Value of Treating All Stages of Chronic Hepatitis C: A Comprehensive Review of Clinical and Economic Evidence

Abstract

IntroductionThe goal of chronic hepatitis C (CHC) treatment is to achieve a sustained virologic response (SVR). The new generation of direct-acting antivirals (DAAs) offers 90–100% SVR rates. However, access to these treatments is generally limited to patients with advanced liver disease. The aim of this review is to provide an overview of the clinical and economic benefits of achieving SVR and to better understand the full value of CHC treatment in all stages of liver disease.MethodsA comprehensive literature review was performed using the PubMed, Embase, and Cochrane library databases to identify articles examining the clinical, economic, and quality of life benefits associated with SVR. Articles were limited to those published in English language from January 2006 through January 2016. Inclusion criteria were (1) patients with CHC, (2) retrospective and prospective studies, (3) reporting of mortality, liver morbidity, extrahepatic manifestations (EHMs), and economic outcomes and, (4) availability of an abstract or full-text publication.ResultsOverall this review identified 354 studies involving more than 500,000 CHC patients worldwide. Evidence from 38 studies (n = 73,861) shows a significant mortality benefit of achieving SVR in patients with all stages of fibrosis. Long-term studies with follow-up of 5–12 years suggest that, particularly among non-cirrhotic patients, there is a significant decrease in mortality in SVR versus non-SVR groups. Ninety-nine studies conducted in 235,891 CHC patients in all stages of fibrosis show that SVR reduces liver-related mortality, incidence of hepatocellular carcinoma (HCC), and decompensation. A total of 233 studies show that chronic HCV infection is associated with several serious EHMs, some of which can have high mortality. Evidence from four modeling studies shows that delaying treatment to CHC patient populations could significantly increase mortality, morbidity, and medical costs.ConclusionsThere is a robust body of evidence demonstrating diverse sources of value from achieving SVR in all stages of liver disease. While access to treatment is generally limited to late-stage patients, less restrictive treatment strategies that target HCV eradication have the potential to abate the burdens of mortality, liver morbidity and extrahepatic manifestations, and the associated healthcare costs.Electronic supplementary materialThe online version of this article (doi:10.1007/s40121-016-0134-x) contains supplementary material, which is available to authorized users.

Impact of sustained virological response on the extrahepatic manifestations of chronic hepatitis C: a meta-analysis

“…Although progressive hepatic fibrosis is responsible for most HCV morbidity and mortality,19 studies with a 5-year to 12-year follow-up have suggested that non-cirrhotic patients in particular benefit from a significant decrease in mortality on achieving SVR 20. In this meta-analysis, data were extracted from 48 predominantly prospective and retrospective cohort studies that examined the effect of achieving SVR on a variety of extrahepatic outcomes in HCV-infected patients.…”

Efficacy and Tolerability of Direct‐Acting Antivirals for Hepatitis C in Older Adults

“…In individuals with decompensated liver disease, SVR can lead to resolution of ascites, a reduction in portal hypertension, and sustained improvement in synthetic liver function. Older adults are less likely to be candidates for liver transplantation, so the improvement in liver function associated with viral eradication can confer a significant mortality benefit for individuals with advanced liver disease …”

Direct medical costs associated with the extrahepatic manifestations of hepatitis C infection in Europe

“…DAAs have shown excellent safety and tolerability in HCV patients of all genotypes, with sustained virologic response (SVR) rates in excess of 95% in most subpopulations and significant improvements on patient‐reported outcomes . There are a large number of studies that document the significant morbidity and mortality benefit of achieving SVR in HCV patients at all stages of fibrosis . Thus, early treatment with DAAs can prevent a substantial portion of direct medical costs related to downstream hepatic HCV complications .…”