Long-Term Treatment Outcomes of Patients Infected With Hepatitis C Virus: A Systematic Review and Meta-analysis of the Survival Benefit of Achieving a Sustained Virological Response

TLDR: There is a significant survival benefit of achieving an sustained virologic response compared with unsuccessful treatment in the general hepatitis C virus-infected population.

Abstract: Hepatitis C virus (HCV) is a significant public health concern with an estimated 185 million people infected worldwide [1]. HCV progression can lead to the development of liver cirrhosis and hepatocellular carcinoma and results in the deaths of over 700 000 people every year [2]. Combined, viral hepatitis kills more people per year than malaria or tuberculosis but has commanded far less attention and access to care and treatment is limited [2, 3]. Traditionally, treatment for HCV has composed of dual-therapy with pegylated-interferon and ribavirin. Dual-therapy is associated with poor sustained virological response (SVR) rates, the surrogate marker for cure defined as undetectable HCV RNA 24 weeks following completion of therapy. A robust treatment pipeline has seen the recent approval of highly efficacious interferon-free regimens with a number of other therapy combinations likely to be approved over the next 2 years. These novel treatment regimens will have the potential to transform the treatment landscape [4, 5]. Promisingly, the high response rate is matched in populations typically considered difficult-to-treat, such as those with advanced fibrosis or coinfection with human immunodeficiency virus (HIV) [6, 7]. Relative to nonresponders or to those untreated, the attainment of an SVR has repeatedly been associated with improved patient outcomes, irrespective of the path to SVR. These include reduced incidence of liver decompensation, hepatocellular carcinoma, and death [8–10]. Evidence suggests that an SVR does not only prevent the progression of liver disease but is associated with histologic improvements with some studies even reporting the complete resolution of fibrosis after SVR [10, 11]. Moreover, SVR-achievement has been associated with a reduction in extra-hepatic events and a reduction in mortality independent of liver disease [10, 12–16]. Despite the evidence for improved prognosis with SVR, there are some contradictory data suggesting that SVR-achievement does not provide a significant clinical benefit [9, 17, 18]. A number of studies have shown that the risk of progression is not eliminated with viral eradication, with some patients experiencing decompensation or developing hepatocellular carcinoma despite achieving an SVR [10, 11, 19, 20]. Furthermore, some evidence suggests that the improved prognosis associated with SVR may be diminished in certain patient groups such as those with decompensation or HIV coinfection [12, 21]. There is a need for definitive evidence evaluating the clinical benefit of achieving an SVR in a range of populations, especially given the high cost of interferon-free regimens [4]. The aim of this study was to systematically review the current literature concerning the survival benefits of achieving SVR through treatment vs the outcomes in nonresponders and relapsers (non-SVR). All-cause mortality was chosen as the endpoint as it is definitive with clear interpretation. Further, given the extra-hepatic benefits of SVR, all-cause mortality may be clinically more relevant than liver-related mortality.