Factors Associated with Progressive Liver Disease in Untreated HBV patients in Tunisia

Background Antiviral therapy is not routinely recommended for chronic hepatitis B virus (HBV) infection in patients exhibiting persistently elevated serum HBV DNA levels (>2000 IU/mL), normal alanine aminotransferase (ALT), and without significant liver fibrosis – a clinical state termed the indeterminate phase. Recognizing the evolving treatment landscape, this study aimed to identify factors associated with liver fibrosis progression in chronic HBV patients within this indeterminate phase. Methods This retrospective longitudinal cohort study was conducted in the Infectious Disease and Hepato-gastroenterology departments of Farhat Hached University Hospital in Sousse, Tunisia, between January 2008 and January 2022. We included HBsAg-positive patients initially untreated, presenting at evaluation with a viral load >2,000 IU/mL for at least six months, normal ALT (<40 IU/L), and a fibrosis score of F0 and/or F1 (determined by liver biopsy or FibroScan). Univariate and logistic regression analyses were performed to identify factors associated with liver fibrosis progression. Results A total of 97 patients were included, with a median age of 32.9 ± 9.1 years, and a female predominance (M/F ratio = 0.64). Fibrosis progression was observed in 16 patients (16.5%), with a mean delay of 70.9 ± 41.1 months. Univariate analysis revealed associations between fibrosis progression and the presence of comorbidities (p=0.001), a high initial viral load (p=0.004), elevated liver enzymes (p=0.001), and an increase in viral load during follow-up (p=0.002). Multivariate analysis identified comorbidities (p<0.001) and changes in ALT levels (p<0.001) as independent predictors of fibrosis progression. The AUROC of the initial viral load was 0.664 (95%CI: 0.500-0.820). Conclusion The presence of comorbidities and changes in ALT levels during follow-up were associated with fibrosis progression in the indeterminate phase of chronic HBV infection. These findings suggest a potential rationale for extending therapeutic indications to include this patient population.