We read with great interest the meta-analysis by Zheng et al.1 They analysed 54 eligible studies and demonstrated a pooled prevalence of hepatic steatosis (HS) in patients with chronic hepatitis B (CHB) of 32.8%. HS was associated with age, male gender as well as metabolic factors, and inversely correlated with hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA. Of note, in the 6232 patients from the 20 selected studies, HS was not associated with hepatic fibrosis. This study provides helpful information regarding the current prevalence of HS on CHB. However, some concerns were raised for the interpretation of the results and the underlying pathophysiology.

First, the non-significant association between HS and fibrosis in this study was derived from the pooled analysis, which was statistically univariate without adjustment for other key variables such as HBeAg, HBV DNA level and aspartate aminotransferase (AST) that were actually negatively correlated with HS in these patients, being potentially misleading. Viral factors play the most essential roles in driving fibrosis progression and carcinogenesis in CHB.2, 3 Whether the degree of fibrosis was mainly determined by viral activity, and whether the absence of steatosis simply reflected the consequential fibrosis caused by CHB, should be clarified before drawing definite conclusions. The authors mentioned the possible mechanisms of viral suppression by steatosis4; however, a study has supported hepatic fat loss in advanced fibrosis (so-called “burnt-out NASH”) as a natural course with plausible pathophysiology.5 As a result, the association remains uncertain in this analysis unless the viral factors could be well controlled.

Second, fatty liver disease has recently been considered as a condition of systemic dysfunction instead of a hepatic disease alone. The new criteria of “metabolic dysfunction-associated fatty liver disease (MAFLD)” proposed in 2020 enrol a different population than the former criteria of “non-alcoholic fatty liver disease (NAFLD).”6 In our previous study on patients with biopsy-proven steatosis (including those with CHB),7 the new MAFLD criteria enrolled more patients and better identified those with advanced fibrosis and higher disease severity than the former NAFLD criteria. Therefore, CHB patients with concurrent MAFLD are expected to have a higher degree of fibrosis according to the novel diagnostic criteria. The classification by only “hepatic steatosis” without consideration of systemic metabolic dysfunction for the diagnosis may underestimate disease severity, select heterogeneous populations in the real-world setting, and not satisfy the clinical needs precisely.

In summary, we thank Zheng et al for providing the excellent meta-analysis revealing the overall prevalence of HS in CHB, and the factors associated with HS. Although there was a non-significant association between HS and fibrosis, the causal relationship and definite impact of HS on fibrosis severity and other long-term outcomes in CHB need future in vitro and in vivo experiments and large longitudinal studies to reach a final conclusion.

Declaration of personal interests: None.