title: Association between inherited monogenic liver disorders and chronic hepatitis C.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  Genetic mutations that cause inherited liver diseases in patients with hepatitis C should be studied in detail.
authors.affiliation: Linda Piekuse, Madara Kreile, Agnese Zarina, Zane Steinberga, Scientific Laboratory of Molecular Genetics, Riga Stradins University, Riga LV-1007, Latvia.
authors.forename: Linda
authors.initials: L
authors.lastname: Piekuse
authors.affiliation: Linda Piekuse, Madara Kreile, Agnese Zarina, Zane Steinberga, Scientific Laboratory of Molecular Genetics, Riga Stradins University, Riga LV-1007, Latvia.
authors.forename: Madara
authors.initials: M
authors.lastname: Kreile
authors.affiliation: Linda Piekuse, Madara Kreile, Agnese Zarina, Zane Steinberga, Scientific Laboratory of Molecular Genetics, Riga Stradins University, Riga LV-1007, Latvia.
authors.forename: Agnese
authors.initials: A
authors.lastname: Zarina
authors.affiliation: Linda Piekuse, Madara Kreile, Agnese Zarina, Zane Steinberga, Scientific Laboratory of Molecular Genetics, Riga Stradins University, Riga LV-1007, Latvia.
authors.forename: Zane
authors.initials: Z
authors.lastname: Steinberga
authors.affiliation: Linda Piekuse, Madara Kreile, Agnese Zarina, Zane Steinberga, Scientific Laboratory of Molecular Genetics, Riga Stradins University, Riga LV-1007, Latvia.
authors.forename: Valentina
authors.initials: V
authors.lastname: Sondore
authors.affiliation: Linda Piekuse, Madara Kreile, Agnese Zarina, Zane Steinberga, Scientific Laboratory of Molecular Genetics, Riga Stradins University, Riga LV-1007, Latvia.
authors.forename: Jazeps
authors.initials: J
authors.lastname: Keiss
authors.affiliation: Linda Piekuse, Madara Kreile, Agnese Zarina, Zane Steinberga, Scientific Laboratory of Molecular Genetics, Riga Stradins University, Riga LV-1007, Latvia.
authors.forename: Baiba
authors.initials: B
authors.lastname: Lace
authors.affiliation: Linda Piekuse, Madara Kreile, Agnese Zarina, Zane Steinberga, Scientific Laboratory of Molecular Genetics, Riga Stradins University, Riga LV-1007, Latvia.
authors.forename: Astrida
authors.initials: A
authors.lastname: Krumina
keywords: ATP7B; HFE; Hepatitis C; Hepatolenticular degeneration (Wilson’s disease); SERPINA1; UGT1A1