Chronic hepatitis B and metabolic risk factors: A call for rigorous longitudinal studies

Long-term nucleos(t)ide analogue therapy in chronic hepatitis B virus (HBV) infection is effective in suppressing viral replication and reducing liver-related complications. However, HBV-related liver events can still occur in different patient sub-groups. There is emerging evidence that, similar to chronic hepatitis C virus infection, metabolic risk factors may play a role in the disease process of chronic HBV. While the mechanistic nature of metabolic-HBV interactions remains uncertain, studies in different HBV-infected populations have demonstrated that hepatic steatosis, increased body-mass index, diabetes, or a combination of different metabolic risk factors are associated with an increased risk of hepatocellular carcinoma and cirrhosis. The impact of metabolic risk factors is especially prominent in patients with quiescent virological activity, including on-treatment patients with effective viral suppression. As the proportion of on-treatment chronic HBV patients increases worldwide, longitudinal studies determining the relative risks of different metabolic parameters with respect to clinical outcomes are needed. Future studies should also determine if metabolic-directed interventions can improve disease outcomes in chronic HBV.