Background and AimsChronic viral hepatitis B (CHB)-infected patients occasionally develop cirrhosis despite having persistent viral suppression with antiviral therapy. We aimed to identify risk factors for developing cirrhosis in HBV-suppressed patients. MethodsWe conducted a case-control study involving 120 non-cirrhotic CHB-infected patients achieving viral suppression with antiviral treatment, with 40 cases developing cirrhosis and 80 age-, sex-, and FIB-4-matched controls. Clinical and laboratory data at viral suppression, including BMI, comorbidities, pre-treatment HBV viral load, HBe antigen status, HCV and HIV co-infections, liver chemistries, and APRI values, were retrospectively abstracted. Risk factors for cirrhosis post-HBV suppression were identified using Cox proportional hazard analysis. ResultsCase and control groups had similar ages (51.4±9.9 vs. 51.4±10.2 years), proportions of males (80% vs. 80%), and FIB-4 values (1.32 vs. 1.31). The cirrhosis group showed significantly higher BMI (25.1 vs. 22.7, p=0.01) and more diabetes prevalence (50.0% vs. 26.3%, p=0.01), while other comorbidities and laboratory parameters were comparable (p>0.05). By univariate analysis, BMI >23 kg/m2, diabetes, and APRI >0.7 were significantly associated with cirrhosis, with hazard ratios (HRs) (95%CI) of 2.99 (1.46–6.13), 2.31 (1.23–4.36), 2.71 (1.05–6.99), p=0.003, 0.010, and 0.039, respectively. In multivariate analyses adjusted for APRI, BMI>23 kg/m2 remained significantly associated with cirrhosis (aHR: 2.76, p=0.006), while diabetes showed borderline significance (aHR: 1.99, p=0.072). ConclusionsIn HBV-infected patients achieving viral suppression with therapy, a BMI > 23 kg/m2 increases the risk of cirrhosis. Therefore, a comprehensive approach addressing metabolic factors is imperative for preventing disease progression in HBV-infected patients.