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Highlights of HCV Research From Digestive Disease Week
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Healio Rheumatology features coverage of the top hepatitis C virus research presented at Digestive Disease Week.
Tarek I. Hassanein, MD, of Southern California Liver Centers and Southern California Research Center in Coronado, Calif., presented findings for a cohort of patients with cirrhosis and genotype 4 hepatitis C virus. The researchers found once-daily treatment with ombitasvir/paritaprevir/ritonavir with ribavirin produced 12-week sustained virologic response (SVR) rates of nearly 100%. Eligible participants in the ongoing, randomized, open-label trial were enrolled in Austria, Belgium, Canada, France, Germany, Greece, Italy and the United States.
Ombitasvir/paritaprevir/ritonavir (Technivie, AbbVie) was co-formulated for a once-daily dose of 25-mg ombitasvir, 150-mg paritaprevir and 100-mg ritonavir with weight-based ribavirin. There were two treatment arms: Arm A included 59 patients treated for 12 weeks; and arm B included 61 patients treated for 16 weeks.
SVR12 rates were 97% for the 12-week group and 98% for the 16-week group. When the researchers conducted a sensitivity analysis that excluded patients who prematurely discontinued therapy, the rates were 98% for 12 weeks and 100% for 16 weeks.
There was one virologic failure in the 12-week arm. The patient was a prior non-responder to pegriba and Child-Pugh 6, according to Hassanein. “The patient had no baseline NS5A variants,” he said.
To that point, SVR12 in the full cohort was not impacted by NS5A variants, according to Hassanein. Adverse event data indicated there were no deaths. Serious adverse events were reported in four patients in each group.
“Tolerance to the treatment and adverse events have been mostly mild to moderate in severity,” Hassanein said.
Laboratory analysis indicated a slight drop in hemoglobin in some patients, but none discontinued therapy as a result.
HIV/HCV Coinfection
Kris V. Kowdley, MD, of the Liver Care Network, Swedish Medical Center in Seattle, and colleagues, aimed to understand real-world outcomes across a heterogeneous population. The analysis included 140 patients who initiated therapy between October 2014 and March 2015. Patients were treated with ledipasvir/sofosbuvir (Harvoni, Gilead Sciences) for 8 weeks (5%), 12 weeks (75%) or 24 weeks (20%).
Ledipasvir/sofosbuvir with or without ribavirin, yielded a 97% SVR rate in a real-world cohort of patients with genotype 1 hepatitis C virus (HCV) and HIV. The population showed heterogeneity, with 59% treated at a community site, 73% were black, 46% HCV treatment-experienced and 35% had cirrhosis. Investigators also assessed for a platelet cutoff level of less than 100 k/mL and a baseline HCV RNA cutoff level of 6 million IU/mL.
“One in five patients had a high viral load,” Kowdley said.
SVR12 rates were 100% among eight patients in the 8-week group, 98% among 112 patients in the 12-week group and 97% among 30 patients in the 24-week group.
For patients with cirrhosis, the SVR12 rate was 100%, regardless of treatment experience. Among non-cirrhotics, 98% of experienced patients and 100% of treatment-naive patients reached SVR12. Response was also 100% in patients with genotype 1a HCV, regardless of baseline viral load. For genotype 1b, 95% of patients with a baseline viral load of less than 6 million IU/mL reached SVR12, while 100% of patients with a viral load above that threshold responded.
Response rates were 100% for patients treated with a proton pump inhibitor and 99% for those who were not. SVR12 was 97% among black patients and 100% among non-black patients. Regarding predictors of response, Kowdley noted two outliers associated with a reduction in SVR.
“One was platelet count less than 100,000 and one was genotype 1b,” he said. He noted, however, that the sample size of genotype 1b patients was small, and that this effect was minimal.
“In conclusion, SVR rates were greater than 97% in this real-world cohort,” Kowdley said. “Only one relapse was documented. These data suggest that LDV/SOF has similar effectiveness in real life as the results reported in the ION-4 study.”
Alcohol Use
Peter Hauser, MD, of the VA Long Beach Healthcare System and the University of California, Irvine, presented research on baclofen, which failed to best placebo in the control of metrics for alcohol use in a cohort of veterans with the hepatitis C virus. He said additional medication options are needed for the treatment of alcohol use disorders and the shortcomings of baclofen.
“Particularly, we need ones that are not metabolized in the liver,” Hauser said. “Some studies have shown that baclofen can reduce alcohol use, while others have failed to show that result,” he said.
The current study included 88 patients treated with 10 mg of baclofen three times daily and 92 patients treated on the same schedule with placebo. The duration was 12 weeks. The double-blind trial was conducted between 2010 and 2014 at four Veteran Affairs centers.
“This is the first study that looked [at] a large sample size of hepatitis C-infected patients,” Hauser said. The primary outcome measure was the percent of days abstinent, according to Hauser. Secondary measures included alcohol craving as measured by the Obsessive Compulsive Drinking Scale.
“Our study was different from many studies in that we did not require prior abstinence for entry,” he said. Exclusion criteria included decompensated liver disease. Baseline data showed no differences between the two arms.
“Veterans in both groups were drinking moderately to heavily,” he said.
After an initial 4-week wash-in period, 8.9% of the cohort became abstinent between weeks 4 and 12 of the study. Results indicated 7.6% of 79 patients in the study drug group and 10.1% of 80 patients in the placebo group reached abstinence. “Both groups had a significant increase over time in reduction in alcohol use,” Hauser said.
Similarly, for the outcome of “no heavy drinking,” results from 4 weeks to 12 weeks indicated this increased 20.6% overall, but that there were no differences between the groups. No heavy drinking increased by 25.3% in the baclofen group and by 16.3% in the placebo group.
Regarding the secondary outcome measures, a similar trend emerged. Alcohol craving as measured by the Obsessive Compulsive Drinking Scale decreased from 20.55 to 8.79 in the baclofen arm and from 19.50 to 9.52 in the placebo arm.
Other findings indicated 67 individuals in the baclofen arm and 73 individuals in the placebo arm completed the study.
“It is possible that higher dose baclofen may prove effective but, at this time, clinicians are encouraged to use other medications to reduce alcohol use in patients with chronic liver disease,” he said. – by Rob Volansky
- References:
- Asselah T, et al. Abstract #503.
- Dieterich D, et al. Abstract #606.
- Hauser P, et al. Abstract #654.
Disclosures: Hassanein reports financial relationships with AbbVie, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Eisai, Gilead Sciences, Idenix, Ikaria, Janssen, La Jolla Pharmaceuticals, Merck, NGM BioPharmaceuticals, Obalon, Ocera Therapeutics, Roche, Salix, Sundise, TaiGen, Takeda, Tobria, Vertex and Vital Therapies. Hauser reports no relevant financial disclosures. Kowdley reports associations with a number of device and pharmaceutical companies.