Brief Article
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World J Hepatol. Feb 27, 2014; 6(2): 92-97
Published online Feb 27, 2014. doi: 10.4254/wjh.v6.i2.92
Association between inherited monogenic liver disorders and chronic hepatitis C
Linda Piekuse, Madara Kreile, Agnese Zarina, Zane Steinberga, Valentina Sondore, Jazeps Keiss, Baiba Lace, Astrida Krumina
Linda Piekuse, Madara Kreile, Agnese Zarina, Zane Steinberga, Scientific Laboratory of Molecular Genetics, Riga Stradins University, Riga LV-1007, Latvia
Valentina Sondore, Jazeps Keiss, Latvian Centre of Infectious Diseases, Riga East University Hospital, Riga LV-1006, Latvia
Baiba Lace, Astrida Krumina, Latvian Biomedical Research and Study Centre, Riga LV-1067, Latvia
Author contributions: Krumina A and Keiss J designed the research protocol; Piekuse L and Lace B performed the research; Piekuse L, Kreile M, Zarina A, and Steinberga Z performed the experiments; Sondore V and Piekuse L analyzed the data; and Piekuse L wrote the manuscript.
Supported by The Latvian Council of Science, National Project, Nos. 09.1384 and 10.0010.02
Correspondence to: Linda Piekuse, MD, Scientific Laboratory of Molecular Genetics, Riga Stradins University, No. 16 Dzirciema Street, Riga LV-1007, Latvia.
Telephone: +37-1-67061542 Fax: +37-1-67471815
Received: September 23, 2013
Revised: December 16, 2013
Accepted: January 15, 2014
Published online: February 27, 2014

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. Case-control 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.

Keywords: Hepatitis C, Hepatolenticular degeneration (Wilson’s disease), ATP7B, SERPINA1, UGT1A1, HFE

Core tip: This is the first study to evaluate the association between hepatitis C and the most frequently inherited monogenic liver diseases (hereditary hemochromatosis, alpha-1 antitrypsin deficiency, Gilbert’s syndrome, and Wilson’s disease) and their causative mutations. This case-control study revealed an association between hepatitis C and the mutation that causes Wilson’s disease. In addition, biochemical data analysis revealed an association between hepatitis C and the mutation that causes Gilbert’s syndrome.