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 with elevated serum HBV DNA levels (>2000 IU/mL), normal alanine aminotransferase (ALT) levels, and no significant liver fibrosis, referred to as the "indeterminate phase." This study aimed to identify factors associated with liver fibrosis progression in chronic HBV patients within this phase. Since the study's design, hepatitis B treatment guidelines have undergone significant evolution. New WHO recommendations published in 2024 advocate for expanded treatment criteria, making terms like "Indeterminate phase" obsolete.

Methods: This retrospective longitudinal cohort study was conducted at Farhat Hached University Hospital in Sousse, Tunisia, from January 2008 to January 2022. We included HBsAg-positive patients who were untreated, had 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 occurred in 16 patients (16.5%), with a mean delay of 70.9 ± 41.1 months. Univariate analysis showed significant associations between fibrosis progression and comorbidities (p = 0.001), high initial viral load (p = 0.004), elevated liver enzymes (p = 0.001), and increased 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.

Conclusion: Comorbidities and changes in ALT levels during follow-up were associated with fibrosis progression in the indeterminate phase of chronic HBV infection. Our findings support recent changes in international guidelines, including those from the WHO in 2024, which expand therapeutic indications for individuals living with hepatitis B.