NAFLD and HBV interplay - related mechanisms underlying liver disease progression

Abstract

Non-alcoholic fatty liver disease (NAFLD) and Hepatitis B virus infection (HBV) constitute common chronic liver diseases with worldwide distribution. NAFLD burden is expected to grow in the coming decade, especially in western countries, considering the increased incidence of diabetes and obesity. Despite the organized HBV vaccinations and use of anti-viral therapies globally, HBV infection remains endemic and challenging public health issue. As both NAFLD and HBV have been associated with the development of progressive fibrosis, cirrhosis and hepatocellular carcinoma (HCC), the co-occurrence of both diseases has gained great research and clinical interest. The causative relationship between NAFLD and HBV infection has not been elucidated so far. Dysregulated fatty acid metabolism and lipotoxicity in NAFLD disease seems to initiate activation of signaling pathways that enhance pro-inflammatory responses and disrupt hepatocyte cell homeostasis, promoting progression of NAFLD disease to NASH, fibrosis and HCC and can affect HBV replication and immune encountering of HBV virus, which may further have impact on liver disease progression. Chronic HBV infection is suggested to have an influence on metabolic changes, which could lead to NAFLD development and the HBV-induced inflammatory responses and molecular pathways may constitute an aggravating factor in hepatic steatosis development. The observed altered immune homeostasis in both HBV infection and NAFLD could be associated with progression to HCC development. Elucidation of the possible mechanisms beyond HBV chronic infection and NAFLD diseases, which could lead to advanced liver disease or increase the risk for severe complications, in the case of HBV-NAFLD co-existence is of high clinical significance in the context of designing effective therapeutic targets.

Fat fraction quantification with MRI estimates tumor proliferation of hepatocellular carcinoma

“…Most of the patients with fatty liver or without fatty liver in this study were accompanied by chronic HBV or HCV infection. Chronic hepatitis is suggested to have an influence on metabolic changes ( 26 ), potentially leading to fatty liver development. Therefore, the observed fatty liver in our study may be attributed to chronic hepatitis rather than non-alcoholic fatty liver disease or metabolic syndrome, explaining the lack of significant differences in tumor fat fraction between the two groups.…”

Metabolic dysfunction-associated steatotic liver disease increases hepatocellular carcinoma risk in chronic hepatitis B patients: a retrospective cohort study

“…These conflicting findings suggest that NAFLD has a complex relationship with CHB, especially after being redefined as MASLD. Although the presence of HS may result in the suppression of HBV viral activity and a reduction in liver damage (Tourkochristou et al, 2022), CMRFs such as DM may increase the risk of HCC (Wang et al, 2012). These findings suggest that the individual components of MASLD may have opposing effects on the clinical manifestations of CHB.…”

Serum ApoB/ApoA1 ratio in patients with CHB and the occurrence of HBV related cirrhosis and HBV related hepatocellular carcinoma

“…When HBV infected patients develop liver injury, individual gene expression is regulated. Notably, the pathway of lipid biosynthetic enzymes is changing, and blood lipid levels correspondingly lose balance 7 . Existing research has suggested that patients with chronic hepatitis B (CHB) are subjected to lower triglyceride (TG), total cholesterol (TCh), and low-density lipoprotein cholesterol (LDL-C) levels, as well as higher high-density lipoprotein cholesterol (HDL-C) levels compared with healthy controls 8 , 9 .…”