Diabetes in CHD patients ups risk of hepatocellular carcinoma

The presence of diabetes mellitus predisposes patients with chronic hepatitis B (CHB) to a higher risk of developing hepatocellular carcinoma (HCC), reveals a study presented at EASL 2025.

Such hazard is also present in untreated patients with low-level viraemia or nonadvanced liver fibrosis. However, antiviral treatment may reduce the risk of HCC development.

“The World Health Organization (WHO) 2024 guidelines recommended antiviral therapy in CHB patients with diabetes mellitus, regardless of hepatitis B virus (HBV) DNA, fibrosis status, or alanine aminotransferase (ALT) levels,” said Dr Rex Wan-Hin Hui from The University of Hong Kong, Hong Kong.

A total of 38,979 patients with CHB, defined via hepatitis B surface antigen positivity or ICD-9 coding, who newly presented to a population-wide electronic health registry between 2011 to 2015, were included. Those with concomitant liver diseases other than metabolic dysfunction-associated steatotic liver disease, history of HCC, or HCC diagnosed within 6 months after the entry date were excluded.

Diabetes mellitus, on the other hand, was characterized by glycosylated haemoglobin ≥6.5 percent, fasting serum glucose ≥7 mmol/L, use of antidiabetic medications, or ICD-9 coding.

Hui and colleagues assessed the primary outcome of incident HCC development and calculated the adjusted hazard ratio (HR) with 95 percent confidence interval (CI) using multivariate Cox regression models. [EASL 2025, abstract OS-101-YI]

The mean age of eligible patients was 47.5 years, and 41.9 percent were male. Less than half of them (43.3 percent) were on antiviral therapy for a median of 5.2 years, and nearly one in four (24.3 percent) had a recent diagnosis of diabetes during the study period.

Concomitant diabetes mellitus was independently associated with an increased HCC risk (adjusted HR, 1.53, 95 percent CI, 1.29‒1.82). This association persisted even after stratifying patients based on age, sex, antiviral treatment, Fibrosis-4 (FIB-4) score, aspartate aminotransferase-to-platelet ratio index, HBV DNA levels, ALT levels (adjusted HR ranged from 1.34 to 4.91).

In 22,096 untreated patients, the presence of diabetes also resulted in a 1.5-fold higher risk of HCC (adjusted HR, 1.50, 95 percent CI, 1.07‒2.10). This risk increase remained significant in those with baseline HBV DNA <2,000 IU/mL (adjusted HR, 1.53, 95 percent CI, 1.09‒2.14) or FIB-4 ≤3.25 (adjusted HR, 1.94, 95 percent CI, 1.24‒3.04).

Antiviral therapy

Among patients with concomitant CHB and diabetes mellitus, treatment with antiviral medications helped lower the risk of HCC development (adjusted HR, 0.76, 95 percent CI, 0.68‒0.84).

The risk-reduction effect of antiviral treatment was more prominent among patients aged <65 years (adjusted HR, 0.64, 95 percent CI, 0.56‒0.74) than among those aged ≥65 years (adjusted HR, 0.91, 95 percent CI, 0.78‒1.07; p_{interaction for age}<0.001).

“The risk reduction effects of antiviral treatment were more pronounced in younger patients,” Hui said. “These findings support the WHO 2024 recommendations in expanding CHB treatment to patients with concomitant diabetes mellitus.”