title: Predictors of malignancies and overall mortality in Japanese patients with biopsy-proven non-alcoholic fatty liver disease.
abstract: OBJECTIVE
  Some patients with non-alcoholic fatty liver disease (NAFLD) develop hepatocellular carcinoma (HCC) and have higher mortality than others. The evidence causally linking NAFLD to extrahepatic malignancies is scarce. Our aim was to determine the incidence of and risk factors for HCC, extrahepatic cancer and mortality in Japanese patients with biopsy-proven NAFLD.
  
  
  METHODS
  This retrospective cohort study analyzed outcomes including onset of malignant tumors and death in 312 patients with NAFLD diagnosed by liver biopsy.
  
  
  RESULTS
  Of 312 patients, 176 (56.4%) were diagnosed with non-alcoholic steatohepatitis. During a median follow-up period of 4.8 years (range, 0.3-15.8), six patients (1.9%) developed HCC, and 20 (6.4%) developed extrahepatic cancer. Multivariate analysis identified fibrosis stage (≥3; hazard ratio [HR], 12.3; 95% confidence interval [CI], 1.11-136.0; P = 0.041) as a predictor for HCC and type IV collagen 7s (>5 ng/mL; HR, 1.74; 95% CI, 1.08-2.79; P = 0.022) as a predictor for extrahepatic cancer. Eight patients (2.6%) died during the follow-up period. The most common cause of death was extrahepatic malignancy. None died of cardiovascular disease. Multivariate analysis identified type IV collagen 7s (>5 ng/mL; HR, 3.38; 95% CI, 1.17-9.76; P = 0.024) as a predictor for mortality.
  
  
  CONCLUSIONS
  The incidence of extrahepatic cancer was higher than that of HCC. Severe fibrosis was a predictor for HCC. Patients with NAFLD and elevated type IV collagen 7s levels are at increased risk for extrahepatic cancer and overall mortality.
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Seko
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Sumida
authors.affiliation: Center for Digestive and Liver Diseases, Nara City Hospital, Nara, Japan.
authors.forename: Saiyu
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Center for Digestive and Liver Diseases, Nara City Hospital, Nara, Japan.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Taketani
authors.affiliation: Center for Digestive and Liver Diseases, Nara City Hospital, Nara, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Kanemasa
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishiba
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Okajima
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nishimura
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Kanji
authors.initials: K
authors.lastname: Yamaguchi
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Michihisa
authors.initials: M
authors.lastname: Moriguchi
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Mitsuyoshi
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Kohichiroh
authors.initials: K
authors.lastname: Yasui
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Minami
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Itoh
keywords: hepatocellular carcinoma; mortality; non-alcoholic fatty liver disease; type IV collagen 7s