Significant liver histological change is not uncommon in ALT normal HBeAg-positive chronic hepatitis B

Abstract

Abstract Background and Aims: Numerous HBeAg-positive chronic hepatitis B(CHB) patients with persistently normal ALT have significant liver histopathology,it is imperative to identify true "immune tolerant" patients.We aimed to evaluate the liver histopathology features of HBeAg-positive CHBpatients with normalALT, and the incidence of liver cirrhosis and HCC in CHB patients during follow-up. Methods:179 HBeAg-positiveCHB patients with normalALT whoperformed liver biopsy from 2009 to 2018 were retrospectively analyzed.Liver necroinflammation ≥ G2 and/or liver fibrosis ≥ S2was defined as significant liver histopathological change. Results:57.5% patients were in the indeterminate phase with significant liver histological changes. The proportion of the patients with evident livernecroinflammation was higher in thehigh-normal ALT group (21-40U/L) when compared with the low-normal ALT group (≤ 20 U/L) (51.3% vs 30.0%, p < 0.05),and patients aged ≥ 40 years had a higher proportion of significant fibrosis than those aged < 40 years (64.5% vs 39.9%, p < 0.05).The percentage of patients with ≥ S2and ≥ G2/S2in the HBV DNA < 107 IU/mL group were higher than those in the HBV DNA ≥ 107 IU/mL group (72.7% vs 40.1%, p < 0.01; 81.8% vs 54.1%, p < 0.05). During follow-up, two of immune tolerant patients and four of indeterminate patients developed into cirrhosis, and one of immune tolerant patients and one of indeterminate patients developed into HCC, respectively. Conclusions:HBeAg-positive CHBpatients with high-normal ALT or HBV DNA < 107 IU/mL were tend to be indeterminate, liver biopsy or noninvasive approaches are recommended to evaluateliver histopathology, and antiviral therapyare recommendedfor patients with significant liver histopathology.