Prevalence and Clinical Significance of the Hepatitis C Virus Core Protein 70Q/H Mutation and Its Association With Hepatocellular Carcinoma-Related Markers in Mexican Patients.

BACKGROUND/AIMS: Hepatitis C virus (HCV) infection is a major risk factor for hepatocellular carcinoma (HCC). Substitutions at residue 70 of the HCV core protein (R70Q/H) have been associated with advanced liver disease and increased HCC risk, particularly in genotype 1b. This study aimed to determine the prevalence of the 70Q/H mutation and its association with clinical and biochemical markers of liver injury. METHODS: Eighty-seven HCV-infected patients were evaluated prior to antiviral treatment. Clinical data, imaging studies, liver enzymes (alkaline phosphatase [ALP], gamma-glutamyl transferase [GGT], alanine aminotransferase, and aspartate aminotransferase [AST]), serological markers (alpha-fetoprotein [AFP] and protein induced by vitamin K absence or antagonist-II [PIVKA-II]), fibrosis indices (AST-to-platelet ratio index [APRI], fibrosis-4 index [FIB-4]), and Child-Pugh scores were collected. Viral RNA was sequenced and analyzed to determine its genotype (G) and presence of R70Q/H substitutions. RESULTS: Genotype distribution was 56.3% (49) G1a, 34.5% (30) G1b, and 9.2% (8) G2. The overall prevalence of the 70Q/H mutation was 27.6% (24/87; 95% confidence interval, 18.5-38.2%), detected exclusively in G1a (30.6%) and G1b (30.0%). Patients carrying the mutation showed significantly (P ≤ 0.05) higher APRI, FIB-4, ALP, GGT, AFP, and PIVKA-II levels compared with wild-type carriers. In univariate analysis, elevated ALP, GGT, FIB-4, and AFP were associated with the presence of the 70Q/H mutation; however, none remained significant in multivariate analysis. CONCLUSION: The 70Q/H substitution was frequent in HCV genotypes 1a and 1b in the group of patients studied and was associated with surrogate markers of advanced liver disease and increased HCC risk.