HBV Dominance Is Associated With a Distinct Inflammatory Milieu in HBV/HCV Coinfection

TL;DR

HBV dominance in coinfected patients creates a unique inflammatory environment that may worsen liver disease.

Contribution

The study identifies distinct immune mediator patterns linked to HBV dominance in HBV/HCV coinfection.

Findings

HBV dominance alters 22 soluble immune mediators and key pathways like JAK–STAT and Th17/IL-17.

CCL27/CTACK and SDF-1alpha levels inversely correlate with HCV-RNA in coinfected patients.

HBV activity increases soluble immune mediator expression, potentially contributing to liver fibrosis.

Abstract

Hepatitis B (HBV) and C (HCV) virus coinfection is linked to a higher risk of cirrhosis and hepatocellular carcinoma (HCC) compared to monoinfection. Despite this, data are limited, and further investigation is needed to understand the underlying mechanisms. While patients are classified based on dominance patterns, the impact on the immune system remains largely unknown. It is recognised that HBV reactivation may occur following HCV clearance. This study aims to explore the potential immune interactivity between HCV and HBV by analysing patterns of soluble immune mediators (SIM). A total of 58 soluble immune mediators were measured in serum or plasma samples of 49 patients chronically infected with hepatitis B and hepatitis C virus in a cross‐sectional study design. Patients were classified based on dominance patterns: HBV dominance (n = 8), HCV dominance (n = 22), HBV and HCV codominance (n = 11) and no dominance (n = 8). SIM expression was distinct based on different dominance patterns. HBV activity induced higher SIM expression and altered the soluble inflammatory milieu (22 SIM altered, p < 0.05). Altered pathways included JAK–STAT pathway (p = 1.36 × 10−20), IL‐17 signalling (p = 2.47 × 10−13) and Th17 cell differentiation (p = 1.69 × 10−9). CCL27/CTACK (r = −0.69, p = 7.02 × 10−6) and SDF‐1alpha (r = −0.55, p = 0.002) correlated inversely with HCV‐RNA. Serologically classifying dominance patterns in HBV and HCV coinfection may manifest in a distinct soluble inflammatory milieu. Elevated HBV activity correlates with an increased expression of soluble immune mediators, particularly influencing the alteration of key signalling pathways such as JAK–STAT and the Th17/IL‐17 axis. These changes have a potential role in the development of liver fibrosis.

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