Abstract
Hepatitis B virus (HBV) infection is not only a major cause of liver cirrhosis and hepatocellular carcinoma, but also contributes to a range of extrahepatic manifestations (EHMs) involving multiple organ systems. These EHMs may reflect underlying immune dysregulation and hepatic injury, yet their clinical characteristics and prognostic implications remain inadequately defined. This retrospective cohort study included 216 HBV-infected patients treated at our hospital between January 2022 and January 2023. Patients were divided into 2 groups based on the presence or absence of EHMs. Demographic data, biochemical profiles, liver function parameters, and immunological markers were collected. All patients were followed for 24 months. Chi-square test, Student t test, and Cox proportional hazards regression models were used to evaluate the association between EHMs and adverse prognosis. In the EHM group (n = 88), the prevalence of hypertension and diabetes was significantly higher than in the non-EHM group (P < .05), along with elevated blood glucose levels. The most commonly affected extrahepatic systems included the kidneys (32.9%), joints (23.9%), and skin (17.0%). Levels of alanine aminotransferase, aspartate aminotransferase, and total bilirubin were significantly higher in the EHM group, and the proportion of patients with Child-Pugh class C was also increased (26.1% vs 12.5%, P = .021). Immunological analysis showed elevated immunoglobulin G levels, decreased complement component 3 and complement component 4 levels, and a significantly higher rate of autoantibody positivity (P = .008). During follow-up, the incidence of composite adverse outcomes was significantly higher in the EHM group (30.7% vs 15.6%, P = .012), and EHMs were identified as an independent risk factor for poor prognosis (HR = 2.14, 95% confidence interval: 1.17-3.91, P = .014). Extrahepatic manifestations are common in patients with HBV infection and are associated with multi-system involvement, immune activation, impaired liver function, and increased risk of adverse outcomes. Early identification and management of EHMs may improve long-term prognosis in HBV-infected patients.