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Systematic review: current concepts and challenges for the direct‐acting antiviral era in hepatitis C cirrhosis
Author(s) -
Majumdar A.,
Kitson M. T.,
Roberts S. K.
Publication year - 2016
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/apt.13633
Subject(s) - medicine , cirrhosis , current (fluid) , hepatitis c , intensive care medicine , medline , virology , gastroenterology , electrical engineering , law , political science , engineering
Summary Background The burden of HCV cirrhosis is high and projected to increase significantly over the next decade. While interferon therapy is problematic in HCV cirrhosis, the era of direct‐acting anti‐viral ( DAA ) therapy provides effective treatment for patients with cirrhosis. Aim To systematically review the results of DAA therapy to date in patients with HCV cirrhosis, and highlight the ongoing challenges for DAA therapy in this population. Methods A structured Medline search was conducted to obtain phase II and III HCV trials in patients with cirrhosis. Citations from review articles were cross‐referenced and conference abstracts from EASL and AASLD liver meetings for the preceding 3 years were reviewed manually. Keywords used included hepatitis C, cirrhosis and the DAA 's: sofosbuvir, ledipasvir, velpatasvir, grazoprevir, elbasvir, daclatasvir, beclabuvir, asunaprevir, simeprevir, paritaprevir, ombitasvir and dasabuvir. Results Successful direct‐acting anti‐viral treatment is now possible in patients with HCV ‐related cirrhosis including those with liver decompensation with several regimens now offering sustained virological response ( SVR ) of 90–95%. Overall success rates in GT 1 cirrhosis are excellent while GT 3‐infected patients with cirrhosis remain hard to cure. The pangenotypic combination of sofosbuvir and velpatasvir holds promise for GT 3 cirrhosis achieving SVR of ~90%. Conclusions Potent DAA therapies provide much needed, safe and highly effective treatment options for persons with HCV cirrhosis including those previously deemed unsuitable for treatment. Combination therapy with two or more classes of drug is essential to achieve high efficacy and minimise viral resistance, with the role of ribavirin still under evaluation. However, several challenges remain including the hard‐to‐cure groups of GT 3 cirrhosis and direct‐acting anti‐viral failures, and managing drug–drug interactions.