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Flatley S, Dixon S, Pilsworth E, Dube A, Hoeroldt B, Harrison L, Gleeson D. Diabetes Mellitus in Patients With Autoimmune Hepatitis: Frequency, Risk Factors and Effect on Outcome. Aliment Pharmacol Ther 2025. [PMID: 40342076 DOI: 10.1111/apt.70188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2024] [Revised: 09/02/2024] [Accepted: 04/30/2025] [Indexed: 05/11/2025]
Abstract
BACKGROUND Treatment for autoimmune hepatitis (AIH) includes corticosteroids, which are associated with the development of diabetes mellitus (DM). Reported new-onset DM rates in patients with AIH have varied, and predisposing factors and prognostic implications are inadequately characterised. AIM To identify the frequency and predisposing factors for DM in AIH and its association with disease progression and mortality. METHODS Retrospective/prospective single-centre study of 494 patients with AIH presenting 1987-2023, 466 receiving corticosteroids (454 prednisolone, 12 budesonide) and followed for (median (range) 9 (0-36) years). RESULTS Forty-seven patients (10%) already had DM at AIH diagnosis. New-onset DM subsequently developed in another 59 (13%). In those receiving prednisolone, new-onset DM incidence was 8% ± 1% after 1 year and 14% ± 2% after 10 years (14- and 3-fold higher than expected population rate), and was independently associated with older age, non-Caucasian ethnicity, higher initial prednisolone dose, higher BMI at diagnosis and more weight gain after 2 years of follow-up. New-onset DM usually persisted despite stopping prednisolone. New-onset DM and DM at any time were independently associated with all-cause death/transplantation rate, along with previously established risk factors (older age, cirrhosis, lower ALT at diagnosis and failure of early ALT normalisation). New-onset DM and DM at any time were also independently associated with cirrhosis development. Similar associations of new-onset DM and DM at any time with liver-related death/transplantation were significant on univariate but not multivariate analysis. CONCLUSION New-onset DM occurred in 13% of patients with AIH, was related to older age, non-Caucasian ethnicity, higher prednisolone dose, higher BMI at diagnosis and weight gain; and was an independent predictor of all-cause death/transplantation and of cirrhosis development, underlining the need to minimise steroid burden in AIH.
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Affiliation(s)
- Sarah Flatley
- Liver Unit, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
- Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, University of Sheffield Medical School, Sheffield, UK
| | - Selena Dixon
- Liver Unit, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - Eleanor Pilsworth
- Liver Unit, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - Asha Dube
- Department of Histopathology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - Barbara Hoeroldt
- Liver Unit, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - Laura Harrison
- Liver Unit, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - Dermot Gleeson
- Liver Unit, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
- Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, University of Sheffield Medical School, Sheffield, UK
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Liu X, Wang X. The prognosis of patients with co-morbid diabetes and hepatitis B and strategies for improving outcome. Am J Med Sci 2025; 369:638-641. [PMID: 39710356 DOI: 10.1016/j.amjms.2024.12.011] [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: 09/08/2024] [Revised: 12/19/2024] [Accepted: 12/19/2024] [Indexed: 12/24/2024]
Abstract
The relationship between diabetes and hepatitis B remains unclear. We have found that there is no general correlation between the incidence of diabetes and hepatitis B, except in certain populations. Patients with co-existing diabetes and hepatitis B tend to have poorer overall prognoses, primarily evidenced by an increased risk of hepatocellular carcinoma (HCC) and all-cause mortality within this population. The optimal selection of medication for these patients should take long-term prognosis into account. To improve long-term outcomes, we recommend specific anti-diabetic medications for this group. Additionally, it is advisable to administer the hepatitis B vaccine as soon as possible following a diagnosis of diabetes in order to enhance the patient's prognosis. Increased attention from health management authorities, revisions of relevant guidelines, and advancements in educational initiatives may also improve outcomes for this demographic.
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Affiliation(s)
- Xiyu Liu
- Department of Endocrinology, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China.
| | - Xiaohong Wang
- Department of Endocrinology, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China
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Mallet M, Silaghi CA, Sultanik P, Conti F, Rudler M, Ratziu V, Thabut D, Pais R. Current challenges and future perspectives in treating patients with NAFLD-related cirrhosis. Hepatology 2024; 80:1270-1290. [PMID: 37183906 DOI: 10.1097/hep.0000000000000456] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Accepted: 04/20/2023] [Indexed: 05/16/2023]
Abstract
Despite the slow, progressive nature of NAFLD, the number of patients with NAFLD-related cirrhosis has significantly increased. Although the management of patients with cirrhosis is constantly evolving, improving the prognosis of patients with NAFLD-related cirrhosis is a challenge because it is situated at the crossroads between the liver, the metabolic, and the cardiovascular diseases. Therefore, the therapeutic interventions should not only target the liver but also the associated cardiometabolic conditions and should be adapted accordingly. The objective of the current review is to critically discuss the particularities in the management of patients with NAFLD-related cirrhosis. We relied on the recommendations of scientific societies and discussed them in the specific context of NAFLD cirrhosis and the surrounding cardiometabolic milieu. Herein, we covered the following aspects: (1) the weight loss strategies through lifestyle interventions to avoid sarcopenia and improve portal hypertension; (2) the optimal control of metabolic comorbidities in particular type 2 diabetes aimed not only to improve cardiovascular morbidity/mortality but also to lower the incidence of cirrhosis-related complications (we discussed various aspects related to the safety of oral antidiabetic drugs in cirrhosis); (3) the challenges in performing bariatric surgery in patients with cirrhosis related to the portal hypertension and the risk of cirrhosis decompensation; (4) the particularities in the diagnosis and management of the portal hypertension and the difficulties in managing patients awaiting for liver transplantation; and (5) the difficulties in developing drugs and conducting clinical trials in patients with NAFLD-related cirrhosis. Moreover, we discussed the emerging options to overcome these obstacles.
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Affiliation(s)
- Maxime Mallet
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Service d'hepato-gastroentérologie, Hôpital Pitié-Salpêtrière, Paris, France
| | - Cristina Alina Silaghi
- Department of Endocrinology, "Iuliu Hatieganu" University of Medicine and Pharmacy Cluj-Napoca, Roumanie
| | - Philippe Sultanik
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Service d'hepato-gastroentérologie, Hôpital Pitié-Salpêtrière, Paris, France
- Brain Liver Pitié-Salpêtrière Study Group (BLIPS), Paris, France
| | - Filomena Conti
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Service d'hepato-gastroentérologie, Hôpital Pitié-Salpêtrière, Paris, France
- Centre de Recherche Saint Antoine, INSERM UMRS_938 Paris, France
| | - Marika Rudler
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Service d'hepato-gastroentérologie, Hôpital Pitié-Salpêtrière, Paris, France
- Brain Liver Pitié-Salpêtrière Study Group (BLIPS), Paris, France
- Centre de Recherche Saint Antoine, INSERM UMRS_938 Paris, France
- Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Vlad Ratziu
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Service d'hepato-gastroentérologie, Hôpital Pitié-Salpêtrière, Paris, France
- Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
- INSERM UMRS 1138 CRC, Paris, France
| | - Dominique Thabut
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Service d'hepato-gastroentérologie, Hôpital Pitié-Salpêtrière, Paris, France
- Brain Liver Pitié-Salpêtrière Study Group (BLIPS), Paris, France
- Centre de Recherche Saint Antoine, INSERM UMRS_938 Paris, France
| | - Raluca Pais
- Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Service d'hepato-gastroentérologie, Hôpital Pitié-Salpêtrière, Paris, France
- Centre de Recherche Saint Antoine, INSERM UMRS_938 Paris, France
- Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
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Martín-Escolano R, Virseda-Berdices A, Berenguer J, González-García J, Brochado-Kith O, Fernández-Rodríguez A, Díez C, Hontañon V, Resino S, Jiménez-Sousa MÁ. Low plasma levels of BTLA and LAG-3 before HCV therapy are associated with metabolic disorders after HCV eradication in persons with HIV/HCV coinfection: a retrospective study. Front Pharmacol 2024; 15:1341612. [PMID: 39530457 PMCID: PMC11551606 DOI: 10.3389/fphar.2024.1341612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Accepted: 10/04/2024] [Indexed: 11/16/2024] Open
Abstract
Background Understanding the predictors of metabolic disorders in persons with HIV/HCV coinfection post-HCV therapy is crucial for improving patient outcomes. Since immune checkpoint proteins are usually upregulated in these persons with HIV/HCV coinfection, we aimed to evaluate the association between plasma immune checkpoint proteins at baseline (before HCV therapy) and metabolic disturbances during the follow-up (about 5 years after successful HCV treatment) in persons with HIV/HCV coinfection. Methods We performed a retrospective study on 80 persons with HIV/HCV coinfection with advanced fibrosis or cirrhosis who cleared HCV infection after successful HCV therapy and were followed for about 5 years after completion of HCV treatment. Plasma samples were collected at baseline. Immune checkpoint proteins were analyzed using a Luminex 200™ analyzer. Outcomes were the development of a metabolic event (type 2 diabetes mellitus and/or dyslipidemia) and the change in Triglycerides and glucose (TyG) index. Results During follow-up, 21 (26%) patients developed metabolic events (type 2 diabetes mellitus/dyslipidemia), and 29 (46.0%) patients had an increase in TyG during the follow-up. Low baseline values of BTLA and LAG-3, two immune checkpoint proteins, were associated with the development of metabolic events (aAMR = 0.69 and aAMR = 0.71, respectively) and with increases in TyG values (aAMR = 0.72 and aAMR = 0.70, respectively). In addition, other immune checkpoint proteins were also inversely associated with increases in TyG. Conclusion We discovered that low plasma levels of BTLA and LAG-3 before HCV therapy significantly correlate with an increased risk of developing metabolic disorders after treatment.
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Affiliation(s)
- Rubén Martín-Escolano
- Centro Nacional de Microbiología (CNM), Unidad de Infección Viral e Inmunidad, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Ana Virseda-Berdices
- Centro Nacional de Microbiología (CNM), Unidad de Infección Viral e Inmunidad, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Juan Berenguer
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario “Gregorio Marañón”, Madrid, Spain
- Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Juan González-García
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Servicio de Medicina Interna-Unidad de VIH, Hospital Universitario La Paz, Madrid, Spain
- Instituto de Investigación Sanitaria La Paz (IdiPAZ), Madrid, Spain
| | - Oscar Brochado-Kith
- Centro Nacional de Microbiología (CNM), Unidad de Infección Viral e Inmunidad, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Amanda Fernández-Rodríguez
- Centro Nacional de Microbiología (CNM), Unidad de Infección Viral e Inmunidad, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Cristina Díez
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario “Gregorio Marañón”, Madrid, Spain
- Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Victor Hontañon
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Servicio de Medicina Interna-Unidad de VIH, Hospital Universitario La Paz, Madrid, Spain
- Instituto de Investigación Sanitaria La Paz (IdiPAZ), Madrid, Spain
| | - Salvador Resino
- Centro Nacional de Microbiología (CNM), Unidad de Infección Viral e Inmunidad, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - María Ángeles Jiménez-Sousa
- Centro Nacional de Microbiología (CNM), Unidad de Infección Viral e Inmunidad, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
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Yadav M, Verma S, Tiwari P, Mugale MN. Unraveling the mechanisms of hepatogenous diabetes and its therapeutic perspectives. Life Sci 2024; 353:122934. [PMID: 39089644 DOI: 10.1016/j.lfs.2024.122934] [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: 05/09/2024] [Revised: 06/26/2024] [Accepted: 07/25/2024] [Indexed: 08/04/2024]
Abstract
The review focused mainly on the pathogenesis of hepatogenous diabetes (HD) in liver cirrhosis (LC). This review reveals parallels between the mechanisms of metabolic dysfunction observed in LC and type II diabetes (T2DM), suggesting a shared pathway leading to HD. It underscores the role of insulin in HD pathogenesis, highlighting key factors such as insulin signaling, glucose metabolism, insulin resistance (IR), and the influence of adipocytes. Furthermore, the impact of adipose tissue accumulation, fatty acid metabolism, and pro-inflammatory cytokines like Tumor necrosis factor-α (TNF-α) on IR are discussed in the context of HD. Altered signaling pathways, disruptions in the endocrine system, liver inflammation, changes in muscle mass and composition, and modifications to the gut microbiota collectively contribute to the complex interplay linking cirrhosis and HD. This study highlights how important it is to identify and treat this complex condition in cirrhotic patients by thoroughly analyzing the link between cirrhosis, IR, and HD. It also emphasizes the vitality of targeted interventions. Cellular and molecular investigations into IR have revealed potential therapeutic targets for managing and preventing HD.
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Affiliation(s)
- Manisha Yadav
- Division of Toxicology and Experimental Medicine, CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Smriti Verma
- Division of Toxicology and Experimental Medicine, CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Purnima Tiwari
- Division of Toxicology and Experimental Medicine, CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, India
| | - Madhav Nilakanth Mugale
- Division of Toxicology and Experimental Medicine, CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
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Maji T, Mahto M, Kumar S, Anand U, Priyadarshi RN, Arya R, Kumar R. Hepatogenous Diabetes as Compared to Type-2 Diabetes Mellitus and Non-diabetes in Patients With Liver Cirrhosis: Magnitude, Characteristics, and Implications. J Clin Exp Hepatol 2024; 14:101411. [PMID: 38699514 PMCID: PMC11061214 DOI: 10.1016/j.jceh.2024.101411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Accepted: 04/07/2024] [Indexed: 05/05/2024] Open
Abstract
AIM Hepatogenous diabetes (HD) is frequently underestimated among cirrhosis patients. The current study assessed the magnitude, clinical characteristics, and implications of HD in cirrhosis patients as compared to the patients with type-2 diabetes mellitus (T2DM) and non-diabetes (ND) cirrhosis. METHODS In a prospective observational study, 338 consecutive eligible cirrhosis patients were screened for diabetes mellitus. A 2-hour oral glucose tolerance test (OGTT) was used to detect HD. The clinical characteristics, complications, and outcomes were ascertained and compared amongst HD, T2DM, and ND patients. RESULTS In the final study cohort of 316 patients, the proportion of HD, T2DM, and ND was 22.5% (n = 71), 26.3% (n = 83), and 51.3% (n = 162), respectively. HD was the predominant form of diabetes (68.9%) in Child-Pugh class-C cirrhosis. The majority (73%) of HD patients had abnormal OGTT without fasting hyperglycaemia. A lower cut-off of 98.5 mg/dl for fasting blood glucose had a modest sensitivity (72%) and specificity (75%) for predicting HD. In comparison to T2DM patients, HD patients were younger, leaner, and had more advanced cirrhosis. In comparison to ND patients, HD patients were leaner but had higher glycemic indices, serum cholesterol, and arterial ammonia levels. During a median follow-up period of 12 (03-21) months, the frequency of hepatic encephalopathy and variceal haemorrhage were higher in HD and T2DM patients compared to that in the ND group. CONCLUSIONS HD is prevalent in about one fifth of cirrhosis patients. It differs from T2DM and ND in a number of ways, and has association with complications of cirrhosis.
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Affiliation(s)
- Tanmoy Maji
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna, India
| | - Mala Mahto
- Department of Biochemistry, All India Institute of Medical Sciences, Patna, India
| | - Sudhir Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna, India
| | - Utpal Anand
- Department of Surgical Gastroenterology, All India Institute of Medical Sciences, Patna, India
| | | | - Rahul Arya
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna, India
| | - Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna, India
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Pompili E, Baldassarre M, Iannone G, Tedesco G, Nardelli S, Piano S, Alessandria C, Neri S, Foschi FG, Levantesi F, Caraceni P, Bernardi M, Zaccherini G. Long-term albumin improves the outcomes of patients with decompensated cirrhosis and diabetes mellitus: Post hoc analysis of the ANSWER trial. Liver Int 2024; 44:2108-2113. [PMID: 38934515 DOI: 10.1111/liv.16020] [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: 04/04/2024] [Revised: 06/07/2024] [Accepted: 06/16/2024] [Indexed: 06/28/2024]
Abstract
Type-2 diabetes mellitus is a frequent comorbidity of cirrhosis independently associated with cirrhosis-related complications and mortality. This post hoc analysis of the ANSWER trial database assessed the effects of long-term human albumin (HA) administration on top of the standard medical treatment (SMT) on the clinical outcomes of a subgroup of 85 outpatients with liver cirrhosis, uncomplicated ascites and insulin-treated diabetes mellitus type 2 (ITDM). Compared to patients in the SMT arm, the SMT + HA group showed a better overall survival (86% vs. 57%, p = .016) and lower incidence rates of paracenteses, overt hepatic encephalopathy, bacterial infections, renal dysfunction and electrolyte disorders. Hospital admissions did not differ between the two arms, but the number of days spent in hospital was lower in the SMT + HA group. In conclusion, in a subgroup of ITDM outpatients with decompensated cirrhosis and ascites, long-term HA administration was associated with better survival and a lower incidence of cirrhosis-related complications.
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Affiliation(s)
- Enrico Pompili
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Maurizio Baldassarre
- Unit of Semeiotics, Liver and Alcohol-related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Giulia Iannone
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Greta Tedesco
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Silvia Nardelli
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Salvatore Piano
- Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padua, Padua, Italy
| | - Carlo Alessandria
- Division of Gastroenterology and Hepatology, A.O.U. Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
| | - Sergio Neri
- Hepatology, Humanitas Istituto Clinico Catanese, Catania, Italy
| | - Francesco G Foschi
- Internal Medicine, Hospital of Faenza, Azienda Unità Sanitaria Locale of Romagna, Faenza, Italy
| | - Fabio Levantesi
- Internal Medicine, Hospital of Bentivoglio, Azienda Unità Sanitaria Locale of Bologna, Bologna, Italy
| | - Paolo Caraceni
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- Unit of Semeiotics, Liver and Alcohol-related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Mauro Bernardi
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Giacomo Zaccherini
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- Unit of Semeiotics, Liver and Alcohol-related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
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Li X, Hong L, Ru M, Cai R, Meng Y, Wang B, Diao H, Li L, Wu Z. S100A8/A9-activated IFNγ + NK cells trigger β-cell necroptosis in hepatitis B virus-associated liver cirrhosis. Cell Mol Life Sci 2024; 81:345. [PMID: 39133305 PMCID: PMC11335268 DOI: 10.1007/s00018-024-05365-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2024] [Revised: 06/19/2024] [Accepted: 07/15/2024] [Indexed: 08/13/2024]
Abstract
BACKGROUND AND AIMS Hepatitis B virus (HBV)-associated liver cirrhosis (LC), a common condition with high incidence and mortality rates, is often associated with diabetes mellitus (DM). However, the molecular mechanisms underlying impaired glucose regulation during HBV-associated LC remain unclear. METHODS Data from 63 patients with LC and 62 patients with LC-associated DM were analysed. Co-culture of NK cells and islet β cell lines were used to study the glucose regulation mechanism. A mouse model of LC was used to verify the effect of S100A8/A9 on the glucose regulation. RESULTS Higher levels of interferon (IFN)-γ derived from natural killer (NK) cells and lower levels of insulin emerged in the peripheral blood of patients with both LC and DM compared with those from patients with LC only. IFN-γ derived from NK cells facilitated β cell necroptosis and impaired insulin production. Furthermore, S100A8/A9 elevation in patients with both LC and DM was found to upregulate IFN-γ production in NK cells. Consistently, in the mouse model for LC, mice treated with carbon tetrachloride (CCL4) and S100A8/A9 exhibited increased blood glucose, impaired insulin production, increased IFN-γ, and increased β cells necroptosis compared with those treated with CCL4. Mechanistically, S100A8/A9 activated the p38 MAPK pathway to increase IFN-γ production in NK cells. These effects were diminished after blocking RAGE. CONCLUSION Together, the data indicate that IFN-γ produced by NK cells induces β cell necroptosis via the S100A8/A9-RAGE-p38 MAPK axis in patients with LC and DM. Reduced levels of S100A8/A9, NK cells, and IFN-γ could be valuable for the treatment of LC with DM. Accumulation of S100A8/A9 in patients with LC may indicate the emergence of DM.
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Affiliation(s)
- Xuehui Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China
| | - Liang Hong
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China
| | - MingHui Ru
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China
| | - Rui Cai
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China
| | - Yuting Meng
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China
| | - Baohua Wang
- Department of Ultrasound, College of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, 310000, People's Republic of China
| | - Hongyan Diao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
| | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
- Jinan Microecological Biomedicine Shandong Laboratory, Jinan, People's Republic of China.
| | - Zhongwen Wu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
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Lin YL, Yao T, Wang YW, Yu JS, Zhen C, Lin JF, Chen SB. Association between primary biliary cholangitis with diabetes and cardiovascular diseases: A bidirectional multivariable Mendelian randomization study. Clin Res Hepatol Gastroenterol 2024; 48:102419. [PMID: 38992425 DOI: 10.1016/j.clinre.2024.102419] [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: 04/29/2024] [Revised: 07/04/2024] [Accepted: 07/09/2024] [Indexed: 07/13/2024]
Abstract
BACKGROUND AND AIMS Primary biliary cholangitis (PBC) is an autoimmune disease often accompanied by multisystem damage. This study aimed to explore the causal association between genetically predicted PBC and diabetes, as well as multiple cardiovascular diseases (CVDs). METHODS Genome-wide association studies (GWAS) summary data of PBC in 24,510 individuals of European ancestry from the European Association for the Study of the Liver was used to identify genetically predicted PBC. We conducted 2-sample single-variable Mendelian randomization (SVMR) and multivariable Mendelian randomization (MVMR) to estimate the impacts of PBC on diabetes (N = 17,685 to 318,014) and 20 CVDs from the genetic consortium (N = 171,875 to 1,030,836). RESULTS SVMR provided evidence that genetically predicted PBC is associated with an increased risk of type 1 diabetes (T1D), type 2 diabetes (T2D), myocardial infarction (MI), heart failure (HF), hypertension, atrial fibrillation (AF), stroke, ischemic stroke, and small-vessel ischemic stroke. Additionally, there was no evidence of a causal association between PBC and coronary atherosclerosis. In the MVMR analysis, PBC maintained independent effects on T1D, HF, MI, and small-vessel ischemic stroke in most models. CONCLUSION Our findings revealed the causal effects of PBC on diabetes and 7 CVDs, and no causal relationship was detected between PBC and coronary atherosclerosis.
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Affiliation(s)
- Yun-Lu Lin
- The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, PR China
| | - Tao Yao
- The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, PR China
| | - Ying-Wei Wang
- The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, PR China
| | - Jia-Sheng Yu
- The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, PR China
| | - Cheng Zhen
- The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, PR China
| | - Jia-Feng Lin
- The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, PR China
| | - Shui-Bing Chen
- The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, PR China.
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10
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Jensen ASH, Ytting H, Werge MP, Rashu EB, Hetland LE, Thing M, Nabilou P, Burisch J, Bojsen-Møller KN, Junker AE, Hobolth L, Mortensen C, Tofteng F, Bendtsen F, Møller S, Vyberg M, Serizawa RR, Gluud LL, Wewer Albrechtsen NJ. Patients with autoimmune liver disease have glucose disturbances that mechanistically differ from steatotic liver disease. Am J Physiol Gastrointest Liver Physiol 2024; 326:G736-G746. [PMID: 38625142 DOI: 10.1152/ajpgi.00047.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Revised: 03/25/2024] [Accepted: 04/09/2024] [Indexed: 04/17/2024]
Abstract
Autoimmune liver diseases are associated with an increased risk of diabetes, yet the underlying mechanisms remain unknown. In this cross-sectional study, we investigated the glucose-regulatory disturbances in patients with autoimmune hepatitis (AIH, n = 19), primary biliary cholangitis (PBC, n = 15), and primary sclerosing cholangitis (PSC, n = 6). Healthy individuals (n = 24) and patients with metabolic dysfunction-associated steatotic liver disease (MASLD, n = 18) were included as controls. Blood samples were collected during a 120-min oral glucose tolerance test. We measured the concentrations of glucose, C-peptide, insulin, glucagon, and the two incretin hormones, glucose insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1). We calculated the homeostasis model assessment of insulin resistance (HOMA-IR), whole body insulin resistance (Matsuda index), insulin clearance, and insulinogenic index. All patient groups had increased fasting plasma glucose and impaired glucose responses compared with healthy controls. Beta-cell secretion was increased in AIH, PBC, and MASLD but not in PSC. Patients with AIH and MASLD had hyperglucagonemia and hepatic, as well as peripheral, insulin resistance and decreased insulin clearance, resulting in hyperinsulinemia. Patients with autoimmune liver disease had an increased GIP response, and those with AIH or PBC had an increased GLP-1 response. Our data demonstrate that the mechanism underlying glucose disturbances in patients with autoimmune liver disease differs from that underlying MASLD, including compensatory incretin responses in patients with autoimmune liver disease. Our results suggest that glucose disturbances are present at an early stage of the disease.NEW & NOTEWORTHY Patients with autoimmune liver disease but without overt diabetes display glucose disturbances early on in their disease course. We identified pathophysiological traits specific to these patients including altered incretin responses.
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Affiliation(s)
- Anne-Sofie H Jensen
- Gastro Unit, Copenhagen University Hospital-Amager and Hvidovre Hospital, Hvidovre, Denmark
- Department of Clinical Biochemistry, Copenhagen University Hospital-Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Henriette Ytting
- Gastro Unit, Copenhagen University Hospital-Amager and Hvidovre Hospital, Hvidovre, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Mikkel P Werge
- Gastro Unit, Copenhagen University Hospital-Amager and Hvidovre Hospital, Hvidovre, Denmark
| | - Elias B Rashu
- Gastro Unit, Copenhagen University Hospital-Amager and Hvidovre Hospital, Hvidovre, Denmark
| | - Liv E Hetland
- Gastro Unit, Copenhagen University Hospital-Amager and Hvidovre Hospital, Hvidovre, Denmark
| | - Mira Thing
- Gastro Unit, Copenhagen University Hospital-Amager and Hvidovre Hospital, Hvidovre, Denmark
| | - Puria Nabilou
- Gastro Unit, Copenhagen University Hospital-Amager and Hvidovre Hospital, Hvidovre, Denmark
| | - Johan Burisch
- Gastro Unit, Copenhagen University Hospital-Amager and Hvidovre Hospital, Hvidovre, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Kirstine N Bojsen-Møller
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Endocrinology, Copenhagen University Hospital-Amager and Hvidovre Hospital, Hvidovre, Denmark
| | - Anders E Junker
- Gastro Unit, Copenhagen University Hospital-Amager and Hvidovre Hospital, Hvidovre, Denmark
| | - Lise Hobolth
- Gastro Unit, Copenhagen University Hospital-Amager and Hvidovre Hospital, Hvidovre, Denmark
| | - Christian Mortensen
- Gastro Unit, Copenhagen University Hospital-Amager and Hvidovre Hospital, Hvidovre, Denmark
| | - Flemming Tofteng
- Gastro Unit, Copenhagen University Hospital-Amager and Hvidovre Hospital, Hvidovre, Denmark
| | - Flemming Bendtsen
- Gastro Unit, Copenhagen University Hospital-Amager and Hvidovre Hospital, Hvidovre, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Søren Møller
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Physiology and Nuclear Medicine, Center for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital-Amager and Hvidovre Hospital, Hvidovre, Denmark
| | - Mogens Vyberg
- Department of Pathology, Copenhagen University Hospital-Amager and Hvidovre Hospital, Hvidovre, Denmark
- Department of Clinical Medicine, Center for RNA Medicine, Aalborg University, Copenhagen, Denmark
| | - Reza R Serizawa
- Department of Pathology, Copenhagen University Hospital-Amager and Hvidovre Hospital, Hvidovre, Denmark
| | - Lise L Gluud
- Gastro Unit, Copenhagen University Hospital-Amager and Hvidovre Hospital, Hvidovre, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Nicolai J Wewer Albrechtsen
- Department of Clinical Biochemistry, Copenhagen University Hospital-Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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11
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Peppas S, Doumas S, Suvarnakar A, Chou J, Arafat A, Ahmad AI, Lewis JH. Clinical outcomes with metformin use in diabetic patients with compensated cirrhosis: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2024; 36:674-682. [PMID: 38477839 DOI: 10.1097/meg.0000000000002754] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/14/2024]
Abstract
BACKGROUND Previous studies have demonstrated a beneficial effect of metformin in patients with cirrhosis, but no improvement in liver histology. AIM To investigate the impact of metformin on mortality and hepatic decompensation in people with diabetes with compensated cirrhosis. METHODS Medline, Embase and Cochrane databases were searched from inception to February 2023 for studies reporting results regarding the impact of metformin on all-cause mortality and hepatic decompensation in people with diabetes with compensated cirrhosis. The risk of bias was assessed by ROBINS-I Cochrane tool. R software 4.3.1 was used for all analyses. RESULTS Six observational studies were included in the final analysis. Metformin use was associated with reduced all-cause mortality or liver transplantation [hazard ratio (HR): 0.55; 95% confidence interval (CI) 0.37-0.82], while no benefit was shown in the prevention of hepatic decompensation (HR: 0.97; 95% CI: 0.77-1.22). In the subgroup analysis, metformin use was associated with reduced all-cause mortality or liver transplantation (HR: 0.50; 95% CI 0.38-0.65) in patients with metabolic-associated steatohepatitis cirrhosis, while two studies reported no survival benefit in patients with cirrhosis due to hepatitis C (HR: 0.39; 95% CI 0.12-1.20). CONCLUSION Metformin use is associated with reduced all-cause mortality, but not with the prevention of hepatic decompensation in people with diabetes with compensated cirrhosis. The mortality benefit is most likely driven by better diabetes and cardiovascular health control.
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Affiliation(s)
- Spyros Peppas
- Department of Medicine, MedStar Washington Hospital Center
| | - Stavros Doumas
- Department of Internal Medicine, MedStar Georgetown University Medical Center
| | | | - Jiling Chou
- MedStar Research Health Institute, Hyattsville, Maryland
| | - Ayah Arafat
- MedStar Research Health Institute, Hyattsville, Maryland
| | - Akram I Ahmad
- Divsion of Gastroenterology & Hepatology, Cleveland Clinic Florida, Weston, Florida
| | - James H Lewis
- Division of Gastroenterology & Hepatology, MedStar Georgetown University Medical Center, Washington, DC, USA
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12
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Yu Y, Tong K, Hu G, Yang X, Wu J, Bai S, Yu R. Love-hate relationship between hepatitis B virus and type 2 diabetes: a Mendelian randomization study. Front Microbiol 2024; 15:1378311. [PMID: 38646627 PMCID: PMC11026703 DOI: 10.3389/fmicb.2024.1378311] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Accepted: 03/15/2024] [Indexed: 04/23/2024] Open
Abstract
Objective The impact of hepatitis B virus (HBV) on the risk of type 2 diabetes (T2D) remains a controversial topic. This study aims to analyze the causal relationship between HBV and T2D using Mendelian randomization (MR). Methods Single nucleotide polymorphisms on chronic hepatitis B (CHB), liver fibrosis, liver cirrhosis, and T2D were obtained from BioBank Japan Project, European Bioinformatics Institute, and FinnGen. Mendelian randomization was utilized to evaluate exposure-outcome causality. Inverse variance weighted was used as the primary method for MR analysis. To assess horizontal pleiotropy and heterogeneity, we conducted MR-Egger intercept analysis and Cochran's Q test, and the robustness of the MR analysis results was evaluated through leave-one-out sensitivity analysis. Results MR analysis revealed that CHB was associated with a decreased genetic susceptibility to T2D (OR, 0.975; 95% CI, 0.962-0.989; p < 0.001) while liver cirrhosis (OR, 1.021; 95% CI, 1.007-1.036; p = 0.004) as well as liver cirrhosis and liver fibrosis (OR, 1.015; 95% CI, 1.002-1.028; p = 0.020) were associated with an increased genetic susceptibility to T2D. MR-Egger intercept showed no horizontal pleiotropy (p > 0.05). Cochran's Q showed no heterogeneity (p > 0.05). Leave-one-out sensitivity analysis showed that the results were robust. Conclusion CHB has the potential to act as a protective factor for T2D, but its effectiveness is constrained by viral load and disease stage. This protective effect diminishes or disappears as viral load decreases, and it transforms into a risk factor with the progression to liver fibrosis and cirrhosis.
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Affiliation(s)
- Yunfeng Yu
- The First Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Keke Tong
- The Hospital of Hunan University of Traditional Chinese Medicine, Changde, China
| | - Gang Hu
- The First Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Xinyu Yang
- College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
| | - Jingyi Wu
- The Third School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Siyang Bai
- College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
| | - Rong Yu
- The First Hospital of Hunan University of Chinese Medicine, Changsha, China
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13
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Cagnin S, Martini A, Donato D, Angeli P, Pontisso P. Electronic sanitary database: a new potential tool to identify occult chronic liver disease in general population. Intern Emerg Med 2024; 19:641-647. [PMID: 38227274 DOI: 10.1007/s11739-023-03507-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Accepted: 12/06/2023] [Indexed: 01/17/2024]
Abstract
Chronic liver disease (CLD) is a leading global cause of mortality, morbidity, and healthcare resource utilization. However, the burden of CLD is underestimated because the course of the disease is often asymptomatic until clinical decompensation and the development of life-threatening complications. In this study, we assessed the use of available blood tests from electronic medical records for identifying individuals with undiagnosed CLD in the general population. We analyzed a total of 202,529 blood tests obtained from 99,848 adults recorded in the Electronic Health Records of the Padova Teaching Hospital. Transaminases levels > 1.5 times the normal value indicated occult CLD, while platelet counts < 120,000/μL identified occult cirrhosis. We characterized patients using Italian Medical Exemptions (IME), excluding oncologic cases. Overt and occult cirrhosis prevalence was 1% and 4.18%, respectively, while overt and occult CLD affected 2.85% and 4.61% of the population. The epidemiology of patients with overt and occult cirrhosis was similar but significantly different from that of the controls. Among subjects aged 60-70 years, working disability was twofold higher in those with occult cirrhosis compared to those with overt cirrhosis. Occult CLD and cirrhosis had higher prevalence rates than diagnosed cases in the general population. Electronic medical record data may serve as a valuable tool for CLD identification, potentially reducing cirrhosis development and clinical decompensation. This, in turn, may lead to a decrease in the economic impact on the healthcare system.
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Affiliation(s)
- Silvia Cagnin
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine (DIMED), Padova Teaching Hospital, Padua, Italy
| | - Andrea Martini
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine (DIMED), Padova Teaching Hospital, Padua, Italy
| | - Daniele Donato
- Medical Head Office, Padova Teaching Hospital, Padua, Italy
| | - Paolo Angeli
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine (DIMED), Padova Teaching Hospital, Padua, Italy
| | - Patrizia Pontisso
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine (DIMED), Padova Teaching Hospital, Padua, Italy.
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14
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Liu Y, Hu H, Li C, Zhang Y, Li M, Lu T, Wu Y, Yang Y, Li Y, Yang F, Shi X, Lin S. Impacts of the development of acute-on-chronic liver failure and bacterial infections on β-cell function and glucose homeostasis in patients with liver cirrhosis. Dig Liver Dis 2024; 56:648-655. [PMID: 37758609 DOI: 10.1016/j.dld.2023.09.009] [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: 04/13/2023] [Revised: 09/04/2023] [Accepted: 09/06/2023] [Indexed: 09/29/2023]
Abstract
BACKGROUND The pathogenesis involved in glucose metabolism disorders (GMDs) in patients with liver cirrhosis remains unclear. AIMS We investigated the effects of acute-on-chronic liver failure (ACLF) development and bacterial infections (BIs) on pancreatic β-cell function and glucose homeostasis in individuals with liver cirrhosis. METHODS A retrospective analysis was conducted on 327 patients experiencing acute deterioration of liver cirrhosis. Oral glucose tolerance tests (OGTTs) and OGTT-based β-cell function indices were employed to assess β-cell function and glucose homeostasis. Univariate and multivariate logistic regression analyses were employed to identify GMD-associated risk factors. RESULTS Both the development of ACLF and BIs significantly increased the prevalence of GMDs. Both ACLF and BIs markedly elevated the homeostasis model of assessment 2-insulin resistance (HOMA2-IR). ACLF significantly impaired glucose-stimulated insulin secretion, as evidenced by reduced insulinogenic index (IGI). Patients with GMDs exhibited significantly lower IGI levels than those without GMDs. Independent risk factors associated with GMDs were prothrombin activity (odds ratio [OR]=0.981, 95% confidence interval [CI]: 0.960-0.995), HOMA2-IR (OR=1.749, 95% CI: 1.130-2.707), and IGI (OR=0.963, 95% CI: 0.947-0.978). CONCLUSIONS In liver cirrhosis, the onset of ACLF impairs glucose-stimulated insulin secretion from β-cells. Both liver impairment and BIs contribute to increased insulin resistance, ultimately disturbing glucose homeostasis.
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Affiliation(s)
- Yujuan Liu
- Suzhou Medical College of Soochow University, Suzhou 215325, China; Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Guizhou, 563003, China
| | - Han Hu
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Guizhou, 563003, China
| | - Chuan Li
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Guizhou, 563003, China
| | - Yin Zhang
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Guizhou, 563003, China
| | - Meichuan Li
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Guizhou, 563003, China
| | - Tao Lu
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Guizhou, 563003, China
| | - Yunchong Wu
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Guizhou, 563003, China
| | - Yanyan Yang
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Guizhou, 563003, China
| | - Ying Li
- Department of Infectious Diseases, Second Affiliated Hospital of Zunyi Medical University, Guizhou, 563000, China
| | - Fangwan Yang
- Department of Infectious Diseases, Second Affiliated Hospital of Zunyi Medical University, Guizhou, 563000, China
| | - Xiuquan Shi
- Department of Epidemiology and Health Statistics, School of Public Health, Zunyi Medical University, Guizhou, 563006, China
| | - Shide Lin
- Suzhou Medical College of Soochow University, Suzhou 215325, China; Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Guizhou, 563003, China; College of Laboratory Medicine, Zunyi Medical University, Guizhou, 563003, China.
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15
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Quiroz-Aldave JE, Gamarra-Osorio ER, Durand-Vásquez MDC, Rafael-Robles LDP, Gonzáles-Yovera JG, Quispe-Flores MA, Concepción-Urteaga LA, Román-González A, Paz-Ibarra J, Concepción-Zavaleta MJ. From liver to hormones: The endocrine consequences of cirrhosis. World J Gastroenterol 2024; 30:1073-1095. [PMID: 38577191 PMCID: PMC10989500 DOI: 10.3748/wjg.v30.i9.1073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2023] [Revised: 01/02/2024] [Accepted: 02/06/2024] [Indexed: 03/06/2024] Open
Abstract
Hepatocrinology explores the intricate relationship between liver function and the endocrine system. Chronic liver diseases such as liver cirrhosis can cause endocrine disorders due to toxin accumulation and protein synthesis disruption. Despite its importance, assessing endocrine issues in cirrhotic patients is frequently neglected. This article provides a comprehensive review of the epidemiology, pathophysiology, diagnosis, and treatment of endocrine disturbances in liver cirrhosis. The review was conducted using the PubMed/Medline, EMBASE, and Scielo databases, encompassing 172 articles. Liver cirrhosis is associated with endocrine disturbances, including diabetes, hypoglycemia, sarcopenia, thyroid dysfunction, hypogonadotropic hypogonadism, bone disease, adrenal insufficiency, growth hormone dysfunction, and secondary hyperaldosteronism. The optimal tools for diagnosing diabetes and detecting hypoglycemia are the oral glucose tolerance test and continuous glucose monitoring system, respectively. Sarcopenia can be assessed through imaging and functional tests, while other endocrine disorders are evaluated using hormonal assays and imaging studies. Treatment options include metformin, glucagon-like peptide-1 analogs, sodium-glucose co-transporter-2 inhibitors, and insulin, which are effective and safe for diabetes control. Established standards are followed for managing hypoglycemia, and hormone replacement therapy is often necessary for other endocrine dysfunctions. Liver transplantation can address some of these problems.
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Affiliation(s)
| | | | | | | | | | | | | | - Alejandro Román-González
- Department of Endocrinology, Hospital Universitario de San Vicente Fundación, Medellin 050010, Colombia
- Internal Medicine, Universidad de Antioquia, Medellín 050010, Colombia
| | - José Paz-Ibarra
- School of Medicine, Universidad Nacional Mayor de San Marcos, Lima 15081, Peru
- Department of Endocrinology, Hospital Nacional Edgardo Rebagliati Martins, Lima 15072, Peru
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Ding Z, Ge M, Tan Y, Chen C, Hei Z. The triglyceride-glucose index: a novel predictor of stroke and all-cause mortality in liver transplantation recipients. Cardiovasc Diabetol 2024; 23:27. [PMID: 38218842 PMCID: PMC10787491 DOI: 10.1186/s12933-023-02113-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Accepted: 12/29/2023] [Indexed: 01/15/2024] Open
Abstract
BACKGROUND The triglyceride-glucose (TyG) index, identified as a reliable indicator of insulin resistance (IR), was reported to be associated with stroke recurrence and morbidity in the general population and critically ill patients. However, the relationship in liver transplantation (LT) recipients remains unknown. This study aimed to investigate the correlation between the TyG index and post-LT stroke along with all-cause mortality and further assess the influence of IR on the LT recipients' prognosis. METHODS The retrospective cohort study enrolled 959 patients who underwent LT at a university-based medical centre between January 2015 and January 2021. The participants were divided into three groups according to their TyG index tertiles. The primary outcome was post-LT stroke. Multivariate logistic regression, COX proportional hazards regression, and restricted cubic spline RCS were used to examine the association between the TyG index and outcomes in LT recipients. RESULTS With a median TyG index of 8.23 (7.78-8.72), 780 (87.18% males) patients were eventually included. The incidence of post-LT stroke was 5.38%, and the in-hospital, 1-year, and 3-year mortality rates were 5.54%, 13.21%, and 15.77%, respectively. Multivariate regression analysis showed an independent association between the TyG index and an increased risk of post-LT stroke [adjusted odds ratio (aOR), 3.398 (95% confidence interval [CI]: 1.371-8.426) P = 0. 008], in-hospital mortality [adjusted hazard ratio (aHR), 2.326 (95% CI: 1.089-4.931) P = 0.025], 1-year mortality [aHR, 1.668 (95% CI: 1.024-2.717) P = 0.039], and 3-year mortality [aHR, 1.837 (95% CI: 1.445-2.950) P = 0.012]. Additional RCS analysis also suggested a linear increase in the risk of postoperative stroke with elevated TyG index (P for nonlinearity = 0.480). CONCLUSIONS The TyG index may be a valuable and reliable indicator for assessing stroke risk and all-cause mortality in patients undergoing LT, suggesting its potential relevance in improving risk stratification during the peri-LT period.
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Affiliation(s)
- Zhendong Ding
- Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, 510630, China
| | - Mian Ge
- Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, 510630, China
| | - Yuexiang Tan
- SageRAN Technology, No. 9-11 Keyun Road, Guangzhou, 510000, China
| | - Chaojin Chen
- Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, 510630, China.
- Center of Big Data and Artificial Intelligence, The Third Affiliated Hospital of Sun Yat-sen University, No.600 Tianhe Road, Guangzhou, 510630, China.
| | - Ziqing Hei
- Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, 510630, China.
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17
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Pashayee-Khamene F, Hatami B, Cheraghpour M, Yari Z. Keeping an eye on the nutrition: The importance of nutrition management on cardiometabolic risk factors in cirrhotic patients. Clin Nutr ESPEN 2023; 58:186-192. [PMID: 38057004 DOI: 10.1016/j.clnesp.2023.09.927] [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: 05/24/2023] [Revised: 08/26/2023] [Accepted: 09/26/2023] [Indexed: 11/07/2023]
Abstract
Chronic liver diseases, especially cirrhosis, are associated with significant morbidity and mortality. Besides predisposing to chronic liver disease per se, diabetes, hypertension, and dyslipidemia worsen the prognosis of patients with cirrhosis induced by other causes. There is no standard of care in the management of these factors in patients with cirrhosis. Also, in particular, it is not known whether nutritional interventions in the modification of cardiometabolic factors can improve the course of cirrhosis or not. This narrative review aimed to investigate the clinical significance of diabetes, hypertension, and dyslipidemia and appropriate nutritional interventions in cirrhotic patients. A comprehensive literature search of the published data was performed in regard to the association of cirrhosis with cardiometabolic factors and the management of cirrhosis and its complications. There is limited evidence on the association of cirrhosis with cardiometabolic risk factors. Cirrhotic cardiometabolic abnormalities are associated with an increased risk of complications, such that the coexistence of diabetes, hypertension, and dyslipidemia increases the risk of clinical decompensation in cirrhosis. Dietary management of cirrhotic patients with risk factors such as diabetes, hypertension, or dyslipidemia does not seem to be considerably different from non-cirrhotic patients.
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Affiliation(s)
- Fereshteh Pashayee-Khamene
- Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Behzad Hatami
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Makan Cheraghpour
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Zahra Yari
- Department of Nutrition Research, National Nutrition and Food Technology Research Institute and Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Jensen ASH, Winther-Sørensen M, Burisch J, Bergquist A, Ytting H, Gluud LL, Wewer Albrechtsen NJ. Autoimmune liver diseases and diabetes: A propensity score matched analysis and a proportional meta-analysis. Liver Int 2023; 43:2479-2491. [PMID: 37752719 DOI: 10.1111/liv.15720] [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: 06/08/2023] [Revised: 08/20/2023] [Accepted: 08/24/2023] [Indexed: 09/28/2023]
Abstract
BACKGROUND AND AIMS Patients with some chronic liver diseases have increased risk of diabetes. Whether this is also the case for patients with autoimmune liver diseases is unknown. The study aimed to calculate risk and worldwide prevalence of diabetes in patients with autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). METHODS We performed a case-control study using data from the United Kingdom Biobank (UKB) and compared frequency of type 1 diabetes (T1D) and type 2 diabetes (T2D) in AIH and PBC with age-, sex-, BMI- and ethnicity-matched controls. Next, we performed a systematic review and proportional meta-analysis searching PubMed, Embase, Cochrane Library and Web of Science (inception to 1 May 2022 [AIH]; 20 August 2022 [PBC]; 11 November 2022 [PSC]). The pooled prevalence of diabetes was calculated using an inverse method random effects model. RESULTS Three hundred twenty-eight AIH patients and 345 PBC patients were identified in UKB and risk of T1D and T2D significantly increased compared with matched controls. Our systematic search identified 6914 records including the UKB study. Of these, 77 studies were eligible for inclusion comprising 36 467, 39 924 and 4877 individuals with AIH, PBC and PSC, respectively. The pooled prevalence of T1D was 3.8% (2.6%-5.7%), 1.7% (0.9%-3.1%), 3.1% (1.9%-4.8%) and of T2D 14.8% (11.1%-19.5%), 18.1% (14.6%-22.2%), 6.3% (2.8%-13.3%) in patients with AIH, PBC and PSC, respectively. CONCLUSIONS Patients with autoimmune liver diseases have increased risk of diabetes. Increased awareness of diabetes risk in patients with autoimmune liver diseases is warranted.
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Affiliation(s)
- Anne-Sofie H Jensen
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Gastro Unit, Copenhagen University Hospital - Amager and Hvidovre Hospital, Hvidovre, Denmark
- Department of Clinical Biochemistry, Copenhagen University Hospital - Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark
| | - Marie Winther-Sørensen
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Biochemistry, Copenhagen University Hospital - Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark
| | - Johan Burisch
- Gastro Unit, Copenhagen University Hospital - Amager and Hvidovre Hospital, Hvidovre, Denmark
| | - Annika Bergquist
- Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
- Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Henriette Ytting
- Gastro Unit, Copenhagen University Hospital - Amager and Hvidovre Hospital, Hvidovre, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, Copenhagen University, Copenhagen, Denmark
| | - Lise L Gluud
- Gastro Unit, Copenhagen University Hospital - Amager and Hvidovre Hospital, Hvidovre, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, Copenhagen University, Copenhagen, Denmark
| | - Nicolai J Wewer Albrechtsen
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Biochemistry, Copenhagen University Hospital - Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark
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Paternostro R, Jachs M, Hartl L, Simbrunner B, Scheiner B, Bauer D, Schwabl P, Semmler G, Trauner M, Mandorfer M, Reiberger T. Diabetes impairs the haemodynamic response to non-selective betablockers in compensated cirrhosis and predisposes to hepatic decompensation. Aliment Pharmacol Ther 2023; 58:805-813. [PMID: 37519146 DOI: 10.1111/apt.17653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Revised: 05/27/2023] [Accepted: 07/11/2023] [Indexed: 08/01/2023]
Abstract
BACKGROUND Non-selective betablockers (NSBBs) reduce the risk of hepatic decompensation in patients with compensated advanced chronic liver disease (cACLD). Metabolic co-morbidities (MetC) are increasingly observed in cACLD patients. AIMS To investigate the impact of MetC on the haemodynamic effects of NSBB and hepatic decompensation in cACLD. METHODS cACLD patients undergoing paired hepatic venous pressure gradient (HVPG) measurements before/under NSBB therapy were retrospectively considered for this study. We recorded baseline characteristics on MetC (obesity, dyslipidaemia and diabetes), as well as hepatic decompensation and liver-related mortality during follow-up. RESULTS We included 92 patients (Child-A n = 80, 87%; Child-B n = 12, 13%). MetC were found in 34 (37%) patients: 19 (20.7%) with obesity, 14 (15.2%) with dyslipidaemia and 23 (34.8%) with diabetes. The median baseline HVPG of 18 (IQR:15-21) mmHg decreased to 15 (IQR:9-12) mmHg under NSBB. HVPG-response (decrease ≥10% or to ≤12 mmHg) was achieved in 60 (65.2.%) patients. Patients with diabetes (OR: 0.35, p = 0.021) and higher BMI (OR: 0.89 per kg/m2 , p = 0.031) were less likely to achieve HVPG-response. During a median follow-up of 2.3 (0.5-4.2) years, 18 (19.5%) patients experienced hepatic decompensation. Child-B (adjusted subdistribution hazard ratio, aSHR: 4.3 [95% CI:1.5-12.2], p = 0.006), HVPG-response (aSHR: 0.3 [95% CI:0.1-0.9], p = 0.037) and diabetes (aSHR: 2.8 [95% CI:1.1-7.2], p = 0.036) were independently associated with hepatic decompensation. CONCLUSIONS In patients with cACLD, diabetes and a higher BMI impair the HVPG-response to NSBB. Furthermore, diabetes-independently from Child B and lack of HVPG-response-increases the risk of hepatic decompensation.
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Affiliation(s)
- Rafael Paternostro
- Divison of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Laboratory, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Mathias Jachs
- Divison of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Laboratory, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Lukas Hartl
- Divison of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Laboratory, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Benedikt Simbrunner
- Divison of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Laboratory, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
| | - Bernhard Scheiner
- Divison of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Laboratory, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - David Bauer
- Divison of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Laboratory, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Philipp Schwabl
- Divison of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Laboratory, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
| | - Georg Semmler
- Divison of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Laboratory, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Michael Trauner
- Divison of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Mattias Mandorfer
- Divison of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Laboratory, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Thomas Reiberger
- Divison of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna Hepatic Hemodynamic Laboratory, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
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Jensen ASH, Ytting H, Winther-Sørensen M, Burisch J, Bergquist A, Gluud LL, Wewer Albrechtsen NJ. Autoimmune liver diseases and diabetes. Eur J Gastroenterol Hepatol 2023; 35:938-947. [PMID: 37505973 DOI: 10.1097/meg.0000000000002594] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/30/2023]
Abstract
Autoimmune liver diseases include autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis. They are chronic, heterogenous diseases affecting the liver which is a key metabolic organ that ensures glucose homeostasis. It is well known that patients with other chronic liver diseases such as cirrhosis and nonalcoholic fatty liver disease (NAFLD) display glucose disturbances like insulin resistance and have an increased risk of diabetes. Previous evidence on glucose disturbances in patients with autoimmune liver disease is scarce but does point towards a potentially increased risk of type 1 diabetes and type 2 diabetes. The underlying mechanisms are unknown but may reflect genetic predisposition, concurrent NAFLD and or cirrhosis development, and treatment (steroid) related impairment of glucose homeostasis. Therefore, increased awareness and surveillance of diabetes development in patients with autoimmune liver disease may be important. Overall, detection and treatment of diabetes generally follow the usual diabetes guidelines; however, in patients with advanced liver cirrhosis, HbA1c may not be a reliable marker of average glucose levels, and treatment with insulin is generally recommended. In addition, it has recently been suggested that sodium-glucose cotransporter 2 inhibitors may be beneficial in treating refractory ascites. Further research on diabetes risk in autoimmune liver disease is warranted.
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Affiliation(s)
- Anne-Sofie H Jensen
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen
- Gastro Unit, Copenhagen University Hospital - Amager and Hvidovre Hospital, Hvidovre
| | - Henriette Ytting
- Gastro Unit, Copenhagen University Hospital - Amager and Hvidovre Hospital, Hvidovre
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Rigshospitalet
- Institute for Clinical Medicine, Faculty of Health and Medical Sciences, Copenhagen University, Copenhagen
| | - Marie Winther-Sørensen
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen
| | - Johan Burisch
- Gastro Unit, Copenhagen University Hospital - Amager and Hvidovre Hospital, Hvidovre
| | - Annika Bergquist
- Gastro Unit, Copenhagen University Hospital - Amager and Hvidovre Hospital, Hvidovre
- Department of Upper GI Diseases, Karolinska University Hospital, Department of Medicine, Karolinska Institutet, Stockholm
| | - Lise Lotte Gluud
- Gastro Unit, Copenhagen University Hospital - Amager and Hvidovre Hospital, Hvidovre
- Institute for Clinical Medicine, Faculty of Health and Medical Sciences, Copenhagen University, Copenhagen
| | - Nicolai J Wewer Albrechtsen
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen
- Department of Clinical Biochemistry, Copenhagen University Hospital - Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark
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21
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Zakharova N, Luo C, Aringazina R, Samusenkov V. The efficacy of L-carnitine in patients with nonalcoholic steatohepatitis and concomitant obesity. Lipids Health Dis 2023; 22:101. [PMID: 37438785 DOI: 10.1186/s12944-023-01867-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Accepted: 06/30/2023] [Indexed: 07/14/2023] Open
Abstract
BACKGROUND In light of the high prevalence of nonalcoholic fatty liver disease and obesity, treatment options for nonalcoholic steatohepatitis are of particular interest. The purpose of the study is to assess the efficacy of L-carnitine and its effects on the functional state of the liver, as well as on lipid and carbohydrate metabolism in patients with nonalcoholic steatohepatitis and concomitant obesity. METHODS People in the control group followed a hypocaloric diet and received 1 tablet of simvastatin 20 mg once a day and 2 capsules of essential phospholipids 600 mg three times a day for 90 days. People in the experimental group followed a hypocaloric diet and received 1 tablet of simvastatin 20 mg once a day and L-carnitine 10 mL orally two times a day for 90 days. RESULTS L-carnitine normalized the blood lipid profile of subjects, as demonstrated by a significant decrease in the blood levels of total cholesterol, triglycerides, low-density lipoproteins, atherogenic index, and insulin resistance. The use of L-carnitine in patients with nonalcoholic steatohepatitis and concomitant obesity contributes to the steady reduction of the main clinical and biochemical symptoms of nonalcoholic steatohepatitis. CONCLUSIONS L-carnitine produces positive effects on the blood lipid profile and carbohydrate metabolism.
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Affiliation(s)
- Natalia Zakharova
- Department of Chemistry, I.M. Sechenov First Moscow State Medical University (Sechenov University, Trubetskaya str., 8-2, Moscow, 119991, Russian Federation
| | - Chenguang Luo
- Department of Hospital Therapy named after Academician G.I. Storozhakov of the Medical Faculty, Pirogov Russian National Research Medical University, Ostrovityanova str., 1 , Moscow, 117997, Russian Federation
| | - Raisa Aringazina
- Department of Internal Diseases № 1, Non-Commercial Joint-Stock Society "West Kazakhstan Marat Ospanov Medical University", Aleksey Maresyev str, Aktobe, 030019, Kazakhstan.
| | - Vadim Samusenkov
- Department of Prosthetic Dentistry, I.M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya str., 8-2, Moscow, 119991, Russian Federation
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Castera L, Cusi K. Diabetes and cirrhosis: Current concepts on diagnosis and management. Hepatology 2023; 77:2128-2146. [PMID: 36631005 DOI: 10.1097/hep.0000000000000263] [Citation(s) in RCA: 32] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Accepted: 10/03/2022] [Indexed: 01/13/2023]
Abstract
Type 2 diabetes mellitus is often associated with cirrhosis as comorbidities, acute illness, medications, and other conditions profoundly alter glucose metabolism. Both conditions are closely related in NAFLD, the leading cause of chronic liver disease, and given its rising burden worldwide, management of type 2 diabetes mellitus in cirrhosis will be an increasingly common dilemma. Having diabetes increases cirrhosis-related complications, including HCC as well as overall mortality. In the absence of effective treatments for cirrhosis, patients with type 2 diabetes mellitus should be systematically screened as early as possible for NAFLD-related fibrosis/cirrhosis using noninvasive tools, starting with a FIB-4 index followed by transient elastography, if available. In people with cirrhosis, an early diagnosis of diabetes is critical for an optimal management strategy (ie, nutritional goals, and glycemic targets). Diagnosis of diabetes may be missed if based on A1C in patients with cirrhosis and impaired liver function (Child-Pugh B-C) as anemia may turn the test unreliable. Clinicians must also become aware of their high risk of hypoglycemia, especially in decompensated cirrhosis where insulin is the only therapy. Care should be within multidisciplinary teams (nutritionists, obesity management teams, endocrinologists, hepatologists, and others) and take advantage of novel glucose-monitoring devices. Clinicians should become familiar with the safety and efficacy of diabetes medications for patients with advanced fibrosis and compensated cirrhosis. Management is conditioned by whether the patient has either compensated or decompensated cirrhosis. This review gives an update on the complex relationship between cirrhosis and type 2 diabetes mellitus, with a focus on its diagnosis and treatment, and highlights knowledge gaps and future directions.
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Affiliation(s)
- Laurent Castera
- Departement of Hepatology, Hospital Beaujon, Assistance Publique-Hôpitaux de Paris, INSERM UMR 1149, Université Paris Cité, Clichy, France
| | - Kenneth Cusi
- Division of Endocrinology, Diabetes and Metabolism, The University of Florida, Gainesville, Florida, USA
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Riaz HA, Nishwa DE, Fatima A, Wahid B, Ali A, Kumari B, Idrees M. Risk of adverse outcomes following treatment with direct acting antiviral drugs in HCV infected patients with liver cirrhosis. Heliyon 2023; 9:e16169. [PMID: 37234654 PMCID: PMC10205523 DOI: 10.1016/j.heliyon.2023.e16169] [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: 10/30/2022] [Revised: 04/23/2023] [Accepted: 05/08/2023] [Indexed: 05/28/2023] Open
Abstract
Introduction Hepatitis C virus (HCV) is the second major cause of death in Pakistan. Previously, interferon-based regimens were considered highly recommended therapy for HCV patients. Since 2015, interferon-based therapy has been replaced with interferon-free therapy also known as Direct Acting Antiviral (DAA) drugs. The treatment response of interferon-free regimens has been reported as highly effective treatment option with more than 90% sustained virological response (SVR) in chronic HCV infected patients in western countries of the world. Objective This study aims to analyze the treatment response of DAA drugs in HCV-infected Pakistani population with liver cirrhosis. Methodology We collected the total 94 sample of the HCV infected patients, from June 2020 to September 2020. Forty-six (46) patients were cirrhotic, and forty-eight (48) patients were non-cirrhotic. Data was analyzed using IBM SPSS version 21 software. Conclusion The findings of our study suggest that the response rate was 82.60% in HCV cirrhotic patients and 68.75% in HCV non-cirrhotic patients. Our study showed that overall treatment response was independent of age and gender. We also observed some adverse effects such as hepatocellular carcinoma, portosystemic encephalopathy (PSE), spontaneous bacterial peritonitis (SBP), hepatorenal syndrome (HRS), upper gastrointestinal bleeding (UGIB), ascites, among patients following treatment with interferon-free regimens.
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Affiliation(s)
- Hafiza Arooba Riaz
- Department of Life Sciences, School of Sciences, University of Management and Technology, Lahore, Pakistan
| | - Dur E. Nishwa
- Department of Life Sciences, School of Sciences, University of Management and Technology, Lahore, Pakistan
| | - Ameer Fatima
- Hepatobiliary and Gastroenterology Unit, Sheikh Zayed Hospital, Lahore, Pakistan
| | - Braira Wahid
- Department of Life Sciences, School of Sciences, University of Management and Technology, Lahore, Pakistan
- Department of Microbiology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3168, Australia
| | - Akhtar Ali
- School of Agriculture and Food, Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, VIC, 3010, Australia
| | - Babita Kumari
- Department of Microbiology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3168, Australia
| | - Muhammad Idrees
- Division of Molecular Virology, Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan
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Bai XP, Du WJ, Xing HB, Yang GH, Bai R. Influence of ursodeoxycholic acid on blood glucose, insulin and GLP-1 in rats with liver fibrosis induced by bile duct ligation. Diabetol Metab Syndr 2023; 15:18. [PMID: 36788623 PMCID: PMC9930340 DOI: 10.1186/s13098-023-00989-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Accepted: 02/04/2023] [Indexed: 02/16/2023] Open
Abstract
BACKGROUND The prevalence of impaired glucose tolerance and diabetes is much higher in people with cirrhosis than that in the general population. However, there are inadequate concrete guidelines for the management of diabetes in these patients, particularly in the early stage. Bile aids (BAs) have been found to exert hormone-like functions in the control of lipid and glucose metabolism. We studied the effect of ursodeoxycholic acid (UDCA) on glucose levels in rats with cirrhosis induced by bile duct ligation (BDL). METHODS SD rats were divided into three groups: sham operation (Group A); BDL (Group B), and UDCA plus BDL (Group C). After 4 weeks, oral glucose tolerance tests were performed. Serum biochemical parameters and the levels of glucose, insulin, and glucagon-like peptide 1 (GLP-1) were measured. Histopathology of the liver and islet was observed. The gene expression of cholesterol 7α-hydroylase (CYP7A1), microsomal oxysterol 7a-hydroxylase (CYP7B1) in the liver, and Takeda G-protein-coupled receptor-5 (TGR5) in the intestine was determined by real-time PCR. RESULTS Compared with Group A, fasting glucose and 1-h and 2-h postprandial glucose levels increased slightly (all P > 0.05), 2-h postprandial insulin levels increased significantly (P < 0.05), 15 min postprandial GLP-1 levels decreased (P < 0.05) in Group B. Compared with Group B, fasting glucose and 1-h postprandial glucose levels decreased (all P < 0.05), 2-h postprandial insulin levels decreased (P < 0.01), and 15 min postprandial GLP-1 levels increased (P < 0.05) in Group C. After UDCA intervention, liver fibrosis induced by BDL was alleviated, and the islet areas were increased (P < 0.05). Compared with Group A, the mRNA expression of CYP7A1 and CYP7B1 in the liver increased, and the mRNA expression of TGR5 in the intestine decreased in Group B (all P < 0.05). Compared with Group B, the mRNA expression of CYP7A1 and CYP7B1 in the liver decreased, and TGR5 in the intestine increased in Group C (P < 0.05). CONCLUSIONS After 4 weeks of BDL, the rats developed liver fibrosis and abnormal glucose metabolism. UDCA administration improved liver fibrosis, increased islet area, decreased glucose levels, inhibited genes in BA synthesis, enhanced TGR5 gene expression in the intestine, and further improved islet function.
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Affiliation(s)
- Xiu-Ping Bai
- Endocrinology Division, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, China.
| | - Wen-Jin Du
- Endocrinology Division, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, China
| | - Hua-Bing Xing
- Endocrinology Division, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, China
| | - Guo-Hua Yang
- Central Laboratory, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, China
| | - Rui Bai
- Central Laboratory, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, China
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Gurlo T, Prakash TP, Wang Z, Archang M, Pei L, Rosenberger M, Pirie E, Lee RG, Butler PC. Efficacy of IAPP suppression in mouse and human islets by GLP-1 analogue conjugated antisense oligonucleotide. Front Mol Biosci 2023; 10:1096286. [PMID: 36814640 PMCID: PMC9939749 DOI: 10.3389/fmolb.2023.1096286] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Accepted: 01/20/2023] [Indexed: 02/09/2023] Open
Abstract
Insulin resistance is the major risk factor for Type 2 diabetes (T2D). In vulnerable individuals, insulin resistance induces a progressive loss of insulin secretion with islet pathology revealing a partial deficit of beta cells and islet amyloid derived from islet amyloid polypeptide (IAPP). IAPP is co-expressed and secreted with insulin by beta cells, expression of both proteins being upregulated in response to insulin resistance. If IAPP expression exceeds the threshold for clearance of misfolded proteins, beta cell failure occurs exacerbated by the action of IAPP toxicity to compromise the autophagy lysosomal pathway. We postulated that suppression of IAPP expression by an IAPP antisense oligonucleotide delivered to beta cells by the GLP-1 agonist exenatide (eGLP1-IAPP-ASO) is a potential disease modifying therapy for T2D. While eGLP1-IAPP-ASO suppressed mouse IAPP and transgenic human IAPP expression in mouse islets, it had no discernable effects on IAPP expression in human islets under the conditions studied. Suppression of transgenic human IAPP expression in mouse islets attenuated disruption of the autophagy lysosomal pathway in beta cells, supporting the potential of this strategy.
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Affiliation(s)
- Tatyana Gurlo
- Larry L. Hillblom Islet Research Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States,*Correspondence: Tatyana Gurlo, ; Peter C. Butler,
| | | | - Zhongying Wang
- Larry L. Hillblom Islet Research Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States
| | - Maani Archang
- Larry L. Hillblom Islet Research Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States
| | - Lina Pei
- Larry L. Hillblom Islet Research Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States
| | - Madeline Rosenberger
- Larry L. Hillblom Islet Research Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States
| | - Elaine Pirie
- IONIS Pharmaceuticals, Carlsbad, CA, United States
| | | | - Peter C. Butler
- Larry L. Hillblom Islet Research Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States,*Correspondence: Tatyana Gurlo, ; Peter C. Butler,
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Marques LP, de Aguiar OB, Paula DP, Oliveira FEG, Chor D, Benseñor I, Ribeiro AL, Brunoni AR, A C Machado L, da Fonseca MDJM, Griep RH. Multimorbidity prevalence and patterns at the baseline of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). JOURNAL OF MULTIMORBIDITY AND COMORBIDITY 2023; 13:26335565231173845. [PMID: 37223823 PMCID: PMC10201182 DOI: 10.1177/26335565231173845] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Accepted: 04/17/2023] [Indexed: 05/25/2023]
Abstract
Background To identify multimorbidity patterns, by sex, according to sociodemographic and lifestyle in ELSA-Brasil. Methods Cross-sectional study with 14,516 participants from ELSA-Brasil (2008-2010). Fuzzy c-means was used to identify multimorbidity patterns of 2+ chronic morbidities, where the consequent morbidity had to occur in at least 5% of all cases. Association rule (O/E≥1.5) was used to identify co-occurrence of morbidities, in each cluster, by sociodemographic and lifestyle factors. Results The prevalence of multimorbidity was higher in women (73.7%) compared to men (65.3%). Among women, cluster 1 was characterized by hypertension/diabetes (13.2%); cluster 2 had no overrepresented morbidity; and cluster 3 all participants had kidney disease. Among men, cluster 1 was characterized by cirrhosis/hepatitis/obesity; cluster 2, most combinations included kidney disease/migraine (6.6%); cluster 3, no pattern reached association ratio; cluster 4 predominated co-occurrence of hypertension/rheumatic fever, and hypertension/dyslipidemia; cluster 5 predominated diabetes and obesity, and combinations with hypertension (8.8%); and cluster 6 presented combinations of diabetes/hypertension/heart attack/angina/heart failure. Clusters were characterized by higher prevalence of adults, married and participants with university degrees. Conclusion Hypertension/diabetes/obesity were highly co-occurred, in both sexes. Yet, for men, morbidities like cirrhosis/hepatitis were commonly clustered with obesity and diabetes; and kidney disease was commonly clustered with migraine and common mental disorders. The study advances in understanding multimorbidity patterns, benefiting simultaneously or gradually prevention of diseases and multidisciplinary care responses.
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Affiliation(s)
- Larissa Pruner Marques
- Post-Graduate Program in
Epidemiology, Sergio Arouca National School of Public
Health, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| | - Odaleia Barbosa de Aguiar
- Department of Applied Nutrition,
Institute of Nutrition, Rio de Janeiro State
University, Rio de Janeiro, Brazil
| | - Daniela Polessa Paula
- National School of Statistical
Sciences, Brazilian Institute of Geography and Statistics, Rio de
Janeiro, Brazil
| | | | - Dóra Chor
- Department of Epidemiology and
Quantitative Methods in Health, National School of Public Health, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| | - Isabela Benseñor
- Clinical and Epidemiologic Research
Center, University Hospital, University of São Paulo, São Paulo, Brazil
| | - Antonio Luiz Ribeiro
- Department of Internal Medicine, Federal University of Minas
Gerais, Belo Horizonte, Brazil
| | - Andre R Brunoni
- Interdisciplinary Neuromodulation
Service, Psychiatry Institute, University of São Paulo School of
Medicine Hospital das Clínicas, HC-FMUSP, São Paulo, Brazil
| | - Luciana A C Machado
- Clinical Hospital/Ebserh, Universidade Federal de Minas
Gerais, HC-UFMG, Belo Horizonte, Brazil
| | - Maria de Jesus Mendes da Fonseca
- Department of Epidemiology and
Quantitative Methods in Health, National School of Public Health, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| | - Rosane Härter Griep
- Laboratory of Health and
Environment Education, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
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27
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Nakatsuka T, Tateishi R. Development and prognosis of hepatocellular carcinoma in patients with diabetes. Clin Mol Hepatol 2023; 29:51-64. [PMID: 35903020 PMCID: PMC9845683 DOI: 10.3350/cmh.2022.0095] [Citation(s) in RCA: 39] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 07/03/2022] [Indexed: 02/02/2023] Open
Abstract
The incidence of diabetes mellitus and hepatocellular carcinoma (HCC) has been increasing worldwide during the last few decades, in the context of an increasing prevalence of obesity and non-alcoholic fatty liver disease (NAFLD). Epidemiologic studies have revealed that patients with diabetes have a 2- to 3-fold increased risk of developing HCC, independent of the severity and cause of the underlying liver disease. A bidirectional relationship exists between diabetes and liver disease: advanced liver disease promotes the onset of diabetes, and HCC is an important cause of death in patients with diabetes; conversely, diabetes is a risk factor for liver fibrosis progression and HCC development, and may worsen the long-term prognosis of patients with HCC. The existence of close interconnections among diabetes, obesity, and NAFLD causes insulin resistance-related hyperinsulinemia, increased oxidative stress, and chronic inflammation, which are assumed to be the underlying causes of hepatocarcinogenesis in patients with diabetes. No appropriate surveillance methods for HCC development in patients with diabetes have been established, and liver diseases, including HCC, are often overlooked as complications of diabetes. Although some antidiabetic drugs are expected to prevent HCC development, further research on the optimal use of antidiabetic drugs aimed at hepatoprotection is warranted. Given the increasing medical and socioeconomic impact of diabetes on HCC development, diabetologists and hepatologists need to work together to develop strategies to address this emerging health issue. This article reviews the current knowledge on the impact of diabetes on the development and progression of HCC.
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Affiliation(s)
- Takuma Nakatsuka
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Ryosuke Tateishi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan,Corresponding author : Ryosuke Tateishi Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan Tel: +81-3-3815-5411, Fax: +81-3-3814-0021, E-mail:
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28
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Kumar R, García-Compeán D, Maji T. Hepatogenous diabetes: Knowledge, evidence, and skepticism. World J Hepatol 2022; 14:1291-1306. [PMID: 36158904 PMCID: PMC9376767 DOI: 10.4254/wjh.v14.i7.1291] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 04/27/2022] [Accepted: 07/05/2022] [Indexed: 02/06/2023] Open
Abstract
The diabetogenic potential of liver cirrhosis (LC) has been known for a long time, and the name "hepatogenous diabetes" (HD) was coined in 1906 to define the condition. Diabetes mellitus (DM) that develops as a consequence of LC is referred to as HD. In patients with LC, the prevalence rates of HD have been reported to vary from 21% to 57%. The pathophysiological basis of HD seems to involve insulin resistance (IR) and pancreatic β-cell dysfunction. The neurohormonal changes, endotoxemia, and chronic inflammation of LC initially create IR; however, the toxic effects eventually lead to β-cell dysfunction, which marks the transition from impaired glucose tolerance to HD. In addition, a number of factors, including sarcopenia, sarcopenic obesity, gut dysbiosis, and hyperammonemia, have recently been linked to impaired glucose metabolism in LC. DM is associated with complications and poor outcomes in patients with LC, although the individual impact of each type 2 DM and HD is unknown due to a lack of categorization of diabetes in most published research. In fact, there is much skepticism within scientific organizations over the recognition of HD as a separate disease and a consequence of LC. Currently, T2DM and HD are being treated in a similar manner although no standardized guidelines are available. The different pathophysiological basis of HD may have an impact on treatment options. This review article discusses the existence of HD as a distinct entity with high prevalence rates, a strong pathophysiological basis, clinical and therapeutic implications, as well as widespread skepticism and knowledge gaps.
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Affiliation(s)
- Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, Bihar, India.
| | - Diego García-Compeán
- Department of Gastroenterology, University Hospital, Universidad Autónoma de Nuevo León, México, Monterrey 64700, México
| | - Tanmoy Maji
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, Bihar, India
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Rojas-Acuña D, Polo-Samillan N, Vasquez-Chavesta AZ, Escalante-Arias C, Rios-Perez CJ, Toro-Huamanchumo CJ. Morbimortality Associated with Liver Cirrhosis in Peru: An Ecological Analysis for the Period of 2004-2016. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:9036. [PMID: 35897403 PMCID: PMC9332628 DOI: 10.3390/ijerph19159036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Revised: 07/20/2022] [Accepted: 07/21/2022] [Indexed: 02/04/2023]
Abstract
Liver cirrhosis (LC) is an irreversible, chronic disease and constitutes the last clinical stage of many different liver diseases. The main cause of death is upper gastrointestinal bleeding caused by esophageal variceal rupture. We aim to depict the trend and estimate the morbimortality. For this, we conducted an ecological study and analyzed data from 2004-2016 using the public information provided by the Peruvian Ministry of Health (Ministerio de Salud del Perú, MINSA). Morbidity and mortality were presented according to 5-year groups. Regions were divided according to age quintiles for each studied year, and standardized morbidity and mortality rates were calculated for each natural geographic region; we found that LC-related morbidity per 100,000 people was 52.3 in 2004 and 117.9 in 2016. LC-related mortality had increased from 13.6 deaths per 100,000 people in 2004-2005 to 16.8 deaths per 100,000 people in 2015-2016. Morbidity showed an upward trend in Peru, especially in the departments of Callao, Ica, and Tumbes, whereas mortality showed an upward trend in the departments of Lambayeque, Ica, and Callao.
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Affiliation(s)
- Daniela Rojas-Acuña
- School of Medicine, Universidad Católica Santo Toribio de Mogrovejo, Chiclayo 14012, Peru; (D.R.-A.); (N.P.-S.); (A.Z.V.-C.); (C.E.-A.); (C.J.R.-P.)
- Asociación Científica Médico Estudiantil USAT, Chiclayo 14012, Peru
| | - Nilo Polo-Samillan
- School of Medicine, Universidad Católica Santo Toribio de Mogrovejo, Chiclayo 14012, Peru; (D.R.-A.); (N.P.-S.); (A.Z.V.-C.); (C.E.-A.); (C.J.R.-P.)
- Asociación Científica Médico Estudiantil USAT, Chiclayo 14012, Peru
| | - Angie Z. Vasquez-Chavesta
- School of Medicine, Universidad Católica Santo Toribio de Mogrovejo, Chiclayo 14012, Peru; (D.R.-A.); (N.P.-S.); (A.Z.V.-C.); (C.E.-A.); (C.J.R.-P.)
- Asociación Científica Médico Estudiantil USAT, Chiclayo 14012, Peru
| | - Crist Escalante-Arias
- School of Medicine, Universidad Católica Santo Toribio de Mogrovejo, Chiclayo 14012, Peru; (D.R.-A.); (N.P.-S.); (A.Z.V.-C.); (C.E.-A.); (C.J.R.-P.)
- Asociación Científica Médico Estudiantil USAT, Chiclayo 14012, Peru
| | - Cristhian J. Rios-Perez
- School of Medicine, Universidad Católica Santo Toribio de Mogrovejo, Chiclayo 14012, Peru; (D.R.-A.); (N.P.-S.); (A.Z.V.-C.); (C.E.-A.); (C.J.R.-P.)
- Asociación Científica Médico Estudiantil USAT, Chiclayo 14012, Peru
| | - Carlos J. Toro-Huamanchumo
- Unidad para la Generación y Síntesis de Evidencias en Salud, Universidad San Ignacio de Loyola, Lima 15024, Peru
- Clínica Avendaño, Unidad de Investigación Multidisciplinaria, Lima 15074, Peru
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Cusi K, Isaacs S, Barb D, Basu R, Caprio S, Garvey WT, Kashyap S, Mechanick JI, Mouzaki M, Nadolsky K, Rinella ME, Vos MB, Younossi Z. American Association of Clinical Endocrinology Clinical Practice Guideline for the Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Primary Care and Endocrinology Clinical Settings: Co-Sponsored by the American Association for the Study of Liver Diseases (AASLD). Endocr Pract 2022; 28:528-562. [PMID: 35569886 DOI: 10.1016/j.eprac.2022.03.010] [Citation(s) in RCA: 543] [Impact Index Per Article: 181.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 03/11/2022] [Accepted: 03/11/2022] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To provide evidence-based recommendations regarding the diagnosis and management of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) to endocrinologists, primary care clinicians, health care professionals, and other stakeholders. METHODS The American Association of Clinical Endocrinology conducted literature searches for relevant articles published from January 1, 2010, to November 15, 2021. A task force of medical experts developed evidence-based guideline recommendations based on a review of clinical evidence, expertise, and informal consensus, according to established American Association of Clinical Endocrinology protocol for guideline development. RECOMMENDATION SUMMARY This guideline includes 34 evidence-based clinical practice recommendations for the diagnosis and management of persons with NAFLD and/or NASH and contains 385 citations that inform the evidence base. CONCLUSION NAFLD is a major public health problem that will only worsen in the future, as it is closely linked to the epidemics of obesity and type 2 diabetes mellitus. Given this link, endocrinologists and primary care physicians are in an ideal position to identify persons at risk on to prevent the development of cirrhosis and comorbidities. While no U.S. Food and Drug Administration-approved medications to treat NAFLD are currently available, management can include lifestyle changes that promote an energy deficit leading to weight loss; consideration of weight loss medications, particularly glucagon-like peptide-1 receptor agonists; and bariatric surgery, for persons who have obesity, as well as some diabetes medications, such as pioglitazone and glucagon-like peptide-1 receptor agonists, for those with type 2 diabetes mellitus and NASH. Management should also promote cardiometabolic health and reduce the increased cardiovascular risk associated with this complex disease.
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Affiliation(s)
- Kenneth Cusi
- Guideine and Algorithm Task Forces Co-Chair, Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida
| | - Scott Isaacs
- Guideline and Algorithm Task Forces Co-Chair, Division of Endocrinology, Emory University School of Medicine, Atlanta, Georgia
| | - Diana Barb
- University of Florida, Gainesville, Florida
| | - Rita Basu
- Division of Endocrinology, University of Virginia School of Medicine, Charlottesville, Virginia
| | - Sonia Caprio
- Yale University School of Medicine, New Haven, Connecticut
| | - W Timothy Garvey
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama
| | | | - Jeffrey I Mechanick
- The Marie-Josee and Henry R. Kravis Center for Cardiovascular Health at Mount Sinai Heart, Icahn School of Medicine at Mount Sinai
| | | | - Karl Nadolsky
- Michigan State University College of Human Medicine, Grand Rapids, Michigan
| | - Mary E Rinella
- AASLD Representative, University of Pritzker School of Medicine, Chicago, Illinois
| | - Miriam B Vos
- Center for Clinical and Translational Research, Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, Georgia
| | - Zobair Younossi
- AASLD Representative, Inova Medicine, Inova Health System, Falls Church, Virginia
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Hsueh KC, Nfor ON, Hsu SY, Yang SF, Liaw YP. Type 2 Diabetes, PNPLA3 rs738409 Polymorphism, and the Risk of Liver Cirrhosis: Analysis of Taiwan Biobank. Front Genet 2022; 13:822700. [PMID: 35330730 PMCID: PMC8940239 DOI: 10.3389/fgene.2022.822700] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Accepted: 02/22/2022] [Indexed: 12/12/2022] Open
Abstract
Type 2 diabetes (T2D) and liver cirrhosis remain significant public health threats in Taiwan. These conditions are reported to be associated with the rs738409 polymorphism of the patatin-like phospholipase domain-containing protein three gene (PNPLA3) in European populations. We assessed the effect of T2D and PNPLA3 rs738409 polymorphism on liver cirrhosis among Taiwan Biobank (TWB) participants. In total, 17,985 participants in TWB had their health records linked to the National Health Insurance Research Database (NHIRD). Participants included those who visited the assessment centers between 2008 and 2015, with an age range between 30 and 70 years of age. We performed logistic regression analysis to investigate the odds ratios (OR) for liver cirrhosis among participants based on the T2D status and rs738409 genotypes. Genotyping was performed using the Axiom Genome-Wide TWB Array Plate. In our analysis, 150 of the 17,619 eligible participants were identified as cirrhosis cases. Based on the univariate analysis, liver cirrhosis was positively associated with T2D (OR, 1.83; 95% CI 1.23–2.70) whereas, the variant rs738409 was not (regardless of the genetic model). The variant and T2D, however, showed significant interactions in the additive, genotype, and dominant models (p values of 0.0302, 0.0395, and 0.0455, respectively). We observed a statistically significant association between T2D and liver cirrhosis and variant rs738409 with an OR of 1.71 (95% CI, 1.03–2.84) for individuals carrying a G allele compared to those with a C allele and 2.92 (95% CI 1.07–7.99) for GG compared to CC individuals. According to our study, Taiwanese adults with T2D and the rs738409 GG genotype are more likely to develop liver cirrhosis.
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Affiliation(s)
- Kuan-Chun Hsueh
- Department of Surgery, Tungs' Taichung Metro Harbor Hospital, Taichung, Taiwan.,Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
| | - Oswald Ndi Nfor
- Department of Public Health and Institute of Public Health, Chung Shan Medical University, Taichung, Taiwan
| | - Shu-Yi Hsu
- Department of Public Health and Institute of Public Health, Chung Shan Medical University, Taichung, Taiwan
| | - Shun-Fa Yang
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.,Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Yung-Po Liaw
- Department of Public Health and Institute of Public Health, Chung Shan Medical University, Taichung, Taiwan.,Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung City, Taiwan
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32
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Puri P, Kotwal N. An Approach to the Management of Diabetes Mellitus in Cirrhosis: A Primer for the Hepatologist. J Clin Exp Hepatol 2022; 12:560-574. [PMID: 35535116 PMCID: PMC9077234 DOI: 10.1016/j.jceh.2021.09.010] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Accepted: 09/07/2021] [Indexed: 12/12/2022] Open
Abstract
The management of diabetes in cirrhosis and liver transplantation can be challenging. There is difficulty in diagnosis and monitoring of diabetes as fasting blood sugar values are low and glycosylated hemoglobin may not be a reliable marker. The challenges in the management of diabetes in cirrhosis include the likelihood of cognitive impairment, risk of hypoglycemia, altered drug metabolism, frequent renal dysfunction, risk of lactic acidosis, and associated malnutrition and sarcopenia. Moreover, calorie restriction and an attempt to lose weight in obese diabetics may be associated with a worsening of sarcopenia. Many commonly used antidiabetic drugs may be unsafe or be associated with a high risk of hypoglycemia in cirrhotics. Post-transplant diabetes is common and may be contributed by immunosuppressive medication. There is inadequate clinical data on the use of antidiabetic drugs in cirrhosis, and the management of diabetes in cirrhosis is hampered by the lack of guidelines focusing on this issue. The current review aims at addressing the practical management of diabetes by a hepatologist.
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Key Words
- ADA, American Diabetes Association
- AGI, Alfa Glucosidase inhibitors
- BMI, Body mass index
- CLD, Chronic liver disease
- CYP-450, Cytochrome P-450
- Dipeptidyl-peptidase 4, DPP-4
- GLP-1, Glucagon-like peptide-1
- HCC, Hepatocellular carcinoma
- HCV, Hepatitis C virus
- HbA1c, Hemoglobin A1c
- IGF, Insulin-like growth factor
- MALA, Metformin-associated lactic acidosis
- NASH, Nonalcoholic steatohepatitis
- NPL, Neutral protamine lispro
- OGTT, Oral glucose tolerance test
- SMBG, Self-monitoring of blood glucose
- Sodium-glucose cotransporter 2, SGLT2
- VEGF, Vascular endothelial growth factor
- antidiabetic agents
- antihyperglycemic drugs
- chronic liver disease
- cirrhosis
- diabetes mellitus
- eGFR, estimated glomerular filtration rates
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Affiliation(s)
- Pankaj Puri
- Fortis Escorts Liver and Digestive Diseases Institute, New Delhi, 110025, India
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Tian C, Zhu Y, Liu Y, Hu H, Cheng Q, Yang F, Pei L, Zhou Y, Li Y, Lin S. High Albumin Level Is Associated With Regression of Glucose Metabolism Disorders Upon Resolution of Acute Liver Inflammation in Hepatitis B-Related Cirrhosis. Front Cell Infect Microbiol 2022; 12:721138. [PMID: 35273920 PMCID: PMC8902754 DOI: 10.3389/fcimb.2022.721138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 01/25/2022] [Indexed: 11/14/2022] Open
Abstract
Background and Aim To investigate the short-term dynamic changes and the factors associated with regression of glucose metabolism disorders in patients with hepatitis flare of chronic hepatitis B virus (HBV) infection. Methods In this study, 118 patients with severe hepatitis flare of chronic HBV infection were prospectively studied. Oral glucose tolerance test was performed on admission and during follow-up to evaluate dynamic changes in glucose metabolism disorders. The factors associated with regression of glucose metabolism disorders were identified using univariate and multivariate logistic regression analyses. Results The prevalence of diabetes was significantly higher in 70 (47.1%) patients with liver cirrhosis than that in 48 (16.8%) patients without liver cirrhosis. The prevalence of impaired glucose tolerance in patients with liver cirrhosis (35.7%) was significantly lower than that in patients without liver cirrhosis (47.8%). After a follow-up of 20.0 ± 18.7 days, 28 of 31 (90.3%) patients without liver cirrhosis experienced regression of glucose metabolism disorders. Additionally, 30 (54.5%) patients with liver cirrhosis experienced regression of glucose metabolism disorders after 42.0 ± 36.2 days. In patients with liver cirrhosis, those with regression of glucose metabolism disorders had significantly higher levels of homeostasis model assessment-β-cell function, albumin (ALB), and a significantly lower level of fibrosis-4 score. ALB was identified as an independent factor associated with the regression of glucose metabolism disorders in patients with liver cirrhosis. Conclusion Severe acute liver inflammation aggravates glucose metabolism disorders in patients with hepatitis B-related liver cirrhosis and high ALB level is associated with regression of glucose metabolism disorders upon resolution of acute liver inflammation.
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Affiliation(s)
- Caiyun Tian
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Yanping Zhu
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Yujuan Liu
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Han Hu
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Qijiao Cheng
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Fangwan Yang
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Lingqi Pei
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Yihong Zhou
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Ying Li
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Shide Lin
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Zunyi, China
- College of Laboratory Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, China
- *Correspondence: Shide Lin,
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Abstract
Background/Objectives Cirrhosis of liver is associated with loss of liver function, portal hypertension, and pancreatic β-cell dysfunction leading to hepatogenous diabetes (HD). Often HD is an underestimated and understudied problem, particularly in the Indian subcontinent, where the prevalence of both Chronic liver disease (CLD) and diabetes is high. Hence this study was planned to highlight the prevalence of HD and its association with the severity of cirrhosis. Methods A total of 121 cirrhotic patients without a history of diabetes were included in this prospective cross-sectional study. Seventy five g oral glucose tolerance test (OGTT) was done in all patients. Fasting serum insulin levels were done to calculate insulin resistance (IR) using homeostatic model assessment-insulin resistance (HOMA-IR). Upper gastrointestinal endoscopy was done to detect varices. Patients were divided into HD group and non-HD group for comparison of results. Results HD was seen in 52 (42.98%) patients; among them, 63.4% did not show evidence of HD by fasting plasma glucose (FPG) levels. Impaired glucose tolerance (IGT) was seen in 58 (47.93%) patients. Compared with the non-HD group, the HD group had significantly higher model for end-stage liver disease (MELD) score (P = 0.038), HOMA-IR (P < 0.001), incidence of large varices (P < 0.001) and variceal bleeding (P < 0.001). A statistically significant association was noted between HD and Hepatocellular carcinoma (HCC) (P < 0.001). Conclusion Patients with cirrhosis had a high prevalence of IGT, IR, and HD. The presence of HD is well associated with the severity of cirrhosis in the form of higher MELD score (>15), CTP score (>10), higher bilirubin levels, large varices, bleeding varices, and HCC. FPG levels and glycated hemoglobin (HbA1c) cannot be relied upon, and OGTT aids in the unmasking of HD in these patients.
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Key Words
- 120-min PG, 120 min plasma glucose
- AASLD, American association for the study of liver diseases
- ADA, American diabetic association
- CLD, chronic liver disease
- CTP score, Child-Turcotte-Pugh score
- DM, diabetes mellitus
- FPG, fasting plasma glucose
- HCC, hepatocellular carcinoma
- HD, hepatogenous diabetes
- HOMA-IR, homeostatic model assessment-insulin resistance
- HVPG, hepatic venous pressure gradient
- HbA1c, glycated hemoglobin
- IGF, insulin-like growth factor
- IGT, impaired glucose tolerance
- IR, insulin resistance
- MELD score, model for end-stage liver disease
- OGTT, oral glucose tolerance test
- SPSS, statistical software for social sciences
- T2DM, type 2 diabetes mellitus
- chronic liver disease
- hepatogenous diabetes
- impaired glucose tolerance
- insulin resistance
- variceal bleeding
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Sun X, Chi X, Zhao Y, Liu S, Xing H. Characteristics and Clinical Significance of Intestinal Microbiota in Patients with Chronic Hepatitis B Cirrhosis and Type 2 Diabetes Mellitus. J Diabetes Res 2022; 2022:1826181. [PMID: 35601017 PMCID: PMC9122699 DOI: 10.1155/2022/1826181] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Revised: 03/24/2022] [Accepted: 04/15/2022] [Indexed: 01/30/2023] Open
Abstract
BACKGROUND Chronic hepatitis B cirrhosis is often accompanied by glucose metabolism disorder, and intestinal microbiota was closely related to both cirrhosis and diabetes. There are few studies on the role of intestinal microbiota in hepatitis B liver cirrhosis and diabetes mellitus (LCDM). The purpose of this study was to investigate the characteristics of intestinal microbiota in patients with LCDM and to evaluate the relationship between the severity of intestinal microbiota imbalance and clinical significance. METHODS A case-controlled study was conducted. People who met the inclusion and exclusion criteria of chronic HBV-related liver cirrhosis (LC), LCDM, and healthy controls (HC) were enrolled in, and their fecal and blood samples were collected. The V3-V4 region of 16s rDNA gene of fecal microbiota was sequenced; the bioinformatics analysis including α-diversity, β-diversity, and linear discriminant analysis (LDA) effect size (LEfSe) was performed; and the correlation between bacteria and clinical indexes was analyzed. RESULTS A total of 70 participants completed fecal and blood tests, including 20 HC, 20 LCDM, and 30 LC. The α diversity of intestinal microbiota in the LCDM decreased than that in the HC. The abundance of Proteobacteria, Streptococcus, Escherichia-Shigella, and Lactobacillus increased, while the abundance of Bacteroidota, Bacteroides, Prevotella, Faecalibacterium, and Lachnospira decreased in the LCDM compared with the HC. The abundance of Lactobacillus, Roseburia, and Veillonella and the degree of hepatitis B cirrhosis dysbiosis indicator (HBCDI) increased in the LCDM than in the LC. The abundance of Escherichia-Shigella, Veillonella, and Lactobacillus positively correlated with liver injury and fasting blood glucose (FBG) level. The abundance of Escherichia-Shigella, Veillonella, Streptococcus, and Lactobacillus increased more significantly when FBG and glycosylated hemoglobin level increased. CONCLUSION Intestinal microbiota of patients with LCDM was significantly disordered, and the degree was more serious than that cirrhosis patients without diabetes.
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Affiliation(s)
- Xiu Sun
- Center of Liver Diseases Division 3, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xin Chi
- Center of Liver Diseases Division 3, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yingying Zhao
- Center of Liver Diseases Division 3, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- National Center for Infectious Diseases, Beijing, China
| | - Shunai Liu
- National Center for Infectious Diseases, Beijing, China
- Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Huichun Xing
- Center of Liver Diseases Division 3, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- National Center for Infectious Diseases, Beijing, China
- Peking University Ditan Teaching Hospital, Beijing, China
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Hijazi G, Paschall A, Young SP, Smith B, Case LE, Boggs T, Amarasekara S, Austin SL, Pendyal S, El-Gharbawy A, Deak KL, Muir AJ, Kishnani PS. A retrospective longitudinal study and comprehensive review of adult patients with glycogen storage disease type III. Mol Genet Metab Rep 2021; 29:100821. [PMID: 34820282 PMCID: PMC8600151 DOI: 10.1016/j.ymgmr.2021.100821] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Accepted: 11/09/2021] [Indexed: 12/03/2022] Open
Abstract
INTRODUCTION A deficiency of glycogen debrancher enzyme in patients with glycogen storage disease type III (GSD III) manifests with hepatic, cardiac, and muscle involvement in the most common subtype (type a), or with only hepatic involvement in patients with GSD IIIb. OBJECTIVE AND METHODS To describe longitudinal biochemical, radiological, muscle strength and ambulation, liver histopathological findings, and clinical outcomes in adults (≥18 years) with glycogen storage disease type III, by a retrospective review of medical records. RESULTS Twenty-one adults with GSD IIIa (14 F & 7 M) and four with GSD IIIb (1 F & 3 M) were included in this natural history study. At the most recent visit, the median (range) age and follow-up time were 36 (19-68) and 16 years (0-41), respectively. For the entire cohort: 40% had documented hypoglycemic episodes in adulthood; hepatomegaly and cirrhosis were the most common radiological findings; and 28% developed decompensated liver disease and portal hypertension, the latter being more prevalent in older patients. In the GSD IIIa group, muscle weakness was a major feature, noted in 89% of the GSD IIIa cohort, a third of whom depended on a wheelchair or an assistive walking device. Older individuals tended to show more severe muscle weakness and mobility limitations, compared with younger adults. Asymptomatic left ventricular hypertrophy (LVH) was the most common cardiac manifestation, present in 43%. Symptomatic cardiomyopathy and reduced ejection fraction was evident in 10%. Finally, a urinary biomarker of glycogen storage (Glc4) was significantly associated with AST, ALT and CK. CONCLUSION GSD III is a multisystem disorder in which a multidisciplinary approach with regular clinical, biochemical, radiological and functional (physical therapy assessment) follow-up is required. Despite dietary modification, hepatic and myopathic disease progression is evident in adults, with muscle weakness as the major cause of morbidity. Consequently, definitive therapies that address the underlying cause of the disease to correct both liver and muscle are needed.
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Key Words
- AFP, Alpha-fetoprotein
- ALT, Alanine aminotransferase
- AST, Aspartate aminotransferase
- BG, Blood glucose
- BMI, Body mass index
- CEA, Carcinoembryonic antigen
- CPK, Creatine phosphokinase
- CT scan, Computerized tomography scan
- Cardiomyopathy
- Cirrhosis
- DM, Diabetes mellitus
- GDE, Glycogen debrancher enzyme
- GGT, Gamma glutamyl transferase
- GSD, Glycogen storage disease
- Glc4, Glucose tetrasaccharide
- Glycogen storage disease type III (GSD III)
- HDL, High density lipoprotein
- Hypoglycemia
- LDL, Low density lipoproteins
- LT, liver transplantation.
- Left ventricular hypertrophy (LVH)
- MRI, Magnetic resonance imaging
- TGs, Triglycerides
- US, Ultrasound
- and myopathy
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Affiliation(s)
- Ghada Hijazi
- Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA
| | - Anna Paschall
- Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA
| | - Sarah P. Young
- Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA
| | - Brian Smith
- Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA
| | - Laura E. Case
- Doctor of Physical Therapy Division, Department of Orthopedic Surgery, Duke University School of Medicine, Durham, NC, USA
| | - Tracy Boggs
- Duke University Health System, Department of Physical Therapy and Occupational Therapy, USA
| | | | - Stephanie L. Austin
- Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA
| | - Surekha Pendyal
- Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA
| | - Areeg El-Gharbawy
- Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA
| | | | - Andrew J. Muir
- Division of Gastroenterology, Duke University School of Medicine, Durham, NC, USA
| | - Priya S. Kishnani
- Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA
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Abstract
As liver is one of the primary organs involved in glucose homeostasis, it is not surprising that patients with liver dysfunction in chronic liver disease usually develop impaired glucose tolerance and subsequently overt diabetes later in their natural course. Diabetes that develops after the onset of cirrhosis of liver is usually referred to as hepatogenous diabetes (HD). It is an underrecognized and a hallmark endocrinological event in chronic liver disease. HD is associated with a higher risk of developing hepatic decompensations, such as ascites, variceal bleeding, hepatic encephalopathy, renal dysfunction, refractory ascites, and hepatocellular carcinoma along with reduced survival rates than normoglycemic patients with cirrhosis of liver. It is quite different from type 2 diabetes mellitus with the absence of classical risk factors, dissimilar laboratory profiles, and decreased incidence of microvascular complications. Furthermore, the management of patients with HD is challenging because of altered pharmacokinetics of most antidiabetic drugs and increased risk of hypoglycemia and other adverse effects. Hence, a clear understanding of the epidemiology, pathophysiology, clinical implications, laboratory diagnosis, and management of HD is essential for both hepatologists as well as endocrinologists, which is narrated briefly in this review.
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Affiliation(s)
- Preetam Nath
- Department of Gastroenterology & Hepatology, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha 751024, India
| | - Anil C. Anand
- Department of Gastroenterology & Hepatology, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha 751024, India
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Management of diabetes mellitus in patients with cirrhosis: An overview and joint statement. DIABETES & METABOLISM 2021; 47:101272. [PMID: 34363981 DOI: 10.1016/j.diabet.2021.101272] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 06/25/2021] [Accepted: 07/12/2021] [Indexed: 12/18/2022]
Abstract
Type 2 diabetes mellitus (T2DM) is a frequent comorbidity in patients with cirrhosis that is projected to rise in prevalence due to the worldwide burden of obesity, insulin-resistance and non-alcoholic fatty liver disease. The management of T2DM in patients with cirrhosis is complex given the requirement for accurate adaptation according to the level of liver function impairment, with lack of summary of the little evidence available in the literature. Here, we summarise the data available with respect to the epidemiology and the impact of T2DM in patients with cirrhosis, as well as those on the management of T2DM in these patients. We provide guidance for the diagnosis of T2DM and the monitoring of glycaemic control in patients with cirrhosis, and for the management of nutrition and pharmacological treatments in relation to the level of liver dysfunction.
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Bai XP, Fan YM, Zhang L, Yang GH, Li X. Influence of Liver Cirrhosis on Blood Glucose, Insulin Sensitivity and Islet Function in Mice. Am J Med Sci 2021; 362:403-417. [PMID: 34274322 DOI: 10.1016/j.amjms.2021.07.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Revised: 02/27/2021] [Accepted: 07/09/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND The relationship between cirrhosis and diabetes is controversial. We studied the influence of cirrhosis on glucose levels and islet function and explored its possible mechanisms. MATERIALS AND METHODS Cirrhosis was induced in male C57BL/6 mice by bile duct ligation (BDL). Serum biochemical parameters were determined, and oral glucose tolerance tests (OGTT) were performed at 4 and 8 weeks after BDL. Histopathology and phospho-NF-κB-p65/I-kappa B α immunohistochemical staining of the liver and islet were observed. The protein levels of the insulin signaling system and the gene expression of insulin-degrading enzyme (IDE) in the liver and muscle were determined. The activity of glucokinase (GCK) and glucose 6-phosphatase (G6P) and glycogen levels in liver homogenates were measured. RESULTS After BDL, the mice developed cirrhosis, and fasting glucose decreased significantly, but 2 h postprandial glucose increased, and the insulin areas under the curves increased. At 4 weeks of BDL, the ratios of phospho-NF-κB-p65/I-kappa B α accumulation in the liver and islet increased, the activity of G6P and the glycogen content in liver homogenates decreased, the insulin signaling system and the gene expression of IDE in the liver was downregulated, and the islet areas were decreased. After 8 weeks, these changes were more severe. CONCLUSIONS In different periods of cirrhosis, the levels of fasting glucose and 2 h postprandial glucose changed in different amplitudes. Glycogen concentrations and the activity of G6P in the liver were decreased. The mice developed insulin resistance and the islet areas were decreased. The NF-κB pathway may play a role in the process.
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Affiliation(s)
- Xiu-Ping Bai
- Endocrinology Division, The Second Hospital of ShanXi Medical University, TaiYuan 030001, ShanXi, China.
| | - Yong-Mei Fan
- Endocrinology Division, The Second Hospital of ShanXi Medical University, TaiYuan 030001, ShanXi, China
| | - Lei Zhang
- Endocrinology Division, The Second Hospital of ShanXi Medical University, TaiYuan 030001, ShanXi, China
| | - Guo-Hua Yang
- Central Laboratory, The Second Hospital of ShanXi Medical University, TaiYuan 030001, ShanXi, China
| | - Xing Li
- Endocrinology Division, The Second Hospital of ShanXi Medical University, TaiYuan 030001, ShanXi, China
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Grottenthaler JM, Füger JK, Mahling M, Königsrainer A, Malek NP, Birkenfeld AL, Nadalin S, Berg CP, Heyne N, Guthoff M. Dynamics of glucose metabolism after liver transplantation: Prediabetes as a window of opportunity for patient survival and long-term kidney function. Transpl Int 2021; 34:1959-1970. [PMID: 34214208 DOI: 10.1111/tri.13967] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 05/30/2021] [Accepted: 06/28/2021] [Indexed: 12/01/2022]
Abstract
Posttransplantation diabetes mellitus (PTDM) is a relevant complication following liver transplantation with profound impact on morbidity and mortality. To date, little is known about the evolution and dynamics of glucose metabolism and the impact of prediabetes in long-term follow-up. To address this issue, all consecutive adult liver transplant recipients (n=429) from a European university hospital transplant center between 2007 and 2017 were analyzed retrospectively. In patients without pre-existing diabetes (n=327), we conducted a longitudinal characterization of glucose metabolism. Median follow-up was 37 [9-64, IQR] months. Median prevalence of prediabetes was 39 [37-39]% and of PTDM 21 [17-22]%. Throughout follow-up, intra-individual glucose regulation of patients was highly variable, continuously fluctuating between different states of glucose metabolism (normal glucose tolerance, prediabetes, PTDM). Whereas overall survival and long-term kidney function of patients with PTDM were significantly lower than that of patients with normal glucose metabolism, prediabetes was not associated with adverse outcome. This study provides new insight into the dynamics and impact of glucose metabolism after liver transplantation. Unlike PTDM, prediabetes is not associated with adverse outcome, providing a window of opportunity for targeted intervention. The results underline the need for constant screening and intervention in post-transplant care of liver allograft recipients.
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Affiliation(s)
- Julia M Grottenthaler
- Department of Gastroenterology, Gastrointestinal Oncology, Hepatology, Infectiology, and Geriatrics, University of Tuebingen, Tuebingen, Germany
| | - Judith K Füger
- Department of Diabetology, Endocrinology, Nephrology, University of Tuebingen, Tuebingen, Germany
| | - Moritz Mahling
- Department of Diabetology, Endocrinology, Nephrology, University of Tuebingen, Tuebingen, Germany.,Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tuebingen, Tuebingen, Germany.,German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
| | - Alfred Königsrainer
- Department of General-, Visceral- and Transplant Surgery, University of Tuebingen, Tuebingen, Germany
| | - Nisar P Malek
- Department of Gastroenterology, Gastrointestinal Oncology, Hepatology, Infectiology, and Geriatrics, University of Tuebingen, Tuebingen, Germany
| | - Andreas L Birkenfeld
- Department of Diabetology, Endocrinology, Nephrology, University of Tuebingen, Tuebingen, Germany.,Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tuebingen, Tuebingen, Germany.,German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
| | - Silvio Nadalin
- Department of General-, Visceral- and Transplant Surgery, University of Tuebingen, Tuebingen, Germany
| | - Christoph P Berg
- Department of Gastroenterology, Gastrointestinal Oncology, Hepatology, Infectiology, and Geriatrics, University of Tuebingen, Tuebingen, Germany
| | - Nils Heyne
- Department of Diabetology, Endocrinology, Nephrology, University of Tuebingen, Tuebingen, Germany.,Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tuebingen, Tuebingen, Germany.,German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
| | - Martina Guthoff
- Department of Diabetology, Endocrinology, Nephrology, University of Tuebingen, Tuebingen, Germany.,Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tuebingen, Tuebingen, Germany.,German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
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Aslam M, Farooq S, Rizwan B, Asghar A. Assessment of nutritional status of the cirrhotic patients on enteral and parenteral feeding. Nutr Health 2021; 28:69-76. [PMID: 34139917 DOI: 10.1177/02601060211020968] [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] [Indexed: 11/15/2022]
Abstract
BACKGROUND Cirrhosis is an irreversible disease that replaces healthy tissues with scar tissues. According to the Pakistan Medical Research Council's national general population survey (2008-2014), the ratio of cirrhosis was 4.8% among the population. OBJECTIVES To assess the nutritional status of cirrhotic patients on enteral and parenteral nutrition and to assess the degree of malnutrition among cirrhotic patients. METHODS A cross-sectional study was conducted at Shalamar and Shiekh Zayed Hospitals of Lahore from January-April 2017. The convenient sampling technique was used. Inclusion criteria were the patients with decompensated liver cirrhosis, whereas compensated patients were excluded from the study. Data were collected through the patient's file, nurse's, and dietitian's notes. The nutritional status of participants was assessed based on socio-demographic characteristics, anthropometric measurements, biochemical assessment, clinical signs, and dietary recall. Variables were categorized and compared to observe the level of significance in enteral and parenteral nutrition. SPSS version 22 was used to analyze data. RESULTS Patients on parenteral nutrition had a higher ratio of malnutrition with a significant Child-Pugh score-61.8% of patients belonged to Class C and 35.3% Class B, while in enteral support, 7.3% belonged to Class C and 43.9% patients belonged to Class B (p-value = 0.000). There was a definite relationship observed in the route of intake and malnutrition among cirrhotic patients. CONCLUSION Enteral route of nutrition is an effective and the safest way to provide appropriate nutrients according to the patient's demands.
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Affiliation(s)
- Mahwish Aslam
- University Institute of Diet and Nutritional Sciences, University of Lahore, Lahore, Pakistan
| | - Sana Farooq
- University Institute of Diet and Nutritional Sciences, University of Lahore, Lahore, Pakistan
| | - Bahisht Rizwan
- University Institute of Diet and Nutritional Sciences, University of Lahore, Lahore, Pakistan
| | - Ayesha Asghar
- Institute of Medical and Molecular Biology, University of Lahore, Lahore, Pakistan
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Lomonaco R, Godinez Leiva E, Bril F, Shrestha S, Mansour L, Budd J, Portillo Romero J, Schmidt S, Chang KL, Samraj G, Malaty J, Huber K, Bedossa P, Kalavalapalli S, Marte J, Barb D, Poulton D, Fanous N, Cusi K. Advanced Liver Fibrosis Is Common in Patients With Type 2 Diabetes Followed in the Outpatient Setting: The Need for Systematic Screening. Diabetes Care 2021; 44:399-406. [PMID: 33355256 PMCID: PMC7818321 DOI: 10.2337/dc20-1997] [Citation(s) in RCA: 226] [Impact Index Per Article: 56.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Accepted: 11/06/2020] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Assess the prevalence of nonalcoholic fatty liver disease (NAFLD) and of liver fibrosis associated with nonalcoholic steatohepatitis in unselected patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS A total of 561 patients with T2DM (age: 60 ± 11 years; BMI: 33.4 ± 6.2 kg/m2; and HbA1c: 7.5 ± 1.8%) attending primary care or endocrinology outpatient clinics and unaware of having NAFLD were recruited. At the visit, volunteers were invited to be screened by elastography for steatosis and fibrosis by controlled attenuation parameter (≥274 dB/m) and liver stiffness measurement (LSM; ≥7.0 kPa), respectively. Secondary causes of liver disease were ruled out. Diagnostic panels for prediction of advanced fibrosis, such as AST-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) index, were also measured. A liver biopsy was performed if results were suggestive of fibrosis. RESULTS The prevalence of steatosis was 70% and of fibrosis 21% (LSM ≥7.0 kPa). Moderate fibrosis (F2: LSM ≥8.2 kPa) was present in 6% and severe fibrosis or cirrhosis (F3-4: LSM ≥9.7 kPa) in 9%, similar to that estimated by FIB-4 and APRI panels. Noninvasive testing was consistent with liver biopsy results. Elevated AST or ALT ≥40 units/L was present in a minority of patients with steatosis (8% and 13%, respectively) or with liver fibrosis (18% and 28%, respectively). This suggests that AST/ALT alone are insufficient as initial screening. However, performance may be enhanced by imaging (e.g., transient elastography) and plasma diagnostic panels (e.g., FIB-4 and APRI). CONCLUSIONS Moderate-to-advanced fibrosis (F2 or higher), an established risk factor for cirrhosis and overall mortality, affects at least one out of six (15%) patients with T2DM. These results support the American Diabetes Association guidelines to screen for clinically significant fibrosis in patients with T2DM with steatosis or elevated ALT.
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Affiliation(s)
- Romina Lomonaco
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL
| | - Eddison Godinez Leiva
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL
| | - Fernando Bril
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL
| | - Sulav Shrestha
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL
| | - Lydia Mansour
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL
| | - Jeff Budd
- Division of General Internal Medicine, University of Florida, Gainesville, FL
| | | | - Siegfried Schmidt
- Department of Family Medicine, University of Florida, Gainesville, FL
| | - Ku-Lang Chang
- Department of Family Medicine, University of Florida, Gainesville, FL
| | - George Samraj
- Department of Family Medicine, University of Florida, Gainesville, FL
| | - John Malaty
- Department of Family Medicine, University of Florida, Gainesville, FL
| | - Katherine Huber
- Division of General Internal Medicine, University of Florida, Gainesville, FL
| | - Pierre Bedossa
- Department of Pathology, Beaujon Hospital Paris Diderot University, Paris, France
| | - Srilaxmi Kalavalapalli
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL
| | - Jonathan Marte
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL
| | - Diana Barb
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL
| | - Danielle Poulton
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL
| | - Nada Fanous
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL
| | - Kenneth Cusi
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL .,Division of Endocrinology, Diabetes and Metabolism, Malcom Randall VA Medical Center, Gainesville, FL
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Chen YC, Pai MH, Chen YT, Hou YC. Dietary exposure to chlorpyrifos affects systemic and hepatic immune-cell phenotypes in diabetic mice. Toxicology 2021; 452:152698. [PMID: 33524429 DOI: 10.1016/j.tox.2021.152698] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Revised: 01/05/2021] [Accepted: 01/26/2021] [Indexed: 01/19/2023]
Abstract
Hyperglycemia induces low-grade systemic inflammation and immune dysregulation, leading to overstated reactions to immune stimuli and diabetes-related organ damage. Tissue inflammation is characterized by leukocyte infiltration, and T cells play crucial roles in directing leukocyte-mediated inflammatory responses. The aim of the study was to investigate the effects of dietary exposure to chlorpyrifos (CPF) on systemic and hepatic immune-cell phenotypes in C57BL/6 mice with streptozotocin (STZ)-induced diabetes. Mice received an intraperitoneal injection of STZ for 5 consecutive days to induce diabetes, and diabetic mice were given either an AIN-93-based control diet or a CPF-containing diet at doses of 0.5, 1, or 2 mg/kg body weight/day for 28 days. Results showed that dietary exposure to CPF had no influence on the body weight or the erythrocyte hemoglobin A1c level in diabetic mice. Both blood and hepatic neutrophil populations were enhanced by CPF exposure. CPF-exposed groups had lower percentages of blood T cells without altering the proportions of CD4+ and CD8+ T-cell subsets, and lower expression levels of the Bcl-2 antiapoptotic gene in the spleen. CPF exposure reduced the percentage of blood regulatory T cells (Tregs); however, the Treg population was upregulated in the liver even when hepatic T cells were not affected by CPF in diabetic mice. Hepatic expressions of Treg-related genes were suppressed in all CPF-exposed groups. Higher plasma levels of aspartate aminotransferase and expression levels of the hepatic interleukin-1β gene were observed in diabetic mice exposed to medium and high doses of CPF. These findings suggest that dietary exposure to CPF affects the distribution of both myeloid and lymphoid immune cells in the blood and liver under hyperglycemic conditions, which may lead to hyperinflammation when encountering immune stimuli.
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Affiliation(s)
- Yi-Ching Chen
- Master Program in Food Safety, College of Nutrition, Taipei Medical University, Taipei, 11031, Taiwan
| | - Man-Hui Pai
- Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan
| | - Yi-Tien Chen
- Master Program in Food Safety, College of Nutrition, Taipei Medical University, Taipei, 11031, Taiwan; School of Food Safety, College of Nutrition, Taipei Medical University, Taipei, 11031, Taiwan
| | - Yu-Chen Hou
- Master Program in Food Safety, College of Nutrition, Taipei Medical University, Taipei, 11031, Taiwan; School of Food Safety, College of Nutrition, Taipei Medical University, Taipei, 11031, Taiwan; Nutrition Research Center, Taipei Medical University Hospital, Taipei, 11031, Taiwan.
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Weng SW, Chang CC, Chen TL, Yeh CC, Hu CJ, Lane HL, Liao CC, Shih CC. Risk of diabetes in stroke patients who used Bu Yang Huan Wu Tang: A nationwide propensity-score matched study. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2021; 80:153376. [PMID: 33086171 DOI: 10.1016/j.phymed.2020.153376] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Revised: 09/25/2020] [Accepted: 10/11/2020] [Indexed: 06/11/2023]
Abstract
BACKGROUND The utilization of traditional Chinese medicine is a common therapeutic approach for stroke patients in Chinese population, but little is known about the effect of Bu Yang Huan Wu Tang (BYHWT) on post-stroke diabetes. PURPOSE We aimed to evaluate the risk of diabetes in stroke patients who used BYHWT. STUDY DESIGN A retrospective cohort study based on a real-world database was conducted. METHODS Newly diagnosed stroke patients receiving inpatient care from 2000 to 2004 were identified using a large-scale insurance database in Taiwan. Propensity score matching was used to select eligible stroke patients who did (n = 9849) and did not (n = 9849) receive BYHWT. These two groups were followed up until the end of 2009 to track incident diabetes. Cox proportional hazard models were used to calculate the adjusted hazard rations (HRs) and 95% confidence intervals (CIs) for post-stroke diabetes associated with BYHWT during the follow-up period. RESULTS Stroke patients who used BYHWT had a reduced incidence of diabetes (14.1% vs. 19.0%, p < 0.0001) and reduced risk of diabetes (HR 0.77; 95% CI 0.72 to 0.83) compared with the control group. The association between BYHWT and reduced risk of post-stroke diabetes was significant across sexe, age group, and stroke subtype. Additionally, the use of BYHWT was associated with a reduced risk of post-stroke diabetes even after excluding the initial three months of diabetes cases in the sensitivity analysis. CONCLUSIONS Stroke patients who received BYHWT therapy had a reduced risk of diabetes, and a positive effect was observed in various subgroups. However, future clinical trials will be necessary to validate the present findings and identify the biochemical mechanism involved.
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Affiliation(s)
- Shu-Wen Weng
- Department of Chinese Medicine, Taichung Hospital, Ministry of Health and Welfare, Taichung, Taiwan
| | - Chuen-Chau Chang
- Department of Anesthesiology, Taipei Medical University Hospital, Taipei, Taiwan Hospital, Taipei, Taiwan; Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Anesthesiology and Health Policy Research Center, Taipei Medical University Hospital, Taipei, Taiwan
| | - Ta-Liang Chen
- Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Anesthesiology and Health Policy Research Center, Taipei Medical University Hospital, Taipei, Taiwan; Department of Anesthesiology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Chun-Chieh Yeh
- Department of Surgery, China Medical University Hospital, Taichung, Taiwan; Department of Surgery, University of Illinois, Chicago, IL, United States
| | - Chaur-Jong Hu
- Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
| | - Hsin-Long Lane
- School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung, Taiwan
| | - Chien-Chang Liao
- Department of Anesthesiology, Taipei Medical University Hospital, Taipei, Taiwan Hospital, Taipei, Taiwan; Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Anesthesiology and Health Policy Research Center, Taipei Medical University Hospital, Taipei, Taiwan; Research Center of Big Data and Meta-Analysis, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan
| | - Chun-Chuan Shih
- School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung, Taiwan; Program for the Clinical Drug Discovery from Botanical Herbs, Taipei Medical University, Taipei, Taiwan
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Saleh P, Infectious and Tropical Disease Research Center, Department of Infectious and Tropical Disease, Tabriz University of Medical Sciences, Tabriz, Iran, Sheikholeslami A, Infectious and Tropical Disease Research Center, Department of Infectious and Tropical Disease, Tabriz University of Medical Sciences, Tabriz, Iran, Salman Mohajer A, Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran, Babapour S, Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran, Hosseini MS, Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran. Association between Different Hepatitis C Virus Genotypes Infection and Type-2 Diabetes Mellitus: A Descriptive-Analytical Study from the Northwest of Iran. JOURNAL OF MEDICAL MICROBIOLOGY AND INFECTIOUS DISEASES 2020; 8:137-142. [DOI: 10.29252/jommid.8.4.137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
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Kim NG, Sharma A, Saab S. Cardiovascular and metabolic disease in the liver transplant recipient. Best Pract Res Clin Gastroenterol 2020; 46-47:101683. [PMID: 33158470 DOI: 10.1016/j.bpg.2020.101683] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Accepted: 08/31/2020] [Indexed: 01/31/2023]
Abstract
Liver transplantation has led to great improvements in long-term survival in patients with decompensated liver disease and hepatocellular carcinoma. Cardiovascular disease is the leading cause of non-graft-related deaths and has increased prevalence in liver allograft recipients. This is partly secondary to higher post-transplant rates of metabolic risk factors-notably obesity, hypertension, dyslipidemia, and diabetes mellitus, which comprise metabolic syndrome. Post-transplantation metabolic syndrome is expected to be a growing factor in morbidity and mortality as transplant candidates trend older, the rates of metabolic risk factors in the general population increase, non-alcoholic steatohepatitis grows disproportionally as an indication for transplantation, and post-transplantation survival lengthens. This review discusses the incidence and contributory factors for post-transplant increases in metabolic disease, as well as the burden of cardiovascular disease in the liver allograft recipient. Patients with pre-transplant diabetes or obesity are at particularly high risk for post-transplant metabolic syndrome, and would likely benefit from closer surveillance and more aggressive medical management of risk factors. In metabolic disease resistant to initial medical therapies, tailoring of immunosuppressive regimens may further assist in minimizing long-term cardiovascular disease, although this must be done with caution to avoid worsening the risk of graft failure.
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Affiliation(s)
- Nathan G Kim
- Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA
| | - Avneesh Sharma
- Virginia Commonwealth University School of Medicine, Richmond, VA, USA
| | - Sammy Saab
- Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA; Department of Surgery, University of California at Los Angeles, Los Angeles, CA, USA.
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Cigrovski Berkovic M, Virovic-Jukic L, Bilic-Curcic I, Mrzljak A. Post-transplant diabetes mellitus and preexisting liver disease - a bidirectional relationship affecting treatment and management. World J Gastroenterol 2020; 26:2740-2757. [PMID: 32550751 PMCID: PMC7284186 DOI: 10.3748/wjg.v26.i21.2740] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2020] [Revised: 04/24/2020] [Accepted: 05/14/2020] [Indexed: 02/06/2023] Open
Abstract
Liver cirrhosis and diabetes mellitus (DM) are both common conditions with significant socioeconomic burden and impact on morbidity and mortality. A bidirectional relationship exists between DM and liver cirrhosis regarding both etiology and disease-related complications. Type 2 DM (T2DM) is a well-recognized risk factor for chronic liver disease and vice-versa, DM may develop as a complication of cirrhosis, irrespective of its etiology. Liver transplantation (LT) represents an important treatment option for patients with end-stage liver disease due to non-alcoholic fatty liver disease (NAFLD), which represents a hepatic manifestation of metabolic syndrome and a common complication of T2DM. The metabolic risk factors including immunosuppressive drugs, can contribute to persistent or de novo development of DM and NAFLD after LT. T2DM, obesity, cardiovascular morbidities and renal impairment, frequently associated with metabolic syndrome and NAFLD, may have negative impact on short and long-term outcomes following LT. The treatment of DM in the context of chronic liver disease and post-transplant is challenging, but new emerging therapies such as glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) targeting multiple mechanisms in the shared pathophysiology of disorders such as oxidative stress and chronic inflammation are a promising tool in future patient management.
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Affiliation(s)
- Maja Cigrovski Berkovic
- Department of Kinesiological Anthropology and Methodology, Faculty of Kinesiology, University of Zagreb, Zagreb 10000, Croatia
- Clinical Hospital Dubrava, Zagreb 10000, Croatia
- Department of Pharmacology, Faculty of Medicine, University of J. J. Strossmayer Osijek, Osijek 31000, Croatia
| | - Lucija Virovic-Jukic
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
- Department of Medicine, Division of Gastroenterology and Hepatology, Sisters of Charity University Hospital, Zagreb 10000, Croatia
| | - Ines Bilic-Curcic
- Department of Pharmacology, Faculty of Medicine, University of J. J. Strossmayer Osijek, Osijek 31000, Croatia
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
- Clinical Hospital Center Osijek, Osijek 31000, Croatia
| | - Anna Mrzljak
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
- Department of Medicine, Merkur University Hospital, Zagreb 10000, Croatia
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da Silva CB, Vieira DA, de Melo LF, Chagas ALS, Gomes AD, Faria Jr CLLD, Teixeira R, de Magalhães Queiroz DM, Rocha GA, Soares MMS, Bezerra JMT, Silva LD. Interleukin-6-174G/C polymorphism is associated with a decreased risk of type 2 diabetes in patients with chronic hepatitis C virus. World J Hepatol 2020; 12:137-148. [PMID: 32685106 PMCID: PMC7336292 DOI: 10.4254/wjh.v12.i4.137] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2019] [Revised: 02/28/2020] [Accepted: 03/22/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Chronic hepatitis C (CHC) is associated with type 2 diabetes mellitus. Although the pathogenesis remains to be elucidated, a growing evidence has suggested a role of pro-inflammatory immune response. Increased serum concentrations of Interleukin 6 (IL-6) have been associated with insulin resistance, type 2 diabetes mellitus as well as advanced forms of liver disease in chronic hepatitis C infection.
AIM To investigate the frequency of IL-6-174G/C (rs1800795) single nucleotide polymorphism (SNP) in CHC patients and in healthy subjects of the same ethnicity. Associations between type 2 diabetes mellitus (dependent variable) and demographic, clinical, nutritional, virological and, IL-6 genotyping data were also investigated in CHC patients.
METHODS Two hundred and forty-five patients with CHC and 179 healthy control subjects (blood donors) were prospectively included. Type 2 diabetes mellitus was diagnosed according to the criteria of the American Diabetes Association. Clinical, biochemical, histological and radiological methods were used for the diagnosis of the liver disease. IL-6 polymorphism was evaluated by Taqman SNP genotyping assay. The data were analysed by logistic regression models.
RESULTS Type 2 diabetes mellitus, blood hypertension and liver cirrhosis were observed in 20.8% (51/245), 40.0% (98/245) and 38.4% (94/245) of the patients, respectively. The frequency of the studied IL-6 SNP did not differ between the CHC patients and controls (P = 0.81) and all alleles were in Hardy-Weinberg equilibrium (P = 0.38). In the multivariate analysis, type 2 diabetes mellitus was inversely associated with GC and CC genotypes of IL-6-174 (OR = 0.42; 95%CI = 0.22-0.78; P = 0.006) and positively associated with blood hypertension (OR = 5.56; 95%CI = 2.79-11.09; P < 0.001).
CONCLUSION This study was the first to show that GC and CC genotypes of IL-6-174 SNP are associated with a decreased risk of type 2 diabetes mellitus in patients chronically infected with hepatitis C virus. The identification of potential inflammatory mediators involved in the crosstalk between hepatitis C virus and the axis pancreas-liver remains important issues that deserve further investigations.
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Affiliation(s)
- Cliviany Borges da Silva
- Sciences Applied to Adult Health Care Post-Graduate Programme, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
- Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
| | - Diego Alves Vieira
- Medical undergraduate student, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
- Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
| | - Luisa Freitas de Melo
- Medical undergraduate student, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
- Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
| | - Anna Luiza Soares Chagas
- Medical undergraduate student, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
- Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
| | - Adriana Dias Gomes
- Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
| | - César Lúcio Lopes de Faria Jr
- Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
| | - Rosângela Teixeira
- Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
- Department of Internal Medicine, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
| | - Dulciene Maria de Magalhães Queiroz
- Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
| | - Gifone Aguiar Rocha
- Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
| | - Maria Marta Sarquis Soares
- Division of Endocrinology, Department of Internal Medicine, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
| | - Juliana Maria Trindade Bezerra
- Epidemiology of Infectious and Parasitic Diseases Laboratory, Department of Parasitology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
| | - Luciana Diniz Silva
- Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
- Department of Internal Medicine, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130100, Minas Gerais, Brazil
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Zhao J, Wang ZY, Li J, Yu HW, Meng QH. Influence of diabetes mellitus on energy metabolism in patients with alcoholic liver cirrhosis. Eur J Gastroenterol Hepatol 2020; 32:110-115. [PMID: 31567641 DOI: 10.1097/meg.0000000000001560] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
OBJECTIVE The objective was to explore the characteristics of energy metabolism in patients with alcoholic liver cirrhosis (ALC) and diabetes mellitus (DM). METHODS Thirty-four male patients with ALC and DM, 30 male patients with ALC without DM and 10 male healthy controls (HC) were enrolled in this study. Resting energy expenditure (REE), respiratory quotient (RQ) were measured by indirect calorimetry. Data were analyzed using the Student's t-test, Mann-Whitney U-test and χ2 tests between two groups. Logistic regression analysis was used to analyze the risk factors for hypermetabolism. RESULTS Measured REE was significantly higher in patients with ALC and DM (1740 ± 338 kcal/d) than in patients with ALC (1400 ± 304 kcal/d, P < 0.01). Fasting blood glucose was an independent factor predicting hypermetabolism in all of the patients with ALC (P = 0.005). RQ was lower in patients with ALC and DM (0.80 ± 0.06) than in patients with ALC (0.83 ± 0.05, P = 0.027) and the HC (0.86 ± 0.03, P = 0.001). In the ALC and DM group, measured REE as percentage of predicted REE by Harris-Benedict formula was higher in patients with HbA1c ≥ 7.5% than in those with HbA1c < 7.5% (126.36 ± 15.19% vs. 109.48 ± 23.89%, P = 0.040). CONCLUSION REE was increased and RQ was significantly decreased in patients with ALC and DM. These changes were associated with poor glucose control. HbA1c less than 7.5% may reduce the risk of hypermetabolism.
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Affiliation(s)
- Juan Zhao
- Department of Critical Care Medicine of Liver Disease, Beijing Youan Hospital, Capital Medical University, Beijing, China
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