Difference of gut microbiota between patients with negative and positive HBeAg in chronic hepatitis B and the effect of tenofovir alafenamide on intestinal flora

Jianfei Long; Jingru Gong; Han Zhu; Xiaolin Liu; Ling Li; Bicui Chen; Hongyan Ren; Chao Liu; Huiping Lu; Jiming Zhang; Bin Wang

doi:10.3389/fmicb.2023.1232180

Difference of gut microbiota between patients with negative and positive HBeAg in chronic hepatitis B and the effect of tenofovir alafenamide on intestinal flora

Front Microbiol. 2023 Sep 20:14:1232180. doi: 10.3389/fmicb.2023.1232180. eCollection 2023.

Authors

Jianfei Long¹, Jingru Gong², Han Zhu², Xiaolin Liu², Ling Li³, Bicui Chen¹, Hongyan Ren⁴, Chao Liu⁴, Huiping Lu², Jiming Zhang^{5

6

7}, Bin Wang^{1

3}

Affiliations

¹ Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, China.
² Department of Pharmacy, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.
³ Department of Pharmacy, Jing'an District Central Hospital, Fudan University, Shanghai, China.
⁴ Shanghai Mobio Biomedical Technology Co., Ltd., Shanghai, China.
⁵ Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
⁶ Shanghai Institute of Infectious Diseases and Biosecurity, Key Laboratory of Medical Molecular Virology (MOE/MOH), Shanghai Medical College, Fudan University, Shanghai, China.
⁷ Department of Infectious Diseases, Jing'An Branch of Huashan Hospital, Fudan University, Shanghai, China.

Abstract

Background: Severe liver diseases, such as liver fibrosis, cirrhosis, and liver cancer, are mainly caused by hepatitis B virus (HBV). This study investigated the differences between gut microbiota in HBeAg-positive and negative groups of patients with chronic hepatitis B (CHB) and investigated the effect of tenofovir alafenamide (TAF) on gut microbiota.

Methods: This prospective study included patients with CHB not taking nucleoside antivirals (No-NAs group, n = 95) and those taking TAF (TAF group, n = 60). We divided CHB patients into two groups according to the HBeAg status of the subjects on the day of data collection. Phase 1 are HBeAg-negative patients and phase 2 are HBeAg-positive patients. We investigated the improvement of clinical symptoms by TAF, as well as differences in gut microbiota between different groups by 16S rRNA high-throughput sequencing.

Results: Gut microbiota demonstrated significant differences between patients with HBeAg-positive and -negative CHB. Both the No-NAs and TAF Phase 2 subgroups demonstrated significantly increased microbiota richness and diversity, showing greater heterogeneity. Additionally, the Phase 2 subgroup exhibited a low abundance of pathways associated with glucose metabolism and amino acid metabolism. The TAF group demonstrated a significantly decreased HBV load, alanine aminotransferase, and aspartate aminotransferase and a significant increase in prealbumin compared with the No-NAs group. No significant difference was found in uric acid, creatinine, blood calcium, inorganic phosphorus, eGFR, and β2-microglobulin concentrations between the two groups. Additionally, the urea level in the TAF group was significantly lower than that in the No-NAs group, but with no significant effect on other indicators such as eGFR and β2-microglobulin.

Conclusion: This study revealed significant differences in gut microbiota composition and function between patients with HBeAg-positive and -negative CHB.

Keywords: HBeAg; HBsAg; gut microbiota; hepatitis B virus; tenofovir alafenamide.

Grants and funding

This study was sponsored by National Natural Science Foundation of China (NSFC82003864 and 81872938), Shanghai Sailing Program (19YF1405700), Key Discipline Construction Project of Pudong Health Bureau of Shanghai: Clinical Pharmacy (Grant No. PWZxk2022-27), and Clinical Pharmacy Key Specialized subject Construction Project of Pudong Hospital affiliated to Fudan University (Grant No. Tszk2020-05).