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Background: weight loss as a result of lifestyle intervention is effective when treating non-alcoholic fatty liver disease (NAFLD). We estimated the effects of  PNPLA3  rs738409 and  HSD17B13  rs6834314 variants in response to diet therapy in Japanese patients with NAFLD. Methods: we analyzed the correlation between the change in liver stiffness and change in body weight in 140 patients administered diet therapy for 1-year, according to  PNPLA3  and  HSD17B13  genotypes. Results: the bodyweight (BW) reduction rate was greater in patients with the  PNPLA3  genotype CC than CG and GG ( p  = 0.035). Change in liver stiffness measurement (LSM) was significantly associated with a change in BW in  PNPLA3  CG/GG (r = 0.279/0.381), but not in  PNPLA3  CC ( p  = 0.187). Change in LSM was correlated with change in BW only in patients with  HSD17B13  AG/GG (r = 0.425), but not the AA genotype ( p  = 0.069). A multivariate analysis identified that a change in LSM was correlated with a change in BW in carriers of  HSD17B13  AG/GG (B = 3.043,  p  = 0.032), but not  HSD17B13  AA. The change in LSM of patients with a BW reduction of more than 7% (0.50) was significantly greater than that of patients with a BW reduction of less than 7% (0.83) ( p  = 0.038). Conclusions: in Japanese patients with NAFLD,  HSD17B13  rs6834314 polymorphism is associated with the change in LSM by lifestyle intervention. The approach, including genetic assessments, may contribute to the establishment of appropriate therapeutic strategies to treat NAFLD.

The Effect of Genetic Polymorphism in Response to Body Weight Reduction in Japanese Patients with Nonalcoholic Fatty Liver Disease