Untreated patients with chronic hepatitis B (CHB) and a heavier burden of metabolic disease faced significantly higher risks of cirrhosis and death, while diabetes alone was independently associated with hepatocellular carcinoma (HCC) and mortality, according to data presented at Digestive Disease Week® (DDW) 2026.
In a propensity-score–matched analysis of more than 5,600 untreated patients drawn from a U.S. and Asia-Pacific consortium, having three or more metabolic conditions was associated with a roughly 2.4-fold increase in overall and liver-related mortality, and diabetes was associated with a more than twofold increase in HCC risk.
Although metabolic conditions are increasingly common in patients with CHB and have been tied to treatment response and adverse outcomes in those receiving antiviral therapy, data on their long-term impact in untreated patients remain scarce, lead author Rui Huang, MD, PhD, of Nanjing Drum Tower Hospital, Nanjing University Medical School, in China, and coauthors wrote in their abstract.
To address that gap, the investigators analyzed data from the Real-world Effectiveness from the Asia Pacific Rim Liver Consortium for HBV (REAL-B), drawing on untreated CHB cohorts from two U.S. centers and seven sites in Taiwan. The metabolic conditions assessed were obesity, diabetes, dyslipidemia, and hypertension.
A total of 5,606 untreated patients were included, 58.0% of whom had at least one metabolic disease. The investigators used 1:1 propensity-score matching to balance baseline clinical characteristics, yielding 1,493 matched pairs.
When patients were stratified by the number of metabolic conditions, only those with three or more showed a significantly higher cumulative incidence of cirrhosis (P = .038), all-cause mortality (P = .003), and liver-related mortality (P = .044) compared with patients without metabolic disease. In Cox regression analysis, having three or more metabolic conditions was associated with overall mortality (hazard ratio [HR], 2.41; 95% CI, 1.57-3.69; P < .001), liver-related mortality (HR, 2.41; 95% CI, 1.26-4.61; P = .008), and non–liver-related mortality (HR, 2.03; 95% CI, 1.10-3.74; P = .023).
Diabetes carried a distinct signal. When patients were stratified by diabetes status, those with diabetes had a significantly higher cumulative incidence of HCC (P = .004), overall mortality (P < .001), and non–liver-related mortality (P < .001). On Cox regression, diabetes was associated with HCC (HR, 2.28; 95% CI, 1.26-4.12; P = .007), overall mortality (HR, 2.49; 95% CI, 1.67-3.74; P < .001), and non–liver-related mortality (HR, 2.94; 95% CI, 1.78-4.85; P < .001).
The authors concluded in their abstract that prevention and management of metabolic diseases — particularly diabetes — “should be prioritized in the care of CHB patients, regardless of antiviral treatment status.”
Dr. Huang and his coauthors reported no relevant disclosures.
DDW is AGA's annual meeting, jointly sponsored by AGA, AASLD, ASGE, and SSAT. Learn more at ddw.org.