RESUMO
BACKGROUND/AIM: The aim of this work was to establish a potential correlation between specific polymorphisms and presence of hepatic fibrosis in Mexican patients with established liver fibrosis (ELF). Second, necroinflammatory index improvement was correlated with Pirfenidone (PFD) treatment response and the same polymorphisms. METHODS: We analyzed TGF-beta polymorphisms in codon 25, a single basepair guanine insertion-deletion polymorphism (4G/5G) for PAI-1 and angiotensin AT-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, TGF-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 TGF-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.
Assuntos
Angiotensinogênio/genética , Cirrose Hepática/genética , Inibidor 1 de Ativador de Plasminogênio/genética , Fator de Crescimento Transformador beta/genética , Adulto , Idoso , Anti-Inflamatórios não Esteroides/uso terapêutico , Sequência de Bases , Primers do DNA/genética , Feminino , Hepatite C/tratamento farmacológico , Hepatite C/genética , Humanos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática Alcoólica/tratamento farmacológico , Cirrose Hepática Alcoólica/genética , Masculino , México , Pessoa de Meia-Idade , Polimorfismo Genético , Piridonas/uso terapêuticoRESUMO
UNLABELLED: Renal failure is a common complication in patients with alcohol-induced cirrhosis who undergo a superimposed severe alcoholic hepatitis. AIM: Our aim was to evaluate renal dysfunction established as a consequence of acute liver damage (ALD) induced by bile duct ligation (BDL) in cirrhotic rats. Hepatic and renal functional assays were performed. RESULTS: Hyperbilirubinemia and increased alanine aminotransferase and aspartate aminotransferase (p<0.05) in rats with BDL were observed since the first day of bile obstruction in cirrhotic rats. Urinary volume and urinary sodium concentration showed a significant reduction (p<0.05) on days 3 and 5 after BDL. Plasma renin activity, plasma renin concentration, serum creatinine, and BUN values increased (p<0.05) from day 1 to day 7 after BDL. Glomerular filtration rate was substantially decreased from day 1 to day 7. Histological changes became apparent since day 3 after BDL in which glomeruli with mesangial hypercellularity took place in the absence of tubular necrosis; with portal inflammation and proliferation of biliar conduits. Results of the present work demonstrate that ALD induced by BDL in cirrhotic rats produces changes in renal function. In conclusion, this experimental model demonstrates that an ALD of variable etiology, either surgical or induced by CCl(4), can cause important damage that eventually results in renal function deterioration. This experimental model may be suitable, to study the physiopathology of this syndrome, as well as for the evaluation of different pharmacological therapies.
Assuntos
Síndrome Hepatorrenal/etiologia , Cirrose Hepática Experimental/complicações , Animais , Ductos Biliares , Pressão Sanguínea , Tetracloreto de Carbono/toxicidade , Síndrome Hepatorrenal/patologia , Rim/patologia , Rim/fisiopatologia , Ligadura , Fígado/patologia , Fígado/fisiopatologia , Masculino , Óxido Nítrico Sintase Tipo II/análise , Ratos , Ratos WistarRESUMO
Hepatocyte growth factor (HGF) also known as "scatter factor" (SF), was identified for the first time as a potent mitogen of primary cultured hepatocytes; it has multiple biological responses in a variety of cells including mitogenic, motogenic, morphogenic and antiapoptotic activities. It is secreted as an inactive single chain protein and isproteolitically cleaved to form an active two chain HGF. The hepatocyte growth factor activator (HGFA) is the principal activator of HGF. HGF exerts its biological effects through transmembrane tyrosine kinase receptor (c-Met). HGF is a growth factor displaying a remarkable ability to promote tissue repair and organ regeneration after injury. Therefore attention should be set on the clinical potential of HGF as a treatment for various diseases.