Liver steatosis is a strong predictor of mortality and cancer in chronic hepatitis B regardless of viral load

Liver steatosis may occur concomitantly in patients with chronic hepatitis B infection (CHB) and is implicated in increased morbidity and mortality. Hepatitis B virus (HBV) viral load is a marker for disease progression and long-term outcomes in CHB. We investigated the association between liver steatosis and HBV viral load and their individual effects on all-cause mortality and the development of cancer in patients with CHB and liver steatosis. Methods: This retrospective study included 524 treatment-naïve patients with CHB, with a mean follow-up of 6 years. Liver biopsy was available for 170 patients and liver steatosis was validated by at least 3 ultrasonographic examinations. Results: A total of 241/524 (46%) patients with CHB had liver steatosis, with a strong correlation between the degree of liver steatosis as assessed by ultrasonography or by liver biopsy (r = 0.9, p < 0.001). Although liver steatosis was not significantly associated with advanced fibrosis, a multivariate analysis showed that liver steatosis was associated with a 4-fold increased risk of all-cause mortality and cancer (hazard ratio 4.35; 95% CI 1.69–8.99; p < 0.001), irrespective of other major metabolic factors. However, baseline HBV viral load was not significantly associated with this composite outcome (hazard ratio 1.65; p = 0.29). In addition, liver steatosis was inversely associated with HBV viral load. Conclusion: Patients with CHB and liver steatosis have an increased risk of all-cause mortality and cancer development compared to patients with CHB without liver steatosis, regardless of their baseline HBV viral load. Although tending to have a lower baseline viral load, patients with CHB and liver steatosis should be closely monitored irrespective of viral load. Lay summary: Patients with chronic hepatitis B infection (CHB) may have liver steatosis at the same time. Here we show that in patients with CHB, liver steatosis is significantly associated with all-cause mortality and cancer, irrespective of other major metabolic factors, and the effect of liver steatosis on mortality and cancer is stronger than the effect of hepatitis B viral load on these outcomes. Thus, patients with CHB and liver steatosis should be closely monitored, irrespective of their viral load.