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• Low HDL cholesterol levels in women and hypertriglyceridemia in men: predictors of MASLD onset in individuals without steatosis.

  Tsutsumi T, Kawaguchi T, Fujii H, Kamada Y, Suzuki Y, Sawada K, Tatsuta M, Maeshiro T, Tobita H, Akahane T, Hasebe C, Kawanaka M, Kessoku T, Eguchi Y, Syokita H, Nakajima A, Kamada T, Yoshiji H, Sakugawa H, Morishita A, Masaki T, Ohmura T, Watanabe T, Yoda Y, Enomoto N, Ono M, Fuyama K, Okada K, Nishimoto N, Ito YM, Takahashi H, Charlton MR, Rinella ME, Sumida Y

  Journal of gastroenterology ( Journal of Gastroenterology )  60 ( 7 ) 891 - 904   2025年07月 [ 査読有り ]

  掲載種別: 研究論文（学術雑誌）

  　概要を見る

  BACKGROUND: Individuals with metabolic-associated steatotic liver disease (MASLD) have a worse prognosis compared to patients without steatosis, and its prevalence is increasing. However, detailed risk factors based on obesity and sex remain unclear. We aimed to investigate the impact of cardiometabolic risk factors (CMRFs) on the risk of MASLD in individuals without pre-existing SLD. METHODS: SLD was diagnosed by ultrasonography. Non-SLD individuals were followed 65,657 person-years. Incidence rates of MASLD were assessed by Kaplan-Meier analysis. Furthermore, independent factors associated with the development of MASLD were identified using Cox regression analysis, stratified by four groups: obese men, non-obese men, obese women, and non-obese women. RESULTS: The overall incidence rate of MASLD was 39.3/1,000 person-years. The cumulative incidence was highest in obese men, followed by obese women, non-obese men, and non-obese women. Two or more CMRFs increased the risk of MASLD in all groups. Low HDL cholesterol level was the strongest independent risk factor in both obese and non-obese women and hypertriglyceridemia for both obese and non-obese men. The impact of these CMRFs was stronger in non-obese individuals. (HR [95% CI]: women non-obese 1.9 [1.5-2.4], obese 1.4 [1.1-1.8]; men non-obese 2.3 [1.9-2.9], obese 1.5 [1.2-2.0]). CONCLUSIONS: Multiple CMRFs are important to MASLD development, regardless of sex and obesity. In this Japanese cohort, low HDL cholesterol in women and hypertriglyceridemia in men were the most significant risk factors, especially among the non-obese group. These findings suggest that sex-specific CMRFs may play a role in the development of MASLD.

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• Tips for Hepatologist Referral of Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease with Alanine Aminotransferase Levels ≤ 30 U/L

  Kawanaka, M; Fujii, H; Iwaki, M; Hayashi, H; Toyoda, H; Oeda, S; Hyogo, H; Morishita, A; Munekage, K; Kawata, K; Tsutsumi, T; Sawada, K; Maeshiro, T; Tobita, H; Yoshida, Y; Naito, M; Araki, A; Arakaki, S; Kawaguchi, T; Noritake, H; Ono, M; Masaki,; Yasuda, S; Tomita, E; Yoneda, M; Tokushige, A; Kamada, Y; Takahashi, H; Ueda, S; Aishima, S; Nishino, K; Ishii, K; Fushimi, T; Kawamoto, H; Sumida, Y; Okanoue, T; Nakajima, A

  DIAGNOSTICS ( Diagnostics )  15 ( 13 )   2025年06月 [ 査読有り ]

  掲載種別: 研究論文（学術雑誌）

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• Alcohol Intake and Cardiometabolic Risk Factors Are Independently Associated With a Higher AST/Platelet Ratio Index in Obese Males

  Hideki Fujii, Yoshihiro Kamada, Yuichiro Suzuki, Koji Sawada, Miwa Tatsuta, Tatsuji Maeshiro, Hiroshi Tobita, Tsubasa Tsutsumi, Takemi Akahane, Chitomi Hasebe, Miwa Kawanaka, Takaomi Kessoku, Yuichiro Eguchi, Hayashi Syokita, Atsushi Nakajima, Tomoari Kamada, Hitoshi Yoshiji, Takumi Kawaguchi, Hiroshi Sakugawa, Asahiro Morishita, Tsutomu Masaki, Takumi Ohmura, Toshio Watanabe, Yoshioki Yoda, Nobuyuki Enomoto, Masafumi Ono, Kanako Fuyama, Kazufumi Okada, Naoki Nishimoto, Yoichi M. Ito, Hirokazu Takahashi, Yoshio Sumida, Japan Study Group of Nonalcoholic Fatty Liver Disease (JSG‐NAFLD)

  Liver International Communications     2025年03月 [ 査読有り ]

  掲載種別: 研究論文（学術雑誌）

  　概要を見る

  <jats:title>ABSTRACT</jats:title><jats:p>It remains unclear whether alcohol intake and cardiometabolic factors are simultaneously associated with liver fibrosis progression in Japanese obese patients. This study investigated factors influencing liver fibrosis progression using the Aspartate Aminotransferase/Platelet Ratio Index (APRI), which does not include age. We conducted a cross‐sectional study of 26 737 obese (BMI ≥ 25 kg/m<jats:sup>2</jats:sup>) adults undergoing health checkups. Steatotic liver disease (SLD) was diagnosed via ultrasonography. Clinical characteristics were analysed according to BMI category and APRI to identify risk factors for advanced liver fibrosis (APRI &gt; 1.0). The prevalence of type 2 diabetes, hypertension, and SLD increased with increasing BMI. On multivariable analysis in male, significant risk factors for advanced liver fibrosis included increased BMI (BMI 30–34.9 kg/m<jats:sup>2</jats:sup>: OR 2.64, 95% CI 1.89–3.69, <jats:italic>p</jats:italic> &lt; 0.001; BMI 35–39.9 kg/m<jats:sup>2</jats:sup>: OR 2.67, 95% CI 1.89–3.69, <jats:italic>p</jats:italic> = 0.002; BMI ≥ 40 kg/m<jats:sup>2</jats:sup>: OR 3.51, 95% CI 1.24–9.96, <jats:italic>p</jats:italic> = 0.018), SLD (OR 2.13, 95% CI 1.49–3.05, <jats:italic>p</jats:italic> &lt; 0.001), moderate alcohol intake (OR 1.36, 95% CI 1.03–1.79, <jats:italic>p</jats:italic> = 0.031), heavy alcohol intake (OR 4.31, 95% CI 2.90–6.40, <jats:italic>p</jats:italic> &lt; 0.001), high blood pressure (OR 1.30, 95% CI 1.01–1.67, <jats:italic>p</jats:italic> = 0.044), and high fasting blood glucose (OR 1.61, 95% CI 1.12–2.28, <jats:italic>p</jats:italic> = 0.008). In female, only age &gt; 65 years (OR 3.02, 95% CI1.93–4.73, <jats:italic>p</jats:italic> &lt; 0.001), BMI, and high uric acid (OR 2.06, 95% CI 1.15–3.68, <jats:italic>p</jats:italic> = 0.015) were extracted. In an obese male, alcohol intake and cardiometabolic factors were associated with liver fibrosis progression based on APRI, independent of elevated BMI and SLD.</jats:p>

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• Prediction of Advanced Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease by Type IV Collagen 7S

  Ishiba, H; Sumida, Y; Kamada, Y; Fujii, H; Iwaki, M; Hayashi, H; Toyoda, H; Oeda, S; Hyogo, H; Kawanaka, M; Morishita, A; Munekage, K; Kawata, K; Tsutsumi, T; Sawada, K; Maeshiro, T; Tobita, H; Yoshida, Y; Naito, M; Araki, A; Arakaki, S; Kawaguchi, T; Noritake, H; Ono, M; Masaki, T; Yasuda, S; Tomita, E; Yoneda, M; Tokushige, A; Takahashi, H; Ueda, S; Aishima, S; Nakajima, A; Okanoue, T

  GASTRO HEP ADVANCES ( Gastro Hep Advances )  4 ( 7 ) 100668   2025年 [ 査読有り ]

  掲載種別: 研究論文（学術雑誌）

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• Hepatic inflammation and fibrosis are profiles related to mid-term mortality in biopsy-proven MASLD: A multicenter study in Japan

  Tsutsumi, T; Kawaguchi, T; Fujii, H; Kamada, Y; Takahashi, H; Kawanaka, M; Sumida, Y; Iwaki, M; Hayashi, H; Toyoda, H; Oeda, S; Hyogo, H; Morishita, A; Munekage, K; Kawata, K; Sawada, K; Maeshiro, T; Tobita, H; Yoshida, Y; Naito, M; Araki, A; Arakaki, S; Noritake, H; Ono, M; Masaki, T; Yasuda, S; Tomita, E; Yoneda, M; Tokushige, A; Ueda, S; Aishima, S; Nakajima, A; Okanoue, T

  ALIMENTARY PHARMACOLOGY & THERAPEUTICS ( Alimentary Pharmacology and Therapeutics )  59 ( 12 ) 1559 - 1570   2024年06月 [ 査読有り ]

  掲載種別: 研究論文（学術雑誌）

  　概要を見る

  AIMS: A multi-stakeholder consensus has proposed MASLD (metabolic dysfunction-associated steatotic liver disease). We aimed to investigate the pathological findings related to the mid-term mortality of patients with biopsy-proven MASLD in Japan. METHODS: We enrolled 1349 patients with biopsy-proven MASLD. The observational period was 8010 person years. We evaluated independent factors associated with mortality in patients with MASLD by Cox regression analysis. We also investigated pathological profiles related to mortality in patients with MASLD using data-mining analysis. RESULTS: The prevalence of MASH and stage 3/4 fibrosis was observed in 65.6% and 17.4%, respectively. Forty-five patients with MASLD died. Of these, liver-related events were the most common cause at 40% (n = 18), followed by extrahepatic malignancies at 26.7% (n = 12). Grade 2/3 lobular inflammation and stage 3/4 fibrosis had a 1.9-fold and 1.8-fold risk of mortality, respectively. In the decision-tree analysis, the profiles with the worst prognosis were characterised by Grade 2/3 hepatic inflammation, along with advanced ballooning (grade 1/2) and fibrosis (stage 3/4). This profile showed a mortality at 8.3%. Furthermore, the random forest analysis identified that hepatic fibrosis and inflammation were the first and second responsible factors for the mid-term prognosis of patients with MASLD. CONCLUSIONS: In patients with biopsy-proven MASLD, the prevalence of MASH and advanced fibrosis was approximately 65% and 20%, respectively. The leading cause of mortality was liver-related events. Hepatic inflammation and fibrosis were significant factors influencing mid-term mortality. These findings highlight the importance of targeting inflammation and fibrosis in the management of patients with MASLD.

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