Chronic Hepatitis B and Steatotic Liver Disease: A Blessing in Disguise?

We read with great interest the study by Huang et al1Huang S.C. et al.Clin Gastroenterol Hepatol. 2023; (Epub 20231021)Google Scholar that proposed a link between the presence of concurrent metabolic dysfunction-associated steatotic liver disease (SLD) and increased rates of HBsAg seroclearance and seroconversion in patients with untreated HBeAg-negative chronic hepatitis B (CHB). Their findings are consistent with our previous study,2Li J. et al.J Infect Dis. 2021; 224: 294-302Crossref PubMed Scopus (48) Google Scholar where we observed that patients with CHB with concomitant fatty liver (FL) had a higher 10-year cumulative incidence of HBsAg loss, compared with those without FL. HBV infection is a major contributor to liver cirrhosis and hepatocellular carcinoma (HCC), particularly in East Asia and African countries.3Hsu Y.C. et al.Nat Rev Gastroenterol Hepatol. 2023; 20: 524-537Crossref PubMed Scopus (16) Google Scholar Simultaneously, SLD affects one-third of the world population, with SLD-related liver cirrhosis and HCC also on the rise. It has been reported to have a stronger association with all-cause mortality and cancer even than hepatitis B virus.4Peleg N. et al.JHEP Rep. 2019; 1: 9-16Abstract Full Text Full Text PDF PubMed Google Scholar, 5Le M.H. et al.Clin Gastroenterol Hepatol. 2022; 20: 2809-2817.e28Abstract Full Text Full Text PDF PubMed Scopus (185) Google Scholar, 6Le M.H. et al.J Hepatol. 2023; 79: 287-295Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar However, with these study findings, as well as our previous studies, it is reassuring to see that the presence of SLD in those with CHB may not increase the risk of liver complications and may even be protective against adverse outcomes due to the increased seroclearance rate. In fact, in our aforementioned study, we found that patients with FL-CHB had lower risks of liver cirrhosis, HCC, and mortality compared with patients without FL-CHB.2Li J. et al.J Infect Dis. 2021; 224: 294-302Crossref PubMed Scopus (48) Google Scholar This finding is also supported by our systematic review and individual patient-level data meta-analysis,7Wong Y.J. et al.Clin Mol Hepatol. 2023; 29: 705-720Crossref PubMed Scopus (5) Google Scholar which included 19 studies involving over 13,232 individuals, and the background risk of patients with and without FL-CHB in the individual patient-level data meta-analysis were matched by inverse probability of treatment weighting methods. However, what was surprising was the additive impact on seroclearance rates with the presence of cardio-metabolic risk factors present in those with metabolic dysfunction-associated SLD. This finding appears counterintuitive, as studies have demonstrated the presence of cardio-metabolic risk factors such as type 2 diabetes increases the risk for fibrosis, HCC, and cirrhosis in those with CHB,8Lee Y.B. et al.Hepatology. 2021; 73: 2266-2277Crossref PubMed Scopus (40) Google Scholar which would suggest that patients had not undergone seroclearance—a point the authors discussed. However, as per the authors' analysis, the extent of steatosis was a predictor for seroclearance, such that those with moderate to severe steatosis had a higher rate of seroclearance. This finding may suggest that there may be multicollinearity present between the amount of steatosis and the presence of cardio-metabolic risk factors, a suggestion that is apparent in Supplementary Table 4, where metabolic burden (per criterion) was not a predictor of seroclearance in those with CHB without steatosis. As the authors noted, unraveling these interactions is imperative to provide accurate and timely treatment of any cardiometabolic risk factors that may be present. In summary, we congratulate the authors for their remarkable work, which presents vital evidence for potential facilitation of HBsAg loss in SLD. We believe that further investigations are warranted to unravel the underlying mechanisms, identify potential therapeutic targets, and develop interventions that can optimize outcomes in patients with CHB and concurrent SLD and how treatment of cardiometabolic risk factors should be conducted. Metabolic Dysfunction-Associated Steatotic Liver Disease Facilitates Hepatitis B Surface Antigen Seroclearance and SeroconversionClinical Gastroenterology and HepatologyPreviewHepatitis B surface antigen (HBsAg) seroclearance is the goal of functional cure for hepatitis B virus (HBV) infection. However, the impact of metabolic dysfunction-associated steatotic liver disease (MASLD) on this favorable outcome remains unclear. Full-Text PDF The Janus-faced nature of SLD in chronic hepatitis BClinical Gastroenterology and HepatologyPreview Full-Text PDF