Fibrogenic polymorphisms (TGF-β, PAI-1, AT) in Mexican patients with established liver fibrosis.: Potential correlation with Pirfenidone treatment

Background/Aim: The aim of this work was to establish a potential correlation between specific poly morphisms and presence of hepatic fibrosis in Mexican patients with established liver fibrosis (ELF). Second, necro-inflammatory index improvement was correlated with Pirfenidone (PFD) treatment response and the same polymorphisms. Methods: We analyzed TG1-beta polymorphisms in codon 25, a single basepair guanine insertion-deletion polymorphism (4G/5G) for PAI-1 and angiotensin A T-6 single nucleotide polymorphism located in -6 promoter region. Twenty patients infected with either hepatitis C Virus (HCV) (n = 13) or affected by alcohol consumption (n = 7) were included. Thirty Subjects with no hepatic damage were included in control group. Blood samples for genomic DNA were obtained and plasminogen activator inhibitor-1 polymorphisms were done by polymerase chain reaction-artificial introduction of a restriction site, TGI-beta by polymerase chain reaction-amplification refractory mutation system and AT by polymerase chain reaction-restriction fragment length polymorphisms. Liver biopsies were obtained at baseline and after 12 months of PFD treatment. Results: Established liver fibrosis patients had the homozygote G/G TGF-beta genotype, which has been associated with increased development of fibrosis. None of our patients had the G/C genotype. All pure HCV and pure alcohol abuse subjects carried G/G TGF-beta genotype (100% vs 37% control) (P = 0.0006). The odds of having beta G/G genotype was 19.5 for HCV patients and 10.83 for alcohol consumption patients as compared with healthy subjects (P < 0.001). Established liver fibrosis patients had an improvement in necroinflammatory index after PFD treatment when correlated with plasminogen activator inhibitor-1 and angiotensinogen-6 genotypes. Conclusion: Our data suggested that a combination of inherited polymorphisms increased the risk of advanced fibrosis in ELF patients. Pure HCV and pure alcohol consumption patients which were homozygous G/G carriers had 19.5- and 10.8-fold higher risk to develop advanced fibrosis respectively.