DAA therapy effective in advanced liver disease in real-world study

An all-oral, sofosbuvir-based therapy is a good option for hepatitis C virus (HCV) patients in genotype 1 or genotype 2 with advanced liver disease, according to a large observational, real-world study.

“Hepatitis C virus infection in those with advanced liver disease can be treated effectively with all-oral medications that are well tolerated and have high efficacy rate. This is a significant advance over previous interferon-based therapy,” K. Rajender Reddy, MD, professor of medicine at the University of Pennsylvania, told Medical Economics. He noted that “such treatment in these patients with advanced liver disease should be pursued in tertiary and specialized centers.”

Reddy and colleagues published their results in the January 2017 Alimentary Pharmacology & Therapeutics.

Successful treatment of HCV has led to a decrease in all-cause mortality and hepatocellular carcinoma, but it remains unknown whether this leads to improved liver function in those with advanced or decompensated liver disease.

Interferon-based therapies for patients with advanced cirrhosis yielded poor tolerability, high rates of adverse events and suboptimal response rates. With several direct-acting antiviral (DAA) options now available, a consortium dedicated to collecting and evaluating clinical care data assessed the use and outcomes of all-oral therapies in patients with advanced liver disease.

The consortium, HCV-TARGET, collected clinical care data for patients treated at tertiary academic and community centers and without predefined criteria for treatment regimen and duration. It analyzed data from the 220 patients who completed 12 weeks of follow-up between December 2013 and October 2014. The patients had a MELD score of 10 or higher and had initiated HCV treatment with an all-oral regimen.

The results show that genotype 1 patients had higher sustained virological response (SVR) when treated with sofosbuvir plus simeprevir, with or without ribavirin (66%–74%) than with sofosbuvir plus ribavirin (54%). Genotype 1b patients had a higher response (84%) than did genotype 1a patients (64%). SVR for genotype 2 patients was 72% with sofosbuvir plus ribavirin; genotype 3 patients had a substantially lower response (35%).

“These rates compare favorably with those from clinical trials and compassionate use programs of all-oral therapy treating patients with advanced liver disease,” said Reddy.

Next: Treatment details

Most patients with genotype 1 were treated with approximately 12 weeks of duration of sofosbuvir and simeprevir, with or without ribavirin. Genotype 2 and genotype 3 patients were treated with approximately 12 and 24 weeks of sofosbuvir plus ribavirin, respectively.

A decrease in MELD score was not clearly related to SVR over the short course of follow-up, although some had improvements in MELD score, serum bilirubin, and albumin, said Reddy.

Albumin level was a predictor of virological response, and elevated bilirubin level and genotype 1a were negative predictors.

“The observations indicate that all-oral, and largely sofosbuvir-based and simeprevir-based therapeutic regimens for genotype 1 HCV in those with advanced liver disease are effective and safe and thus reassuring that observations from clinical trials can be substantiated in clinical practice,” said Reddy.

Long-term follow-up is needed to more convincingly address the benefits of eradicating HCV infection in those with advanced liver disease, he said.