Prognostic Divergence in Human Immunodeficiency Virus/Hepatitis B Virus Versus Hepatitis B Virus-Associated Hepatocellular Carcinoma After Resection: Intrahepatic Pre-S Deletions Mutants and T-Cell Depletion Under Viral Suppression.

Abstract

Despite effective antiretroviral use, the incidence of hepatocellular carcinoma (HCC) has not decreased in human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfection. Our study compared postoperative prognosis, HBV Pre-S deletion, and immune microenvironment in coinfected and HBV-mono-infected individuals. This retrospective study included 143 HBV-associated HCC patients who underwent curative resection. Virologically suppressed patients (HBV DNA < 1000 IU/mL and HIV RNA < 20 copies/mL) were matched by 1:3 propensity score matching (PSM). Hepatitis B virus Pre-S region was amplified by nested polymerase chain reaction (PCR) and sequenced. Tumor-infiltrating lymphocytes (CD3, CD4, CD8) were quantified by immunohistochemistry. Survival outcomes (recurrence-free survival [RFS] and overall survival [OS]) were analyzed using Kaplan-Meier curves. Baseline analysis showed higher rates of microvascular invasion (76.9% vs 40.0%, P = 0.010) and capsular invasion (30.8% vs 8.5%, P = 0.043) in the HIV/HBV-HCC group. After PSM, compared with HBV-HCC, HIV/HBV-HCC had a higher rate of RFS (hazard ratio [HR] = 4.03, 95% CI 0.96-16.81; P = 0.0058) and OS (HR = 12.04, 95% CI 2.24-64.65; P < 0.0001) was significantly worse. The HIV/HBV-HCC liver tissues showed an increased frequency of Pre-S quasispecies deletion (p = 0.003) and decreased intrahepatic CD4+ infiltration (tumor: P = 0.01; adjacent: P = 0.007). CD8+ expression was lower in coinfected tumors than in HBV-mono-infected tumors (P = 0.039). Virus-suppressed HIV/HBV-HCC showed a worse prognosis, with more Pre-S deletion mutants and more severe T-cell depletion observed in the liver, requiring further investigation of the mechanism.