Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Feb 27;6(2):92-7.
doi: 10.4254/wjh.v6.i2.92.

Association between inherited monogenic liver disorders and chronic hepatitis C

Linda Piekuse  1 , Madara Kreile  1 , Agnese Zarina  1 , Zane Steinberga  1 , Valentina Sondore  1 , Jazeps Keiss  1 , Baiba Lace  1 , Astrida Krumina  1
Affiliations

Association between inherited monogenic liver disorders and chronic hepatitis C

Linda Piekuse et al. World J Hepatol. .

Abstract

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: ATP7B; HFE; Hepatitis C; Hepatolenticular degeneration (Wilson’s disease); SERPINA1; UGT1A1.

PubMed Disclaimer

References

    1. Ghany MG, Nelson DR, Strader DB, Thomas DL, Seeff LB. An update on treatment of genotype 1 chronic hepatitis C virus infection: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology. 2011;54:1433–1444. - PMC - PubMed
    1. Milman N, Pedersen P. Evidence that the Cys282Tyr mutation of the HFE gene originated from a population in Southern Scandinavia and spread with the Vikings. Clin Genet. 2003;64:36–47. - PubMed
    1. Lace B, Sveger T, Krams A, Cernevska G, Krumina A. Age of SERPINA1 gene PI Z mutation: Swedish and Latvian population analysis. Ann Hum Genet. 2008;72:300–304. - PubMed
    1. Krumina A, Keiss J, Sondore V, Chernushenko A, Cernevska G, Zarina A, Micule I, Piekuse L, Kreile M, Lace B, et al. From clinical and biochemical to molecular genetic diagnosis of Wilson disease in Latvia. Genetika. 2008;44:1379–1384. - PubMed
    1. Kucinskas L, Juzenas S, Sventoraityte J, Cedaviciute R, Vitkauskiene A, Kalibatas V, Kondrackiene J, Kupcinskas L. Prevalence of C282Y, H63D, and S65C mutations in hereditary HFE-hemochromatosis gene in Lithuanian population. Ann Hematol. 2012;91:491–495. - PubMed