Haptoglobin 2-2 Genotype is Associated with More Advanced Disease in Subjects with Non-Alcoholic Steatohepatitis: A Retrospective Study

Introduction: Haptoglobin (Hp) genotypes were reported as an independent risk factor for metabolic diseases. This study aimed to investigate the association between Hp gene polymorphism and the severity of nonalcoholic fatty liver disease (NAFLD). Methods: A total of 441 subjects (NAFLD group, n = 272; healthy control, n = 169) were recruited, and their clinical biochemical parameters were measured in all subjects. Haptoglobin genotyping was performed using genomic DNA extracted from peripheral blood leukocytes. Among the NAFLD group, 107 patients underwent liver biopsy, and histology was evaluated by a pathologist on the basis of the CRN scoring system. Results: NAFLD patients had much lower frequency of Hp 1-1 genotype and higher frequency of Hp 2-2 than healthy controls (0.4% vs 9.5%, 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); patients with significant fibrosis had higher frequency of Hp 2-2 genotype (78.3% vs 54.8%, P < 0.05) than no/mild fibrosis patients. NAFLD patients with Hp 2-2 genotype had higher proportion with higher steatosis scores, lobular inflammation scores, ballooning scores, NAFLD activity scores (NAS), and fibrosis stages (P < 0.05 for all) than Hp 2-2 groups. Furthermore, Hp 2-2 genotype was independently associated with NASH (OR = 5.985, P < 0.05) and significant fibrosis (OR = 6.584, P < 0.05). Conclusions: Hp 2-2 genotype is closely associated with the severity of NAFLD.