Effects of Non-Alcoholic Fatty Liver Disease on Baseline Histology and 96-Week Entecavir Response in Treatment-Naïve Chronic Hepatitis B

Xiaohui Gu,1,* Weiguang Yang,2,* Yue Hu,3 Yixin Li,4 Liwei Zheng,5 Bei Jiang3 1The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Department of Cardiovascular Surgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 3Tianjin Second People’s Hospital, Tianjin Institute of Hepatology, Tianjin, People’s Republic of China; 4School of Medical Technology, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, People’s Republic of China; 5Division of Infectious Diseases, Anschutz Medical Campus, University of Colorado School of Medicine, Aurora, CO, USA*These authors contributed equally to this workCorrespondence: Bei Jiang, Tianjin Second People’s Hospital, Tianjin Institute of Hepatology, Tianjin, People’s Republic of China, Email [email protected] Liwei Zheng, Division of Infectious Diseases, Anschutz Medical Campus, University of Colorado School of Medicine, Aurora, CO, USA, Email [email protected] and Aims: The coexistence of chronic hepatitis B (CHB) and non-alcoholic fatty liver disease (NAFLD) is increasingly common, yet their combined impact on antiviral outcomes remains unclear. This study aimed to compare baseline histopathological features and longitudinal virological responses to entecavir (ETV) therapy in CHB patients with and without NAFLD.Methods: From October 2014 to January 2022, 299 treatment-naïve CHB patients (130 with NAFLD, 169 without NAFLD) were enrolled in a real-world observational cohort at Tianjin Second People’s Hospital. NAFLD diagnosis was confirmed by liver biopsy and (or) ultrasound examination following AASLD guidelines. Baseline characteristics (histopathology, metabolic profiles, HBV markers) and serial virological outcomes (HBV DNA seroconversion, HBsAg/HBeAg loss rate) were analyzed over 96 weeks of ETV therapy. Statistical comparisons utilized Mann–Whitney U and chi-square tests.Results: At baseline, NAFLD-comorbid patients exhibited milder hepatic inflammation (G≥ 3: 6.9% vs 17.2%, P =0.022) and fibrosis (S≥ 3: 10.8% vs 17.2%, P =0.020) despite higher metabolic dysregulation (BMI: 24.8 vs 21.5 kg/m2, TG: 1.05 vs 0.89 mmol/L, P < 0.001). While early virological responses (4– 48 weeks) were comparable, NAFLD patients showed significantly lower HBV DNA seroconversion rates at 96 weeks (82.7% vs 92.1%, P =0.038) and persistently reduced HBsAg levels (3.17± 1.07 vs 3.57± 0.67, P = 0.017).Conclusion: Despite milder baseline histology, NAFLD comorbidity predicts suboptimal 96-week HBV DNA seroconversion and slower HBsAg decline during entecavir therapy, underscoring the need for intensified, integrated metabolic-antiviral management in this cohort.Keywords: NAFLD, chronic hepatitis B, clinical cohort study, virological response, entecavir