All-Oral Direct-Acting Antiviral Therapy in HCV-Advanced Liver Disease is Effective in Real-world Practice

Observations Through HCV-Target Database

K. R. Reddy; J. K. Lim; A. Kuo; A. M. Di Bisceglie; J. S. Galati; G. Morelli; G. T. Everson; P.Y. Kwo; R. S. Brown Jr.; M. S. Sulkowski; L. Akuschevich; A. S. Lok; P. J. Pockros; M. Vainorius; N. A. Terrault; D. R. Nelson; M. W. Fried; M. P. Manns

Disclosures

Aliment Pharmacol Ther. 2017;45(1):115-126. 

In This Article

Abstract and Introduction

Abstract

Background Chronic hepatitis C virus therapy in patients with advanced liver disease remains a clinical challenge. HCV-TARGET collects data in patients treated at tertiary academic and community centres.

Aim To assess efficacy of all-oral HCV therapy in advanced liver disease.

Methods Between December 2013 and October 2014, 240 patients with a MELD score of ≥10 initiated HCV treatment with an all-oral regimen. Data from the 220 patients who completed 12-week follow-up were analysed.

Results Genotype 1 (GT1) patients had higher sustained virological response (SVR) when treated with sofosbuvir plus simeprevir ± ribavirin than with sofosbuvir plus ribavirin (66–74% vs. 54%); GT1b vs GT1a (84% vs. 64%). SVR for GT2 was 72% with sofosbuvir plus ribavirin, while GT3 patients had a substantially lower response (35%). 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. A predictor of virological response was albumin level while negative predictors were elevated bilirubin level and GT1a. Most patients with GT1 were treated with approximately 12-week duration of sofosbuvir and simeprevir ± ribavirin therapy while GT2 and GT3 patients were treated with approximately 12 and 24 weeks of sofosbuvir plus ribavirin respectively.

Conclusions All-oral therapies are effective among patients with advanced liver disease with high levels of success in GT2 and GT1b, and may serve to reduce the severity of liver disease after SVR. Treatment for GT3 patients remains an unmet need.

Introduction

Hepatitis C virus (HCV) infection is a progressive disease leading to fibrosis, cirrhosis, hepatocellular carcinoma (HCC) and liver failure.[1,2] HCV mortality rates have eclipsed those of the human immunodeficiency virus (HIV) infection in USA, and the disease burden resulting from HCV is predicted to further increase over the next decade.[3–5] On a positive note, successful treatment of HCV has been associated with a decrease in all-cause mortality and HCC.[6,7] However, it remains unknown whether treatment of HCV in those with advanced or decompensated liver disease will lead to improved liver function analogous to previous observations in those with hepatitis B virus (HBV)-related liver disease after the initiation of HBV therapy.[8]

Hitherto, interferon (IFN)-based therapies presented major challenges in patients with advanced cirrhosis with poor tolerability, high rates of adverse events, and suboptimal response rates.[9,10] To that end, effective, better tolerated treatments were felt to be urgently needed for these patients. Sofosbuvir, a nucleotide NS5B polymerase inhibitor, in combination with ribavirin, has shown excellent responses with good safety and tolerability in those with cirrhosis, providing a much needed IFN-free regimen for these difficult-to-treat patients.[11–13] Combination therapies including NS3/4A (grazoprevir), NS5A (ledipasvir, daclatasvir and elbasvir) and NS5B polymerase (sofosbuvir) inhibitors have demonstrated high efficacy and good tolerability largely in clinical trials in patients with advanced liver disease.[14–16] In the USA, regimens containing sofosbuvir and simeprevir (an NS3/4A protease inhibitor) were approved in 2013 for treatment of chronic HCV, but not for treatment in patients with decompensated liver disease.[17,18] Yet, based on a single phase II study of sofosbuvir plus simeprevir showing excellent results in patients with well-compensated liver disease, this regimen presented an option for patients with more advanced liver disease.[19,20] With several options becoming available in this important population, HCV-TARGET, 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.

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