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Association between inherited monogenic liver disorders and chronic hepatitis C

World Journal of Hepatology 2014年第2期6卷 92-97页

作者： Linda Piekuse Madara Kreile agnese zarina Zane Steinberga Valentina Sondore Jazeps Keiss Baiba Lace Astrida Krumina Scientific Laboratory of Molecular Genetics Riga Stradins University Latvian Centre of Infectious Diseases Riga East University Hospital Latvian Biomedical Research and Study Centre

AIM:To determine the frequencies of mutations that cause inherited monogenic liver disorders in patients with chronic hepatitis C. METHODS:This study included 86 patients with chronic hepatitis C(55 men, 31 women; mean age at diagnosis, 38.36 ± 14.52 years) who had undergone antiviral therapy comprising pegylated interferon and ribavirin. Viral load, biochemical parameter changes, and liver biopsy morphological data were evaluated in all patients. The control group comprised 271 unrelated individuals representing the general population of Latvia for mutation frequency calculations. The most frequent mutations that cause inherited liver disorders [gene(mutation): ATP7B(H1069Q), HFE(C282Y, H63D),UGT1A1(TA)7, and SERPINA1(PiZ)] were detected by polymerase chain reaction(PCR), bidirectional PCR allele-specific amplification, restriction fragment length polymorphism analysis, and sequencing. RESULTS: The viral genotype was detected in 80 of the 86 patients. Viral genotypes 1, 2, and 3 were present in 61(76%), 7(9%), and 12(15%) patients, respectively. Among all 86 patients, 50(58%) reached an early viral response and 70(81%) reached a sustained viral response. All 16 patients who did not reach a sustained viral response had viral genotype 1. Casecontrol analysis revealed a statistically significant difference in only the H1069Q mutation between patients and controls(patients, 0.057; controls, 0.012; odds ratio, 5.514; 95%CI: 1.119-29.827, P = 0.022). However, the H1069Q mutation was not associated with antiviral treatment outcomes or biochemical indices. The(TA) 7 mutation of the UGT1A1 gene was associated with decreased ferritin levels(beta regression coefficient =-295.7, P = 0.0087). CONCLUSION: Genetic mutations that cause inherited liver diseases in patients with hepatitis C should be studied in detail.

关键词： Hepatitis C Hepatolenticular degeneration(Wilson’s disease) ATP7B SERPINA1 UGT1A1 HFE

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