| Summary: | Background: weight loss as a result of lifestyle intervention is effective when treating non-alcoholic fatty liver disease (NAFLD). We estimated the effects of <i>PNPLA3</i> rs738409 and <i>HSD17B13</i> 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 <i>PNPLA3</i> and <i>HSD17B13</i> genotypes. Results: the bodyweight (BW) reduction rate was greater in patients with the <i>PNPLA3</i> genotype CC than CG and GG (<i>p</i> = 0.035). Change in liver stiffness measurement (LSM) was significantly associated with a change in BW in <i>PNPLA3</i> CG/GG (r = 0.279/0.381), but not in <i>PNPLA3</i> CC (<i>p </i>=<i> </i>0.187). Change in LSM was correlated with change in BW only in patients with <i>HSD17B13</i> AG/GG (r = 0.425), but not the AA genotype (<i>p </i>=<i> </i>0.069). A multivariate analysis identified that a change in LSM was correlated with a change in BW in carriers of <i>HSD17B13</i> AG/GG (B = 3.043, <i>p </i>=<i> </i>0.032), but not <i>HSD17B13</i> 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) (<i>p </i>=<i> </i>0.038). Conclusions: in Japanese patients with NAFLD, <i>HSD17B13</i> 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.
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