Outcomes of Japanese patients with non-alcoholic fatty liver disease according to genetic background and lifestyle-related diseases

Introduction and objectives: Genetic background may be involved in the mechanisms of liver injury and the development of non-alcoholic fatty liver disease (NAFLD). However, its contributions to the long-term outcome of NAFLD have been unclear. Methods: We enrolled 314 Japanese patients with biopsy-confirmed NAFLD from 2000 to 2018 (161 men [51.3%]; median age, 53 [14-84] years; 114 with advanced fibrosis [37.5%]) in the patients without hepatocellular carcinoma at diagnosis. Genomic DNA was extracted from peripheral blood and single nucleotide polymorphisms (SNPs) were analyzed. Associations of mortality with patatin-like phospholipase 3 (PNPLA3) and aldehyde dehydrogenase 2 (ALDH2) were analyzed. Finally, a subgroup analysis according to lifestyle-related disease was performed. Results: During the median 7 years of follow-up, 20 patients (6.4%) died (13 liver-related [4.1%] and 7 non-liver-related deaths [2.2%]). Patients with ALDH2 (non-GG genotype) who had reduced alcohol metabolism tended to have a poor prognosis (p = 0.06). Patients carrying both risk SNPs of PNPLA3 (GG) and ALDH2 (non-GG) had a significantly poor prognosis (p = 0.01). In the subgroup analysis, patients with PNPLA3 (GG) who were non-diabetics (p = 0.06) or non-dyslipidemic (p = 0.03), with ALDH2 (nonGG) who were non-dyslipidemic (p = 0.01) or hypertensive (p = 0.03), also had a poor prognosis. The Cox analysis revealed that ALDH2 (non-GG) was associated with a poor prognosis (Hazard ratio: 4.568, 95% Confidence Interval: 1.294-16.131, p = 0.02) similar to the liver function tests. Conclusions: Genetic background may affect NAFLD prognosis and ALDH2 SNP could predict the outcome. (C) 2020 Fundacion Clinica Medica Sur, A.C. Published by Elsevier Espana, S.L.U.

Automated summary

The study on 314 Japanese NAFLD patients found that ALDH2 gene SNP may affect the prognosis of NAFLD, and patients carrying the risk genes PNPLA3 (GG) and ALDH2 (non-GG) have a poorer prognosis. Subgroup analysis revealed that the disease status and genotypes of some patients were associated with prognosis.