Rischio di progressione della fibrosi epatica nei pazienti con epatite B cronica e APRI score indeterminato: definizione dei predittori degli outcome a lungo termine in un ospedale di terzo livello italiano

ABSTRACT Background Chronic hepatitis B virus (HBV) infection remains one of the leading causes of liver cirrhosis and hepatocellular carcinoma (HCC) worldwide. Several non-invasive scores have been proposed for liver fibrosis stratification, including the APRI score, calculated as the ratio between aspartate aminotransferase and platelet count. APRI identifies three risk categories: low risk of fibrosis (<0.5), intermediate risk (0.5–1.5), and high risk (>1.5). Patients with APRI values between 0.5 and 1.5 represent a “grey zone” in which the long-term risk of fibrosis progression remains unclear. Objectives The aims of this study were: (1) to evaluate the risk of progression to advanced fibrosis in a cohort of non-cirrhotic patients with chronic HBV infection stratified according to baseline APRI score; and (2) to identify the main epidemiological, clinical, and virological factors associated with liver disease progression, with particular attention to the impact of metabolic risk factors (MRFs). Methods This retrospective observational study included patients with chronic HBV infection followed at the Padua University Hospital (2003–2026). Demographic, biochemical, and virological parameters, non-invasive fibrosis scores (APRI, FIB-4), and liver stiffness measurements by transient elastography (FibroScan®) were collected. Patients with a diagnosis of cirrhosis or HCC within 12 months from the first visit, with follow-up <12 months, or with hepatitis C or hepatitis delta coinfection were excluded. Advanced fibrosis was defined as liver stiffness >8 kPa or FIB-4 ≥3.25 when elastography was not available. Univariable and multivariable logistic regression models were used to identify predictors of liver disease progression. Results A total of 172 HBsAg-positive patients were included [91 (52,9%) male, median age 51 (41-61)]. During a median follow-up of 4.2 years, 12.8% of patients developed advanced fibrosis. The presence of at least one metabolic risk factor was associated with liver disease progression (OR 3.24), independently of viral load, hepatic necroinflammatory activity, and baseline APRI score and liver stiffness. Among patients with low (<0.5; 67%) and intermediate (0.5–1.5; 24%) baseline APRI scores, progression to advanced fibrosis occurred in 2.9% and 8.1% of patients, respectively. In patients with intermediate APRI scores, the presence of at least one metabolic risk factor was the only predictor of liver disease progression (OR 4.89). In this subgroup, the probability of developing advanced fibrosis in the absence of metabolic risk factors was 0% at 5 years, compared with 24% in patients with metabolic risk factors, despite the two groups being comparable at baseline in terms of epidemiological, biochemical, virological characteristics and disease stage. Conclusions In patients with chronic HBV infection, the presence of at least one metabolic risk factor is associated with a three-fold higher risk of developing advanced fibrosis, independently of biochemical and virological parameters. Notably, in our cohort of patients with intermediate APRI scores, progression to advanced fibrosis occurred exclusively in those with metabolic risk factors, while no cases were observed in patients without such factors. These findings suggest that metabolic profiling should be incorporated into the prognostic stratification of patients with chronic HBV infection in order to identify individuals at higher risk who may benefit from closer monitoring and targeted management of modifiable comorbidities.