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Souza M, Al-Sharif L, Khalil SM, Villela-Nogueira CA, Mantovani A. Global Epidemiology and Characteristics of Metabolic Dysfunction-associated Steatotic Liver Disease in Type 1 Diabetes Mellitus: An Updated Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2024:S1542-3565(24)01066-8. [PMID: 39672250 DOI: 10.1016/j.cgh.2024.09.038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Revised: 09/09/2024] [Accepted: 09/10/2024] [Indexed: 12/15/2024]
Abstract
BACKGROUND & AIMS Metabolic dysfunction-associated steatotic liver disease (MASLD) is often overlooked in patients with type 1 diabetes mellitus (T1DM). Our study aims to provide a comprehensive overview of the burden of MASLD in T1DM by assessing the prevalence of MASLD and its advanced forms in individuals with T1DM. METHODS We systematically searched PubMed and Embase databases (from inception to May 5, 2024) for original articles on the prevalence or characteristics of MASLD (as detected by blood biomarkers/scores, imaging techniques, or liver biopsy) in adults with T1DM. Data were extracted, and we performed a meta-analysis of proportions using generalized linear mixed model, and pairwise meta-analysis using the DerSimonian-Laird method. Heterogeneity was investigated with further subgroup and meta-regression analyses, and publication bias was assessed. RESULTS We identified 23 studies for a total of 13,006 individuals with T1DM. Of these, 22.24% (95% confidence interval [CI], 15.62-30.66; I2 = 99.2%) had MASLD. Significant fibrosis (≥F2) and advanced fibrosis (≥F3) were found in 13.25% (95% CI, 11.15-15.67; I2 = 0%) and 5.12% (95% CI, 3.78-6.91; I2 = 0%) of patients with T1DM and MASLD, respectively. Patients with MASLD and T1DM were more likely to be older, overweight, male, have a longer duration of diabetes, require higher daily doses of insulin, have metabolic dysfunction, and were at a higher risk of microvascular complications. CONCLUSION MASLD is relatively common in T1DM. Patients with MASLD-T1DM have a distinct clinical profile compared with those with T1DM, with only a small proportion having significant or advanced fibrosis.
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Affiliation(s)
- Matheus Souza
- Department of Internal Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
| | - Lubna Al-Sharif
- Faculty of Medicine and Health Sciences, Department of Biomedical Sciences and Basic Clinical Skills, An-Najah National University, Nablus, Palestine
| | | | | | - Alessandro Mantovani
- Section of Endocrinology, Diabetes and Metabolism, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
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Mobasheri L, Ahadi M, Beheshti Namdar A, Alavi MS, Bemidinezhad A, Moshirian Farahi SM, Esmaeilizadeh M, Nikpasand N, Einafshar E, Ghorbani A. Pathophysiology of diabetic hepatopathy and molecular mechanisms underlying the hepatoprotective effects of phytochemicals. Biomed Pharmacother 2023; 167:115502. [PMID: 37734266 DOI: 10.1016/j.biopha.2023.115502] [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: 07/01/2023] [Revised: 09/05/2023] [Accepted: 09/12/2023] [Indexed: 09/23/2023] Open
Abstract
Patients with diabetes are at risk for liver disorders including glycogen hepatopathy, non-alcoholic fatty liver disease, cirrhosis, and hepatic fibrosis. The pathophysiological mechanisms behind diabetic hepatopathy are complex, some of them include fatty acid accumulation, increased reactive oxygen species, increased advanced glycation end-products, hyperactivity of polyol pathways, increased apoptosis and necrosis, and promotion of fibrosis. A growing number of studies have shown that herbal extracts and their active phytochemicals have antihyperglycemic properties and beneficial effects on diabetic complications. The current review, for the first time, focused on herbal agents that showed beneficial effects on diabetic hepatopathy. For example, animal studies have shown that Moringa oleifera and Morus alba improve liver function in both type-1 and type-2 diabetes. Also, evidence from clinical trials suggests that Boswellia serrata, Juglans regia, Melissa officinalis, Portulaca oleracea, Silybum marianum, Talapotaka Churna, and Urtica dioica reduce serum liver enzymes in diabetic patients. The main active ingredient of these plants to protect the liver seems to be phenolic compounds such as niazirin, chlorogenic acid, resveratrol, etc. Mechanisms responsible for the hepatoprotective activity of herbal agents include improving glucose metabolism, restoring adipokines levels, antioxidant defense, and anti-inflammatory activity. Several signaling pathways are involved in hepatoprotective effects of herbal agents in diabetes, such as phosphoinositide 3-kinase, adenosine monophosphate-activated protein kinase, mitogen-activated protein kinase, and c-Jun NH2-terminal kinase.
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Affiliation(s)
- Leila Mobasheri
- Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mitra Ahadi
- Department of Gastroenterology and Hepatology, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ali Beheshti Namdar
- Department of Gastroenterology and Hepatology, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohaddeseh Sadat Alavi
- Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Abolfazl Bemidinezhad
- Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Mahdi Esmaeilizadeh
- Innovative Medical Research Center, Department of Basic Sciences, Faculty of Medicine, Mashhad Medical Sciences, Islamic Azad University, Mashhad, Iran
| | - Niloofar Nikpasand
- Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Elham Einafshar
- Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ahmad Ghorbani
- Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran.
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Mertens J, Weyler J, Dirinck E, Vonghia L, Kwanten WJ, Mortelmans L, Peleman C, Chotkoe S, Spinhoven M, Vanhevel F, Van Gaal LF, De Winter BY, De Block CE, Francque SM. Prevalence, risk factors and diagnostic accuracy of non-invasive tests for NAFLD in people with type 1 diabetes. JHEP Rep 2023; 5:100753. [PMID: 37274774 PMCID: PMC10232726 DOI: 10.1016/j.jhepr.2023.100753] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Revised: 03/16/2023] [Accepted: 03/30/2023] [Indexed: 06/07/2023] Open
Abstract
Background & Aims The epidemiology of non-alcoholic fatty liver disease (NAFLD) in people with type 1 diabetes (T1D) is not yet elucidated. This study aimed to assess the diagnostic accuracy of non-invasive tests for NAFLD, to investigate the prevalence and severity of NAFLD, and to search for factors contributing to NAFLD in people with T1D. Methods In this prospective cohort study, we consecutively screened 530 adults with T1D from a tertiary care hospital, using ultrasound (US), vibration-controlled transient elastography equipped with liver stiffness measurement (LSM) and controlled attenuation parameter, and the fatty liver index. Magnetic resonance spectroscopy (MRS) was performed in a representative subgroup of 132 individuals to validate the diagnostic accuracy of the non-invasive tests. Results Based on MRS as reference standard, US identified individuals with NAFLD with an AUROC of 0.98 (95% CI 0.95-1.00, sensitivity: 1.00, specificity: 0.96). The controlled attenuation parameter was also accurate with an AUROC of 0.85 (95% CI 0.77-0.93). Youden cut-off was ≥270 dB/m (sensitivity: 0.90, specificity: 0.74). The fatty liver index yielded a similar AUROC of 0.83 (95% CI 0.74-0.91), but the conventional cut-off used to rule in (≥60) had low sensitivity and specificity (0.62, 0.78). The prevalence of NAFLD in the overall cohort was 16.2% based on US. Metabolic syndrome was associated with NAFLD (OR: 2.35 [1.08-5.12], p = 0.031). The overall prevalence of LSM ≥8.0 kPa indicating significant fibrosis was 3.8%, but reached 13.2% in people with NAFLD. Conclusions NAFLD prevalence in individuals with T1D is 16.2%, with approximately one in 10 featuring elevated LSM. US-based screening could be considered in people with T1D and metabolic syndrome. Impact and Implications We aimed to report on the prevalence, disease severity, and risk factors of NAFLD in type 1 diabetes (T1D), while also tackling which non-invasive test for NAFLD is the most accurate. We found that ultrasound is the best test to diagnose NAFLD. NAFLD prevalence is 16.2%, and is associated with metabolic syndrome and BMI. Elevated liver stiffness indicating fibrosis is overall not prevalent in people with T1D (3.8%), but it reaches 13.2% in those with T1D and NAFLD.
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Affiliation(s)
- Jonathan Mertens
- Department of Endocrinology, Diabetology & Metabolism, Antwerp University Hospital, Antwerp, Belgium
- Laboratory of Experimental Medicine and Paediatrics and Member of the Infla-Med Centre of Excellence, University of Antwerp, Faculty of Medicine & Health Sciences, Antwerp, Belgium
- Department of Gastroenterology & Hepatology, Antwerp University Hospital, Antwerp, Belgium
| | - Jonas Weyler
- Laboratory of Experimental Medicine and Paediatrics and Member of the Infla-Med Centre of Excellence, University of Antwerp, Faculty of Medicine & Health Sciences, Antwerp, Belgium
- Department of Gastroenterology & Hepatology, Antwerp University Hospital, Antwerp, Belgium
| | - Eveline Dirinck
- Department of Endocrinology, Diabetology & Metabolism, Antwerp University Hospital, Antwerp, Belgium
- Laboratory of Experimental Medicine and Paediatrics and Member of the Infla-Med Centre of Excellence, University of Antwerp, Faculty of Medicine & Health Sciences, Antwerp, Belgium
| | - Luisa Vonghia
- Laboratory of Experimental Medicine and Paediatrics and Member of the Infla-Med Centre of Excellence, University of Antwerp, Faculty of Medicine & Health Sciences, Antwerp, Belgium
- Department of Gastroenterology & Hepatology, Antwerp University Hospital, Antwerp, Belgium
| | - Wilhelmus J. Kwanten
- Laboratory of Experimental Medicine and Paediatrics and Member of the Infla-Med Centre of Excellence, University of Antwerp, Faculty of Medicine & Health Sciences, Antwerp, Belgium
- Department of Gastroenterology & Hepatology, Antwerp University Hospital, Antwerp, Belgium
| | - Laura Mortelmans
- Department of Gastroenterology & Hepatology, Antwerp University Hospital, Antwerp, Belgium
| | - Cedric Peleman
- Laboratory of Experimental Medicine and Paediatrics and Member of the Infla-Med Centre of Excellence, University of Antwerp, Faculty of Medicine & Health Sciences, Antwerp, Belgium
- Department of Gastroenterology & Hepatology, Antwerp University Hospital, Antwerp, Belgium
| | - Shivani Chotkoe
- Laboratory of Experimental Medicine and Paediatrics and Member of the Infla-Med Centre of Excellence, University of Antwerp, Faculty of Medicine & Health Sciences, Antwerp, Belgium
| | - Maarten Spinhoven
- Department of Radiology, Antwerp University Hospital, Antwerp, Belgium
| | - Floris Vanhevel
- Department of Radiology, Antwerp University Hospital, Antwerp, Belgium
| | - Luc F. Van Gaal
- Department of Endocrinology, Diabetology & Metabolism, Antwerp University Hospital, Antwerp, Belgium
| | - Benedicte Y. De Winter
- Laboratory of Experimental Medicine and Paediatrics and Member of the Infla-Med Centre of Excellence, University of Antwerp, Faculty of Medicine & Health Sciences, Antwerp, Belgium
| | - Christophe E.M. De Block
- Department of Endocrinology, Diabetology & Metabolism, Antwerp University Hospital, Antwerp, Belgium
- Laboratory of Experimental Medicine and Paediatrics and Member of the Infla-Med Centre of Excellence, University of Antwerp, Faculty of Medicine & Health Sciences, Antwerp, Belgium
| | - Sven M. Francque
- Laboratory of Experimental Medicine and Paediatrics and Member of the Infla-Med Centre of Excellence, University of Antwerp, Faculty of Medicine & Health Sciences, Antwerp, Belgium
- Department of Gastroenterology & Hepatology, Antwerp University Hospital, Antwerp, Belgium
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Safari Z, Bagherniya M, Khoram Z, Ebrahimi Varzaneh A, Heidari Z, Sahebkar A, Askari G. The effect of curcumin on anthropometric indices, blood pressure, lipid profiles, fasting blood glucose, liver enzymes, fibrosis, and steatosis in non-alcoholic fatty livers. Front Nutr 2023; 10:1163950. [PMID: 37275651 PMCID: PMC10233031 DOI: 10.3389/fnut.2023.1163950] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2023] [Accepted: 04/17/2023] [Indexed: 06/07/2023] Open
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease. Curcumin is a natural polyphenol that may be effective against liver steatosis and steatohepatitis. The present study aimed to evaluate the effects of phytosomal curcumin on lipid profile, fasting blood sugar, anthropometric indices, liver enzymes, fibrosis, and steatosis in non-alcoholic fatty liver patients. Methods The participants were randomized to the curcumin-phosphatidylserine phytosomal receiving group and the placebo receiving group and were followed up for 12 weeks. Data on anthropometric indices, lipid profile, blood glucose, blood pressure, liver enzymes, hepatic steatosis, and fibrosis were collected at the beginning and the end of the clinical trial. Results Supplementation for 12 weeks with phytosomal curcumin significantly reduced fibrosis and steatosis in the phytosomal curcumin receiving group compared with the placebo group (p < 0.05). Phytosomal curcumin also significantly reduced waist circumference and blood pressure compared with the placebo group (p < 0.05). There was no significant difference between the phytosomal curcumin and the placebo groups regarding changes in weight, body mass index, fasting blood glucose, liver enzymes, and lipid profile. Conclusion Curcumin, at a dose of 250 mg per day, might be effective in treating patients with NAFLD. Further studies are necessary to confirm these findings and to discover the underlying mechanisms. Clinical trial registration https://www.irct.ir/trial/43730, identifier: IRCT20121216011763N39.
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Affiliation(s)
- Zahra Safari
- Nutrition and Food Security Research Center and Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohammad Bagherniya
- Nutrition and Food Security Research Center and Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
- Anesthesia and Critical Care Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Ziba Khoram
- Gastroenterology and Hepatology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | | | - Zahra Heidari
- Department of Biostatistics and Epidemiology, School of Health, Isfahan University of Medical Sciences, Isfahan, Iran
- Isfahan Cardiac Rehabilitation Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- School of Medicine, The University of Western Australia, Perth, WA, Australia
| | - Gholamreza Askari
- Nutrition and Food Security Research Center and Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
- Anesthesia and Critical Care Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
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Lee XH, Nor LM, Ang CS, Yeow TP, Lim SL. The Prevalence of Advanced Liver Fibrosis Among Patients With Type 2 Diabetes Mellitus: A Single-Centre Experience in Penang, Malaysia. J ASEAN Fed Endocr Soc 2023; 38:52-61. [PMID: 37252406 PMCID: PMC10213172 DOI: 10.15605/jafes.038.01.08] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Accepted: 09/09/2022] [Indexed: 06/29/2024] Open
Abstract
OBJECTIVES Type 2 diabetes mellitus (T2DM) is an important risk factor for Non-alcoholic fatty liver disease (NAFLD). It worsens the course of NAFLD. We investigated the prevalence of advanced liver fibrosis among patients with T2DM. Our secondary objectives were to describe patient demographics, to explore associated clinical factors, and to compare FIB-4 Index and liver stiffness measurement (LSM). METHODOLOGY This was a cross-sectional study on 258 patients with T2DM duration of at least 10 years. Transient elastography (FibroScan®) was performed on all subjects. Advanced liver fibrosis was diagnosed based on LSM results. The FIB-4 index formula was used. RESULTS The prevalence of advanced liver fibrosis was 22.1%. Associated factors were body mass index (BMI), alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), triglyceride (TG) and high-density lipoprotein (HDL) cholesterol. Independent factors were BMI and GGT (p=0.003 and p<0.001). FIB-4 index has 30.0% sensitivity, 85.0% specificity, 38.7% positive predictive value, and 79.4% negative predictive value in detecting advanced liver fibrosis by LSM criteria. CONCLUSION Our study confirmed the high prevalence of advanced liver fibrosis among patients with long-standing T2DM. This study suggests the benefit of advanced liver fibrosis screening in patients with a minimum of 10 years of T2DM, especially those with high BMI and GGT.
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Affiliation(s)
- Xe Hui Lee
- Endocrinology Unit, Department of Medicine, Penang General Hospital, Penang, Malaysia
| | - Lisa Mohamed Nor
- Clinical Research Center, Putrajaya Hospital, Wilayah Persekutuan Putrajaya, Malaysia
| | - Choon Seong Ang
- Clinical Research Center, Penang General Hospital, Penang, Malaysia
| | - Toh Peng Yeow
- Endocrinology Unit, Department of Medicine, Penang General Hospital, Penang, Malaysia
| | - Shueh Lin Lim
- Endocrinology Unit, Department of Medicine, Penang General Hospital, Penang, Malaysia
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Canivet CM, Boursier J. Screening for Liver Fibrosis in the General Population: Where Do We Stand in 2022? Diagnostics (Basel) 2022; 13:diagnostics13010091. [PMID: 36611384 PMCID: PMC9818643 DOI: 10.3390/diagnostics13010091] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Revised: 12/19/2022] [Accepted: 12/20/2022] [Indexed: 12/30/2022] Open
Abstract
Approximately 30% of the worldwide population has at least one risk factor for liver disease. Identifying advanced liver disease before the occurrence of complications remains a difficult challenge in clinical practice, where diagnosis comes too late for many patients, at the time of liver decompensation or palliative hepatocellular carcinoma, with poor short-term prognosis. Noninvasive, blood- or elastography-based tests of liver fibrosis (NITs) have been developed for the early diagnosis of advanced liver fibrosis. Recent population-based studies evaluating the screening of liver fibrosis with these NITs have provided important information on at-risk groups that should be targeted. New measures based on the sequential use of NITs help to better organize the referral of at-risk patients to the liver specialist. However, energizing these measures will require increased awareness of both chronic liver diseases and the use of NITs among non-specialists.
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Affiliation(s)
- Clémence M. Canivet
- Service d’Hépato-Gastroentérologie et Oncologie Digestive, Centre Hospitalier Universitaire d’Angers, 49100 Angers, France
- Laboratoire HIFIH, UPRES EA3859, SFR 4208, Université d’Angers, 49035 Angers, France
- Correspondence: ; Tel.: +33-241353410; Fax: +33-241354119
| | - Jérôme Boursier
- Service d’Hépato-Gastroentérologie et Oncologie Digestive, Centre Hospitalier Universitaire d’Angers, 49100 Angers, France
- Laboratoire HIFIH, UPRES EA3859, SFR 4208, Université d’Angers, 49035 Angers, France
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Cazac GD, Lăcătușu CM, Mihai C, Grigorescu ED, Onofriescu A, Mihai BM. Ultrasound-Based Hepatic Elastography in Non-Alcoholic Fatty Liver Disease: Focus on Patients with Type 2 Diabetes. Biomedicines 2022; 10:biomedicines10102375. [PMID: 36289643 PMCID: PMC9598125 DOI: 10.3390/biomedicines10102375] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2022] [Revised: 09/17/2022] [Accepted: 09/19/2022] [Indexed: 12/16/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease and is the hepatic expression of metabolic syndrome. The development of non-invasive methods for the diagnosis of hepatic steatosis and advanced fibrosis in high-risk patients, especially those with type 2 diabetes mellitus, is highly needed to replace the invasive method of liver biopsy. Elastographic methods can bring significant added value to screening and diagnostic procedures for NAFLD in patients with diabetes, thus contributing to improved NAFLD management. Pharmacological development and forthcoming therapeutic measures that address NAFLD should also be based on new, non-invasive, and reliable tools that assess NAFLD in at-risk patients and be able to properly guide treatment in individuals with both diabetes and NAFLD. This is the first review aiming to outline and discuss recent studies on ultrasound-based hepatic elastography, focusing on NAFLD assessment in patients with diabetes.
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Affiliation(s)
- Georgiana-Diana Cazac
- Unit of Diabetes, Nutrition and Metabolic Diseases, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Clinical Center of Diabetes, Nutrition and Metabolic Diseases, “Sf. Spiridon” County Clinical Emergency Hospital, 700111 Iasi, Romania
| | - Cristina-Mihaela Lăcătușu
- Unit of Diabetes, Nutrition and Metabolic Diseases, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Clinical Center of Diabetes, Nutrition and Metabolic Diseases, “Sf. Spiridon” County Clinical Emergency Hospital, 700111 Iasi, Romania
- Correspondence: (C.-M.L.); (E.-D.G.); Tel.: +40-72-321-1116 (C.-M.L.); +40-74-209-3749 (E.-D.G.)
| | - Cătălina Mihai
- Unit of Medical Semiology and Gastroenterology, Faculty of Medicine,, “Grigore T. Popa”, University of Medicine and Pharmacy, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “Sf. Spiridon” Emergency Hospital, 700111 Iași, Romania
| | - Elena-Daniela Grigorescu
- Unit of Diabetes, Nutrition and Metabolic Diseases, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Correspondence: (C.-M.L.); (E.-D.G.); Tel.: +40-72-321-1116 (C.-M.L.); +40-74-209-3749 (E.-D.G.)
| | - Alina Onofriescu
- Unit of Diabetes, Nutrition and Metabolic Diseases, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Clinical Center of Diabetes, Nutrition and Metabolic Diseases, “Sf. Spiridon” County Clinical Emergency Hospital, 700111 Iasi, Romania
| | - Bogdan-Mircea Mihai
- Unit of Diabetes, Nutrition and Metabolic Diseases, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Clinical Center of Diabetes, Nutrition and Metabolic Diseases, “Sf. Spiridon” County Clinical Emergency Hospital, 700111 Iasi, Romania
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Ciardullo S, Perseghin G. Prevalence of elevated liver stiffness in patients with type 1 and type 2 diabetes: A systematic review and meta-analysis. Diabetes Res Clin Pract 2022; 190:109981. [PMID: 35798217 DOI: 10.1016/j.diabres.2022.109981] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 06/26/2022] [Accepted: 07/01/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Liver stiffness is an indirect marker of liver fibrosis, which predicts clinical outcomes in patients with nonalcoholic fatty liver disease (NAFLD). The aim of the present systematic review and meta-analysis is to summarize evidence on the prevalence of elevated liver stiffness in patients with diabetes. METHODS We systematically searched PubMed-MEDLINE and Scopus from inception to May 2022 for observational studies reporting the prevalence of elevated liver stiffness diagnosed by vibration controlled transient elastography (VCTE) in adult patients with either type 1 (T1D) or type 2 diabetes (T2D). Prevalence values from individual studies were meta-analyzed using random effects models. Subgroup and sensitivity analyses were performed to identify potential sources of heterogeneity. RESULTS Of the 428 titles initially scrutinized, 29 studies fulfilled the criteria and were included, providing data on 390 patients with T1D and 10,487 patients with T2D. Prevalence rates of elevated liver stiffness were 5.2% (95% CI 1.1-9.2) in patients with T1D and 19.8% (95% CI 16.8-22.8) in patients with T2D. In studies performed in patients with T2D, multivariate meta-regression analysis showed that higher body mass index, higher age, a higher proportion of males, lower VCTE cut-off and Asian ethnicity were associated with increased prevalence rates. This model explained 32.7% of the observed heterogeneity. No signs of publication bias were identified by visual inspection of the funnel plot or by Egger's test. CONCLUSIONS This meta-analysis indicates that 1 in 20 patients with T1D and 1 in 5 patients with T2D has elevated liver stiffness, indicative of potential significant or advanced liver fibrosis.
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Affiliation(s)
- Stefano Ciardullo
- Department of Medicine and Rehabilitation, Policlinico di Monza, Monza, Italy; School of Medicine and Surgery, University of Milano Bicocca, Milan, Italy.
| | - Gianluca Perseghin
- Department of Medicine and Rehabilitation, Policlinico di Monza, Monza, Italy; School of Medicine and Surgery, University of Milano Bicocca, Milan, Italy
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de Vries M, El-Morabit F, van Erpecum KJ, Westerink J, Bac ST, Kaasjager HAHK, de Valk HW. Non-alcoholic fatty liver disease: identical etiologic factors in patients with type 1 and type 2 diabetes. Eur J Intern Med 2022; 100:77-82. [PMID: 35387749 DOI: 10.1016/j.ejim.2022.03.025] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Revised: 02/18/2022] [Accepted: 03/18/2022] [Indexed: 01/08/2023]
Abstract
AIMS To compare NAFLD prevalence, distribution and its etiologic determinants in patients with type 1 diabetes (T1D) and type 2 diabetes (T2D). METHODS In this cross-sectional study, NAFLD was evaluated by transient elastography in adult outpatients with T1D and T2D. NAFLD was defined as hepatic steatosis with or without fibrosis. Associations between insulin resistance related factors and NAFLD and advanced fibrosis (≥ F3) were explored in T1D and T2D separately, using multivariate logistic regression models. Interaction analysis was performed to compare the associations in patients with T1D and T2D. RESULTS One hundred and fifty patients with T1D (mean age 47 years, male 55%, mean diabetes duration 25 years, median BMI 25 kg/m2) and 100 patients with T2D (median age 67 years, male 56%, median diabetes duration 17 years, mean BMI 30 kg/m2) were included. NAFLD prevalence was 20% in patients with T1D and 76% in patients with T2D. Advanced fibrosis prevalence was 2.0% in patients with T1D and 22% in patients with T2D. In both patients with T1D and T2D, waist circumference, BMI and metabolic syndrome were positively associated, and estimated insulin sensitivity was negatively associated with the presence of NAFLD, adjusted for age, sex and diabetes duration. There was no effect modification by diabetes type for any of these associations. CONCLUSIONS Despite differences in population characteristics and pathophysiology between T1D and T2D, insulin resistance related factors are similarly associated with NAFLD in both groups.
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Affiliation(s)
- Marieke de Vries
- Department of Internal Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
| | - Fatima El-Morabit
- Department of Gastroenterology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Karel J van Erpecum
- Department of Gastroenterology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Jan Westerink
- Department of Internal Medicine, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Simon T Bac
- Department of Gastroenterology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - H A H Karin Kaasjager
- Department of Internal Medicine, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Harold W de Valk
- Department of Internal Medicine, University Medical Center Utrecht, Utrecht, the Netherlands
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Cusi K, Isaacs S, Barb D, Basu R, Caprio S, Garvey WT, Kashyap S, Mechanick JI, Mouzaki M, Nadolsky K, Rinella ME, Vos MB, Younossi Z. American Association of Clinical Endocrinology Clinical Practice Guideline for the Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Primary Care and Endocrinology Clinical Settings: Co-Sponsored by the American Association for the Study of Liver Diseases (AASLD). Endocr Pract 2022; 28:528-562. [PMID: 35569886 DOI: 10.1016/j.eprac.2022.03.010] [Citation(s) in RCA: 512] [Impact Index Per Article: 170.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 03/11/2022] [Accepted: 03/11/2022] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To provide evidence-based recommendations regarding the diagnosis and management of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) to endocrinologists, primary care clinicians, health care professionals, and other stakeholders. METHODS The American Association of Clinical Endocrinology conducted literature searches for relevant articles published from January 1, 2010, to November 15, 2021. A task force of medical experts developed evidence-based guideline recommendations based on a review of clinical evidence, expertise, and informal consensus, according to established American Association of Clinical Endocrinology protocol for guideline development. RECOMMENDATION SUMMARY This guideline includes 34 evidence-based clinical practice recommendations for the diagnosis and management of persons with NAFLD and/or NASH and contains 385 citations that inform the evidence base. CONCLUSION NAFLD is a major public health problem that will only worsen in the future, as it is closely linked to the epidemics of obesity and type 2 diabetes mellitus. Given this link, endocrinologists and primary care physicians are in an ideal position to identify persons at risk on to prevent the development of cirrhosis and comorbidities. While no U.S. Food and Drug Administration-approved medications to treat NAFLD are currently available, management can include lifestyle changes that promote an energy deficit leading to weight loss; consideration of weight loss medications, particularly glucagon-like peptide-1 receptor agonists; and bariatric surgery, for persons who have obesity, as well as some diabetes medications, such as pioglitazone and glucagon-like peptide-1 receptor agonists, for those with type 2 diabetes mellitus and NASH. Management should also promote cardiometabolic health and reduce the increased cardiovascular risk associated with this complex disease.
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Affiliation(s)
- Kenneth Cusi
- Guideine and Algorithm Task Forces Co-Chair, Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida
| | - Scott Isaacs
- Guideline and Algorithm Task Forces Co-Chair, Division of Endocrinology, Emory University School of Medicine, Atlanta, Georgia
| | - Diana Barb
- University of Florida, Gainesville, Florida
| | - Rita Basu
- Division of Endocrinology, University of Virginia School of Medicine, Charlottesville, Virginia
| | - Sonia Caprio
- Yale University School of Medicine, New Haven, Connecticut
| | - W Timothy Garvey
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama
| | | | - Jeffrey I Mechanick
- The Marie-Josee and Henry R. Kravis Center for Cardiovascular Health at Mount Sinai Heart, Icahn School of Medicine at Mount Sinai
| | | | - Karl Nadolsky
- Michigan State University College of Human Medicine, Grand Rapids, Michigan
| | - Mary E Rinella
- AASLD Representative, University of Pritzker School of Medicine, Chicago, Illinois
| | - Miriam B Vos
- Center for Clinical and Translational Research, Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, Georgia
| | - Zobair Younossi
- AASLD Representative, Inova Medicine, Inova Health System, Falls Church, Virginia
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de Vries M, Westerink J, El-Morabit F, Kaasjager HAHK, de Valk HW. Prevalence of non-alcoholic fatty liver disease (NAFLD) and its association with surrogate markers of insulin resistance in patients with type 1 diabetes. Diabetes Res Clin Pract 2022; 186:109827. [PMID: 35283265 DOI: 10.1016/j.diabres.2022.109827] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 02/17/2022] [Accepted: 03/08/2022] [Indexed: 01/09/2023]
Abstract
AIMS Assess prevalence of hepatic steatosis (HS) and of fibrosis in an unselected population of patients with type 1 diabetes. Describe their clinical profile and explore the association between insulin resistance and NAFLD as secondary objectives. METHODS We prospectively assessed NAFLD by transient elastography in adult outpatients with type 1 diabetes. Patients were eligible if they did not have any known secondary cause of liver disease. NAFLD was defined as HS with or without fibrosis/cirrhosis. Associations between estimated glucose disposal rate (eGDR) and metabolic syndrome, as surrogate markers of insulin resistance, and NAFLD were explored using multivariate logistic regression models, adjusting for age, sex and diabetes duration. RESULTS We enrolled 150 consecutive subjects (age 47 ± 14 years, male 55%, diabetes duration 25 ± 14 years, median BMI 25 kg/m2). NAFLD prevalence was 20% (n = 30). Thirty patients (20%) had HS. Five patients (3.3%) had HS with fibrosis. eGDR and metabolic syndrome were statistically significantly associated with the presence of NAFLD (OR 0.62, 95% CI 0.49-0.77, OR 7.62, 95% CI 2.95-19.77). CONCLUSIONS NAFLD prevalence in patients with type 1 diabetes is considerable, mainly restricted to isolated HS, while fibrosis is rare. Insulin resistance is associated with NAFLD in patients with type 1 diabetes.
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Affiliation(s)
- Marieke de Vries
- Department of Internal Medicine, Diabetology and Vascular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
| | - Jan Westerink
- Department of Internal Medicine, Diabetology and Vascular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
| | - Fatima El-Morabit
- Department of Gastroenterology, University Medical Center Utrecht, Utrecht, the Netherlands.
| | - H A H Karin Kaasjager
- Department of Internal Medicine, Diabetology and Vascular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
| | - Harold W de Valk
- Department of Internal Medicine, Diabetology and Vascular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
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Clinical Interest of Serum Alpha-2 Macroglobulin, Apolipoprotein A1, and Haptoglobin in Patients with Non-Alcoholic Fatty Liver Disease, with and without Type 2 Diabetes, before or during COVID-19. Biomedicines 2022; 10:biomedicines10030699. [PMID: 35327501 PMCID: PMC8945355 DOI: 10.3390/biomedicines10030699] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 03/06/2022] [Accepted: 03/14/2022] [Indexed: 02/04/2023] Open
Abstract
In patients with non-alcoholic fatty liver disease (NAFLD) with or without type 2 diabetes mellitus (T2DM), alpha-2 macroglobulin (A2M), apolipoprotein A1 (ApoA1), and haptoglobin are associated with the risk of liver fibrosis, inflammation (NASH), and COVID-19. We assessed if these associations were worsened by T2DM after adjustment by age, sex, obesity, and COVID-19. Three datasets were used: the “Control Population”, which enabled standardization of protein serum levels according to age and sex (N = 27,382); the “NAFLD-Biopsy” cohort for associations with liver features (N = 926); and the USA “NAFLD-Serum” cohort for protein kinetics before and during COVID-19 (N = 421,021). The impact of T2DM was assessed by comparing regression curves adjusted by age, sex, and obesity for the liver features in “NAFLD-Biopsy”, and before and during COVID-19 pandemic peaks in “NAFLD-Serum”. Patients with NAFLD without T2DM, compared with the values of controls, had increased A2M, decreased ApoA1, and increased haptoglobin serum levels. In patients with both NAFLD and T2DM, these significant mean differences were magnified, and even more during the COVID-19 pandemic in comparison with the year 2019 (all p < 0.001), with a maximum ApoA1 decrease of 0.21 g/L in women, and a maximum haptoglobin increase of 0.17 g/L in men. In conclusion, T2DM is associated with abnormal levels of A2M, ApoA1, and haptoglobin independently of NAFLD, age, sex, obesity, and COVID-19.
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Gupta A, Anoop S, Ansari IA, Prakash S, Misra A. High prevalence of hepatic steatosis and hepatic fibrosis in patients with type 2 diabetes mellitus. Clin Nutr ESPEN 2021; 46:519-526. [PMID: 34857244 DOI: 10.1016/j.clnesp.2021.08.028] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Revised: 07/29/2021] [Accepted: 08/23/2021] [Indexed: 01/10/2023]
Abstract
AIM To determine the prevalence of hepatic steatosis and fibrosis in patients with T2DM from North India. RESEARCH DESIGN AND METHODS In this cross-sectional study, Asian Indian patients with T2DM (n,250) underwent liver ultrasonography (USG), Fibroscan for assessment of hepatic steatosis (Controlled Attenuation Parameter, CAP) and hepatic fibrosis (Kilopascals, kPa) respectively. Pearson's correlation analysis & logistic regression analysis for significant predictors of hepatic steatosis and fibrosis were done. The cut-off value of liver span was calculated by ROC-AUC analysis. RESULTS Grade 3 hepatic steatosis was seen in 213 T2DM patients (85.2%). It was higher in males than females and in those with high BMI values. Any degree of fibrosis and severe fibrosis were seen in 205 (62%) and 46 (18.4%) patients, respectively; these were higher in males, specifically in those with BMI >30 kg/m2, and diabetes of a duration more than 5 years. BMI and SGPT were the significant predictors of hepatic steatosis. An increase of 1 unit of BMI above 23 kg/m2 led to 19.6 times increased risk of hepatic steatosis in T2DM patients aged 50 years and above. SGOT and GGTP were significant predictors of any degree of hepatic fibrosis. On ROC-AUC analysis, liver span cut-off values of ≥16.4 cms and ≥16.8 cm in males and females respectively, were predictive of hepatic fibrosis. CONCLUSION High prevalence of grade 3 hepatic steatosis and hepatic fibrosis needs increased vigilance and corrective lifestyle and pharmacological measures. Asian Indian patients with T2DM and BMI >30 kg/m2, with duration of diabetes above 5 years & an ultrasound derived liver span ≥16.4 cms, should be further evaluated for hepatic fibrosis.
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Affiliation(s)
- Aanchal Gupta
- Fortis C-DOC Centre of Excellence for Diabetes, Metabolic Diseases and Endocrinology, Chirag Enclave, Nehru Place, New Delhi, India
| | - Shajith Anoop
- Centre of Nutrition & Metabolic Research (C-NET), National Diabetes, Obesity and Cholesterol Foundation (N-DOC), SDA, New Delhi, India; Diabetes Foundation (India), SDA, New Delhi, India
| | - Irshad Ahmad Ansari
- Fortis C-DOC Centre of Excellence for Diabetes, Metabolic Diseases and Endocrinology, Chirag Enclave, Nehru Place, New Delhi, India; Centre of Nutrition & Metabolic Research (C-NET), National Diabetes, Obesity and Cholesterol Foundation (N-DOC), SDA, New Delhi, India
| | - Satya Prakash
- Fortis C-DOC Centre of Excellence for Diabetes, Metabolic Diseases and Endocrinology, Chirag Enclave, Nehru Place, New Delhi, India
| | - Anoop Misra
- Fortis C-DOC Centre of Excellence for Diabetes, Metabolic Diseases and Endocrinology, Chirag Enclave, Nehru Place, New Delhi, India; Centre of Nutrition & Metabolic Research (C-NET), National Diabetes, Obesity and Cholesterol Foundation (N-DOC), SDA, New Delhi, India; Diabetes Foundation (India), SDA, New Delhi, India; Fortis Flt. Lt. Rajan Dhall Hospital, Vasant Kunj, New Delhi, India.
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14
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Yang Q, Li X. The presence of diabetes impacts liver fibrosis and steatosis by transient elastography in a primary care population. Ann Hepatol 2021; 25:100346. [PMID: 33864950 DOI: 10.1016/j.aohep.2021.100346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 03/19/2021] [Accepted: 03/29/2021] [Indexed: 02/04/2023]
Affiliation(s)
- Qunying Yang
- Department of Infectious Diseases, YiWu Central Hospital, Zhejiang, 322000, China
| | - Xiaofei Li
- Department of Infectious Diseases, YiWu Central Hospital, Zhejiang, 322000, China.
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15
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Meyer G, Dauth N, Grimm M, Herrmann E, Bojunga J, Friedrich-Rust M. Shear Wave Elastography Reveals a High Prevalence of NAFLD-related Fibrosis Even in Type 1 Diabetes. Exp Clin Endocrinol Diabetes 2021; 130:532-538. [PMID: 34784620 DOI: 10.1055/a-1666-0431] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND The association between type 2 diabetes mellitus (T2DM) and advanced stages of non-alcoholic fatty liver disease is well known. Some studies indicate a relevant prevalence also in type 1 diabetes mellitus (T1DM), but so far there is only limited data. OBJECTIVE To determine the prevalence of non-alcoholic fatty liver disease (NAFLD)-related liver fibrosis in individuals with T1DM and compare to those with type 2 diabetes. METHODS Diabetic patients from a single diabetes care centre were screened for liver fibrosis by sonographic shear wave elastography (SWE). In addition, all patients received laboratory evaluation including non-alcoholic fatty liver fibrosis score and Fibrosis-4 Index. RESULTS Three hundred and forty patients were included in the study, of these, 310 received SWE. Overall 254 patients (93 with type 1 and 161 with type 2 diabetes) had reliable measurements and were included in the final analysis. In patients with type 1 diabetes, the prevalence of NAFLD-related liver fibrosis was 16-21%, depending on the method of detection. Significant liver fibrosis was observed in 30-46% of patients with type 2 diabetes. CONCLUSIONS Our data revealed an unexpectedly high prevalence of NAFLD-related liver fibrosis in patients with type 1 diabetes. To our knowledge, this is one of the first studies using SWE to diagnose advanced NAFLD in type 1 diabetes in a non-preselected cohort. Considering the findings of our study, regular screening for hepatic complications must be recommended for all diabetic patients, even for those with type 1 diabetes.
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Affiliation(s)
- Gesine Meyer
- Department of Internal Medicine, Goethe-University Hospital, Frankfurt, Germany
| | - Nina Dauth
- Department of Internal Medicine, Goethe-University Hospital, Frankfurt, Germany
| | - Matthias Grimm
- Department of Internal Medicine, Goethe-University Hospital, Frankfurt, Germany
| | - Eva Herrmann
- Institute of Biostatistics and Mathematic Modelling, Goethe-University, Frankfurt, Germany
| | - Joerg Bojunga
- Department of Internal Medicine, Goethe-University Hospital, Frankfurt, Germany
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Modi S, Syed Gaggatur N, Sange AH, Srinivas N, Sarnaik MK, Hassan M, Gajjela H, Sange I. An Emerging Facet of Diabetes Mellitus: The Nexus of Gastrointestinal Disorders. Cureus 2021; 13:e18245. [PMID: 34712528 PMCID: PMC8542353 DOI: 10.7759/cureus.18245] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/24/2021] [Indexed: 11/05/2022] Open
Abstract
Diabetes mellitus (DM) is a chronic metabolic disorder with a multi-systemic involvement, the gastrointestinal (GI) system being one of them. In this study, we have compiled and analyzed findings from various studies to conclude that peripheral insulin resistance and hyperglycemia are the two key factors that play a role in the pathogenesis of the web of disorders associated with diabetes. These two key factors, when clubbed with autoimmunity, autonomic neuropathy, and genetic and environmental factors, play a substantial role in the development of GI disorders in DM. This article examines GI disorders such as gastric autonomic neuropathy, non-alcoholic fatty liver disease (NAFLD), celiac disease (CD), etc. It also highlights the importance of regular screening and assessment of DM in preventing the GI tangent of the disease. A prompt blood glucose control through lifestyle modifications, dietary management, and weight reduction, coupled with pharmacotherapy for existing DM, can lead to a better outcome and an optimistic perspective on the disease.
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Affiliation(s)
- Srimy Modi
- Research, K.J. Somaiya Medical College, Mumbai, IND
| | | | | | - Natasha Srinivas
- Research, BGS Global Institute of Medical Sciences, Bangalore, IND
| | | | - Mohammad Hassan
- Internal Medicine, Mohiuddin Islamic Medical College, Mirpur, PAK
| | - Harini Gajjela
- Research, Our Lady of Fatima University College of Medicine, Valenzuela, Metro Manila, PHL
| | - Ibrahim Sange
- Research, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA.,Research, K.J. Somaiya Medical College, Mumbai, IND
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Galangin Attenuates Liver Injury, Oxidative Stress and Inflammation, and Upregulates Nrf2/HO-1 Signaling in Streptozotocin-Induced Diabetic Rats. Processes (Basel) 2021. [DOI: 10.3390/pr9091562] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Chronic hyperglycemia increases the risk of liver damage. Oxidative stress and aberrant inflammatory response are entangled in diabetes-associated liver injury. This study evaluated the protective effect of the flavonoid galangin (Gal) on glucose intolerance, liver injury, oxidative stress, inflammatory response, and Nrf2/HO-1 signaling in diabetic rats. Diabetes was induced by streptozotocin (STZ), and the rats received Gal for six weeks. STZ-induced rats showed glucose intolerance, hypoinsulinemia, elevated glycated hemoglobin (HbA1c), and decreased liver glycogen. Gal ameliorated glucose intolerance, reduced HbA1c%, increased serum insulin and liver glycogen and hexokinase activity, and suppressed glycogen phosphorylase, glucose-6-phosphatase and fructose-1,6-biphosphatase in diabetic rats. Circulating transaminases, ALP and LDH, and liver ROS, MDA, TNF-α, IL-1β, and IL-6 were increased and GSH, SOD, and CAT were diminished in diabetic rats. In addition, diabetic rats exhibited multiple histopathological alterations and marked collagen deposition. Treatment with Gal mitigated liver injury, prevented histopathological alterations, decreased ROS, MDA, pro-inflammatory cytokines, Bax and caspase-3, and enhanced cellular antioxidants and Bcl-2. Gal downregulated hepatic Keap1 in diabetic rats and upregulated Nrf2 and HO-1 mRNA as well as HO-1 activity. Molecular modeling studies revealed the ability of Gal to bind to and inhibit NF-κB and Keap1, and also showed its binding pattern with HO-1. In conclusion, Gal ameliorates hyperglycemia, glucose intolerance, oxidative stress, inflammation, and apoptosis in diabetic rats. Gal improved carbohydrate metabolizing enzymes and upregulated Nrf2/HO-1 signaling.
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Alhinai A, Patel K, Fonseca VA, Sebastiani G. Non-invasive diagnosis of nonalcoholic fatty liver disease in patients with type 2 diabetes. J Diabetes Complications 2021; 35:107978. [PMID: 34183247 DOI: 10.1016/j.jdiacomp.2021.107978] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 05/19/2021] [Accepted: 06/12/2021] [Indexed: 02/07/2023]
Abstract
Liver disease has emerged as a significant cause of death in people with type 2 diabetes (T2D). Due to a common underlying pathogenic mechanism, namely insulin resistance, T2D represents the main risk factor for nonalcoholic fatty liver disease (NAFLD), characterized by a buildup of fat in the liver. Globally, NAFLD is the most common liver disease, affecting a quarter of the general adult population. The development of nonalcoholic steatohepatitis (NASH) signifies an increased risk of liver fibrosis progression that can result in cirrhosis, hepatocellular carcinoma (HCC), and death. Liver fibrosis progression and development of cirrhosis is mostly asymptomatic until complications from decompensated end-stage liver disease arise. Traditionally, liver biopsy is used to diagnose NASH and stage fibrosis, however, it is invasive and costly. Non-invasive diagnostic alternatives include serum biomarkers and imaging techniques. Early identification of advanced liver fibrosis is pivotal to prompt initiation of targeted surveillance, including screening for HCC, as well as providing options for current and investigational therapeutic interventions to reduce fibrosis progression. This review gives an update on non-invasive diagnostic tools for NAFLD and liver fibrosis in the specific context of T2D, providing clinicians a pragmatic diagnostic approach to this frequent comorbidity in diabetes medicine.
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Affiliation(s)
- Alshaima Alhinai
- Division of Experimental Medicine, McGill University, Montreal, QC, Canada
| | - Keyur Patel
- Division of Gastroenterology and Hepatology, University Health Network Toronto, Toronto General Hospital, Toronto, ON, Canada
| | - Vivian A Fonseca
- Department of Medicine, Division of Endocrinology and Metabolism, School of Medicine, Tulane University Health Sciences Center, New Orleans, LA, USA
| | - Giada Sebastiani
- Division of Experimental Medicine, McGill University, Montreal, QC, Canada; Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC, Canada.
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Abstract
PURPOSE OF REVIEW Aging-related comorbidities, including liver disease, represent the main drivers of morbidity and mortality in people with HIV (PWH). Nonalcoholic fatty liver disease (NAFLD) seems a frequent comorbidity in aging PWH nowadays. NAFLD results from a fat deposition into the liver parenchyma that may evolve to nonalcoholic steatohepatitis (NASH), a state of hepatocellular inflammation and injury in response to the accumulated fat leading to liver fibrosis and cirrhosis. We here review the current status of knowledge regarding this emerging comorbidity in PWH. RECENT FINDINGS Recent studies suggest that PWH are at higher risk for both NASH and NASH-related liver fibrosis. Several hypothesized pathogenic mechanisms may account for this finding, including increased metabolic comorbidities, hepatotoxic effect of lifelong antiretroviral therapy, and chronic HIV infection. In clinical practice, non-invasive diagnostic tests, such as serum biomarkers and elastography, may help identify patients with NASH-related fibrosis, thus improving risk stratification, and enhancing clinical management decisions, including early initiation of interventions such as lifestyle changes and potential pharmacologic interventions. Clinicians should remain informed of the frequency, significance, and diagnostic and management approach to NASH in PWH.
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Affiliation(s)
- Adriana Cervo
- Division of Infectious Diseases, Chronic Viral Illness Service, McGill University Health Centre, Montreal, Canada
- Department of Health Promotion Sciences and Mother and Child Care "Giuseppe D'Alessandro", University of Palermo, Palermo, Italy
| | - Mohamed Shengir
- Division of Experimental Medicine, McGill University, Montreal, Canada
| | - Keyur Patel
- Division of Gastroenterology, University Health Network Toronto, Toronto General Hospital, Toronto, Canada
| | - Giada Sebastiani
- Division of Gastroenterology and Hepatology, Chronic Viral Illness Service Royal Victoria Hospital, McGill University Health Centre, 1001 Blvd. Décarie, Montreal, QC H4A 3J1, Canada.
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Makker J, Tariq H, Kumar K, Ravi M, Shaikh DH, Leung V, Hayat U, Hassan MT, Patel H, Nayudu S, Chilimuri S. Prevalence of advanced liver fibrosis and steatosis in type-2 diabetics with normal transaminases: A prospective cohort study. World J Gastroenterol 2021; 27:523-533. [PMID: 33642826 PMCID: PMC7896434 DOI: 10.3748/wjg.v27.i6.523] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2021] [Revised: 12/12/2020] [Accepted: 12/27/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) and type-2 diabetes mellitus (T2DM) have an intricate bidirectional relationship. Individuals with T2DM, not only have a higher prevalence of non-alcoholic steatosis, but also carry a higher risk of progression to nonalcoholic steatohepatitis. Experts still differ in their recommendations of screening for NAFLD among patients with T2DM. AIM To study the prevalence of NAFLD and advanced fibrosis among our patient population with T2DM. METHODS During the study period (November 2018 to January 2020), 59 adult patients with T2DM and 26 non-diabetic control group individuals were recruited prospectively. Patients with known significant liver disease and alcohol use were excluded. Demographic data and lab parameters were recorded. Liver elastography was performed in all patients. RESULTS In the study group comprised of patients with T2DM and normal alanine aminotransferase levels (mean 17.8 ± 7 U/L), 81% had hepatic steatosis as diagnosed by elastography. Advanced hepatic fibrosis (stage F3 or F4) was present in 12% of patients with T2DM as compared to none in the control group. Patients with T2DM also had higher number of individuals with grade 3 steatosis [45.8% vs 11.5%, (P < 0.00001) and metabolic syndrome (84.7% vs 11.5%, P < 0.00001)]. CONCLUSION A significant number of patients with T2DM, despite having normal transaminase levels, have NAFLD, grade 3 steatosis and advanced hepatic fibrosis as measured by liver elastography.
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Affiliation(s)
- Jasbir Makker
- Division of Gastroenterology, Department of Medicine, BronxCare Health System, Bronx, NY 10457, United States
| | - Hassan Tariq
- Division of Gastroenterology, Department of Medicine, BronxCare Health System, Bronx, NY 10457, United States
| | - Kishore Kumar
- Division of Gastroenterology, Department of Medicine, BronxCare Health System, Bronx, NY 10457, United States
| | - Madhavi Ravi
- Division of Gastroenterology, Department of Medicine, BronxCare Health System, Bronx, NY 10457, United States
| | - Danial Haris Shaikh
- Division of Gastroenterology, Department of Medicine, BronxCare Health System, Bronx, NY 10457, United States
| | - Vivien Leung
- Division of Gastroenterology, Department of Medicine, BronxCare Health System, Bronx, NY 10457, United States
| | - Umar Hayat
- KU School of Medicine-Wichita, University of Kansas, Wichita, KS 67214, United States
| | - Muhammad T Hassan
- Department of Medicine, BronxCare Health System, Bronx, NY 10457, United States
| | - Harish Patel
- Division of Gastroenterology, Department of Medicine, BronxCare Health System, Bronx, NY 10457, United States
| | - Suresh Nayudu
- Division of Gastroenterology, Department of Medicine, BronxCare Health System, Bronx, NY 10457, United States
| | - Sridhar Chilimuri
- Division of Gastroenterology, Department of Medicine, BronxCare Health System, Bronx, NY 10457, United States
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Mertens J, Van Gaal LF, Francque SM, De Block C. NAFLD in type 1 diabetes: overrated or underappreciated? Ther Adv Endocrinol Metab 2021; 12:20420188211055557. [PMID: 34840719 PMCID: PMC8613893 DOI: 10.1177/20420188211055557] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 10/04/2021] [Indexed: 12/18/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in western countries, affecting 25-30% of the general population and up to 65% in those with obesity and/or type 2 diabetes. Accumulation of visceral adipose tissue and insulin resistance (IR) contributes to NAFLD. NAFLD is not an innocent entity as it not only may cause nonalcoholic steatohepatitis and cirrhosis but also contribute to cardiovascular morbidity and mortality. More and more people with type 1 diabetes (T1D) are becoming overweight and present with features of IR, but the prevalence and impact of NAFLD in this population are still unclear. The utility of noninvasive screening tools for NAFLD in T1D is being explored. Recent data indicate that based upon ultrasonographic criteria NAFLD is present in 27% (ranging between 19% and 31%) of adults with T1D. Magnetic resonance imaging data indicate a prevalence rate of 8.6% (ranging between 2.1% and 18.6%). There are, however, multiple factors affecting these data, ranging from study design and referral bias to discrepancies in between diagnostic modalities. Individuals with T1D have a 7-fold higher risk of cardiovascular disease (CVD) and cardiovascular mortality is the most prominent cause of death in T1D. Patients with T1D and NALFD are also more prone to develop CVD, but the independent contribution of NAFLD to cardiovascular events has to be determined in this population. Furthermore, limited data in T1D also point towards a 2 to 3 times higher risk for microvascular complications in those with NAFLD. In this article, we will discuss epidemiological and diagnostic challenges of NAFLD in T1D, explore the link between IR and NAFLD and chronic complications, and examine the independent contribution of NAFLD to the presence of macro-, and microvascular complications.
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Affiliation(s)
- Jonathan Mertens
- Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, Drie Eikenstraat 655, 2650 Edegem, Belgium
- Laboratory of Experimental Medicine and Pediatrics and Member of the Infla-Med Centre of Excellence, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
- Department of Gastroenterology & Hepatology, Antwerp University Hospital, Edegem, Belgium
| | - Luc F. Van Gaal
- Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, Edegem, Belgium
- Laboratory of Experimental Medicine and Pediatrics and Member of the Infla-Med Centre of Excellence, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
| | - Sven M. Francque
- Department of Gastroenterology & Hepatology, Antwerp University Hospital, Drie Eikenstraat 655, 2650 Edegem, Belgium
- Laboratory of Experimental Medicine and Pediatrics and Member of the Infla-Med Centre of Excellence, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
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22
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Boursier J, Tsochatzis EA. Case-finding strategies in non-alcoholic fatty liver disease. JHEP Rep 2020; 3:100219. [PMID: 33659890 PMCID: PMC7896150 DOI: 10.1016/j.jhepr.2020.100219] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Revised: 11/18/2020] [Accepted: 11/23/2020] [Indexed: 12/18/2022] Open
Abstract
Among the large population of patients with non-alcoholic fatty liver disease (NAFLD), identifying those with advanced disease remains challenging. Many patients are diagnosed late, following the development of liver-related complications, leading to poor clinical outcomes. Accumulating evidence suggests that using non-invasive tests for liver fibrosis in patients with metabolic risk factors improves the detection of patients in need of specialised management and is cost-effective. Because of the vast number of patients requiring evaluation, the active participation of general practitioners and physicians who manage patients with metabolic disorders, such as diabetologists, is crucial; this calls for the increased awareness of NAFLD beyond liver clinics. Non-invasive case-finding strategies will need to be further validated and generalised for upcoming drug therapies to have the required impact on the worldwide burden of NAFLD.
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Key Words
- ALD, alcohol-related liver disease
- ALT, alanine aminotransferase
- AST, aspartate aminotransferase
- Awareness
- Case-finding
- Cirrhosis
- Cost-effectiveness
- ELF, enhanced liver fibrosis
- Elastography
- FIB-4
- FIB-4, fibrosis-4
- GP, general practitioner
- Liver fibrosis
- NAFLD, non-alcoholic fatty liver disease
- NAS, NAFLD activity score
- NASH, non-alcoholic steatohepatitis
- NFS, NAFLD fibrosis score
- NICE, National Institute of Clinical Excellence
- NIT, non-invasive test
- Patient pathway
- Primary care
- QALY, quality-adjusted life year
- Screening
- T2DM, type 2 diabetes mellitus
- TE, transient elastography
- Type 2 diabetes mellitus
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Affiliation(s)
- Jerome Boursier
- Service d'Hépato-Gastroentérologie et Oncologie Digestive, Centre Hospitalier Universitaire d'Angers, Angers, France.,Laboratoire HIFIH, UPRES EA3859, SFR 4208, Université d'Angers, Angers, France
| | - Emmanuel A Tsochatzis
- Sheila Sherlock Liver Centre, Royal Free Hospital, London, UK.,UCL Institute for Liver and Digestive Health, Royal Free Campus, UCL, London, UK
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de Vries M, Westerink J, Kaasjager KHAH, de Valk HW. Prevalence of Nonalcoholic Fatty Liver Disease (NAFLD) in Patients With Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis. J Clin Endocrinol Metab 2020; 105:5896010. [PMID: 32827432 PMCID: PMC7526735 DOI: 10.1210/clinem/dgaa575] [Citation(s) in RCA: 94] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Accepted: 08/20/2020] [Indexed: 02/07/2023]
Abstract
CONTEXT Nonalcoholic fatty liver disease (NAFLD) prevalence is high, especially in patients with obesity and type 2 diabetes, and is expected to rise steeply in the coming decades. OBJECTIVE We estimated NAFLD prevalence in patients with type 1 diabetes and explored associated characteristics and outcomes. DATA SOURCES We reviewed PubMed and Embase for studies on NAFLD and type 1 diabetes to March 2020. We screened references of included articles. STUDY SELECTION Two authors independently screened titles/abstracts. One author screened full text articles. NAFLD was defined as described in the individual studies: steatosis and/or fibrosis. Studies not reporting alternative causes of hepatic steatosis or defining NAFLD only as elevated liver enzymes, were excluded. Initially, 919 articles met the selection criteria. DATA EXTRACTION One researcher performed data extraction and risk of bias assessment using standardized tables. DATA SYNTHESIS We assessed pooled prevalence rates by meta-analysis using a random-effects model, subsequently exploring heterogeneity by subgroup-, meta-regression-, and sensitivity analysis. Twenty studies between 2009 and 2019 were included (n = 3901). Pooled NAFLD prevalence was 19.3% (95% CI, 12.3%-27.5%), increasing to 22.0% (95% CI, 13.9%-31.2%) in adults only. Pooled prevalence of ultrasound studies was high (27.1%, 95% CI, 18.7%-36.3%) compared to studies using magnetic resonance imaging (8.6%, 95% CI, 2.1%-18.6%), liver biopsy (19.3%, 95% CI, 10.0%-30.7%), or transient elastography (2.3%, 95% CI, 0.6%-4.8%). CONCLUSION NAFLD prevalence in patients with type 1 diabetes is considerable and is highly dependent on the specific diagnostic modality and NAFLD definition used. These data are helpful in directing actions to standardize NAFLD diagnosis, which will help defining contributing mechanisms and outcomes.
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Affiliation(s)
- Marieke de Vries
- Department of Internal Medicine, Diabetology and Vascular Medicine, University Medical Center Utrecht, GA Utrecht, the Netherlands
- Correspondence and Reprint Requests: Marieke de Vries, MD, University Medical Center Utrecht, Department of Internal Medicine, House number F02.126, P.O. Box 85500, 3508 GA Utrecht, the Netherlands. E-mail:
| | - Jan Westerink
- Department of Internal Medicine, Diabetology and Vascular Medicine, University Medical Center Utrecht, GA Utrecht, the Netherlands
| | - Karin H A H Kaasjager
- Department of Internal Medicine, Diabetology and Vascular Medicine, University Medical Center Utrecht, GA Utrecht, the Netherlands
| | - Harold W de Valk
- Department of Internal Medicine, Diabetology and Vascular Medicine, University Medical Center Utrecht, GA Utrecht, the Netherlands
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24
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Aboulmagd YM, El-Bahy AAZ, Menze ET, Azab SS, El-Demerdash E. Role of linagliptin in preventing the pathological progression of hepatic fibrosis in high fat diet and streptozotocin-induced diabetic obese rats. Eur J Pharmacol 2020; 881:173224. [PMID: 32454118 DOI: 10.1016/j.ejphar.2020.173224] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Revised: 05/16/2020] [Accepted: 05/20/2020] [Indexed: 01/05/2023]
Abstract
Liver fibrosis is a common complication of diabetes mellitus, with a major global public health concern. Linagliptin, a dipeptidyl peptidase-4 inhibitor (DPP-4), is classically used to treat type 2 diabetes mellitus and improves insulin resistance. Additional potential influences of linagliptin on liver fibrosis are still unclear. The present study was undertaken to investigate the therapeutic credit of linagliptin in hepatic fibrosis induced by a high-fat diet (HFD) and streptozotocin (STZ) in rats. Moreover, the mechanisms underline its anti-fibrotic effect were explored. To induce liver fibrosis with T2DM; male Sprague-Dawley albino rats were fed on a high-fat high-sucrose diet for 28 days then exposed to a single dose of STZ (30 mg/kg, IP). After two days of STZ injection, a diabetes confirmation test was done and all diabetic rats were constantly fed on HFD for thirty days with or without treatment with linagliptin (6 mg/kg). Hepatotoxicity markers, lipid profile screening, insulin signaling, inflammatory cytokines (TNF-α, IL-6, NF-κB p65), fibrosis markers (Collagen, α-SMA, TGF-β1) and histopathological studies including hematoxylin and eosin (H&E) as well Masson's trichrome stains were performed. In our preliminary study, linagliptin at a dose of 6 mg/kg was chosen as the optimum anti-diabetic dose in rats challenged with STZ. Linagliptin significantly improved insulin sensitivity and lipid profile and reduced inflammatory mediators, and collagen depositions in rats with liver fibrosis and T2DM. In conclusion, above and beyond its anti-diabetic effect, this study introduced linagliptin as a promising option for preventing the pathological progression of liver fibrosis associated with T2DM.
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Affiliation(s)
- Yara M Aboulmagd
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Heliopolis University for Sustainable Development, Cairo, Egypt
| | - Alshaymaa A Z El-Bahy
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Heliopolis University for Sustainable Development, Cairo, Egypt
| | - Esther T Menze
- Pharmacology & Toxicology Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
| | - Samar S Azab
- Pharmacology & Toxicology Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
| | - Ebtehal El-Demerdash
- Pharmacology & Toxicology Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
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25
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Tuong TTK, Tran DK, Phu PQT, Hong TND, Chu Dinh T, Chu DT. Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes: Evaluation of Hepatic Fibrosis and Steatosis Using Fibroscan. Diagnostics (Basel) 2020; 10:E159. [PMID: 32183383 PMCID: PMC7151057 DOI: 10.3390/diagnostics10030159] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Revised: 03/11/2020] [Accepted: 03/12/2020] [Indexed: 12/16/2022] Open
Abstract
Patients with type 2 diabetes mellitus (T2DM) are at increased risk of non-alcoholic fatty liver disease (NAFLD) and might eventually progress to advanced fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Recommendations on whether to screen for NAFLD in diabetic patients remains conflicted between major guidelines. Transient elastography using FibroScan with CAP (controlled attenuation parameter) can assess both liver steatosis and fibrosis simultaneously. This paper took a new look at the prevalence of NAFLD and the severity of fibrosis among T2DM patients in Vietnam. The study was conducted using a cross-sectional design in T2DM adults who attended Dai Phuoc Ho Chi Minh Polyclinic and Polyclinic of Pham Ngoc Thach University of Medicine. Liver steatosis and fibrosis was assessed by FibroScan. NAFLD was diagnosed if CAP > 233 dB/m (steatosis > 5%). Data were analyzed using STATA 12 software program. We found that a total of 307 type 2 diabetic patients qualified for the study's criteria. The prevalence of NAFLD in T2DM patients based on FibroScan was 73.3%. Rates of mild, moderate and severe steatosis were 20.5%, 21.8% and 30.9%, respectively. The prevalence of significant fibrosis (≥ F2), advanced fibrosis (≥ F3) and cirrhosis (F4) was 13.0%, 5.9% and 3.6%, respectively. On multivariate analysis, aspartate aminotransferase (AST) (OR: 1.067; 95% CI: 1.017-1.119; p = 0.008) and platelet levels (OR: 0.985; 95% CI: 0.972-0.999; p = 0.034) were independent of risk factors of advanced fibrosis. Thus, our study supports screening for NAFLD and for evaluating the severity of liver fibrosis in T2DM patients.
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Affiliation(s)
- Tran Thi Khanh Tuong
- Department of Internal Medicine, Pham Ngoc Thach University of Medicine, Ho Chi Minh City 700000, Vietnam; (T.T.K.T.); (P.Q.T.P.)
| | - Dang Khoa Tran
- Department of Anatomy, Pham Ngoc Thach University of Medicine (PNTU), Ho Chi Minh City 700000, Vietnam;
| | - Pham Quang Thien Phu
- Department of Internal Medicine, Pham Ngoc Thach University of Medicine, Ho Chi Minh City 700000, Vietnam; (T.T.K.T.); (P.Q.T.P.)
| | | | - Thien Chu Dinh
- Institute for Research and Development, Duy Tan University, 03 Quang Trung, Danang 550000, Vietnam
| | - Dinh Toi Chu
- Department of Human and Animal Physiology, Faculty of Biology, Hanoi National University of Education, Hanoi 100000, Vietnam
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Mikolasevic I, Lukenda Zanko V, Jakopcic I, Domislovic V, Mijic A, Stevanovic T, Delija B, Bokun T, Dinjar Kujundzic P, Ostojic A, Filipec Kanizaj T, Grgurevic I, Krznaric Z, Stimac D, Targher G. Prospective evaluation of non-alcoholic fatty liver disease by elastographic methods of liver steatosis and fibrosis; controlled attenuation parameter and liver stiffness measurements. J Diabetes Complications 2020; 34:107512. [PMID: 31882273 DOI: 10.1016/j.jdiacomp.2019.107512] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2019] [Revised: 11/29/2019] [Accepted: 12/12/2019] [Indexed: 02/07/2023]
Abstract
AIMS To examine the temporal changes of both controlled attenuation parameter (CAP) and liver stiffness measurements (LSM), assessed by Fibroscan, in a large sample of patients with non-alcoholic fatty liver disease (NAFLD). METHODS In this prospective, observational study, we consecutively enrolled 507 adult individuals with Fibroscan-defined NAFLD who were followed for a mean period of 21.2 ± 11.7 months. RESULTS During the follow-up period, 84 patients (16.5%) had a progression of CAP of at least 20% with a median time of 39.93 months, while 201 (39.6%) patients had a progression of LSM of at least 20% with median time of 30.46 months. There were significant differences in the proportion of LSM progression across body mass index (BMI) categories, with obese patients having the highest risk of progression over the follow-up (hazard ratio 1.66; 95%CI 1.23-2.25). Multivariable regression analysis showed that BMI and serum creatinine levels were the strongest predictors for CAP progression in the whole population, while HOMA-estimated insulin resistance was an independent predictor of LSM progression over time in the subgroup of obese patients. CONCLUSION This prospective study shows for the first time that the progression risk of both liver steatosis and fibrosis, detected non-invasively by Fibroscan, is relevant and shares essentially the same metabolic risk factors that are associated with NAFLD progression detected by other invasive methods.
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Affiliation(s)
- I Mikolasevic
- Department of gastroenterology, UHC Rijeka, Rijeka, Croatia; School of medicine, Rijeka, Croatia; Department of gastroenterology, UH Merkur, Zagreb, Croatia.
| | - V Lukenda Zanko
- Department of Internal medicine, General hospital "Josip Benčević", Slavonski Brod, Croatia
| | | | - V Domislovic
- Department of gastroenterology and hepatology, UHC Zagreb, Zagreb, Croatia
| | - A Mijic
- School of medicine, Rijeka, Croatia
| | | | - B Delija
- School of medicine, Rijeka, Croatia
| | - T Bokun
- Department of gastroenterology and hepatology, UH Dubrava, Zagreb, Croatia
| | | | - A Ostojic
- Department of gastroenterology, UH Merkur, Zagreb, Croatia
| | - T Filipec Kanizaj
- Department of gastroenterology, UH Merkur, Zagreb, Croatia; School of medicine, Zagreb, Croatia
| | - I Grgurevic
- Department of gastroenterology and hepatology, UH Dubrava, Zagreb, Croatia; School of medicine, Zagreb, Croatia
| | - Z Krznaric
- Department of gastroenterology and hepatology, UHC Zagreb, Zagreb, Croatia; School of medicine, Zagreb, Croatia
| | - D Stimac
- Department of gastroenterology, UHC Rijeka, Rijeka, Croatia; School of medicine, Rijeka, Croatia
| | - G Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
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27
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Lombardi R, Airaghi L, Targher G, Serviddio G, Maffi G, Mantovani A, Maffeis C, Colecchia A, Villani R, Rinaldi L, Orsi E, Pisano G, Adinolfi LE, Fargion S, Fracanzani AL. Liver fibrosis by FibroScan ® independently of established cardiovascular risk parameters associates with macrovascular and microvascular complications in patients with type 2 diabetes. Liver Int 2020; 40:347-354. [PMID: 31612634 DOI: 10.1111/liv.14274] [Citation(s) in RCA: 56] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Revised: 09/01/2019] [Accepted: 09/23/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are closely associated, and liver fibrosis has been related to macrovascular complications. We examined whether liver fibrosis, diagnosed by FibroScan® , correlates with chronic vascular complications in a cohort of T2DM. METHODS We recruited 394 outpatients with T2DM attending five Italian diabetes centres who underwent liver ultrasonography (US), FibroScan® and extensive evaluation of macrovascular and microvascular diabetic complications. RESULTS Steatosis by US was present in 89%. Almost all patients (96%) were on hypoglycaemic drugs, 58% had at least one chronic vascular complication, 19% a macrovascular complication (prior myocardial infarction and/or ischaemic stroke) and 33% a microvascular one (26% chronic kidney disease [CKD]; 16% retinopathy; 6% neuropathy). In all, 171 (72%) patients had CAP ≥ 248dB/m (ie hepatic steatosis), whereas 83 (21%) patients had LSM ≥ 7.0/6.2 kPa (M/XL probes) (significant liver fibrosis). CAP was not associated with any macro/microvascular complications, whereas LSM ≥ 7.0/6.2 kPa was independently associated with prior cardiovascular disease (adjusted OR 3.3, 95%CI 1.2-8.8; P = .02) and presence of microvascular complications (adjusted OR 4.2, 95%CI 1.5-11.4; P = .005), mainly CKD (adjusted OR 3.6, 95%CI 1.3-10.1; P = .01) and retinopathy (adjusted OR 3.7, CI 95% 1.2-11.9; P = .02). Neither diabetes duration nor haemoglobin A1c differed according to CAP or LSM values. CONCLUSION Significant fibrosis, detected by FibroScan® , is independently associated with increased prevalence of macrovascular and microvascular complications, thus opening a new scenario in the use of this tool for a comprehensive evaluation of hepatic and vascular complications in patients with T2DM.
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Affiliation(s)
- Rosa Lombardi
- Department of Pathophysiology and Transplantation, Ca' Granda IRCCS Foundation, Policlinico Hospital, University of Milan, Milan, Italy
| | - Lorena Airaghi
- Department of Pathophysiology and Transplantation, Ca' Granda IRCCS Foundation, Policlinico Hospital, University of Milan, Milan, Italy
| | - Giovanni Targher
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University Hospital of Verona, Verona, Italy
| | - Gaetano Serviddio
- Centro C.U.R.E, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Gabriele Maffi
- Department of Pathophysiology and Transplantation, Ca' Granda IRCCS Foundation, Policlinico Hospital, University of Milan, Milan, Italy
| | - Alessandro Mantovani
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University Hospital of Verona, Verona, Italy
| | - Claudio Maffeis
- Pediatric Diabetes and Metabolic Disorders Unit, Department of Surgical Sciences, Dentistry, and Pediatrics, and Gynaecology, University Hospital of Verona, Verona, Italy
| | - Antonio Colecchia
- Gastroenterology Unit, Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Rosanna Villani
- Centro C.U.R.E, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Luca Rinaldi
- Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Emanuela Orsi
- Department of Medical Science, Endocrinology and Diabetes Unit, Ca' Granda IRCCS Foundation, Policlinico Hospital, University of Milan, Milan, Italy
| | - Giuseppina Pisano
- Department of Pathophysiology and Transplantation, Ca' Granda IRCCS Foundation, Policlinico Hospital, University of Milan, Milan, Italy
| | - Luigi E Adinolfi
- Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Silvia Fargion
- Department of Pathophysiology and Transplantation, Ca' Granda IRCCS Foundation, Policlinico Hospital, University of Milan, Milan, Italy
| | - Anna L Fracanzani
- Department of Pathophysiology and Transplantation, Ca' Granda IRCCS Foundation, Policlinico Hospital, University of Milan, Milan, Italy
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Prediabetes Is Associated With Increased Liver Stiffness Identified by Noninvasive Liver Fibrosis Assessment. Ultrasound Q 2019; 35:330-338. [PMID: 30724873 DOI: 10.1097/ruq.0000000000000419] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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30
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Transient elastography for assessing severe hepatic fibrosis in diabetic patients with nonalcoholic fatty liver disease: definitions matter. Eur J Gastroenterol Hepatol 2019; 31:1601-1602. [PMID: 31464785 DOI: 10.1097/meg.0000000000001505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
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31
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Bril F, McPhaul MJ, Caulfield MP, Castille JM, Poynard T, Soldevila-Pico C, Clark VC, Firpi-Morell RJ, Lai J, Cusi K. Performance of the SteatoTest, ActiTest, NashTest and FibroTest in a multiethnic cohort of patients with type 2 diabetes mellitus. J Investig Med 2018; 67:303-311. [PMID: 30309884 PMCID: PMC6581087 DOI: 10.1136/jim-2018-000864] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/15/2018] [Indexed: 02/05/2023]
Abstract
Fibromax is a diagnostic tool composed of the combination of 4 non-invasive biomarker panels for the diagnosis of steatosis (SteatoTest), necrosis and inflammation (ActiTest and NashTest-2) and fibrosis (FibroTest). The purpose of this study was to assess the performance of these biomarker panels in patients with type 2 diabetes mellitus (T2DM). All patients underwent routine labs, a 75 g oral glucose tolerance test, a liver proton magnetic resonance spectroscopy (1H-MRS) to measure intrahepatic triglyceride content, and a percutaneous liver biopsy to establish the diagnosis of non-alcoholic steatohepatitis (NASH) and to grade and stage the disease in those patients with non-alcoholic fatty liver disease (NAFLD) by 1H-MRS. For determination of the scores, plasma samples were blindly provided to establish the SteatoTest, ActiTest, NashTest-2 and FibroTest scores. A total of 220 patients with T2DM were included in this study. When the ability of the SteatoTest to identify patients with T2DM with NAFLD by 1H-MRS was assessed, the overall performance expressed as the area under the receiver operating characteristic curve was 0.73 (95% CI 0.65 to 0.81). The performance of the ActiTest and NashTest-2 to diagnose definite NASH among patients with T2DM was 0.70 (95% CI 0.63 to 0.77) and 0.69 (95% CI 0.62 to 0.76), respectively. Regarding the FibroTest score, its performance to identify patients with moderate or advanced fibrosis was 0.67 (95% CI 0.58 to 0.76) and 0.72 (95% CI 0.61 to 0.83), respectively. Non-invasive panels for the diagnosis of steatosis, NASH and/or fibrosis, which were developed and validated in non-diabetic cohorts, underperformed when applied to a large cohort of patients with T2DM. Results from non-diabetic populations should not be extrapolated to patients with T2DM.
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Affiliation(s)
- Fernando Bril
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida, USA.,Malcom Randall Veterans Administration Medical Center, Quest Diagnostics Nichols Institute, Gainesville, Florida, USA
| | - Michael J McPhaul
- Quest Diagnostics Nichols Institute, San Juan Capistrano, California, USA
| | | | | | | | - Consuelo Soldevila-Pico
- Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, Florida, USA
| | - Virginia C Clark
- Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, Florida, USA
| | - Roberto J Firpi-Morell
- Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, Florida, USA
| | - Jinping Lai
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida, USA
| | - Kenneth Cusi
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida, USA.,Malcom Randall Veterans Administration Medical Center, Quest Diagnostics Nichols Institute, Gainesville, Florida, USA
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Roulot D, Roudot-Thoraval F, NKontchou G, Kouacou N, Costes JL, Elourimi G, Le Clesiau H, Ziol M, Beaugrand M. Concomitant screening for liver fibrosis and steatosis in French type 2 diabetic patients using Fibroscan. Liver Int 2017; 37:1897-1906. [PMID: 28556413 DOI: 10.1111/liv.13481] [Citation(s) in RCA: 59] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2016] [Accepted: 05/20/2017] [Indexed: 02/13/2023]
Abstract
BACKGROUND Type 2 diabetes is a risk factor for steatohepatitis and fibrosis. Non-invasive liver stiffness (LS) and controlled attenuation parameter (CAP) measurements by Fibroscan allow assessing liver fat and fibrosis. AIM To determine the prevalence of steatosis and significant fibrosis in a community-based diabetic population. METHODS LS and CAP were measured in 705 patients using the standard "M probe." A second "XL probe" was used, without CAP measurement, in case of failure with the "M probe." RESULTS LS and CAP measurements were obtained in 437 patients (the M group), LS measurements (LSM) with the XL probe being available in additional 232 patients. After the combined use of both probes, LSM failure and unreliable result were 1.6% and 5.6% respectively. Overall, 12.7% (n=85), 7.3% and 2.1% exhibited significant or advanced fibrosis or cirrhosis (LSM≥8 kPa, ≥9.6 kPa, ≥13 kPa respectively), half of the patients with LSM≥8 kPa displayed normal liver tests. Significant and severe steatosis were measured in 75% and 24% of the M group patients. By multivariate analysis, factors associated with severe fibrosis were age, overweight, high GGT. Forty-seven patients with LSM≥8 kPa underwent liver biopsy; 93% had steatosis and 51% severe fibrosis. A significant correlation was found between LSM values and fibrosis score with an accuracy rate of 83%, 68% and 83% for LSM≥8 kPa, ≥9.6 kPa and ≥13 kPa respectively. CONCLUSIONS The prevalence of significant steatosis is very high and significant fibrosis affect 12.7% of the patients. Fibroscan is an effective procedure to screen for fibrosis and steatosis in diabetic patients.
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Affiliation(s)
- Dominique Roulot
- Department of Hepatology, Avicenne Hospital, Assistance Publique-Hôpitaux de Paris, Paris 13 University, Sorbonne Paris Cité, UFR SMBH, Bobigny, France
| | - Françoise Roudot-Thoraval
- Department of Public Health, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris, Paris-Est-Créteil University, Créteil, France
| | - Gisele NKontchou
- Department of Hepatogastroenterology, Jean Verdier Hospital, Assistance Publique-Hôpitaux de Paris, Paris 13 University, Sorbonne Paris Cité, Bobigny, France
| | | | | | - Ghassan Elourimi
- Department of Hepatology, Avicenne Hospital, Assistance Publique-Hôpitaux de Paris, Paris 13 University, Sorbonne Paris Cité, UFR SMBH, Bobigny, France
| | | | - Marianne Ziol
- Department of Anatomopathology, Jean Verdier Hospital, Assistance Publique-Hôpitaux de Paris, Paris 13 University, Sorbonne Paris Cité, UFR SMBH, Bobigny, France
| | - Michel Beaugrand
- Department of Hepatogastroenterology, Jean Verdier Hospital, Assistance Publique-Hôpitaux de Paris, Paris 13 University, Sorbonne Paris Cité, Bobigny, France
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Yeung MW, Wong GLH, Choi KC, Luk AOY, Kwok R, Shu SST, Chan AWH, Lau ESH, Ma RCW, Chan HLY, Chan JCN, Wong VWS, Kong APS. Advanced liver fibrosis but not steatosis is independently associated with albuminuria in Chinese patients with type 2 diabetes. J Hepatol 2017; 68:S0168-8278(17)32334-6. [PMID: 28989092 DOI: 10.1016/j.jhep.2017.09.020] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2017] [Revised: 08/25/2017] [Accepted: 09/23/2017] [Indexed: 12/25/2022]
Abstract
BACKGROUND & AIMS Increasing evidence suggests that non-alcoholic fatty liver disease (NAFLD) may be an independent risk factor for chronic kidney disease (CKD). Given the high prevalence of NAFLD among patients with diabetes who are also at risk of CKD, we aimed to investigate the association between NAFLD and albuminuria, a marker commonly found in diabetic nephropathy. METHODS This study included a cohort of Chinese patients with type 2 diabetes from the Hong Kong Diabetes Registry recruited between March 2013 and May 2014. Liver stiffness measurement (LSM), with probe-specific cut-offs, was used to detect advanced liver fibrosis. While controlled attenuation parameter (CAP) was used to assess liver steatosis using transient elastography. RESULTS A total of 1,763 Chinese patients with type 2 diabetes were recruited in this analysis. The mean (standard deviation) age and duration of diabetes were 60.7 (11.5) years and 10.8 (8.5) years, respectively. The prevalence of albuminuria was higher in diabetic patients with liver steatosis and those with advanced fibrosis (no NAFLD vs. liver steatosis vs. advanced fibrosis: 41.4% vs. 46.2% vs. 64.2%, p <0.001). After adjustment for potential confounders including glycated hemoglobin, hypertension and body mass index, advanced fibrosis, but not liver steatosis, was associated with increased risk of albuminuria (odds ratio [OR] 1.52; 95% confidence interval [CI] 1.02-2.28; p = 0.039) in patients with eGFR ≥60 ml/min/1.73 m2. The odds of albuminuria increased with greater severity of liver fibrosis in a dose dependent manner, with the highest odds observed in patients with LSM scores ≥11.5 kPa assessed by M probe or ≥11.0 kPa assessed by XL probe (adjusted OR 1.53; 95% CI 1.07-2.20; p = 0.021). CONCLUSIONS Advanced liver fibrosis, but not steatosis, is independently associated with albuminuria in Chinese patients with type 2 diabetes. Attention should be paid to liver fibrosis in patients with obesity and type 2 diabetes complicated with albuminuria. LAY SUMMARY In this study, we assessed the link between non-alcoholic fatty liver disease (NAFLD) and albuminuria in a cohort of 1,763 Chinese patients with type 2 diabetes. This study shows that advanced liver fibrosis, a severe form of NAFLD, was independently associated with increased risk of albuminuria. The risk of albuminuria increased with greater severity of liver fibrosis.
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Affiliation(s)
- Ming-Wai Yeung
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
| | - Grace Lai-Hung Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong; Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Kai Chow Choi
- Nethersole School of Nursing, The Chinese University of Hong Kong, Hong Kong
| | - Andrea On-Yan Luk
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong
| | - Raymond Kwok
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
| | - Sally She-Ting Shu
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
| | | | - Eric Siu Him Lau
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
| | - Ronald Ching Wan Ma
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
| | - Henry Lik-Yuen Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong; Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Juliana Chung-Ngor Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong; Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong.
| | - Alice Pik-Shan Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong.
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Ginès P, Graupera I, Lammert F, Angeli P, Caballeria L, Krag A, Guha IN, Murad SD, Castera L. Screening studies of transient elastography and FibroTest in the general population - Authors' reply. Lancet Gastroenterol Hepatol 2017; 2:246-247. [PMID: 28404149 DOI: 10.1016/s2468-1253(17)30050-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2017] [Accepted: 02/13/2017] [Indexed: 10/20/2022]
Affiliation(s)
- Pere Ginès
- Liver Unit, Hospital Clinic, Universitat de Barcelona, Institut d'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), Barcelona, Spain; Centro d'Investigaciones Biomedicas en Red, Enfermedades Hepatologia y Digestivas (CIBEReHD), Barcelona, Spain.
| | - Isabel Graupera
- Liver Unit, Hospital Clinic, Universitat de Barcelona, Institut d'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), Barcelona, Spain; Centro d'Investigaciones Biomedicas en Red, Enfermedades Hepatologia y Digestivas (CIBEReHD), Barcelona, Spain
| | - Frank Lammert
- Department of Medicine II, Saarland University Medical Center, Homburg, Germany
| | - Paolo Angeli
- Unit of Hepatic Emergencies and Liver Transplantation, Department of Medicine (DIMED), University of Padova, Padova, Italy
| | - Llorenç Caballeria
- Centro d'Investigaciones Biomedicas en Red, Enfermedades Hepatologia y Digestivas (CIBEReHD), Barcelona, Spain; Unitat de Suport a la Recerca (USR) Metropolitana Nord, Institut d'Investigació en Atenció Primària (IDIAP) Jordi Gol, Barcelona, Spain
| | - Aleksander Krag
- Department of Gastroenterology and Hepatology, Odense Patient data Exploratory Network (OPEN), Odense University Hospital, Odense, Denmark
| | - I Nehil Guha
- NIHR Nottingham Digestive Diseases Biomedical Research Unit, University of Nottingham, Nottingham, UK
| | - S Darwish Murad
- Department of Gastroenterology and Hepatology, Erasmus Medical Center Rotterdam, Rotterdam, Netherlands
| | - Laurent Castera
- Department of Hepatology, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France; Université Paris VII, INSERM UMR 1149, Centre de Recherche sur l'Inflammation, Paris, France
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Poynard T, Peta V, Pollo-Flores P, Munteanu M, Ratziu V. Screening studies of transient elastography and FibroTest in the general population. Lancet Gastroenterol Hepatol 2017; 2:246. [DOI: 10.1016/s2468-1253(17)30034-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2017] [Revised: 02/02/2017] [Accepted: 02/02/2017] [Indexed: 12/12/2022]
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Elkabbany ZA, Elbarbary NS, Ismail EA, Mohamed NA, Ragab D, Abdel Alem S, Ezzat YM, Maurice SS, Hashem NU. Transient elastography as a noninvasive assessment tool for hepatopathies of different etiology in pediatric type 1 diabetes mellitus. J Diabetes Complications 2017; 31:186-194. [PMID: 27742550 DOI: 10.1016/j.jdiacomp.2016.09.009] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2016] [Revised: 09/17/2016] [Accepted: 09/21/2016] [Indexed: 02/08/2023]
Abstract
AIM To identify the prevalence and effect of hepatopathies of different etiologies among pediatric patients with type 1 diabetes mellitus (T1DM) using transient elastography (TE) and its relation to glycemic control. METHODS One hundred T1DM patients were studied focusing on liver functions, fasting lipid profile, hemoglobin A1c (HbA1c), hepatitis C virus (HCV), serum immunoglobulins, autoimmune antibodies; anti-nuclear antibody (ANA), anti-smooth muscle antibody (ASMA), and anti-liver kidney microsomal antibody (anti-LKM). Abdominal ultrasound was performed and TE was done for patients with HCV, positive autoimmune antibody and/or abnormal ultrasound findings. RESULTS Thirty-one patients were found to have one or more hepatic abnormalities; clinical hepatomegaly in 8%, elevated alanine aminotransferase (ALT) in 10%, HCV in 6%, autoimmune hepatitis (AIH) in 11% (10 were positive for ASMA and 2 were positive for ANA while anti-LKM antibodies were negative) and abnormal hepatic ultrasound in 20% (12 non-alcoholic fatty liver disease, 5 AIH, 2 HCV, 1 Mauriac syndrome). Mean liver stiffness in those 31 patients was 7.0±2.1kPa (range, 3.1-11.8kPa); 24 were Metavir F0-F1, 7 were F2-F3 while none was F4. Type 1 diabetic patients with abnormal hepatic ultrasound had higher fasting blood glucose, HbA1c and total cholesterol than those with normal findings. Liver stiffness was significantly higher in patients with abnormal liver ultrasound compared with normal sonography. Liver stiffness was positively correlated to HbA1c and ALT. CONCLUSIONS Hepatic abnormalities are prevalent in T1DM and related to poor metabolic control. TE provides a non-invasive method for detection of hepatopathy-induced fibrosis.
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Affiliation(s)
- Zeinab A Elkabbany
- Department of Pediatrics, Faculty of medicine, Ain shams University, Cairo, Egypt
| | - Nancy S Elbarbary
- Department of Pediatrics, Faculty of medicine, Ain shams University, Cairo, Egypt.
| | - Eman A Ismail
- Department of Clinical Pathology, Faculty of medicine, Ain shams University, Cairo, Egypt
| | - Nesrine A Mohamed
- Department of Clinical Pathology, Faculty of medicine, Ain shams University, Cairo, Egypt
| | - Dina Ragab
- Department of Clinical Pathology, Faculty of medicine, Ain shams University, Cairo, Egypt
| | - Shereen Abdel Alem
- Department of Endemic medicine and Hepatology, Faculty of medicine, Cairo University, Cairo, Egypt
| | - Yasmine M Ezzat
- Department of Pediatrics, Faculty of medicine, Ain shams University, Cairo, Egypt
| | - Sarah S Maurice
- Department of Pediatrics, Faculty of medicine, Ain shams University, Cairo, Egypt
| | - Noha U Hashem
- Department of Pediatrics, Faculty of medicine, Ain shams University, Cairo, Egypt
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Mikolasevic I, Orlic L, Franjic N, Hauser G, Stimac D, Milic S. Transient elastography (FibroScan(®)) with controlled attenuation parameter in the assessment of liver steatosis and fibrosis in patients with nonalcoholic fatty liver disease - Where do we stand? World J Gastroenterol 2016; 22:7236-7251. [PMID: 27621571 PMCID: PMC4997649 DOI: 10.3748/wjg.v22.i32.7236] [Citation(s) in RCA: 187] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2016] [Revised: 06/28/2016] [Accepted: 08/01/2016] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Currently, the routinely used modalities are unable to adequately determine the levels of steatosis and fibrosis (laboratory tests and ultrasonography) or cannot be applied as a screening procedure (liver biopsy). Among the non-invasive tests, transient elastography (FibroScan(®), TE) with controlled attenuation parameter (CAP) has demonstrated good accuracy in quantifying the levels of liver steatosis and fibrosis in patients with NAFLD, the factors associated with the diagnosis and NAFLD progression. The method is fast, reliable and reproducible, with good intra- and interobserver levels of agreement, thus allowing for population-wide screening and disease follow-up. The initial inability of the procedure to accurately determine fibrosis and steatosis in obese patients has been addressed with the development of the obese-specific XL probe. TE with CAP is a viable alternative to ultrasonography, both as an initial assessment and during follow-up of patients with NAFLD. Its ability to exclude patients with advanced fibrosis may be used to identify low-risk NAFLD patients in whom liver biopsy is not needed, therefore reducing the risk of complications and the financial costs.
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Kwok R, Choi KC, Wong GLH, Zhang Y, Chan HLY, Luk AOY, Shu SST, Chan AWH, Yeung MW, Chan JCN, Kong APS, Wong VWS. Screening diabetic patients for non-alcoholic fatty liver disease with controlled attenuation parameter and liver stiffness measurements: a prospective cohort study. Gut 2016; 65:1359-68. [PMID: 25873639 DOI: 10.1136/gutjnl-2015-309265] [Citation(s) in RCA: 352] [Impact Index Per Article: 39.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2015] [Accepted: 03/31/2015] [Indexed: 12/16/2022]
Abstract
OBJECTIVE Type 2 diabetes is an important risk factor for non-alcoholic fatty liver disease (NAFLD), but current guidelines provide conflicting recommendations on whether diabetic patients should be screened for NAFLD. We therefore studied the strategy of screening diabetic patients by FibroScan. DESIGN Liver fat and fibrosis were assessed by controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) by FibroScan at a diabetic centre for patients from primary care and hospital clinics. Probe-specific LSM cut-offs were used to detect advanced fibrosis. RESULTS Of 1918 patients examined, 1799 (93.8%) had valid CAP and 1884 (98.2%) had reliable LSM (1770 with the M probe and 114 with the XL probe). The proportion of patients with increased CAP and LSM was 72.8% (95% CI 70.7% to 74.8%) and 17.7% (95% CI 16.0% to 19.5%), respectively. By multivariable analysis, female gender, higher body mass index, triglycerides, fasting plasma glucose and alanine aminotransferase (ALT) and non-insulin use were associated with increased CAP. Longer duration of diabetes, higher body mass index, increased ALT and spot urine albumin:creatinine ratio and lower high-density lipoprotein-cholesterol were associated with increased LSM. Ninety-four patients (80% had increased LSM) underwent liver biopsy: 56% had steatohepatitis and 50% had F3-4 disease. CONCLUSIONS Diabetic patients have a high prevalence of NAFLD and advanced fibrosis. Those with obesity and dyslipidaemia are at particularly high risk and may be the target for liver assessment. Our data support screening for NAFLD and/or advanced fibrosis in patients with type 2 diabetes.
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Affiliation(s)
- Raymond Kwok
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Kai Chow Choi
- Nethersole School of Nursing, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Grace Lai-Hung Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong State Key Laboratory in Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Yuying Zhang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Henry Lik-Yuen Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong State Key Laboratory in Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Andrea On-Yan Luk
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Sally She-Ting Shu
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong State Key Laboratory in Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Anthony Wing-Hung Chan
- Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Ming-Wai Yeung
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Juliana Chung-Ngor Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Alice Pik-Shan Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong State Key Laboratory in Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
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Leite NC, Villela-Nogueira CA, Ferreira MT, Cardoso CRL, Salles GF. Increasing aortic stiffness is predictive of advanced liver fibrosis in patients with type 2 diabetes: the Rio-T2DM cohort study. Liver Int 2016; 36:977-85. [PMID: 26509555 DOI: 10.1111/liv.12994] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2015] [Accepted: 10/20/2015] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIMS Type 2 diabetes mellitus (T2DM) is a risk factor for cardiovascular disease (CVD) and advanced stages of non-alcoholic fatty liver disease (NAFLD). The aim was to evaluate the association between aortic stiffness, a preclinical CVD marker, with advanced liver fibrosis identified by transient elastography (TE) in T2DM outpatients with NAFLD. METHODS This longitudinal study included 291 T2DM patients with NAFLD detected by ultrasonography, who had two carotid-femoral pulse wave velocity (cf-PWV) measurements and a TE examination (Fibroscan(®) ) performed over a median follow-up of 7 years. Advanced liver fibrosis (corresponding to ≥ F3 stage) was considered as median values >7.9 kPa (M probe) or >7.2 kPa (XL probe). Increased aortic stiffness was defined as cf-PWV >10 m/s. RESULTS Eighty patients (27.5%) had advanced liver fibrosis. Overall, there was an increase in cf-PWV of 0.1 m/s/year (1% per year). Both a high aortic stiffness at the 2nd cf-PWV examination [odds ratios (OR): 3.0; 95% CI: 1.3-7.2; P = 0.011] and a serial increase in aortic stiffness (OR: 2.1; 95% CI: 1.0-4.3; P = 0.046) were associated with increased odds of having advanced liver fibrosis. Patients who presented either an increase in aortic stiffness or persisted with high values had significantly higher mean liver stiffness than those who either decreased aortic stiffness or persisted with normal cf-PWV values (mean difference: 2.1 kPa, 95% CI: 0.5-3.7 kPa, P = 0.012), after adjustments for anthropometric-demographic and clinical laboratory covariates. CONCLUSIONS In T2DM patients with NAFLD, a high or increasing aortic stiffness predicted development of advanced liver fibrosis on TE.
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Affiliation(s)
- Nathalie C Leite
- Department of Internal Medicine, Medical School and University Hospital Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Cristiane A Villela-Nogueira
- Department of Internal Medicine, Medical School and University Hospital Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Marcel T Ferreira
- Department of Internal Medicine, Medical School and University Hospital Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Claudia R L Cardoso
- Department of Internal Medicine, Medical School and University Hospital Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Gil F Salles
- Department of Internal Medicine, Medical School and University Hospital Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
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Automatic detection of cirrhosis in hospitalized patients: a pragmatic experience. Eur J Gastroenterol Hepatol 2016; 28:74-81. [PMID: 26317562 DOI: 10.1097/meg.0000000000000464] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
BACKGROUND/AIM We evaluated the relevance of a systematic automatic detection of cirrhosis using biochemical markers in hospitalized patients. METHODS We automatically calculated three free biochemical tests (APRI, Fib-4, and Forns) in patients consecutively hospitalized in our university hospital between July and September, 2010. Patients >18 years not known to suffer from chronic liver disease, were contacted to undergo liver stiffness measurement (LSM) as a reference diagnostic tool. To limit false positives, we required at least one APRI≥2 (indicating cirrhosis) and Fib-4>3.25 and/or Forns>6.9, without obvious overestimation. RESULTS A total of 10,035 APRI, 9903 Fib-4, and 1250 Forns were available in 4074 patients. The fibrosis tests were independently influenced by the location of the patient, especially Cardiology (Lower Forns) and Hematology/Oncology Departments (higher APRI, Fib-4, and Forns). Overall, 101 patients (2.48%) were suspected to have cirrhosis. LSM identified two cases of cirrhosis (LSM>13 kPa). In intent-to-diagnose analyses, the highest positive predictive values of the APRI, Fib-4, and Forns for the diagnosis of cirrhosis were 1.98, 1.98, and 11.76%, respectively. The positive predictive value never exceeded 50% in per-protocol analyses when considering patients with numerous positive results of the fibrosis tests. CONCLUSION In hospitalized patients, automatic detection of cirrhosis on the basis of APRI, Fib-4, and Forns was inefficient because of too many false-positive results.
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Poynard T, Deckmyn O, Munteanu M, Ngo Y, Drane F, Castille JM, Housset C, Ratziu V. Awareness of the severity of liver disease re-examined using software-combined biomarkers of liver fibrosis and necroinflammatory activity. BMJ Open 2015; 5:e010017. [PMID: 26700292 PMCID: PMC4691773 DOI: 10.1136/bmjopen-2015-010017] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2015] [Revised: 11/10/2015] [Accepted: 11/11/2015] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Effective antiviral treatment (direct-acting antiviral agents (DAAs)), the requirement for a fibrosis score to support DDA reimbursement and a screening strategy, such as the USA baby boomer campaign, should lead to an increased awareness of liver disease severity. OBJECTIVE To compare the awareness of liver disease severity between the USA and France, two countries with similar access to hepatitis C virus (HCV) and hepatitis B virus (HBV) treatments, similar rules for treatment reimbursement and similar availability of validated fibrosis tests, but with different policies, as France has no screening. METHOD The global database of the FibroTest-ActiTest, including 1,085,657 subjects between 2002 and 2014, was retrospectively analysed. Awareness was defined as the test prescription rate and was compared between the USA and France, according to year of birth, gender and dates of DAA availability and screening campaign (2013-2014). RESULTS In the USA 252,688 subjects were investigated for HCV, with a dramatic increase (138%) in the test rate in 2013-2014 (119,271) compared with 2011-2012 (50,031). In France 470,762 subjects were investigated (subjects with HCV and other disease) and the rates were stable. In USA 82.4% of subjects and in France 84.6% were classified as either the highest or lowest priority. The most striking difference was the higher test rate in women born between 1935 and 1944 in France 30,384/200,672 (15.1%) compared with the USA 8035/97,079 (8.3%) (OR=1.98 (95% CI 1.93 to 2.03) p<0.0001). This resulted in twice as many cases of cirrhosis being detected, 2.6% (5191/200,672 women) and 1.3% (1303/97,079), respectively, despite the same prevalence of cirrhosis in this age group (17.1% vs 16.2%) and without any clear explanation as to why they had not been included in the USA screening. CONCLUSIONS This study highlighted in the USA the association between awareness of liver disease and both the HCV campaign and DAA availability. In comparison with France, there was a dramatically lower awareness of cirrhosis in the USA for women born between 1935 and 1944.
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Affiliation(s)
- Thierry Poynard
- Groupe Hospitalier Pitié Salpêtrière APHP, Paris, France
- Sorbonne Universités, UPMC Univ Paris 06, UMR_S 938 and Institute of Cardiometabolism and Nutrition (ICAN), INSERM, Paris, France
| | | | | | - Yen Ngo
- BioPredictive, Paris, France
| | | | | | - Chantal Housset
- Sorbonne Universités, UPMC Univ Paris 06, UMR_S 938 and Institute of Cardiometabolism and Nutrition (ICAN), INSERM, Paris, France
| | - Vlad Ratziu
- Groupe Hospitalier Pitié Salpêtrière APHP, Paris, France
- Sorbonne Universités, UPMC Univ Paris 06, UMR_S 938 and Institute of Cardiometabolism and Nutrition (ICAN), INSERM, Paris, France
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Williams KH, Burns K, Constantino M, Shackel NA, Prakoso E, Wong J, Wu T, George J, McCaughan GW, Twigg SM. An association of large-fibre peripheral nerve dysfunction with non-invasive measures of liver fibrosis secondary to non-alcoholic fatty liver disease in diabetes. J Diabetes Complications 2015; 29:1240-7. [PMID: 26297218 DOI: 10.1016/j.jdiacomp.2015.06.015] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2015] [Revised: 06/24/2015] [Accepted: 06/29/2015] [Indexed: 01/13/2023]
Abstract
AIM To examine for an association of elevated lower-limb vibration perception threshold (VPT) with NAFLD fibrosis. METHODS Two cohorts from a tertiary diabetes centre were studied - Cohort 1, n=456 with type 1 or 2 diabetes, and Cohort 2, n=106 with type 2 diabetes mellitus. All underwent a detailed assessment, including VPT measurement. Cohort 2 also had liver ultrasound and transient elastography (TE). NAFLD Fibrosis Score (NFS) was calculated for all with available data. Follow-up VPT measurements on participants in Cohort 1 to 2014 were also collected if available. RESULTS Adjusted risk of higher VPT category (≥25V but <50V, or ≥50V, c.f. < 25V) was greater for high-risk NFS in both cohorts (Cohort 1, OR 2.22 [95% CI 1.24-3.98, p=0.007] and Cohort 2, OR 4.51 [95% CI 1.08-18.87], p=0.039) and higher liver stiffness measurement (LSM) by TE in Cohort 2 (OR for each unit natural log increase in LSM of 2.42 (95% CI 1.13-5.19), p=0.023). In Cohort 1, in those with VPT<50V and complete data, those with higher NFS had greater odds of increasing VPT category after 2.2 (IQR 1.5-2.9) years. CONCLUSIONS Higher VPT associates with markers of liver fibrosis due to NAFLD in diabetes mellitus.
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Affiliation(s)
- Kathryn H Williams
- Central Clinical School, Room 408, Blackburn Building D06, The University of Sydney, New South Wales, Australia, 2006; Royal Prince Alfred Hospital, Missenden Road, Camperdown, New South Wales, Australia, 2050; Charles Perkins Centre and Bosch Institute, Building D17, The University of Sydney, New South Wales, Australia, 2006.
| | - Kharis Burns
- Central Clinical School, Room 408, Blackburn Building D06, The University of Sydney, New South Wales, Australia, 2006; Westmead Hospital, Cnr Darcy Road and Bridge Street, Westmead, NSW, Australia, 2145.
| | - Maria Constantino
- Royal Prince Alfred Hospital, Missenden Road, Camperdown, New South Wales, Australia, 2050.
| | - Nicholas A Shackel
- Central Clinical School, Room 408, Blackburn Building D06, The University of Sydney, New South Wales, Australia, 2006; Royal Prince Alfred Hospital, Missenden Road, Camperdown, New South Wales, Australia, 2050; Centenary Institute, Locked Bag 9, Newtown, New South Wales, Australia, 2042.
| | - Emilia Prakoso
- Royal Prince Alfred Hospital, Missenden Road, Camperdown, New South Wales, Australia, 2050; Centenary Institute, Locked Bag 9, Newtown, New South Wales, Australia, 2042.
| | - Jencia Wong
- Central Clinical School, Room 408, Blackburn Building D06, The University of Sydney, New South Wales, Australia, 2006; Royal Prince Alfred Hospital, Missenden Road, Camperdown, New South Wales, Australia, 2050.
| | - Ted Wu
- Royal Prince Alfred Hospital, Missenden Road, Camperdown, New South Wales, Australia, 2050.
| | - Jacob George
- Central Clinical School, Room 408, Blackburn Building D06, The University of Sydney, New South Wales, Australia, 2006; Westmead Hospital, Cnr Darcy Road and Bridge Street, Westmead, NSW, Australia, 2145; Westmead Millennium Institute for Clinical Research, P.O. Box 412, Westmead, New South Wales, Australia, 2145.
| | - Geoffrey W McCaughan
- Central Clinical School, Room 408, Blackburn Building D06, The University of Sydney, New South Wales, Australia, 2006; Royal Prince Alfred Hospital, Missenden Road, Camperdown, New South Wales, Australia, 2050; Centenary Institute, Locked Bag 9, Newtown, New South Wales, Australia, 2042.
| | - Stephen M Twigg
- Central Clinical School, Room 408, Blackburn Building D06, The University of Sydney, New South Wales, Australia, 2006; Royal Prince Alfred Hospital, Missenden Road, Camperdown, New South Wales, Australia, 2050; Charles Perkins Centre and Bosch Institute, Building D17, The University of Sydney, New South Wales, Australia, 2006.
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Rhou YJJ, Henshaw FR, McGill MJ, Twigg SM. Congestive heart failure presence predicts delayed healing of foot ulcers in diabetes: An audit from a multidisciplinary high-risk foot clinic. J Diabetes Complications 2015; 29:556-62. [PMID: 25804931 DOI: 10.1016/j.jdiacomp.2015.02.009] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2014] [Revised: 02/11/2015] [Accepted: 02/15/2015] [Indexed: 12/17/2022]
Abstract
AIMS This retrospective study aimed to investigate both established and less well-explored factors as potential predictive variables for failed and delayed ulcer healing. METHODS Patients with type 1 or 2 diabetes with foot ulceration presenting consecutively to, and then subsequently managed at, a multidisciplinary, high-risk foot clinic were followed until ulcer healing, amputation or death. Data comprised prospective standardised documentation at each visit and retrospective collection from hospital records, and included patient demographics, comorbidities, laboratory variables, and ulcer infection, depth and area at each presentation. Multiple regression analysis was used to determine independent predictors of failure to heal and delayed healing. RESULTS Of the 107 consecutive patients studied, 95 (89%) healed overall, 50 (47%) had healed in 12 weeks and the mean healing rate was a 10% decrease in ulcer area per week. Amongst all variables examined, comorbid congestive heart failure (CHF) was the only factor independently predictive of all measured outcomes of failure to heal overall, delayed healing at 12 weeks, and reduced healing rate. Ulcer infection at presentation, longer duration of antibiotic use, and liver enzyme abnormalities of raised ALT and AST:ALT<1 (each suggestive of non-alcoholic fatty liver disease), were also predictive of poor ulcer outcomes. CONCLUSIONS Comorbid congestive cardiac failure is predictive of delayed foot ulcer healing rate as well as a lower probability of healing overall. Liver enzyme abnormalities also predicted delayed ulcer healing outcomes. The mechanisms underlying these associations with foot ulcer outcomes in diabetes are unclear. Further studies are needed to determine the role of systematic routine documentation of heart failure and its severity, and then targeting of heart failure to potentially aid the management of foot ulcers in diabetes.
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Affiliation(s)
| | | | - M J McGill
- Sydney Medical School, University of Sydney; Diabetes Centre, Dept of Endocrinology, Royal Prince Alfred Hospital, Sydney
| | - S M Twigg
- Sydney Medical School, University of Sydney; Diabetes Centre, Dept of Endocrinology, Royal Prince Alfred Hospital, Sydney.
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Katsiki N, Maltezos E, Papanas N. Diabetic foot: lipids, new and old vascular risk markers. J Diabetes Complications 2014; 28:913-4. [PMID: 25139046 DOI: 10.1016/j.jdiacomp.2014.07.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2014] [Accepted: 07/23/2014] [Indexed: 11/25/2022]
Affiliation(s)
- Niki Katsiki
- Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippocration Hospital, Thessaloniki, Greece
| | - Efstratios Maltezos
- Outpatient Clinic of the Diabetic Foot, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis, Greece
| | - Nikolaos Papanas
- Outpatient Clinic of the Diabetic Foot, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis, Greece.
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45
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Ahn JM, Paik YH, Kim SH, Lee JH, Cho JY, Sohn W, Gwak GY, Choi MS, Lee JH, Koh KC, Paik SW, Yoo BC. Relationship of liver stiffness and controlled attenuation parameter measured by transient elastography with diabetes mellitus in patients with chronic liver disease. J Korean Med Sci 2014; 29:1113-9. [PMID: 25120322 PMCID: PMC4129204 DOI: 10.3346/jkms.2014.29.8.1113] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2014] [Accepted: 05/07/2014] [Indexed: 12/17/2022] Open
Abstract
High prevalence of diabetes mellitus in patients with liver cirrhosis has been reported in many studies. The aim of our study was to evaluate the relationship of hepatic fibrosis and steatosis assessed by transient elastography with diabetes in patients with chronic liver disease. The study population consisted of 979 chronic liver disease patients. Liver fibrosis and steatosis were assessed by liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) on transient elastography. Diabetes was diagnosed in 165 (16.9%) of 979 patients. The prevalence of diabetes had significant difference among the etiologies of chronic liver disease. Higher degrees of liver fibrosis and steatosis, assessed by LSM and CAP score, showed higher prevalence of diabetes (F0/1 [14%], F2/3 [18%], F4 [31%], P<0.001; S0/1 [15%], S2 [17%], S3 [26%], P=0.021). Multivariate analysis showed that the independent predictive risk factors for diabetes were hypertension (OR, 1.98; P=0.001), LSM F4 (OR, 1.86; P=0.010), male gender (OR, 1.60; P=0.027), and age>50 yr (OR, 1.52; P=0.046). The degree of hepatic fibrosis but not steatosis assessed by transient elastography has significant relationship with the prevalence of diabetes in patients with chronic liver disease.
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Affiliation(s)
- Jem Ma Ahn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yong-Han Paik
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - So Hyun Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jun Hee Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Ju Yeon Cho
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Won Sohn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Geum-Youn Gwak
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Moon Seok Choi
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Joon Hyeok Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kwang Cheol Koh
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Seung Woon Paik
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Byung Chul Yoo
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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46
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Cui XW, Friedrich-Rust M, Molo CD, Ignee A, Schreiber-Dietrich D, Dietrich CF. Liver elastography, comments on EFSUMB elastography guidelines 2013. World J Gastroenterol 2013; 19:6329-6347. [PMID: 24151351 PMCID: PMC3801303 DOI: 10.3748/wjg.v19.i38.6329] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2013] [Revised: 08/11/2013] [Accepted: 09/17/2013] [Indexed: 02/06/2023] Open
Abstract
Recently the European Federation of Societies for Ultrasound in Medicine and Biology Guidelines and Recommendations have been published assessing the clinical use of ultrasound elastography. The document is intended to form a reference and to guide clinical users in a practical way. They give practical advice for the use and interpretation. Liver disease forms the largest section, reflecting published experience to date including evidence from meta-analyses with shear wave and strain elastography. In this review comments and illustrations on the guidelines are given.
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Sharma P, Kirnake V, Tyagi P, Bansal N, Singla V, Kumar A, Arora A. Spleen stiffness in patients with cirrhosis in predicting esophageal varices. Am J Gastroenterol 2013; 108:1101-7. [PMID: 23629600 DOI: 10.1038/ajg.2013.119] [Citation(s) in RCA: 129] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2012] [Accepted: 02/04/2013] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Screening for esophageal varices (EV) is recommended in patients with cirrhosis. Noninvasive tests had shown varying sensitivity (Se) and specificity (Sp) for predicting EV. Splenomegaly is a common finding in liver cirrhosis because of portal and splenic congestion. These changes can be quantified by transient elastography; hence, the aim of this study was to investigate the utility of spleen stiffness (SS) in evaluating EV in comparison with other noninvasive tests. METHODS We measured SS and liver stiffness (LS) by using FibroScan in 200 consecutive cirrhotic patients who met the inclusion criteria. Patients were also assessed by hepatic venous pressure gradient (HVPG), upper gastrointestinal endoscopy, LS-spleen diameter to platelet ratio score (LSPS), and platelet count to spleen diameter ratio (PSR). RESULTS Of 200 patients enrolled, 174 patients had valid LS and SS measurement, and 124 (71%) patients had EV (small, n=46 and large n=78). There was a significant difference in median LS (51.4 vs. 23.9 kPa, P=0.001), SS (54 vs. 32 kPa, P=0.001), LSPS (6.1 vs. 2.5, P=0.001), and PSR (812 vs. 1,165, P=0.001) between patients with EV and those without EV. LS ≥27.3 kPa had an Se of 91%, Sp of 72%, positive predictive value (PPV) of 89%, negative predictive value (NPV) of 76%, and a diagnostic accuracy of 86% in predicting EV. LSPS ≥3.09 had Se and Sp of 89% and 76%, respectively, and a PSR cutoff value of 909 or less had Se of 64%, Sp of 76%, and diagnostic accuracy of 68% in predicting EV. SS ≥40.8 kPa had Se (94%), Sp (76%), PPV (91%), NPV (84%), and diagnostic accuracy of 86% for predicting EV. SS was significantly higher in patients who had large varices (56 vs. 49 kPa, P=0.001) and variceal bleed (58 vs. 50.2 kPa, P=0.001). Combining LS+SS (27.3+40.8 kPa) had Se of 90%, Sp 90%, PPV 96%, NPV 79%, and a diagnostic accuracy of 90%. HVPG (n=52) showed significant correlation with SS (r=0.433, P=0.001), LSPS (r=0.335, P=0.01), and PSR (r=-0.270, P=0.05), but not with LS (r=0.178, P=0.20). CONCLUSIONS Measurement of SS can be used for noninvasive assessment of EV and can differentiate large vs. small varices and nonbleeder vs. bleeder.
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Affiliation(s)
- Praveen Sharma
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital, New Delhi, India.
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Williams KH, Shackel NA, Gorrell MD, McLennan SV, Twigg SM. Diabetes and nonalcoholic Fatty liver disease: a pathogenic duo. Endocr Rev 2013; 34:84-129. [PMID: 23238855 DOI: 10.1210/er.2012-1009] [Citation(s) in RCA: 171] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Recent data increasingly support a complex interplay between the metabolic condition diabetes mellitus and the pathologically defined nonalcoholic fatty liver disease (NAFLD). NAFLD predicts the development of type 2 diabetes and vice versa, and each condition may serve as a progression factor for the other. Although the association of diabetes and NAFLD is likely to be partly the result of a "common soil," it is also probable that diabetes interacts with NAFLD through specific pathogenic mechanisms. In particular, through interrelated metabolic pathways currently only partly understood, diabetes appears to accelerate the progression of NAFLD to nonalcoholic steatohepatitis, defined by the presence of necroinflammation, with varying degrees of liver fibrosis. In the research setting, obstacles that have made the identification of clinically significant NAFLD, and particularly nonalcoholic steatohepatitis, difficult are being addressed with the use of new imaging techniques combined with risk algorithms derived from peripheral blood profiling. These techniques are likely to be used in the diabetes population in the near future. This review examines the pathogenic links between NAFLD and diabetes by exploring the epidemiological evidence in humans and also through newer animal models. Emerging technology to help screen noninvasively for differing pathological forms of NAFLD and the potential role of preventive and therapeutic approaches for NAFLD in the setting of diabetes are also examined.
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Affiliation(s)
- K H Williams
- Sydney Medical School and the Bosch Institute, The University of Sydney, Sydney, New South Wales 2006, Australia
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Marshall RP, Simpson JK, Lukey PT. Strategies for biomarker discovery in fibrotic disease. Biochim Biophys Acta Mol Basis Dis 2013; 1832:1079-87. [PMID: 23376113 DOI: 10.1016/j.bbadis.2013.01.018] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2012] [Revised: 01/18/2013] [Accepted: 01/22/2013] [Indexed: 01/06/2023]
Abstract
The discovery and development of biomarkers for fibrotic diseases have potential utility in clinical decision-making as well as in pharmaceutical research and development. This review describes strategies for identifying diagnostic, prognostic and theranostic biomarkers. A range of technologies and platforms for biomarker discovery are highlighted, including several with specific relevance for fibrosis. Some challenges specific to fibrotic diseases are outlined including; benchmarking biomarkers against imperfect clinical measures of fibrosis, the complexity resulting from diverse aetiologies and target organs, and the availability of samples (including biopsy) from well-characterised patients with fibrotic disease. To overcome these challenges collaboration amongst clinical specialities as well as between academia and industry is essential. This article is part of a Special Issue entitled: Fibrosis: Translation of basic research to human disease.
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Affiliation(s)
- Richard P Marshall
- Fibrosis Discovery Performance Unit, GlaxoSmithKline R&D, GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, UK.
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Brea A, Puzo J. Non-alcoholic fatty liver disease and cardiovascular risk. Int J Cardiol 2012; 167:1109-17. [PMID: 23141876 DOI: 10.1016/j.ijcard.2012.09.085] [Citation(s) in RCA: 66] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2012] [Revised: 05/26/2012] [Accepted: 09/15/2012] [Indexed: 02/07/2023]
Abstract
The term "Non-alcoholic fatty liver disease" (NAFLD) covers a series of liver lesions similar to those induced by alcohol, but not caused by alcohol use. The importance of NAFLD lies in the high prevalence in Western societies and, from the point of view of the liver, in its progression from steatosis to cirrhosis and liver cancer. More recently, NAFLD has been found to be associated with lipid metabolism disorders, the deposition of fat outside of the adipocytes, insulin resistance and Metabolic Syndrome. Also attributed to NAFLD is a heightened systemic pro-inflammatory state, which accelerates arteriosclerosis, thereby increasing cardiovascular risk and associated cardiovascular events. Here we provide an update to the etiopathogenesis of NAFLD, its influence on cardiovascular disease, and the treatment options.
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Affiliation(s)
- Angel Brea
- Unidad de Lípidos, Servicio de Medicina Interna, Hospital San Pedro, Logroño, Spain
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