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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   2024.06 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  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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• Validation study of age-independent fibrosis score (Fibrosis-3 index) in patients with metabolic dysfunction-associated steatotic liver disease

  Nouso, K; Kawanaka, M; Fujii, H; Kariyama, K; Toyoda, H; Iwaki, M; Hayashi, 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, T; Yasuda, S; Tomita, E; Yoneda, M; Tokushige, A; Kamada, Y; Takahashi, H; Ueda, S; Aishima, S; Sumida, Y; Nakajima, A; Kumada, T; Okanoue, T

  HEPATOLOGY RESEARCH ( Hepatology Research )    2024.04 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  BACKGROUND AND AIMS: Because the accuracy of the Fibrosis-4 (FIB-4) index for predicting liver fibrosis changes with age, the need for different cut-offs in various age groups has frequently been discussed. We developed the age-independent score, the Fibrosis-3 (FIB-3) index, and have shown its usefulness in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to validate the diagnostic ability of the FIB-3 index to predict fibrosis progression using a large new patient cohort. METHODS: The ability of the FIB-3 index to predict liver fibrosis was analyzed by comparing it with that of the FIB-4 index using data from 1398 patients with MASLD enrolled in the Asia-based clinical outcome NAFLD study. RESULTS: The areas under the receiver operating characteristic curves for predicting fibrosis stage F3 or higher were not different between the FIB-3 and FIB-4 indices in the entire cohort. Using the single ideal cut-offs of the indices (3.41 for FIB-3 index and 2.01 for FIB-4 index), the predictive accuracy of the FIB-3 index was not significantly different from that of the FIB-4 index among patients aged <60 years; however, the accuracy of the FIB-3 index was significantly higher than that of the FIB-4 index in those aged ≥60 years (0.645 and 0.529, respectively; p < 0.0001). CONCLUSION: The high ability of the FIB-3 index with a single cut-off to predict liver fibrosis in patients with MASLD was confirmed. The FIB-3 index could serve as a useful tool for assessing liver fibrosis regardless of age.

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• Importance of ALT levels of >30 in patients with MASLD: Nara Declaration 2023

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

  Kanzo ( The Japan Society of Hepatology )  65 ( 4 ) 186 - 191   2024.04 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  <p>The Nara Declaration 2023 recommends that patients with ALT levels of >30 U/L and those who have steatosis, diabetes, hypertension, and/or dyslipidemia should be referred to a hepatologist, considering the results of the FIB4 index and/or platelet count. ALT levels of >30 U/L is a simple and useful indicator and, when combined with the FIB4 index and platelet count, can detect MASLD cases that require further treatment and follow-up. Moreover, among patients with MAFLD and ALT levels of ≤30 U/L, the FIB4 index may be useful for identifying those at risk of MASLD. The Nara Declaration 2023 is an important and convenient guideline that provides primary care doctors with specific indications for referral to a hepatologist. When combined with the FIB4 index, ALT levels of >30 U/L is expected to predict high-risk MASLD cases.</p>

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• Prognosis of biopsy-confirmed metabolic dysfunction-associated steatotic liver disease: A sub-analysis of the CLIONE study

  Iwaki, M; Fujii, H; 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; Kamada, Y; Takahashi, H; Ueda, S; Aishima, S; Sumida, Y; Nakajima, A; Okanoue, T

  CLINICAL AND MOLECULAR HEPATOLOGY ( Clinical and Molecular Hepatology )  30 ( 2 ) 225 - 234   2024.04 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  BACKGROUND/AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) was recently proposed as an alternative disease concept to nonalcoholic fatty liver disease (NAFLD). We aimed to investigate the prognosis of patients with biopsy-confirmed MASLD using data from a multicenter study. METHODS: This was a sub-analysis of the Clinical Outcome Nonalcoholic Fatty Liver Disease (CLIONE) study that included 1,398 patients with NAFLD. Liver biopsy specimens were pathologically diagnosed and histologically scored using the NASH Clinical Research Network system, the FLIP algorithm, and the SAF score. Patients who met at least one cardiometabolic criterion were diagnosed with MASLD. RESULTS: Approximately 99% of cases (n=1,381) were classified as MASLD. Patients with no cardiometabolic risk (n=17) had a significantly lower BMI than patients with MASLD (20.9 kg/m2 vs. 28.0 kg/m2, P<0.001), in addition to significantly lower levels of inflammation, ballooning, NAFLD activity score, and fibrosis stage based on liver histology. These 17 patients had a median follow-up of 5.9 years, equivalent to 115 person-years, with no deaths, liver-related events, cardiovascular events, or extrahepatic cancers. The results showed that the prognosis for pure MASLD was similar to that for the original CLIONE cohort, with 47 deaths and one patient who underwent orthotopic liver transplantation. The leading cause of death was extrahepatic cancer (n=10), while the leading causes of liver-related death were liver failure (n=9), hepatocellular carcinoma (n=8), and cholangiocarcinoma (n=4). CONCLUSION: Approximately 99% of NAFLD cases were considered MASLD based on the 2023 liver disease nomenclature. The NAFLD-only group, which is not encompassed by MASLD, had a relatively mild histopathologic severity and a favorable prognosis. Consequently, the prognosis of MASLD is similar to that previously reported for NAFLD.

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• Prevalence and associated metabolic factors of nonalcoholic fatty liver disease in the general population from 2014 to 2018 in Japan: A large-scale multicenter retrospective study

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

  HEPATOLOGY RESEARCH ( Hepatology Research )  53 ( 11 ) 1059 - 1072   2023.11 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  AIM: The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. The aim of this study was to determine the recent prevalence and clinical characteristics of NAFLD in Japan. METHODS: This study initially included 410 061 retrospectively enrolled adults from the medical health checkup registry for metabolic syndrome, chronic kidney disease, and fatty liver in Japan (MIRACLE-J; UMIN-CTR no. UMIN000049419), who were evaluated between 2014 and 2018 at 13 health centers in Japan. Individuals consuming >20 g of alcohol/day or with chronic liver disease were excluded. Fatty liver was diagnosed by ultrasonography. The probability of NAFLD with advanced fibrosis was estimated based on the fibrosis-4 index and NAFLD fibrosis score. RESULTS: A total of 71 254 participants were included in the final analysis. The overall prevalence of NAFLD was 25.8%. There was a significant, twofold difference in NAFLD prevalence between men (37.4%) and women (18.1%). Nonalcoholic fatty liver disease prevalence increased linearly with body mass index, triglycerides, and low-density lipoprotein cholesterol regardless of threshold values, even in the absence of obesity. Among patients with NAFLD, 14% had diabetes mellitus, 31% had hypertension, and 48% had dyslipidemia. The estimated prevalence of NAFLD with advanced fibrosis was 1.7% and 1.0% according to the fibrosis-4 index and NAFLD fibrosis score, respectively. CONCLUSIONS: The prevalence of NAFLD was approximately one-quarter of the general population in Japan. There was a linear relationship between NAFLD prevalence and various metabolic parameters, even in nonobese participants. The prevalence of NAFLD with advanced fibrosis was estimated to be 1%-2%.

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Other Papers 【 display / non-display 】

Other Papers 【 display / non-display 】

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  日本消化器病学会九州支部例会プログラム・抄録集 ( 日本消化器病学会-九州支部 )  113回   161 - 161   2019.05

   

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