Hepatic benefits of HCV cure

Direct-acting antiviral (DAA)-induced HCV clearance conceivably leads to improved outcomes at all stages of liver disease. However, available data suggest that the maximum measurable benefit is obtained by treating patients before they reach the stage of compensated advanced chronic liver disease (cACLD). Ideally, all patients with chronic hepatitis C should be treated before they develop advanced fibrosis or cirrhosis, since even if sustained virologic response (SVR) reduces the risk of hepatic events (e.g. decompensation and hepatocellular carcinoma [HCC]) and improves survival, further progression of liver disease and adverse outcomes, including hepatic deaths, cannot be entirely avoided. The hepatic venous pressure gradient (HVPG) correlates closely with the stage of liver disease. Measurements of HVPG in patients with severe fibrosis or cirrhosis treated with DAAs show that those with the highest degree of portal hypertension have the lowest probability of a meaningful reduction of portal pressure after SVR, and remain at significant risk of decompensation. Reduced liver stiffness is commonly observed in patients with cACLD but its role in predicting prognosis is yet to be demonstrated. In patients with decompensated cirrhosis, prevention of further decompensation and of HCC is only weakly associated with SVR. Overall, the main clinical predictors of a high risk of HCC in patients who obtain SVR on DAAs are all indexes strongly reflecting advanced fibrosis and impaired hepatic function. Long-term follow-up of large real-life cohorts of patients treated at all stages of liver disease, but mainly those with mild to moderate fibrosis, will be needed to confirm the impact of SVR among diverse HCV-infected populations and, more importantly, to better stratify patients at higher risk of complications in order to define their correct surveillance.