Concomitant liver steatosis in chronic HBV infection is linked to a distinct cytokine profile and reduced viral load.

Abstract

Chronic hepatitis B virus (HBV) infection coexists with liver steatosis in about one third of cases. Increasing evidence indicates that concomitant liver steatosis contributes to liver disease progression and hepatocellular carcinoma (HCC) development in chronic HBV infection. However, the impact of liver steatosis on the immune response and viral load remains largely unknown. In the present study we investigated cytokine and chemokine patterns in plasma samples of treatment-naïve patients with chronic HBV infection (n = 66) in the absence or presence of liver steatosis using a multiplex technique. In addition, viral load and aminotransferase levels were assessed in blood samples. HBV-infected patients with liver steatosis revealed a lower viral load than patients without liver steatosis. Despite significantly lower HBV-DNA and HBsAg levels, HBV patients with steatosis showed reduced plasma cytokine (IL-2, IL-9, IL-15, and IL-18), chemokine (IP-10, CCL2, and CCL4) and aminotransferase levels compared to HBV patients without liver steatosis. In contrast, levels of other cytokines, such as IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-17, and TNF-α, did not significantly differ between both patient groups. In chronic HBV infection, concomitant liver steatosis is associated with lower viral load but a dampened systemic cytokine and chemokine response. This pattern is compatible with an impaired immune response and may contribute to disease progression and HCC risk independently of viral load. Long-term studies are needed to clarify the clinical implications of this observation.