Validation of Noninvasive Markers for HCC Risk Stratification in 1389 Patients With Biopsy-proven NAFLD

Hidenori Toyoda; Hideki Fujii; Michihiro Iwaki; Hideki Hayashi; Satoshi Oeda; Hideyuki Hyogo; Miwa Kawanaka; Asahiro Morishita; Kensuke Munekage; Kazuhito Kawata; Sakura Yamamura; Koji Sawada; Tatsuji Maeshiro; Hiroshi Tobita; Yuichi Yoshida; Masafumi Naito; Asuka Araki; Shingo Arakaki; Takumi Kawaguchi; Hidenao Noritake; Masafumi Ono; Tsutomu Masaki; Satoshi Yasuda; Eiichi Tomita; Masato Yoneda; Norifumi Kawada; Akihiro Tokushige; Yoshihiro Kamada; Hirokazu Takahashi; Shinichiro Ueda; Shinichi Aishima; Yoshio Sumida; Atsushi Nakajima; Takeshi Okanoue; Japan Study Group of Nonalcoholic Fatty Liver Disease (JSG-NAFLD)

doi:10.1016/j.gastha.2023.07.018

Validation of Noninvasive Markers for HCC Risk Stratification in 1389 Patients With Biopsy-proven NAFLD

Gastro Hep Adv. 2023 Aug 2;2(8):1093-1102. doi: 10.1016/j.gastha.2023.07.018. eCollection 2023.

Authors

Hidenori Toyoda¹, Hideki Fujii^{2

3}, Michihiro Iwaki⁴, Hideki Hayashi⁵, Satoshi Oeda^{6

7}, Hideyuki Hyogo⁸, Miwa Kawanaka⁹, Asahiro Morishita¹⁰, Kensuke Munekage¹¹, Kazuhito Kawata¹², Sakura Yamamura¹³, Koji Sawada¹⁴, Tatsuji Maeshiro¹⁵, Hiroshi Tobita¹⁶, Yuichi Yoshida¹⁷, Masafumi Naito¹⁷, Asuka Araki¹⁶, Shingo Arakaki¹⁵, Takumi Kawaguchi¹³, Hidenao Noritake¹², Masafumi Ono¹⁸, Tsutomu Masaki¹⁰, Satoshi Yasuda¹, Eiichi Tomita⁵, Masato Yoneda⁴, Norifumi Kawada², Akihiro Tokushige¹⁹, Yoshihiro Kamada²⁰, Hirokazu Takahashi⁶, Shinichiro Ueda¹⁹, Shinichi Aishima²¹, Yoshio Sumida²², Atsushi Nakajima³, Takeshi Okanoue²³; Japan Study Group of Nonalcoholic Fatty Liver Disease (JSG-NAFLD)

Affiliations

¹ Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan.
² Departments of Premier Preventive Medicine, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan.
³ Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan.
⁴ Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
⁵ Department of Gastroenterology and Hepatology, Gifu Municipal Hospital, Gifu, Japan.
⁶ Liver Center, Saga University Hospital, Saga, Japan.
⁷ Department of Laboratory Medicine, Saga University Hospital, Saga, Japan.
⁸ Department of Gastroenterology, JA Hiroshima Kouseiren General Hospital, Hatsukaichi, Japan.
⁹ Department of General Internal Medicine2, Kawasaki Medical Center, Kawasaki Medical School, Okayama, Japan.
¹⁰ Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kita-gun, Japan.
¹¹ Department of Gastroenterology and Hepatology, Kochi Medical School, Kochi, Japan.
¹² Hepatology Division, Department of Internal Medicine II, Hamamatsu University School of Medicine, Hamamatsu, Japan.
¹³ Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
¹⁴ Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Asahikawa Medical University, Asahikawa, Japan.
¹⁵ First Department of Internal Medicine, University of the Ryukyus Hospital, Okinawa, Japan.
¹⁶ Department of Hepatology, Shimane University Hospital, Izumo, Japan.
¹⁷ Department of Gastroenterology and Hepatology, Suita Municipal Hospital, Suita, Japan.
¹⁸ Division of Innovative Medicine for Hepatobiliary & Pancreatology, Faculty of Medicine, Kagawa University, Takamatsu, Japan.
¹⁹ Department of Clinical Pharmacology and Therapeutics, Graduate School of Medicine, University of the Ryukyu, Okinawa, Japan.
²⁰ Department of Advanced Metabolic Hepatology, Osaka University Graduate School of Medicine, Suita, Japan.
²¹ Department of Pathology and Microbiology, Faculty of Medicine, Saga University, Saga, Japan.
²² Graduate School of Healthcare Management, International University of Healthcare and Welfare, Tokyo, Japan.
²³ Hepatology Center, Saiseikai Suita Hospital, Suita, Japan.

Abstract

Background and aims: Nonalcoholic fatty liver diseases (NAFLD) and nonalcoholic steatohepatitis (NASH) can cause hepatocellular carcinoma (HCC). We examined histological features and reported noninvasive markers/models for stratifying the risk of HCC development in patients with biopsy-proven NAFLD or NASH.

Methods: A total of 1389 patients who had a histological diagnosis of NAFLD or NASH based on liver biopsy and underwent regular surveillance for HCC were included. The ability to predict HCC development was compared between histological features including liver fibrosis and NAFLD activity score, and noninvasive markers/models including aMAP (age, male, albumin-bilirubin, and platelet) score, FIB-4 (Fibrosis-4) index, and ALBI (albumin-bilirubin) score calculated at the time of biopsy.

Results: The C index of aMAP score was 0.887, which was consistent with the original report, comparable to FIB-4 index (0.878), and higher than those of ALBI score (0.789), histological liver fibrosis (0.723), and NAFLD activity score (0.589). The hazard ratios for HCC development in the aMAP intermediate and high-risk groups were 21.0 (95% confidence interval [CI], 3.6-402.0) and 110.3 (95% CI, 16.3-2251.4), respectively, in comparison to the aMAP score low-risk group. Those in the FIB-4 index moderate- and high-fibrosis groups were 10.3 (95% CI, 1.7-199.8) and 93.1 (95% CI, 16.3-1773.8), respectively, in comparison to the FIB-4 index mild-fibrosis group. No patients in the aMAP score low-risk group developed HCC during the study period.

Conclusion: For stratifying the risk of HCC development in patients with biopsy-proven NAFLD or NASH, both aMAP score and FIB-4 index showed high discriminative ability as noninvasive markers, which were superior histological features.

Keywords: ALBI Score; FIB-4 Index; Hepatocellular Carcinoma; Nonalcoholic Fatty Liver Disease; aMAP Score.