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Bale G, Clarembeau F, Stärkel P, Dahlqvist G, Horsmans Y, Lanthier N. Patients with chronic liver diseases are at risk for diabetes even before development of cirrhosis. Clin Res Hepatol Gastroenterol 2024; 48:102428. [PMID: 39048075 DOI: 10.1016/j.clinre.2024.102428] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Revised: 07/17/2024] [Accepted: 07/22/2024] [Indexed: 07/27/2024]
Abstract
BACKGROUND AND AIMS The prevalence of insulin resistance (IR) and type 2 diabetes mellitus (T2DM) is higher in patients with cirrhosis, compared to control patients without liver disease. The exact mechanism for this is unknown but could include liver inflammation. In this study we investigate whether cirrhosis is the primum movens of IR or if impaired insulin sensitivity is already present in non-cirrhotic patients with chronic liver diseases. METHODS Patients were recruited and divided into three groups: control (CTL), chronic liver disease without cirrhosis (CLD) and cirrhosis (CIR). In patients not taking pharmacological treatment for T2DM, IR was quantified using the homeostasis model assessment of insulin resistance (HOMA-IR). The proportion of patients with T2DM as well as HOMA-IR levels among different disease etiologies were recorded and compared. RESULTS 532 patients were included in our study. Median glycemia and insulinemia and therefore HOMA-IR values were significantly different between the three cohorts (p-value <0.001): IR levels in CLD subjects lie between those seen in CTL and CIR subjects. The proportion of diabetic patients in the two case categories also differs (p-value = 0.027): one quarter of CLD subjects and one third of CIR patients suffer from T2DM. Finally, HOMA-IR levels vary according to disease etiology (p-value <0.001): metabolic steatosis and chronic viral hepatitis C are at greater risk than alcohol and other disease causes. CONCLUSION CLD is already a predisposing factor to T2DM, regardless of the presence of CIR. CIR is a factor which elicits additional increase in insulin levels. Metabolic steatosis and hepatitis C are associated with more severe IR.
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Affiliation(s)
- Georgia Bale
- Service d'Hépato-Gastroentérologie, Cliniques universitaires Saint-Luc, UCLouvain, Brussels, Belgium
| | - Frédéric Clarembeau
- Service d'Hépato-Gastroentérologie, Cliniques universitaires Saint-Luc, UCLouvain, Brussels, Belgium; Laboratory of Hepatology and Gastroenterology, Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, Belgium
| | - Peter Stärkel
- Service d'Hépato-Gastroentérologie, Cliniques universitaires Saint-Luc, UCLouvain, Brussels, Belgium; Laboratory of Hepatology and Gastroenterology, Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, Belgium
| | - Géraldine Dahlqvist
- Service d'Hépato-Gastroentérologie, Cliniques universitaires Saint-Luc, UCLouvain, Brussels, Belgium
| | - Yves Horsmans
- Service d'Hépato-Gastroentérologie, Cliniques universitaires Saint-Luc, UCLouvain, Brussels, Belgium; Laboratory of Hepatology and Gastroenterology, Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, Belgium
| | - Nicolas Lanthier
- Service d'Hépato-Gastroentérologie, Cliniques universitaires Saint-Luc, UCLouvain, Brussels, Belgium; Laboratory of Hepatology and Gastroenterology, Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, Belgium.
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Trinh B, Rasmussen Rinnov A, Winning Iepsen U, Winding Munch G, Munch Winding K, Lauridsen C, Gluud LL, van Hall G, Ellingsgaard H. Glucose turnover at whole-body and skeletal muscle level in response to parenteral nutrition in male patients with alcoholic liver cirrhosis. Clin Nutr ESPEN 2024; 60:240-246. [PMID: 38479917 DOI: 10.1016/j.clnesp.2024.02.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Revised: 01/21/2024] [Accepted: 02/09/2024] [Indexed: 04/13/2024]
Abstract
BACKGROUND & AIMS Cirrhosis is associated with insulin resistance and impaired glucose tolerance, which may be caused by impairments at different tissue levels (liver, skeletal muscle, and/or beta cell). METHODS Here, glucose kinetics at whole-body and skeletal muscle level in patients with cirrhosis (Child-Pugh A and B) were studied during parenteral nutrition using the isotope dilution technique and arteriovenous balance approach across the leg. As opposed to the euglycemic hyperinsulinemic clamp or glucose tolerance tests applied in previous studies, this approach provides a nutrient composition more similar to a normal meal while circumventing any possible portal-systemic shunting, impaired hepatic uptake and incretin effect. RESULTS We confirmed the presence of hepatic and peripheral insulin resistance in our patient population. Endogenous glucose production was less suppressed in response to parenteral nutrition. However, glucose uptake in skeletal muscle was increased. CONCLUSION Our results suggests that in our study participants with cirrhosis, the hepatic and peripheral insulin resistance is compensated for by increased insulin secretion and thus, increased glucose uptake in muscle. Hereby, glucose homeostasis is maintained.
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Affiliation(s)
- Beckey Trinh
- The Centre for Physical Activity Research, Copenhagen University Hospital - Rigshospitalet, Denmark.
| | - Anders Rasmussen Rinnov
- The Centre for Physical Activity Research, Copenhagen University Hospital - Rigshospitalet, Denmark
| | - Ulrik Winning Iepsen
- The Centre for Physical Activity Research, Copenhagen University Hospital - Rigshospitalet, Denmark; Department of Anaesthesiology and Intensive Care, Copenhagen University Hospital - Hvidovre Hospital, Copenhagen, Denmark
| | - Gregers Winding Munch
- The Centre for Physical Activity Research, Copenhagen University Hospital - Rigshospitalet, Denmark
| | - Kamilla Munch Winding
- The Centre for Physical Activity Research, Copenhagen University Hospital - Rigshospitalet, Denmark
| | - Carsten Lauridsen
- Department of Diagnostic Radiology, Copenhagen University Hospital - Rigshospitalet, Denmark; Department of Technology, Copenhagen University College, Denmark
| | - Lise Lotte Gluud
- Gastrounit, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark
| | - Gerrit van Hall
- Clinical Metabolomics Core Facility, Clinical Biochemistry, Copenhagen University Hospital, Department of Biomedical Sciences, Health & Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Helga Ellingsgaard
- The Centre for Physical Activity Research, Copenhagen University Hospital - Rigshospitalet, Denmark
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Characterization of glucose metabolism in youth with vs. without cystic fibrosis liver disease: A pilot study. J Clin Transl Endocrinol 2022; 28:100296. [PMID: 35342717 PMCID: PMC8942823 DOI: 10.1016/j.jcte.2022.100296] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2022] [Revised: 03/02/2022] [Accepted: 03/15/2022] [Indexed: 11/24/2022] Open
Abstract
Severe CF-liver disease may exaggerate glucose abnormalities in patients with CFRD. CF-liver disease may decrease insulin clearance that fosters insulin resistance. Patients with CFRD and liver disease may warrant treatment other than insulin. Background Diabetes and liver disease are life-threatening complications of cystic fibrosis (CF). CF-liver disease is a risk factor for CF related diabetes (CFRD) development, but the underlying mechanisms linking the two co-morbidities are not known. The objective of this pilot study was to characterize glucose metabolism in youth with CF with and without liver disease. Methods In this two-center cross-sectional study, 20 youth with CF with and without liver disease underwent a 3-hour oral glucose tolerance test. Subjects were categorized by liver disease (LD) status [no LD, mild LD, severe LD] and diabetes status. Measures of glucose excursion, islet cell secretory responses, insulin sensitivity and clearance were obtained. Results Participants with severe LD had the highest fasting, peak, and glucose area under the curve over 3 h (AUC3h) among individuals with CFRD (interaction p < 0.05). In parallel with glycemic changes, prandial β-cell secretory response (AUC C-peptide 3h) was lower in those with severe LD compared to mild or no LD (p < 0.01). There was a trend of higher HOMA-IR in those with severe LD (p = 0.1) as well as lower fasting insulin clearance in those with mild and severe LD compared to no LD (p = 0.06) and lower prandial insulin clearance in severe LD among those with CFRD (interaction p = 0.1). Conclusion In this small cohort, subjects with severe LD tended to have more impaired glycemia, insulin secretion, insulin sensitivity and clearance. Larger studies are imperative to define the pathogenesis to inform clinical care guidelines in terms of CFRD screening, diagnosis, and treatment options.
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Quinlan JI, Dhaliwal A, Williams F, Allen SL, Breen L, Greig CA, Lord JM, Armstrong MJ, Elsharkawy AM. Feasibility, Efficacy, and Safety of Percutaneous Muscle Biopsies in Patients With Chronic Liver Disease. Front Physiol 2022; 12:817152. [PMID: 35242045 PMCID: PMC8886882 DOI: 10.3389/fphys.2021.817152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Accepted: 12/14/2021] [Indexed: 11/13/2022] Open
Abstract
INTRODUCTION Sarcopenia is present in many chronic disease states including decompensated end stage liver disease (ESLD) and non-cirrhotic non-alcoholic fatty liver disease (NAFLD). Sarcopenia in ESLD can negatively impact quality of life and increase mortality. Despite this, very little is understood about the mechanisms of sarcopenia in these conditions. One key reason for this is the reluctance to undertake percutaneous muscle biopsies due to the perceived increased risks. ESLD can induce thrombocytopaenia and coagulopathy which significantly increases the risk of bleeding. In addition, patients with either NAFLD or ESLD often have co-morbidities that would require additional care and risk assessment. Thus, the aim of this study was to establish an effective and safe protocol for the implementation of percutaneous muscle biopsies in patients with NAFLD and ESLD. METHODS A total of 47 patients with ESLD and 9 patients with non-cirrhotic NAFLD were recruited from the Liver Unit, Queen Elizabeth Hospital (Birmingham, United Kingdom). A total of 71 percutaneous vastus lateralis biopsies were attempted over two study visits. A vigorous safety screening occurred prior to and during each visit and a strict protocol was followed to mitigate against complications and risk. RESULTS A total of 85% of patients consented to the muscle biopsy at either visit (48/56). A total of 9% of consented biopsies could not occur due to medical considerations, including high international normalised ratio (INR) (n = 3) and the use of aspirin (n = 4). Muscle tissue was obtained from 90% of attempts, with a mean average yield (wet weight tissue) of 98.1 ± 52.9 mg. CONCLUSION Percutaneous muscle biopsies are both feasible and yield sufficient tissue in an ESLD population. The procedure is effective for obtaining muscle tissue whilst also safe, with only one adverse event. This study provides evidence for the successful use of muscle biopsies in this population, even in consideration of disease specific complications, medications, and comorbidities.
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Affiliation(s)
- Jonathan I Quinlan
- NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, United Kingdom.,School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, United Kingdom
| | - Amritpal Dhaliwal
- NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, United Kingdom.,Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom
| | - Felicity Williams
- NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, United Kingdom.,Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom
| | - Sophie L Allen
- NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, United Kingdom.,School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, United Kingdom
| | - Leigh Breen
- NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, United Kingdom.,School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, United Kingdom.,MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research, University of Birmingham, Birmingham, United Kingdom
| | - Carolyn A Greig
- NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, United Kingdom.,School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, United Kingdom.,MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research, University of Birmingham, Birmingham, United Kingdom
| | - Janet M Lord
- NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, United Kingdom.,Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom.,MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research, University of Birmingham, Birmingham, United Kingdom
| | - Matthew J Armstrong
- NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, United Kingdom.,Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom
| | - Ahmed M Elsharkawy
- NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, United Kingdom.,Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom
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Lee SJ, Lee HJ, Jung YJ, Han M, Lee SG, Hong SK. Comparison of Measured Energy Expenditure Using Indirect Calorimetry vs Predictive Equations for Liver Transplant Recipients. JPEN J Parenter Enteral Nutr 2020; 45:761-767. [PMID: 32458439 PMCID: PMC8447869 DOI: 10.1002/jpen.1932] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2019] [Accepted: 05/21/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND To assess the appropriate energy expenditure requirement for liver transplant (LT) recipients in South Korea, 4 commonly used predictive equations were compared with indirect calorimetry (IC). METHODS A prospective observational study was conducted in the surgical intensive care unit (ICU) of an academic tertiary hospital between December 2017 and September 2018. The study population comprised LT recipients expected to remain in the ICU >48 hours postoperatively. Resting energy expenditure (REE) was measured 48 hours after ICU admission using open-circuit IC. Theoretical REE was estimated using 4 predictive equations (simple weight-based equation [25 kcal/kg/day], Harris-Benedict, Ireton-Jones [ventilated], and Penn State 1988). Derived and measured REE values were compared using an intraclass correlation coefficient (ICC) and Bland-Altman plots. RESULTS Of 50 patients screened, 46 were enrolled, were measured, and completed the study. The Penn State equation showed 65.0% agreement with IC (ICC, 0.65); the simple weight-based (25 kcal/kg/day), Harris-Benedict, and Ireton-Jones equations showed 62.0%, 56.0% and 39.0% agreement, respectively. Bland-Altman analysis showed that all 4 predictive equations had fixed bias, although the simple weight-based equation (25 kcal/kg/day) showed the least. CONCLUSION Although predicted REE calculated using the Penn State method agreed with the measured REE, all 4 equations showed fixed bias and appeared to be inaccurate for predicting REE in LT recipients. Precise measurement using IC may be necessary when treating LT recipients to avoid underestimating or overestimating their metabolic needs.
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Affiliation(s)
- Seok Joon Lee
- College of Medicine, University of Ulsan, Songpa-gu, Seoul, South Korea
| | - Hak-Jae Lee
- Division of Acute Care Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Songpa-gu, Seoul, South Korea
| | - Yooun-Joong Jung
- Division of Acute Care Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Songpa-gu, Seoul, South Korea
| | - Minkyu Han
- Department of Clinical Epidemiology and Biostatistics, University of Ulsan, Songpa-gu, Seoul, South Korea
| | - Sung-Gyu Lee
- Division of Liver Transplantation and Hepatobiliary Surgery, Departments of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Suk-Kyung Hong
- Division of Acute Care Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Songpa-gu, Seoul, South Korea
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Košuta I, Mrzljak A, Kolarić B, Vučić Lovrenčić M. Leptin as a Key Player in Insulin Resistance of Liver Cirrhosis? A Cross-Sectional Study in Liver Transplant Candidates. J Clin Med 2020; 9:560. [PMID: 32092909 PMCID: PMC7073684 DOI: 10.3390/jcm9020560] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Revised: 02/11/2020] [Accepted: 02/17/2020] [Indexed: 02/07/2023] Open
Abstract
Insulin resistance is associated with increased risk of death and liver transplantation in the cirrhotic population, independent of disease aetiology. However, factors accounting for insulin resistance in the context of cirrhosis are incompletely understood. This study aimed to investigate the association between adiponectin and leptin with insulin resistance in cirrhotic patients and to assess the influence of disease severity on insulin resistance and metabolic status. This cross-sectional study included 126 non-diabetic cirrhotic transplant candidates. The homeostasis model assessment 2 model was used to determine the insulin resistance index, and fasting adiponectin, leptin, insulin, c-peptide, glucose, HbA1c, and lipid profiles were analysed. Insulin resistance was detected in 83% of subjects and associated with increased leptin, fasting plasma glucose and body mass index, and lower triglyceride levels. Logistic regression analysis identified leptin and triglycerides as independent predictors of insulin resistance (OR 1.247, 95% CI 1.076-1.447, p = 0.003; OR 0.357, 95% CI 0.137-0.917, p = 0.032.). Leptin levels remained unchanged, whereas adiponectin levels increased (p < 0.001) with disease progression, and inversely correlated with HbA1c (ρ = -0.349, p < 0.001). Our results indicate that leptin resistance, as indicated by elevated leptin levels, can be regarded as a contributing factor to insulin resistance in cirrhotic patients, whereas triglycerides elicited a weak protective effect. Progressively increasing adiponectin levels elicited a positive effect on glucose homeostasis, but not insulin sensitivity across disease stages.
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Affiliation(s)
- Iva Košuta
- Department of Gastroenterology, Merkur University Hospital, Zajčeva 19, 10000 Zagreb, Croatia;
| | - Anna Mrzljak
- Department of Gastroenterology, Merkur University Hospital, Zajčeva 19, 10000 Zagreb, Croatia;
- School of Medicine, University of Zagreb, Šalata 3, 10000 Zagreb, Croatia
| | - Branko Kolarić
- Department of Epidemiology, Andrija Štampar Teaching Institute of Public Health, Mirogojska cesta 16, 10000 Zagreb, Croatia;
- Faculty of Medicine, University of Rijeka, Ul. Braće Branchetta 20/1, 51000 Rijeka, Croatia
| | - Marijana Vučić Lovrenčić
- Department of Clinical Chemistry and Laboratory Medicine, Merkur University Hospital, Zajčeva 19, 10000 Zagreb, Croatia;
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Schobert I, Chapiro J, Pucar D, Saperstein L, Savic LJ. Fluorodeoxyglucose PET for Monitoring Response to Embolotherapy (Transarterial Chemoembolization) in Primary and Metastatic Liver Tumors. PET Clin 2019; 14:437-445. [DOI: 10.1016/j.cpet.2019.06.008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Diabetes Mellitus and Risk of Hepatic Fibrosis/Cirrhosis. BIOMED RESEARCH INTERNATIONAL 2019; 2019:5308308. [PMID: 31080822 PMCID: PMC6475555 DOI: 10.1155/2019/5308308] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/25/2018] [Accepted: 03/27/2019] [Indexed: 02/06/2023]
Abstract
Development of cirrhosis is two- to threefold greater in patients with diabetes mellitus (DM), and in this setting, the prevalence of cirrhosis is surging worldwide. The present review served to examine clinical ties between DM and liver fibrosis and hepatic cirrhosis and explore related biologic mechanisms. Pathways contributing to various etiologies of cirrhosis in conjunction with DM were key investigative targets.
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Ishikawa T, Sasaki R, Nishimura T, Matsuda T, Maeda M, Iwamoto T, Saeki I, Hidaka I, Takami T, Sakaida I. Liver stiffness measured by transient elastography as predictor of prognoses following portosystemic shunt occlusion. J Gastroenterol Hepatol 2019; 34:215-223. [PMID: 30070412 DOI: 10.1111/jgh.14410] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2018] [Revised: 07/22/2018] [Accepted: 07/25/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIM This study aimed to identify predictors of model for end-stage liver disease sodium score reductions and improvements in vital prognoses following portosystemic shunt occlusion in portal hypertension patients. METHODS Seventy cirrhotic patients with major portosystemic shunts and a mean model for end-stage liver disease sodium score of 10.5 underwent balloon-occluded retrograde transvenous obliteration between February 2008 and March 2017. We calculated the scores before and 1 month after shunt occlusion. The long-term outcomes were monitored, and vital prognoses were analyzed. RESULTS The model for end-stage liver disease sodium score did not change significantly 1 month post-balloon-occluded retrograde transvenous obliteration, and the score decreased postoperatively in 31 (44.3%) patients. Univariate analyses showed that decline in the score after portosystemic shunt occlusion was strongly associated with hepatic encephalopathy as a procedural indication, lower liver volumes, and lower liver stiffness levels measured by transient elastography before treatment (P < 0.05). Multivariate logistic regression analysis identified preoperative liver stiffness level as an independent predictor of model for end-stage liver disease sodium score amelioration following balloon-occluded retrograde transvenous obliteration (P < 0.05), and receiver operating characteristic curve analysis determined a liver stiffness cutoff value of 21.6 kPa, with a sensitivity of 76.0% and specificity of 69.6%. The Kaplan-Meier method determined that overall survival rates after treatment in patients with liver stiffness < 21.6 kPa were significantly higher than in patients with liver stiffness ≥ 21.6 kPa (P < 0.05). CONCLUSIONS Liver stiffness measured by transient elastography may predict improvements in model for end-stage liver disease sodium scores and in survival rates after portosystemic shunt occlusion in portal hypertension patients.
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Affiliation(s)
- Tsuyoshi Ishikawa
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
| | - Ryo Sasaki
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
| | - Tatsuro Nishimura
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
| | - Takashi Matsuda
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
| | - Masaki Maeda
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
| | - Takuya Iwamoto
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
| | - Issei Saeki
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
| | - Isao Hidaka
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
| | - Taro Takami
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
| | - Isao Sakaida
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
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Abstract
Food plays an essential role in normal cellular processes; however, certain foods may also trigger or worsen certain disease states. This article focuses particularly on the role of food in common gastrointestinal and liver diseases, and discusses the current evidence that either supports or debunks common dietary recommendations. Nutrition topics discussed include the use of artificial sweetener for weight loss, avoidance of all dairy products in the setting of lactose intolerance, dietary recommendations for diverticular disease, and dietary management in cirrhotic patients with hepatic encephalopathy.
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Affiliation(s)
- Michelle Pearlman
- Gastroenterology and Hepatology Fellow, Department of Internal Medicine, Division of Digestive and Liver Diseases, University of Texas Southwestern, 5323 Harry Hines Boulevard, Dallas, TX 75390-9151, USA.
| | - Oviea Akpotaire
- Department of Internal Medicine, University of Texas Southwestern, 5323 Harry Hines Boulevard, Dallas, TX 75390-9151, USA
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Silva TE, Ronsoni MF, Schiavon LL. Challenges in diagnosing and monitoring diabetes in patients with chronic liver diseases. Diabetes Metab Syndr 2018; 12:431-440. [PMID: 29279271 DOI: 10.1016/j.dsx.2017.12.013] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2017] [Accepted: 12/19/2017] [Indexed: 02/07/2023]
Abstract
The prevalence and mortality of diabetes mellitus and liver disease have risen in recent years. The liver plays an important role in glucose homeostasis, and various chronic liver diseases have a negative effect on glucose metabolism with the consequent emergence of diabetes. Some aspects related to chronic liver disease can affect diagnostic tools and the monitoring of diabetes and other glucose metabolism disorders, and clinicians must be aware of these limitations in their daily practice. In cirrhotic patients, fasting glucose may be normal in up until 23% of diabetes cases, and glycated hemoglobin provides falsely low results, especially in advanced cirrhosis. Similarly, the performance of alternative glucose monitoring tests, such as fructosamine, glycated albumin and 1,5-anhydroglucitol, also appears to be suboptimal in chronic liver disease. This review will examine the association between changes in glucose metabolism and various liver diseases as well as the particularities associated with the diagnosis and monitoring of diabetes in liver disease patients. Alternatives to routinely recommended tests will be discussed.
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Affiliation(s)
- Telma E Silva
- Division of Gastroenterology, Federal University of Santa Catarina, Campus Universitário Reitor João David Ferreira Lima, Trindade Florianópolis, SC, 88040-970, Brazil.
| | - Marcelo F Ronsoni
- Division of Endocrinology, Federal University of Santa Catarina, Campus Universitário Reitor João David Ferreira Lima, Trindade, Florianópolis, SC, 88040-970, Brazil
| | - Leonardo L Schiavon
- Division of Gastroenterology, Federal University of Santa Catarina, Campus Universitário Reitor João David Ferreira Lima, Trindade Florianópolis, SC, 88040-970, Brazil
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Stine JG, Wang J, Cornella SL, Behm BW, Henry Z, Shah NL, Caldwell SH, Northup PG. Treatment of Type-1 Hepatorenal Syndrome with Pentoxifylline: A Randomized Placebo Controlled Clinical Trial. Ann Hepatol 2018; 17:300-306. [PMID: 29469046 PMCID: PMC7485043 DOI: 10.5604/01.3001.0010.8660] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Type-1 hepatorenal syndrome (HRS-1) portends a poor prognosis in patients with cirrhosis. Currently available medical therapies are largely ineffective, save for liver transplantation. We aimed to determine if pentoxifylline (PTX) therapy in addition to the standard of care of volume expansion with albumin and vasoconstriction with midodrine and octreotide (AMO) is safe and efficacious compared to AMO in HRS-1 treatment. MATERIAL AND METHODS Hospitalized subjects with decompensated cirrhosis and HRS-1 were enrolled. PTX or placebo was administered with AMO therapy for up to 14 days. The primary endpoint was HRS-1 resolution (serum creatinine ≤ 1.5 g/dL for > 24 h). Secondary endpoints were change in creatinine and MELD score, partial treatment response, 30-and 180-day overall and transplant free survival. RESULTS Twelve subjects with mean age 58.9 ± 6.2 years were enrolled and randomized. Mean MELD score was 26.5 ± 7.4 and 58.3% were male. Overall cohort 30- and 180-day survival was 58.3% and 33.3% respectively. Two subjects underwent liver transplantation. HRS-1 resolution (16.7% vs. 16.7%, p = 1.000), partial treatment response (33.3% vs. 16.7%, p = 0.505), change in creatinine (+0.48 g/dL, 95% CI -0.49-1.46 vs. +0.03 g/dL, 95% CI -0.64- 0.70, p = 0.427), 30-day survival (66.6% vs. 50.0%, p = 0.558) and 180-day survival (50.0% vs. 16.7%, p = 0.221) were similar between the two groups. Serious adverse events necessitating treatment discontinuation were rare (n = 1, PTX). DISCUSSION The addition of PTX to AMO in the treatment of HRS-1 is safe when compared to the current standard of care. Future large-scale prospective study to validate the efficacy of this treatment seems warranted.
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Affiliation(s)
- Jonathan G. Stine
- Division of Gastroenterology & Hepatology, Department of Medicine, University of Virginia, Charlottesville, VA, United States
| | - Jennifer Wang
- Department of Medicine, University of Virginia, Charlottesville, VA, United States
| | - Scott L. Cornella
- Division of Gastroenterology & Hepatology, Department of Medicine, University of Virginia, Charlottesville, VA, United States
| | - Brian W. Behm
- Division of Gastroenterology & Hepatology, Department of Medicine, University of Virginia, Charlottesville, VA, United States
| | - Zachary Henry
- Division of Gastroenterology & Hepatology, Department of Medicine, University of Virginia, Charlottesville, VA, United States
| | - Neeral L. Shah
- Division of Gastroenterology & Hepatology, Department of Medicine, University of Virginia, Charlottesville, VA, United States
| | - Stephen H. Caldwell
- Division of Gastroenterology & Hepatology, Department of Medicine, University of Virginia, Charlottesville, VA, United States
| | - Patrick G. Northup
- Division of Gastroenterology & Hepatology, Department of Medicine, University of Virginia, Charlottesville, VA, United States
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13
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Ogasawara S, Chiba T, Ooka Y, Kanogawa N, Motoyama T, Suzuki E, Tawada A, Nagai K, Nakagawa T, Sugawara T, Hanaoka H, Kanai F, Yokosuka O. A randomized placebo-controlled trial of prophylactic dexamethasone for transcatheter arterial chemoembolization. Hepatology 2018; 67:575-585. [PMID: 28746788 DOI: 10.1002/hep.29403] [Citation(s) in RCA: 57] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2016] [Revised: 06/21/2017] [Accepted: 07/23/2017] [Indexed: 02/06/2023]
Abstract
This randomized, double-blind, placebo-controlled trial evaluated dexamethasone efficacy at preventing fever, anorexia, and nausea/vomiting, the most frequent adverse events of transcatheter arterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). Child-Pugh class A/B patients with HCC and no macrovascular invasion/extrahepatic metastases were randomly assigned to either a dexamethasone regimen (day 1, intravenous dexamethasone [20 mg] and granisetron [3 mg] before TACE; days 2 and 3, intravenous dexamethasone [8 mg]) or a control regimen (day 1, intravenous placebo [saline] and granisetron [3 mg]; days 2 and 3, intravenous placebo). The primary endpoint was complete response, defined as the absence of grade ≥1 fever, anorexia, or nausea/vomiting according to the Common Terminology Criteria for Adverse Events (version 4.0) and no use of rescue therapy for 120 hours after TACE. A total of 120 patients between October 2010 and June 2013 were randomly assigned to treatment groups. Overall the complete response rate was greater with the dexamethasone regimen than with the control regimen (47.5%, 95% confidence interval 34.3%-60.9%, versus 10.2%, 95% confidence interval 3.8%-20.8%; P < 0.001). Cumulative incidences of fever, anorexia, and nausea/vomiting were higher in the control regimen group compared with the dexamethasone group (P < 0.001, P < 0.001, and P = 0.095, respectively). The dexamethasone regimen was generally well tolerated by HCC patients including those with well-controlled diabetes mellitus and those with hepatitis B virus infection. Conclusion: The dexamethasone regimen was more effective than the control regimen at preventing TACE-induced fever, anorexia, and nausea/vomiting in patients with HCC. (Hepatology 2018;67:575-585).
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Affiliation(s)
- Sadahisa Ogasawara
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Tetsuhiro Chiba
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Yoshihiko Ooka
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Naoya Kanogawa
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Tenyu Motoyama
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Eiichiro Suzuki
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Akinobu Tawada
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Kazue Nagai
- Clinical Research Centre, Chiba University Hospital, Chiba, Japan
| | - Tomoo Nakagawa
- Clinical Research Centre, Chiba University Hospital, Chiba, Japan
| | - Takeshi Sugawara
- Clinical Research Centre, Chiba University Hospital, Chiba, Japan
| | - Hideki Hanaoka
- Clinical Research Centre, Chiba University Hospital, Chiba, Japan
| | - Fumihiko Kanai
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Osamu Yokosuka
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
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14
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Ramos-Prol A, Hervás-Marín D, García-Castell A, Merino-Torres JF. Outcomes in patients with diabetes 10 years after liver transplantation. J Diabetes 2017; 9:1033-1039. [PMID: 28039959 DOI: 10.1111/1753-0407.12520] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2016] [Revised: 12/04/2016] [Accepted: 12/28/2016] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND There are discrepancies between studies regarding the effect of diabetes mellitus on morbidity and mortality in patients undergoing liver transplantation. The aim of the present study was to compare mortality, risk of liver graft rejection, and cardiovascular events in patients with and without diabetes undergoing liver transplantation over a 10-year follow-up period. METHODS A retrospective study was performed on 183 patients who underwent liver transplantation in 2005 and 2006. Mortality and morbidity data were collected until 2016, including information on mortality and survival time, graft rejection and graft survival time, coronary heart disease, stroke, and peripheral arterial ischemia. RESULTS During the follow-up, 41.3% and 27.8% of patients in the groups with and without diabetes, respectively, died. A trend for lower survival time was observed in patients with diabetes, although this effect was not confirmed by the Cox regression model. There was an increased risk of graft rejection in the group with diabetes compared with the group without diabetes ( P < 0.001). In the survival analysis, diabetes was associated with reduced graft survival time ( P = 0.001). Cardiovascular events were also more likely in the group with diabetes ( P = 0.005). CONCLUSIONS In the present study diabetes was associated with a higher risk of liver graft rejection and cardiovascular events. There was also a trend for higher mortality, although the effect was not statistically significant. These findings suggest that patients with diabetes require a more rigorous pretransplant evaluation and closer monitoring after transplantation in order to try to reduce associated complications.
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Affiliation(s)
- Agustín Ramos-Prol
- Department of Internal Medicine (Endocrinology and Nutrition), Francesc de Borja Hospital, Gandía, Spain
- Joint Research Unit of Endocrinology, Nutrition and Clinical Dietetics, Valencia, Spain
| | | | - Alia García-Castell
- Endocrinology and Nutrition Department, University and Polytechnic La Fe Hospital, Valencia, Spain
| | - Juan F Merino-Torres
- Joint Research Unit of Endocrinology, Nutrition and Clinical Dietetics, Valencia, Spain
- Endocrinology and Nutrition Department, University and Polytechnic La Fe Hospital, Valencia, Spain
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15
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Yang CH, Perumpail BJ, Yoo ER, Ahmed A, Kerner JA. Nutritional Needs and Support for Children with Chronic Liver Disease. Nutrients 2017; 9:nu9101127. [PMID: 29035331 PMCID: PMC5691743 DOI: 10.3390/nu9101127] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2017] [Revised: 10/08/2017] [Accepted: 10/11/2017] [Indexed: 12/31/2022] Open
Abstract
Malnutrition has become a dangerously common problem in children with chronic liver disease, negatively impacting neurocognitive development and growth. Furthermore, many children with chronic liver disease will eventually require liver transplantation. Thus, this association between malnourishment and chronic liver disease in children becomes increasingly alarming as malnutrition is a predictor of poorer outcomes in liver transplantation and is often associated with increased morbidity and mortality. Malnutrition requires aggressive and appropriate management to correct nutritional deficiencies. A comprehensive review of the literature has found that infants with chronic liver disease (CLD) are particularly susceptible to malnutrition given their low reserves. Children with CLD would benefit from early intervention by a multi-disciplinary team, to try to achieve nutritional rehabilitation as well as to optimize outcomes for liver transplant. This review explains the multifactorial nature of malnutrition in children with chronic liver disease, defines the nutritional needs of these children, and discusses ways to optimize their nutritional.
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Affiliation(s)
- Christine H Yang
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Lucile Packard Children's Hospital, Palo Alto, Stanford, CA 94304, USA.
| | - Brandon J Perumpail
- Department of Medicine, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
| | - Eric R Yoo
- Department of Medicine, Santa Clara Valley Medical Center, San Jose, CA 95128, USA.
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
| | - John A Kerner
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Lucile Packard Children's Hospital, Palo Alto, Stanford, CA 94304, USA.
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16
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Masuda K, Noguchi S, Ono M, Ochi T, Munekage K, Okamoto N, Suganuma N, Saibara T. High fasting insulin concentrations may be a pivotal predictor for the severity of hepatic fibrosis beyond the glycemic status in non-alcoholic fatty liver disease patients before development of diabetes mellitus. Hepatol Res 2017; 47:983-990. [PMID: 27794176 DOI: 10.1111/hepr.12832] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2016] [Revised: 09/13/2016] [Accepted: 10/19/2016] [Indexed: 12/26/2022]
Abstract
BACKGROUND Insulin resistance and type 2 diabetes mellitus (T2DM) contribute to the progression of non-alcoholic fatty liver disease (NAFLD). However, the relationship between glucose metabolic factors and the histological severity in NAFLD patients before development of T2DM is not well known. METHODS In 103 biopsy-proven NAFLD patients (68 men and 35 women) with hemoglobin A1c of <6.5% and fasting blood glucose of <126 mg/dL, we investigated whether glucose metabolic factors influenced the severity of hepatic fibrosis without prior known T2DM. RESULTS Female gender, age, serum aspartate aminotransferase, the aspartate aminotransferase/alanine aminotransferase ratio, fasting immunoreactive insulin (f-IRI), homeostasis model assessment - insulin resistance, hemoglobin A1c, hyaluronic acid, and type IV collagen 7 s were significantly higher, and 1,5-anhydroglucitol was significantly lower, in the fibrosis stage F3 group than in the F0-2 group. Multiple logistic regression analysis showed that only f-IRI (P = 0.006; odds ratio, 1.15151; 95% confidence interval, 1.04198-1.27254) was significantly indicated as a predictive factor for F3. As determined by both forward and backward stepwise selection analyses to optimize the model, f-IRI (P = 0001; odds ratio, 1.16788) remained an independent predictive factor for F3. To discriminate the F3 group from the F0-2 group, the area under the receiver operating characteristic curves showed that fasting insulin was 0.7219, and the best cut-off value of f-IRI was 13.2 μU/mL in the receiver operating characteristic curve analysis. CONCLUSIONS High fasting insulin concentrations may be a pivotal glucose metabolic predictor for the severity of hepatic fibrosis beyond the glycemic status in NAFLD patients before development of T2DM.
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Affiliation(s)
- Kosei Masuda
- Departments of Gastroenterology and Hepatology, Kochi Medical School, Kochi, Japan
| | - Shuhei Noguchi
- Department of Environmental Medicine, Kochi Medical School, Kochi, Japan
| | - Masafumi Ono
- Departments of Gastroenterology and Hepatology, Kochi Medical School, Kochi, Japan
| | - Tsunehiro Ochi
- Departments of Gastroenterology and Hepatology, Kochi Medical School, Kochi, Japan
| | - Kensuke Munekage
- Departments of Gastroenterology and Hepatology, Kochi Medical School, Kochi, Japan
| | - Nobuto Okamoto
- Departments of Gastroenterology and Hepatology, Kochi Medical School, Kochi, Japan
| | - Narufumi Suganuma
- Department of Environmental Medicine, Kochi Medical School, Kochi, Japan
| | - Toshiji Saibara
- Departments of Gastroenterology and Hepatology, Kochi Medical School, Kochi, Japan
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17
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Orsi E, Grancini V, Menini S, Aghemo A, Pugliese G. Hepatogenous diabetes: Is it time to separate it from type 2 diabetes? Liver Int 2017; 37:950-962. [PMID: 27943508 DOI: 10.1111/liv.13337] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2016] [Accepted: 11/29/2016] [Indexed: 12/12/2022]
Abstract
By definition, hepatogenous diabetes is directly caused by loss of liver function, implying that it develops after cirrhosis onset. Therefore, it should be distinguished from type 2 diabetes developing before cirrhosis onset, in which specific causes of liver disease play a major role, in addition to traditional risk factors. Currently, although hepatogenous diabetes shows distinct pathophysiological and clinical features, it is not considered as an autonomous entity. Recent evidence suggests that the failing liver exerts an independent "toxic" effect on pancreatic islets resulting in β-cell dysfunction. Moreover, patients with hepatogenous diabetes usually present with normal fasting glucose and haemoglobin A1c levels and abnormal response to an oral glucose tolerance test, which is therefore required for diagnosis. This article discusses the need to separate hepatogenous diabetes from type 2 diabetes occurring in subjects with chronic liver disease and to identify individuals suffering from this condition for prognostic and therapeutic purposes.
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Affiliation(s)
- Emanuela Orsi
- Diabetes Service, Endocrinology and Metabolic Diseases Unit, IRCCS "Cà Granda-Ospedale Maggiore Policlinico" Foundation, University of Milan, Milan, Italy.,Department of Medical Sciences, University of Milan, Milan, Italy
| | - Valeria Grancini
- Diabetes Service, Endocrinology and Metabolic Diseases Unit, IRCCS "Cà Granda-Ospedale Maggiore Policlinico" Foundation, University of Milan, Milan, Italy.,Department of Medical Sciences, University of Milan, Milan, Italy
| | - Stefano Menini
- Department of Clinical and Molecular Medicine, "La Sapienza" University, Rome, Italy.,Diabetes Unit, Sant'Andrea Hospital, Rome, Italy
| | - Alessio Aghemo
- Division of Gastroenterology and Hepatology, A.M. and A. Migliavacca Center for Liver Disease, IRCCS "Cà Granda-Ospedale Maggiore Policlinico" Foundation, University of Milan, Milan, Italy
| | - Giuseppe Pugliese
- Department of Clinical and Molecular Medicine, "La Sapienza" University, Rome, Italy.,Diabetes Unit, Sant'Andrea Hospital, Rome, Italy
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18
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The risk of transient postprandial oxyhypoglycemia in nonalcoholic fatty liver disease. J Gastroenterol 2017; 52:253-262. [PMID: 27351871 DOI: 10.1007/s00535-016-1236-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2016] [Accepted: 06/17/2016] [Indexed: 02/04/2023]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is frequently associated with insulin resistance (IR) and abnormalities in glucose metabolism. Prevalent postprandial hyperinsulinemia along with insulin resistance in NAFLD may lead to hypoglycemia. This study investigated the prevalence of postprandial oxyhypoglycemia in patients with NAFLD. METHODS The oral glucose tolerance test (OGTT) with 75 g glucose was performed in 375 biopsy-proven NAFLD patients with prior unknown type 2 diabetes mellitus (DM). Serum glucose and insulin levels were measured for 3 h after glucose loading and the clinical parameters were compared. RESULTS Normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and DM were observed in 36, 36, and 28 %, respectively. Hypoglycemia (≤70 mg/dL) after 3 h was observed in 14.4 % of all patients. The rate of hypoglycemia was significantly higher in NGT (63 % of NGT) than in IGT (30 % of IGT) and DM (7 % of DM) (P < 0.05). In patients with hypoglycemia, the levels of insulin were significantly higher at 30 and 60 min than those without hypoglycemia (P < 0.05). By multivariate analysis, high-LDL cholesterolemia (P < 0.05), low-HDL cholesterolemia (P < 0.05), and fibrosis (P < 0.05) were significant factors that contributed to hypoglycemia after 3 h on 75 g OGTT. CONCLUSIONS A relatively higher proportion of NAFLD cases exhibited transient postprandial hypoglycemia after 3 h on OGTT, especially in NAFLD patients with early-stage fibrosis. By performing 75 g OGTT for 3 h, hypoglycemia would be diagnosed earlier and the treatment intervention would decrease the progression of NAFLD and deterioration of glucose metabolism.
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19
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Maruyama H, Kobayashi K, Kiyono S, Yokosuka O. Interrelationship between insulin resistance and portal haemodynamic abnormality in cirrhosis. Int J Med Sci 2017; 14:240-245. [PMID: 28367084 PMCID: PMC5370286 DOI: 10.7150/ijms.17738] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2016] [Accepted: 12/28/2016] [Indexed: 01/16/2023] Open
Abstract
Background: There are only limited data regarding the effect of impaired portal circulation on the glucose metabolism. The study prospectively examined the interrelationship between insulin resistance (IR) and portal haemodynamic abnormality in cirrhosis. Methods: There were 53 cirrhosis patients (61.6 ± 13.0 years) all presenting gastroesophageal varices. Portal haemodynamics by both hepatic venous catheterisation and Doppler ultrasound were examined with respect to the homeostasis model assessment (HOMA)-IR and HOMA2-IR. The IR was defined by HOMA-IR > 3.0 or HOMA2-IR > 2.0. Results: Forty-two patients (79.2%) had collateral vessels, 38 with left gastric vein, 12 with short/posterior gastric vein, 9 with splenorenal shunt, and 3 with inferior mesenteric vein. Multivariate analysis provided significant factors; wedged hepatic venous pressure (HR1.183, 95% CI 1.012-1.383, p=0.035) for HOMA-IR > 3.0, body mass index for HOMA2-IR > 2.0 (HR1.490, 95% CI 1.176-1.888, p=0.001), and collateral flow volume for both HOMA-IR > 3.0 (HR1.007, 95% CI 1.001-1.014, p=0.015) and HOMA2-IR > 2.0 (HR 1.007, 95% CI 1.002-1.013, p=0.009). The best cut-off value of collateral flow volume was 165 ml/min for detecting the HOMA-IR > 3.0 showing area under the receiver operating characteristic curve (AUROC) 0.688 (Odds ratio, 5.33) with sensitivity 70% and specificity 69.6%, and was 165 ml/min for detecting median value of HOMA2-IR > 2.0 showing AUROC 0.698 (odds ratio, 5.7) with sensitivity 75% and specificity 65.5%. Conclusion: There is a close linkage between the IR and impaired portal haemodynamics presented by the collateral development, suggesting the underlying pathogenesis of portal hypertension in cirrhosis patients.
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Affiliation(s)
- Hitoshi Maruyama
- Department of Gastroenterology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba, 260-8670, Japan
| | - Kazufumi Kobayashi
- Department of Gastroenterology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba, 260-8670, Japan
| | - Soichiro Kiyono
- Department of Gastroenterology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba, 260-8670, Japan
| | - Osamu Yokosuka
- Department of Gastroenterology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba, 260-8670, Japan
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20
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Kishimoto M, Noda M. Verification of glycemic profiles using continuous glucose monitoring: cases with steroid use, liver cirrhosis, enteral nutrition, or late dumping syndrome. THE JOURNAL OF MEDICAL INVESTIGATION 2016; 62:1-10. [PMID: 25817276 DOI: 10.2152/jmi.62.1] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Abstract
Glycemic control is often difficult to achieve in patients with diabetes, especially in the presence of comorbid diseases or conditions such as steroid-use or liver cirrhosis, or in patients receiving enteral nutrition. Moreover, reactive hypoglycemia due to late dumping syndrome in people having undergone gastrectomy is also a matter of concern. Empirically and theoretically, the typical glycemic profiles associated with these conditions have been determined; however, what actually happens during a 24-h span is still somewhat obscure. In order to verify and provide information about the 24-h glycemic profiles associated with these conditions, 8 patients with the 4 above-mentioned conditions were monitored using a continuous glucose monitoring system (CGMS). For all 8 patients, CGMS provided detailed information regarding the 24-h glycemic profiles. The CGM results showed typical glycemic patterns for each condition, and we were moreover able to observe the effects of various practical treatments. Based on these cases, we conclude that the CGMS is highly useful for determining the glycemic patterns of patients with the aforementioned conditions in a practical setting; and this system may be used to monitor the treatment success of such cases.
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Affiliation(s)
- Miyako Kishimoto
- Department of Diabetes, Endocrinology, and Metabolism Center Hospital; 2.Diabetes and Metabolism Information Center, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine
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21
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Karnchanasorn R, Ou HY, Lin J, Chuang LM, Chiu KC. Viral Hepatitis and Diabetes: Clinical Implications of Diabetes Prevention Through Hepatitis Vaccination. Curr Diab Rep 2016; 16:101. [PMID: 27620495 DOI: 10.1007/s11892-016-0790-y] [Citation(s) in RCA: 3] [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] [Indexed: 12/25/2022]
Abstract
Viral hepatitis has been posited to play a role in the development of type 2 diabetes. Thus, prevention of viral hepatitis through vaccination has the potential to reduce the burden of type 2 diabetes. We have shown that successful hepatitis B vaccination reduces the risk of diabetes by 33 %. Although diabetes can be prevented by behavior modification and pharmaceutical agents, these require significant personal commitment and cost. In contrast, diabetes prevention through hepatitis B vaccination would require little personal commitment and relatively low cost. In this review, we discuss hepatitis viruses A, B, and C and their interaction with diabetes; explore the potential underlying mechanisms and potential for hepatitis vaccination to reduce diabetes; and estimate the medical expense savings that would result from such an intervention. Given the projected increase of diabetes prevalence in the developing regions, where hepatitis B is endemic, exploration of such an intervention is very timely.
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Affiliation(s)
- Rudruidee Karnchanasorn
- Division of Endocrinology, Metabolism and Genetics, Department of Internal Medicine, University of Kansas Medical Center, Kansas, KS, USA
| | - Horng-Yih Ou
- Division of Endocrinology and Metabolism, Department of Internal Medicine, National Cheng-Kung University Medical College and Hospital, Tainan, Taiwan
| | - James Lin
- Department of Gastroenterology, City of Hope National Medical Center, Duarte, CA, USA
| | - Lee-Ming Chuang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Preventive Medicine, School of Public Health, National Taiwan University, Taipei, Taiwan
| | - Ken C Chiu
- Department of Clinical Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, Duarte, CA, 91010-3000, USA.
- Division of Endocrinology, Metabolism and Nutrition, Department of Internal Medicine, Harbor-UCLA Medical Center, Torrance, CA, USA.
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22
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Calzadilla-Bertot L, Vilar-Gomez E, Torres-Gonzalez A, Socias-Lopez M, Diago M, Adams LA, Romero-Gomez M. Impaired glucose metabolism increases risk of hepatic decompensation and death in patients with compensated hepatitis C virus-related cirrhosis. Dig Liver Dis 2016; 48:283-90. [PMID: 26797261 DOI: 10.1016/j.dld.2015.12.002] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2015] [Revised: 11/30/2015] [Accepted: 12/03/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND Glucose metabolism abnormalities frequently coexist with liver cirrhosis; however, the impact of these on liver-related outcomes has not been fully investigated. AIMS We examined the influence of glucose abnormalities on overall mortality and liver-related complications in cirrhotic patients. METHODS A prospective cohort of 250 subjects with compensated hepatitis C virus-related cirrhosis and without known diabetes underwent an oral glucose tolerance test and were subsequently followed for a median 201 weeks. RESULTS At baseline, 67 (27%) had type 2 diabetes. During follow-up, 28 deaths and 55 first events of decompensation occurred. After adjustment for potential confounding covariates, overall mortality/liver transplant (sHR: 2.2, 95% CI: 1.04-4.6, P=0.04) and hepatic decompensation events (sHR: 1.9, 95% CI: 1.05-3.3, P=0.03) were significantly higher in diabetic patients. Subjects with a HOMA-IR >5 showed higher rates of mortality (sHR: 2.2, 95% CI: 1.03-4.8, P=0.04). The rates of hepatic decompensation were higher in patients with HOMA-IR >3 (sHR: 1.7, 95% CI: 1.04-2.9, P=0.03). Overall, 2h-plasma glucose was the most robust predictor of overall mortality (sHR: 2.5, 95% CI: 1.03-6, P=0.04) and decompensation (sHR: 2.7, 95% CI: 1.4-5.5, P<0.01). CONCLUSIONS In compensated HCV-related cirrhotic patients, diabetes and marked insulin resistance are independently associated with poorer overall survival and increased risk of hepatic decompensation.
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Affiliation(s)
| | - Eduardo Vilar-Gomez
- Department of Hepatology, National Institute of Gastroenterology, Havana, Cuba; Unit for the Clinical Management of Digestive Diseases, Macarena and Virgen del Rocio University Hospital, Ciberehd, Institute of Biomedicine, University of Seville, Seville, Spain.
| | - Ana Torres-Gonzalez
- Department of Hepatology, National Institute of Gastroenterology, Havana, Cuba
| | - Maray Socias-Lopez
- Department of Hepatology, National Institute of Gastroenterology, Havana, Cuba
| | - Moises Diago
- Liver Unit, Department of Gastroenterology, Valencia University General Hospital, Valencia, Spain
| | - Leon A Adams
- Department of Gastroenterology and Hepatology, Sir Charles Gairdner Hospital, Perth, Australia
| | - Manuel Romero-Gomez
- Unit for the Clinical Management of Digestive Diseases, Macarena and Virgen del Rocio University Hospital, Ciberehd, Institute of Biomedicine, University of Seville, Seville, Spain
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23
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Ramos-Prol A, Hervás-Marín D, Rodríguez-Medina B, Campos-Alborg V, Berenguer M, Moya-Herraiz Á, Merino-Torres JF. Alterations in carbohydrate metabolism in cirrhotic patients before and after liver transplant. Diabetes Res Clin Pract 2015; 110:123-8. [PMID: 26506435 DOI: 10.1016/j.diabres.2015.10.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2015] [Revised: 09/06/2015] [Accepted: 10/01/2015] [Indexed: 12/15/2022]
Abstract
AIM The main objective of this study is to demonstrate whether carbohydrate metabolism alterations identified in patients with advanced cirrhosis show any improvement after liver transplant. METHODS The study included 86 patients who underwent liver transplant between March 2010 and February 2011. An oral glucose tolerance test was performed before the liver transplant, and 6 and 12 months after. Beta cell function and insulin resistance were also calculated, applying formulae that use basal plasma glycaemia and insulin, and plasma glycaemia and insulin during an oral glucose tolerance test. Risk factors for pre- and post-transplant diabetes were also studied. The diagnosis of diabetes was based on an OGTT. RESULTS The proportion of patients with diabetes before transplant, and at month 6 and 12 after transplant were 70.9%, 48.8% and 39.2%, respectively. Compared to baseline, at month 6 the odds ratio of having diabetes was 0.39 (IC 95% [0.21, 0.73]) and at month 12 it was 0.26 (IC 95% [0.14, 0.50]). The composite insulin sensitivity index values at 6 and 12 months were 1.72 units higher (IC 95% [0.84, 2.58]) and 1.58 units higher (IC 95% [0.68, 2.44)] than baseline. A statistically significant association was found between high MELD values and high body mass index, and risk of pre-transplant diabetes (p=0.001 and p=0.033, respectively). Cirrhosis aetiology did not influence the risk of diabetes. CONCLUSIONS In this study, we were able to ascertain that alterations in carbohydrate metabolism typical of advanced cirrhosis improve after liver transplant. This improvement is mainly due to an improvement in insulin resistance.
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Affiliation(s)
- Agustín Ramos-Prol
- Endocrinology and Nutrition Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain; Instituto de Investigación Sanitaria La Fe (Health Research Institute La Fe), Valencia, Spain
| | | | - Beatriz Rodríguez-Medina
- Liver Transplantation and Hepatology Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain
| | - Vicente Campos-Alborg
- Endocrinology and Nutrition Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain
| | - Marina Berenguer
- Liver Transplantation and Hepatology Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain
| | - Ángel Moya-Herraiz
- Liver Transplantation and Hepatology Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain
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Arias-Loste MT, García-Unzueta MT, Llerena S, Iruzubieta P, Puente A, Cabezas J, Alonso C, Cuadrado A, Amado JA, Crespo J, Fábrega E. Plasma betatrophin levels in patients with liver cirrhosis. World J Gastroenterol 2015; 21:10662-10668. [PMID: 26457026 PMCID: PMC4588088 DOI: 10.3748/wjg.v21.i37.10662] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2015] [Revised: 04/18/2015] [Accepted: 07/08/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the plasma levels of betatrophin in patients with cirrhosis.
METHODS: Forty patients diagnosed at the clinic with liver cirrhosis according to biological, ultrasonographic, or histological criteria were included. The severity of cirrhosis was classified according to Pugh’s modification of Child’s classification and MELD score. Insulin resistance (IR) was assessed by the Homeostasis Model Assessment. A total of 20 patients showed a MELD score higher than 14. The control group consisted in 15 sex-and aged-matched subjects. Fasting blood samples were obtained for subsequent analysis. Serum insulin was determined by Liaison automated immune chemiluminiscence assay (DiaSorin S.p.A.) using a sandwich assay. The sensitivity of the assay was 0.2 μU/mL. The intra and interassay variation coefficients were < 4% and < 10%, respectively. The normal values were between 2 and 17 μU/mL. Human active betatrophin was analyzed by specific quantitative sandwich ELISA (Aviscera Bioscience®). The sensitivity of the assay was 0.4 ng/mL, and the intra and interassay reproducibility were < 6% and < 10%, respectively.
RESULTS: Plasma betatrophin levels were significantly increased in patients with cirrhosis compared with those in healthy subjects (P = 0.0001). Betatrophin levels were also associated with disease severity, being higher in Child-Pugh C patients compared to Child-Pugh B (P < 0.0005) and in patients who displayed a MELD score higher than 14 points compared to patients with lower punctuation (P = 0.01). In addition, we found a positive correlation between plasma betatrophin levels and the severity of cirrhosis according to Child-Pugh classification (r = 0.53; P < 0.01) or MELD score (r = 0.45; P < 0.01). In the overall cohort, a moderate correlation between serum betatrophin and plasmatic bilirrubin (r = 0.39; P < 0.01) has been observed, as well as an inverse correlation between betatrophin and albumin (r = -0.41; P < 0.01) or prothrombin time (r = -0.44; P <0.01). Moreover, insulin resistance was observed in 82.5% of the cirrhotic patients. In this group of patients, betatrophin levels were significantly higher than those in the group of patients without IR (P < 0.05).
CONCLUSION: Plasma betatrophin is increased in patients with cirrhosis. This increase is related to the severity of cirrhosis, as well as with the emergence of insulin resistance.
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Kawanaka M, Nishino K, Oka T, Urata N, Nakamura J, Suehiro M, Kawamoto H, Chiba Y, Yamada G. Tyrosine levels are associated with insulin resistance in patients with nonalcoholic fatty liver disease. Hepat Med 2015; 7:29-35. [PMID: 26082668 PMCID: PMC4461125 DOI: 10.2147/hmer.s79100] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVE Amino acid imbalance is often found in patients with cirrhosis, and this imbalance is associated with insulin resistance. However, the mechanism underlying the relationship between amino acid imbalance and insulin resistance remains unclear. We evaluated serum amino acid concentrations in patients with nonalcoholic fatty liver disease to determine if any of the levels of amino acids were associated with the biochemical markers and fibrosis stage of nonalcoholic steatohepatitis (NASH). METHODS In 137 patients with nonalcoholic fatty liver disease who underwent liver biopsy, plasma levels of branched-chain amino acid (BCAA), tyrosine (Tyr), and the BCAA-to-Tyr ratio values were determined using mass spectroscopy. These values were then assessed for associations with fibrosis stage, anthropometric markers (age, sex, and body mass index), biochemical markers (alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, albumin, platelet count, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and glycosylated hemoglobin), and relevant disease-specific biomarkers (homeostasis model assessment of insulin resistance [HOMA-IR], serum iron, ferritin, leptin, adiponectin, high-sensitivity C-reactive protein, and hyaluronic acid). RESULTS Serum albumin levels, plasma BCAA levels, and BCAA-to-Tyr ratio values were negatively associated with the fibrosis stage. In contrast, Tyr levels increased with increasing fibrotic staging. Tyr levels were also correlated with HOMA-IR results. CONCLUSION Plasma BCAA levels in patients with NASH decreased with increasing liver fibrosis, while Tyr levels increased with increasing fibrotic stage. These results suggest that amino acid imbalance and insulin resistance are intimately involved in a complex pathogenic mechanism for NASH.
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Affiliation(s)
- Miwa Kawanaka
- Department of General Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan
| | - Ken Nishino
- Department of General Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan
| | - Takahito Oka
- Department of General Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan
| | - Noriyo Urata
- Department of General Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan
| | - Jun Nakamura
- Department of General Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan
| | - Mitsuhiko Suehiro
- Department of General Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan
| | - Hirofumi Kawamoto
- Department of General Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan
| | - Yasutaka Chiba
- Clinical Research Center, Kinki University Hospital, Sayama, Japan
| | - Gotaro Yamada
- Department of General Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan
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Kuroda T, Hirooka M, Koizumi M, Ochi H, Hisano Y, Bando K, Matsuura B, Kumagi T, Hiasa Y. Pancreatic congestion in liver cirrhosis correlates with impaired insulin secretion. J Gastroenterol 2015; 50:683-93. [PMID: 25283134 DOI: 10.1007/s00535-014-1001-8] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2014] [Accepted: 09/24/2014] [Indexed: 02/04/2023]
Abstract
BACKGROUND Although impaired glucose tolerance is common in cirrhosis, this condition's pathogenesis remains undefined. This study aimed to clarify pathogenesis related to the pancreas in cirrhotic patients, and to evaluate associations between insulin secretion and pancreatic congestion due to portal hypertension. METHODS Pancreatic perfusion parameters were analyzed by dynamic contrast-enhanced ultrasound (CE-US) in 41 patients (20 cirrhotic, 21 non-cirrhotic; age, 67.9 ± 13.3; female, 19), and prospectively compared to delta C-peptide immunoreactivity (ΔCPR). In a separate study, a retrospective chart review with human autopsy specimens was conducted, and vessels and islets of the pancreas were analyzed in 43 patients (20 cirrhotic, 23 controls; age, 71.5 ± 11.6; female, 15). RESULTS In the CE-US study, the clinical characteristics indicative of portal hypertension (e.g., ascites and varices) had significantly higher incidences in the cirrhotic group than in the control group. Pancreatic drainage times were greater in the cirrhotic group (p < 0.0001), and had a significant negative correlation with ΔCPR (R = 0.42, p = 0.0069). In the histopathological study, the islets were enlarged in the cirrhotic group (p < 0.0001). However, the percentage of insulin-positive area per islet was decreased in the cirrhotic group (p < 0.0001), and had a significant negative correlation with the wall thickness of the pancreatic vein (R = 0.63, p < 0.0001). CONCLUSIONS Pancreatic congestion was present in cirrhotic patients. Moreover, pancreatic congestion and insulin secretion were significantly correlated. This pathogenesis could be a key factor underlying the development of hepatogenous diabetes in cirrhotic patients.
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Affiliation(s)
- Taira Kuroda
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan
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Scheen AJ. Pharmacokinetics in patients with chronic liver disease and hepatic safety of incretin-based therapies for the management of type 2 diabetes mellitus. Clin Pharmacokinet 2015; 53:773-85. [PMID: 25091053 DOI: 10.1007/s40262-014-0157-y] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Patients with type 2 diabetes mellitus have an increased risk of chronic liver disease (CLD) such as non-alcoholic fatty liver disease and steatohepatitis, and about one-third of cirrhotic patients have diabetes. However, the use of several antidiabetic agents, such as metformin and sulphonylureas, may be a concern in case of hepatic impairment (HI). New glucose-lowering agents targeting the incretin system are increasingly used for the management of type 2 diabetes. Incretin-based therapies comprise oral inhibitors of dipeptidyl peptidase-4 (DPP-4) (gliptins) or injectable glucagon-like peptide-1 (GLP-1) receptor agonists. This narrative review summarises the available data regarding the use of both incretin-based therapies in patients with HI. In contrast to old glucose-lowering agents, they were evaluated in specifically designed acute pharmacokinetic studies in patients with various degrees of HI and their hepatic safety was carefully analysed in large clinical trials. Only mild changes in pharmacokinetic characteristics of DPP-4 inhibitors were observed in patients with different degrees of HI, presumably without major clinical relevance. GLP-1 receptor agonists have a renal excretion rather than liver metabolism. Specific pharmacokinetic data in patients with HI are only available for liraglutide. No significant changes in liver enzymes were reported with DPP-4 inhibitors or GLP-1 receptor agonists, alone or in combination with various other glucose-lowering agents, in clinical trials up to 2 years in length. On the contrary, preliminary data suggested that incretin-based therapies may be beneficial in patients with CLD, more particularly in the presence of non-alcoholic fatty liver disease. Nevertheless, caution should be recommended, especially in patients with advanced cirrhosis, because of a lack of clinical experience with incretin-based therapies in these vulnerable patients.
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Affiliation(s)
- André J Scheen
- Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, University of Liège, Liège, Belgium,
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Nakahara T, Hyogo H, Yoneda M, Sumida Y, Eguchi Y, Fujii H, Ono M, Kawaguchi T, Imajo K, Aikata H, Tanaka S, Kanemasa K, Fujimoto K, Anzai K, Saibara T, Sata M, Nakajima A, Itoh Y, Chayama K, Okanoue T. Type 2 diabetes mellitus is associated with the fibrosis severity in patients with nonalcoholic fatty liver disease in a large retrospective cohort of Japanese patients. J Gastroenterol 2014; 49:1477-84. [PMID: 24277052 DOI: 10.1007/s00535-013-0911-1] [Citation(s) in RCA: 113] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2013] [Accepted: 11/07/2013] [Indexed: 02/06/2023]
Abstract
BACKGROUND The prevalence of nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome have been increasing worldwide. The associations between metabolic factors and the histologic severity of NAFLD have not yet been clarified. Therefore, we studied the relationships between relevant metabolic factors and the histological severity of NAFLD. METHODS In a cross-sectional multicenter study conducted in Japan, we examined 1,365 biopsy-proven NAFLD patients. The frequencies of underlying lifestyle-related diseases and their relationships to the NAFLD histology were investigated. RESULTS The hepatic fibrosis stages (Stage 0/1/2/3/4) were 22.6/34.1/26.7/14.5/2.1 (%) in the male patients, and 16.2/31.7/23.9/21.6/6.6 (%) in the female patients. Dyslipidemia was present in 65.7% (hypertriglyceridemia, 45.3%; increased low-density lipoprotein cholesterol, 37.5%; decreased high density lipoprotein cholesterol, 19.5%) of patients. Hypertension was present in 30.2%, and diabetes mellitus (DM) in 47.3%. The fibrosis stage increased with age, especially in postmenopausal females. The body mass index was positively correlated with the fibrosis stage. Deterioration of glucose control was positively correlated with the fibrosis stage, this correlation being more prominent in females. Multivariate analysis identified age and DM as significant risk factors for advanced fibrosis. No significant correlation of the fibrosis stage was observed with hypertension. There was a negative correlation between the serum triglyceride levels and the fibrosis stage. CONCLUSIONS DM appeared to be a significant risk factor for advanced fibrosis in patients with NAFLD, and would therefore need to be properly managed to prevent the progression of NAFLD.
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Affiliation(s)
- Takashi Nakahara
- Department of Medicine and Molecular Sciences, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
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Occlusion of portosystemic shunts improves hyperinsulinemia due to insulin resistance in cirrhotic patients with portal hypertension. J Gastroenterol 2014; 49:1333-41. [PMID: 24096983 DOI: 10.1007/s00535-013-0893-z] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2013] [Accepted: 09/25/2013] [Indexed: 02/04/2023]
Abstract
BACKGROUND Liver cirrhosis (LC) is often complicated by hyperinsulinemia due to insulin resistance (IR), which is considered to be closely related to shunt formation and impaired liver function. This study evaluates whether balloon-occluded retrograde transvenous obliteration (B-RTO) can affect glucose and insulin metabolism in patients with LC. METHODS Twenty-five cirrhotic patients (mean age = 69.6 years; female/male = 12/13; hepatitis C virus/alcohol/nonalcoholic steatohepatitis = 14/6/5; Child-Pugh's class A/B = 10/15) with gastric varices and/or hepatic encephalopathy caused by portosystemic shunts (PSS) due to portal hypertension (PH) underwent B-RTO at our hospital. Testing was performed before and at 1 month after the procedure. RESULTS Shunt occlusion resulted in a decrease in extrahepatic collateral blood flow and an increase in portal venous flow, as well as a dramatic improvement in hepatic function markers. In addition, B-RTO significantly decreased homeostasis model assessment (HOMA) of IR without a statistical decline of HOMA of β-cell function. The 75-g oral glucose tolerance test (75-OGTT) revealed that occlusion of PSS reduced both fasting immunoreactive insulin (IRI) levels and the area under the curve for IRI. However, no significant change in preprandial or postprandial plasma glucose levels was observed. Furthermore, according to the criteria of the American Diabetes Association, B-RTO led to an improved 75-OGTT profile in 58.3 % of patients who had impaired glucose tolerance or diabetes mellitus before the procedure. CONCLUSIONS Shunt occlusion improves IR-related hyperinsulinemia through increased portal venous flow, ameliorated liver function, and consequent augmented hepatic insulin clearance in cirrhotic patients with PH.
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Scheen AJ. Pharmacokinetic and toxicological considerations for the treatment of diabetes in patients with liver disease. Expert Opin Drug Metab Toxicol 2014; 10:839-57. [PMID: 24669954 DOI: 10.1517/17425255.2014.902444] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Patients with type 2 diabetes have an increased risk of chronic liver disease (CLD) such as non-alcoholic fatty liver disease and steatohepatitis and about one-third of cirrhotic patients have diabetes. However, the use of several antidiabetic agents may be a cause for concern in the case of hepatic impairment (HI). AREAS COVERED An extensive literature search was performed to analyze the influence of HI on the pharmacokinetics (PK) of glucose-lowering agents and the potential consequences for clinical practice as far as the efficacy/safety balance of their use in diabetic patients with CLD is concerned. EXPERT OPINION Almost no PK studies have been published regarding metformin, sulfonylureas, thiazolidinediones and α-glucosidase inhibitors in patients with HI. Only mild changes in PK of glinides, dipeptidyl peptidase-4 inhibitors and sodium glucose cotransporters type 2 inhibitors were observed in dedicated PK studies in patients with various degrees of HI, presumably without major clinical relevance although large clinical experience is lacking. Glucagon-like peptide-1 receptor agonists have a renal excretion rather than liver metabolism. Rare anecdotal case reports of hepatotoxicity have been described with various glucose-lowering agents contrasting with numerous reassuring data. Nevertheless, caution should be recommended, especially in patients with advanced cirrhosis, including with the use of metformin.
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Affiliation(s)
- André J Scheen
- University of Liège, CHU Sart Tilman (B35), Center for Interdisciplinary Research on Medicines (CIRM), Division of Diabetes, Nutrition and Metabolic Disorders and Division of Clinical Pharmacology, Department of Medicine , B-4000 Liege 1 , Belgium +32 4 3667238 ; +32 4 3667068 ;
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Duvivier A. Enjeux et intérêts de l’épreuve d’effort cardiorespiratoire en transplantation hépatique. MEDECINE INTENSIVE REANIMATION 2014. [DOI: 10.1007/s13546-013-0830-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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Berzigotti A, Abraldes JG. Impact of obesity and insulin-resistance on cirrhosis and portal hypertension. GASTROENTEROLOGIA Y HEPATOLOGIA 2013; 36:527-33. [PMID: 23731977 DOI: 10.1016/j.gastrohep.2013.03.005] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/11/2013] [Accepted: 03/15/2013] [Indexed: 12/14/2022]
Abstract
Obesity is sharply rising worldwide and is increasingly recognized in patients with cirrhosis. This review summarizes the available data documenting a detrimental role of obesity and insulin-resistance on the risk of appearance of clinical events in patients with cirrhosis. Molecular pathways explaining the harmful effect of obesity and insulin resistance in the natural history of cirrhosis are largely unknown. Increasing knowledge of mechanisms leading to white adipose tissue dysfunction on one side, and to portal hypertension on the other side, allow hypothesizing that a link between the pathophysiology of obesity, insulin resistance and portal hypertension in cirrhosis exists. Mechanisms likely involved in this interplay are discussed in this article.
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Affiliation(s)
- Annalisa Berzigotti
- Laboratorio de Hemodinámica Hepática, Unidad de Hepatología, Hospital Clínic, IDIBAPS, Barcelona, Spain; CIBERehd, Barcelona, Spain.
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Zhu X, Wu Y, Qiu Y, Jiang C, Ding Y. Effects of ω-3 fish oil lipid emulsion combined with parenteral nutrition on patients undergoing liver transplantation. JPEN J Parenter Enteral Nutr 2013; 37:68-74. [PMID: 22421017 DOI: 10.1177/0148607112440120] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
BACKGROUND The effect of parenteral nutrition (PN) support supplemented with ω-3 fatty acids was investigated in a randomized, controlled clinical trial at the Affiliated Drum Tower Hospital, Medical School of Nanjing University. MATERIALS AND METHODS Ninety-eight patients with the diagnosis of end-stage liver disease or hepatic cellular carcinoma were admitted for orthotopic liver transplantation at the Affiliated Drum Tower Hospital. The patients were randomly divided into 3 groups: diet group (n = 32), PN group (n = 33), and polyunsaturated fatty acid (PUFA) group (n = 33). Patients in the PN and PUFA groups received isocaloric and isonitrogenous PN for 7 days after surgery. Venous heparin blood samples were obtained for assay on days 2 and 9 after surgery. A pathological test was performed after reperfusion of the donor liver and on day 9. RESULTS Alanine aminotransferase levels were improved significantly by PUFA treatment compared with traditional PN support (P < .05). Compared with the results on day 9 in the PN group, a significant difference was seen in the extent of increase of the prognostic nutrition index and prealbumin in the PUFA group. The pathological results also showed that ω-3 fatty acid supplementation reduced hepatic cell injury. PUFA therapy also decreased the incidence of infectious morbidities and shortened the posttransplant hospital stay significantly. CONCLUSION Posttransplant PN support can greatly improve metabolism of protein and nutrition states of patients. ω-3 fatty acid-supplemented PN significantly reduces injury of the transplanted liver, decreases the incidence of infectious morbidities, and shortens posttransplant hospital stay.
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Affiliation(s)
- Xinhua Zhu
- Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
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Miyake T, Abe M, Furukawa S, Tokumoto Y, Toshimitsu K, Ueda T, Yamamoto S, Hirooka M, Kumagi T, Hiasa Y, Matsuura B, Onji M. Long-term branched-chain amino acid supplementation improves glucose tolerance in patients with nonalcoholic steatohepatitis-related cirrhosis. Intern Med 2012; 51:2151-5. [PMID: 22892494 DOI: 10.2169/internalmedicine.51.7578] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Branched-chain amino acid (BCAA) supplements have mainly been administered as a nutritional intervention for decompensated liver cirrhosis. Several studies have shown that short-term BCAA supplementation improves insulin and glucose tolerance in patients with liver cirrhosis. However, the long-term effects of BCAA supplementation on glucose tolerance and in patients with nonalcoholic steatohepatitis (NASH)-related liver cirrhosis are unknown. Herein, we report 2 cases of NASH-related liver cirrhosis in which long-term BCAA supplementation improved glycemic control. We conclude that in the absence of an effective conventional therapy for NASH-related liver cirrhosis, BCAA supplementation should be considered as an alternative treatment.
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Affiliation(s)
- Teruki Miyake
- Department of Gastroenterology and Metabiology, Ehime University Graduate School of Medicine, Japan
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Namvaran F, Rahimi-Moghaddam P, Azarpira N, Nikeghbalian S. The association between adiponectin (+45T/G) and adiponectin receptor-2 (+795G/A) single nucleotide polymorphisms with cirrhosis in Iranian population. Mol Biol Rep 2011; 39:3219-23. [PMID: 21706165 DOI: 10.1007/s11033-011-1089-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2011] [Accepted: 06/11/2011] [Indexed: 01/07/2023]
Abstract
Adiponectin which possesses anti-inflammatory and insulin-sensitizing properties is elevated in blood circulation of liver cirrhosis patients. The genetic variations in the adiponectin gene can affect the circulating adiponectin level and stimulation of adiponectin receptor that may affect the activity of adiponectin. We investigated the effect of adiponectin single nucleotide polymorphisms (SNP) 45 T/G and adiponectin receptor-2 gene SNP 795G/A in cirrhotic Iranian population. A total of 97 cirrhotic patients and 128 healthy controls from Iranian population were genotyped for the adiponectin and adiponectin receptor 2 gene (+45T>G and 795G/A) by polymerase chain reaction-restriction fragment length polymorphism. G frequency was 21.1% versus 12.89% (P = 0.001) for SNP45, and G frequency was 75.8% versus 76.2% (P = 0.526) for SNP795G/A in the patients and control group, respectively. Based on our findings, the expression of the G allele at SNP45 is higher in the patient group compared with healthy subjects, suggesting that it may affect liver injury through changes in the plasma adiponectin level.
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Affiliation(s)
- Fatemeh Namvaran
- Department of Pharmacology, College of Medicine, Iran University of Medical Sciences, Tehran, Iran
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Abstract
The global risk of hepatocellular carcinoma (HCC) has been largely driven by hepatitis B virus (HBV) infection for the past century, along with hepatitis C virus (HCV), aflatoxin, excessive alcohol consumption, and obesity/diabetes. The dominant effect of HBV on global HCC risk should decline as the population vaccinated against HBV grows older. Infection with HCV is also expected to decline. Projections of HCV-related HCC rates remaining high for another 30 years may be overly pessimistic. Alcohol may be less of a factor in HCC in coming years. However, obesity and diabetes may become even more important risk factors for HCC.
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Affiliation(s)
- Katherine A McGlynn
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, EPS-5020, 6120 Executive Boulevard, Rockville, MD 20852-7234, USA.
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Basseri B, Yamini D, Chee G, Enayati PDP, Tran T, Poordad F. Comorbidities associated with the increasing burden of hepatitis C infection. Liver Int 2010; 30:1012-8. [PMID: 20408945 DOI: 10.1111/j.1478-3231.2010.02235.x] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is implicated in an increasing number of liver transplantations, hospitalizations and healthcare costs. AIMS We present an updated assessment of comorbidities associated with HCV in comparison to the general US population. METHODS Cross-sectional retrospective review of data from 800 patients with HCV evaluated between January 1998 and November 2007. Patient data were prospectively collected using a standardized questionnaire completed at the first encounter and was compared with general US epidemiological data. Odds ratios and 95% confidence intervals (CI) are reported. RESULTS HCV conferred a 44% (CI 1.16-1.78) and 25% (CI 1.01-1.54) increased risk of diabetes (12.5 vs. 7.3-8.4%; P=0.001) and obesity (23.9 vs. 19.8-33.1%; P=0.041), respectively, compared with the US population. Human immunodeficiency virus (HIV) (5.3 vs. 0.3%; P<0.001) and end-stage renal disease (ESRD) (4.5 vs. 0.2%; P<0.001) were 16- and 13-fold more prevalent in HCV. Interestingly, HCV bestowed 90% decreased odds (CI 0.09-0.15) for hyperlipidaemia (12.3 vs. 53.2-56.1%; P<0.001). The HCV population had a higher prevalence of significant alcohol consumption (41.5 vs. 4.7%; P<0.001), current smoking (57.7 vs. 18.8-20.8%; P<0.001), drug use (46.8 vs. 14.6-15.6%; P<0.001), incarceration (6.6 vs. 2.7%; P<0.001) and tattoos (20.3 vs. 14%; P=0.011), as well as chronic fatigue (44.6 vs. 11.3-19%; P<0.001) and depression (29.3 vs. 5.0-10.3%; P<0.001). CONCLUSION HCV poses an increasing healthcare burden associated with increased prevalence of diabetes, obesity, HIV, ESRD, maladaptive lifestyle habits and poor quality of life. Practitioners should be cognizant of these trends in order to appropriately manage these comorbidities.
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Affiliation(s)
- Benjamin Basseri
- Hepatology Section, Division of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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Kumamoto M, Toyonaga A, Inoue H, Miyakoda K, Morita Y, Emori K, Sakamoto Y, Oho K, Sata M. Long-term results of balloon-occluded retrograde transvenous obliteration for gastric fundal varices: hepatic deterioration links to portosystemic shunt syndrome. J Gastroenterol Hepatol 2010; 25:1129-35. [PMID: 20594229 DOI: 10.1111/j.1440-1746.2010.06262.x] [Citation(s) in RCA: 85] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS It is well known that a large portosystemic shunt develops during portal hypertension. In this study, we studied the long-term effects of a large splenorenal shunt (SRS) on liver function and survival. METHODS The subjects were divided into three groups: an SRS (-) group consisting of cirrhotic patients without SRS; an SRS (+) group consisting of patients with gastric fundal varices and SRS; and a balloon-occluded retrograde transvenous obliteration (B-RTO) group with a completely obliterated SRS by B-RTO. We compared the following among these groups: the total bilirubin levels, serum albumin levels, prothrombin times, changes in Child-Pugh scores, and survival rates. RESULTS After a 3-year follow-up period the Child-Pugh scores showed significant differences among the SRS (+), SRS (-), and B-RTO groups. The score worsened for the SRS (+) group. The cumulative survival rates were significantly different between the SRS (+) and SRS (-) groups and between the SRS (+) and B-RTO groups. The vital prognosis worsened for the SRS (+) group. CONCLUSIONS The presence of a large splenorenal shunt (portosystemic shunt) was indicated to lower liver function and vital prognosis. B-RTO, which completely obliterates large splenorenal shunts, inhibited the lowering of hepatic functional reserve and the worsening of vital prognosis, indicating a protective role. Liver pathology and the presence of a large portosystemic shunt each separately result in progressive liver dysfunction and worsen the survival rate. We found that such a pathological condition had occurred due to a large portosystemic shunt, and it should be called 'portosystemic shunt syndrome.'
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Affiliation(s)
- Masafumi Kumamoto
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
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Montomoli J, Holland-Fischer P, Bianchi G, Grønbæk H, Vilstrup H, Marchesini G, Zoli M. Body composition changes after transjugular intrahepatic portosystemic shunt in patients with cirrhosis. World J Gastroenterol 2010; 16:348-53. [PMID: 20082481 PMCID: PMC2807956 DOI: 10.3748/wjg.v16.i3.348] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effect of transjugular intrahepatic porto-systemic shunt (TIPS) on malnutrition in portal hypertensive cirrhotic patients.
METHODS: Twenty-one patients with liver cirrhosis and clinical indications for TIPS insertion were investigated before and 1, 4, 12, 52 wk after TIPS. For each patient we assayed body composition parameters [dry lean mass, fat mass, total body water (TBW)], routine liver and kidney function tests, and free fatty acids (FFA). Glucose and insulin were measured for the calculation of the homeostasis model assessment insulin resistance (HOMA-IR); liver function was measured by the galactose elimination capacity (GEC); the severity of liver disease was graded by model for end-stage liver disease (MELD).
RESULTS: Porto-systemic gradient decreased after TIPS (6.0 ± 2.1 mmHg vs 15.8 ± 4.8 mmHg, P < 0.001). Patients were divided in two groups according to initial body mass index. After TIPS, normal weight patients had an increase in dry lean mass (from 10.9 ± 5.9 kg to 12.7 ± 5.6 kg, P = 0.031) and TBW (from 34.5 ± 7.6 L to 40.2 ± 10.8 L, P = 0.007), as well as insulin (from 88.9 ± 49.2 pmol/L to 164.7 ± 107.0 pmol/L, P = 0.009) and HOMA-IR (from 3.36% ± 2.18% to 6.18% ± 4.82%, P = 0.023). In overweight patients only FFA increased significantly (from 0.59 ± 0.24 mmol/L to 0.93 ± 0.34 mmol/L, P = 0.023).
CONCLUSION: TIPS procedure is effective in lowering portal pressure in patients with portal hypertension and improves body composition without significant changes in metabolic parameters.
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Arai H, Awane N, Mizuno A, Fukaya M, Sakuma M, Harada N, Kawaura A, Yamamoto H, Okumura H, Taketani Y, Doi T, Takeda E. Increasing early insulin secretion compensate adequately for hepatic insulin resistance in CCl4-induced cirrhosis rats. THE JOURNAL OF MEDICAL INVESTIGATION 2010; 57:54-61. [DOI: 10.2152/jmi.57.54] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Affiliation(s)
- Hidekazu Arai
- Department of Laboratory of Clinical Nutrition Management, School of Food and Nutritional Sciences, the University of Shizuoka
- Department of Clinical Nutrition, Institute of Health Biosciences, the University of Tokushima Graduate School
| | - Naomi Awane
- Department of Clinical Nutrition, Institute of Health Biosciences, the University of Tokushima Graduate School
| | - Akira Mizuno
- Department of Clinical Biology and Medicine, Institute of Health Biosciences, the University of Tokushima Graduate School
| | - Makiko Fukaya
- Department of Clinical Nutrition, Institute of Health Biosciences, the University of Tokushima Graduate School
| | - Masae Sakuma
- Department of Laboratory of Clinical Nutrition Management, School of Food and Nutritional Sciences, the University of Shizuoka
- Department of Clinical Nutrition, Institute of Health Biosciences, the University of Tokushima Graduate School
| | - Nagakatsu Harada
- Department of Nutrition and Metabolism, Institute of Health Biosciences, the University of Tokushima Graduate School
| | - Akihiko Kawaura
- Department of Clinical Nutrition, Institute of Health Biosciences, the University of Tokushima Graduate School
- Department of Physical Therapy, School of Health Science, KIBI International University
| | - Hironori Yamamoto
- Department of Clinical Nutrition, Institute of Health Biosciences, the University of Tokushima Graduate School
| | - Hisami Okumura
- Department of Clinical Nutrition, Institute of Health Biosciences, the University of Tokushima Graduate School
| | - Yutaka Taketani
- Department of Clinical Nutrition, Institute of Health Biosciences, the University of Tokushima Graduate School
| | - Toshio Doi
- Department of Clinical Biology and Medicine, Institute of Health Biosciences, the University of Tokushima Graduate School
| | - Eiji Takeda
- Department of Clinical Nutrition, Institute of Health Biosciences, the University of Tokushima Graduate School
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Plauth M, Schuetz T. Hepatology - Guidelines on Parenteral Nutrition, Chapter 16. GERMAN MEDICAL SCIENCE : GMS E-JOURNAL 2009; 7:Doc12. [PMID: 20049084 PMCID: PMC2795384 DOI: 10.3205/000071] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/14/2009] [Indexed: 12/13/2022]
Abstract
Parenteral nutrition (PN) is indicated in alcoholic steatohepatitis (ASH) and in cirrhotic patients with moderate or severe malnutrition. PN should be started immediately when sufficientl oral or enteral feeding is not possible. ASH and cirrhosis patients who can be sufficiently fed either orally or enterally, but who have to abstain from food over a period of more than 12 hours (including nocturnal fasting) should receive basal glucose infusion (2–3 g/kg/d). Total PN is required if such fasting periods last longer than 72 h. PN in patients with higher-grade hepatic encephalopathy (HE); particularly in HE IV° with malfunction of swallowing and cough reflexes, and unprotected airways. Cirrhotic patients or patients after liver transplantation should receive early postoperative PN after surgery if they cannot be sufficiently rally or enterally nourished. No recommendation can be made on donor or organ conditioning by parenteral administration of glutamine and arginine, aiming at minimising ischemia/reperfusion damage. In acute liver failure artificial nutrition should be considered irrespective of the nutritional state and should be commenced when oral nutrition cannot be restarted within 5 to 7 days. Whenever feasible, enteral nutrition should be administered via a nasoduodenal feeding tube.
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Affiliation(s)
- M Plauth
- Dept. of Internal Medicine, Municipal Clinic Dessau, Germany
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Nightingale S, Ng VL. Optimizing nutritional management in children with chronic liver disease. Pediatr Clin North Am 2009; 56:1161-83. [PMID: 19931069 DOI: 10.1016/j.pcl.2009.06.005] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Malnutrition is common in infants and children with chronic liver disease (CLD) and may easily be underestimated by clinical appearance alone. The cause of malnutrition in CLD is multifactorial, although insufficient dietary intake is probably the most important factor and is correctable. Fat malabsorption occurs in cholestatic disorders, and one must also consider any accompanying fat-soluble vitamin and essential fatty acid deficiencies. The clinician should proactively evaluate, treat, and re-evaluate response to treatment of nutritional deficiencies. Because a better nutritional state is associated with better survival before and after liver transplantation, aggressive nutritional management is an important part of the care of these children.
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Affiliation(s)
- Scott Nightingale
- SickKids Transplant Center, Division of Gastroenterology, Hepatology, and Nutrition, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada
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ESPEN Guidelines on Parenteral Nutrition: hepatology. Clin Nutr 2009; 28:436-44. [PMID: 19520466 DOI: 10.1016/j.clnu.2009.04.019] [Citation(s) in RCA: 141] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2009] [Accepted: 04/27/2009] [Indexed: 12/13/2022]
Abstract
Parenteral nutrition (PN) offers the possibility to increase or to ensure nutrient intake in patients, in whom sufficient nutrition by oral or enteral alone is insufficient or impossible. Complementary to the ESPEN guideline on enteral nutrition of liver disease (LD) patients the present guideline is intended to give evidence-based recommendations for the use of PN in LD. For this purpose three paradigm conditions of LD were chosen: alcoholic steatohepatitis (ASH), liver cirrhosis and acute liver failure. The guideline was developed by an interdisciplinary expert group in accordance with officially accepted standards and is based on all relevant publications since 1985. The guideline was presented on the ESPEN website and visitors' criticism and suggestions were welcome and included in the final revision. PN improves nutritional state and liver function in malnourished patients with ASH. PN is safe and improves mental state in patients with cirrhosis and severe HE. Perioperative (including liver transplantation) PN is safe and reduces the rate of complications. In acute liver failure PN is a safe second-line option to adequately feed patients in whom enteral nutrition is insufficient or impossible.
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de Boer JF, Bahr MJ, Böker KHW, Manns MP, Tietge UJF. Plasma levels of PBEF/Nampt/visfatin are decreased in patients with liver cirrhosis. Am J Physiol Gastrointest Liver Physiol 2009; 296:G196-201. [PMID: 19074645 DOI: 10.1152/ajpgi.00029.2008] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Liver cirrhosis is a catabolic disease associated with a high incidence of insulin resistance and diabetes mellitus. Pre-B cell colony-enhancing factor/ nicotinamide phosphoribosyltransferase/visfatin has been characterized as a novel adipokine with a potential role in glucose metabolism and nicotinamide dinucleotide (NAD) generation. We studied plasma levels and metabolic relevance of visfatin in 19 patients with cirrhosis and 19 body mass index-, age-, and sex-matched controls. In addition, hepatic mRNA expression was assessed by qPCR in livers of seven patients with cirrhosis and four controls. Circulating visfatin was 78% lower in cirrhotics (P < 0.001) and decreased with worsening of the clinical stage of liver disease. Hepatic visfatin secretion decreased with clinical stage (P < 0.05) and reduced liver function (P = 0.01). Consistent with these data, hepatic visfatin mRNA expression was significantly lower in cirrhotic livers (P < 0.05). Circulating visfatin in cirrhosis was correlated with body cell mass (r = 0.72, P < 0.01) as well as with body fat mass (r = 0.53, P < 0.05) but not with plasma glucose, insulin, the degree of insulin resistance, or whole body glucose oxidation rates. Higher visfatin levels were associated with higher hepatic glucose production (r = 0.53, P < 0.05) and also with a higher arterial ketone body ratio (KBR) (r = 0.48, P < 0.05), an indicator of increased hepatic NAD generation. In conclusion, circulating visfatin levels are significantly decreased in liver cirrhosis, presumably attributable to decreased hepatic expression and production. Plasma visfatin in cirrhosis is not associated with insulin resistance but correlates with hepatic glucose production and the arterial KBR, indicating a potential link between the NAD-generating properties of visfatin and metabolism.
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Affiliation(s)
- Jan Freark de Boer
- Center for Liver, Digestive and Metabolic Diseases, University Medical Center Groningen, Groningen, The Netherlands
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Bahr MJ, Boeker KHW, Manns MP, Tietge UJF. Decreased hepatic RBP4 secretion is correlated with reduced hepatic glucose production but is not associated with insulin resistance in patients with liver cirrhosis. Clin Endocrinol (Oxf) 2009; 70:60-5. [PMID: 18466349 DOI: 10.1111/j.1365-2265.2008.03295.x] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
OBJECTIVE Patients with liver cirrhosis have a high incidence of insulin resistance and diabetes. This study was designed to determine circulating levels and hepatic production of retinol-binding protein 4 (RBP4) in relation to parameters of hepatic and systemic metabolism in patients with liver cirrhosis. DESIGN AND METHOD Circulating RBP4 levels were measured in 19 patients with liver cirrhosis at different clinical stages of the disease and in 20 age-, sex- and body mass index (BMI)-matched controls. Hepatic production rates of RBP4 and glucose were assessed by measuring the arterial hepatic venous concentration difference together with hepatic blood flow. Insulin resistance was determined by the Quantitative Insulin Sensitivity Check Index (QUICKI) and the homeostasis model assessment of insulin resistance (HOMA-IR), energy expenditure by indirect calorimetry and body composition by bioelectrical impedance analysis (BIA). RESULTS Compared with controls, RBP4 levels in cirrhosis were decreased (8.1 +/- 1.8 vs. 22.6 +/- 2.4 mg/l, P < 0.001) due to decreased hepatic production (P < 0.05). RBP4 correlated with hepatic protein synthesis capacity (P < 0.01), but not with insulin resistance, energy expenditure, BMI or body fat mass. Plasma RBP4 correlated with hepatic glucose production (P < 0.05). CONCLUSIONS These data demonstrate that RBP4 in cirrhosis (i) is decreased due to reduced hepatic production, (ii) is not associated with insulin resistance, and (iii) might have a beneficial role by decreasing hepatic glucose production and could thus also be regarded as a hepatokine.
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Affiliation(s)
- Matthias J Bahr
- Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany
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46
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Shimizu H, Takatsuka K, Yoshida A, Yoshimatsu E, Matsui K, Iwabuchi S. Partial splenic embolization reverses insulin resistance in patients with liver cirrhosis. Intern Med 2009; 48:747-51. [PMID: 19443968 DOI: 10.2169/internalmedicine.48.1649] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND It is well known that patients with liver cirrhosis often develop insulin resistance and diabetes mellitus. Recently, we encountered a liver cirrhosis patient in whom partial splenic embolization (PSE) improved insulin sensitivity. Therefore, we conducted further investigation about PSE and insulin resistance. METHODS Thirty-seven consecutive patients with liver cirrhosis underwent PSE. Hemodynamic changes, blood counts, and homeostasis model assessment of insulin resistance (HOMA-IR) were assessed before and 2 weeks after PSE. RESULTS PSE resulted in decreased splenic venous flow and increased intestinal venous flow to the liver. Platelet counts before and after PSE were 7.7+/-0.5 x 10(4) /microL, 15.0+/-1.4 x 10(4) /microL, respectively (p<0.01). HOMA-IR before and after PSE were 6.5+/-2.1, 3.3+/-0.6, respectively (p<0.05). HCV core antigen before and after PSE were 6,340+/-1,296 fmol/L, 4,112+/-873 fmol/L, respectively (p<0.05). Conclusion PSE significantly reverses insulin resistance in patients with liver cirrhosis. The increase in intestinal venous flow to the liver and reduced HCV viral load were thought to be mechanisms of improvement in insulin sensitivity after PSE.
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Affiliation(s)
- Hirohito Shimizu
- Center for Digestive and Liver Diseases, Ofuna Chuo Hospital, Kanagawa
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O'Brien A, Williams R. Nutrition in end-stage liver disease: principles and practice. Gastroenterology 2008; 134:1729-40. [PMID: 18471550 DOI: 10.1053/j.gastro.2008.02.001] [Citation(s) in RCA: 95] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2007] [Revised: 01/25/2008] [Accepted: 02/01/2008] [Indexed: 02/07/2023]
Affiliation(s)
- Alastair O'Brien
- Institute of Hepatology, Royal Free and University College Medical School, University College London, London, England. a.o'
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48
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Tamura M, Kihara Y, Otsuki M. Carotid intima-media thickness in patients with liver cirrhosis associated with diabetes mellitus. Diabetes Res Clin Pract 2007; 78:176-81. [PMID: 17467107 DOI: 10.1016/j.diabres.2007.03.013] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2006] [Revised: 03/01/2007] [Accepted: 03/08/2007] [Indexed: 11/22/2022]
Abstract
OBJECTIVE In patients with liver cirrhosis (LC), the incidence of diabetes mellitus (DM) is high, whereas that of hypertension and ischemic heart diseases is low. We measured carotid artery intima-media thickness (IMT) to determine the incidence of atherosclerosis in patients with LC+DM and to compare it with that in patients with type 2 DM, and evaluated the risk factors for atherosclerosis in these patients. RESEARCH DESIGN AND METHODS We determined IMT of the common carotid artery by B-mode ultrasound, serum lipid levels, C-reactive protein (CRP), plasma levels of fasting and postprandial glucose, glycated hemoglobin (HbA1c), fibrinogen and platelet counts in 14 patients of the LC+DM group, 16 patients with type 2 DM (DM group) and 14 patients with LC without impaired glucose tolerance (LC group). RESULTS The IMT in the LC+DM group (0.694+/-0.175mm) was similar to that in the LC group (0.693+/-0.151mm) but significantly smaller than the DM group (0.904+/-0.337mm). There were no significant differences between the LC+DM group and DM group in the duration of DM, proportion of smokers, arterial blood pressure, fasting and postprandial plasma glucose levels, and CRP, but HbA1c, platelet counts and fibrinogen were significantly lower in the LC+DM group than in the DM group. CONCLUSIONS Our study suggests that the development of atherosclerosis in patients with DM is suppressed by the presence of LC, probably due to reduced platelet counts and fibrinogen levels.
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Affiliation(s)
- Miho Tamura
- Department of Gastroenterology and Metabolism, University of Occupational and Environmental Health, Japan School of Medicine, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyusyu Fukuoka 807-8555, Japan
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Holland-Fischer P, Andersen PH, Lund S, Pedersen SB, Vinter-Jensen L, Nielsen MF, Kaal A, Dall R, Schmitz O, Vilstrup H. Muscle GLUT4 in cirrhosis. J Hepatol 2007; 47:212-9. [PMID: 17448565 DOI: 10.1016/j.jhep.2007.02.012] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2006] [Revised: 02/06/2007] [Accepted: 02/20/2007] [Indexed: 01/17/2023]
Abstract
BACKGROUND/AIMS The insulin-dependent glucose transporter GLUT4 mediates 50-80% of whole body glucose uptake, but its relation to the frequent glucose intolerance in patients with liver cirrhosis is unknown. METHODS Thirty patients and seven healthy controls underwent a 2-h oral glucose tolerance test and later a muscle biopsy. Levels of GLUT4 total protein and mRNA content were determined in muscle biopsies by polyclonal antibody labelling and RT-PCR, respectively. RESULTS GLUT4 protein content in the cirrhosis group was not different from that of the controls, but at variance with the control subjects it correlated closely with measures of glucose tolerance (R(2)=0.45; p=0.003). GLUT4 mRNA of the patients with cirrhosis was reduced to 56% of control value (95% ci: 27-86%; p=0.015) and was inversely related to the level of basal hyper-insulinemia (R(2)=0.39; p=0.004). CONCLUSIONS In cirrhosis GLUT4 protein content was quantitatively intact, while limiting glucose tolerance. This indicates loss of redundancy of the major glucose transport system, possibly related to the markedly decreased expression of its gene. Hyper-insulinemia may be a primary event. Our findings implicate the muscular GLUT4 system in the glucose intolerance of liver cirrhosis by a mechanism different from that in diabetes.
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Affiliation(s)
- Peter Holland-Fischer
- Department of Medicine V (Hepatology and Gastroenterology), Aarhus University Hospital, 44 Noerrebrogade, DK-8000 Aarhus C, Denmark.
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Buyse S, Valla D. [Carbohydrate metabolism dysregulation in cirrhosis: pathophysiology, prognostic impact and therapeutic implications]. ACTA ACUST UNITED AC 2007; 31:266-73. [PMID: 17396083 DOI: 10.1016/s0399-8320(07)89371-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The liver plays a key-role in carbohydrates metabolism. Glucose intole-rance, overt diabetes mellitus and insulin resistance are characteristic features of patients with cirrhosis. Central hyperinsulinemia and peripheral insulin-resistance are the main explanations for the high prevalence of diabetes in patients with cirrhosis. On the other hand, type 2 diabetes is associated with a wide spectrum of liver diseases ranging from nonalcoholic fatty liver to cirrhosis and hepatocellular carcinoma. Carbohydrate metabolism abnormalities are a major aggravating risk factor in cirrhosis. Diabetes is also an independent negative prognostic factor in cirrhotic patients. This leads to specific diagnostic procedures and therapeutic issues. Patients with diabetes and liver disease frequently need insulin treatment. The presence of liver disease makes the treatment of diabetes complex, and additional research is needed to determine the best treatment strategies in these patients.
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Affiliation(s)
- Sophie Buyse
- Fédération d'Hépato-Gastroentérologie Médico-Chirurgicale, Hôpital Beaujon, Clichy
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