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Siriwong N, Sriphoosanaphan S, Decharatanachart P, Yongpisarn T, Kerr SJ, Treeprasertsuk S, Tiyarattanachai T, Apiparakoon T, Hagström H, Akbari C, Ekstedt M, Yip TCF, Wong GLH, Ito T, Ishigami M, Toyoda H, Peleg N, Shlomai A, Seko Y, Sumida Y, Kawanaka M, Hino K, Chaiteerakij R. Role of noninvasive tests on the prediction of hepatocellular carcinoma in nonalcoholic fatty liver disease patients without cirrhosis: a systematic review and meta-analysis of aggregate and individual patient data. Eur J Gastroenterol Hepatol 2025; 37:358-369. [PMID: 39919008 DOI: 10.1097/meg.0000000000002912] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/09/2025]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) has been identified as an emerging risk factor for hepatocellular carcinoma (HCC). Identifying non-cirrhotic NAFLD patients at risk for HCC is crucial. We aimed to investigate the utility of noninvasive tests (NITs) as predictors for HCC and to determine optimal and cost-effective NIT cutoffs for HCC surveillance in non-cirrhotic NAFLD patients. METHODS Medline, EMBASE, and Scopus databases were searched for studies evaluating the relationship between NITs and HCC in this population. Random-effects models were used to estimate hazard ratios or risk ratios and 95% confidence interval (95% CI). Cutoffs of NITs for identifying high-risk patients for HCC were determined. RESULTS This systematic review comprised 20 studies. A meta-analysis of 379 194 patients was conducted using six studies with individual patient data and five studies with aggregate data. Among NITs studied, fibrosis-4 index (FIB-4), aspartate aminotransferase to platelet ratio index (APRI), and NAFLD fibrosis score (NFS) were significantly associated with HCC, with pooled risk ratio (95% CI) of 9.21 (5.79-14.64), pooled hazard ratio of 12.53 (6.57-23.90), and 13.32 (6.48-27.37), respectively. FIB-4, APRI, and NFS of more than 2.06, 0.65, and 0.51 resulted in the highest area under the receiver operating characteristics of 0.83, 0.80, and 0.85, respectively. Surveillance in patients with FIB-4 ≥ 5.91 and NFS ≥ 2.85 would be cost-effective with an annual HCC incidence of ≥15 per 1000 patient-years. CONCLUSION FIB-4, APRI, and NFS are associated with HCC development in non-cirrhotic NAFLD patients. Different NIT cutoffs may be used to enroll high-risk NAFLD patients for HCC surveillance, according to resource availability in different settings.
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Affiliation(s)
- Nanicha Siriwong
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, and King Chulalongkorn Memorial Hospital, Thai Red Cross Society
| | - Supachaya Sriphoosanaphan
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, and King Chulalongkorn Memorial Hospital, Thai Red Cross Society
| | | | - Tanat Yongpisarn
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, and King Chulalongkorn Memorial Hospital, Thai Red Cross Society
| | - Stephen J Kerr
- Biostatistics Excellence Centre, Faculty of Medicine, Chulalongkorn University
| | - Sombat Treeprasertsuk
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, and King Chulalongkorn Memorial Hospital, Thai Red Cross Society
| | - Thodsawit Tiyarattanachai
- Department of Medicine, Faculty of Medicine, Chulalongkorn University, and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Terapap Apiparakoon
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, and King Chulalongkorn Memorial Hospital, Thai Red Cross Society
| | - Hannes Hagström
- Department of Medicine, Huddinge, Karolinska Institutet
- Division of Hepatology, Department of Upper GI, Karolinska University Hospital, Stockholm
| | | | - Mattias Ekstedt
- Division of Diagnostics and Specialist Medicine, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
| | - Terry Cheuk-Fung Yip
- Department of Medicine and Therapeutics
- Medical Data Analytics Centre
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Grace Lai-Hung Wong
- Department of Medicine and Therapeutics
- Medical Data Analytics Centre
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Takanori Ito
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya
| | - Masatoshi Ishigami
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Gifu, Japan
| | - Noam Peleg
- Department of Gastroenterology and Hepatology, Rabin Medical Center, Beilinson Hospital, Petach-Tikva
| | - Amir Shlomai
- Department of Medicine D, Beilinson Hospital, Rabin Medical Center and the Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel
| | - Yuya Seko
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto
| | - Yoshio Sumida
- Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University, Nagakute, Aichi
| | - Miwa Kawanaka
- Department of General Internal Medicine, Kawasaki Medical Center, Kawasaki Medical School, Okayama
| | - Keisuke Hino
- Department of Hepatology and Pancreatology, Kawasaki Medical School, Kurashiki, Japan
| | - Roongruedee Chaiteerakij
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, and King Chulalongkorn Memorial Hospital, Thai Red Cross Society
- Center of Excellence for Innovation and Endoscopy in Gastrointestinal Oncology, Division of Gastroenterology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
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Shibata N, Ito T, Morita Y, Toyoda H, Kanzaki Y, Watanabe N, Yoshioka N, Miyazawa H, Shimojo K, Ohi T, Goto H, Karasawa H, Morishima I. Impact of the fibrosis-4 index in patients with ST-elevated myocardial infarction. Coron Artery Dis 2025; 36:99-107. [PMID: 39373125 DOI: 10.1097/mca.0000000000001431] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/08/2024]
Abstract
BACKGROUND The fibrosis-4 (FIB4) index, a simple, noninvasive marker used for hepatic diseases, represents adverse outcomes. The aim of the present study was to evaluate whether the FIB4 index can predict adverse outcomes in patients with ST-elevation myocardial infarction (STEMI). METHODS We investigated patients with STEMI who underwent primary percutaneous coronary intervention (PCI) and were alive at discharge. The cut-off FIB4 index at discharge was investigated using the survival classification and regression tree (CART) model to predict adverse outcomes. The primary outcome was all-cause mortality. RESULTS Between January 2006 and December 2018, 1354 patients with STEMI (median age, 68 years; men, 76.1%) were investigated. The median value of the FIB4 index was 1.21 (0.84-1.78). The CART model divided the study population into low (FIB4 index <0.945; n = 435), intermediate (0.945 ≤ FIB4 index < 2.185; n = 692), and high (FIB4 index ≥2.185; n = 227) groups based on the significant predictive values for all-cause death. During a median follow-up period of 4.3 years, all-cause death occurred in 208 patients (15.4%). The Kaplan-Meier analysis showed a significant increase in mortality with higher FIB4 index values (log-rank, P < 0.001). The multivariate Cox regression model revealed that the FIB4 index was an independent risk predictor for all-cause death in patients with STEMI [low group as reference vs. intermediate group, hazard ratio: 1.975; 95% confidence interval (CI): 1.166-3.346; P = 0.011 and vs. high group, hazard ratio: 4.633; 95% CI: 2.549-8.418; P < 0.001]. CONCLUSIONS The FIB4 index was associated with the risk of all-cause mortality in patients with STEMI who underwent primary PCI.
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Affiliation(s)
| | - Takanori Ito
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | | | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki
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Argenziano ME, Kim MN, Montori M, Di Bucchianico A, Balducci D, Ahn SH, Svegliati Baroni G. Epidemiology, pathophysiology and clinical aspects of Hepatocellular Carcinoma in MAFLD patients. Hepatol Int 2024; 18:922-940. [PMID: 39012579 DOI: 10.1007/s12072-024-10692-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2024] [Accepted: 04/24/2024] [Indexed: 07/17/2024]
Abstract
Hepatocellular carcinoma (HCC) is undergoing a transformative shift, with metabolic-associated fatty liver disease (MAFLD) emerging as a dominant etiology. Diagnostic criteria for MAFLD involve hepatic steatosis and metabolic dysregulation. Globally, MAFLD prevalence stands at 38.77%, significantly linked to the escalating rates of obesity. Epidemiological data indicate a dynamic shift in the major etiologies of hepatocellular carcinoma (HCC), transitioning from viral to metabolic liver diseases. Besides the degree of liver fibrosis, several modifiable lifestyle risk factors, such as type 2 diabetes, obesity, alcohol use, smoking, and HBV, HCV infection contribute to the pathogenesis of HCC. Moreover gut microbiota and genetic variants may contribute to HCC development.The pathophysiological link between MAFLD and HCC involves metabolic dysregulation, impairing glucose and lipid metabolism, inflammation and oxidative stress. Silent presentation poses challenges in early MAFLD-HCC diagnosis. Imaging, biopsy, and AI-assisted techniques aid diagnosis, while HCC surveillance in non-cirrhotic MAFLD patients remains debated.ITA.LI.CA. group proposes a survival-based algorithm for treatment based on Barcelona clinic liver cancer (BCLC) algorithm. Liver resection, transplantation, ablation, and locoregional therapies are applied based on the disease stage. Systemic treatments is promising, with initial immunotherapy results indicating a less favorable response in MAFLD-related HCC.Adopting lifestyle interventions and chemopreventive measures with medications, including aspirin, metformin, and statins, constitute promising approaches for the primary prevention of HCC.Prognosis is influenced by multiple factors, with MAFLD-HCC associated with prolonged survival. Emerging diagnostic biomarkers and epigenomic markers, show promising results for early HCC detection in the MAFLD population.
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Affiliation(s)
- Maria Eva Argenziano
- Clinic of Gastroenterology, Hepatology, and Emergency Digestive Endoscopy, Università Politecnica Delle Marche, 60126,, Ancona, Italy
- Faculty of Medicine and Health Sciences, University of Ghent, Ghent, Belgium
| | - Mi Na Kim
- Department of Internal Medicine, Yonsei University College of Medicine, 50 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Michele Montori
- Clinic of Gastroenterology, Hepatology, and Emergency Digestive Endoscopy, Università Politecnica Delle Marche, 60126,, Ancona, Italy
| | - Alessandro Di Bucchianico
- Clinic of Gastroenterology, Hepatology, and Emergency Digestive Endoscopy, Università Politecnica Delle Marche, 60126,, Ancona, Italy
| | - Daniele Balducci
- Clinic of Gastroenterology, Hepatology, and Emergency Digestive Endoscopy, Università Politecnica Delle Marche, 60126,, Ancona, Italy
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, 50 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea.
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea.
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea.
| | - Gianluca Svegliati Baroni
- Liver Disease and Transplant Unit, Obesity Center, Azienda Ospedaliero-Universitaria Delle Marche, Polytechnic University of Marche, Ancona, Italy
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Yokoyama S, Muto H, Honda T, Kurokawa Y, Ogawa H, Nakajima R, Kawashima H, Tani H. Identification of Two Long Noncoding RNAs, Kcnq1ot1 and Rmst, as Biomarkers in Chronic Liver Diseases in Mice. Int J Mol Sci 2024; 25:8927. [PMID: 39201613 PMCID: PMC11354866 DOI: 10.3390/ijms25168927] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2024] [Revised: 08/12/2024] [Accepted: 08/14/2024] [Indexed: 09/02/2024] Open
Abstract
This study investigates novel short-lived long noncoding RNAs (lncRNAs) in mice with altered expression in metabolic dysfunction-associated steatotic liver (MASH) and liver fibrosis. LncRNAs share similarities with mRNAs in their transcription by RNA polymerase II, possession of a 5' cap structure, and presence of a polyA tail. We identified two lncRNAs, Kcnq1ot1 and Rmst, significantly decreased in both conditions. These lncRNAs showed dramatic expression changes in MASH livers induced by Western diets and CCl4, and in fibrotic livers induced by CCl4 alone. The decrease was more pronounced in liver fibrosis, suggesting their potential as biomarkers for disease progression. Our findings are consistent across different fibrosis models, indicating a crucial role for these lncRNAs in MASH and liver fibrosis in mice. With MASH becoming a global health issue and its progression to fibrosis associated with hepatocarcinogenesis and poor prognosis, understanding the underlying mechanisms is critical. This research contributes to elucidating lncRNA functions in murine liver diseases and provides a foundation for developing novel therapeutic strategies targeting lncRNAs in MASH and liver fibrosis, offering new avenues for potential therapeutic interventions.
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Affiliation(s)
- Shinya Yokoyama
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8560, Japan; (S.Y.); (H.M.); (T.H.); (H.K.)
| | - Hisanori Muto
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8560, Japan; (S.Y.); (H.M.); (T.H.); (H.K.)
- Department of Gastroenterology and Hepatology, Fujita Health University Bantane Hospital, 3-6-10, Otoubashi, Nakagawa-ku, Nagoya 454-8509, Japan
| | - Takashi Honda
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8560, Japan; (S.Y.); (H.M.); (T.H.); (H.K.)
| | - Yoichi Kurokawa
- Department of Bioscience and Biotechnology, Fukui Prefectural University, Eiheiji-cho, Fukui 910-1195, Japan;
| | - Hirotaka Ogawa
- Nagoya Industrial Science Research Institute, Nagoya 460-0008, Japan;
| | - Riku Nakajima
- Department of Health Pharmacy, Yokohama University of Pharmacy, 601 Matano, Totsuka, Yokohama 245-0066, Japan;
| | - Hiroki Kawashima
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8560, Japan; (S.Y.); (H.M.); (T.H.); (H.K.)
| | - Hidenori Tani
- Department of Health Pharmacy, Yokohama University of Pharmacy, 601 Matano, Totsuka, Yokohama 245-0066, Japan;
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Wongtrakul W, Charatcharoenwitthaya N, Charatcharoenwitthaya P. Lean non-alcoholic fatty liver disease and the risk of all-cause mortality: An updated meta-analysis. Ann Hepatol 2024; 29:101288. [PMID: 38278181 DOI: 10.1016/j.aohep.2024.101288] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Revised: 11/11/2023] [Accepted: 01/04/2024] [Indexed: 01/28/2024]
Abstract
INTRODUCTION AND OBJECTIVES Cohort studies reported controversial results regarding the long-term prognosis of patients with lean non-alcoholic fatty liver disease (NAFLD) compared to non-lean NAFLD patients. This updated meta-analysis aimed to estimate the magnitude of the association between lean body mass index and all-cause mortality risk in NAFLD patients. MATERIALS AND METHODS We systematically searched the EMBASE and MEDLINE databases from inception to March 2023 to identify observational studies that reported hazard ratio (HR) for all-cause mortality of patients with lean NAFLD versus those with non-lean, overweight, or obese NAFLD. Multivariable-adjusted hazard ratios (HRs) for all-cause mortality were pooled using a random effects model. RESULTS Fourteen studies with 94,181 NAFLD patients (11.3 % with lean NAFLD) and 7,443 fatal events over a median follow-up of 8.4 years (IQR, 6.6-17.4 years) were included. Patients with lean NAFLD had a higher risk of all-cause mortality than those with non-lean NAFLD (random-effects HR 1.61, 95 % CI 1.37-1.89; I2=77 %). The magnitude of this risk remained unchanged even after stratified analysis by measures of NAFLD diagnosis, study country, cohort setting, length of follow-up, adjustment with fibrosis stage/cirrhosis, and the Newcastle-Ottawa Scale. The risk was independent of age, sex, and cardiometabolic risk factors. Sensitivity analyses did not alter these findings. The funnel plot and Egger's test revealed no significant publication bias. CONCLUSIONS This meta-analysis revealed that lean NAFLD is associated with an approximately 1.6-fold increased mortality risk. Further studies are needed to unravel the existing but complex link between lean NAFLD and an increased risk of death.
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Affiliation(s)
- Wasit Wongtrakul
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Natthinee Charatcharoenwitthaya
- Division of Endocrinology and Metabolism. Department of Medicine, Faculty of Medicine Thammasat University, Pathumthani, Thailand
| | - Phunchai Charatcharoenwitthaya
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
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Huang CF, Liang PC, Wang CW, Jang TY, Hsu PY, Tsai PC, Wei YJ, Yeh ML, Hsieh MY, Lin YH, Huang CK, Dai CY, Huang JF, Chuang WL, Yu ML. Performance of noninvasive seromarkers in predicting liver fibrosis among MAFLD patients with or without viral hepatitis. Kaohsiung J Med Sci 2024; 40:374-383. [PMID: 38234005 DOI: 10.1002/kjm2.12804] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2023] [Revised: 12/11/2023] [Accepted: 12/25/2023] [Indexed: 01/19/2024] Open
Abstract
The accuracy of noninvasive seromarkers in predicting liver fibrosis in metabolic dysfunction-associated fatty liver disease (MAFLD) patients with or without viral hepatitis is elusive. The AST to platelet ratio index (APRI), fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS) were assessed in 871 MAFLD patients who received elastography in a viral hepatitis-endemic area. The area under the receiver operating characteristic (AUROC) curve increased substantially with increasing fibrotic stage across the three biomarkers. APRI (AUROC range 0.73-0.80) and FIB-4 (AUROC range 0.66-0.82) performed better than NFS (AUROC range 0.63-0.75). When patients were divided into viral and non-viral MAFLD groups, a better AUROC of APRI (range 0.76-0.80) and FIB-4 (range 0.68-0.78) than NFS (range 0.62-70) existed only in viral MALFD but not in non-viral MAFLD. Regarding the NFS, the AUROC was higher in non-viral MAFLD (range 0.69-0.86) and outperformed viral MAFLD at all fibrotic stages. The accuracy in predicting liver fibrosis increased with the advancement of liver disease for the three biomarkers. NFS exerted better diagnostic accuracy in non-viral than in viral MAFLD patients across different fibrotic stages. The best accuracy was 91.1% using the cutoff value of -9.98 for the NFS in predicting liver cirrhosis in non-viral MAFLD patients. The APRI and FIB-4 performed better than the NFS in predicting liver fibrosis in MAFLD as a whole. The suboptimal performance and accuracy of the NFS existed only in viral MAFLD patients. Caution should be taken when assessing the NFS in MAFLD patients with viral hepatitis.
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Affiliation(s)
- Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Ph.D. Program in Translational Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Academia Sinica, Taipei City, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Po-Cheng Liang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chih-Wen Wang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Tyng-Yuan Jang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Po-Yao Hsu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Pei-Chien Tsai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yu-Ju Wei
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Yen Hsieh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yi-Hung Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chao-Kuan Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung, Taiwan
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
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Chayama K, Hiramatsu A, Shima T, Itoh Y, Yamaguchi K, Nakajima T, Hoshikawa K, Kawamura Y, Akuta N, Ito K, Kawanaka M, Sakamoto M, Harada K, Goto Y, Nakayama T, Kumada H, Okanoue T. Impact of fibrosis on liver-related event incidence in nonalcoholic fatty liver disease: A multicenter observational study. Hepatol Res 2023; 53:1169-1184. [PMID: 37534742 DOI: 10.1111/hepr.13950] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2023] [Revised: 07/26/2023] [Accepted: 07/31/2023] [Indexed: 08/04/2023]
Abstract
AIM There are few reports on the prognosis of liver-related events in Japanese patients with nonalcoholic fatty liver disease (NAFLD). We undertook an observational study to compare the prognosis between fibrotic and nonfibrotic groups in Japanese NAFLD patients. METHODS Prognosis in 393 NAFLD patients who underwent liver biopsy between April 2013 and April 2015 at multiple centers were investigated. The time to onset of liver-related events, cardiovascular events, development of extrahepatic cancers, and death were compared between the pathologically fibrotic nonalcoholic steatohepatitis (NASH) group and nonalcoholic fatty liver (NAFL) + nonfibrotic NASH group. A similar analysis was carried out based on the fibrotic classification diagnosed using four noninvasive fibrosis prediction models. RESULTS The mean age and body mass index at the time of liver biopsy was 55.7 years old and 28.04 kg/m2 , respectively The cumulative incidence of liver-related events at 1080 days after liver biopsy was 5.79% in the pathologically fibrotic NASH group and 0% in the NAFL + nonfibrotic NASH group, with a significant difference (p = 0.0334). The cumulative incidence of liver-related events was significantly higher in the positive group for the prediction model than in the negative group in all four models (all p values were <0.0001). There was no significant difference between the pathologically fibrotic NASH group and NAFL + nonfibrotic NASH group in terms of cumulative incidence of cardiovascular events, development of extrahepatic cancers, and death. CONCLUSIONS The incidence of liver-related events was significantly higher in the fibrotic NASH group than that of the NAFL + nonfibrotic NASH group in Japanese NAFLD patients.
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Affiliation(s)
- Kazuaki Chayama
- Collaborative Research Laboratory of Medical Innovation, Hiroshima University, Hiroshima, Japan
| | - Akira Hiramatsu
- Department of Gastroenterology, Hiroshima Memorial Hospital, Hiroshima, Japan
| | - Toshihide Shima
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Japan
| | - Yoshito Itoh
- Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Kanji Yamaguchi
- Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Tomoaki Nakajima
- Department of Hepatology, Sapporo Kosei General Hospital, Sapporo, Japan
| | - Kyoko Hoshikawa
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, Japan
| | | | - Norio Akuta
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan
| | - Kiyoaki Ito
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Aichi Medical University, Nagakute, Japan
| | - Miwa Kawanaka
- Department of General Internal Medicine 2, Kawasaki Medical Center, Kawasaki Medical School, Okayama, Japan
| | - Michiie Sakamoto
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Kenichi Harada
- Department of Human Pathology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan
| | - Yoshihito Goto
- Department of Health Informatics, Kyoto University School of Public Health, Kyoto, Japan
| | - Takeo Nakayama
- Department of Health Informatics, Kyoto University School of Public Health, Kyoto, Japan
| | | | - Takeshi Okanoue
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Japan
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Motta BM, Masarone M, Torre P, Persico M. From Non-Alcoholic Steatohepatitis (NASH) to Hepatocellular Carcinoma (HCC): Epidemiology, Incidence, Predictions, Risk Factors, and Prevention. Cancers (Basel) 2023; 15:5458. [PMID: 38001718 PMCID: PMC10670704 DOI: 10.3390/cancers15225458] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Revised: 11/07/2023] [Accepted: 11/15/2023] [Indexed: 11/26/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) affects up to a quarter of the adult population in many developed and developing countries. This spectrum of liver disease ranges from simple steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis. The incidence of NASH is projected to increase by up to 56% over the next 10 years. There is growing epidemiological evidence that NAFLD has become the fastest-growing cause of hepatocellular carcinoma (HCC) in industrialized countries. The annual incidence of HCC varies between patients with NASH cirrhosis and patients with noncirrhotic NAFLD. In this review, NAFLD/NASH-associated HCC will be described, including its epidemiology, risk factors promoting hepatocarcinogenesis, and management of HCC in patients with obesity and associated metabolic comorbidities, including preventive strategies and therapeutic approaches to address this growing problem.
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Affiliation(s)
| | | | | | - Marcello Persico
- Department of Medicine, Surgery and Dentistry, Scuola Medica Salernitana, University of Salerno, 84081 Baronissi, Italy; (B.M.M.); (M.M.); (P.T.)
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9
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Ito T, Morooka H, Takahashi H, 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, Ishigami M, Kamada Y, Ueda S, Aishima S, Sumida Y, Nakajima A, Okanoue T. Identification of clinical phenotypes associated with poor prognosis in patients with nonalcoholic fatty liver disease via unsupervised machine learning. J Gastroenterol Hepatol 2023; 38:1832-1839. [PMID: 37596843 DOI: 10.1111/jgh.16326] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2023] [Revised: 07/22/2023] [Accepted: 08/01/2023] [Indexed: 08/20/2023]
Abstract
BACKGROUND AND AIMS Both fibrosis status and body weight are important for assessing prognosis in nonalcoholic fatty liver disease (NAFLD). The aim of this study was to identify population clusters for specific clinical outcomes based on fibrosis-4 (FIB-4) index and body mass index (BMI) using an unsupervised machine learning method. METHODS We conducted a multicenter study of 1335 biopsy-proven NAFLD patients from Japan. Using the Gaussian mixture model to divide the cohort into clusters based on FIB-4 index and BMI, we investigated prognosis for these clusters. RESULTS The cohort consisted of 223 cases (16.0%) with advanced fibrosis (F3-4) as assessed from liver biopsy. Median values of BMI and FIB-4 index were 27.3 kg/m2 and 1.67. The patients were divided into four clusters by Bayesian information criterion, and all-cause mortality was highest in cluster d, followed by cluster b (P = 0.001). Regarding the characteristics of each cluster, clusters d and b presented a high FIB-4 index (median 5.23 and 2.23), cluster a presented the lowest FIB-4 index (median 0.78), and cluster c was associated with moderate FIB-4 level (median 1.30) and highest BMI (median 34.3 kg/m2 ). Clusters a and c had lower mortality rates than clusters b and d. However, all-cause of death in clusters a and c was unrelated to liver disease. CONCLUSIONS Our clustering approach found that the FIB-4 index is an important predictor of mortality in NAFLD patients regardless of BMI. Additionally, non-liver-related diseases were identified as the causes of death in NAFLD patients with low FIB-4 index.
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Affiliation(s)
- Takanori Ito
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Hikaru Morooka
- Department of Emergency and Critical Care Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | | | - Hideki Fujii
- Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Michihiro Iwaki
- Division of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Hideki Hayashi
- Department of Gastroenterology and Hepatology, Gifu Municipal Hospital, Gifu, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Satoshi Oeda
- Liver Center, Saga University Hospital, Saga, Japan
- Department of Laboratory Medicine, Saga University Hospital, Saga, Japan
| | - Hideyuki Hyogo
- Department of Gastroenterology, JA Hiroshima Kouseiren General Hospital, Hiroshima, Japan
- Hyogo Life Care Clinic Hiroshima, Hiroshima, Japan
| | - Miwa Kawanaka
- Department of General Internal Medicine 2, Kawasaki Medical Center, Kawasaki Medical School, Okayama, Japan
| | - Asahiro Morishita
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Takamatsu, Japan
| | - Kensuke Munekage
- Department of Gastroenterology and Hepatology, Kochi Medical School, Kochi, Japan
| | - Kazuhito Kawata
- Hepatology Division, Department of Internal Medicine II, Hamamatsu University School of Medicine, Shizuoka, Japan
| | - Tsubasa Tsutsumi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Koji Sawada
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Asahikawa Medical University, Asahikawa, Japan
| | - Tatsuji Maeshiro
- First Department of Internal Medicine, University of the Ryukyus Hospital, Okinawa, Japan
| | - Hiroshi Tobita
- Division of Hepatology, Shimane University Hospital, Izumo, Japan
| | - Yuichi Yoshida
- Department of Gastroenterology and Hepatology, Suita Municipal Hospital, Osaka, Japan
| | - Masafumi Naito
- Department of Gastroenterology and Hepatology, Suita Municipal Hospital, Osaka, Japan
| | - Asuka Araki
- Division of Hepatology, Shimane University Hospital, Izumo, Japan
| | - Shingo Arakaki
- First Department of Internal Medicine, University of the Ryukyus Hospital, Okinawa, Japan
| | - Takumi Kawaguchi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Hidenao Noritake
- Hepatology Division, Department of Internal Medicine II, Hamamatsu University School of Medicine, Shizuoka, Japan
| | - Masafumi Ono
- Division of Innovative Medicine for Hepatobiliary and Pancreatology, Faculty of Medicine, Kagawa University, Takamatsu, Japan
| | - Tsutomu Masaki
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Takamatsu, Japan
| | - Satoshi Yasuda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Eiichi Tomita
- Department of Gastroenterology and Hepatology, Gifu Municipal Hospital, Gifu, Japan
| | - Masato Yoneda
- Division of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Akihiro Tokushige
- Department of Cardiovascular Medicine and Hypertension, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Masatoshi Ishigami
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yoshihiro Kamada
- Department of Advanced Metabolic Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Shinichiro Ueda
- Department of Clinical Pharmacology and Therapeutics, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan
| | - Shinichi Aishima
- Department of Pathology and Microbiology, Faculty of Medicine, Saga University, Saga, Japan
| | - Yoshio Sumida
- Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University, Nagakute, Japan
| | - Atsushi Nakajima
- Division of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
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10
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Polyzos SA, Chrysavgis L, Vachliotis ID, Chartampilas E, Cholongitas E. Nonalcoholic fatty liver disease and hepatocellular carcinoma:Insights in epidemiology, pathogenesis, imaging, prevention and therapy. Semin Cancer Biol 2023; 93:20-35. [PMID: 37149203 DOI: 10.1016/j.semcancer.2023.04.010] [Citation(s) in RCA: 47] [Impact Index Per Article: 23.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 04/23/2023] [Accepted: 04/27/2023] [Indexed: 05/08/2023]
Abstract
Hepatocellular carcinoma (HCC) is estimated to be the third leading cause of cancer-related mortality and is characterized by low survival rates. Nonalcoholic fatty liver disease (NAFLD) is emerging as a leading cause of HCC, whose rates are increasing, owing to the increasing prevalence of NAFLD. The pathogenesis of NAFLD-associated HCC is multifactorial: insulin resistance, obesity, diabetes and the low-grade hepatic inflammation, which characterizes NAFLD, seem to play key roles in the development and progression of HCC. The diagnosis of NAFLD-associated HCC is based on imaging in the presence of liver cirrhosis, preferably computerized tomography or magnetic resonance imaging, but liver biopsy for histological confirmation is usually required in the absence of liver cirrhosis. Some preventive measures have been recommended for NAFLD-associated HCC, including weight loss, cessation of even moderate alcohol drinking and smoking, as well as the use of metformin, statins and aspirin. However, these preventive measures are mainly based on observational studies, thus they need validation in trials of different design before introducing in clinical practice. The treatment of NAFLD should be tailored on an individual basis and should be ideally determined by a multidisciplinary team. In the last two decades, new medications, including tyrosine kinase inhibitors and immune checkpoints inhibitors, have improved the survival of patients with advanced HCC, but trials specifically designed for patients with NAFLD-associated HCC are scarce. The aim of this review was to overview evidence on the epidemiology and pathophysiology of NAFLD-associated HCC, then to comment on imaging tools for its appropriate screening and diagnosis, and finally to critically summarize the currently available options for its prevention and treatment.
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Affiliation(s)
- Stergios A Polyzos
- First Laboratory of Pharmacology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
| | - Lampros Chrysavgis
- First Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, General Hospital Laiko, Athens, Greece
| | - Ilias D Vachliotis
- First Laboratory of Pharmacology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Evangelos Chartampilas
- Department of Radiology, University General Hospital of Thessaloniki AHEPA, Thessaloniki, Greece
| | - Evangelos Cholongitas
- First Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, General Hospital Laiko, Athens, Greece
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11
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Zhang J, Fu S, Liu D, Wang Y, Tan Y. Statin can reduce the risk of hepatocellular carcinoma among patients with nonalcoholic fatty liver disease: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2023; 35:353-358. [PMID: 36719824 DOI: 10.1097/meg.0000000000002517] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Currently, nonalcoholic fatty liver disease (NAFLD) is the main cause of chronic liver disease and liver-related mortality worldwide. Hepatocellular carcinoma (HCC) is a fatal complication in patients with NAFLD. However, whether statins can reduce the risk of HCC in patients with NAFLD remains controversial. We aimed to determine the relationship between statin use and HCC occurrence among patients with NAFLD. We independently retrieved related studies from PubMed, EMBASE, Cochrane Library, Web of Science, and ClinicalTrial.gov (from 1 January 2000 to 27 February 2022). The main outcome was the development of HCC. A fixed-effects model was used to merge odds ratio (OR) in the meta-analysis. Five studies involving 684 363 patients were included. The results of the meta-analysis suggested a significantly lower risk of HCC among statin users with NAFLD [OR = 0.59; 95% confidence interval (CI), 0.39-0.89; I2 = 87.90%]. Additionally, a lower risk of HCC was observed among patients with NAFLD aged less than 65 years (OR = 0.59; 95% CI, 0.46-0.77; I2 = 20.50%). Statins can reduce the risk of HCC in patients aged less than 65 years with NAFLD.
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Affiliation(s)
- Jie Zhang
- Department of Gastroenterology, the Second Xiangya Hospital of Central South University
- Research Center of Digestive Disease, Central South University, Changsha, China
| | - Shifeng Fu
- Department of Gastroenterology, the Second Xiangya Hospital of Central South University
- Research Center of Digestive Disease, Central South University, Changsha, China
| | - Deliang Liu
- Department of Gastroenterology, the Second Xiangya Hospital of Central South University
- Research Center of Digestive Disease, Central South University, Changsha, China
| | - Yongjun Wang
- Department of Gastroenterology, the Second Xiangya Hospital of Central South University
- Research Center of Digestive Disease, Central South University, Changsha, China
| | - Yuyong Tan
- Department of Gastroenterology, the Second Xiangya Hospital of Central South University
- Research Center of Digestive Disease, Central South University, Changsha, China
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12
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Ng CH, Lim WH, Hui Lim GE, Hao Tan DJ, Syn N, Muthiah MD, Huang DQ, Loomba R. Mortality Outcomes by Fibrosis Stage in Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2023; 21:931-939.e5. [PMID: 35513235 PMCID: PMC10792524 DOI: 10.1016/j.cgh.2022.04.014] [Citation(s) in RCA: 96] [Impact Index Per Article: 48.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Revised: 03/19/2022] [Accepted: 04/06/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Fibrosis is a key determinant of clinical outcomes in nonalcoholic fatty liver disease (NAFLD), but time-dependent risk of mortality has not been reported in previous meta-analyses. We performed an updated time-to-event meta-analysis to provide robust estimates for all-cause and liver-related mortality in biopsy-confirmed NAFLD with comparisons between fibrosis stages. METHODS Medline and Embase databases were searched to include cohort studies reporting survival outcomes by fibrosis stage in biopsy-proven NAFLD. Survival estimates were pooled using reconstructed individual participant data. Conventional meta-analysis was conducted to pool adjusted hazard ratios (HRs) using DerSimonian and Laird random effects model. RESULTS A total of 14 articles involving 17,301 patients with NAFLD were included. All-cause mortality at 1, 5, and 10 years for stage 0 to 2 fibrosis was 0.1%, 3.3%, and 7.7% vs 0.3%, 20.6%, and 41.5% for stage 4 fibrosis. Compared with stage 0 fibrosis, all-cause mortality increased with fibrosis stage: stage 2; HR, 1.46 (95% confidence interval [CI], 1.08-1.98), stage 3; HR, 1.96 (95% CI, 1.41-2.72), and stage 4; HR, 3.66 (95% CI, 2.65-5.05). Risk for liver-related mortality increased exponentially as fibrosis stage increased: stage 2; HR, 4.07 (95% CI, 1.44-11.5), stage 3; HR, 7.59 (95% CI, 2.80-20.5), and stage 4; HR, 15.1 (95% CI, 5.27-43.4). Stage 3 to 4 fibrosis had a higher all-cause (HR, 3.32) and liver-related mortality (HR, 10.40) compared with stage 0 to 2 fibrosis, whereas stage 4 fibrosis had higher all-cause (HR, 2.67; 95% CI, 1.47-4.83) and liver-related mortality (HR, 2.57; 95% CI, 1.22-5.42) vs stage 3 fibrosis. CONCLUSIONS Risk of all-cause and liver-related mortality increases substantially with fibrosis stage. These data have important implications for prognostication and trial design.
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Affiliation(s)
- Cheng Han Ng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Wen Hui Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Grace En Hui Lim
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
| | - Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Nicholas Syn
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Biostatistics & Modelling Domain, Saw Swee Hock School of Public Health, National University of Singapore, Singapore
| | - Mark D Muthiah
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Daniel Q Huang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore; NAFLD Research Centre, University of California at San Diego, La Jolla, California
| | - Rohit Loomba
- NAFLD Research Centre, University of California at San Diego, La Jolla, California; Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, California.
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13
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Reinson T, Buchanan RM, Byrne CD. Noninvasive serum biomarkers for liver fibrosis in NAFLD: current and future. Clin Mol Hepatol 2023; 29:S157-S170. [PMID: 36417894 PMCID: PMC10029954 DOI: 10.3350/cmh.2022.0348] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Revised: 11/17/2022] [Accepted: 11/21/2022] [Indexed: 11/24/2022] Open
Abstract
In the last 20 years, noninvasive serum biomarkers to identify liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) have been developed, validated against liver biopsy (the gold standard for determining the presence of liver fibrosis) and made available for clinicians to use to identify ≥F3 liver fibrosis. The aim of this review is firstly to focus on the current use of widely available biomarkers and their performance for identifying ≥F3. Secondly, we discuss whether noninvasive biomarkers have a role in identifying F2, a stage of fibrosis that is now known to be a risk factor for cirrhosis and overall mortality. We also consider whether machine learning algorithms offer a better alternative for identifying individuals with ≥F2 fibrosis. Thirdly, we summarise the utility of noninvasive serum biomarkers for predicting liver related outcomes (e.g., ascites and hepatocellular carcinoma) and non-liver related outcomes (e.g., cardiovascular-related mortality and extra hepatic cancers). Finally, we examine whether serial measurement of biomarkers can be used to monitor liver disease, and whether the use of noninvasive biomarkers in drug trials for non-alcoholic steatohepatitis can accurately, compared to liver histology, monitor liver fibrosis progression/regression. We conclude by offering our perspective on the future of serum biomarkers for the detection and monitoring of liver fibrosis in NAFLD.
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Affiliation(s)
- Tina Reinson
- Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, U.K.
- National Institute for Health and Care Research, Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, U.K.
| | - Ryan M. Buchanan
- National Institute for Health and Care Research, Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, U.K.
- Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Christopher D. Byrne
- Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, U.K.
- National Institute for Health and Care Research, Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, U.K.
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14
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Fujii H, Iwaki M, Hayashi H, Toyoda H, Oeda S, Hyogo H, Kawanaka M, Morishita A, Munekage K, Kawata K, Yamamura S, 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, Kawada N, Tokushige A, Kamada Y, Takahashi H, Ueda S, Aishima S, Sumida Y, Nakajima A, Okanoue T. Clinical Outcomes in Biopsy-Proven Nonalcoholic Fatty Liver Disease Patients: A Multicenter Registry-based Cohort Study. Clin Gastroenterol Hepatol 2023; 21:370-379. [PMID: 35051649 DOI: 10.1016/j.cgh.2022.01.002] [Citation(s) in RCA: 52] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 12/24/2021] [Accepted: 01/03/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS There are no detailed reports of clinical outcomes in Asian patients with nonalcoholic fatty liver disease (NAFLD) who undergo liver biopsy. We aimed to investigate the clinical outcomes of a large cohort of Asian patients with biopsy-proven NAFLD and evaluate the specific effects of nonalcoholic steatohepatitis and fibrosis stage. METHODS This multicenter registry-based retrospective cohort study, called the CLIONE (Clinical Outcome Nonalcoholic Fatty Liver Disease) in Asia, included 1398 patients. RESULTS The median follow-up period was 4.6 years (range, 0.3-21.6 years), representing a total of 8874 person-years of follow-up. During that time, 47 patients died, and 1 patient underwent orthotopic liver transplantation. The leading cause of death was nonhepatic cancer (n = 10). The leading causes of liver-related death were liver failure (n = 9), hepatocellular carcinoma (HCC) (n = 8), and cholangiocellular carcinoma (n = 4). During follow-up, 37 patients developed HCC, 31 developed cardiovascular disease, and 68 developed nonhepatic cancer (mainly breast, stomach, and colon/rectum). Among our cohort of patients with NAFLD, liver-specific mortality was 2.34/1000 person-years (95% confidence interval [CI], 1.52-3.58), overall mortality was 5.34/1000 person-years (95% CI, 4.02-7.08), and HCC incidence was 4.17/1000 person-years (95% CI, 3.02-5.75). Liver fibrosis was independently associated with liver-related events but not overall mortality. CONCLUSIONS Liver-related mortality was the leading cause of mortality in Asian patients with biopsy-confirmed NAFLD. Although fibrosis stage was independently associated with liver-related events, it was not associated with overall mortality after adjusting for confounders, such as histologic features of steatohepatitis.
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Affiliation(s)
- Hideki Fujii
- Departments of Premier Preventive Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan; Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan
| | - Michihiro Iwaki
- Division of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Hideki Hayashi
- Department of Gastroenterology and Hepatology, Gifu Municipal Hospital, Gifu, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Satoshi Oeda
- Liver Center, Saga University Hospital, Saga, Japan; Department of Laboratory Medicine, Saga University Hospital, Saga, Japan
| | - Hideyuki Hyogo
- Department of Gastroenterology, JA Hiroshima Kouseiren General Hospital, Hatsukaichi, Hiroshima, Japan
| | - Miwa Kawanaka
- Department of General Internal Medicine 2, Kawasaki Medical Center, Kawasaki Medical School, Okayama, Japan
| | - Asahiro Morishita
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | - Kensuke Munekage
- Department of Gastroenterology and Hepatology, Kochi Medical School, Kochi, Japan
| | - Kazuhito Kawata
- Hepatology Division, Department of Internal Medicine II, Hamamatsu University School of Medicine, Shizuoka, Japan
| | - Sakura Yamamura
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Koji Sawada
- Liver Disease Care Unit, Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Asahikawa Medical University, Asahikawa, Japan; Department of Medicine, Asahikawa Medical University, Asahikawa, Japan
| | - Tatsuji Maeshiro
- First Department of Internal Medicine, University of the Ryukyus Hospital, Okinawa, Japan
| | - Hiroshi Tobita
- Division of Hepatology, Shimane University Hospital, Shimane, Japan
| | - Yuichi Yoshida
- Department of Gastroenterology and Hepatology, Suita Municipal Hospital, Osaka, Japan
| | - Masafumi Naito
- Department of Gastroenterology and Hepatology, Suita Municipal Hospital, Osaka, Japan
| | - Asuka Araki
- Division of Hepatology, Shimane University Hospital, Shimane, Japan
| | - Shingo Arakaki
- First Department of Internal Medicine, University of the Ryukyus Hospital, Okinawa, Japan
| | - Takumi Kawaguchi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Hidenao Noritake
- Hepatology Division, Department of Internal Medicine II, Hamamatsu University School of Medicine, Shizuoka, Japan
| | - Masafumi Ono
- Division of Innovative Medicine for Hepatobiliary & Pancreatology, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | - Tsutomu Masaki
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | - Satoshi Yasuda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Eiichi Tomita
- Department of Gastroenterology and Hepatology, Gifu Municipal Hospital, Gifu, Japan
| | - Masato Yoneda
- Division of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Norifumi Kawada
- Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan
| | - Akihiro Tokushige
- Department of Cardiovascular Medicine and Hypertension, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Yoshihiro Kamada
- Department of Advanced Metabolic Hepatology, Osaka University, Graduate School of Medicine, Osaka, Japan
| | | | - Shinichiro Ueda
- Department of Clinical Pharmacology and Therapeutics, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan
| | - Shinichi Aishima
- Department of Pathology and Microbiology, Faculty of Medicine, Saga University, Saga, Japan
| | - Yoshio Sumida
- Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University, Aichi, Karimata, Japan.
| | - Atsushi Nakajima
- Division of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Takeshi Okanoue
- Hepatology Center, Saiseikai Suita Hospital, Suita, Osaka, Japan
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15
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Ito T, Nguyen MH. Perspectives on the Underlying Etiology of HCC and Its Effects on Treatment Outcomes. J Hepatocell Carcinoma 2023; 10:413-428. [PMID: 36926055 PMCID: PMC10013586 DOI: 10.2147/jhc.s347959] [Citation(s) in RCA: 33] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 02/25/2023] [Indexed: 03/11/2023] Open
Abstract
Hepatocellular carcinoma (HCC) continues to be a serious medical problem with poor prognosis worldwide. The distribution of the major etiologies of HCC is changing due to the progress of anti-viral treatments, including hepatitis B virus (HBV) suppression by nucleoside/nucleotide analogues (NAs) and increased sustained virologic response (SVR) rates by direct-acting antivirals (DAAs) for hepatitis C virus (HCV), as well as the rising trend of nonviral liver disease. Although viral hepatitis remains the most common cause of HCC, non-alcoholic liver disease (NAFLD) with metabolic syndrome and alcohol-associated liver disease (ALD) are increasing. Effective and well-tolerated NAs treatment can slow the disease progression of chronic HBV infection to cirrhosis, end-stage liver disease, and reduce HCC risk. Treatment with NAs is also associated with significant improvement in the long-term survival of patients with HBV infection who already have HCC. DAAs have achieved viral elimination in almost all patients with HCV without significant adverse events, even in patients with decompensated liver cirrhosis and HCC. Similarly, DAA therapy can reduce disease progression, liver and non-liver complications, and improve the long-term survival of patients with chronic HCV infection with or without HCC. Meanwhile, NAFLD is a rapidly increasing cause of HCC along with the epidemics of obesity and type 2 diabetes globally. NAFLD-related HCC can occur in patients without cirrhosis and is known to have a lower survival rate than viral hepatitis-related HCC. Since there is currently no specific pharmacotherapy effective for NAFLD, lifestyle modification and prevention of complications are important to improve prognosis. Additionally, ALD is the second fastest-growing cause of HCC-related deaths, especially with an accelerated trend since the COVID-19 pandemic. This review provides an overview of the epidemiologic trends in the etiologies of HCC, and the progress of treatments for each etiology and the impact on outcome in the patients with HCC.
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Affiliation(s)
- Takanori Ito
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, CA, USA.,Department of Epidemiology and Population Health, Stanford University Medical Center, Palo Alto, CA, USA
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16
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Choo BP, Goh GBB, Chia SY, Oh HC, Tan NC, Tan JYL, Ang TL, Bee YM, Wong YJ. Non-alcoholic fatty liver disease screening in type 2 diabetes mellitus: A cost-effectiveness and price threshold analysis. ANNALS OF THE ACADEMY OF MEDICINE, SINGAPORE 2022. [DOI: 10.47102/annals-acadmedsg.2022284] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Introduction: The cost-effectiveness of screening asymptomatic non-alcoholic fatty liver disease (NAFLD) patients remains debatable, with current studies assuming lifelong benefits of NAFLD screening while neglecting cardiovascular outcomes. This study aims to assess the cost-effectiveness of NAFLD screening among type 2 diabetes mellitus (T2DM) patients, and to establish a price threshold for NAFLD treatment, when it becomes available.
Method: A Markov model was constructed comparing 4 screening strategies (versus no screening) to identify NAFLD with advanced fibrosis among T2DM patients: fibrosis-4 (FIB-4), vibration-controlled transient elastography (VCTE), FIB-4 and VCTE (simultaneous), and FIB-4 and VCTE (sequential). Sensitivity analyses and price threshold analyses were performed to assess parameter uncertainties in the results.
Results: VCTE was the most cost-effective NAFLD screening strategy (USD24,727/quality-adjusted life year [QALY]), followed by FIB-4 (USD36,800/QALY), when compared to no screening. Probabilistic sensitivity analysis revealed a higher degree of certainty for VCTE as a cost-effective strategy compared to FIB-4 (90.7% versus 73.2%). The duration of expected screening benefit is the most influential variable based on incremental cost-effectiveness ratio tornado analysis. The minimum duration of screening benefit for NAFLD screening to be cost-effective was at least 2.6 years. The annual cost of NAFLD treatment should be less than USD751 for NAFLD screening to be cost-effective.
Conclusion: Both VCTE and FIB-4 are cost-effective NAFLD screening strategies among T2DM patients in Singapore. However, given the lack of access to VCTE at primacy care and potential budget constraints, FIB-4 can also be considered for NAFLD screening among T2DM patients in Singapore.
Keywords: Cost-effectiveness analysis, fatty liver, screening, liver fibrosis, population health
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17
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Ueno M, Takeda H, Takai A, Seno H. Risk factors and diagnostic biomarkers for nonalcoholic fatty liver disease-associated hepatocellular carcinoma: Current evidence and future perspectives. World J Gastroenterol 2022; 28:3410-3421. [PMID: 36158261 PMCID: PMC9346451 DOI: 10.3748/wjg.v28.i27.3410] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Revised: 04/24/2022] [Accepted: 06/16/2022] [Indexed: 02/06/2023] Open
Abstract
High rates of excessive calorie intake diets and sedentary lifestyles have led to a global increase in nonalcoholic fatty liver disease (NAFLD). As a result, this condition has recently become one of the leading causes of hepatocellular carcinoma (HCC). Furthermore, the incidence of NAFLD-associated HCC (NAFLD-HCC) is expected to increase in the near future. Advanced liver fibrosis is the most common risk factor for NAFLD-HCC. However, up to 50% of NAFLD-HCC cases develop without underlying liver cirrhosis. Epidemiological studies have revealed many other risk factors for this condition; including diabetes, other metabolic traits, obesity, old age, male sex, Hispanic ethnicity, mild alcohol intake, and elevated liver enzymes. Specific gene variants, such as single-nucleotide polymorphisms of patatin-like phospholipase domain 3, transmembrane 6 superfamily member 2, and membrane-bound O-acyl-transferase domain-containing 7, are also associated with an increased risk of HCC in patients with NAFLD. This clinical and genetic information should be interpreted together for accurate risk prediction. Alpha-fetoprotein (AFP) is the only biomarker currently recommended for HCC screening. However, it is not sufficiently sensitive in addressing this diagnostic challenge. The GALAD score can be calculated based on sex, age, lectin-bound AFP, AFP, and des-carboxyprothrombin and is reported to show better diagnostic performance for HCC. In addition, emerging studies on genetic and epigenetic biomarkers have also yielded promising diagnostic potential. However, further research is needed to establish an effective surveillance program for the early diagnosis of NAFLD-HCC.
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Affiliation(s)
- Masayuki Ueno
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto 6068507, Japan
| | - Haruhiko Takeda
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto 6068507, Japan
| | - Atsushi Takai
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto 6068507, Japan
| | - Hiroshi Seno
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto 6068507, Japan
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18
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Tokushige K, Ikejima K, Ono M, Eguchi Y, Kamada Y, Itoh Y, Akuta N, Yoneda M, Iwasa M, Yoneda M, Otsuka M, Tamaki N, Kogiso T, Miwa H, Chayama K, Enomoto N, Shimosegawa T, Takehara T, Koike K. Evidence-based clinical practice guidelines for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis 2020. J Gastroenterol 2021; 56:951-963. [PMID: 34533632 PMCID: PMC8531062 DOI: 10.1007/s00535-021-01796-x] [Citation(s) in RCA: 176] [Impact Index Per Article: 44.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 05/14/2021] [Indexed: 02/04/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) has become a serious public health issue not only in Western countries but also in Japan. Within the wide spectrum of NAFLD, nonalcoholic steatohepatitis (NASH) is a progressive form of disease that often develops into liver cirrhosis and increases the risk of hepatocellular carcinoma (HCC). While a definite diagnosis of NASH requires liver biopsy to confirm the presence of hepatocyte ballooning, hepatic fibrosis is the most important prognostic factor in NAFLD. With so many NAFLD patients, it is essential to have an effective screening method for NAFLD with hepatic fibrosis. As HCC with non-viral liver disease has increased markedly in Japan, effective screening and surveillance of HCC are also urgently needed. The most common death etiology in NAFLD patients is cardiovascular disease (CVD) event. Gastroenterologists must, therefore, pay close attention to CVD when examining NAFLD patients. In the updated guidelines, we propose screening and follow-up methods for hepatic fibrosis, HCC, and CVD in NAFLD patients. Several drug trials are ongoing for NAFLD/NASH therapy, however, there is currently no specific drug therapy for NAFLD/NASH. In addition to vitamin E and thiazolidinedione derivatives, recent trials have focused on sodium glucose co-transporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) analogues, and effective therapies are expected to be developed. These practical guidelines for NAFLD/NASH were established by the Japanese Society of Gastroenterology in conjunction with the Japan Society of Hepatology. Clinical evidence reported internationally between 1983 and October 2018 was collected, and each clinical and background question was evaluated using the Grades of Recommendation Assessment, Development and Evaluation (GRADE) system. This English summary provides the core essentials of these clinical practice guidelines, which include the definition and concept, screening systems for hepatic fibrosis, HCC and CVD, and current therapies for NAFLD/NASH in Japan.
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Affiliation(s)
- Katsutoshi Tokushige
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis'', The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan.
- Institute of Gastroenterology, Department of Internal Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, Japan.
| | - Kenichi Ikejima
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis'', The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Masafumi Ono
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis'', The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Yuichiro Eguchi
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis'', The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Yoshihiro Kamada
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis'', The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Yoshito Itoh
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis'', The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Norio Akuta
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis'', The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Masato Yoneda
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis'', The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Motoh Iwasa
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis'', The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Masashi Yoneda
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis'', The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Motoyuki Otsuka
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis'', The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Nobuharu Tamaki
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis'', The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Tomomi Kogiso
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis'', The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Hiroto Miwa
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis'', The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Kazuaki Chayama
- The Japan Society of Hepatology, Kashiwaya 2 Building 5F, 3-28-10 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
| | - Nobuyuki Enomoto
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis'', The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Tooru Shimosegawa
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis'', The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Tetsuo Takehara
- The Japan Society of Hepatology, Kashiwaya 2 Building 5F, 3-28-10 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
| | - Kazuhiko Koike
- Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis'', The Japanese Society of Gastroenterology / The Japan Society of Hepatology, 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
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19
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Tokushige K, Ikejima K, Ono M, Eguchi Y, Kamada Y, Itoh Y, Akuta N, Yoneda M, Iwasa M, Yoneda M, Otsuka M, Tamaki N, Kogiso T, Miwa H, Chayama K, Enomoto N, Shimosegawa T, Takehara T, Koike K. Evidence-based clinical practice guidelines for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis 2020. Hepatol Res 2021; 51:1013-1025. [PMID: 34533266 DOI: 10.1111/hepr.13688] [Citation(s) in RCA: 84] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Accepted: 06/30/2021] [Indexed: 12/12/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) has become a serious public health issue not only in Western countries but also in Japan. Within the wide spectrum of NAFLD, nonalcoholic steatohepatitis (NASH) is a progressive form of disease that often develops into liver cirrhosis and increases the risk of hepatocellular carcinoma (HCC). While a definite diagnosis of NASH requires liver biopsy to confirm the presence of hepatocyte ballooning, hepatic fibrosis is the most important prognostic factor in NAFLD. With so many NAFLD patients, it is essential to have an effective screening method for NAFLD with hepatic fibrosis. As HCC with non-viral liver disease has increased markedly in Japan, effective screening and surveillance of HCC are also urgently needed. The most common death etiology in NAFLD patients is cardiovascular disease event. Gastroenterologists must, therefore, pay close attention to CVD when examining NAFLD patients. In the updated guidelines, we propose screening and follow-up methods for hepatic fibrosis, HCC, and CVD in NAFLD patients. Several drug trials are ongoing for NAFLD/NASH therapy, however, there is currently no specific drug therapy for NAFLD/NASH. In addition to vitamin E and thiazolidinedione derivatives, recent trials have focused on sodium glucose co-transporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) analogues, and effective therapies are expected to be developed. These practical guidelines for NAFLD/NASH were established by the Japanese Society of Gastroenterology in conjunction with the Japan Society of Hepatology. Clinical evidence reported internationally between 1983 and October 2018 was collected, and each clinical and background question was evaluated using the Grades of Recommendation Assessment, Development and Evaluation (GRADE) system. This English summary pro- vides the core essentials of these clinical practice guidelines, which include the definition and concept, screening systems for hepatic fibrosis, HCC and CVD, and current therapies for NAFLD/NASH in Japan.
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Affiliation(s)
- Katsutoshi Tokushige
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis", The Japanese Society of Gastroenterology, The Japan Society of Hepatology, Tokyo, Japan
- Institute of Gastroenterology, Department of Internal Medicine, Tokyo Women's Medical University, Tokyo, Japan
| | - Kenichi Ikejima
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis", The Japanese Society of Gastroenterology, The Japan Society of Hepatology, Tokyo, Japan
| | - Masafumi Ono
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis", The Japanese Society of Gastroenterology, The Japan Society of Hepatology, Tokyo, Japan
| | - Yuichiro Eguchi
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis", The Japanese Society of Gastroenterology, The Japan Society of Hepatology, Tokyo, Japan
| | - Yoshihiro Kamada
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis", The Japanese Society of Gastroenterology, The Japan Society of Hepatology, Tokyo, Japan
| | - Yoshito Itoh
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis", The Japanese Society of Gastroenterology, The Japan Society of Hepatology, Tokyo, Japan
| | - Norio Akuta
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis", The Japanese Society of Gastroenterology, The Japan Society of Hepatology, Tokyo, Japan
| | - Masato Yoneda
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis", The Japanese Society of Gastroenterology, The Japan Society of Hepatology, Tokyo, Japan
| | - Motoh Iwasa
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis", The Japanese Society of Gastroenterology, The Japan Society of Hepatology, Tokyo, Japan
| | - Masashi Yoneda
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis", The Japanese Society of Gastroenterology, The Japan Society of Hepatology, Tokyo, Japan
| | - Motoyuki Otsuka
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis", The Japanese Society of Gastroenterology, The Japan Society of Hepatology, Tokyo, Japan
| | - Nobuharu Tamaki
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis", The Japanese Society of Gastroenterology, The Japan Society of Hepatology, Tokyo, Japan
| | - Tomomi Kogiso
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis", The Japanese Society of Gastroenterology, The Japan Society of Hepatology, Tokyo, Japan
| | - Hiroto Miwa
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis", The Japanese Society of Gastroenterology, The Japan Society of Hepatology, Tokyo, Japan
| | | | - Nobuyuki Enomoto
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis", The Japanese Society of Gastroenterology, The Japan Society of Hepatology, Tokyo, Japan
| | - Tooru Shimosegawa
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis", The Japanese Society of Gastroenterology, The Japan Society of Hepatology, Tokyo, Japan
| | | | - Kazuhiko Koike
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis", The Japanese Society of Gastroenterology, The Japan Society of Hepatology, Tokyo, Japan
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20
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Pellicori P, Vaduganathan M, Ferreira JP, Zannad F, Sanyal AJ. Cross-talk between non-alcoholic fatty liver disease and cardiovascular disease: Implications for future trial design. DIABETES & METABOLISM 2021; 48:101281. [PMID: 34543735 DOI: 10.1016/j.diabet.2021.101281] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 08/30/2021] [Accepted: 09/04/2021] [Indexed: 02/07/2023]
Abstract
The natural history of non-alcoholic fatty liver disease (NAFLD) is still not fully elucidated. Patients with NAFLD have a low risk of liver complications, unless substantial liver fibrosis has developed. On the other hand, NAFLD has been linked with excess metabolic and cardiovascular complications. Therapies targeting common pathways may benefit both NAFLD and underlying cardiometabolic risk. Therefore, there is a rationale for considering cardiovascular endpoints in the context of NAFLD trials and, vice-versa, to consider the concomitant presence of NAFLD in drug development for cardiometabolic disorders. This manuscript provides a framework for consideration for future trials examining the inter-relationship between cardiovascular disease and NAFLD.
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Affiliation(s)
- Pierpaolo Pellicori
- Robertson Institute of Biostatistics and Clinical Trials Unit, University of Glasgow, University Avenue, Glasgow, G12 8QQ.
| | - Muthiah Vaduganathan
- Division of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
| | - João Pedro Ferreira
- Centre d'Investigation Clinique Plurithématique Pierre Drouin-INSERM CHU de Nancy, Nancy, France & Université de Lorraine, FCRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists) Network, France; Cardiovascular R&D Centre (UnIC), Faculty of Medicine, University of Porto, Porto, Portugal
| | - Faiez Zannad
- Centre d'Investigation Clinique Plurithématique Pierre Drouin-INSERM CHU de Nancy, Nancy, France & Université de Lorraine, FCRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists) Network, France
| | - Arun J Sanyal
- Dept. of Internal medicine, Virginia Commonwealth University School of Medicine, Richmond, VA 23298
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21
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Lee JS, Sinn DH, Park SY, Shin HJ, Lee HW, Kim BK, Park JY, Kim DY, Ahn SH, Oh JH, Lee JI, Kim SU. Liver Stiffness-Based Risk Prediction Model for Hepatocellular Carcinoma in Patients with Nonalcoholic Fatty Liver Disease. Cancers (Basel) 2021; 13:4567. [PMID: 34572795 PMCID: PMC8472221 DOI: 10.3390/cancers13184567] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 09/07/2021] [Accepted: 09/09/2021] [Indexed: 12/15/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is associated with an increased hepatocellular carcinoma (HCC) risk. We established and validated a liver stiffness (LS)-based risk prediction model for HCC development in patients with NAFLD. A total of 2666 and 467 patients with NAFLD were recruited in the training and validation cohorts, respectively. NAFLD was defined as controlled attenuated parameter ≥238 dB/m by transient elastography. Over a median of 64.6 months, HCC developed in 22 (0.8%) subjects in the training cohort. Subjects who developed HCC were older and had higher prevalence of diabetes and cirrhosis, lower platelet count, and higher AST levels compared to those who did not develop HCC (all p < 0.05). In multivariate analysis, age ≥60 years (hazard ratio (HR) = 9.1), platelet count <150 × 103/μL (HR = 3.7), and LS ≥9.3 kPa (HR = 13.8) were independent predictors (all p < 0.05) that were used to develop a risk prediction model for HCC development, together with AST ≥34 IU/L. AUCs for predicting HCC development at 2, 3, and 5 years were 0.948, 0.947, and 0.939, respectively. This model was validated in the validation cohort (AUC 0.777, 0.781, and 0.784 at 2, 3, and 5 years, respectively). The new risk prediction model for NAFLD-related HCC development showed acceptable performance in the training and validation cohorts.
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Affiliation(s)
- Jae Seung Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea; (J.S.L.); (H.W.L.); (B.K.K.); (J.Y.P.); (D.Y.K.); (S.H.A.)
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea
- Yonsei Liver Center, Severance Hospital, Seoul 03722, Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Seoul 06351, Korea;
| | - Soo Young Park
- Department of Internal Medicine, School of Medicine, Kyungpook National University Hospital, Daegu 41944, Korea;
| | - Hye Jung Shin
- Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul 03722, Korea;
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea; (J.S.L.); (H.W.L.); (B.K.K.); (J.Y.P.); (D.Y.K.); (S.H.A.)
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea
- Yonsei Liver Center, Severance Hospital, Seoul 03722, Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea; (J.S.L.); (H.W.L.); (B.K.K.); (J.Y.P.); (D.Y.K.); (S.H.A.)
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea
- Yonsei Liver Center, Severance Hospital, Seoul 03722, Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea; (J.S.L.); (H.W.L.); (B.K.K.); (J.Y.P.); (D.Y.K.); (S.H.A.)
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea
- Yonsei Liver Center, Severance Hospital, Seoul 03722, Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea; (J.S.L.); (H.W.L.); (B.K.K.); (J.Y.P.); (D.Y.K.); (S.H.A.)
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea
- Yonsei Liver Center, Severance Hospital, Seoul 03722, Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea; (J.S.L.); (H.W.L.); (B.K.K.); (J.Y.P.); (D.Y.K.); (S.H.A.)
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea
- Yonsei Liver Center, Severance Hospital, Seoul 03722, Korea
| | - Joo Hyun Oh
- Department of Medicine, Nowon Eulji Medical Center, Seoul 01830, Korea;
| | - Jung Il Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea; (J.S.L.); (H.W.L.); (B.K.K.); (J.Y.P.); (D.Y.K.); (S.H.A.)
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea
- Department of Internal Medicine, Gangnam Severance Hospital, Seoul 06273, Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea; (J.S.L.); (H.W.L.); (B.K.K.); (J.Y.P.); (D.Y.K.); (S.H.A.)
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea
- Yonsei Liver Center, Severance Hospital, Seoul 03722, Korea
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22
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Liu CH, Ampuero J, Pavlides M, Wong VWS, Fan JG, Bai L, Li H, Wu DB, Zhou LY, Du LY, Yang TK, Jiang W, Shi Y, Gil-Gómez A, Zhang WT, Liang JX, Romero-Gómez M, Tang H. Simple non-invasive scoring systems and histological scores in predicting mortality in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis. J Gastroenterol Hepatol 2021; 36:1754-1768. [PMID: 33569851 DOI: 10.1111/jgh.15431] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Revised: 12/24/2020] [Accepted: 01/31/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND AND AIM There is debate among the hepatology community regarding the simple non-invasive scoring systems and histological scores (even it was developed for histological classification) in predicting clinical outcomes in patients with non-alcoholic fatty liver disease (NAFLD). This study aimed to determine whether the presence of simple non-invasive scoring systems and histological scores could predict all-cause mortality, liver-related mortality, and liver disease decompensation (liver failure, cirrhosis, hepatocellular carcinoma, or decompensated liver disease). METHODS The pooled hazard ratio of prognostic factors and incidence rate per 1000 person-years in patients with NAFLD was calculated and further adjusted by two different models of handling the duplicated data. RESULTS A total of 19 longitudinal studies were included. Most simple non-invasive scoring systems (Fibrosis-4 Score, BARD, and aspartate aminotransferase-to-platelet ratio index ) and histological scores (NAFLD activity score, Brunt, and "steatosis, activity, and fibrosis" ) failed in predicting mortality, and only the NAFLD fibrosis score > 0.676 showed prognostic ability to all-cause mortality (four studies, 7564 patients, 118 352 person-years followed up, pooled hazard ratio 1.44, 95% confidence interval [CI] 1.05-1.96). The incidence rate per 1000 person-years of all-cause mortality, liver-related mortality, cardiovascular-related mortality, and liver disease decompensation resulted in a pooled incidence rate per 1000 person-years of 22.65 (14 studies, 95% CI 9.62-53.31), 3.19 (7 studies, 95% CI 1.14-8.93), 6.02 (6 studies, 95% CI 4.69-7.74), and 11.46 (4 studies, 95% CI 5.33-24.63), respectively. CONCLUSION Non-alcoholic fatty liver disease fibrosis score showed promising prognostic value to all-cause mortality. Most present simple non-invasive scoring systems and histological scores failed to predict clinical outcomes.
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Affiliation(s)
- Chang-Hai Liu
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Disease, West China Hospital, Sichuan University, Chengdu, China
| | - Javier Ampuero
- Digestive Diseases Unit, Virgen del Rocío University Hospital, SeLiver Group at Institute of Biomedicine of Seville (IBIS), University of Seville, Seville, Spain
| | - Michael Pavlides
- Oxford NIHR Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust and the University of Oxford, Oxford, UK
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
| | - Jian-Gao Fan
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lang Bai
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Disease, West China Hospital, Sichuan University, Chengdu, China
| | - Hong Li
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Disease, West China Hospital, Sichuan University, Chengdu, China
| | - Dong-Bo Wu
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Disease, West China Hospital, Sichuan University, Chengdu, China
| | - Ling-Yun Zhou
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Disease, West China Hospital, Sichuan University, Chengdu, China
| | - Ling-Yao Du
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Disease, West China Hospital, Sichuan University, Chengdu, China
| | - Tian-Kuo Yang
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Disease, West China Hospital, Sichuan University, Chengdu, China
| | - Wei Jiang
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Disease, West China Hospital, Sichuan University, Chengdu, China
| | - Ying Shi
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Disease, West China Hospital, Sichuan University, Chengdu, China
| | - Antonio Gil-Gómez
- Digestive Diseases Unit, Virgen del Rocío University Hospital, SeLiver Group at Institute of Biomedicine of Seville (IBIS), University of Seville, Seville, Spain
| | - Wen-Ting Zhang
- Digestive Diseases Unit, Virgen del Rocío University Hospital, SeLiver Group at Institute of Biomedicine of Seville (IBIS), University of Seville, Seville, Spain
| | - Jia-Xu Liang
- Digestive Diseases Unit, Virgen del Rocío University Hospital, SeLiver Group at Institute of Biomedicine of Seville (IBIS), University of Seville, Seville, Spain
| | - Manuel Romero-Gómez
- Digestive Diseases Unit, Virgen del Rocío University Hospital, SeLiver Group at Institute of Biomedicine of Seville (IBIS), University of Seville, Seville, Spain
| | - Hong Tang
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Disease, West China Hospital, Sichuan University, Chengdu, China
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23
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Jayarajah U, Widyarathne T, Nawarathne M, Raguvaran S, Subramaniam N, Riza R, De Zoysa I, Seneviratne SL. Clinical characteristics and quality of life among Sri Lankan patients with chronic pancreatitis. J Int Med Res 2021; 48:300060520979875. [PMID: 33372809 PMCID: PMC7783889 DOI: 10.1177/0300060520979875] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Objective We aimed to describe the clinical characteristics of chronic pancreatitis
(CP) and patient quality of life (QOL) in a resource-limited setting. Methods We performed a cross-sectional study including patients with clinical and
radiological features of CP. We collected clinical data and assessed QOL
using the European Organization for the Research and Treatment of Cancer
Quality of Life Questionnaire. Results We included 103 patients (median age 44 years, 84 men). Median age at symptom
onset was 36 (4–78) years. Around 70% of patients had diabetes mellitus and
62.1% had consumed alcohol; 36 (35%) were current smokers. The mean overall
global QOL score was 68.7. Most patients (91.3%) sought treatment from
multiple centers. Nineteen (18.5%) had pancreatic stone disease, 38 (36.9%)
had persistent abdominal pain (median severity 7.8/10, 59 (57.3%) had
steatorrhea, and 56 (54.4%) had jaundice. Poor QOL was significantly
associated with weight loss, loss of appetite, and intractable pain. No
correlation with age, sex, or alcohol consumption was noted. Conclusion A considerable proportion of patients with CP had troublesome symptoms.
Intractable pain, loss of appetite, and weight loss were significantly
associated with poor QOL. Further assessment is needed of patients’
psychosocial well-being and its association with QOL.
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Affiliation(s)
- Umesh Jayarajah
- Department of Surgery, Faculty of Medicine, University of Colombo, Sri Lanka
| | - Thisaru Widyarathne
- Department of Surgery, Faculty of Medicine, University of Colombo, Sri Lanka
| | - Metthananda Nawarathne
- Gastroenterology and Hepatology Unit, National Hospital of Sri Lanka, Colombo, Sri Lanka
| | | | | | - Rishdha Riza
- Department of Surgery, Faculty of Medicine, University of Colombo, Sri Lanka
| | - Ishan De Zoysa
- Department of Surgery, Faculty of Medicine, University of Colombo, Sri Lanka
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Huang DQ, El-Serag HB, Loomba R. Global epidemiology of NAFLD-related HCC: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol 2021; 18:223-238. [PMID: 33349658 PMCID: PMC8016738 DOI: 10.1038/s41575-020-00381-6] [Citation(s) in RCA: 1165] [Impact Index Per Article: 291.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/23/2020] [Indexed: 02/06/2023]
Abstract
One quarter of the global population is estimated to have nonalcoholic fatty liver disease (NAFLD). The incidence of nonalcoholic steatohepatitis (NASH) is projected to increase by up to 56% in the next 10 years. NAFLD is already the fastest growing cause of hepatocellular carcinoma (HCC) in the USA, France and the UK. Globally, the prevalence of NAFLD-related HCC is likely to increase concomitantly with the growing obesity epidemic. The estimated annual incidence of HCC ranges from 0.5% to 2.6% among patients with NASH cirrhosis. The incidence of HCC among patients with non-cirrhotic NAFLD is lower, approximately 0.1 to 1.3 per 1,000 patient-years. Although the incidence of NAFLD-related HCC is lower than that of HCC of other aetiologies such as hepatitis C, more people have NAFLD than other liver diseases. Urgent measures that increase global awareness and tackle the metabolic risk factors are necessary to reduce the impending burden of NAFLD-related HCC. Emerging evidence indicates that reduced immune surveillance, increased gut inflammation and gut dysbiosis are potential key steps in tumorigenesis. In this Review, we discuss the global epidemiology, projections and risk factors for NAFLD-related HCC, and propose preventive strategies to tackle this growing problem.
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Affiliation(s)
- Daniel Q Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Hashem B El-Serag
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA
- Section of Gastroenterology, Michael E. DeBakey VA Medical Center, Houston, TX, USA
- Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA
- Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | - Rohit Loomba
- Division of Epidemiology, Department of Family Medicine and Public Health, University of California at San Diego, San Diego, CA, USA.
- NAFLD Research Center, Division of Gastroenterology. University of California at San Diego, La Jolla, CA, USA.
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25
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Sumida Y, Yoneda M, Tokushige K, Kawanaka M, Fujii H, Yoneda M, Imajo K, Takahashi H, Eguchi Y, Ono M, Nozaki Y, Hyogo H, Koseki M, Yoshida Y, Kawaguchi T, Kamada Y, Okanoue T, Nakajima A, Japan Study Group of NAFLD (JSG-NAFLD). FIB-4 First in the Diagnostic Algorithm of Metabolic-Dysfunction-Associated Fatty Liver Disease in the Era of the Global Metabodemic. Life (Basel) 2021; 11:143. [PMID: 33672864 PMCID: PMC7917687 DOI: 10.3390/life11020143] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2021] [Revised: 01/22/2021] [Accepted: 01/25/2021] [Indexed: 12/16/2022] Open
Abstract
The prevalence of obesity or metabolic syndrome is increasing worldwide (globally metabodemic). Approximately 25% of the adult general population is suffering from nonalcoholic fatty liver disease (NAFLD), which has become a serious health problem. In 2020, global experts suggested that the nomenclature of NAFLD should be updated to metabolic-dysfunction-associated fatty liver disease (MAFLD). Hepatic fibrosis is the most significant determinant of all cause- and liver -related mortality in MAFLD. The non-invasive test (NIT) is urgently required to evaluate hepatic fibrosis in MAFLD. The fibrosis-4 (FIB-4) index is the first triaging tool for excluding advanced fibrosis because of its accuracy, simplicity, and cheapness, especially for general physicians or endocrinologists, although the FIB-4 index has several drawbacks. Accumulating evidence has suggested that vibration-controlled transient elastography (VCTE) and the enhanced liver fibrosis (ELF) test may become useful as the second step after triaging by the FIB-4 index. The leading cause of mortality in MAFLD is cardiovascular disease (CVD), extrahepatic malignancy, and liver-related diseases. MAFLD often complicates chronic kidney disease (CKD), resulting in increased simultaneous liver kidney transplantation. The FIB-4 index could be a predictor of not only liver-related mortality and incident hepatocellular carcinoma, but also prevalent and incident CKD, CVD, and extrahepatic malignancy. Although NITs as milestones for evaluating treatment efficacy have never been established, the FIB-4 index is expected to reflect histological hepatic fibrosis after treatment in several longitudinal studies. We here review the role of the FIB-4 index in the management of MAFLD.
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Affiliation(s)
- Yoshio Sumida
- Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University, Nagakute, Aichi 480-1195, Japan;
| | - Masashi Yoneda
- Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University, Nagakute, Aichi 480-1195, Japan;
| | - Katsutoshi Tokushige
- Department of Internal Medicine, Institute of Gastroenterology, Tokyo Women’s Medical University, Tokyo 162-8666, Japan;
| | - Miwa Kawanaka
- Department of General Internal Medicine2, Kawasaki Medical School, Okayama 700-8505, Japan;
| | - Hideki Fujii
- Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka 558-8585, Japan;
| | - Masato Yoneda
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Yokohama City University, Yokohama 236-0004, Japan; (M.Y.); (K.I.); (A.N.)
| | - Kento Imajo
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Yokohama City University, Yokohama 236-0004, Japan; (M.Y.); (K.I.); (A.N.)
| | - Hirokazu Takahashi
- Department of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga 840-8502, Japan;
| | | | - Masafumi Ono
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokyo Women’s Medical University Medical Center East, Tokyo 116-8567, Japan;
| | - Yuichi Nozaki
- Department of Gastroenterology, National Center for Global Health and Medicine, Tokyo 162-8655, Japan;
| | - Hideyuki Hyogo
- Department of Gastroenterology, JA Hiroshima General Hospital, Hiroshima 738-8503, Japan;
| | - Masahiro Koseki
- Division of Cardiovascular Medicine, Department of Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan;
| | - Yuichi Yoshida
- Department of Gastroenterology and Hepatology, Suita Municipal Hospital, Osaka 564-8567, Japan;
| | - Takumi Kawaguchi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan;
| | - Yoshihiro Kamada
- Department of Advanced Gastroenterology & Hepatology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan;
| | - Takeshi Okanoue
- Hepatology Center, Saiseikai Suita Hospital, Osaka 564-0013, Japan;
| | - Atsushi Nakajima
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Yokohama City University, Yokohama 236-0004, Japan; (M.Y.); (K.I.); (A.N.)
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26
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Li Y, Wu S. Liver stiffness measured with two-dimensional shear wave elastography comparable to histopathology falls dominantly on the severe liver fibrosis. Clin Hemorheol Microcirc 2021; 79:587-596. [PMID: 34334386 DOI: 10.3233/ch-211223] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
BACKGROUND Two-dimensional shear-wave elastography (2D-SWE) has been used for years for liver assessment of patients with chronic hepatitis B (CHB), but its effectiveness remains unclear in different populations and using different ultrasound systems. OBJECTIVE This study investigated the effectiveness of 2D-SWE in evaluating liver fibrosis in patients with CHB. METHODS A prospective investigation was conducted after approval by the institutional ethics committee, with 116 out of 133 patients with CHB referred for liver biopsy included and 50 patients with healthy livers selected as controls. Assessment with 2D-SWE of liver stiffness measurement (LSM) was compared with histopathological results. Cutoff values for LSM were set to determine the degree of fibrosis, and area under the receiver operating characteristic (AUROC) curve, sensitivity, and specificity were calculated. RESULTS The optimal LSM cutoff for differentiating healthy livers from livers with CHB and any liver fibrosis was 6.485 kPa, with an AUROC of 0.927, sensitivity of 94%, and specificity of 19.8%. The optimal LSM cutoff values for F1, F2, F3, and F4 were 6.19 kPa, 6.485 kPa, 7.46 kPa, and 9.62 kPa, respectively, with corresponding AUROCs of 0.516, 0.625, 0.779, and 0.881, respectively. Comparisons of AUROCs between F1 and F3, F1 and F4, F2 and F3, and F2 and F4 were all significantly different (P = 0.0001, P < 0.0001, P = 0.0139, and P = 0.0003, respectively); comparisons of AUROCs between F1 and F2 and between F3 and F4 were not significantly different (P = 0.1232 and P = 0.2462, respectively). Comparisons of LSMs between healthy livers and F0 and between healthy livers and a combination of F0 and F1 were significantly different (P = 0.002 and P = 0.001, respectively). Comparisons of LSMs between F1 and F2 and between F3 and F4 were not significantly different (P = 0.233 and P = 0.072, respectively). Other comparisons between fibrosis score groups were significantly different (F1 and F3, P = 0.003; F1 and F4, P = 0.007; F2 and F3, P = 0.013; F2 and F4, P = 0.015). CONCLUSION 2D-SWE using a specific diagnostic ultrasound system is effective for the assessment of severe liver fibrosis and cirrhosis, but is limited in diagnosing mild liver fibrosis.
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Affiliation(s)
- Ya Li
- Department of Ultrasound, The First Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Size Wu
- Department of Ultrasound, The First Affiliated Hospital of Hainan Medical University, Haikou, China
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27
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Ogawa M, Tsuchiya A, Watanabe T, Setsu T, Kimura N, Matsuda M, Hoshiyama Y, Saito H, Kanazawa T, Shiotani M, Sato T, Yagi T, Igarashi K, Yoshimura N, Takamura M, Aoyama H, Terai S. Screening and follow-up of chronic liver diseases with understanding their etiology in clinics and hospitals. JGH Open 2020; 4:827-837. [PMID: 33102751 PMCID: PMC7578295 DOI: 10.1002/jgh3.12406] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Revised: 07/21/2020] [Accepted: 07/27/2020] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND AIM Considering the increasing prevalence of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (NASH), the development of an effective screening and follow-up system that enables the recognition of etiological changes by primary physicians in clinics and specialists in hospitals is required. METHODS Chronic hepatitis B (HBV) and C (HCV), NASH, and alcoholic steatohepatitis (ASH) patients who were assayed for Mac-2-binding protein glycosylation isomer (M2BPGi) (n = 272) and underwent magnetic resonance elastography (MRE) (n = 119) were enrolled. Patients who underwent MRE were also tested by ultrasound elastography (USE) (n = 80) and for M2BPGi (n = 97), autotaxin (ATX) (n = 62), and platelet count (n = 119), and their fibrosis-4 (FIB-4) index was calculated (n = 119). RESULTS FIB-4 index >2, excluding HBV-infected patients, M2BPGi >0.5, ATX >0.5, and platelet count <20 × 104/μL were the benchmark indices, and we took into consideration other risk factors, such as diabetes mellitus and age, to recommend further examinations, such as USE, based on the local situation to avoid overlooking hepatocellular carcinoma (HCC) in the clinic. During specialty care in the hospital, MRE exhibited high diagnostic ability for fibrosis stages >F3 or F4; it could efficiently predict collateral circulation with high sensitivity, which can replace USE. We also identified etiological features and found that collateral circulation in NASH/ASH patients tended to exceed high-risk levels; moreover, these patients exhibited more variation in HCC-associated liver stiffness than the HBV and HCV patients. CONCLUSIONS Using appropriate markers and tools, we can establish a stepwise, practical, noninvasive, and etiology-based screening and follow-up system in primary and specialty care.
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Affiliation(s)
- Masahiro Ogawa
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental SciencesNiigata UniversityNiigataJapan
| | - Atsunori Tsuchiya
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental SciencesNiigata UniversityNiigataJapan
| | - Takayuki Watanabe
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental SciencesNiigata UniversityNiigataJapan
| | - Toru Setsu
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental SciencesNiigata UniversityNiigataJapan
| | - Naruhiro Kimura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental SciencesNiigata UniversityNiigataJapan
| | - Masato Matsuda
- Medical Laboratory DivisionNiigata University Medical and Dental HospitalNiigataJapan
| | - Yoshiki Hoshiyama
- Medical Laboratory DivisionNiigata University Medical and Dental HospitalNiigataJapan
| | - Hiroaki Saito
- Division of Radiology, Department of Clinical TechnologyNiigata University Medical and Dental HospitalNiigataJapan
| | - Tsutomu Kanazawa
- Division of Radiology, Department of Clinical TechnologyNiigata University Medical and Dental HospitalNiigataJapan
| | - Motoi Shiotani
- Department of Radiology and Radiation OncologyNiigata University Graduate School of Medical and Dental SciencesNiigataJapan
| | - Tatsuhiko Sato
- Department of Radiology and Radiation OncologyNiigata University Graduate School of Medical and Dental SciencesNiigataJapan
| | - Takuya Yagi
- Department of Radiology and Radiation OncologyNiigata University Graduate School of Medical and Dental SciencesNiigataJapan
| | | | - Norihiko Yoshimura
- Department of Radiology and Radiation OncologyNiigata University Graduate School of Medical and Dental SciencesNiigataJapan
| | - Masaaki Takamura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental SciencesNiigata UniversityNiigataJapan
| | - Hidefumi Aoyama
- Department of Radiology and Radiation OncologyNiigata University Graduate School of Medical and Dental SciencesNiigataJapan
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental SciencesNiigata UniversityNiigataJapan
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28
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Sung KC, Johnston MP, Lee MY, Byrne CD. Non-invasive liver fibrosis scores are strongly associated with liver cancer mortality in general population without liver disease. Liver Int 2020; 40:1303-1315. [PMID: 32090451 DOI: 10.1111/liv.14416] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 02/15/2020] [Accepted: 02/18/2020] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS In a general population without known liver disease, we tested whether: (a) increased liver fibrosis scores (FIB-4 and APRI) are associated with liver cancer mortality and (b) the probability that a person with a higher score died of liver cancer. METHODS In a retrospective occupational cohort who underwent annual/biennial health examinations (between 2002 and 2015), subjects were excluded with known chronic liver disease. Based on their baseline FIB-4 and APRI scores, subjects were categorised in low-/intermediate-/high-risk groups for advanced liver fibrosis. Using Cox proportional hazards regression analyses adjusted hazard ratios (aHR) were estimated for liver cancer mortality, with the low-risk FIB-4/APRI group as the reference. Harrell's C statistics were also calculated. RESULTS In 200 479 participants, mean (SD) age was 36.4 (7.7) years. Median follow-up was 4.1 years (IQR 2.10-8.03) with 80 liver cancer deaths. High baseline FIB-4 or APRI scores occurred in 0.25% and 0.09% of subjects respectively. A high FIB-4 or APRI score was associated with a markedly increased risk of liver cancer mortality (aHRs 629.10 [95% CI 228.74-1730.20] and 80.42 [95% CI 34.37-188.18]) respectively. C statistics were FIB-4 = 0.841 (95% CI 0.735-0.946) and APRI = 0.933 (95% CI 0.864-0.999). CONCLUSIONS In a general population without known liver disease, high FIB-4 or high APRI (in keeping with a high probability of advanced fibrosis) occurred in 0.25% (FIB-4) and 0.09% (APRI) of subjects. Both scores were associated with a markedly increased risk of liver cancer mortality and FIB-4 and APRI models both strongly predicted liver cancer mortality.
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Affiliation(s)
- Ki-Chul Sung
- Division of Cardiology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Michael P Johnston
- Department of Hepatology, University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Mi Y Lee
- Division of Biostatistics, Department of R&D Management, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Christopher D Byrne
- Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK
- National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton National Health Service (NHS) Foundation Trust, Southampton, UK
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29
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Taylor RS, Taylor RJ, Bayliss S, Hagström H, Nasr P, Schattenberg JM, Ishigami M, Toyoda H, Wai-Sun Wong V, Peleg N, Shlomai A, Sebastiani G, Seko Y, Bhala N, Younossi ZM, Anstee QM, McPherson S, Newsome PN. Association Between Fibrosis Stage and Outcomes of Patients With Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis. Gastroenterology 2020; 158:1611-1625.e12. [PMID: 32027911 DOI: 10.1053/j.gastro.2020.01.043] [Citation(s) in RCA: 713] [Impact Index Per Article: 142.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Revised: 01/19/2020] [Accepted: 01/22/2020] [Indexed: 12/02/2022]
Abstract
BACKGROUND & AIMS Biopsy-confirmed liver fibrosis is a prognostic factor for patients with nonalcoholic fatty liver disease (NAFLD). We performed a systematic review to quantify the prognostic value of fibrosis stage in patients with NAFLD and the subgroup of patients with nonalcoholic steatohepatitis (NASH) and to assess the evidence that change in fibrosis stage is a surrogate endpoint. METHODS We searched the MEDLINE, Embase, Cochrane Library, and trial registry databases through August 2018 for prospective or retrospective cohort studies of liver-related clinical events and outcomes in adults with NAFLD or NASH. We collected data on mortality (all cause and liver related) and morbidity (cirrhosis, liver cancer, and all liver-related events) by stage of fibrosis, determined by biopsy, for patients with NAFLD or NASH. Using fibrosis stage 0 as a reference population, we calculated fibrosis stage-specific relative risk (RR) and 95% confidence interval (CI) values for mortality and morbidities. We performed fixed-effect and random-effect model meta-analyses. Metaregression was used to examine associations among study design (prospective vs retrospective cohort), overall risk of bias (medium or high), and mean duration of follow-up (in years). RESULTS Our meta-analysis included 13 studies, comprising 4428 patients with NAFLD; 2875 of these were reported to have NASH. Compared with no fibrosis (stage 0), unadjusted risk increased with increasing stage of fibrosis (stage 0 vs 4): all-cause mortality RR, 3.42 (95% CI, 2.63-4.46); liver-related mortality RR, 11.13 (95% CI, 4.15-29.84); liver transplant RR, 5.42 (95% CI, 1.05-27.89); and liver-related events RR, 12.78 (95% CI, 6.85-23.85). The magnitude of RR did not differ significantly after adjustment for confounders, including age or sex in the subgroup of NAFLD patients with NASH. Three studies examined the effects of increasing fibrosis on quality of life had inconsistent findings. CONCLUSIONS In a systematic review and meta-analysis, we found biopsy-confirmed fibrosis to be associated with risk of mortality and liver-related morbidity in patients with NAFLD, with and without adjustment for confounding factors and in patients with reported NASH. Further studies are needed to assess the association between fibrosis stage and patient quality of life and establish that change in liver fibrosis stage is a valid endpoint for use in clinical trials.
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Affiliation(s)
- Rod S Taylor
- Institute of Health and Well Being, University of Glasgow, United Kingdom.
| | | | - Sue Bayliss
- Institute of Applied Health Research, University of Birmingham, United Kingdom
| | - Hannes Hagström
- Unit of Hepatology, Department of Upper GI Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - Patrik Nasr
- Department of Gastroenterology and Hepatology, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden
| | - Jorn M Schattenberg
- University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany
| | - Masatoshi Ishigami
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong
| | - Noam Peleg
- Department of Gastroenterology and Hepatology, Rabin Medical Center, Beilinson Hospital, Petach-Tikva Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Medicine D, Rabin Medical Center, Beilinson hospital, Petach-Tikva
| | - Amir Shlomai
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Giada Sebastiani
- Department of Medicine, McGill University Health Centre, Montréal, Quebec, Canada
| | - Yuya Seko
- Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Neeraj Bhala
- Institute of Applied Health Research, University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham, United Kingdom
| | - Zobair M Younossi
- Department of Medicine, Inova Fairfax Hospital, Falls Church, Virginia
| | - Quentin M Anstee
- Institute of Clinical and Translational Research, Faculty of Medical Sciences, Newcastle University, Newcastle-upon-Tyne, United Kingdom; Newcastle National Institute of Health Research Biomedical Research Centre and Liver Transplant Unit, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, United Kingdom
| | - Stuart McPherson
- Liver Transplant Unit, The Newcastle upon Tyne Hospitals NHS Foundation Trust; Institute of Clinical and Translational Research, Newcastle University, Newcastle-upon-Tyne, United Kingdom; Newcastle National Institute of Health Research Biomedical Research Centre, Newcastle-upon-Tyne, United Kingdom
| | - Philip N Newsome
- National Institute for Health Research Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham, United Kingdom; Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, United Kingdom; Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom
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30
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Wang L, Zhu M, Cao L, Yao M, Lu Y, Wen X, Zhang Y, Ning J, Long H, Zhu Y, Hu G, Dang S, Fu Q, Chen L, Zhang X, Zhao J, Gao Z, Nan Y, Lu F. Liver Stiffness Measurement Can Reflect the Active Liver Necroinflammation in Population with Chronic Liver Disease: A Real-world Evidence Study. J Clin Transl Hepatol 2019; 7:313-321. [PMID: 31915600 PMCID: PMC6943212 DOI: 10.14218/jcth.2019.00040] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Revised: 11/01/2019] [Accepted: 11/05/2019] [Indexed: 02/07/2023] Open
Abstract
Background and Aims: Non-invasive evaluation of liver necroinflammation in patients with chronic liver disease is an unmet need in clinical practice. The diagnostic accuracy of transient elastography-based liver stiffness measurement (LSM) for liver fibrosis could be affected by liver necroinflammation, the latter of which could intensify stiffness of the liver. Such results have prompted us to explore the diagnosis potential of LSM for liver inflammation. Methods: Three cross-sectional cohorts of liver biopsy-proven chronic liver disease patients were enrolled, including 1417 chronic hepatitis B (CHB) patients from 10 different medical centers, 106 non-alcoholic steatohepatitis patients, and 143 patients with autoimmune-related liver diseases. Another longitudinal cohort of 14 entecavir treatment patients was also included. The receiver operating characteristic (ROC) curve was employed to explore the diagnostic value of LSM. Results: In CHB patients, LSM value ascended with the increased severity of liver necroinflammation in patients with the same fibrosis stage. Such positive correlation between LSM and liver necroinflammation was also found in non-alcoholic steatohepatitis and autoimmune-related liver diseases populations. Furthermore, the ROC curve exhibited that LSM could identify moderate and severe inflammation in CHB patients (area under the ROC curve as 0.779 and 0.838) and in non-alcoholic steatohepatitis patients (area under the ROC curve as 0.826 and 0.871), respectively. Such moderate diagnostic value was also found in autoimmune-related liver diseases patients. In addition, in the longitudinal entecavir treated CHB cohort, a decline of LSM values was observed in parallel with the control of inflammatory activity in liver. Conclusions: Our study implicates a diagnostic potential of LSM to evaluate the severity of liver necroinflammation in chronic liver disease patients.
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Affiliation(s)
- Leijie Wang
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Mingyu Zhu
- Department of Infectious Diseases, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lihua Cao
- Liver Disease Center, Qinhuangdao Third Hospital, Qinhuangdao, Hebei, China
| | - Mingjie Yao
- Department of Anatomy and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Yiwei Lu
- Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA
| | - Xiajie Wen
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Ying Zhang
- Department of Traditional and Western Medical Hepatology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Jing Ning
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Huiling Long
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Yueyong Zhu
- Liver Research Center, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Guoxin Hu
- Department of Infectious Diseases, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
| | - Shuangsuo Dang
- Department of Infectious Diseases, Second Affiliated Hospital of Medical College of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Qingchun Fu
- Shanghai Liver Diseases Research Center, 85th Hospital, Nanjing Military Command, Shanghai, China
| | - Liang Chen
- Department of Liver Disease, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Xinxin Zhang
- Department of Infectious Diseases, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jingmin Zhao
- Department of Pathology and Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Zhiliang Gao
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Yuemin Nan
- Department of Traditional and Western Medical Hepatology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Fengmin Lu
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
- Intervention and Cell Therapy Center, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
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31
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Ito T, Ishigami M, Ishizu Y, Kuzuya T, Honda T, Ishikawa T, Toyoda H, Kumada T, Fujishiro M. Serum Nutritional Markers as Prognostic Factors for Hepatic and Extrahepatic Carcinogenesis in Japanese Patients with Nonalcoholic Fatty Liver Disease. Nutr Cancer 2019; 72:884-891. [PMID: 31433263 DOI: 10.1080/01635581.2019.1653474] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Serum zinc (Zn) levels and the branched chain amino acid/tyrosine molar ratio (BTR) were reported to decrease with the progression of various chronic liver diseases. We investigated the impact of BTR and Zn on the incidence of malignancies in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD). A total of 179 Japanese NAFLD patients who underwent liver biopsy were enrolled. Hepatocellular carcinoma (HCC) and extrahepatic malignancies developed in 7 (3.9%) and 10 (5.6%) patients, respectively, during the follow-up period (median 7.9 years). Patients with low BTR levels (<5.0) and Zn deficiency (<70 μg/dL) had significantly higher incidences of HCC and extrahepatic malignancies (P < 0.001 and 0.026), respectively. Multiple logistic regression analyses revealed the following risk factors: liver fibrosis (F3-4) (hazard ratio [HR] 24.292, 95% confidence interval [CI] 2.802-210.621, P = 0.004) and BTR < 5.0 (HR 5.462, 95% CI 1.095-27.253, P = 0.038) for HCC, and serum Zn level <70 μg/dL (HR 3.504, 95% CI 1.010-12.157, P = 0.048) and liver inflammation (A2-3) (HR 3.445, 95% CI 0.886-13.395, P = 0.074) for extra-hepatic malignancies. In conclusion, serum BTR and Zn levels were useful for predicting HCC and extrahepatic malignancies in NAFLD, respectively.
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Affiliation(s)
- Takanori Ito
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Masatoshi Ishigami
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yoji Ishizu
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Teiji Kuzuya
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Takashi Honda
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Tetsuya Ishikawa
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Takashi Kumada
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
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32
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Tamaki N, Higuchi M, Kurosaki M, Kirino S, Osawa L, Watakabe K, Wang W, Okada M, Shimizu T, Takaura K, Takada H, Kaneko S, Yasui Y, Tsuchiya K, Nakanishi H, Itakura J, Takahashi Y, Enomoto N, Izumi N. Wisteria floribunda agglutinin-positive mac-2 binding protein as an age-independent fibrosis marker in nonalcoholic fatty liver disease. Sci Rep 2019; 9:10109. [PMID: 31300805 PMCID: PMC6626055 DOI: 10.1038/s41598-019-46172-1] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2019] [Accepted: 06/21/2019] [Indexed: 12/13/2022] Open
Abstract
The assessment of liver fibrosis is essential because it correlates with mortality risk in nonalcoholic fatty liver disease (NAFLD). This study aims to examine whether serum fibrosis markers could identify candidate patients likely to have advanced fibrosis. We enrolled 352 patients with NAFLD and performed liver biopsies in 97 patients. The area under the receiver operating characteristic curve (AUROC) of liver stiffness by magnetic resonance elastography for histological advanced fibrosis was 0.910, and the optimal cutoff value was 4.07 kPa. To predict severe liver stiffness (≥4.07 kPa), the AUROC for Wisteria floribunda agglutinin-positive mac-2 binding protein (WFA+-M2BP) and FIB-4 were 0.897 (cutoff value, 1.08) and 0.880 (cutoff value, 2.53), respectively. After stratification of patients into four age groups as quartile, the optimal cutoff values of WFA+-M2BP for predicting severe liver stiffness were similar in each group (1.09, 1.08, 1.10, and 1.12). On the other hand, those of FIB-4 increased in parallel with age (1.47, 2.19, 2.99, and 3.88). In conclusion, WFA+-M2BP was precise for estimating severe liver stiffness in NAFLD with single cutoff value independent of age. Hence, identifying high-risk cases using WFA+-M2BP from a large number of NAFLD patients is clinically significant.
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Affiliation(s)
- Nobuharu Tamaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Japan
| | - Mayu Higuchi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Sakura Kirino
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Leona Osawa
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Keiya Watakabe
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Wan Wang
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Mao Okada
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Takao Shimizu
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Kenta Takaura
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Hitomi Takada
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Japan
| | - Shun Kaneko
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yutaka Yasui
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Kaoru Tsuchiya
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Hiroyuki Nakanishi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Jun Itakura
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yuka Takahashi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Nobuyuki Enomoto
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Japan
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
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33
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Zhou WJ, Yang J, Zhang G, Hu ZQ, Jiang YM, Yu F. Association between red cell distribution width-to-platelet ratio and hepatic fibrosis in nonalcoholic fatty liver disease: A cross-sectional study. Medicine (Baltimore) 2019; 98:e16565. [PMID: 31348282 PMCID: PMC6709090 DOI: 10.1097/md.0000000000016565] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND We aimed to assess the association between red cell distribution width-to-platelet ratio (RPR) and hepatic fibrosis in nonalcoholic fatty liver disease. METHODS The 388 subjects fulfilling the diagnostic criteria of Nonalcoholic fatty liver disease (NAFLD) were enrolled in this cross-sectional study. Red cell distribution, platelet, and other clinical and laboratory parameters were measured. RESULTS NAFLD patients with advanced fibrosis had significantly higher RPR than those without fibrosis (P < .001). Spearman correlation analysis showed that RPR were significantly correlated with age, sex, creatinine, hemoglobin, white blood cell, and advanced fibrosis (all with P < .05). Multivariate logistic regression analysis showed that RPR was an independent factor predicting advanced fibrosis (fibrosis-4 calculator ≥1.3) in NAFLD patients (OR: 5.718, 95%CI: 3.326-9.830, P < .001). CONCLUSIONS Our findings suggested that RPR were significantly associated with advanced fibrosis in nonalcoholic fatty liver disease patients.
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Affiliation(s)
- Wen-Jie Zhou
- Department of Laboratory Medicine, West China Second University Hospital, Sichuan University
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China
| | - Jing Yang
- Department of Laboratory Medicine, West China Second University Hospital, Sichuan University
| | - Ge Zhang
- Department of Laboratory Medicine, West China Second University Hospital, Sichuan University
| | - Zheng-Qiang Hu
- Department of Laboratory Medicine, West China Second University Hospital, Sichuan University
| | - Yong-Mei Jiang
- Department of Laboratory Medicine, West China Second University Hospital, Sichuan University
| | - Fan Yu
- Department of Laboratory Medicine, West China Second University Hospital, Sichuan University
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China
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