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Risk of hepatitis C virus related hepatocellular carcinoma between subjects with spontaneous and treatment-induced viral clearance.

ABSTRACT: BACKGROUND/AIMS:Both spontaneous hepatitis C virus (HCV) clearance and the achievement of sustained virological response (SVR) by anti-viral therapy greatly reduce the incidence of hepatocellular carcinoma (HCC). The current study aimed to compare the risk of HCC between the two patient groupsMethods: A total of 313 subjects with spontaneous HCV clearance (SC) and 564 age- and sex-matched patients in the treatment-induced SVR group were enrolled for analysis. RESULTS:Nineteen (2.2%) of the 877 patients developed HCC during 6,963 person-years of follow-up. Fourteen (2.5%) SVR patients and 5 (1.6%) SC patients developed HCC (P=0.004). Cox regression analysis of factors predictive of HCC included SVR (versus SC: hazard ratio [HR]/ 95% confidence interval [CI]: 5.83/1.27-26.88), diabetes (HR/CI:3.41/1.21-9.58), and age (HR/CI: 1.07/1.01-1.14). Of the 564 SVR patients, eleven (5.9%) of the 187 patients with fibrosis stage 2-4 (F2-4) and 2 (0.9%) of the 226 patients with F01 developed HCC (P=0.01). Compared to SC subjects, only SVR patients with F2-4 (P<0.001) but not F0-1(P=0.60) had a higher risk of HCC development. Cox-regression analysis using liver fibrosis as a variable demonstrated that factors associated with HCC included SVR with F2-4 (versus SC: HR/CI: 10.06/2.20-45.98), diabetes (HR/CI:3.23/1.14-9.19), and age (HR/CI: 1.08 1.02-1.15). CONCLUSIONS:Compared to subjects with spontaneous viral clearance, subjects with antiviral treatment-induced HCV viral clearance remain at high risk for HCC development, especially if they have significant hepatic fibrosis. These results may provide important information for decision-making regarding the prioritization of current direct antiviral agents in resource-limited countries.

SUBMITTER: Huang CF

PROVIDER: S-EPMC5546450 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Risk of hepatitis C virus related hepatocellular carcinoma between subjects with spontaneous and treatment-induced viral clearance.

Huang Chung-Feng CF Yeh Ming-Lun ML Huang Ching-I CI Lin Yu-Ju YJ Tsai Pei-Chien PC Lin Zu-Yau ZY Chan Soa-Yu SY Chen Shinn-Cherng SC Yang Hwai-I HI Huang Jee-Fu JF Lu Sheng-Nan SN Dai Chia-Yen CY Jen Chin-Lan CL Yuan Yong Y L'Italien Gilbert G Wang Li-Yu LY Lee Mei-Hsuan MH Yu Ming-Lung ML Chuang Wan-Long WL Chen Chien-Jen CJ

Oncotarget 20170701 27

<h4>Background/aims</h4>Both spontaneous hepatitis C virus (HCV) clearance and the achievement of sustained virological response (SVR) by anti-viral therapy greatly reduce the incidence of hepatocellular carcinoma (HCC). The current study aimed to compare the risk of HCC between the two patient groupsMethods: A total of 313 subjects with spontaneous HCV clearance (SC) and 564 age- and sex-matched patients in the treatment-induced SVR group were enrolled for analysis.<h4>Results</h4>Nineteen (2.2 ...[more]

PMID: 28159934

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Project description:AimTo investigate the relationship between hepatitis B virus (HBV) genotype with spontaneous YMDD mutations and hepatocellular carcinoma (HCC) in HBV-related cirrhosis.MethodsWe investigated 264 liver cirrhosis patients who were not treated with antiviral drugs, including 81 patients with HCC. YMDD mutations were detected by fluorescent hybridization bioprobe polymerase chain reaction (PCR) and melting curve assay using the Diagnosis Kit for HBV YMDD Mutation. Serum HBV genotypes were detected by real-time PCR using genotype-specific TaqMan probes. Statistical analysis was performed according to data type using the t test, χ(2) test and unconditional logistic regression analysis.ResultsIn the HCC group, genotype C strains, spontaneous YMDD mutations, and genotype C strains with YMDD mutations were detected in 33 (40.74%), 13 (16.05%) and 11 (13.58%) patients, respectively. In the liver cirrhosis (LC) group, HBV genotype C strains, spontaneous YMDD mutations, and genotype C strains with YMDD mutations were detected in 33 (18.03%), 7 (3.83%) and 2 (1.09%) patients, respectively. The differences in genotype C strains, spontaneous YMDD mutations, and genotype C strains with YMDD mutations between the two groups were statistically significant (χ(2) = 15.441, P = 0.000; χ(2) = 11.983, P = 0.001; P = 0.000). In the HCC and LC groups, there were seven patients infected by genotype B strains with YMDD mutations and 13 by genotype C strains with YMDD mutations. Further research revealed that HCC occurred in 2 patients infected by genotype B strains with YMDD mutations and 11 infected by genotype C strains with YMDD mutations. The difference was statistically significant (P = 0.000). Unconditional logistic regression analysis revealed that patients infected by genotype C strains with spontaneous YMDD mutations had a 7.775-fold higher risk for the development of HBV-related HCC than patients infected by other type HBV strains (P = 0.013, 95%CI: 1.540-39.264).ConclusionGenotype C strains with spontaneous YMDD mutations are an independent risk factor for HCC in LC patients and are important for early warning of HCC.

Project description:Chronic infections by hepatitis B virus (HBV) and hepatitis C virus (HCV) appear to be the most significant causes of hepatocellular carcinoma (HCC). Aberrant promoter methylation is known to be deeply involved in cancer, including HCC. In this study, we analyzed aberrant promoter methylation on genome-wide scale in 6 HCCs including 3 HBV-related and 3 HCV-related HCCs, 6 matched noncancerous liver tissues and 3 normal liver tissues by methylated DNA immunoprecipitation-on-chip analysis. Candidate genes with promoter methylation were detected more frequently in HCV-related HCC. Candidate genes methylated preferentially to HBV-related or HCV-related HCCs were detected and selected, and methylation levels of the selected genes were validated using 125 liver tissue samples, including 61 HCCs (28 HBV-related HCCs and 33 HCV-related HCCs) and matched 59 matched noncancerous livers, and 5 normal livers, by quantitative methylation analysis using MALDI-TOF mass spectrometry. Among analyzed genes, preferential methylation in HBV-related HCC was validated in 1 gene only. However, 15 genes were found methylated preferentially in HCV-related HCC, which was independent from age. Hierarchical clustering of HCC using these 15 genes stratified HCV-related HCC as a cluster of frequently methylated samples. The 15 genes included genes inhibitory to cancer-related signaling such as RAS/RAF/ERK and Wnt/b-catenin pathways. It was indicated that genes methylated preferentially in HCV-related HCC exist, and it was suggested that DNA methylation might play an important role in HCV-related HCC by silencing cancer-related pathway inhibitors. we analyzed aberrant promoter methylation in 6 HCC clinical samples (including 3 HBV-related HCCs and 3 HCV-related HCCs) and their matched noncancerous tissues on genome-wide scale by the method. Candidate regions of promoter methylation preferentially to HBV-related HCC and HCV-related HCC were selected, and the methylation levels of these genes were measured quantitatively using MALDI-TOF mass spectrometry. Expression levels of these 6 pairs of HCC and 4 more pairs of HCCs and surrounding noncancerous tissues were analyzed by expression array and are reported in this Series. <br><br>This experiment was reloaded in November 2010 after additional curation. this dataset is part of the TransQST collection.

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Risk of hepatitis C virus related hepatocellular carcinoma between subjects with spontaneous and treatment-induced viral clearance.

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Risk of hepatitis C virus related hepatocellular carcinoma between subjects with spontaneous and treatment-induced viral clearance.

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