Management of patients with pre-therapeutic advanced liver fibrosis following HCV eradication

Abstract

Patients with HCV-related bridging fibrosis or cirrhosis remain at risk of developing life-threatening complications even after achieving a sustained virological response. Although it is reduced, the risk of liver-related events in these patients justifies their inclusion in surveillance programmes dedicated to the early detection of hepatocellular carcinoma and the screening for portal hypertension. Biochemical parameters or non-invasive tests might indicate the potential progression of liver injury despite viral clearance. Specific attention must be focused on the management of comorbidities, while dedicated educational programmes must be encouraged to increase compliance and commitment to surveillance. Better knowledge of the long-term evolution of these patients, who now live longer, is essential to improve risk stratification and refine screening strategies in this growing population.

Keywords: AFP, alpha-fetoprotein; ALT, alanine aminotransferase; APRI, AST-to-platelet ratio index; AST, aspartate aminotransferase; DAAs, direct-acting antivirals; EHC, extrahepatic cancer; FIB-4, fibrosis-4; HCC, hepatocellular carcinoma; HCV; HR, hazard ratio; Hepatocellular carcinoma; LSM, liver stiffness measurement; Liver failure; MACEs, major adverse cardiovascular events; PHT, portal hypertension; Portal hypertension; SMR, standardised mortality ratio; SVR; SVR, sustained virological response; surveillance.

Fig. 1

Impact of SVR on life-threatening events and overall/specific mortality in patients with HCV-related cirrhosis or bridging fibrosis. Positive impact: multiple and adequately powered longitudinal observational studies of cirrhotic patients with appropriate adjustment for confounders. Suspected improvement: findings supported by some observational studies but may be limited by insufficient follow-up time, incomplete adjustment for confounders, small sample size or the existence of contradictory reports. SVR, sustained virological response.

Fig. 2

Incidences of liver-related and extrahepatic events as a function of SVR status in patients with compensated biopsy-proven cirrhosis included in the ANRS CO12 CirVir cohort. (A) Risks of hepatocellular carcinoma, liver decompensation, major adverse cardiovascular events and bacterial infection are decreased following SVR resulting from treatment with interferon- and DAA-based regimens. (B) Presence of metabolic syndrome (diabetes and/or overweight and/or dyslipidaemia) at the time of SVR is a major contributor to residual HCC risk in cirrhotic patients following SVR. SVR1: SVR and no metabolic syndrome; SVR2: SVR and metabolic syndrome; non-SVR1: no SVR and no metabolic syndrome; non-SVR2: no SVR and metabolic syndrome. (C) Increased incidence of EHCs in HCV-related cirrhosis patients with SVR compared with age-matched and sex-matched controls from the general French population. EHC was the leading cause of death in the CirVir cohort in patients who achieved SVR. Reproduced from Nahon et al.,^, Allaire et al. and Cacoub et al. with permission. BI, bacterial infection; DAA, direct-acting antiviral; EHCs, extrahepatic cancers; SVR, sustained virological response.

Fig. 3

Pragmatic management of patients with bridging fibrosis or cirrhosis who achieved HCV eradication according to international guidelines (adapted from the available literature on SVR patients). AFP, alpha-fetoprotein; ALT, alanine aminotransferase; AST, aspartate aminotransferase; LSM, liver stiffness measurement; SVR, sustained virological response.