Systematic review and meta-analysis: Significant histological changes among treatment-naive chronic hepatitis B patients with normal alanine aminotransferase levels by different criteria

BackgroundThe upper limits of normal (ULNs) of ALT are not consistent across the major international guidelines which may affect the eligibility for antiviral therapy for chronic hepatitis B (CHB). AimTo estimate the proportions of histological changes among treatment-naive patients with CHB within differently defined ALT ULNs. MethodsWe searched PubMed and Embase up to May 15th, 2023, to identify studies of treatment-naive CHB patients with liver biopsies. We pooled proportions of moderate to severe necroinflammation, significant fibrosis, and cirrhosis in those patients within different ALT ULNs by using random-effect models. ResultsWe included 23 studies with 4010 participants. Within ALT ULN at 40 IU/L, the pooled proportions of moderate to severe necroinflammation, significant fibrosis, and cirrhosis were 33% (95% CI: 26%-42%), 32% (95% CI: 27%-38%), and 3% (95% CI: 1%-5%), respectively. Within ALT ULN at 30 IU/L for men and 19 IU/L for women, the pooled proportion of significant fibrosis remained at 30% (95% CI: 25%-34%; 432 participants). However, it was 21% (95% CI: 11%-37%; 361 participants) even in those within ALT ULN at 20 IU/L. Subgroup analyses suggested a significantly higher proportion of significant fibrosis among studies with prospective design or enrolled patients' mean age >35 or >40 years. ConclusionsSignificant histological changes occurred in approximately 1/3 of treatment-naive CHB patients within ALT ULN at 40 IU/L, whereas the proportion of significant fibrosis was approximately 1/5 even in those within ALT ULN at 20 IU/L.