Correlation Between Haptoglobin 2-2 Genotype And Disease Progression In Patients With Nonalcoholic Steatohepatitis

Introduction: Haptoglobin(Hp)genotypes were reported as an independent risk factor for metabolic diseases.This aim of this study was to investigate the association between Hp gene polymorphism and the severity of nonalcoholic fatty liver disease(NAFLD).Methods: 441 subjects were recruited(NAFLD group,n = 272;healthy control group,n=169)and their clinical biochemical parameters were measured in all subjects.Haptoglobin genotyping was performed using genomic DNA extracted from peripheral blood leukocytes.Among NAFLD group,107 patients underwent liver biopsy and histology was evaluated by pathologist based on CRN scoring system.Results: NAFLD patients had much higher frequency of Hp 2-2 than healthy controls(55.8% vs 47.9%,P < 0.001).NAFLD patients with Hp 2-2 genotype had much higher levels of body mass index(BMI),total cholesterol(TC),liver enzymes,ferritin and controlled attenuation parameter(CAP)values than non-Hp 2-2 genotype(P < 0.05).In histology,patients with nonalcoholic steatohepatitis(NASH)had higher frequency of Hp 2-2 genotype than non-NASH patients(71.3% vs 22.2%,P<0.001),At the same time,the frequency of Hp2-2 genotype was higher in patients with obvious fibrosis(78.3% vs 54.8%,P < 0.05)than that of no/mild fibrosis patients.NAFLD patients with Hp 2-2 genotype had higher proportion with higher steatosis scores,lobular inflammation score,ballooning score,NAFLD activity score(NAS)and fibrosis stages(P < 0.05 for all)than Hp 2-2 groups.Furthermore,Hp2-2 genotype was independently correlated with "NASH"(OR = 5.985,P < 0.05)and "significant fibrosis"(OR = 6.584,P < 0.05).Conclusions: The Hp 2-2 genotype is closely related to the severity of NAFLD.