New prognostic model for hepatocellular carcinoma in chronic hepatitis B

1. In this cohort study involving noncirrhotic patients with chronic hepatitis B, a new prognostic model based on viral load was found to have good overall performance in predicting risk for hepatocellular carcinoma.

2. Additional predictors of hepatocellular carcinoma risk in the model included platelet counts, ALT levels, and hepatitis B e antigen result.

Evidence Rating Level: 2 (Good)

Study Rundown: Chronic hepatitis B virus (HBV) infection is the most common chronic viral infection and the leading cause of hepatocellular carcinoma (HCC). While suppression of HBV replication with antiviral medications have been shown to reduce the risk of HCC, current guidelines recommend initiation of these drugs only in patients with significant liver injury as evidenced by histologic disease or elevated ALT titers. However, recent studies have demonstrated that the risk of HCC appears to be parabolic over the disease course rather than linear. The risk of HCC has been found to be relatively low both when viral load peaks in the initial stages of infection and once the virus has been effectively cleared in the case of inactive infection, but highest during the “immune-active” phase during which HBV-infected hepatocytes are eliminated. Hence, this study aimed to develop a new prognostic model for HCC in patients with chronic hepatitis B infection who do not meet current criteria for antiviral treatment. Both the derivation and validation cohorts were found to corroborate the expected non-linear, parabolic associations between HBV DNA levels and risk of HCC. The new prognostic model, reREACH-B (Revised Risk Estimation for HCC in Chronic Hepatitis B), integrated this relationship with five additional risk factors, ultimately demonstrating satisfactory discrimination, calibration, and overall performance for predicting HCC risk. This study was limited by the lack of racial diversity among its patient population. Nonetheless, these results highlight the need to optimize medical management for patients with chronic HBV.

Click to read the study in AIM

Relevant Reading: Risk estimation for hepatocellular carcinoma in chronic hepatitis B (REACH-B): development and validation of a predictive score

In-Depth [prospective cohort]: This multinational cohort study aimed to develop a new prognostic model for predicting HCC risk that incorporates HBV DNA levels. Overall, 19,846 treatment-naïve adults from Taiwan, Hong Kong, and Korea who had chronic hepatitis B infection and serum ALT levels less than twice the upper limit of normal were included. Surveillance for HCC was performed using ultrasonography and serum α-fetoprotein measurements every 6 months. A total of 6,949 and 7,429 patients were included in the derivation and validation cohorts, respectively. HBeAg was positive in 29.9% of patients, the median HBV DNA levels were 3.1 log₁₀ IU/mL, and the median ALT titer was 25 U/L in the derivation cohort. HBeAg was positive in 21.0% of patients, the median HBV DNA levels were 3.4 log₁₀ IU/mL, and the median ALT titer was 20 U/L in the validation cohort. Overall, 435 patients (6.3%) and 467 patients (6.3%) developed HCC over a median follow-up period of 10.0 and 12.2 years for the derivation and validation cohorts, respectively. The estimated cumulative probability of developing HCC at 10 years was 6.4% for the derivation cohort and 3.1% for the validation cohort. In both cohorts, a non-linear parabolic association between baseline HBV DNA level and HCC risk was seen, with moderate viral loads between 5 and 6 log₁₀ IU/mL associated with the highest risk. This association, along with five other variables (age, sex, platelet counts, ALT, and HBeAg), was taken into consideration to develop the reREACH-B model. Using this model, c-statistics of 0.844 and 0.813 were obtained for the derivation and validation cohorts with multiple imputation, respectively, suggesting satisfactory discrimination and precision.

Image: PD

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