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Editorial: central obesity is a risk factor for hepatocellular carcinoma in Asian patients with chronic hepatitis B on anti‐viral therapy—authors' reply

We thank Drs Yip and Wong for their thoughtful editorial and for further discussing the association between central obesity and hepatocellular carcinoma (HCC) development in nucleos(t)ide analogue (NA)treated patients with chronic hepatitis B (CHB).1,2 In this study, we found that HCC risk in patients with waisttoheight ratio loss in the first year did not decrease as theoretically proposed but rather increased.2 The possible reason is that waist loss may not only be caused by a reduced calorie diet or exercise, but also by the progression of underlying liver disease. To eliminate or reduce interference of the heterogeneity in the causes of waist loss, collection of dietary fat intake and exercise information, and assessment of body composition in each visit are effective methods. Regarding the issue of coexisting fatty liver on top of hepatitis B virus (HBV) infection, concomitant fatty liver has been associated with worse prognosis and disease progression in patients with CHB,35 as Yip et al mentioned. However, there are also several studies with different findings, where hepatic steatosis did not appear to affect liver fibrosis.68 One recent study showed that reduced hepatic steatosis was significantly associated with a higher risk of HCC in CHB infection.9 Additionally, in a multicentre retrospective cohort of 7816 Asian patients with CHB, fatty liver was significantly associated with lower risks of cirrhosis and HCC.10 In our CHB cohort (SearchB cohort), we also found that patients with coexisting fatty liver had significantly lower 5year incidence of HCC than those without fatty liver (2.0% vs 3.4%, P = 0.004) (Figure 1). Hence, the impact of concomitant fatty liver on disease progression in patients with CHB is complex and controversial. The effects of central obesity and fatty liver on HCC development may exist together. Central obesity commonly reflects abnormal metabolic status, while fatty liver may be induced by combinations of factors together (e.g., alcoholism, malnutrition, pregnancy or drug therapy) and have a complex relationship with liver fibrosis. The underlying mechanism also needs further investigation. In summary, the occurrence of HCC in patients with CHB is affected by various known and unknown factors. There are still many issues to be resolved.