The Co-occurrence of Chronic Hepatitis B and Fibrosis Is Associated With a Decrease in Hepatic Global DNA Methylation Levels in Patients With Non-alcoholic Fatty Liver Disease.

Fangyuan Li,Lirong Wang,Yaoyao Wang,Xiaoping Liang,Jun Wei,Lijun Wang,Huilian Zhu,Qian Ou,Zhiwei Lai,Liuzhen Pu,Feng Wu,Xingyi Chen,Liuqiao Sun,Hang Xu

doi:10.3389/fgene.2021.671552

Abstract

Global DNA hypomethylation has been reported in patients with chronic hepatitis B (CHB) and non-alcoholic fatty-liver disease (NAFLD). However, the global DNA methylation profile of patients with concurrent NAFLD and CHB (NAFLD + CHB) is still unclear. We aimed to detect the hepatic global DNA methylation levels of NAFLD + CHB patients and assess the associated risk factors. Liver biopsies were collected from 55 NAFLD patients with or without CHB. The histological characteristics of the biopsy were then assessed. Hepatic global DNA methylation levels were quantified by fluorometric method. The hepatic global DNA methylation levels in NAFLD + CHB group were significantly lower than that in NAFLD group. Participants with fibrosis showed lower levels of hepatic global DNA methylation than those without fibrosis. Participants with both CHB and fibrosis had lower levels of hepatic global DNA methylation than those without either CHB or fibrosis. The co-occurrence of CHB and fibrosis was significantly associated with a reduction in global DNA methylation levels compared to the absence of both CHB and fibrosis. Our study suggests that patients with NAFLD + CHB exhibited lower levels of global DNA methylation than patients who had NAFLD alone. The co-occurrence of CHB and liver fibrosis in NAFLD patients was associated with a decrease in global DNA methylation levels.

Highlights

Non-alcoholic fatty-liver disease (NAFLD) is poised to become a predominant cause of chronic liver disease worldwide (Loomba and Sanyal, 2013)
NAFLD progression based on the NAFLD activity score (NAS), graded as simple steatosis (SS) and steatohepatitis borderline (NASH-B)
Data are expressed as means ± standard deviation (SD). ∗P-values in bold indicate a significant difference. #NAFLD progression based on the NAFLD activity score (NAS), graded as simple steatosis (SS) and steatohepatitis borderline (NASH-B)

Summary

Introduction

Non-alcoholic fatty-liver disease (NAFLD) is poised to become a predominant cause of chronic liver disease worldwide (Loomba and Sanyal, 2013). The rising prevalence of obesity and metabolic syndrome has resulted in an increase in the number of patients with concurrent NAFLD and CHB (NAFLD + CHB). Both CHB and NAFLD are leading causes of liver-related morbidity and mortality. In a follow-up study, patients with NAFLD + CHB were found to have a 7.3-fold increased risk of HCC compared to patients with CHB alone (Chan et al, 2017). These studies highlight the challenge of preventing and treating NAFLD + CHB. The underlying mechanisms of this compound disease remain unclear

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Conclusion