Non-invasive prediction of liver-related events in patients with HCV-associated compensated advanced chronic liver disease after oral antivirals

Background & aims: It is important to know which patients with hepatitis C are likely to develop liver-related complications after achieving a sustained virological response (SVR) to direct-acting antiviral (DAA) therapy. We aimed to describe the incidence of liver-related events in a population of patients with HCV-associated compensated advanced chronic liver disease (cACLD) who achieved SVR and to identify non-invasive parameters that predict the occurrence of liver-related events.

Methods: This 2-center prospective study included 572 patients with cACLD who had been treated with DAAs and had achieved SVR. Patients had liver stiffness measurement (LSM) ≥10 kPa at baseline and had never decompensated (Child-Pugh class A). Laboratory work-up and LSM were performed at baseline and at 1 year of follow-up.

Results: The median follow-up was 2.8 years during which 32 patients (5.6%) presented with a liver-related event. The incidence rate (IR) of portal hypertension-related decompensation was 0.34/100 patient-years. These patients all had baseline LSM >20 kPa, and LSM did not improve during follow-up in 4 out of 5 of them. Hepatocellular carcinoma (HCC) occurred in 25 patients (IR 1.5/100 patient-years). Albumin levels at follow-up (hazard ratio [HR] 0.08; 95% CI 0.02-0.25) and LSM <10 kPa at follow-up (HR 0.33; 95% CI 0.11-0.96) were independently associated with the risk of HCC. Combining both predictors identified 2 groups with differing risk of HCC occurrence: those with LSM ≥20 kPa at follow-up or those with LSM between 10-20 kPa and albumin levels <4.4 g/dl were at the highest risk (IR ≥1.9/100 patient-years). Visual nomograms predicting HCC risk based on LSM and albumin at 1 year of follow-up were constructed.

Conclusion: In patients with HCV-related cACLD who have achieved SVR with DAAs, HCC is the most frequent liver-related event. Both albumin levels and LSM are useful for stratifying patients based on their risk of developing HCC during follow-up.

Lay summary: New oral antivirals can cure chronic hepatitis C infection, however patients with advanced chronic liver disease are still at risk of presenting with liver-related complications. The most frequent complication after oral antiviral therapy in asymptomatic patients with advanced chronic liver disease was liver cancer. The use of simple parameters such liver stiffness and albumin levels after treatment can help to identify patients at higher or lower risk of liver cancer.