Insulin Resistance and Hepatocellular Carcinoma Development in Chronic Hepatitis B Patients Under Antiviral Therapy

Hepatocellular carcinoma (HCC) remains a significant concern in patients with liver cirrhosis due to chronic hepatitis B virus (HBV) infection, even among those who achieve a virological response with antiviral therapy. This study aimed to evaluate whether insulin resistance (IR), assessed using the Homeostatic Model Assessment 2 for Insulin Resistance (HOMA2-IR) index, can serve as a surrogate marker for stratifying HCC risk in this population.

In this multicenter prospective cohort study, 334 patients with HBV-related cirrhosis who achieved virological response to nucleos(t)ide analogue therapy were enrolled. The primary outcome was the incidence of HCC during follow-up. Baseline HOMA2-IR was calculated using serum C-peptide and fasting glucose levels.

During a median follow-up of 7.45 years (range, 0.5-8.9 years), 62 patients (18.6%) developed HCC. In a fully adjusted Cox proportional hazards model, each unit increase in HOMA2-IR was associated with a higher risk of HCC (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.16-2.04). Patients with HOMA2-IR ≥ 2.3 had a significantly higher 5-year cumulative incidence of HCC compared to those with HOMA2-IR < 2.3 (30.6% vs. 12.3%; adjusted HR, 2.62; 95% CI, 1.40-4.91). The association between HOMA2-IR and HCC risk was consistent across subgroups, including those with and without metabolic comorbidities such as obesity, diabetes, hypertension, or dyslipidemia.

IR, as measured by HOMA2-IR, independently predicted HCC development in cirrhotic patients with chronic HBV infection. HOMA2-IR may serve as a useful surrogate marker for identifying high-risk individuals. Intervention trials are warranted to determine whether reducing HOMA2-IR can lower HCC risk in this population.