for vigilance at the state and local levels with respect to detecting and controlling similar outbreaks in other communities across the United States.

The Indiana outbreak began in November, with 11 new HIV infections diagnosed by January in Scott County, where fewer than 5 infections per year had been identified previously; since January, an unprecedented 135 infections have been confirmed, and 6 others are under investigation, according to Dr. Jerome M. Adams, Indiana State Health Commissioner.

“To put this in further perspective, from 2009 through 2013, the county only reported three new cases of HIV,” Dr. Adams said in a joint Indiana State Department of Health/CDC teleconference.

New cases are being reported every day on an hourly basis, he added.

The affected community includes only 4,200 people, and 84% of those diagnosed with HIV also tested positive for hepatitis C virus (HCV) infection, Dr. Joan Duwve, chief medical consultant, Indiana State Department of Health, said during the teleconference.

According to the CDC advisory, 96% of 108 infected individuals who were interviewed reported injecting dissolved prescription-type oxymorphone, as well as sharing syringes. The advisory states that “urgent action is needed to prevent further HIV and HCV transmission in this area and to investigate and control any similar outbreaks in other communities.”

Although the national incidence of HIV infections has declined markedly – by about 90% – since peaking in the 1990s, about 50,000 new infections occur each year in the United States, and about 8% of those are associated with intravenous drug use.

“The United States is facing an epidemic of prescription opioid abuse that must be addressed. Opioid poisoning deaths have nearly quadrupled from 1999 through 2011. This epidemic of opioid abuse has already contributed to a severe and growing epidemic of viral hepatitis among people who inject drugs,” said Dr. Jonathan Mermin, director of the National Center for HIV/AIDS Viral Hepatitis, STD, and TB Prevention, who also participated in the teleconference.

New CDC data on HCV show a 150% increase in reports of acute HCV infections nationwide between 2010 to 2013, he said.

“The majority of these infections are believed to be attributable to injection drug use, so we must act now to reverse this trend and to prevent this from undoing progress in HIV prevention to date,” he said.

To identify and control outbreaks quickly, the CDC made several recommendations for both health departments and healthcare providers.

Health departments should review the most recent sources of data on HIV and HCV diagnoses, overdose deaths, admissions for drug treatment, and drug arrests, looking specifically for recent increases in the number of HIV infections attributed to intravenous drug use, and the number of HCV infections among those aged 35 years and younger.

These, as well as high rates of prescription-type opioid abuse and overdose, drug treatment admissions, or drug arrests, are attributes of communities at risk for unrecognized clusters of infections, according to the advisory.

Other recommendations for health departments include ensuring complete contact tracing for new diagnoses and testing of all contacts, ensuring that people who inject drugs and those at high risk of drug injection have access to integrated prevention services, and reminding venues such as emergency departments and community-based clinical practices of the importance of routine opt-out of HIV testing as well as HCV testing per current recommendations.

Additionally, local health department should notify state health departments and the CDC of any suspected clusters of HIV or HCV infection.

Likewise, health care professionals should report suspected clusters to their local or state health department, ensure that HCV-infected patients are also tested for HIV and vice versa, and ensure that those receiving treatment for either HIV or HCV are adhering to prescribed therapy and are engaged in ongoing care.

Syringe-sharing and sexual partners of those diagnosed with HIV or HCV should be encouraged to undergo testing, and providers should report all newly diagnosed infections to the health department, and should refer all persons with substance abuse problems for medication-assisted treatment and counseling. Effective treatments should be used as appropriately indicated.

The risks and benefits of all pain treatment options, and the fact that long-term opioid therapy is not associated with reduced chronic pain, should be discussed with any person for whom opioids are under consideration for pain management, according to the advisory.

In Indiana, where a public health emergency was declared on March 26 and has been extended until May 24, the only local health care provider in the county where all the cases occurred, along with local health officials, law enforcement, community partners, regional health care providers, and the CDC, provided a comprehensive response, including a public education campaign, establishment of an incident command center and community outreach center, short-term authorization of syringe exchange, and support for comprehensive medical care. The care includes HIV and HCV treatment, as well as substance abuse counseling and treatment, according to a “Notes From the Field Report” in the Morbidity and Mortality Weekly Report (MMWR 2015 April 24;64 [early release]:1-2).

“State and local health departments and academic partners, with the assistance of CDC, are working to implement and improve the community outreach programs supported by the executive order and to interrupt injection drug use-related HIV and hepatitis C virus transmission. Contact tracing by state and CDC disease intervention specialists continues to identify those potentially exposed,” the report states.

During the teleconference, Dr. Duwve described the response in detail, noting that the HIV treatment clinic is staffed by Indiana University infectious disease physicians and is supported by the Indiana State Department of Health and local partners.

Testing and treatment services are also provided at the county jail, she said.

“The outbreak highlights the vulnerability of many rural, resource poor populations to drug use, misuse, and addiction. This outbreak also demonstrates the importance of timely HIV surveillance activity and rapid response to interrupt disease transmission,” she said, noting that it also points to the need for expanded mental health and substance use treatment programs in medically under-served rural areas.

Dr. Mermin of the CDC added that “the situation in Indiana should serve as a warning that we cannot let down our guard against these deadly infections.”

sworcester@frontlinemedcom.com

As health officials continue to battle an intravenous drug use–related HIV outbreak in a rural county in Indiana, the Centers for Disease Control and Prevention has issued an official health advisory stressing the need for vigilance at the state and local levels with respect to detecting and controlling similar outbreaks in other communities across the United States.

The Indiana outbreak began in November, with 11 new HIV infections diagnosed by January in Scott County, where fewer than 5 infections per year had been identified previously; since January, an unprecedented 135 infections have been confirmed, and 6 others are under investigation, according to Dr. Jerome M. Adams, Indiana State Health Commissioner.

“To put this in further perspective, from 2009 through 2013, the county only reported three new cases of HIV,” Dr. Adams said in a joint Indiana State Department of Health/CDC teleconference.

New cases are being reported every day on an hourly basis, he added.

The affected community includes only 4,200 people, and 84% of those diagnosed with HIV also tested positive for hepatitis C virus (HCV) infection, Dr. Joan Duwve, chief medical consultant, Indiana State Department of Health, said during the teleconference.

According to the CDC advisory, 96% of 108 infected individuals who were interviewed reported injecting dissolved prescription-type oxymorphone, as well as sharing syringes. The advisory states that “urgent action is needed to prevent further HIV and HCV transmission in this area and to investigate and control any similar outbreaks in other communities.”

Although the national incidence of HIV infections has declined markedly – by about 90% – since peaking in the 1990s, about 50,000 new infections occur each year in the United States, and about 8% of those are associated with intravenous drug use.

“The United States is facing an epidemic of prescription opioid abuse that must be addressed. Opioid poisoning deaths have nearly quadrupled from 1999 through 2011. This epidemic of opioid abuse has already contributed to a severe and growing epidemic of viral hepatitis among people who inject drugs,” said Dr. Jonathan Mermin, director of the National Center for HIV/AIDS Viral Hepatitis, STD, and TB Prevention, who also participated in the teleconference.

New CDC data on HCV show a 150% increase in reports of acute HCV infections nationwide between 2010 to 2013, he said.

“The majority of these infections are believed to be attributable to injection drug use, so we must act now to reverse this trend and to prevent this from undoing progress in HIV prevention to date,” he said.

To identify and control outbreaks quickly, the CDC made several recommendations for both health departments and healthcare providers.

Health departments should review the most recent sources of data on HIV and HCV diagnoses, overdose deaths, admissions for drug treatment, and drug arrests, looking specifically for recent increases in the number of HIV infections attributed to intravenous drug use, and the number of HCV infections among those aged 35 years and younger.

These, as well as high rates of prescription-type opioid abuse and overdose, drug treatment admissions, or drug arrests, are attributes of communities at risk for unrecognized clusters of infections, according to the advisory.

Other recommendations for health departments include ensuring complete contact tracing for new diagnoses and testing of all contacts, ensuring that people who inject drugs and those at high risk of drug injection have access to integrated prevention services, and reminding venues such as emergency departments and community-based clinical practices of the importance of routine opt-out of HIV testing as well as HCV testing per current recommendations.

Additionally, local health department should notify state health departments and the CDC of any suspected clusters of HIV or HCV infection.

Likewise, health care professionals should report suspected clusters to their local or state health department, ensure that HCV-infected patients are also tested for HIV and vice versa, and ensure that those receiving treatment for either HIV or HCV are adhering to prescribed therapy and are engaged in ongoing care.

Syringe-sharing and sexual partners of those diagnosed with HIV or HCV should be encouraged to undergo testing, and providers should report all newly diagnosed infections to the health department, and should refer all persons with substance abuse problems for medication-assisted treatment and counseling. Effective treatments should be used as appropriately indicated.

The risks and benefits of all pain treatment options, and the fact that long-term opioid therapy is not associated with reduced chronic pain, should be discussed with any person for whom opioids are under consideration for pain management, according to the advisory.

In Indiana, where a public health emergency was declared on March 26 and has been extended until May 24, the only local health care provider in the county where all the cases occurred, along with local health officials, law enforcement, community partners, regional health care providers, and the CDC, provided a comprehensive response, including a public education campaign, establishment of an incident command center and community outreach center, short-term authorization of syringe exchange, and support for comprehensive medical care. The care includes HIV and HCV treatment, as well as substance abuse counseling and treatment, according to a “Notes From the Field Report” in the Morbidity and Mortality Weekly Report (MMWR 2015 April 24;64 [early release]:1-2).

“State and local health departments and academic partners, with the assistance of CDC, are working to implement and improve the community outreach programs supported by the executive order and to interrupt injection drug use-related HIV and hepatitis C virus transmission. Contact tracing by state and CDC disease intervention specialists continues to identify those potentially exposed,” the report states.

During the teleconference, Dr. Duwve described the response in detail, noting that the HIV treatment clinic is staffed by Indiana University infectious disease physicians and is supported by the Indiana State Department of Health and local partners.

Testing and treatment services are also provided at the county jail, she said.

“The outbreak highlights the vulnerability of many rural, resource poor populations to drug use, misuse, and addiction. This outbreak also demonstrates the importance of timely HIV surveillance activity and rapid response to interrupt disease transmission,” she said, noting that it also points to the need for expanded mental health and substance use treatment programs in medically under-served rural areas.

Dr. Mermin of the CDC added that “the situation in Indiana should serve as a warning that we cannot let down our guard against these deadly infections.”

sworcester@frontlinemedcom.com

The Food and Drug Administration has approved changes to the warnings and precautions section of the package insert for Olysio (simeprevir).

One addition to the insert is that serious symptomatic bradycardia has been reported by individuals who have taken amiodarone with sofosbuvir and another HCV direct-acting antiviral, including Olysio.

Another change is the inclusion of a statement that hepatic decompensation and hepatic failure have been reported in patients treated with Olysio in combination with peginterferon alfa and ribavirin. Related to this finding, is the other new recommendation that patients with moderate or severe hepatic impairment not take Olysio.

More details on these and other related label changes for Olysio can be found at the FDA website.

The Food and Drug Administration has approved changes to the warnings and precautions section of the package insert for Olysio (simeprevir).

One addition to the insert is that serious symptomatic bradycardia has been reported by individuals who have taken amiodarone with sofosbuvir and another HCV direct-acting antiviral, including Olysio.

Another change is the inclusion of a statement that hepatic decompensation and hepatic failure have been reported in patients treated with Olysio in combination with peginterferon alfa and ribavirin. Related to this finding, is the other new recommendation that patients with moderate or severe hepatic impairment not take Olysio.

More details on these and other related label changes for Olysio can be found at the FDA website.

The Food and Drug Administration has approved changes to the warnings and precautions section of the package insert for Olysio (simeprevir).

One addition to the insert is that serious symptomatic bradycardia has been reported by individuals who have taken amiodarone with sofosbuvir and another HCV direct-acting antiviral, including Olysio.

Another change is the inclusion of a statement that hepatic decompensation and hepatic failure have been reported in patients treated with Olysio in combination with peginterferon alfa and ribavirin. Related to this finding, is the other new recommendation that patients with moderate or severe hepatic impairment not take Olysio.

More details on these and other related label changes for Olysio can be found at the FDA website.

Repurposing the antihistamine medication chlorcyclizine may be a viable option in the treatment of hepatitis C, reported Dr. Shanshan He and coauthors.

In a study of mice carrying human hepatocytes infected with hepatitis C virus, chlorcyclizine significantly inhibited infection of HCV genotypes 1b and 2a without drug resistance at 4 and 6 weeks of treatment (P < .05), respectively, Dr. He and associates reported.

The findings suggest that the use of chlorcyclizine in treating HCV infection may “provide a more affordable alternative to the current costly options, especially in low-resource settings where chronic HCV infection is endemic,” the investigators said in the paper.

Read the full article in Science Translational Medicine 2015 at: doi/10.1126/scitranslmed.3010286.

Repurposing the antihistamine medication chlorcyclizine may be a viable option in the treatment of hepatitis C, reported Dr. Shanshan He and coauthors.

In a study of mice carrying human hepatocytes infected with hepatitis C virus, chlorcyclizine significantly inhibited infection of HCV genotypes 1b and 2a without drug resistance at 4 and 6 weeks of treatment (P < .05), respectively, Dr. He and associates reported.

The findings suggest that the use of chlorcyclizine in treating HCV infection may “provide a more affordable alternative to the current costly options, especially in low-resource settings where chronic HCV infection is endemic,” the investigators said in the paper.

Read the full article in Science Translational Medicine 2015 at: doi/10.1126/scitranslmed.3010286.

Repurposing the antihistamine medication chlorcyclizine may be a viable option in the treatment of hepatitis C, reported Dr. Shanshan He and coauthors.

In a study of mice carrying human hepatocytes infected with hepatitis C virus, chlorcyclizine significantly inhibited infection of HCV genotypes 1b and 2a without drug resistance at 4 and 6 weeks of treatment (P < .05), respectively, Dr. He and associates reported.

The findings suggest that the use of chlorcyclizine in treating HCV infection may “provide a more affordable alternative to the current costly options, especially in low-resource settings where chronic HCV infection is endemic,” the investigators said in the paper.

Read the full article in Science Translational Medicine 2015 at: doi/10.1126/scitranslmed.3010286.