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Bharatselvam S, Schwenger KJP, Ghorbani Y, Fischer SE, Jackson TD, Okrainec A, Allard JP. Assessing clinical and metabolic responses related to hyperlipidemia, MASLD and type 2 diabetes: sleeve versus RYGB. Nutrition 2024; 126:112530. [PMID: 39111098 DOI: 10.1016/j.nut.2024.112530] [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: 04/03/2024] [Revised: 06/28/2024] [Accepted: 07/11/2024] [Indexed: 09/10/2024]
Abstract
OBJECTIVE Both Roux-en-Y gastric bypass (RYGB) and laparoscopic sleeve gastrectomy (LSG) are effective at inducing weight loss, but more information is needed on their comparative effectiveness at improving clinical/biochemical outcomes related to the presence of hyperlipidemia, metabolic dysfunction-associated steatotic liver disease (MASLD), or type 2 diabetes (T2D) at baseline. Here we aimed to assess this in real-world practice. METHODS This is a prospective cross-sectional and cohort study of 142 patients who underwent RYGB or LSG as per clinical practice. Clinical/biochemical data were collected at baseline, prior to surgery and 12 months post-bariatric surgery. Liver biopsy was performed during surgery to diagnose MASLD. The main outcome was 12-month changes in lipid parameters, mainly total cholesterol, between types of surgery. RESULTS A TOTAL OF: 107 participants underwent RYGB and 35 underwent LSG. Both groups were similar at baseline except for a higher proportion of males and waist circumference in the LSG group. At 12 months postsurgery, RYGB versus LSG resulted in a significantly lower body mass index, triglycerides, total cholesterol, and low-density lipoprotein. However, alanine aminotransferase was significantly lower in those who underwent LSG. In subgroup analyses RYGB was superior at improving lipid-related parameters in those with hyperlipidemia, whereas LSG was superior at reducing alanine aminotransferase in those with MASLD. CONCLUSIONS RYGB versus LSG leads to greater reductions in body mass index and lipid parameters, especially in those with hyperlipidemia, whereas LSG showed greater improvements in liver enzymes in those with MASLD.
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Affiliation(s)
| | | | - Yasaman Ghorbani
- Toronto General Hospital, University Health Network, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada
| | - Sandra E Fischer
- Toronto General Hospital, University Health Network, Toronto, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada
| | - Timothy D Jackson
- Division of Surgery, University of Toronto, Toronto, Canada; Division of General Surgery, Toronto Western Hospital, University Health Network, Toronto, Canada
| | - Allan Okrainec
- Division of Surgery, University of Toronto, Toronto, Canada; Division of General Surgery, Toronto Western Hospital, University Health Network, Toronto, Canada
| | - Johane P Allard
- Toronto General Hospital, University Health Network, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada; Department of Medicine, University of Toronto, Toronto, Canada; Department of Nutritional Sciences, University of Toronto, Toronto, Canada.
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Wang S, Zhang Q, Qin B. Association between remnant cholesterol and insulin resistance levels in patients with metabolic-associated fatty liver disease. Sci Rep 2024; 14:4596. [PMID: 38409335 PMCID: PMC10897142 DOI: 10.1038/s41598-024-55282-4] [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: 10/22/2023] [Accepted: 02/22/2024] [Indexed: 02/28/2024] Open
Abstract
The relationship between remnant cholesterol (RC) and homeostasis model assessment-insulin resistance (HOMA-IR) in the context of metabolic-associated fatty liver disease (MAFLD) remains an area of ambiguity. This investigation was designed to elucidate the potential association between RC and HOMA-IR in a cohort of American adults diagnosed with MAFLD. Data from 5533 participants were procured from the 2017-2018 US National Health and Nutrition Examination (NHANES) databases. A weighted linear regression model was employed to analyze the association between RC and HOMA-IR in the context of MAFLD. Preliminary analysis revealed that 44.67% of the participants were diagnosed with MAFLD, with a higher prevalence observed in individuals aged 50-64 years (31.84%, p < 0.0001) and in males compared to females (53.48% vs. 46.52%, p < 0.0001). A positive correlation was identified between RC and HOMA-IR in MAFLD patients. The threshold effect analysis model indicated a breakpoint at RC = 30 mg/dl, with a more pronounced positive correlation when RC < 30 mg/dl (β = 0.17, p < 0.001). Receiver operating characteristic analysis further demonstrated that among all lipid parameters, RC exhibited the largest area under the curve. The study findings suggest a positive correlation between RC and HOMA-IR in MAFLD patients, indicating that elevated RC may serve as an independent risk factor for MAFLD.
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Affiliation(s)
- Shuang Wang
- Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Qiang Zhang
- Department of Gastroenterology, The People's Hospital of Changshou, Chongqing, China
| | - Bo Qin
- Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
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Schwenger KJP, Ghorbani Y, Rezaei K, Fischer SE, Jackson TD, Okrainec A, Allard JP. Relationship between dietary intake components and hepatic fibrosis in those with obesity before and 1 year after bariatric surgery. Nutrition 2023; 114:112095. [PMID: 37437418 DOI: 10.1016/j.nut.2023.112095] [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: 02/24/2023] [Revised: 05/05/2023] [Accepted: 05/22/2023] [Indexed: 07/14/2023]
Abstract
OBJECTIVES Non-alcoholic fatty liver disease is highly prevalent in the bariatric population but not all patients develop liver fibrosis. Considering that fibrosis may affect clinical outcomes, it is important to assess and treat contributing factors. In this population, it is not clear whether dietary intake is a contributor. The objective was to determine the relationship between dietary intake components and liver fibrosis before and 1 y after Roux-en-Y gastric bypass (RYGB). METHODS This was a prospective cross-sectional (n = 133) study conducted between 2013 and 2022. In addition, a subgroup of 44 patients were followed for 1 y post-RYGB. Anthropometrics, biochemical measurements, and 3-d food records and liver biopsies were obtained presurgery and, in a subgroup of patients, as for the cohort, 1 y post-RYGB. RESULTS In the cross-sectional study, 78.2% were female, with a median age of 48 y and body mass index of 46.8 kg/m2; 33.8% had type 2 diabetes mellitus and 57.1% had metabolic syndrome. In a multivariate analysis, age (odds ratio; 95% CI) (1.076; 1.014-1.141), alanine transaminase (1.068; 1.025-1.112), calorie intake (1.001; 1.000-1.002), and dietary copper (0.127; 0.022-0.752) were independently associated with fibrosis (<0.05). At 1 y post-RYGB, no independent risk factors were associated with persistent fibrosis. CONCLUSIONS In bariatric patients before surgery, higher age, alanine transaminase, and total calorie and lower copper intakes were independent risk factors associated with liver fibrosis. These relationships were no longer observed after RYGB, likely due to the effect of surgery on weight and similar postsurgery diet among patients.
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Affiliation(s)
| | - Yasaman Ghorbani
- Toronto General Hospital, University Health Network, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada
| | - Kuorosh Rezaei
- Toronto General Hospital, University Health Network, Toronto, Canada
| | - Sandra E Fischer
- Toronto General Hospital, University Health Network, Toronto, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada
| | - Timothy D Jackson
- Division of Surgery, University of Toronto, Toronto, Ontario, Canada; Division of General Surgery, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada
| | - Allan Okrainec
- Division of Surgery, University of Toronto, Toronto, Ontario, Canada; Division of General Surgery, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada
| | - Johane P Allard
- Toronto General Hospital, University Health Network, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada; Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada.
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Omran M, Omr M, Mohamed AA, Abdelghafour RA, Muharram NM, Hassan MB, Fangry A, Emran T, Arab JP, Arnold J, Diaz LA, Zheng MH, El-Kassas M. Development and validation of nonalcoholic fatty liver disease test: a simple sensitive and specific marker for early diagnosis of nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol 2023; 35:874-880. [PMID: 37395240 DOI: 10.1097/meg.0000000000002575] [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: 07/04/2023]
Abstract
AIM This study aimed to develop a noninvasive test for identifying patients with nonalcoholic fatty liver disease (NAFLD) based on clinical and routine laboratory data. METHODS The developed model 'NAFLD test' was compared to the most commonly used NAFLD scores and then validated in three groups of NAFLD patients from five centers in Egypt, China, and Chile. Patients were divided into the discovery cohort (n = 212) and the validation study (n = 859). The ROC curve and stepwise multivariate discriminant analysis were used to develop and validate the NAFLD test and evaluate its diagnostic performance, which was then compared to other NAFLD scores. RESULTS Elevated C-reactive protein (CRP), cholesterol, BMI, and alanine aminotransferase (ALT) levels were significantly associated with NAFLD (P < 0.0001). NAFLD test is depicted as (-0.695 + 0.031 × BMI + 0.003 × cholesterol + 0.014 × ALT + 0.025 × CRP) to discriminate patients with NAFLD from healthy individuals. The area under the ROC curve (AUC) of the NAFLD test was 0.92 [95% confidence interval (CI): 0.88-0.96]. The NAFLD test was the most accurate diagnostic indicator of NAFLD when compared to widely used NAFLD indices. Upon validating the NAFLD test, its AUC (95% CI) for distinguishing patients with NAFLD from healthy individuals was 0.95 (0.94-0.97), 0.90 (0.87-0.93), and 0.94 (0.91-0.97) in Egyptian, Chinese, and Chilean patients with NAFLD respectively. CONCLUSION The NAFLD test is a new validated diagnostic biomarker that can be utilized for the early diagnosis of NAFLD with high diagnostic performance.
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Affiliation(s)
- Mohamed Omran
- Chemistry Department, Faculty of Science, Helwan University, Cairo
| | - Mona Omr
- Chemistry Department, Faculty of Science, Damietta University, Damietta
| | - Amal A Mohamed
- Biochemistry Department, National Hepatology Tropical Medicine Research Institute, Cairo
| | | | - Nashwa M Muharram
- Medical Biochemistry and Molecular Biology, Faculty of Medicine, Menoufia University, Shebin ElKom
| | - Mohamed B Hassan
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo
| | | | - Tarek Emran
- Clinical Pathology Department, Faculty of Medicine, Al-Azhar University, Damietta, Egypt
| | - Juan P Arab
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University & London Health Sciences Centre, London, Ontario, Canada
| | - Jorge Arnold
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Luis Antonio Diaz
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Ming-Hua Zheng
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University & London Health Sciences Centre, London, Ontario, Canada
- Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China
| | - Mohamed El-Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo
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Reliability of Non-invasive Liver Fibrosis Assessment Tools Versus Biopsy in Pre- and Post-bariatric Surgery Patients with Non-alcoholic Fatty Liver Disease. Obes Surg 2023; 33:247-255. [PMID: 36464738 DOI: 10.1007/s11695-022-06380-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 11/17/2022] [Accepted: 11/27/2022] [Indexed: 12/07/2022]
Abstract
PURPOSE Liver biopsy (LBx) remains the gold standard to assess fibrosis in non-alcoholic fatty liver disease (NAFLD). Biochemical markers are also useful, but their reliability is not clear in patients with morbid obesity. We assessed the performance of six non-invasive fibrosis assessment tools before and after bariatric surgery (BSx) using LBx. MATERIALS AND METHODS This is a cross-sectional and prospective cohort study. LBx was performed at the time of BSx and 12-month post-operatively and assessed using the Brunt system. Clinical and biochemical measurements were collected at the same time points and six non-invasive fibrosis assessment tools were calculated. RESULTS One hundred seventy patients had BSx; 79.4% female; age was 46.6 ± 9.8 years, and BMI was 48.6 ± 7.5 kg/m2. From liver histology, 88% had F0-F2 and 11.2% F3-F4. At BSx, aspartate aminotransferase to platelet ratio index (APRI) and FIB-4 had better accuracy (0.86 and 0.88) with specificity of 96.6% and 94.0% and negative predictive values (NPV) of 88.9% and 93.7%. However, sensitivity (6.7% and 40.0%) and positive predictive values (PPV) (20.0% and 46.2%) were low. Twelve months post-surgery (n = 54), 88.9% of patients had F0-F2 and 11.1% had F3-F4. Fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS) had the best accuracy (0.79 and 0.77) with specificity of 83.7% and 86.9% and NPV of 92.3% and 86.9%. However, sensitivity (25% and 0%) and PPV (12.5% and 0%) were low. CONCLUSION Overall, FIB-4, APRI, and NFS showed similar performances with higher accuracy, specificity, and NPV. Sensitivity and PPV were low. These tests are more useful at excluding advanced fibrosis.
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Li M, Zhao Z, Qin G, Chen L, Lu J, Huo Y, Chen L, Zeng T, Xu M, Chen Y, Wang T, Wang S, Xu Y, Shi L, Tang X, Su Q, Yu X, Yan L, Wan Q, Chen G, Gao Z, Wang G, Shen F, Luo Z, Zhang Y, Liu C, Wang Y, Hu R, Ye Z, Wu S, Deng H, Yang T, Li Q, Qin Y, Mu Y, Zhao J, Ning G, Bi Y, Xu Y, Wang W. Non-alcoholic fatty liver disease, metabolic goal achievement with incident cardiovascular disease and eGFR-based chronic kidney disease in patients with prediabetes and diabetes. Metabolism 2021; 124:154874. [PMID: 34517014 DOI: 10.1016/j.metabol.2021.154874] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 08/27/2021] [Accepted: 08/29/2021] [Indexed: 02/07/2023]
Abstract
AIMS/HYPOTHESIS We aimed to evaluate the effect of NAFLD on the risk of incident cardiovascular disease (CVD) and estimated glomerular filtration rate (eGFR)-based chronic kidney disease (CKD), and further test the joint effects and interactions between NAFLD status and individual metabolic element, as well as the total 'ABCs' metabolic goal achievement, on the CVD and CKD risk among 101,296 patients with prediabetes or diabetes from a prospective cohort study. METHODS We conducted the study based on the China Cardiometabolic Disease and Cancer Cohort (4C) study, a large-scale, population-based prospective cohort. After excluding alcohol abuse and other cause of hepatic diseases, we used fatty liver index (FLI) ≥ 60 as a proxy of NAFLD and stratified the probability of fibrosis by aspartate transaminase/alanine transaminase ratio (AAR) with cut-offs of 0.8 and 1.4. 'ABCs' metabolic goal was defined as subjects who had HbA1c < 6.5% (A), SBP/DBP < 130/80 mmHg (B), and LDL-C < 100 mg/dL (C). During 3.8 years follow-up, we validated 2340 CVD events based on medical records and identified 1943 participants developed CKD based on centrally tested eGFR. RESULTS The multivariable adjusted hazard ratios (HRs) were 1.15 (95% confidence interval (CI), 1.05-1.27) for CVD events and 1.33 (95% CI, 1.20-1.48) for CKD among NAFLD patients, compared with participants without NAFLD. Of NAFLD patients, relative to individuals with low AAR (<0.8), those with high AAR (≥1.4) were more likely to experience CVD events [1.62 (1.21-2.18)] and CKD [1.63 (1.17-2.28)]. Participants with NAFLD and comorbid poorly controlled metabolic risk factors had higher risk of CVD events or CKD than having either alone, with a significant interaction between poor glycemic control and NAFLD on the risk of vascular complications. CONCLUSIONS NAFLD was associated with incident CVD and CKD among patients with prediabetes or diabetes. Such associations were substantially modified by the comprehensive achievement of metabolic goal.
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Affiliation(s)
- Mian Li
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the People's Republic of China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
| | - Zhiyun Zhao
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the People's Republic of China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
| | - Guijun Qin
- The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Li Chen
- Qilu Hospital of Shandong University, Jinan, China
| | - Jieli Lu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the People's Republic of China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
| | - Yanan Huo
- Jiangxi Provincial People's Hospital Affiliated to Nanchang University, Nanchang, China
| | - Lulu Chen
- Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tianshu Zeng
- Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Min Xu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the People's Republic of China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
| | - Yuhong Chen
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the People's Republic of China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
| | - Tiange Wang
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the People's Republic of China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
| | - Shuangyuan Wang
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the People's Republic of China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
| | - Yiping Xu
- Clinical Trials Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Lixin Shi
- Affiliated Hospital of Guiyang Medical College, Guiyang, China
| | - Xulei Tang
- The First Hospital of Lanzhou University, Lanzhou, China
| | - Qing Su
- Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Xuefeng Yu
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Li Yan
- Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Qin Wan
- The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Gang Chen
- Fujian Provincial Hospital, Fujian Medical University, Fuzhou, China
| | - Zhengnan Gao
- Dalian Municipal Central Hospital, Dalian, China
| | - Guixia Wang
- The First Hospital of Jilin University, Changchun, China
| | - Feixia Shen
- The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Zuojie Luo
- The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Yinfei Zhang
- Central Hospital of Shanghai Jiading District, Shanghai, China
| | - Chao Liu
- Jiangsu Province Hospital on Integration of Chinese and Western Medicine, Nanjing, China
| | - Youmin Wang
- The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Ruying Hu
- Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China
| | - Zhen Ye
- Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China
| | - Shengli Wu
- Karamay Municipal People's Hospital, Xinjiang, China
| | - Huacong Deng
- The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Tao Yang
- The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Qiang Li
- The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Yingfen Qin
- The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Yiming Mu
- Chinese People's Liberation Army General Hospital, Beijing, China
| | - Jiajun Zhao
- Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
| | - Guang Ning
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the People's Republic of China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
| | - Yufang Bi
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the People's Republic of China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
| | - Yu Xu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the People's Republic of China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
| | - Weiqing Wang
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the People's Republic of China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
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Mohamed AA, El-Demery A, Al-Hussain E, Mousa S, Halim AA, Mostafa SM, Abdelghany RS, Mahmoud SM, Elkady MA, Raafat K, Hassnine AA, Omran MM. NAFLD mark: an accurate model based on microRNA-34 for diagnosis of non-alcoholic fatty liver disease patients. J Genet Eng Biotechnol 2021; 19:157. [PMID: 34661762 PMCID: PMC8523615 DOI: 10.1186/s43141-021-00257-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Accepted: 09/28/2021] [Indexed: 11/10/2022]
Abstract
BACKGROUND It remains essential for non-alcoholic fatty liver (NAFLD) patients, to develop a sensitive and specific diagnostic model. Data regarding the use of micro (mi)RNA-34 for NAFLD diagnosis are few. Routine clinical assessment, laboratory tests were done for Egyptian individuals (n = 314) were included (100 healthy individuals and 214 NAFLD patients). Quantification of miRNA-34 was done using real-time PCR. Extremely significant variables were entered into stepwise logistic regression. The diagnostic power of variables was estimated by the area under the ROC (AUC). RESULTS MiRNA-34 levels were higher in NAFLD patients than healthy individuals with a significant difference (P< 0.0001). The multivariate analysis was used to evaluate the NAFLD-associated variables (CRP, cholesterol, body mass index (BMI), ALT had p< 0.0001 while mRNA-34 had (p=0.0004). The AUCs (CI) of candidate NAFLD markers were in the order of miRNA-34 0.72 (0.66-0.77) < ALT 0.73 (0.67-0.79) < BMI 0.81 (0.76-0.86) < cholesterol < 0.85 (0.79-0.90) < CRP 0.88 (0.84-0.92). We developed a novel index for discriminating patients with NAFLD named NAFLD Mark. AUC was jumped to 0.98 (0.93-0.99) when five markers were combined. The AUC of NAFLD mark for NAFLD detection was higher than the AUCs of seven common NAFLD indexes (0.44-0.86). CONCLUSIONS The NAFLD mark is a non-invasive and highly sensitive and specific model for NAFLD diagnosis.
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Affiliation(s)
- Amal A Mohamed
- Biochemistry Department, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Ahmed El-Demery
- Biochemistry Department, Faculty of Medicine, October 6 University, 6th of October City, Egypt
| | - Eman Al-Hussain
- Clinical and Chemical Pathology, Faculty of Medicine, Cairo university, Giza, Egypt
| | - Shroouk Mousa
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed Abdel Halim
- Tropical Department, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Sahar M Mostafa
- Tropical Department, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Reda S Abdelghany
- Tropical Medicine Department, Ahmed Maher Teaching Hospital, Cairo, Egypt
| | - Seham M Mahmoud
- Tropical Department, El-Sahel Teaching Hospital, Cairo, Egypt
| | - Mohammad A Elkady
- Theodor Bilharz Research Institute Gastroenterology and Hepatology department, Cairo, Egypt
| | - Khaled Raafat
- Gastroenterology and Hepatology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Alshymaa A Hassnine
- Department of Gastroenterology and Tropical Medicine, Faculty of Medicine, Minia University, Minia, Egypt
| | - Mohamed M Omran
- Chemistry Department, Faculty of Science, Helwan University, Ain Helwan, Cairo, 11795, Egypt.
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Seen TK, Sayed M, Bilal M, Reyes JV, Bhandari P, Lourdusamy V, Al-khazraji A, Syed U, Sattar Y, Bansal R. Clinical indicators for progression of nonalcoholic steatohepatitis to cirrhosis. World J Gastroenterol 2021; 27:3238-3248. [PMID: 34163108 PMCID: PMC8218360 DOI: 10.3748/wjg.v27.i23.3238] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2020] [Revised: 12/06/2020] [Accepted: 04/20/2021] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD), is a disease spectrum characterized by fat accumulation in hepatocytes presenting as hepatic steatosis to advance disease with active hepatic inflammation, known as nonalcoholic steatohepatitis. Chronic steatohepatitis will lead to progressive hepatic fibrosis causing cirrhosis and increased risk for developing hepatocellular carcinoma (HCC). Fatty liver disease prevalence has increased at alarming rates alongside obesity, diabetes and metabolic syndrome to become the second most common cause of cirrhosis after alcohol related liver disease worldwide. Given this rise in prevalence, it is becoming increasingly more important to find non-invasive methods to diagnose disease early and stage hepatic fibrosis. Providing clinicians with the tools to diagnose and treat the full spectrum of NAFLD will help prevent known complications such as cirrhosis and HCC and improve quality of life for the patients suffering from this disease. This article discusses the utility of current non-invasive liver function testing in the clinical progression of fatty liver disease along with the imaging modalities that are available. Additionally, we summarize available treatment options including targeted medical therapy through four different pathways, surgical or endoscopic intervention.
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Affiliation(s)
- Tasur Kumar Seen
- Division of Internal Medicine, Icahn School of Medicine, Elmhurst Hospital and Mount Sinai Hospital, Elmhurst, NY 11375, United States
| | - Muntazir Sayed
- Division of Internal Medicine, R.C.S.M. Government College, Mahrashta 416013, India
| | - Muhammad Bilal
- Division of Gastroenterology, Hepatology and Endoscopy, Pakistan Institute of Medical Sciences, Islamabad 45710, Pakistan
| | - Jonathan Vincent Reyes
- Division of Internal Medicine, Icahn School of Medicine, Elmhurst Hospital and Mount Sinai Hospital, Elmhurst, NY 11375, United States
| | - Priyanka Bhandari
- Division of Internal Medicine, Icahn School of Medicine, Elmhurst Hospital and Mount Sinai Hospital, Elmhurst, NY 11375, United States
| | - Vennis Lourdusamy
- Division of Gastroenterology, Icahn School of Medicine, Elmhurst Hospital and Mount Sinai Hospital, Elmhurst, NY 11375, United States
| | - Ahmed Al-khazraji
- Division of Gastroenterology, Icahn School of Medicine, Elmhurst Hospital and Mount Sinai Hospital, Elmhurst, NY 11375, United States
| | - Umer Syed
- Division of Gastroenterology, Icahn School of Medicine, Elmhurst Hospital and Mount Sinai Hospital, Elmhurst, NY 11375, United States
| | - Yasar Sattar
- Division of Internal Medicine, Icahn School of Medicine, Elmhurst Hospital and Mount Sinai Hospital, Elmhurst, NY 11375, United States
| | - Raghav Bansal
- Division of Gastroenterology, Icahn School of Medicine, Elmhurst Hospital, Elmhurst, NY 11375, United States
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9
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Abstract
BACKGROUND AND OBJECTIVES Little is known regarding the diagnostic performance of fibrosis scoring systems in the diagnosis of nonalcoholic fatty liver disease (NAFLD). We aimed to determine the risk factors of NAFLD and evaluate the diagnostic performance of noninvasive fibrosis scoring systems. MATERIALS AND METHODS The study included consecutive patients presented with dyspepsia from January 2017 to January 2019. Clinicodemographic and laboratory parameters including HOMA-IR were recorded. Anthropometric measurements were performed. NAFLD was diagnosed with ultrasonography. The FIB4, NAFLD, BARD, and Nippon scores were calculated. RESULTS Totally, 1008 patients were enrolled. The mean age was 52.3 ± 15 years in the NAFLD group (25.8%) and 36.7 ± 15.7 years in the non-NAFLD group (74.2%). The frequency of NAFLD was 25.8%. Age, body mass index (BMI), diabetes mellitus (DM), platelet count, HbA1c, HDL, ALT, and AST/ALT ratio were independent risk factors for NAFLD. The most sensitive and specific tests in diagnosing NAFLD were HOMA-IR and Nippon score, respectively. CONCLUSIONS Age, BMI, DM, HbA1c, platelet count, HDL, ALT, and AST/ALT ratio were independent predictors of NAFLD. The most specific and sensitive predictors of the presence of NAFLD were Nippon score and HOMA-IR value, respectively. The place of fibrosis scores in the diagnosis of NAFLD patients requires further scrutinization.
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Affiliation(s)
- Muharrem Bayrak
- Department of Internal Medicine, University of Health Sciences, Erzurum Regional Training and Research Hospital, Erzurum, Turkey
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10
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Zhong HJ, Xiao P, Lin D, Zhou HM, He XX. Cirrhosis in Wilson Disease is characterized by Impaired Hepatic Synthesis, Leukopenia and Thrombocytopenia. Int J Med Sci 2020; 17:1345-1350. [PMID: 32624691 PMCID: PMC7330668 DOI: 10.7150/ijms.44338] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2020] [Accepted: 05/21/2020] [Indexed: 12/12/2022] Open
Abstract
Background: Patients with Wilson disease (WD) progress to cirrhosis at an early age but have good prognoses. This study aimed to delineate hepatic features in WD patients with or without cirrhosis. Methods: Medical data were retrospectively collected from 27 July 2015 to 27 June 2018. WD patients were divided into two groups based on whether or not they progressed to cirrhosis. Liver function, portal hypertension features and hematocytopenia rates were compared between groups. Results: The study enrolled 119 WD patients with cirrhosis and 53 WD patients without cirrhosis. There were no differences between groups for liver enzyme levels or incidence rates of Kayser-Fleischer ring (all P > 0.05). Ascites and hepatic encephalopathy were nearly absent in both groups, and almost all patients were Child-Pugh group A. However, WD-associated cirrhotic patients had a higher prothrombin time (beta = 0.908, P = 0.004) and international normalized ratio (beta = 0.089, P = 0.040), wider portal vein diameter (beta = 1.330, P < 0.001), and an increased risk of splenomegaly/splenectomy (odds ratio [OR] = 4.36, 95% confidence interval [CI]: 2.15-8.84, P < 0.001). Moreover, WD-associated cirrhotic patients have significantly increased risks of leukopenia (OR = 2.30, 95% CI: 1.00-5.25, P = 0.049) and thrombocytopenia (OR = 6.89, 95% CI: 2.01-23.59, P = 0.002). Conclusions: Despite presenting good outcomes, mild hepatocyte injury, and good hepatic metabolic function, WD-associated cirrhotic patients show more serious impairment of hepatic synthetic function, wider portal vein diameter, and higher risk of splenomegaly due to portal hypertension.
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Affiliation(s)
- Hao-Jie Zhong
- Guangdong Medical University, Zhanjiang, China
- Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
- ✉ Corresponding authors: Hao-Jie Zhong. Guangdong Medical University, No. 2 Wenmingdong Road, Zhanjiang, China, E-mail address: ; Xing-Xiang He. Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University; No.19 Nonglinxia Road, Yuexiu District, Guangzhou, Guangdong, China, E-mail address:
| | - Ping Xiao
- Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Da Lin
- Department of Gastroenterology, Jieyang People's Hospital, Jieyang, China
| | - Hui-Min Zhou
- Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Xing-Xiang He
- Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
- ✉ Corresponding authors: Hao-Jie Zhong. Guangdong Medical University, No. 2 Wenmingdong Road, Zhanjiang, China, E-mail address: ; Xing-Xiang He. Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University; No.19 Nonglinxia Road, Yuexiu District, Guangzhou, Guangdong, China, E-mail address:
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11
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Poynard T, Munteanu M, Charlotte F, Perazzo H, Ngo Y, Deckmyn O, Pais R, Mathurin P, Ratziu V. Impact of steatosis and inflammation definitions on the performance of NASH tests. Eur J Gastroenterol Hepatol 2018; 30:384-391. [PMID: 29280921 PMCID: PMC5865485 DOI: 10.1097/meg.0000000000001033] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2017] [Accepted: 11/08/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM One of the unmet needs in subjects with metabolic risks is the prediction of metabolic liver disease by noninvasive tests. The construction of performant tests is dependent on the appropriateness of the histological reference definition. The aim of this study was to analyze the limitations of similar European (Fatty Liver Inhibition of Progression) and USA (Clinical-Research-Network) standard definitions and their impact on the construction of tests. METHODS We hypothesized that a simpler histological definition of non-alcoholo steato-hepatitis (NASH), which does not require the presence of steatosis and the presence of both lobular inflammation and ballooning, should improve the concordance rates with previously validated blood tests. We reviewed the landmark studies in metabolic liver disease, sources of the standard definitions, and we compared the adequacy of these standards to other possible definitions in 1081 subjects with biopsies, by concordance and accuracy rates. RESULTS The limitations of standard definitions included the presence of appropriate controls in only 6.6% of landmark studies, an arbitrary definition of steatosis and NASH covering only four (15%) out of 27 possible combinations of features, compared with 18 (67%) for a simplified NASH definition, which did not require steatosis. A total of 39/1081 (3.6%) cases were not identified by standard definition, but were identified by the simplified definition as significant active disease, including 15 cases with significant fibrosis. The simplified definition increased the κ concordance (P<0.0001) between test prediction and histological reference. CONCLUSION A simplified definition of NASH could help in the construction of biomarkers with higher performances.
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Affiliation(s)
- Thierry Poynard
- Groupe Hospitalier Pitié Salpêtrière APHP, Sorbonne Universités, UPMC Univ Paris 06, UMR_S 938
- Institute of Cardiometabolism and Nutrition (ICAN)
- INSERM
| | | | - Frederic Charlotte
- Groupe Hospitalier Pitié Salpêtrière APHP, Sorbonne Universités, UPMC Univ Paris 06, UMR_S 938
- Institute of Cardiometabolism and Nutrition (ICAN)
| | - Hugo Perazzo
- Groupe Hospitalier Pitié Salpêtrière APHP, Sorbonne Universités, UPMC Univ Paris 06, UMR_S 938
- Institute of Cardiometabolism and Nutrition (ICAN)
- INSERM
| | | | | | - Raluca Pais
- Groupe Hospitalier Pitié Salpêtrière APHP, Sorbonne Universités, UPMC Univ Paris 06, UMR_S 938
- Institute of Cardiometabolism and Nutrition (ICAN)
- INSERM
| | - Philippe Mathurin
- Service Maladie de l’Appareil Digestif, Hôpital Huriez, CHRU Lille, Lille, France
| | - Vlad Ratziu
- Groupe Hospitalier Pitié Salpêtrière APHP, Sorbonne Universités, UPMC Univ Paris 06, UMR_S 938
- Institute of Cardiometabolism and Nutrition (ICAN)
- INSERM
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12
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Harrison E, Chang M, Hao Y, Flower A. Using machine learning to predict near-term mortality in cirrhosis patients hospitalized at the University of Virginia health system. 2018 SYSTEMS AND INFORMATION ENGINEERING DESIGN SYMPOSIUM (SIEDS) 2018:112-117. [DOI: 10.1109/sieds.2018.8374719] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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13
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Yoneda M, Imajo K, Takahashi H, Ogawa Y, Eguchi Y, Sumida Y, Yoneda M, Kawanaka M, Saito S, Tokushige K, Nakajima A. Clinical strategy of diagnosing and following patients with nonalcoholic fatty liver disease based on invasive and noninvasive methods. J Gastroenterol 2018; 53:181-196. [PMID: 29177681 PMCID: PMC5846871 DOI: 10.1007/s00535-017-1414-2] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2017] [Accepted: 11/13/2017] [Indexed: 02/04/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is an important cause of chronic liver injury in many countries. The incidence of NAFLD is rising rapidly in both adults and children, because of the currently ongoing epidemics of obesity and type 2 diabetes. Notably, histological liver fibrosis is recognized as the main predictive factor for the overall long-term outcome of NAFLD, including cardiovascular disease and liver-related mortality. Thus, staging of liver fibrosis is essential in determining the prognosis and optimal treatment for patients with NAFLD and in guiding surveillance for the development of hepatocellular carcinoma (HCC). Whereas liver biopsy remains the gold standard for staging liver fibrosis, it is impossible to enforce liver biopsy in all patients with NAFLD. Noninvasive biological markers, scoring systems and noninvasive modalities are increasingly being developed and investigated to evaluate fibrosis stage of NAFLD patients. This review will highlight recent studies on the diagnosis and staging of NAFLD based on invasive (liver biopsy) or noninvasive (biomarker, scoring systems, US-based elastography and MR elastography) methods.
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Affiliation(s)
- Masato Yoneda
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
| | - Kento Imajo
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
| | - Hirokazu Takahashi
- Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan
| | - Yuji Ogawa
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
| | - Yuichiro Eguchi
- Liver Center, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan
| | - Yoshio Sumida
- Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan
| | - Masashi Yoneda
- Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan
| | - Miwa Kawanaka
- General Internal Medicine 2, General Medical Center, Kawasaki Medical School, 2-6-1 Nakasange, Kutaku, Okayama, 700-8505, Japan
| | - Satoru Saito
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
| | - Katsutoshi Tokushige
- Department of Internal Medicine and Gastroenterology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan
| | - Atsushi Nakajima
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
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14
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Okajima A, Sumida Y, Taketani H, Hara T, Seko Y, Ishiba H, Nishimura T, Umemura A, Nishikawa T, Yamaguchi K, Moriguchi M, Mitsuyoshi H, Yasui K, Minami M, Itoh Y. Liver stiffness measurement to platelet ratio index predicts the stage of liver fibrosis in non-alcoholic fatty liver disease. Hepatol Res 2017; 47:721-730. [PMID: 27539017 DOI: 10.1111/hepr.12793] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2016] [Revised: 08/08/2016] [Accepted: 08/10/2016] [Indexed: 12/18/2022]
Abstract
AIM Platelet count and liver stiffness measurement (LSM) using transient elastography could identify significant fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). We constructed a novel index combining LSM with platelet count for staging fibrosis in Japanese patients with NAFLD. METHODS We recruited 173 Japanese patients with liver biopsy-proven NAFLD. The areas under the receiver operating characteristic curves were calculated and compared with established parameters and scoring systems for staging liver fibrosis. RESULTS After excluding 10 patients in whom LSM failed, 163 patients with NAFLD were enrolled. The areas under the receiver operating characteristic curves of the LSM/platelet ratio (LPR) index for detecting fibrosis ≥stage 1, ≥stage 2, and ≥stage 3 were the greatest (0.835, 0.913, and 0.936, respectively) compared with those for various other parameters and established scoring systems, such as LSM, type IV collagen 7 s domain, platelet count, NAFIC score, fibrosis-4 index, NAFLD fibrosis score, aspartate aminotransferase/alanine aminotransferase ratio, and aspartate aminotransferase to platelet ratio index. The optimal cut-off, positive predictive, and negative predictive values of the LPR index for detecting ≥stage 3 fibrosis were 0.60, 48.9%, and 99.2%, whereas those of LSM were 10.0 kPa, 35.0%, and 99.0%, respectively. The novel LPR index helps avoid biopsies in a larger percentage of patients with NAFLD compared with that LSM alone. CONCLUSIONS The LPR index was the best predictor for staging fibrosis in patients with NAFLD. It represents a simple and non-invasive alternative to liver biopsy in clinical practice.
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Affiliation(s)
- Akira Okajima
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yoshio Sumida
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Hiroyoshi Taketani
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Tasuku Hara
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yuya Seko
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Hiroshi Ishiba
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Takeshi Nishimura
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Atsushi Umemura
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Taichiro Nishikawa
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Kanji Yamaguchi
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Michihisa Moriguchi
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Hironori Mitsuyoshi
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Kohichiroh Yasui
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Masahito Minami
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yoshito Itoh
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
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15
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Akuta N, Kawamura Y, Arase Y, Suzuki F, Sezaki H, Hosaka T, Kobayashi M, Kobayashi M, Saitoh S, Suzuki Y, Ikeda K, Kumada H. Relationships between Genetic Variations of PNPLA3, TM6SF2 and Histological Features of Nonalcoholic Fatty Liver Disease in Japan. Gut Liver 2017; 10:437-45. [PMID: 26610348 PMCID: PMC4849698 DOI: 10.5009/gnl15163] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Background/Aims It is important to determine the noninvasive parameters of histological features in nonalcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the value of genetic variations as surrogate markers of histological features. Methods The parameters that affected the histological features of NAFLD were investigated in 211 Japanese patients with biopsy-proven NAFLD. The relationships between genetic variations in PNPLA3 rs738409 or TM6SF2 rs58542926 and histological features were analyzed. Furthermore, the impact of genetic variations that affected the pathological criteria for the diagnosis of nonalcoholic steatohepatitis (NASH) (Matteoni classification and NAFLD activity score) was evaluated. Results The fibrosis stage of PNPLA3 GG was significantly more progressive than that of CG by multiple comparisons. Multivariate analysis identified PNPLA3 genotypes as predictors of fibrosis of stage 2 or more, but the impact tended to decrease at stage 3 or greater. There were no significant differences among the histological features of the three genotypes of TM6SF2. PNPLA3 genotypes partly affected the definition of NASH by the NAFLD activity score, but TM6SF2 genotypes did not affect the definition of NASH. Conclusions In Japanese patients with biopsy-proven NAFLD, PNPLA3 genotypes may partly affect histological features, including stage of fibrosis, but the TM6SF2 genotype does not affect histological features.
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Affiliation(s)
- Norio Akuta
- Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | - Yusuke Kawamura
- Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | - Yasuji Arase
- Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | - Fumitaka Suzuki
- Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | - Hitomi Sezaki
- Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | - Tetsuya Hosaka
- Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | - Masahiro Kobayashi
- Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | | | - Satoshi Saitoh
- Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | - Yoshiyuki Suzuki
- Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | - Kenji Ikeda
- Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | - Hiromitsu Kumada
- Department of Hepatology, Toranomon Hospital, and Okinaka Memorial Institute for Medical Research, Tokyo, Japan
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16
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Mizuno M, Shima T, Oya H, Mitsumoto Y, Mizuno C, Isoda S, Kuramoto M, Taniguchi M, Noda M, Sakai K, Koyama N, Okanoue T. Classification of patients with non-alcoholic fatty liver disease using rapid immunoassay of serum type IV collagen compared with liver histology and other fibrosis markers. Hepatol Res 2017; 47:216-225. [PMID: 26997642 DOI: 10.1111/hepr.12710] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2016] [Revised: 03/11/2016] [Accepted: 03/15/2016] [Indexed: 12/12/2022]
Abstract
AIM Non-alcoholic fatty liver disease (NAFLD) can progress to non-alcoholic fatty liver (NAFL) or non-alcoholic steatohepatitis (NASH). We investigated the association among serum type IV collagen level, liver histology, and other fibrosis markers in NAFLD progression. METHODS We evaluated 184 patients diagnosed with NAFLD following biopsy, including 89 males and 95 females with an average age of 52.6 and 62.6 years, respectively. Non-alcoholic fatty liver disease was classified as NAFL or NASH using Matteoni's classification, and the grade and stage of NASH were assessed using Brunt's classification. Serum type IV collagen was measured by a rapid and sensitive latex particle-enhanced turbidimetric immunoassay. RESULTS Forty-two patients with NAFL and 142 patients with NASH were included in this study. Compared with patients with NAFL, patients with NASH showed more significant liver function disorder and increased expression of fibrosis markers including type IV collagen, collagen 7S, Mac2-binding protein (M2BP), and hyaluronic acid (HA). Expression of type IV collagen and collagen 7S, but not M2BP and HA, was more significantly elevated in patients with stage 1 NASH than in patients with NAFL, indicating that type IV collagen and collagen 7S may be better discriminators of NASH and NAFL than M2BP and HA at an early stage of fibrosis. When patients were stratified by NAFLD activity score, type IV collagen and collagen 7S were significantly elevated as NAFLD activity score progressed, whereas M2BP and HA expression were not significantly elevated. CONCLUSION Type IV collagen may be a useful measure of NASH severity as latex particle-enhanced turbidimetric immunoassay-based rapid type IV collagen assay can be carried out routinely.
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Affiliation(s)
- Masayuki Mizuno
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Osaka, Japan
| | - Toshihide Shima
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Osaka, Japan
| | - Hirohisa Oya
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Osaka, Japan
| | - Yasuhide Mitsumoto
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Osaka, Japan
| | - Chiemi Mizuno
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Osaka, Japan
| | - Satoshi Isoda
- Department of Clinical Laboratory, Saiseikai Suita Hospital, Osaka, Japan
| | - Mizue Kuramoto
- Department of Clinical Laboratory, Saiseikai Suita Hospital, Osaka, Japan
| | - Masanori Taniguchi
- Department of Clinical Laboratory, Saiseikai Suita Hospital, Osaka, Japan
| | - Masashi Noda
- Department of Clinical Laboratory, Saiseikai Suita Hospital, Osaka, Japan
| | - Kyoko Sakai
- Department of Clinical Laboratory, Saiseikai Suita Hospital, Osaka, Japan
| | | | - Takeshi Okanoue
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Osaka, Japan
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17
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Yu SM, Ki SH, Baek HM. Nonalcoholic Fatty Liver Disease: Correlation of the Liver Parenchyma Fatty Acid with Intravoxel Incoherent Motion MR Imaging-An Experimental Study in a Rat Model. PLoS One 2015; 10:e0139874. [PMID: 26460614 PMCID: PMC4603664 DOI: 10.1371/journal.pone.0139874] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2015] [Accepted: 08/31/2015] [Indexed: 02/07/2023] Open
Abstract
Purpose To prospectively evaluate the changes in fatty acid concentration after administrating a 60% high-fat diet to a non-alcoholic fatty liver disease rat model and to perform a correlation analysis between fatty acid with molecular diffusion (Dtrue), perfusion-related diffusion (Dfast), and perfusion fraction (Pfraction). Material and Methods This prospective study was approved by the appropriate ethics committee. Ten male Sprague-Dawley rats were fed a 60% high-fat diet until the study was finished. Point-resolved spectroscopy sequence 1H-MRS with TR = 1,500 msec, TE = 35 msec, NEX = 64, and 8×8×8 mm3 voxel was used to acquire magnetic resonance spectroscopy (MRS) data. Diffusion-weighted imaging was performed on a two-dimensional multi-b value spin echo planar image with the following parameters: repetition time msec/echo time msec, 4500 /63; field of view, 120×120 msec2; matrix, 128×128; section thickness, 3 mm; number of repetition, 8; and multiple b value, 0, 25, 50, 75, 100, 200, 500, 1000 sec/mm2. Baseline magnetic resonance imaging and magnetic resonance spectroscopy data (control) were acquired. 1H proton MRS and diffusion-weighted imaging were obtained every 2 weeks for 8 weeks. The individual contributions of the true molecular diffusion and the incoherent motions of water molecules in the capillary network to the apparent diffusion changes were estimated using a least-square nonlinear fitting in MatLab. A Wilcoxon signed-rank test with the Kruskal-Wallis test was used to compare each week’s fatty acid mean quantification. Spearman’s correlation coefficient was used to evaluate the correlation between each fatty acid (e.g., total lipid (TL), total saturated fatty acid (TSFA), total unsaturated fatty acid (TUSFA), total unsaturated bond (TUSB), and polyunsaturated bond (PUSB)) and intravoxel incoherent motion (IVIM) mapping images (e.g., Dtrue, Dfast, and Pfraction). Results The highest mean TL value was at week 8 (0.278 ± 0.10) after the administration of the 60% high-fat diet, followed by weeks 6, 4, 2, and 0. The concentration level (16.99±2.29) of TSFA at week 4 was the highest. No significant differences in the concentrations of TUSFA, TUSB, or PUSB were observed in different weeks. Conclusion After the administration of the 60% high-fat diet in nonalcoholic fatty liver disease model, TL and TSFA depositions had significant changes. The mean concentrations of TUSFA, TUSB, PUSB did not significantly change. Total unsaturated fatty acid and polyunsaturated bond showed positive correlations with Dtrue and Pfraction.
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Affiliation(s)
- Seung-Man Yu
- Department of Biomedical Engineering, Research Institute of Biomedical Engineering, College of Medicine, The Catholic University of Korea, Seoul, Korea; Department of Radiological Science, Gimcheon University, Gimcheon, Gyeongsangbuk-do, Korea
| | - Sung Hwan Ki
- Department of Toxicology, College of pharmacy, Chosun University, Gwangju, Korea
| | - Hyeon-Man Baek
- Korea Basic Science Institute, Yeongudanji-Ro, Ochang-eup, Cheongwon-gun, Chungbuk, Korea
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Pang Q, Qu K, Bi JB, Liu SS, Zhang JY, Song SD, Lin T, Xu XS, Wan Y, Tai MH, Liu HC, Dong YF, Liu C. Thrombocytopenia for prediction of hepatocellular carcinoma recurrence: Systematic review and meta-analysis. World J Gastroenterol 2015; 21:7895-7906. [PMID: 26167090 PMCID: PMC4491977 DOI: 10.3748/wjg.v21.i25.7895] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2015] [Revised: 03/01/2015] [Accepted: 04/03/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the association between thrombocytopenia and relapse after treatment for hepatocellular carcinoma (HCC).
METHODS: We searched the PubMed, EMBASE, and Web of Science databases to obtain eligible studies. The hazard ratios (HRs) values and 95% confidence intervals (CIs) were pooled by random effects model. Subsequently, we estimated the heterogeneity, performed a sensitivity analysis, determined the publication bias, and performed subgroup and meta-regression analyses. Study quality was assessed by using the Oxford Center for Evidence Based Medicine tool.
RESULTS: We identified 18 eligible studies by retrieval (published during 2000-2014). Out of the 4163 patients with HCC who were recruited, 2746 (66.0%) experienced recurrence. In general, our meta-analysis suggested that low platelet count (PLT) before therapy significantly increased the probability of postoperative recurrence (HR = 1.53, 95%CI: 1.29-1.81). PLT was also valuable in the prediction of intrahepatic distant recurrence (HR = 1.49, 95%CI: 1.25-1.77). Subgroup and meta-regression analyses identified various therapeutic modalities as the source of a high degree of heterogeneity. The pooled HR values showed no obvious change when a single study was removed, but otherwise, an opposite-effects model was used. In addition, no significant publication bias was detected.
CONCLUSION: Thrombocytopenia before treatment might be an inexpensive and useful predictor of postoperative recurrence in patients with HCC.
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Insulin resistance correlated with the severity of liver histology in Japanese NAFLD patients: a multicenter retrospective study. J Clin Gastroenterol 2015; 49:169-70. [PMID: 25014241 DOI: 10.1097/mcg.0000000000000186] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
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