Metabolic and cardiovascular complications after virological cure in hepatitis C: What awaits beyond

Abstract

The association between chronic hepatitis C (CHC) infection and extrahepatic manifestations (EHMs), particularly cardiometabolic diseases, has been extensively examined. However, there has still been insufficient evaluation for these EHMs after virological cure. Several multidirectional mechanisms have been proposed explaining the ability of hepatitis C virus (HCV) developing EHMs, cardiometabolic ones, as well as the effect of antiviral therapy to resolve these EHMs. Data on these manifestations after achieving sustained virologic response (SVR) are still conflicting. However, current evidence suggests that reversal of hepatic steatosis and its coexistent hypocholesterolemia after successful viral eradication led to unfavorable lipid profile, which increases cardiovascular disease (CVD) risk. Additionally, most observations showed that metabolic alterations, such as insulin resistance and diabetes mellitus (DM), undergo some degree of reduction after viral clearance. These changes seem HCV-genotype dependent. Interferon-based antiviral therapy and direct acting antiviral drugs were shown to minimize incidence of DM. Large epidemiological studies that investigated the effect of SVR on CVD showed great discrepancies in terms of results, with predominant findings indicating that CVD events decreased in patients with SVR compared to non-responders or untreated ones. In this review, we present a summary of the current knowledge regarding extrahepatic sequelae of CHC following SVR, which may have an impact on healthcare providers’ clinical practice.

Keywords: Chronic hepatitis C; Sustained virologic response; Hepatic steatosis; Diabetes mellitus; Cardiovascular disease

Core Tip: The implementation of direct acting antiviral drugs has dramatically changed the landscape of hepatitis C virus (HCV) treatment, with over 95% of patients achieving sustained virologic response (SVR). Although consistent evidence demonstrated better outcomes for both hepatic and extrahepatic complications after viral clearance, data on cardiometabolic manifestation showed inconsistent results. In this review, we are shading light on the latest findings about cardiometabolic extrahepatic manifestations post-SVR. These updates may guide clinicians engaged in HCV care to integrate in their management post-viral eradication risks and subsequent long-term care.