A Distinct Immune Signature Characterizes Cirrhosis in Ethiopian Individuals With Chronic <scp>HBV</scp> Infection

ABSTRACT Background and Aims The immune cell phenotype of African patients living with chronic hepatitis B virus (HBV) infection is rarely described, despite high infection rates. This study investigated the differences in immune cell phenotypes in four distinct clinical phases of disease in an Ethiopian cohort. Methods Two hundred eighty‐seven patients with untreated HBV infection, and no human immunodeficiency virus and hepatitis C virus infection, were included at Adama Hospital, Ethiopia. Patients were categorized based on clinical parameters into the following groups: low‐replicative infection, “greyzone”, active hepatitis, and cirrhosis. Whole blood samples were cryopreserved using Cytodelics Whole Blood Cell Stabilizer and analysed using two high‐dimensional flow cytometry panels to define immune cell phenotypes. Results Patients with cirrhosis displayed a distinct immunophenotype compared to other phases of chronic HBV infection with an increase in monocytes and a reduction in all lymphocytes alongside a shift from a mature to a naïve phenotype in NK cells, CD4 + T cells, and B cells. The emergence of activated CD38 + HLA‐DR + cells across lymphocyte lineages defined patients with cirrhosis and the frequency of these double positive cells correlated positively with the AST to Platelet Ratio Index used as a measure of cirrhosis severity. Conclusions HBV‐associated cirrhosis in Ethiopia displayed a unique immunophenotype, in which the frequency of CD38 + HLA‐DR + NK cells and T cells correlated strongly with the severity of cirrhosis.