Prognostic Divergence in HIV/HBV vs. HBV- Associated HCC after Resection: Intrahepatic Pre-S Deletions Mutants and T-cell Depletion under Viral Suppression.

Abstract

BACKGROUND Despite effective antiretroviral (ART) 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 co-infected and HBV mono-infected individuals. METHODS 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). HBV Pre-S region was amplified by nested PCR and sequenced. Tumor infiltrating lymphocytes (CD3, CD4, CD8) were quantified by immunohistochemistry (IHC). Survival outcomes (recurrence-free survival [RFS] and overall survival [OS]) were analyzed using Kaplan-Meier curves. RESULTS 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) were significantly worse. 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 co-infected tumors than in HBV mono-infected tumors (p=0.039). CONCLUSIONS 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.