Prediction of Hepatocellular Carcinoma in Hepatitis C-Compensated Advanced Chronic Liver Disease

Hepatocellular carcinoma (HCC) is the most common liver-related event in patients with hepatitis C-compensated advanced chronic liver disease (cACLD) who have achieved sustained virologic response (SVR) with direct-acting antiviral (DAA) therapy, and the best way to stratify HCC risk in this population is by measuring albumin levels and liver stiffness during follow-up, according to a study published in the Journal Of Hepatology.

This 2-center prospective cohort study was designed to describe the incidence of liver-related events with hepatitis C cACLD who had SVR after DAA therapy, and to identify noninvasive parameters that can predict the occurrence of liver-related events. The 572 study participants (mean age 63.7 years, 49.3% men) had a baseline liver stiffness measurement of ≥10 kPa and had never decompensated according to Baveno VI definition; had confirmed SVR 12 weeks post-DAA therapy; and were Child Pugh class A. The researchers collected data on renal function, platelet count, albumin, transaminases, bilirubin, and other parameters at baseline, and repeated these work-ups every 6 months after SVR was confirmed, per standard clinical practice. Liver stiffness was measured at baseline and 1-year follow up.

During a median follow up of 2.9 years (range 0.3-3.8), 5.6% of patients (n=32) presented with liver-related events. Five patients (0.9%) presented with portal hypertension-related decompensation for an incidence rate of 0.31/100 patient-years. These patients all had baseline liver stiffness measurements >20 kPa and in 4 out of 5 cases, these measurements did not improve during follow-up. However, the low incidence of these events made it impossible to identify the predictors of portal hypertension-related events, although patients with baseline liver stiffness ≥20 kPa and no improvement during follow-up had an increased risk of liver decompensation (HR, 39.7; 95% CI, 4.4-355.4).

Twenty-five patients developed HCC (incidence rate, 1.5/100 patient-years). A multivariate analysis of baseline parameters demonstrated that only albumin levels (HR, 0.29; 95% CI, 0.11-0.76; P =.012) were independently associated with HCC risk during follow-up. At follow up, both albumin levels (HR, 0.08; 95% CI, 0.02-0.25; P <.001) and liver stiffness <10 kPa (HR, 0.33; 95% CI, 0.11-0.96; P =.042) were independently associated with HCC risk. Patients with liver stiffness between 10-20 kPa had an increased, but not significant, HCC risk compared with patients with measurements <10 kPa (HR, 2.48; 95% CI, 0.79-7.80; P =.120), and patients with albumin levels <4.4 g/dL (based on mean value) had a high HCC risk (HR, 2.36; 95% CI, 1.02-5.47; P =.046).

By combining predictors, study investigators determined that patients with liver stiffness of ≥20 kPa at follow-up and those with liver stiffness between 10-20 kPa and low albumin levels (<4.4 g/dL) have HCC incidence rates of ≥1.9/100 patient-years, which indicates that albumin levels only impact HCC risk in patients with liver stiffness between 10-20 kPa. A Cox regression model using these variables was constructed (albumin <4.4/≥4.4 and liver stiffness at follow-up <10 kPa/10-20 kPa/≥20 kPa), with good predictive power (Harrell’s C index=0.73), which allowed for the creation of visual nomograms for the prediction of HCC risk at 1-year follow-up.

Study limitations included a short follow-up and the use of data from patients from whom liver stiffness measurement (LSM) was obtained and reliable. However, the study investigators concluded that albumin levels and liver stiffness can help to identify patients with the highest HCC risk during follow-up. “Although patients with LSM <10 kPa at follow up have a low risk of presenting HCC, a zero-risk subpopulation cannot be found, thus, HCC surveillance needs to be considered for all patients classified as having cACLD before therapy. However, with the information provided by our study, patients and clinicians will possess the right information about the expected risk of HCC on an individual basis and more importantly, it will serve to stress the importance of continuing HCC screening (especially in the high-risk groups) and maintaining adherence to these programs by the patients.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference
Pons M, Rodríguez-Tajes S, Esteban JI, et al. Non-invasive prediction of liver related events in HCV compensated advanced chronic liver disease patients after oral antivirals [published online October 17, 2019]. J Hepatol. doi: 10.1016/j.jhep.2019.10.005