Polymorphisms Of Enzymes Of Alcohol Metabolism And Sex Hormone Levels For Development To Significant Fibrosis In Patients With Hepatitis C

Background:Hepatitis C virus(HCV)infection is a major worldwide health problem.The remaining 55?85%of persons will develop chronic chronic hepatitis C,of which 10?20%can progress to cirrhosis.Liver fibrosis,a dynamic process of progress,is the intermediate link in the progression of chronic liver disease to cirrhosis.Many epidemiological studies have shown that most patients with cirrhosis have a history of alcohol,and the liver is the main organ of alcohol metabolism,alcohol is an independent risk factor for the development of chronic hepatitis.ALDH2 rs671 and ADH1B rs 1229984 polymorphism are the most important alcohol metabolism-related genes,which determine the metabolic rate of alcohol.Lots of studies have shown that among patients with hepatitis C,drinking habits of the crowd suffering from advanced chronic liver disease(such as cirrhosis,liver cancer)account for a larger proportion,and the vast majority is male.In this study,Sanger,HRM and Tetra-primer ARMS PCR used in this study are designed to detect the polymorphisms of ALDH2 and ADH1B in male patients with chronic hepatitis C.As well as serum sex hormones were included in the assay.Thus,this study focus on whether there is such a phenomenon that the polymorphisms of enzymes of alcohol metabolism and sex hormone levels for development to significant fibrosis in males with hepatitis C by Univariate and Multivariate Logistic Regression Analysis.Objective:1.To study the risk factors of liver fibrosis in patients with chronic hepatitis C;2.To study the relationship between hepatic fibrosis and alcohol metabolism-related genes in males with chronic hepatitis C;3.To study the correlation between hepatic fibrosis,and sex hormone levels in males with chronic hepatitis C.Methods:1.Retrospective analysis of 359 cases of chronic hepatitis C patients treated by Renmin Hospital of Wuhan University,and explore the risk factors affecting the progress of liver fibrosis in patients;2.The genotypes of ALDH2 rs671 and ADH1B rs1229984 gene polymorphisms were screened by Sanger sequencing.The high resolution melting curve analysis(HRM)and Tetra-primer ARMS-PCR were used to detect ALDH2 and ADH1B genes.And the accuracy of the above two methods is verified by Sanger sequencing.3.Using ALDH2 and ADH1B genotypes,alcohol consumption,smoking,diabetes,antiviral therapy,blood transfusion history and other hepatitis virus infection as independent variable and patients with significant fibrosis as the dependent variable to study the possible risk factors for the progression of fibrosis in chronic hepatitis C patients by Univariate and Multivariate Logistic Regression Analysis.4.The levels of testosterone and estradiol in male patients with chronic hepatitis C were measured.Multivariate Logistic Regression Analysis was performed to evaluate the risk of significant hepatic fibrosis in male patients with chronic hepatitis C with significant hepatic fibrosis as a dependent variable,and the serum testosterone,estradiol,testosterone/estradiol ratio,y-glutamyl transpeptidase,albumin,total bilirubin,HCV genotype and HCV-RNA load as independent variables.Results:1.This study showed that men are risk factors for progressive hepatic fibrosis in chronic hepatitis C(P<0.05).That is to say,in chronic hepatitis C patients,gender difference affects the process of hepatic fibrosis.The level of serum ?-glutamyl transpeptidase(GGT)increased in significant fibrosis group(P<0.05),which could reflect the process of hepatic fibrosis.In patients with mild hepatic fibrosis and significant fibrosis,HCV-RNA levels and genotyping of hepatitis C virus were not associated with the risk of progressive hepatic fibrosis in patients with chronic hepatitis C,and there was no significant difference in levels of HCV RNA and HCV genotype(P>0.05).2.This study successfully established Sanger sequencing,HRM analysis,Tetra-primer ARMS PCR to detect alcohol metabolism related genes ALDH2 rs671 and ADH1B rs1229984 polymorphism.3.In this study,in the univariate analysis ADH1B AA,drinking,smoking 20 or more cigarettes per day,blood transfusion were risk factors for progressive hepatic fibrosis in male patients with chronic hepatitis C P<0.05).However,in the multivariate analysis,only AA type(OR = 2.23,95%CI 1.13-4.41,P<0.05),drinking(OR = 5.70,95%CI 2.83-11.50,P<0.05)were independent risk factors for patients with significant hepatic fibrosis.4.In this study,testosterone and estradiol levels were elevated in male patients with chronic hepatitis C,but only testosterone was elevated in the significant fibrosis group.Multivariate Logistic Regression Analysis showed that serum testosterone levels in male patients with chronic hepatitis C(OR= 1.01,95%CI 1.0-1.02,P<0.05)and albumin(OR = 0.84,95%CI 0.77-0.92,P<0.05),and ?-glutamyl transpeptidase(OR = 1.01,95%CI 1.00-1.02,P<0.05)were independent indicators of the risk of significant hepatic fibrosis.Conclusions:ADH1B AA genotype,drinking,higher serum testosterone are significantly associated with an increased risk of significant hepatitis C-related liver fibrosis in males...