Abstract
Correlation of Histopathological Features and Genetic Variations with Prognosis of Japanese Patients with Nonalcoholic Fatty Liver Disease
Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is common worldwide. The aims of this study were to determine the long-term prognosis of NAFLD, including survival and development of hepatocellular carcinoma (HCC), and the effects of histopathological features and genetic variations on prognosis.
Methods: Potential factors that affect survival and HCC developmentafter up to 35 years of follow-up, were investigated in 284 Japanese patients with histopathologically-confirmed NAFLD (including 37 patients with history of malignancy). Especially, we analyzed the impact of PNPLA3 rs738409, TM6SF2 rs58542926, A2BP1 rs3785233, and IL28B rs8099917 genetic variations on prognosis.
Results: The cancer development rate (per 1,000 person years) was 12.8, and that of HCC was 3.05. Multivariate analysis identified TM6SF2 (non-CC type) and fibrosis stage (stage ≥3) as significant determinants of HCC at diagnosis of NAFLD. In 247 patients free of cancers at diagnosis, multivariate analysis identified fibrosis stage 4 and old age (≥60 years) as significant determinants of cancer development Univariate, but not multivariate, analysis showed a significant relation between PNPLA3 GG type and cancer development. In 262 patients free of HCC at diagnosis of NAFLD, cumulative HCC and survival rates varied significantly according to severity of fibrosis, but not by genetic variation. Conclusions: Genetic variants and histopathological features affect, at least in part, the prognosis of Japanese patients with NAFLD, including survival and cancer development. Further prospective studies are needed to determine the impact of clinical parameters on prognosis.
Author(s):
Norio Akuta, Yusuke Kawamura, Fumitaka Suzuki, Satoshi Saitoh,Yasuji Arase, Hideo Kunimoto, Yushi Sorin, Shunichiro Fujiyama, Hitomi Sezaki, Tetsuya Hosaka, Masahiro Kobayashi, Yoshiyuki Suzuki, Mariko Kobayashi, Kenji Ikeda, and Hiromitsu Kumada
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