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Elbaz T, Al-Naamani K, Abosheaishaa H, Alswat K, El-Kassas M. Leading Role of Sofosbuvir/Daclatasvir in Achieving Hepatitis C Elimination in Egypt. J Viral Hepat 2025; 32:e70032. [PMID: 40433912 DOI: 10.1111/jvh.70032] [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: 12/04/2024] [Revised: 01/09/2025] [Accepted: 05/03/2025] [Indexed: 05/29/2025]
Abstract
Chronic hepatitis C virus (HCV) management has historically been challenging, particularly in Egypt, the country with the highest global disease prevalence. The introduction of direct-acting antivirals (DAAs) has revolutionised treatment, providing high rates of sustained virologic response (SVR) with fewer adverse events compared to previous therapies. In Egypt, the locally produced generics of sofosbuvir/daclatasvir (SOF/DAC) have been integral to the national HCV elimination programme, treating millions effectively and affordably, demonstrating similar efficacy and safety to brand-name drugs. Although not currently present in most international guidelines, this cost-effective regimen offers a viable option for large-scale elimination programmes similar to Egypt's successful experience. This review synthesises real-world Egyptian data and highlights the efficacy and safety of the SOF/DAC combination in various population groups. High sustained virological response (SVR) rates were observed across diverse patient populations, including those with advanced liver disease. However, limitations regarding long-term follow-up, especially HCC surveillance, were identified, underscoring the need for further research. Additionally, the review underscores the success of local Egyptian pharmaceutical policies in reducing treatment costs and securing access for all infected individuals. The Egyptian experience offers valuable insights into the potential for replicating its success, particularly in other high-burden regions.
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Affiliation(s)
- Tamer Elbaz
- Endemic Hepatology and Gastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
- Hepatology and Gastroenterology Department, Faculty of Medicine, New Giza University, Cairo, Egypt
| | - Khalid Al-Naamani
- Department of Medicine, Division of Gastroenterology and Hepatology, The Medical City for Military and Security Services, Muscat, Oman
| | - Hazem Abosheaishaa
- Internal Medicine, Icahn School of Medicine at Mount Sinai, New York City Health and Hospitals, Queens Hospital Center, New York, New York, USA
| | - Khalid Alswat
- Liver Disease Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Mohamed El-Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
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Filip R, Bélanger É, Chen X, Lefebvre D, Uguccioni SM, Pezacki JP. LYPLAL1 enzyme activity is linked to hepatic glucose metabolism. Biochem Biophys Res Commun 2025; 759:151656. [PMID: 40147354 DOI: 10.1016/j.bbrc.2025.151656] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Revised: 03/14/2025] [Accepted: 03/17/2025] [Indexed: 03/29/2025]
Abstract
The serine hydrolase LYPLAL1 is a poorly characterised enzyme with emerging roles in hepatic metabolism. A multitude of association studies have shown links between variants of this gene locus and metabolic conditions such as obesity and insulin resistance. However, the enzyme's function is still largely unknown. Recent biochemical studies have revealed that it may play a role in hepatic glucose metabolism and that its activity is allosterically regulated. Herein, we use a selective activity-based probe to delineate LYPLAL1's involvement in hepatic metabolism. We show that the enzyme's activity is modulated during metabolic stress, specifically pointing to a putative role in negatively regulating gluconeogenesis and upregulating glycolysis. We also determine that knock-out of the enzyme does not affect liver lipid profiles and bring forth evidence for insulin-mediated control of LYPLAL1 in HepG2 cells. Furthermore, LYPLAL1 activity appears to be largely post-translationally regulated as gene expression levels remain largely constant under insulin and glucagon treatments. Taken together these data point to an enzymatic role in regulating glucose metabolism that may be part of a feedback mechanism of signal transduction.
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Affiliation(s)
- Roxana Filip
- Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, K1N 6N5, Canada
| | - Étienne Bélanger
- Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, K1N 6N5, Canada
| | - Xinhzu Chen
- Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, K1N 6N5, Canada
| | - David Lefebvre
- Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, K1N 6N5, Canada
| | - Spencer M Uguccioni
- Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, K1N 6N5, Canada
| | - John Paul Pezacki
- Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, K1N 6N5, Canada.
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Kassaw AT, Tarekegn TB, Derbie A, Ashagrie G, Girmaw F, Mengesha A. Non-adherence to antidiabetic medications and associated factors among adult type 2 diabetes mellitus patients in Northeast Ethiopia: institutional based cross-sectional study. BMJ Open 2025; 15:e093413. [PMID: 40233966 PMCID: PMC12004487 DOI: 10.1136/bmjopen-2024-093413] [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: 09/06/2024] [Accepted: 04/04/2025] [Indexed: 04/17/2025] Open
Abstract
BACKGROUND Non-adherence to antidiabetic medication remains a major barrier to achieve optimal health outcomes among individuals with diabetes, particularly in developing countries. This issue exacerbates poor health outcomes and leads to the wastage of limited healthcare resources. OBJECTIVE This study aimed to assess the prevalence of non-adherence to antidiabetic medications and identify associated factors among adult type 2 diabetes mellitus (DM) patients in the North Wollo zone. STUDY DESIGN An institutional-based cross-sectional study. SETTING The study was conducted in three randomly selected public hospitals in the North Wollo zone: Woldia Comprehensive Specialized Hospital, Lalibela General Hospital and Mersa Primary Hospital. PARTICIPANTS A total of 327 adult type 2 DM patients receiving follow-up care were included. Participants were selected proportionally from each hospital using consecutive sampling. Inclusion criteria included individuals aged ≥18 years, on antidiabetic treatment for at least 6 months and actively on follow-up care during the study period. Patients with hearing impairment, severe illness or incomplete medical records were excluded. MAIN OUTCOME MEASURES Adherence was assessed using the Morisky Medication Adherence Scale-8, a validated eight-item, self-reported questionnaire. Scores ranged from 0 to 8, with adherence levels classified as high (≥8), medium (6-7.75) and low (<6). Patients scoring ≥6 were considered adherent, while those scoring <6 were non-adherent. STATISTICAL ANALYSIS Data were analysed using SPSS V.27. Descriptive statistics were used to summarise the data, and multivariable logistic regression analysis was performed to identify factors associated with non-adherence. A p value ≤0.05 was considered statistically significant. RESULTS The overall prevalence of medication non-adherence was 24.5%. Factors significantly associated with non-adherence included living with diabetes for less than 3 years (adjusted OR (AOR) 3.37, 95% CI 1.91 to 5.95), residing in rural areas (AOR 2.67, 95% CI 1.49 to 4.79), having comorbidities (AOR 2.99, 95% CI 1.67 to 5.34) and having no formal education (AOR 3.26, 95% CI 1.49 to 7.00). CONCLUSION The prevalence of non-adherence to antidiabetic medications (24.5%) exceeded the widely accepted benchmark of ≤20%. Key factors such as rural residence, comorbidities, lower education levels and shorter duration since diagnosis were significantly associated with non-adherence. These findings underscore the need for targeted interventions, including patient education, improved rural healthcare access and integrated care models, to enhance adherence and diabetes management outcomes.
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Affiliation(s)
- Abebe Tarekegn Kassaw
- Department of Pharmacy, College of Health Science, Woldia University, Woldia, Ethiopia
| | - Tenaw Baye Tarekegn
- Department of Pharmacy, College of Health Science, Woldia University, Woldia, Ethiopia
| | | | - Getachew Ashagrie
- Department of Pharmacy, College of Health Science, Woldia University, Woldia, Ethiopia
| | - Fentaw Girmaw
- Department of Pharmacy, College of Health Science, Woldia University, Woldia, Ethiopia
| | - Ayelgn Mengesha
- Department of Adult Health Nursing, School of Nursing, College of Health Science, Woldia University, Woldia, Ethiopia
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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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Niu B, Ma L, Yao L, Zhang Y, Su H. HCV affects K ATP channels through GnT-IVa-mediated N-glycosylation of GLUT2 on the surface of pancreatic β-cells leading to impaired insulin secretion. Endocrine 2024; 84:427-440. [PMID: 37962815 PMCID: PMC11076383 DOI: 10.1007/s12020-023-03589-z] [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: 07/03/2023] [Accepted: 10/29/2023] [Indexed: 11/15/2023]
Abstract
PURPOSE To explore the mechanism of insulin secretion dysfunction in pancreatic beta cells induced by N-glycosylation mediated by an infection from the hepatitis C virus (HCV). METHODS Min6 cell models infected with HCV and stimulated with glucose were constructed. Meanwhile, an HCV-infected animal model and a type 2 diabetes mellitus (T2DM) rat model were constructed. Glucose uptake in the Min6 cells was detected, and insulin secretion was detected by ELISA. Flow cytometry, immunofluorescence staining, Western blotting, RT-qPCR, and lectin blotting were used to detect the expression levels of related proteins and mRNA, as well as the level of N-glycosylation. HE staining was used to observe the pathological changes in the pancreatic tissue, and an oral glucose tolerance test (OGTT) was used to evaluate the glucose tolerance of the rats. RESULTS Compared with the NC group, the expression levels of GnT-IVa, GLUT2, galectin-9, and voltage-dependent calcium channel 1.2 (Cav1.2) were significantly downregulated in the HCV-infected group. The ATP-sensitive potassium channel (KATP) component proteins SUR1 and Kir6.2 were significantly upregulated, while intracellular glucose intake and insulin secretion decreased, N-glycosylation levels and ATP levels significantly decreased, and the overexpression of GnT-IVa reversed the effect of the HCV infection. However, treatment with the glycosylation inhibitor kifunensine (KIF) or the KATP channel activator diazine (Dia) reversed the effects of the overexpression of GnT-IVa. In the animal experiments, HE staining revealed serious pathological injuries in the pancreatic tissue of the HCV-infected rats, with decreased glucose tolerance and glycosylation levels, decreased insulin secretion, downregulated expression of GnT-IVa, GLUT2, and Cav1.2, and upregulated expression of SUR1 and Kir6.2. The overexpression treatment of GnT-IVa or the KATP channel antagonist miglinide reversed the effects of HCV. CONCLUSION HCV infection inhibits GLUT2 N-glycosylation on the pancreatic β cell surface by downregulating the expression of GnT-IVa and then activates the KATP pathway, which ultimately leads to disturbances in insulin secretion.
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Affiliation(s)
- Ben Niu
- Department of Endocrinology and Metabolism, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650032, Yunnan, China
| | - Lijing Ma
- Department of Endocrinology and Metabolism, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650032, Yunnan, China
| | - Lixuan Yao
- Department of Nephrology, Bao Ji People's Hospital, Baoji, 721000, Shaanxi, China
| | - Yating Zhang
- Department of Endocrinology and Metabolism, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650032, Yunnan, China
| | - Heng Su
- Department of Endocrinology and Metabolism, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650032, Yunnan, China.
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Marzaban RN, AlMekhzangy HI, ElAkel W, ElBaz TM, ElShazly YM, ElSaeed K, Anees M, Said M, ElSerafy MA, Esmat GG, Doss WH. Diabetic patients with chronic hepatitis C virus response compared to non diabetics when treated with directly acting antiviral therapy. Arab J Gastroenterol 2024; 25:118-124. [PMID: 38378359 DOI: 10.1016/j.ajg.2023.12.006] [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: 03/31/2022] [Revised: 11/30/2023] [Accepted: 12/30/2023] [Indexed: 02/22/2024]
Abstract
BACKGROUND AND STUDY AIMS Hepatitis C virus (HCV) impairs glucose homoestasis, thus influences its clinical picture and prognosis. This study aimed at evaluating Diabetes mellitus (DM) on Egyptian patients with chronic hepatitis C (CHC), and its impact on their virologic response when treated with directly acting antiviral (DAA) medications. PATIENTS AND METHODS Adult patients with CHC were divided into 2 groups; Diabetic patients, and Non diabetic patients serving as control group. All patients were subjected to thorough clinical evaluation, basic biochemical laboratory tests including fasting blood glucose/glycosylated haemoglobin (HbA1C), and virologic assay. They were treated with various combined DAAs, and were monitored during, at and after end of treatment. RESULTS Diabetic patients constituted 9.85 % of CHC, and had generally worse laboratory tests (significantly higher transaminases, platelet count, Fib4 and hepatic steatosis) than non diabetic patients, and a less sustained virologic response (SVR) (significantly in Sofosbuvir (SOF) + pegylated interferon (PegIFN) + ribavirin (RBV), SOF + RBV, SOF + daclatasvir (DAC)). Although DM did not play a significant influence on SVR, yet Fib4 and SOF + RBV + PEG-IFN were significant factors affecting SVR among diabetics, while female gender and viraemia were significant factors affecting SVR among non diabetics. Hepatic fibrosis and SOF/RBV significantly influenced SVR in both groups. CONCLUSIONS Diabetic patients with CHC have worse liver biochemical profile, yet DM per se did not influence the virologic response to DAAs, however, some factors played roles in affecting SVR among them.
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Affiliation(s)
- Raghda N Marzaban
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Egypt.
| | | | - Wafaa ElAkel
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Egypt.
| | - Tamer M ElBaz
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Egypt
| | - Yehia M ElShazly
- Internal Medicine, Faculty of Medicine, Ain Shams University, Egypt
| | - Kadry ElSaeed
- Tropical Medicine, Faculty of Medicine, Ain Shams University, Egypt
| | - Mahmoud Anees
- Tropical Medicine, Faculty of Medicine, Tanta University, Egypt
| | - Mohamed Said
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Egypt
| | - Magdy A ElSerafy
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Egypt
| | - Gamal G Esmat
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Egypt.
| | - Wahid H Doss
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Egypt
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Ben Nasr M, D’Addio F, Montefusco L, Usuelli V, Loretelli C, Rossi A, Pastore I, Abdelsalam A, Maestroni A, Dell’Acqua M, Ippolito E, Assi E, Seelam AJ, Fiorina RM, Chebat E, Morpurgo P, Lunati ME, Bolla AM, Abdi R, Bonventre JV, Rusconi S, Riva A, Corradi D, Santus P, Clark P, Nebuloni M, Baldi G, Finzi G, Folli F, Zuccotti GV, Galli M, Herold KC, Fiorina P. Indirect and Direct Effects of SARS-CoV-2 on Human Pancreatic Islets. Diabetes 2022; 71:1579-1590. [PMID: 35499468 PMCID: PMC9490452 DOI: 10.2337/db21-0926] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Accepted: 04/04/2022] [Indexed: 01/08/2023]
Abstract
Recent studies have shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may induce metabolic distress, leading to hyperglycemia in patients affected by coronavirus disease 19 (COVID-19). We investigated the potential indirect and direct effects of SARS-CoV-2 on human pancreatic islets in 10 patients who became hyperglycemic after COVID-19. Although there was no evidence of peripheral anti-islet autoimmunity, the serum of these patients displayed toxicity on human pancreatic islets, which could be abrogated by the use of anti-interleukin-1β (IL-1β), anti-IL-6, and anti-tumor necrosis factor α, cytokines known to be highly upregulated during COVID-19. Interestingly, the receptors of those aforementioned cytokines were highly expressed on human pancreatic islets. An increase in peripheral unmethylated INS DNA, a marker of cell death, was evident in several patients with COVID-19. Pathology of the pancreas from deceased hyperglycemic patients who had COVID-19 revealed mild lymphocytic infiltration of pancreatic islets and pancreatic lymph nodes. Moreover, SARS-CoV-2-specific viral RNA, along with the presence of several immature insulin granules or proinsulin, was detected in postmortem pancreatic tissues, suggestive of β-cell-altered proinsulin processing, as well as β-cell degeneration and hyperstimulation. These data demonstrate that SARS-CoV-2 may negatively affect human pancreatic islet function and survival by creating inflammatory conditions, possibly with a direct tropism, which may in turn lead to metabolic abnormalities observed in patients with COVID-19.
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Affiliation(s)
- Moufida Ben Nasr
- International Center for Type 1 Diabetes, Pediatric Clinical Research Center Romeo and Enrica Invernizzi, Dipartimento di Scienze Biomediche e Cliniche (DIBIC), Università di Milano, Milan, Italy
- Nephrology Division, Boston Children’s Hospital, Harvard Medical School, Boston, MA
| | - Francesca D’Addio
- International Center for Type 1 Diabetes, Pediatric Clinical Research Center Romeo and Enrica Invernizzi, Dipartimento di Scienze Biomediche e Cliniche (DIBIC), Università di Milano, Milan, Italy
- Division of Endocrinology, Azienda Socio-Sanitaria Territoriale (ASST) Fatebenefratelli-Sacco, Milan, Italy
| | - Laura Montefusco
- International Center for Type 1 Diabetes, Pediatric Clinical Research Center Romeo and Enrica Invernizzi, Dipartimento di Scienze Biomediche e Cliniche (DIBIC), Università di Milano, Milan, Italy
| | - Vera Usuelli
- International Center for Type 1 Diabetes, Pediatric Clinical Research Center Romeo and Enrica Invernizzi, Dipartimento di Scienze Biomediche e Cliniche (DIBIC), Università di Milano, Milan, Italy
| | - Cristian Loretelli
- International Center for Type 1 Diabetes, Pediatric Clinical Research Center Romeo and Enrica Invernizzi, Dipartimento di Scienze Biomediche e Cliniche (DIBIC), Università di Milano, Milan, Italy
| | - Antonio Rossi
- Division of Endocrinology, Azienda Socio-Sanitaria Territoriale (ASST) Fatebenefratelli-Sacco, Milan, Italy
| | - Ida Pastore
- Division of Endocrinology, Azienda Socio-Sanitaria Territoriale (ASST) Fatebenefratelli-Sacco, Milan, Italy
| | - Ahmed Abdelsalam
- International Center for Type 1 Diabetes, Pediatric Clinical Research Center Romeo and Enrica Invernizzi, Dipartimento di Scienze Biomediche e Cliniche (DIBIC), Università di Milano, Milan, Italy
| | - Anna Maestroni
- International Center for Type 1 Diabetes, Pediatric Clinical Research Center Romeo and Enrica Invernizzi, Dipartimento di Scienze Biomediche e Cliniche (DIBIC), Università di Milano, Milan, Italy
| | - Marco Dell’Acqua
- International Center for Type 1 Diabetes, Pediatric Clinical Research Center Romeo and Enrica Invernizzi, Dipartimento di Scienze Biomediche e Cliniche (DIBIC), Università di Milano, Milan, Italy
- Division of Endocrinology, Azienda Socio-Sanitaria Territoriale (ASST) Fatebenefratelli-Sacco, Milan, Italy
| | - Elio Ippolito
- International Center for Type 1 Diabetes, Pediatric Clinical Research Center Romeo and Enrica Invernizzi, Dipartimento di Scienze Biomediche e Cliniche (DIBIC), Università di Milano, Milan, Italy
| | - Emma Assi
- International Center for Type 1 Diabetes, Pediatric Clinical Research Center Romeo and Enrica Invernizzi, Dipartimento di Scienze Biomediche e Cliniche (DIBIC), Università di Milano, Milan, Italy
| | - Andy Joe Seelam
- International Center for Type 1 Diabetes, Pediatric Clinical Research Center Romeo and Enrica Invernizzi, Dipartimento di Scienze Biomediche e Cliniche (DIBIC), Università di Milano, Milan, Italy
| | - Roberta Maria Fiorina
- International Center for Type 1 Diabetes, Pediatric Clinical Research Center Romeo and Enrica Invernizzi, Dipartimento di Scienze Biomediche e Cliniche (DIBIC), Università di Milano, Milan, Italy
| | - Enrica Chebat
- Division of Endocrinology, Azienda Socio-Sanitaria Territoriale (ASST) Fatebenefratelli-Sacco, Milan, Italy
| | - Paola Morpurgo
- Division of Endocrinology, Azienda Socio-Sanitaria Territoriale (ASST) Fatebenefratelli-Sacco, Milan, Italy
| | - Maria Elena Lunati
- Division of Endocrinology, Azienda Socio-Sanitaria Territoriale (ASST) Fatebenefratelli-Sacco, Milan, Italy
| | - Andrea Mario Bolla
- Division of Endocrinology, Azienda Socio-Sanitaria Territoriale (ASST) Fatebenefratelli-Sacco, Milan, Italy
| | - Reza Abdi
- Transplantation Research Center and Nephrology Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
| | - Joseph V. Bonventre
- Transplantation Research Center and Nephrology Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
| | - Stefano Rusconi
- Infectious Diseases Unit, ASST Fatebenefratelli-Sacco, Milan, Italy
| | - Agostino Riva
- Infectious Diseases Unit, ASST Fatebenefratelli-Sacco, Milan, Italy
| | - Domenico Corradi
- Unit of Pathology, Department of Biomedical, Biotechnological and Translational Sciences, University of Parma, Parma, Italy
| | - Pierachille Santus
- Division of Respiratory Diseases, ASST Fatebenefratelli-Sacco, Milan, Italy
- Department of Biomedical and Clinical Sciences, DIBIC, Università di Milano, Milan, Italy
| | - Pamela Clark
- Departments of Immunobiology and Internal Medicine, Yale University, New Haven, CT
| | - Manuela Nebuloni
- Department of Biomedical and Clinical Sciences, DIBIC, Università di Milano, Milan, Italy
- Department of Pathology, ASST Fatebenefratelli-Sacco, Milan, Italy
| | - Gabriella Baldi
- Endocrinology Laboratory, ASST Fatebenefratelli-Sacco, Milan, Italy
| | - Giovanna Finzi
- Department of Pathology, University Hospital ASST-Settelaghi, Varese, Italy
| | - Franco Folli
- Endocrinology and Metabolism, Department of Health Science, Università di Milano, ASST Santi Paolo e Carlo, Milan, Italy
| | | | - Massimo Galli
- Infectious Diseases Unit, ASST Fatebenefratelli-Sacco, Milan, Italy
| | - Kevan C. Herold
- Departments of Immunobiology and Internal Medicine, Yale University, New Haven, CT
| | - Paolo Fiorina
- International Center for Type 1 Diabetes, Pediatric Clinical Research Center Romeo and Enrica Invernizzi, Dipartimento di Scienze Biomediche e Cliniche (DIBIC), Università di Milano, Milan, Italy
- Nephrology Division, Boston Children’s Hospital, Harvard Medical School, Boston, MA
- Division of Endocrinology, Azienda Socio-Sanitaria Territoriale (ASST) Fatebenefratelli-Sacco, Milan, Italy
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De Sanctis V, Soliman A, Tzoulis P, Daar S, Pozzobon GC, Kattamis C. A study of isolated hyperglycemia (blood glucose ≥155 mg/dL) at 1-hour of oral glucose tolerance test (OGTT) in patients with β-transfusion dependent thalassemia (β-TDT) followed for 12 years. ACTA BIO-MEDICA : ATENEI PARMENSIS 2021; 92:e2021322. [PMID: 34487089 PMCID: PMC8477110 DOI: 10.23750/abm.v92i4.11105] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Accepted: 12/11/2020] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Subjects with normal glucose tolerance (NGT) but 1-hour post-load plasma glucose (1-h OGTT) ≥ 155 mg/dl (8.6 mmol/L; H-NGT) have an increased risk for developing Type 2 diabetes mellitus (T2DM), determining a new risk factor category with deeper metabolic impairment. The aim of this study was to evaluate the H-NGT as a diagnostic predictor of future dysglycemia in β-transfusion dependent thalassemia (β-TDT). Indices of insulin secretion and insulin sensitivity derived at baseline from OGTTs, were also reviewed. STUDY DESIGN AND METHODS OGTT and indices of insulin secretion and insulin sensitivity, derived at baseline during OGTT, in 17 β-TDT with H-NGT and 29 β-TDT with normal OGTT (NGT) and without H-NGT followed for 12 years were studied. RESULTS H-NGT was associated with decreased insulin sensitivity and progressive deterioration of glucose tolerance. At baseline, serum ferritin and serum alanine aminotransferase (ALT) levels were higher in patients with H-NGT compared to patients with NGT. A strong correlation was observed between ALT and 1-hour plasma glucose value during OGTT in the total group of 36 patients . Compliance to iron chelation therapy was poor in β-TDT patients with H-NGT. An inverse correlation was found between 1-hour plasma glucose value during OGTT and insulin secretion-sensitivity index-2 (ISSI-2) (r: -0.3298; p: 0.025), between ISSI-2 and ALT (r: -0.3262; p: 0.027), and between 1-hour plasma glucose value and ISSI-2 (r: -0.537; p: 0.005) in the whole group of β-TDT patients enrolled in our study. CONCLUSIONS This retrospective study displayed that finding an isolated high 1-hour post-load glucose level (≥155 mg/dL; H-NGT) during the OGTT may serve as a simple biomarker to detect high-risk patients, with chronic liver disease and/or iron overload, who need periodic glycemic surveillance. Measuring the ISSI 2 represented another valuable predictive marker in the assessment of glycemia in these patients.
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Affiliation(s)
| | - Ashraf Soliman
- Department of Pediatrics, Division of Endocrinology, Hamad General Hospital, Doha, Qatar and Department of Pediatrics, Division of Endocrinology, Alexandria University Children's Hospital, Alexandria, Egypt.
| | - Ploutarchos Tzoulis
- Department of Diabetes & Endocrinology, Whittington Hospital, University College London, London, UK.
| | - Shahina Daar
- Department of Haematology, College of Medicine and Health Sciences, Sultan Qaboos University, Sultanate of Oman.
| | | | - Christos Kattamis
- First Department of Paediatrics, National Kapodistrian University of Athens, Greece..
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Changes of Gut-Microbiota-Liver Axis in Hepatitis C Virus Infection. BIOLOGY 2021; 10:biology10010055. [PMID: 33451143 PMCID: PMC7828638 DOI: 10.3390/biology10010055] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Revised: 01/02/2021] [Accepted: 01/08/2021] [Indexed: 12/12/2022]
Abstract
Simple Summary Gut microbiota alteration is linked to many health disorders including hepatitis C virus (HCV) infection. This dysbiosis in turn impacts the coordination between the gut and the liver that is known as the gut–liver-axis. Here, we discuss the latest findings regarding the changes in gut microbiota structure and functionality post HCV infection and its treatment regimens. In addition, we underline the contribution of the microbiota alterations to HCV associated liver complications. Abstract The gut–liver-axis is a bidirectional coordination between the gut, including microbial residents, the gut microbiota, from one side and the liver on the other side. Any disturbance in this crosstalk may lead to a disease status that impacts the functionality of both the gut and the liver. A major cause of liver disorders is hepatitis C virus (HCV) infection that has been illustrated to be associated with gut microbiota dysbiosis at different stages of the disease progression. This dysbiosis may start a cycle of inflammation and metabolic disturbance that impacts the gut and liver health and contributes to the disease progression. This review discusses the latest literature addressing this interplay between the gut microbiota and the liver in HCV infection from both directions. Additionally, we highlight the contribution of gut microbiota to the metabolism of antivirals used in HCV treatment regimens and the impact of these medications on the microbiota composition. This review sheds light on the potential of the gut microbiota manipulation as an alternative therapeutic approach to control the liver complications post HCV infection.
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Impaired insulin exocytosis in chronic hepatitis C infection: contributory role of p38δ MAPK-protein kinase D-golgi complex axis. Clin Sci (Lond) 2020; 134:1449-1456. [PMID: 32556178 DOI: 10.1042/cs20200686] [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: 05/23/2020] [Revised: 05/31/2020] [Accepted: 06/03/2020] [Indexed: 11/17/2022]
Abstract
Hepatitis C virus (HCV) infection and chronic hepatitis C (CHC) are associated with a measurable risk of insulin resistance (IR)/impaired glucose tolerance (IGT)/diabetes mellitus (DM). While loss of hepatic endocrine function contributes to liver cirrhosis in diabetic patients, onset and progression of IR/IGT to diabetes and exacerbation of incident hyperglycemia are ostensibly linked with chronic HCV infection. In this regard, the study by Chen J et al. appearing in Clinical Science (2020) (134(5) https://doi.org/10.1042/CS20190900) attempts to understand the mechanisms underlying the savaging effects of chronic HCV infection on insulin-producing pancreatic β-cells and hence diabetic onset. The study investigated the role of mitogen-activated protein kinase (MAPK) p38δ-protein kinase D (PKD)-golgi complex axis in impacting insulin exocytosis. It was inferred that an insulin secretory defect of pancreatic β-cells, owing to disrupted insulin exocytosis, to an extent explains β-cell dysfunction in HCV-infected or CHC milieu. HCV infection negatively regulates first-phase and second-phase insulin secretion by impinging on PKD-dependent insulin secretory granule fission at trans-golgi network and insulin secretory vesicle membrane fusion events. This commentary highlights the study in question, that deciphered the contribution of p38δ MAPK-PKD-golgi complex axis to β-cell dysfunction in CHC milieu. This pivotal axis proffers a formidable therapeutic opportunity for alleviation of double burden of glucose abnormalities/DM and CHC.
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11
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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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12
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Elhendawy M, Abo-Ali L, Abd-Elsalam S, Hagras MM, Kabbash I, Mansour L, Atia S, Esmat G, Abo-ElAzm AR, El-Kalla F, Kobtan A. HCV and HEV: two players in an Egyptian village, a study of prevalence, incidence, and co-infection. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2020; 27:33659-33667. [PMID: 32533486 PMCID: PMC7292573 DOI: 10.1007/s11356-020-09591-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/07/2020] [Accepted: 06/01/2020] [Indexed: 05/04/2023]
Abstract
The highest recorded hepatitis C virus (HCV) prevalence worldwide is in Egypt. A high prevalence of hepatitis E virus (HEV) in chronic liver disease has been reported. The aim of this study was to study prevalence, incidence, and outcome of HCV infection in an Egyptian Nile Delta village and the relation between HEV infection and HCV-related chronic hepatic affection. This prospective cohort study included 2085 Nagreej village residents. Mass HCV screening was conducted and testing for HEV antibodies among HCV-infected patients performed. The annual incidence of HCV was recorded. Five hundred five (24.22%) of the tested villagers were positive for HCV RNA. Prevalence escalated with age and male sex. The main recorded risk factors were a history of surgery, dental procedures, hospitalization, blood transfusion, and antischistosomal treatment. HEV IgG antibody was positive in 71.4% of individuals with chronic HCV and 96.1% with advanced liver disease (cirrhosis ± hepatocellular carcinoma (HCC)). After 1 year, 29 of the 1390 HCV Ab negative villagers had a positive HCV PCR, placing an annual incidence of new HCV infections at 2.09%. The Egyptian HCV prevalence remains high with infection particularly among the elderly. The annual incidence in a small Nile Delta village is 2.086%. HCV-HEV co-infection may lead to a worse prognosis among Egyptians with chronic liver disease.
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Affiliation(s)
- Mohammed Elhendawy
- Tropical Medicine Department, Faculty of Medicine, Tanta University Hospital, Tanta University, El Geish Street, Tanta, Gharbia Governorate, Egypt
| | - Lobna Abo-Ali
- Tropical Medicine Department, Faculty of Medicine, Tanta University Hospital, Tanta University, El Geish Street, Tanta, Gharbia Governorate, Egypt
| | - Sherief Abd-Elsalam
- Tropical Medicine Department, Faculty of Medicine, Tanta University Hospital, Tanta University, El Geish Street, Tanta, Gharbia Governorate, Egypt.
| | - Maha M Hagras
- Clinical Pathology Department, Tanta University, Tanta, Egypt
| | - Ibrahim Kabbash
- Public Health and Community Medicine, Tanta University, Tanta, Egypt
| | - Loai Mansour
- Tropical Medicine Department, Faculty of Medicine, Tanta University Hospital, Tanta University, El Geish Street, Tanta, Gharbia Governorate, Egypt
| | - Sherief Atia
- Kafr El Sheikh Liver Institute, Kafr El Sheikh, Egypt
| | - Gamal Esmat
- Tropical Medicine Department, Cairo University, Cairo, Egypt
| | - Abdel-Raouf Abo-ElAzm
- Tropical Medicine Department, Faculty of Medicine, Tanta University Hospital, Tanta University, El Geish Street, Tanta, Gharbia Governorate, Egypt
| | - Ferial El-Kalla
- Tropical Medicine Department, Faculty of Medicine, Tanta University Hospital, Tanta University, El Geish Street, Tanta, Gharbia Governorate, Egypt
| | - Abdelrahman Kobtan
- Tropical Medicine Department, Faculty of Medicine, Tanta University Hospital, Tanta University, El Geish Street, Tanta, Gharbia Governorate, Egypt
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13
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Chronic hepatitis C virus infection impairs insulin secretion by regulation of p38δ MAPK-dependent exocytosis in pancreatic β-cells. Clin Sci (Lond) 2020; 134:529-542. [PMID: 32100852 DOI: 10.1042/cs20190900] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Revised: 02/13/2020] [Accepted: 02/26/2020] [Indexed: 12/12/2022]
Abstract
Chronic hepatitis C virus (HCV) infection has a close association with type 2 diabetes mellitus. Although the mechanisms of insulin resistance in chronic hepatitis C (CHC) patients have been extensively studied, little attention has been given to the role of β-cell function in HCV-associated diabetes. Here, we analysed β-cell function in CHC patients and HCV-infected mouse model and found in addition to insulin resistance, impaired pancreatic β-cell function occurred in CHC patients and HCV-infected C/OTg mice, not only in diabetic individuals but also in individuals with impaired fasting glucose levels. Both first-phase and second-phase insulin secretion were impaired, at least partially due to the reduction of exocytosis of secretory insulin-containing granules following HCV infection. Up-regulated p38δ in HCV-infected β-cells resulted in inactivation of protein kinase D (PKD), which was responsible for impaired insulin secretory capacity of β-cells. Thus, impaired insulin secretion due to HCV infection in β-cells contributes to HCV-associated type 2 diabetes. These findings provided a new inspiration for the important prognostic and therapeutic implications in the management of CHC patients with impaired fasting glucose.
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Wang Q, Wei S, Zhou S, Qiu J, Shi C, Liu R, Zhou H, Lu L. Hyperglycemia aggravates acute liver injury by promoting liver-resident macrophage NLRP3 inflammasome activation via the inhibition of AMPK/mTOR-mediated autophagy induction. Immunol Cell Biol 2019; 98:54-66. [PMID: 31625631 PMCID: PMC7004066 DOI: 10.1111/imcb.12297] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2019] [Revised: 09/08/2019] [Accepted: 10/15/2019] [Indexed: 12/14/2022]
Abstract
Although the detrimental effects of diabetes mellitus/hyperglycemia have been observed in many liver disease models, the function and mechanism of hyperglycemia regulating liver‐resident macrophages, Kupffer cells (KCs), in thioacetamide (TAA)‐induced liver injury remain largely unknown. In this study, we evaluated the role of hyperglycemia in regulating NOD‐like receptor family pyrin domain‐containing 3 protein (NLRP3) inflammasome activation by inhibiting autophagy induction in KCs in the TAA‐induced liver injury model. Type I diabetes/hyperglycemia was induced by streptozotocin treatment. Compared with the control group, hyperglycemic mice exhibited a significant increase in intrahepatic inflammation and liver injury. Enhanced NLRP3 inflammasome activation was detected in KCs from hyperglycemic mice, as shown by increased gene induction and protein levels of NLRP3, cleaved caspase‐1, apoptosis‐associated speck‐like protein containing a caspase recruitment domain and interleukin‐1β, compared with control mice. NLRP3 inhibition by its antagonist CY‐09 effectively suppressed inflammasome activation in KCs and attenuated liver injury in hyperglycemic mice. Furthermore, inhibited autophagy activation was revealed by transmission electron microscope detection, decreased LC3B protein expression and p‐62 protein degradation in KCs isolated from TAA‐stressed hyperglycemic mice. Interestingly, inhibited 5′ AMP‐activated protein kinase (AMPK) but enhanced mammalian target of rapamycin (mTOR) activation was found in KCs from TAA‐stressed hyperglycemic mice. AMPK activation by its agonist 5‐aminoimidazole‐4‐carboxamide ribonucleotide (AICAR) or mTOR signaling knockdown by small interfering RNA restored autophagy activation, and subsequently, inhibited NLRP3 inflammasome activation in KCs, leading to ultimately reduced TAA‐induced liver injury in the hyperglycemic mice. Our findings demonstrated that hyperglycemia aggravated TAA‐induced acute liver injury by promoting liver‐resident macrophage NLRP3 inflammasome activation via inhibiting AMPK/mTOR‐mediated autophagy. This study provided a novel target for prevention of toxin‐induced acute liver injury under hyperglycemia.
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Affiliation(s)
- Qi Wang
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Nanjing, China.,Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China.,NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing, China
| | - Song Wei
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Nanjing, China.,Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China.,NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing, China.,School of Medical, Southeast University, Nanjing, China
| | - Shun Zhou
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Nanjing, China.,Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China.,NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing, China
| | - Jiannan Qiu
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Nanjing, China.,Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China.,NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing, China
| | - Chenyu Shi
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Nanjing, China.,Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China.,NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing, China
| | - Rui Liu
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Nanjing, China.,Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China.,NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing, China
| | - Haoming Zhou
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Nanjing, China.,Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China.,NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing, China
| | - Ling Lu
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Nanjing, China.,Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China.,NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing, China.,School of Medical, Southeast University, Nanjing, China
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Muñoz Díaz HA, Lúquez Mindiola AJ, Gómez Aldana AJ. Fisiopatología de la hepatitis C y diabetes mellitus. Hacia la cura de dos epidemias en el siglo XXI. REVISTA COLOMBIANA DE GASTROENTEROLOGÍA 2019; 34:277-287. [DOI: 10.22516/25007440.322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/01/2024]
Abstract
La infección crónica por virus de la hepatitis C (VHC) y la diabetes mellitus (DM) son dos problemas de salud pública que impactan los sistemas de salud, con una alta carga económica global. La infección por VHC produce manifestaciones hepáticas tales como hepatitis, cirrosis y carcinoma hepatocelular; asimismo, se ha involucrado en la patogénesis de manifestaciones extrahepáticas, entre las cuales se ha asociado con alteraciones metabólicas como la DM. Estudios longitudinales y transversales han reportado mayor incidencia y prevalencia de DM en pacientes con infección crónica por VHC. La DM acelera la progresión histológica y clínica en pacientes con infección crónica por VHC y las complicaciones cardiovasculares. Recientemente se ha avanzado en el tratamiento y la introducción de nuevos medicamentos como los antivirales de acción directa, que mejoran el control glucémico en estos pacientes.
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Lee WG, Wells CI, McCall JL, Murphy R, Plank LD. Prevalence of diabetes in liver cirrhosis: A systematic review and meta-analysis. Diabetes Metab Res Rev 2019; 35:e3157. [PMID: 30901133 DOI: 10.1002/dmrr.3157] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2018] [Revised: 03/05/2019] [Accepted: 03/19/2019] [Indexed: 12/20/2022]
Abstract
An association between diabetes mellitus (DM) and liver cirrhosis is well-known, but estimates of the prevalence of DM in patients with liver cirrhosis vary widely. A systematic review was undertaken to determine the prevalence of DM in adult patients with liver cirrhosis. The Medline, EMBASE, and Cochrane Library databases were searched for peer-reviewed studies published in English (1979-2017) that investigated the prevalence of diabetes in adult patients with cirrhosis. Pooled estimates of prevalence of DM were determined for all eligible patients and according to aetiology and severity of liver disease. Fifty-eight studies satisfied criteria for inclusion, with 9705 patients included in the pooled prevalence analysis. The overall prevalence of DM was 31%. The prevalence of DM was highest in patients with nonalcoholic fatty liver disease (56%), cryptogenic (51%), hepatitis C (32%), or alcoholic (27%) cirrhosis. For assessing prevalence of DM as a function of severity of liver disease, evaluable data were available only for hepatitis C and hepatitis B cirrhosis. DM may be more prevalent in cirrhosis than previously thought. This has implications for prognosis and treatment in these patients.
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Affiliation(s)
- Wai Gin Lee
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Cameron I Wells
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - John L McCall
- Section of Surgery, Department of Medical and Surgical Sciences, University of Otago, Dunedin, New Zealand
| | - Rinki Murphy
- Department of Medicine, University of Auckland, Auckland, New Zealand
| | - Lindsay D Plank
- Department of Surgery, University of Auckland, Auckland, New Zealand
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Amjo OO, Soyoye DO, Amjo I, Yusuff OT, Kolawole BA, Ikem RT, Adekanle O, Ndububa DA. Insulin resistance and plasma glucose tolerance abnormalities in Nigerians with chronic liver disease. Diabetes Metab Syndr 2019; 13:2208-2213. [PMID: 31235158 DOI: 10.1016/j.dsx.2019.05.014] [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: 05/15/2019] [Accepted: 05/21/2019] [Indexed: 02/07/2023]
Abstract
AIMS Glucose tolerance abnormalities are frequently observed in patients with chronic liver disease (CLD). Insulin resistance (IR) has been suggested to be a major factor responsible for these abnormalities in CLD. However studies relating IR with severity of CLD are scarce in Nigeria. This study assessed insulin resistance and glucose tolerance abnormalities in CLD and their relationship with the severity of CLD in a tertiary hospital in South-West, Nigeria. METHODS This cross sectional study involved 100 subjects with CLD. Ethical clearance was obtained and informed consent was granted by participants. Participants were interviewed using a structured proforma; physical examination and relevant investigations were performed. Insulin resistance was measured using the homeostasis model assessment (HOMA-IR) Data was analysed using Statistical Package for Social Sciences version 20.0 and p value of <0.05 was considered significant. RESULTS Mean age of the study participants was 51.9 ± 11.9 years, and mean duration of CLD was 15.9 ± 5.8 months. Glucose tolerance abnormalities were present in 66 subjects (66%) and increased from 16.1% in Child Pugh's class A to 90.0% in class C. HOMA-IR positively correlated with age, body mass index, serum blood glucose, duration and severity of CLD. Increasing age, presence of hepatocellular carcinoma, Child Pugh's class B and class C were associated with glucose tolerance abnormalities. CONCLUSION Glucose tolerance abnormalities and insulin resistance were highly prevalent among chronic liver disease subjects studied and seemed to parallel the severity of CLD, determined by the Child Pugh's score.
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Affiliation(s)
- Oluwadamilola O Amjo
- Department of Medicine, Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria
| | - David O Soyoye
- Department of Medicine, Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria; Department of Medicine, Obafemi Awolowo University, Ile-Ife, Nigeria.
| | - Ifeoluwa Amjo
- Department of Medicine, Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria
| | - Olaoluwatomi T Yusuff
- Department of Medicine, Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria
| | - Babatope A Kolawole
- Department of Medicine, Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria; Department of Medicine, Obafemi Awolowo University, Ile-Ife, Nigeria
| | - Rosemary T Ikem
- Department of Medicine, Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria; Department of Medicine, Obafemi Awolowo University, Ile-Ife, Nigeria
| | - Olusegun Adekanle
- Department of Medicine, Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria; Department of Medicine, Obafemi Awolowo University, Ile-Ife, Nigeria
| | - Dennis A Ndububa
- Department of Medicine, Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria; Department of Medicine, Obafemi Awolowo University, Ile-Ife, Nigeria
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Grancini V, Resi V, Palmieri E, Pugliese G, Orsi E. Management of diabetes mellitus in patients undergoing liver transplantation. Pharmacol Res 2019; 141:556-573. [PMID: 30690071 DOI: 10.1016/j.phrs.2019.01.042] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2018] [Revised: 01/24/2019] [Accepted: 01/24/2019] [Indexed: 02/07/2023]
Abstract
Diabetes is a common feature in cirrhotic individuals both before and after liver transplantation and negatively affects prognosis. Certain aetiological agents of chronic liver disease and loss of liver function per se favour the occurrence of pre-transplant diabetes in susceptible individuals, whereas immunosuppressant treatment, changes in lifestyle habits, and donor- and procedure-related factors contribute to diabetes development/persistence after transplantation. Challenges in the management of pre-transplant diabetes include the profound nutritional alterations characterizing cirrhotic individuals and the limitations to the use of drugs with liver metabolism. Special issues in the management of post-transplant diabetes include the diabetogenic potential of immunosuppressant drugs and the increased cardiovascular risk characterizing solid organ transplant survivors. Overall, the pharmacological management of cirrhotic patients undergoing liver transplantation is complicated by the lack of specific guidelines reflecting the paucity of data on the impact of glycaemic control and the safety and efficacy of anti-hyperglycaemic agents in these individuals.
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Affiliation(s)
- Valeria Grancini
- Diabetes Service, Endocrinology and Metabolic Diseases Unit, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, and Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | - Veronica Resi
- Diabetes Service, Endocrinology and Metabolic Diseases Unit, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, and Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | - Eva Palmieri
- Diabetes Service, Endocrinology and Metabolic Diseases Unit, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, and Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | - Giuseppe Pugliese
- Department of Clinical and Molecular Medicine, "La Sapienza" University, and Diabetes Unit, Sant'Andrea University Hospital, Rome, Italy
| | - Emanuela Orsi
- Diabetes Service, Endocrinology and Metabolic Diseases Unit, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, and Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
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Nwose EU, Obianke J, Richards RS, Bwitit PT, Igumbor EO. Prevalence and correlations of hepatorenal functions in diabetes and cardiovascular disease among stratified adults. ACTA BIO-MEDICA : ATENEI PARMENSIS 2019; 90:97-103. [PMID: 30889161 PMCID: PMC6502162 DOI: 10.23750/abm.v90i1.6576] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/29/2017] [Accepted: 08/20/2018] [Indexed: 11/23/2022]
Abstract
BACKGROUND The vulnerability of older adults to diabetes and cardiovascular complications is a global concern. Hepatorenal pathophysiology is implicated in these complications, but has yet to be clearly established, especially from rural low-mid income countries. This study investigates differences in prevalence of diabetes in aging groups and correlations of age with hepatorenal variables. METHODS 203 participants of both sexes above the age of 18 years underwent anthropometric measurements at Catholic Hospital, Abbi, Nigeria. Questionnaires collected demographic information and medical history. Urinalysis as well as routine liver and renal function tests were performed. Data analysis included determination of levels of hepatorenal abnormalities and prevalence of diseases in age groups. Percentage of disease subpopulations made up by each age-group was also determined as well as Pearson's correlation coefficient between age and hepatorenal variables, and comparison of average age and hepatorenal variables in disease subgroups. RESULTS Percentage hepatorenal abnormalities are not significantly different between age-groups. There is no significant difference in percentage level of disease between groups, but in age-groups constituting disease sub-populations (p<0.00001). The apparently healthy subpopulation comprises of younger adults compared to older adults constituting diabetes and hypertension (p < 0…). Age shows moderate correlation with renal function parameters, especially urea and chloride (r = 0.42), but relatively insignificant with liver function variables. CONCLUSION This report affirms that diabetes cardiovascular co-morbidity comes with aging. It also indicates that renal pathophysiology may be more associated, than liver, functions in the vulnerability of adults.
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Fabiani S, Fallahi P, Ferrari SM, Miccoli M, Antonelli A. Hepatitis C virus infection and development of type 2 diabetes mellitus: Systematic review and meta-analysis of the literature. Rev Endocr Metab Disord 2018; 19:405-420. [PMID: 29322398 DOI: 10.1007/s11154-017-9440-1] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Type 2 diabetes mellitus (T2DM) is an endocrine disorder encompassing multifactorial mechanisms, and chronic hepatitis C virus infection (CHC) is a multifaceted disorder, associated with extrahepatic manifestations, including endocrinological disorders. CHC and T2DM are associated, but the subject remains controversial. We performed a systematic review and meta-analysis evaluating such association, searching on PubMed until February 29, 2016. Inclusion criteria were: 1) presence of at least one internal control group age- and gender-matched (non-hepatopathic controls; and/or hepatopathic, not HCV-positive, controls); 2) sufficient data to calculate odds ratio and relative risk. Exclusion criteria were: 1) literature reviews on the topic; 2) publications regarding special populations [human immunodeficiency virus and human T-lymphotropic virus-1 coinfections, hepatocellular carcinoma (HCC), post-transplantation DM, gender selection]; 3) no clear differentiation among HCV patients with CHC, cirrhosis or HCC. Data from each study were independently extracted by two reviewers and cross-checked by AA. Our systematic review returned 544 records, and 33 were included in our meta-analysis. HCV infection is associated with an increased risk of T2DM independently from the severity of the associated liver disease, in CHC and cirrhotic HCV patients. As expected T2DM risk is higher in cirrhotic HCV patients, than CHC, and the prevalence of HCV infection in T2DM patients is higher than in non-diabetic controls. Regarding HBV infection prevalence, no difference exists in diabetic and non-diabetic subjects. An unequivocal CHC and T2DM association was shown. A proactive, integrated approach to HCV and T2DM therapies should maximize benefits of both diseases treatment.
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Affiliation(s)
- Silvia Fabiani
- Department of Clinical and Experimental Medicine, School of Medicine, University of Pisa, Via Savi 10, I-56126, Pisa, Italy
| | - Poupak Fallahi
- Department of Clinical and Experimental Medicine, School of Medicine, University of Pisa, Via Savi 10, I-56126, Pisa, Italy
| | - Silvia Martina Ferrari
- Department of Clinical and Experimental Medicine, School of Medicine, University of Pisa, Via Savi 10, I-56126, Pisa, Italy
| | - Mario Miccoli
- Department of Clinical and Experimental Medicine, School of Medicine, University of Pisa, Via Savi 10, I-56126, Pisa, Italy
| | - Alessandro Antonelli
- Department of Clinical and Experimental Medicine, School of Medicine, University of Pisa, Via Savi 10, I-56126, Pisa, Italy.
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Abstract
In the past few years, a growing body of clinical evidence has highlighted the risk of vitamin D deficiency in patients with chronic hepatitis C and that vitamin D levels are associated with the course of hepatitis C virus (HCV) infection, adverse effects, and treatment response to peginterferon/ribavirin. Recently, studies have found that vitamin D status is related to drug resistance and increased risk of infection in patients with liver cirrhosis. Vitamin D-related gene polymorphisms have been found to explain the interactions between vitamin D deficiency and HCV infection, offering a new perspective toward understanding the current problems such as the development of insulin resistance and racial differences in sustained virological response. Studies have been conducted to determine whether vitamin D supplementation as an adjuvant yields a better result compared with traditional HCV treatment. Here, we provide a brief review of the past and present knowledge of vitamin D in HCV infection.
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22
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Castedal M, Skoglund C, Axelson C, Bennet W. Steroid-free immunosuppression with low-dose tacrolimus is safe and significantly reduces the incidence of new-onset diabetes mellitus following liver transplantation. Scand J Gastroenterol 2018; 53:741-747. [PMID: 29688072 DOI: 10.1080/00365521.2018.1463390] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES Corticosteroids (CS) are traditionally used as part of the basal immunosuppression (IS) following liver transplantation (LT) but are known to be associated with an increased risk of new-onset diabetes mellitus (NODM), cardiovascular morbidity and mortality. The aim of this study was to retrospectively compare the incidence of transient as well as persistent NODM, rejection rate and patient- and graft survival between patients receiving steroid-based and steroid-free maintenance IS. MATERIALS AND METHODS A total of 238 patients liver transplanted (2008-2011) with deceased donor livers were divided into two groups, one group that received steroid-based IS (tacrolimus (TAC), corticosteroids (CS), ± mycophenolate mofetil (MMF); n = 155) (2008-2011) and another group of non-autoimmune recipients that received steroid-free IS (TAC, MMF; n = 83) according to our new maintenance IS-protocol starting January 2010. The primary and secondary end-points were patient- and graft survival, rejection rates and the incidence of NODM. The median follow-up times were 1248 days and 681 days, respectively. RESULTS The one-year patient- and graft survival in the steroid-based and steroid-free group was 92.7% and 93.3% (ns) and 87.6% and 84.9% (ns), respectively. The incidence of biopsy proven acute rejection (BPAR) was 27.7% in both groups (ns) during follow-up. The overall incidence of persistent NODM in the two groups were 16.8% and 2.9%, respectively (p < .01). CONCLUSIONS The results show that steroid-free low-dose tacrolimus-based IS following LT is safe and decreases the incidence of NODM significantly.
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Affiliation(s)
- M Castedal
- a The Transplant Institute , Sahlgrenska University Hospital, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden
| | - C Skoglund
- a The Transplant Institute , Sahlgrenska University Hospital, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden
| | - C Axelson
- a The Transplant Institute , Sahlgrenska University Hospital, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden
| | - W Bennet
- a The Transplant Institute , Sahlgrenska University Hospital, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden
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23
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Campana B, Calabrese D, Matter MS, Terracciano LM, Wieland SF, Heim MH. In vivo analysis at the cellular level reveals similar steatosis induction in both hepatitis C virus genotype 1 and 3 infections. J Viral Hepat 2018; 25:262-271. [PMID: 29086446 DOI: 10.1111/jvh.12816] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2017] [Accepted: 09/26/2017] [Indexed: 12/12/2022]
Abstract
Steatosis is a frequent histological feature of hepatitis C virus (HCV) infection. Cohort studies of patients with chronic hepatitis C identified HCV genotype 3 (HCV GT3) as the prevalent steatotic genotype. Moreover, Huh-7 cells over-expressing HCV GT3 core protein accumulate more triglyceride in larger lipid droplets than cells expressing core proteins of other HCV genotypes. However, little is known about the relationship of steatosis and HCV infection at the cellular level in vivo. In this study, we used highly sensitive multiplex in situ hybridization methodology together with lipid staining to investigate HCV-induced lipid droplet accumulation at the cellular level in liver biopsies. Consistent with previous reports, histological steatosis grades were significantly higher in GT3 compared to GT1 infected livers, but independent of viral load. Using nile red lipid stainings, we observed that the frequency of lipid droplet containing cells was similar in HCV GT1- and HCV GT3-infected livers. Lipid droplet formation preferentially occurred in HCV-infected cells irrespective of the genotype, but was also observed in noninfected cells. These findings demonstrate that the main difference between GT1- and GT3-induced steatosis is the size of lipid droplets, but not the number or relative distribution of lipid droplets in infected vs uninfected hepatocytes.
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Affiliation(s)
- B Campana
- Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.,Division of Gastroenterology and Hepatology, University Hospital Basel, University of Basel, Basel, Switzerland
| | - D Calabrese
- Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - M S Matter
- Institute of Pathology, Molecular Pathology Division, University Hospital of Basel, University of Basel, Basel, Switzerland
| | - L M Terracciano
- Institute of Pathology, Molecular Pathology Division, University Hospital of Basel, University of Basel, Basel, Switzerland
| | - S F Wieland
- Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - M H Heim
- Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.,Division of Gastroenterology and Hepatology, University Hospital Basel, University of Basel, Basel, Switzerland
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24
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Ciancio A, Bosio R, Bo S, Pellegrini M, Sacco M, Vogliotti E, Fassio G, Bianco Mauthe Degerfeld AGF, Gallo M, Giordanino C, Terzi di Bergamo L, Ribaldone D, Bugianesi E, Smedile A, Rizzetto M, Saracco GM. Significant improvement of glycemic control in diabetic patients with HCV infection responding to direct-acting antiviral agents. J Med Virol 2017; 90:320-327. [DOI: 10.1002/jmv.24954] [Citation(s) in RCA: 75] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2017] [Accepted: 09/19/2017] [Indexed: 02/06/2023]
Affiliation(s)
- Alessia Ciancio
- Gastroenterology Unit; Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Roberta Bosio
- Gastroenterology Unit; San Luigi Hospital; University of Turin; Torino Italy
| | - Simona Bo
- Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Marianna Pellegrini
- Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Marco Sacco
- Gastroenterology Unit; Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Edoardo Vogliotti
- Gastroenterology Unit; Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Giulia Fassio
- Gastroenterology Unit; San Luigi Hospital; University of Turin; Torino Italy
| | | | - Monica Gallo
- Gastroenterology Unit; San Luigi Hospital; University of Turin; Torino Italy
| | - Chiara Giordanino
- Gastroenterology Unit; San Luigi Hospital; University of Turin; Torino Italy
| | - Lodovico Terzi di Bergamo
- Gastroenterology Unit; Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Davide Ribaldone
- Gastroenterology Unit; Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Elisabetta Bugianesi
- Gastroenterology Unit; Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Antonina Smedile
- Gastroenterology Unit; Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Mario Rizzetto
- Gastroenterology Unit; Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Giorgio Maria Saracco
- Gastroenterology Unit; Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
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25
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Bajaj S, Kashyap R, Srivastava A, Singh S. Metabolic Derangement in Acute and Chronic Liver Disorders. Indian J Endocrinol Metab 2017; 21:695-698. [PMID: 28989876 PMCID: PMC5628538 DOI: 10.4103/ijem.ijem_146_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
AIMS This study aims to assess glycemic and lipid derangement in acute and chronic liver disorders. MATERIALS AND METHODS A cross-sectional study was conducted on 104 patients diagnosed with acute or chronic liver disorder. Acute liver disease (ALD) patients were 40 and chronic liver disease (CLD) patients were 64. RESULTS The mean value of fasting plasma glucose (FPG) in patients with ALD was 91.8 ± 5.4 mg/dl and in CLD was 115.7 ± 17.9 mg/dl, the difference was significant. The mean value of A1c was 4.3 ± 0.6 in ALD and 6.1 ± 0.8 in CLD, the difference was significant. In patients with CLD mean cholesterol was higher 177.4 ± 28.8 mg/dl when compared to ALD 140 ± 35.1 mg/dl, but the difference was not significant. ALD patients' high-density lipoprotein (HDL) was 50.4 ± 5.1 mg/dl, and in CLD patients, HDL was 44.4 ± 6.1 mg/dl. In CLD mean triglyceride (T) was 148.9 ± 6.4 mg/dl while in ALD T was 134.8 ± 14.2 mg/dl, the difference was significant. CONCLUSIONS CLD is associated with glycemic derangement demonstrated by deranged FPG and A1c. In patients of ALD, no metabolic derangement was observed.
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Affiliation(s)
- Sarita Bajaj
- Department of Medicine, Motilal Nehru Medical College, Allahabad, Uttar Pradesh, India
| | - Richi Kashyap
- Department of Medicine, Motilal Nehru Medical College, Allahabad, Uttar Pradesh, India
| | - Anubha Srivastava
- Department of Medicine, Motilal Nehru Medical College, Allahabad, Uttar Pradesh, India
| | - Smriti Singh
- Department of Medicine, Motilal Nehru Medical College, Allahabad, Uttar Pradesh, India
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26
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Diabetes Among People With Tuberculosis, HIV Infection, Viral Hepatitis B and C, and STDs in New York City, 2006-2010. JOURNAL OF PUBLIC HEALTH MANAGEMENT AND PRACTICE 2017; 23:461-467. [PMID: 27997475 DOI: 10.1097/phh.0000000000000466] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Matching infectious disease surveillance data has become a routine activity for many health departments. With the increasing focus on chronic disease, it is also useful to explore opportunities to match infectious and chronic disease surveillance data. To understand the burden of diabetes in New York City (NYC), adults with select infectious diseases (tuberculosis, HIV infection, hepatitis B, hepatitis C, chlamydial infection, gonorrhea, and syphilis) reported between 2006 and 2010 were matched with hemoglobin A1c results reported in the same period. Persons were considered to have diabetes with 2 or more hemoglobin A1c test results of 6.5% or higher. The analysis was restricted to persons who were 18 years or older at the time of first report, either A1c or infectious disease. Overall age-adjusted diabetes prevalence was 8.1%, and diabetes prevalence was associated with increasing age; among NYC residents, prevalence ranged from 0.6% among 18- to 29-year-olds to 22.4% among those 65 years and older. This association was also observed in each infectious disease. Diabetes prevalence was significantly higher among persons with tuberculosis born in Mexico, Jamaica, Honduras, Guyana, Bangladesh, Dominican Republic, the Philippines, and Haiti compared with those born in the United States after adjusting for age and sex. Hepatitis C virus-infected women had higher age-adjusted prevalence of diabetes compared with the NYC population as a whole. Recognizing associations between diabetes and infectious diseases can assist early diagnosis and management of these conditions. Matching chronic disease and infectious disease surveillance data has important implications for local health departments and large health system practices, including increasing opportunities for integrated work both internal to systems and with the local community. Large health systems may consider opportunities for increased collaboration across infectious and chronic disease programs facilitated through data linkages of routinely collected surveillance data.
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27
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Orsi E, Grancini V, Menini S, Aghemo A, Pugliese G. Hepatogenous diabetes: Is it time to separate it from type 2 diabetes? Liver Int 2017; 37:950-962. [PMID: 27943508 DOI: 10.1111/liv.13337] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2016] [Accepted: 11/29/2016] [Indexed: 12/12/2022]
Abstract
By definition, hepatogenous diabetes is directly caused by loss of liver function, implying that it develops after cirrhosis onset. Therefore, it should be distinguished from type 2 diabetes developing before cirrhosis onset, in which specific causes of liver disease play a major role, in addition to traditional risk factors. Currently, although hepatogenous diabetes shows distinct pathophysiological and clinical features, it is not considered as an autonomous entity. Recent evidence suggests that the failing liver exerts an independent "toxic" effect on pancreatic islets resulting in β-cell dysfunction. Moreover, patients with hepatogenous diabetes usually present with normal fasting glucose and haemoglobin A1c levels and abnormal response to an oral glucose tolerance test, which is therefore required for diagnosis. This article discusses the need to separate hepatogenous diabetes from type 2 diabetes occurring in subjects with chronic liver disease and to identify individuals suffering from this condition for prognostic and therapeutic purposes.
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Affiliation(s)
- Emanuela Orsi
- Diabetes Service, Endocrinology and Metabolic Diseases Unit, IRCCS "Cà Granda-Ospedale Maggiore Policlinico" Foundation, University of Milan, Milan, Italy.,Department of Medical Sciences, University of Milan, Milan, Italy
| | - Valeria Grancini
- Diabetes Service, Endocrinology and Metabolic Diseases Unit, IRCCS "Cà Granda-Ospedale Maggiore Policlinico" Foundation, University of Milan, Milan, Italy.,Department of Medical Sciences, University of Milan, Milan, Italy
| | - Stefano Menini
- Department of Clinical and Molecular Medicine, "La Sapienza" University, Rome, Italy.,Diabetes Unit, Sant'Andrea Hospital, Rome, Italy
| | - Alessio Aghemo
- Division of Gastroenterology and Hepatology, A.M. and A. Migliavacca Center for Liver Disease, IRCCS "Cà Granda-Ospedale Maggiore Policlinico" Foundation, University of Milan, Milan, Italy
| | - Giuseppe Pugliese
- Department of Clinical and Molecular Medicine, "La Sapienza" University, Rome, Italy.,Diabetes Unit, Sant'Andrea Hospital, Rome, Italy
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28
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Lerat H, Imache MR, Polyte J, Gaudin A, Mercey M, Donati F, Baudesson C, Higgs MR, Picard A, Magnan C, Foufelle F, Pawlotsky JM. Hepatitis C virus induces a prediabetic state by directly impairing hepatic glucose metabolism in mice. J Biol Chem 2017; 292:12860-12873. [PMID: 28559285 DOI: 10.1074/jbc.m117.785030] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2017] [Revised: 05/18/2017] [Indexed: 12/15/2022] Open
Abstract
Virus-related type 2 diabetes is commonly observed in individuals infected with the hepatitis C virus (HCV); however, the underlying molecular mechanisms remain unknown. Our aim was to unravel these mechanisms using FL-N/35 transgenic mice expressing the full HCV ORF. We observed that these mice displayed glucose intolerance and insulin resistance. We also found that Glut-2 membrane expression was reduced in FL-N/35 mice and that hepatocyte glucose uptake was perturbed, partly accounting for the HCV-induced glucose intolerance in these mice. Early steps of the hepatic insulin signaling pathway, from IRS2 to PDK1 phosphorylation, were constitutively impaired in FL-N/35 primary hepatocytes via deregulation of TNFα/SOCS3. Higher hepatic glucose production was observed in the HCV mice, despite higher fasting insulinemia, concomitant with decreased expression of hepatic gluconeogenic genes. Akt kinase activity was higher in HCV mice than in WT mice, but Akt-dependent phosphorylation of the forkhead transcription factor FoxO1 at serine 256, which triggers its nuclear exclusion, was lower in HCV mouse livers. These findings indicate an uncoupling of the canonical Akt/FoxO1 pathway in HCV protein-expressing hepatocytes. Thus, the expression of HCV proteins in the liver is sufficient to induce insulin resistance by impairing insulin signaling and glucose uptake. In conclusion, we observed a complete set of events leading to a prediabetic state in HCV-transgenic mice, providing a valuable mechanistic explanation for HCV-induced diabetes in humans.
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Affiliation(s)
- Hervé Lerat
- INSERM, U955, Team "Pathophysiology and Therapy of Chronic Viral Hepatitis and Related Cancers", 94010 Créteil, France; Université Paris-Est Créteil Val de Marne, 94010 Créteil, France.
| | - Mohamed Rabah Imache
- INSERM, U955, Team "Pathophysiology and Therapy of Chronic Viral Hepatitis and Related Cancers", 94010 Créteil, France
| | - Jacqueline Polyte
- INSERM, U955, Team "Pathophysiology and Therapy of Chronic Viral Hepatitis and Related Cancers", 94010 Créteil, France
| | - Aurore Gaudin
- INSERM, U955, Team "Pathophysiology and Therapy of Chronic Viral Hepatitis and Related Cancers", 94010 Créteil, France
| | - Marion Mercey
- INSERM, U955, Team "Pathophysiology and Therapy of Chronic Viral Hepatitis and Related Cancers", 94010 Créteil, France
| | - Flora Donati
- INSERM, U955, Team "Pathophysiology and Therapy of Chronic Viral Hepatitis and Related Cancers", 94010 Créteil, France
| | - Camille Baudesson
- INSERM, U955, Team "Pathophysiology and Therapy of Chronic Viral Hepatitis and Related Cancers", 94010 Créteil, France
| | - Martin R Higgs
- INSERM, U955, Team "Pathophysiology and Therapy of Chronic Viral Hepatitis and Related Cancers", 94010 Créteil, France
| | - Alexandre Picard
- Unité de Biologie Fonctionnelle et Adaptative, Sorbonne Paris Cité, CNRS UMR 8251, Université Paris Diderot, 75013 Paris, France
| | - Christophe Magnan
- Unité de Biologie Fonctionnelle et Adaptative, Sorbonne Paris Cité, CNRS UMR 8251, Université Paris Diderot, 75013 Paris, France
| | - Fabienne Foufelle
- INSERM, UMRS 1138, Centre de Recherche des Cordeliers, 75006 Paris, France
| | - Jean-Michel Pawlotsky
- INSERM, U955, Team "Pathophysiology and Therapy of Chronic Viral Hepatitis and Related Cancers", 94010 Créteil, France; Université Paris-Est Créteil Val de Marne, 94010 Créteil, France; National Reference Center for Viral Hepatitis B, C and Delta, Department of Virology, Hôpital Henri Mondor, AP-HP, 94010 Créteil, France
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29
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Gastaldi G, Goossens N, Clément S, Negro F. Current level of evidence on causal association between hepatitis C virus and type 2 diabetes: A review. J Adv Res 2017; 8:149-159. [PMID: 28149650 PMCID: PMC5272937 DOI: 10.1016/j.jare.2016.11.003] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2016] [Revised: 11/16/2016] [Accepted: 11/23/2016] [Indexed: 12/15/2022] Open
Abstract
The association between hepatitis C virus (HCV) infection and type 2 diabetes (T2D) has been known for over 20 years. Cross-sectional and longitudinal studies have shown a higher prevalence and incidence, respectively, of T2D in patients with chronic HCV infection. HCV induces glucose metabolism alterations mostly interfering with the insulin signaling chain in hepatocytes, although extrahepatic mechanisms seem to contribute. Both IR and T2D accelerate the histological and clinical progression of chronic hepatitis C as well as the risk of extra-hepatic complications such as nephropathy, acute coronary events and ischemic stroke. Before the availability of direct-acting antivirals (DAAs), the therapeutic choice was limited to interferon (IFN)-based therapy, which reduced the incidence of the extra-hepatic manifestations but was burdened with several contraindications and poor tolerability. A better understanding of HCV-associated glucose metabolism derangements and their reversibility is expected with the use of DAAs.
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Affiliation(s)
- Giacomo Gastaldi
- Divisions of Endocrinology, Diabetology, Hypertension and Nutrition, Geneva University Hospitals, Rue Gabrielle Perret-Gentil, 1211 Genève 14, Switzerland
| | - Nicolas Goossens
- Gastroenterology and Hepatology, Geneva University Hospitals, Rue Gabrielle Perret-Gentil, 1211 Genève 14, Switzerland
| | - Sophie Clément
- Clinical Pathology, Geneva University Hospitals, Rue Gabrielle Perret-Gentil, 1211 Genève 14, Switzerland
| | - Francesco Negro
- Gastroenterology and Hepatology, Geneva University Hospitals, Rue Gabrielle Perret-Gentil, 1211 Genève 14, Switzerland
- Clinical Pathology, Geneva University Hospitals, Rue Gabrielle Perret-Gentil, 1211 Genève 14, Switzerland
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30
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Stine JG, Wynter JA, Niccum B, Kelly V, Caldwell SH, Shah NL, Marquez V. Effect of Treatment with Direct Acting Antiviral on Glycemic Control in Patients with Diabetes Mellitus and Chronic Hepatitis C. Ann Hepatol 2017; 16:215-220. [PMID: 31153414 PMCID: PMC6600819 DOI: 10.5604/16652681.1231581] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2016] [Accepted: 07/17/2017] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND AIM The effect of the new direct acting antiviral drugs (DAAs) for chronic hepatitis C (HCV) on glycemic control is unknown. MATERIALS AND METHODS We conducted a retrospective cohort study of patients who were treated for chronic HCV with direct-acting antiviral medications at a single academic institution between May 2013 and April 2016. Univariate analysis was performed comparing subjects pre- and post-treatment. RESULTS One hundred seventy-five consecutive adult patients were treated for chronic HCV and met enrollment criteria. The majority (80.8%) were genotype 1 and overall cohort sustained virologic response at week 12 (SVR12) was 97.8%. Thirty-one (18.5%) had diabetes mellitus (DM); twenty-six had pre- and post-treatment HbA1c values. Of these, 76.9% were male and 61.5% had cirrhosis. Ninety-six percent were prescribed sofosbuvir-based therapy and all but one (96.8%) achieved SVR12. Three patients were started on treatment despite meeting the definition for poorly controlled DM (HbA1c > 9 mg/dL). There was no significant difference when comparing pre-treatment (7.36 mg/dL, 95% CI 6.55-8.16) to post-treatment HbA1c (7.11 mg/dL, 95% CI 6.34-7.88, p = 0.268). Thirty-one percent of subjects required dose escalation or the initiation of insulin based therapy during treatment. DISCUSSION Although chronic HCV is associated with exacerbation of insulin resistance, our results showed HbA1c to be unaffected by eradication of chronic HCV with DAA in diabetic patients with and without cirrhosis. Paradoxically, almost 1/3 of patients required escalation of anti-diabetic therapy during treatment. Long-term studies are warranted to understand the relationship between HCV viral eradication and insulin metabolism.
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Affiliation(s)
- Jonathan G. Stine
- Division of Gastroenterology & Hepatology, University of Virginia, Charlottesville, Virginia, United States
| | - Javelle A. Wynter
- Department of Medicine, University of Virginia, Charlottesville, Virginia, United States
| | - Blake Niccum
- School of Medicine, University of Virginia, Charlottesville, Virginia, United States
| | - Virginia Kelly
- Division of Gastroenterology & Hepatology, University of Virginia, Charlottesville, Virginia, United States
| | - Stephen H. Caldwell
- Division of Gastroenterology & Hepatology, University of Virginia, Charlottesville, Virginia, United States
| | - Neeral L. Shah
- Division of Gastroenterology & Hepatology, University of Virginia, Charlottesville, Virginia, United States
| | - Vladimir Marquez
- Division of Gastroenterology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada
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31
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Cho SH, Kim YJ, Lee SY, Cho BM, Hwang HL, Yi YH, Cho YH, Tak YJ, Jeong DW, Lee SH, Lee JG. Comparison of the Serum Cholesterol, Insulin Resistance and Markers of Metabolic Syndrome Based on Hepatitis C Virus RNA. JOURNAL OF AGRICULTURAL MEDICINE AND COMMUNITY HEALTH 2016; 41:205-216. [DOI: 10.5393/jamch.2016.41.4.205] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/30/2024]
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32
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Huang CF, Yeh ML, Huang CY, Tsai PC, Ko YM, Chen KY, Lin ZY, Chen SC, Dai CY, Chuang WL, Huang JF, Yu ML. Pretreatment glucose status determines HCC development in HCV patients with mild liver disease after curative antiviral therapy. Medicine (Baltimore) 2016; 95:e4157. [PMID: 27399135 PMCID: PMC5058864 DOI: 10.1097/md.0000000000004157] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2016] [Revised: 06/03/2016] [Accepted: 06/14/2016] [Indexed: 12/15/2022] Open
Abstract
Although diabetes mellitus (DM) is known to increase the risk of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC), the impact of dynamic glucose status on HCC occurrence in chronic hepatitis C (CHC) patients receiving antiviral therapy is unclear. In total, 1112 biopsy-proven patients treated with peginterferon/ribavirin were enrolled in this study. Both pretreatment and post-treatment glucose status, including 75 g oral glucose tolerance test (OGTT), were measured to evaluate the association between glucose status and the development of HCC. Of the 1112 patients evaluated, 93 (8.4%) developed HCC >5183.8 person-years of follow-up (annual incidence rate: 1.79%). DM only influenced the risk of developing CC in patients with mild liver disease (F0-2) and a sustained virological response (SVR) but not in other patient subpopulations. Cox-regression analysis demonstrated that the strongest factor associated with HCC in patients with mild liver disease and SVR was the presence of DM (hazard ratio [HR]/95 % confidence intervals [CI]: 3.79/1.420-10.136, P = 0.008), followed by age (HR/CI: 1.06/1.001-1.117, P = 0.046) and platelet count (HR/CI: 0.989/0.979-1.000, P = 0.05). The percentages of SVR patients with F0-2 with normoglycemia, pre-DM, sub-DM (pre-sDM), and DM before treatment were 45.3% (n = 267), 29.9% (n = 176), 15.6% (n = 92), and 9.2% (n = 54), respectively. The percentages of HCC in patients with normoglycemia, pre-sDM, and DM were 1.1%, 3.7%, and 11.1%, respectively (trend P < 0.001). Sixteen of the 19 (84.2 %) HCC patients possessed glucose abnormality (including 6 patients with DM and 10 patients with pre-sDM) before antiviral therapy. Compared to patients with normoglycemia, the incidence of HCC increased gradually from pre-sDM (HR: 3.6, P = 0.05) to DM (HR: 11.6, P = 0.001) (adjusted trend P = 0.004). We concluded that DM is a critical determinant for the development of HCC in SVR patients with mild liver disease. Pre-sDM status carried an additional risk for HCC, and these patients should also be carefully monitored for HCC after viral eradication.
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Affiliation(s)
- Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Occupational Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Health Management Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Cing-Yi Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Pei-Chien Tsai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yu-Min Ko
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Kuan-Yu Chen
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Zu-Yau Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shinn-Cherng Chen
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Health Management Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Occupational Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Institute of Biomedical Sciences, National Sun Yat-Sen University
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García-Compeán D, González-González JA, Lavalle-González FJ, González-Moreno EI, Villarreal-Pérez JZ, Maldonado-Garza HJ. Current Concepts in Diabetes Mellitus and Chronic Liver Disease: Clinical Outcomes, Hepatitis C Virus Association, and Therapy. Dig Dis Sci 2016; 61:371-380. [PMID: 26462490 DOI: 10.1007/s10620-015-3907-2] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Accepted: 09/27/2015] [Indexed: 02/07/2023]
Abstract
Hereditary type 2 diabetes mellitus is a risk factor for chronic liver disease, and ~30 % of patients with liver cirrhosis develop diabetes. Diabetes mellitus has been associated with cirrhotic and non-cirrhotic hepatitis C virus liver infection, can aggravate the course the liver infection, and can induce a lower sustained response to antiviral treatment. Evidences that HCV may induce metabolic and autoimmune disturbances leading to hypobetalipoproteinemia, steatosis, insulin resistance, impaired glucose tolerance, thyroid disease, and gonadal dysfunction have been found. Prospective studies have demonstrated that diabetes increases the risk of liver complications and death in patients with cirrhosis. However, treatment of diabetes in these patients is complex, as antidiabetic drugs can promote hypoglycemia and lactic acidosis. There have been few therapeutic studies evaluating antidiabetic treatments in patients with liver cirrhosis published to date; thus, the optimal treatment for diabetes and the impact of treatment on morbidity and mortality are not clearly known. As numbers of patients with chronic liver disease and diabetes mellitus are increasing, largely because of the global epidemics of obesity and nonalcoholic fatty liver disease, evaluation of treatment options is becoming more important. This review discusses new concepts on hepatogenous diabetes, the diabetes mellitus–hepatitis C virus association, and clinical implications of diabetes mellitus in patients with chronic liver disease. In addition, the effectiveness and safety of old and new antidiabetic drugs, including incretin-based therapies, will be described.
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Vanni E, Bugianesi E, Saracco G. Treatment of type 2 diabetes mellitus by viral eradication in chronic hepatitis C: Myth or reality? Dig Liver Dis 2016; 48:105-11. [PMID: 26614641 DOI: 10.1016/j.dld.2015.10.016] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2015] [Revised: 10/05/2015] [Accepted: 10/16/2015] [Indexed: 12/15/2022]
Abstract
Chronic hepatitis C is a systemic disease inducing metabolic alterations leading to extrahepatic consequences. In particular, hepatitis C virus (HCV) infection seems to increase the risk of incident type 2 diabetes mellitus in predisposed individuals, independently of liver disease stage. The mechanisms through which hepatitis C induces T2DM involve direct viral effects, insulin resistance, pro-inflammatory cytokines and other immune-mediated processes. Many studies have reported the clinical consequences of type 2 diabetes mellitus on hepatitis C outcome, but very few studies have addressed the issue of microangiopathic complications among patients with hepatitis C only, who develop type 2 diabetes mellitus. Moreover, clinical trials in HCV-positive patients have reported improvement in glucose metabolism after antiviral treatment; recent studies have suggested that this metabolic amelioration might have a clinical impact on type 2 diabetes mellitus-related complications. These observations raise the question as to whether the HCV eradication may also have an impact on the future morbidity and mortality due to type 2 diabetes mellitus. The scope of this review is to summarise the current evidence linking successful antiviral treatment and the prevention of type 2 diabetes mellitus and its complications in hepatitis C-infected patients.
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Affiliation(s)
- Ester Vanni
- Gastro-hepatology Unit, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Elisabetta Bugianesi
- Gastro-hepatology Unit, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Giorgio Saracco
- Gastroenterology Unit, Oncology Department, University of Turin, Italy.
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Knobler H, Malnick S. Hepatitis C and insulin action: An intimate relationship. World J Hepatol 2016; 8:131-138. [PMID: 26807209 PMCID: PMC4716529 DOI: 10.4254/wjh.v8.i2.131] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2015] [Revised: 12/10/2015] [Accepted: 12/29/2015] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis C virus (HCV) infection has been shown to be linked to a higher prevalence of type 2 diabetes compared with the general population or with patients with chronic hepatitis B infection and diabetes is the most common extra-hepatic manifestation of HCV. The HCV-diabetes association is due to insulin resistance (IR) that occurs early in the course of the disease even in patients without or with minimal fibrosis. The mechanisms for HCV-induced IR are only partly understood and include a direct inhibitory effect of HCV on insulin signaling pathway. IR in chronic HCV results in an increased progression rate of hepatic fibrosis, cirrhosis and hepatocellular carcinoma. Some but not all studies found that IR reduces the response rate to interferon/ribavirin therapy. Whether IR affects the response to the new direct-acting antiviral treatments is still unknown.
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Affiliation(s)
- Hilla Knobler
- Hilla Knobler, Diabetes and Metabolic Disease Unit, Kaplan Medical Center, Rehovot 76100, Israel
| | - Stephen Malnick
- Hilla Knobler, Diabetes and Metabolic Disease Unit, Kaplan Medical Center, Rehovot 76100, Israel
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Bo Q, Orsenigo R, Wang J, Griffel L, Brass C. Glucose abnormalities in Asian patients with chronic hepatitis C. DRUG DESIGN DEVELOPMENT AND THERAPY 2015; 9:6009-17. [PMID: 26609222 PMCID: PMC4644176 DOI: 10.2147/dddt.s92060] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Many studies have demonstrated a potential association between type 2 diabetes (T2D) and hepatitis C virus infection in Western countries, while similar evidence is limited in Asia. We compared the prevalence of glucose abnormalities (impaired fasting glucose [IFG] and T2D) and their risk factors between Asian and non-Asian chronic hepatitis C (CHC) patients, and evaluated whether glucose abnormalities impacted the viral responses to peginterferon plus ribavirin treatment (current standard of care in most Asian countries). This study retrospectively analyzed data of 1,887 CHC patients from three Phase II/III studies with alisporivir (DEB025) as treatment for CHC. The chi-square test was used to compare the prevalence of IFG/T2D between Asian and non-Asian CHC patients, and logistic regression was used to adjust for sex, age, and cirrhosis status. Risk factors for IFG/T2D were evaluated using univariate and multivariate analysis. Our results indicated that the prevalence of IFG/T2D was high in both Asian and non-Asian CHC patients (23.0% vs 20.9%), and no significant difference was found between these two populations (adjusted odds ratio: 1.3, 95% confidence interval: 0.97, 1.7; P=0.08). Age, sex, and cirrhosis status were risk factors for IFG/T2D in both populations, while body mass index was positively associated with IFG/T2D in non-Asian but not in Asian participants. No significant differences in sustained virological response rates were seen between patients with normal fasting glucose and patients with IFG/T2D for both populations. These results demonstrate that the prevalence of glucose abnormalities in Asian CHC patients was similar to that in non-Asians, and glucose abnormalities had no impact on viral response to peginterferon plus ribavirin.
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Affiliation(s)
- Qingyan Bo
- Beijing Novartis Pharma Co. Ltd., Shanghai, People's Republic of China
| | | | - Junyi Wang
- Beijing Novartis Pharma Co. Ltd., Shanghai, People's Republic of China
| | - Louis Griffel
- Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA
| | - Clifford Brass
- Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA
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Dai CY, Yeh ML, Huang CF, Hou CH, Hsieh MY, Huang JF, Lin IL, Lin ZY, Chen SC, Wang LY, Chuang WL, Yu ML, Tung HD. Chronic hepatitis C infection is associated with insulin resistance and lipid profiles. J Gastroenterol Hepatol 2015; 30:879-884. [PMID: 23808794 DOI: 10.1111/jgh.12313] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/12/2013] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIM Chronic hepatitis C virus (HCV) infection has been suggested to be associated with non-insulin-dependent diabetes mellitus and lipid profiles. This study aimed to investigate the possible relationships of insulin resistance (IR) and lipid profiles with chronic hepatitis C (CHC) patients in Taiwan. METHODS We enrolled 160 hospital-based CHC patients with liver biopsy and the 480 controlled individuals without CHC and chronic hepatitis B from communities without known history of non-insulin-dependent diabetes mellitus. Fasting plasma glucose, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), alanine aminotransferase, and serum insulin levels, and homeostasis model assessment (HOMA-IR) were tested. RESULTS When comparing factors between CHC patients, and sex- and age-matched controls who had no HCV infection, patients with HCV infection had a significantly higher alanine aminotransferase level, fasting plasma glucose level, insulin level, and HOMA-IR (P < 0.001, P = 0.023, P = 0.017, and P = 0.011, respectively), and significantly lower TG level (P = 0.023), total cholesterol, and HDL-C and LDL-C levels (all P < 0.001) than 480 controls. In multivariate logistic regression analyses, a low total cholesterol, a low TGs, and a high HOMA-IR are independent factors significantly associated with chronic HCV infection. In the 160 CHC patients (41 patients with high HOMA-IR [> 2.5]), a high body mass index, TGs, and HCV RNA level are independent factors significantly associated with high HOMA-IR in multivariate logistic analyses. CONCLUSIONS Chronic HCV infection was associated with metabolic characteristics including IR and lipid profile. IR was also associated with virological characteristics.
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Affiliation(s)
- Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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Kaur H, Singh P, Pannu HS, Sood A, Jain NP, Bhoday HS. To study the prevalence of impaired glucose tolerance in patients with hepatitis C virus related chronic liver disease. J Clin Diagn Res 2015; 9:OC16-20. [PMID: 25954649 DOI: 10.7860/jcdr/2015/11444.5665] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2014] [Accepted: 01/20/2015] [Indexed: 01/07/2023]
Abstract
BACKGROUND Hepatitis C infection is a major cause of Chronic Liver Disease and the prevalence of Diabetes Mellitus is also high. Diabetes has been hypothesised as one of Extrahepatic manifestations of Hepatitis C. AIMS AND OBJECTIVES The objective of our study was to study the prevalence of impaired glucose tolerance in patients with HCV related liver disease. STUDY DESIGN The study was a prospective study conducted over a period of one and half year in Dayanand Medical College and Hospital, Ludhiana, Punjab, India. MATERIALS AND METHODS The study was conducted taking total of 100 Hepatitis C virus positive patients above 40 years of age who had fasting blood glucose levels ≥110mg/dl on two occasions, 24 hours apart. These patients underwent an oral glucose tolerance test. Blood sugar levels were tested at 0 and 2 hours. Based on the findings, patients were classified to have impaired glucose tolerance if levels were between 140-200mg/dl and frank diabetes if the levels were ≥ 200mg/dl. These findings were further assessed according to age, gender, Body Mass Index (BMI) Child Turcott Pugh score and Ultrasonography findings. STATISTICAL ANALYSIS In our study all the statistical analysis was done using simple z-test and student t-test. The p-values were calculated and the results assessed accordingly. RESULTS AND CONCLUSION Out of 100 patients, 78 were males and rest females. The mean age of the study group was 55.89±11.22 years. Mean BMI of males was higher than in females (21.98kg/m² v/s 20.13kg/m²). Maximum patients belonged to Child Turcott Pugh class C. Out of 100 patients,80 had cirrhosis on ultrasound. On doing Glucose Tolerance Test, 40 patients were found to have impaired glucose tolerance and one patient to be diabetic. The prevalence increased significantly as age increased and had significant relation with gender. On assessing according to BMI, there was not much significant relation but prevalence was significantly related to severity of disease.
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Affiliation(s)
- Harpreet Kaur
- Attending Consultant, Department of Internal Medicine, Fortis Hospital , Ludhiana, India
| | - Parminder Singh
- Professor and Head, Department of Endocrinology, Dayanand Medical College and Hospital , Ludhiana, India
| | - Harminder Singh Pannu
- Professor, Department of Internal Medicine, Dayanand Medical College and Hospital , Ludhiana, India
| | - Ajit Sood
- Professor and Head, Department of Gastroenterology, Dayanand Medical College and Hospital , Ludhiana, India
| | - Narender Pal Jain
- Professor, Department of Internal Medicine, Dayanand Medical College and Hospital , Ludhiana, India
| | - Harpreet Singh Bhoday
- Post Graduate, Department of Pediatrics, Dayanand Medical College and Hospital , Ludhiana, India
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De Sanctis V, Soliman AT, Candini G, Elsedfy H. Hepatitis C virus infection in thalassemic patients with and without insulin dependent diabetes. Indian J Endocrinol Metab 2015; 19:303-304. [PMID: 25729698 PMCID: PMC4319276 DOI: 10.4103/2230-8210.149327] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Affiliation(s)
- Vincenzo De Sanctis
- Department of Pediatrics, Pediatric and Adolescent Outpatient Clinic, Quisisana Hospital, Ferrara, Italy
| | - Ashraf T Soliman
- Department of Pediatrics, Division of Endocrinology, Hamad General Hospital, Doha, Qatar
| | | | - Heba Elsedfy
- Department of Pediatrics, Ain Shams University, Cairo, Egypt
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Antonelli A, Ferrari SM, Giuggioli D, Di Domenicantonio A, Ruffilli I, Corrado A, Fabiani S, Marchi S, Ferri C, Ferrannini E, Fallahi P. Hepatitis C virus infection and type 1 and type 2 diabetes mellitus. World J Diabetes 2014; 5:586-600. [PMID: 25317237 PMCID: PMC4138583 DOI: 10.4239/wjd.v5.i5.586] [Citation(s) in RCA: 71] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2013] [Revised: 04/10/2014] [Accepted: 07/12/2014] [Indexed: 02/05/2023] Open
Abstract
Hepatitis C virus (HCV) infection and diabetes mellitus are two major public health problems that cause devastating health and financial burdens worldwide. Diabetes can be classified into two major types: type 1 diabetes mellitus (T1DM) and T2DM. T2DM is a common endocrine disorder that encompasses multifactorial mechanisms, and T1DM is an immunologically mediated disease. Many epidemiological studies have shown an association between T2DM and chronic hepatitis C (CHC) infection. The processes through which CHC is associated with T2DM seem to involve direct viral effects, insulin resistance, proinflammatory cytokines, chemokines, and other immune-mediated mechanisms. Few data have been reported on the association of CHC and T1DM and reports on the potential association between T1DM and acute HCV infection are even rarer. A small number of studies indicate that interferon-α therapy can stimulate pancreatic autoimmunity and in certain cases lead to the development of T1DM. Diabetes and CHC have important interactions. Diabetic CHC patients have an increased risk of developing cirrhosis and hepatocellular carcinoma compared with non-diabetic CHC subjects. However, clinical trials on HCV-positive patients have reported improvements in glucose metabolism after antiviral treatment. Further studies are needed to improve prevention policies and to foster adequate and cost-effective programmes for the surveillance and treatment of diabetic CHC patients.
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The impact of hepatitis C infection on ischemic heart disease via ischemic electrocardiogram. Am J Med Sci 2014; 347:478-84. [PMID: 24335568 DOI: 10.1097/maj.0b013e3182a5587d] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is a serious disease worldwide and it leads to several serious hepatic sequels. Some studies find possible correlation between HCV and ischemic heart disease in retrospective observations. Based on lacked community-based evidence, the study aims to assess correlation between ischemic heart disease and chronic HCV infection via electrocardiogram (ECG) because its abnormalities is strongly associating with cardiovascular disease mortality. METHODS The population was from one community health examination in December 2010 in a southern village of Taiwan. A total of 9856 participants were evaluated and finally 5015 eligible residents with age older than 40 years were included. The baseline characteristics and laboratory data in nonischemic ECG and ischemic ECG groups were compared, and multivariate-adjusted analysis was used to evaluate the risks to ischemic ECG. RESULTS The higher prevalence of hypertension, metabolic syndrome and even HCV infection (25.3% versus 11.6%; P < 0.001) in ischemic ECG group than those in nonischemic ECG group. In the multivariate adjusted analysis, HCV infection would lead to a 1.759-fold risk to ischemic ECG when compared with non-HCV subjects. CONCLUSIONS HCV was strongly associated with ischemic ECG findings in this community study, and it could be a nonconventional risk factor for coronary artery disease.
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Caselli E, Rizzo R, Ingianni A, Contini P, Pompei R, Di Luca D. High prevalence of HHV8 infection and specific killer cell immunoglobulin-like receptors allotypes in Sardinian patients with type 2 diabetes mellitus. J Med Virol 2013; 86:1745-51. [PMID: 24122895 DOI: 10.1002/jmv.23771] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/09/2013] [Indexed: 02/05/2023]
Abstract
The development of type 2 diabetes is thought to involve both environmental, possibly infectious, and genetic factors. Recently, a high prevalence of human herpesvirus 8 (HHV8) infection was observed in type 2 diabetes patients, and specific killer cell immunoglobulin-like receptors (KIR) allotypes were associated to both increased susceptibility to herpesvirus infection and risk to develop diabetes. However, no clear gene-disease or virus-disease associations have been established. To investigate the possible interplay between HHV8 infection, KIR allotype and type 2 diabetes, virus prevalence and KIR genotype were analyzed by PCR in 168 patients affected by type 2 diabetes and 108 control individuals belonging to the Sardinian population. Results showed a significant increase of HHV8 prevalence in type 2 diabetes patients versus controls (57% vs. 17%, P < 0.001), and a significant increase of KIR2DL2/DS2 homozygosity in diabetes patients infected with HHV8 compared to uninfected ones (64% vs. 14%, P < 0.0001), resulting in a significant OR of 11.31. In addition, the analysis of the frequency of the KIR2DL2/DS2 receptor and its HLA-C1 ligand, accordingly to the status of HHV8 infection, showed a significant increased correlation between KIR2DL2/DS2, type 2 diabetes and HLA-C1C1 genotype in the type 2 diabetes patients infected with HHV8 compared to uninfected ones (62% vs. 15%, P < 0.0001, OR = 8.64). These findings provide preliminary evidence that HHV8 infection might be a cofactor for type 2 diabetes in a specific subset of genetically susceptible individuals, and suggest the possibility that such patients might have an impaired immune-mediated component contributing to the development of type 2 diabetes.
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Affiliation(s)
- Elisabetta Caselli
- Department of Medical Sciences, Microbiology Unit, University of Ferrara, Ferrara, Italy
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Virus C hepatitis and type 2 diabetes: a cohort study in southern Italy. Am J Gastroenterol 2013; 108:1108-11. [PMID: 23567360 DOI: 10.1038/ajg.2013.90] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2012] [Accepted: 02/18/2013] [Indexed: 12/15/2022]
Abstract
OBJECTIVES The relationship between hepatitis C virus (HCV) infection and type 2 diabetes mellitus (DM 2) is still uncertain. The objective of this study was to evaluate the association between HCV infection, measured as positivity to anti-HCV antibodies, and the incidence of DM 2 in a cohort of subjects sampled from the general population and followed up for 20 years. METHODS At baseline, the cohort consisted of a random sample of 2,472 subjects (72% response rate, age range 30-69 years) from the electoral register of a town in Southern Italy. The cohort subjects were examined three times: in 1985 (M1), in 1992 (M2), and in 2005 (M3). At M1, M2, and M3, each participant filled in a questionnaire and had a blood sample taken to measure blood glucose and other serum variables including glutamic pyruvic alanine aminotransferase (ALT). Anti-HCV antibodies were analyzed with standard techniques at M1 and M2. Diabetes type 2 diagnosis was a history of diabetes and/or serum glucose ≥126 mg/dl and/or treatment with insulin or hypoglycemic drugs. Logistic regression was used for multivariable data analysis. RESULTS Diabetes prevalence was higher in subjects with positive anti-HCV antibodies at M1 and M2, and diabetes incidence was higher in subjects with baseline positive anti-HCV antibodies at M1-M2 and lower at M2-M3. In multivariable models, controlling for gender, age, and body mass index (BMI), there was no association between incident cases of diabetes and positive anti-HCV antibodies at baseline, either at M1-M2 (odds ratio (OR) 0.73, 95% confidence interval (CI) 0.43-1.22) or at M2-M3 (0.65, 0.41-1.04). HCV was associated with DM 2 only in subjects with elevated ALT (OR 0.58, 95% CI 0.31-1.08, if ALT normal; OR 1.47, 95% CI 1-2.16, if ALT elevated, controlling for age, gender, and BMI). CONCLUSIONS Our findings, in a cohort study at population level, support an association between the presence of anti-HCV antibodies at baseline and a higher incidence of type 2 diabetes in the following 20 years only in subjects with elevated ALT.
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Huang JF, Yu ML, Dai CY, Chuang WL. Glucose abnormalities in hepatitis C virus infection. Kaohsiung J Med Sci 2013; 29:61-68. [PMID: 23347806 DOI: 10.1016/j.kjms.2012.11.001] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2012] [Accepted: 11/20/2012] [Indexed: 02/07/2023] Open
Abstract
Hepatitis C virus (HCV) infection is one of the most important causes of cirrhosis and hepatocellular carcinoma and has a tremendous impact on public health worldwide. HCV is both hepatotropic and lymphotropic. Replication of HCV in diseased extrahepatic organs and tissues may either trigger latent autoimmunity or induce autoimmune disorders. In addition to established liver injury, type 2 diabetes mellitus (T2DM) is an important feature of extrahepatic metabolic disorders which is attributed to HCV infection. It also has some impact on the disease activity, disease course, clinical outcomes, and treatment efficacy of antiviral therapy. Previous experimental and clinical findings have highly suggested that HCV per se is diabetogenic. The cause-effect interaction between a common endocrine disorder and an infectious disease is an important issue to elucidate. Although the precise mechanisms whereby HCV infection leads to insulin resistance (IR) and glucose abnormalities are not entirely clear, it differs from the usual pathogenesis of T2DM in those with non-HCV liver diseases. This review initially highlights epidemiological and pathophysiological studies addressing the mutual link between chronic HCV infection (CHC) and T2DM. The characteristics of glucose abnormalities in this special population are depicted from the current evidence. The mutual roles of IR and CHC with respect to the prediction of treatment efficacy, how treatment response affects IR, and the role of pancreatic beta cell function in the entire suite are discussed. With the rapid progression of antiviral therapy for CHC in the past decade, we have also listed some points of future perspective in this issue.
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Affiliation(s)
- Jee-Fu Huang
- Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
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Memon MS, Arain ZI, Naz F, Zaki M, Kumar S, Burney AA. Prevalence of type 2 diabetes mellitus in hepatitis C virus infected population: a Southeast Asian study. J Diabetes Res 2013; 2013:539361. [PMID: 23984431 PMCID: PMC3747388 DOI: 10.1155/2013/539361] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2013] [Revised: 07/09/2013] [Accepted: 07/15/2013] [Indexed: 02/06/2023] Open
Abstract
PURPOSE The study was aimed to investigate the frequency of diabetes mellitus type 2 in patients infected with chronic hepatitis C virus and its association with cirrhosis. PATIENTS AND METHODS This prospective case series was conducted at Section of Gastroenterology and Hepatology, Isra University Hospital, Hyderabad, over a period of 4 months from June 2009 to October 2009. Hepatitis C virus seropositive patients who were older than 18 years, diabetic or nondiabetic, were included. Basic demographic data collected by questionnaire and laboratory investigations including fasting blood glucose levels, serum cholesterol, and liver function tests were done. A logistic regression model was used to explore the association between diabetic and nondiabetic HCV seropositives and type 2 diabetes mellitus with cirrhosis. RESULTS A total of 361 patients with hepatitis C were analyzed; the prevalence of type 2 diabetes mellitus in HCV patients was 31.5%. Out of the total number of the participants, 58.4% (n = 211) were cirrhotics, while 41.6% (n = 150) were noncirrhotic HCV seropositives. In multivariate analysis, cirrhotic patients appeared significantly more likely (P = 0.01) to be diabetic as compared with noncirrhotic patients (OR = 2.005, 95% CI: 1.15, 3.43). CONCLUSION Advancing age, increased weight, and HCV genotype 3 are independent predictors of type 2 diabetes in HCV seropositive patients, and there is a statistically significant association of cirrhosis observed with type 2 diabetes mellitus.
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Hsieh MJ, Lan KP, Liu HY, Zhang XZ, Lin YF, Chen TY, Chiou HL. Hepatitis C virus E2 protein involve in insulin resistance through an impairment of Akt/PKB and GSK3β signaling in hepatocytes. BMC Gastroenterol 2012; 12:74. [PMID: 22721429 PMCID: PMC3464126 DOI: 10.1186/1471-230x-12-74] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2012] [Accepted: 06/21/2012] [Indexed: 12/25/2022] Open
Abstract
Background Hepatitis C virus (HCV) infection may cause liver diseases of various severities ranging from primary acute infection to life-threatening diseases, such as cirrhosis or hepatocellular carcinoma with poor prognosis. According to clinical findings, HCV infection may also lead to some extra-hepatic symptoms, including type 2 diabetes mellitus (DM). Since insulin resistance is the major etiology for type 2 DM and numerous evidences showed that HCV infection associated with insulin resistance, the involvement of E2 in the pathogenesis of type 2 DM and underlying mechanisms were investigated in this study. Methods Reverse transcription and real-time PCR, Western blot assay, Immunoprecipitation, Glucose uptake assay and analysis of cellular glycogen content. Results Results showed that E2 influenced on protein levels of insulin receptor substrate-1 (IRS-1) and impaired insulin-induced Ser308 phosphorylation of Akt/PKB and Ser9 phosphorylation of GSK3β in Huh7 cells, leading to an inhibition of glucose uptake and glycogen synthesis, respectively, and eventually insulin resistance. Conclusions Therefore, HCV E2 protein indeed involved in the pathogenesis of type 2 DM by inducing insulin resistance.
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Affiliation(s)
- Ming-Ju Hsieh
- School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan
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Wang Q, Chen J, Wang Y, Han X, Chen X. Hepatitis C virus induced a novel apoptosis-like death of pancreatic beta cells through a caspase 3-dependent pathway. PLoS One 2012; 7:e38522. [PMID: 22675572 PMCID: PMC3366942 DOI: 10.1371/journal.pone.0038522] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2011] [Accepted: 05/06/2012] [Indexed: 12/17/2022] Open
Abstract
Epidemiological and experimental studies have suggested that Hepatitis C virus (HCV) infection is associated with the development of type 2 diabetes. Pancreatic beta cell failure is central to the progression of type 2 diabetes. Using virus infection system, we investigate the influence of HCV infection on the fate of the insulinoma cell line, MIN6. Our experiments demonstrate that the HCV virion itself is indispensable and has a dose- and time-dependent cytopathic effect on the cells. HCV infection inhibits cell proliferation and induces death of MIN6 cells with apoptotic characteristics, including cell surface exposure of phosphatidylserine, decreased mitochondrial membrane potential, activation of caspase 3 and poly (ADP-ribose) polymerase, and DNA fragmentation in the nucleus. However, the fact that HCV-infected cells exhibit a dilated, low-density nucleus with intact plasma and nuclear membrane indicates that a novel apoptosis-like death occurs. HCV infection also causes endoplasmic reticulum (ER) stress. Further, HCV RNA replication was detected in MIN6 cells, although the infection efficiency is very low and no progeny virus particle generates. Taken together, our data suggest that HCV infection induces death of pancreatic beta cells through an ER stress-involved, caspase 3-dependent, special pathway.
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Affiliation(s)
- Qian Wang
- State Key Lab of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China
- Key Laboratory of Human Functional Genomics of Jiangsu Province, School of Basic Medical Science, Nanjing Medical University, Nanjing, China
| | - Jizheng Chen
- State Key Lab of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China
| | - Yun Wang
- State Key Lab of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China
| | - Xiao Han
- Key Laboratory of Human Functional Genomics of Jiangsu Province, School of Basic Medical Science, Nanjing Medical University, Nanjing, China
| | - Xinwen Chen
- State Key Lab of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China
- * E-mail:
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Naing C, Mak JW, Ahmed SI, Maung M. Relationship between hepatitis C virus infection and type 2 diabetes mellitus: meta-analysis. World J Gastroenterol 2012; 18:1642-1651. [PMID: 22529694 PMCID: PMC3325531 DOI: 10.3748/wjg.v18.i14.1642] [Citation(s) in RCA: 105] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2011] [Revised: 12/04/2011] [Accepted: 01/18/2012] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the association between hepatitis C infection and type 2 diabetes mellitus. METHODS Observational studies assessing the relationship between hepatitis C infection and type 2 diabetes mellitus were identified via electronic and hand searches. Studies published between 1988 to March 2011 were screened, according to the inclusion criteria set for the present analysis. Authors performed separate analyses for the comparisons between hepatitis C virus (HCV) infected and not infected, and HCV infected and hepatitis B virus infected. The included studies were further subgrouped according to the study design. Heterogenity was assessed using I(2) statistics. The summary odds ratios with their corresponding 95% CIs were calculated based on a random-effects model. The included studies were subgrouped according to the study design. To assess any factor that could potentially affect the outcome, results were further stratified by age group (proportion of ≥ 40 years), gender (proportion of male gender), body mass index (BMI) (proportion of BMI ≥ 27), and family history of diabetes (i.e., self reported). For stability of results, a sensitivity analysis was conducted including only prospective studies. RESULTS Combining the electronic database and hand searches, a total of 35 observational studies (in 31 articles) were identified for the final analysis. Based on random-effects model, 17 studies (n = 286,084) compared hepatitis C-infected patients with those who were uninfected [summary odds ratio (OR): 1.68, 95% CI: 1.15-2.45]. Of these 17 studies, 7 were both a cross-sectional design (41.2%) and cohort design (41.2%), while 3 were case-control studies (17.6%). Nineteen studies (n = 51,156) compared hepatitis C-infected participants with hepatitis B-infected (summary OR: 1.92, 95% CI: 1.41-2.62). Of these 19 studies, 4 (21.1%), 6 (31.6%) and 9 (47.4%) were cross-sectional, cohort and case-control studies, respectively. A sensitivity analysis with 3 prospective studies indicated that hepatitis C-infected patients had a higher risk of developing type 2 diabetes compared with uninfected controls (summary odds ratio: 1.41, 95% CI: 1.17-1.7; I(2) = 0%). Among hepatitis C-infected patients, male patients (OR: 1.26, 95% CI: 1.03-1.54) with age over 40 years (summary OR: 7.39, 95% CI: 3.82-9.38) had an increased frequency of type 2 diabetes. Some caution must be taken in the interpretation of these results because there may be unmeasured confounding factors which may introduce bias. CONCLUSION The findings support the association between hepatitis C infection and type 2 diabetes mellitus. The direction of association remains to be determined, however. Prospective studies with adequate sample sizes are recommended.
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Affiliation(s)
- Cho Naing
- Faculty of Medicine and Health, International Medical University, Kuala Lumpur 57000, Malaysia.
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Zuwała-Jagiello J, Pazgan-Simon M, Simon K, Warwas M. Picolinic acid in patients with chronic hepatitis C infection: a preliminary report. Mediators Inflamm 2012; 2012:762863. [PMID: 22701277 PMCID: PMC3368595 DOI: 10.1155/2012/762863] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2012] [Revised: 03/09/2012] [Accepted: 03/26/2012] [Indexed: 12/30/2022] Open
Abstract
Macrophage activation seems to be a feature of chronic liver diseases. Picolinic acid (PA) as a macrophage secondary signal causes the activation of interferon-gamma- (IFN-γ-) prime macrophage and triggers cytokine-driven inflammatory reactions. The rationale for seeking increased PA formation in chronic viral hepatitis is based on the involvement of activated macrophages in chronic viral hepatitis-associated inflammation. The aim of this study was to determine serum PA levels in patients with chronic hepatitis C infection, taking into account the presence of diabetes. We assessed PA and high-sensitivity C-reactive protein (hsCRP) as a marker of inflammation in 51 patients with chronic hepatitis C infection (CHC), both with and without diabetes and 40 controls. Compared with the controls, the patients with CHC showed a significant increase in plasma concentrations of PA and hsCRP (P < 0.01 and P < 0.05, resp.). The values of PA and hsCRP were more elevated in patients with diabetes than without diabetes (both P < 0.01). The positive relationships were between PA and hsCRP levels (P < 0.05) and the presence of diabetes (P < 0.001). We documented that significant elevation in serum PA levels is associated with diabetes prevalence and increased inflammatory response reflected in hsCRP levels in CHC patients.
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Basaranoglu M, Basaranoglu G. Pathophysiology of insulin resistance and steatosis in patients with chronic viral hepatitis. World J Gastroenterol 2011; 17:4055-62. [PMID: 22039318 PMCID: PMC3203355 DOI: 10.3748/wjg.v17.i36.4055] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2011] [Revised: 05/16/2011] [Accepted: 05/23/2011] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis due to any cause leads to cirrhosis and end-stage liver disease. A growing body of literature has also shown that fatty liver due to overweight or obesity is a leading cause of cirrhosis. Due to the obesity epidemic, fatty liver is now a significant problem in clinical practice. Steatosis has an impact on the acceleration of liver damage in patients with chronic hepatitis due to other causes. An association between hepatitis C virus (HCV) infection, steatosis and the onset of insulin resistance has been reported. Insulin resistance is one of the leading factors for severe fibrosis in chronic HCV infections. Moreover, hyperinsulinemia has a deleterious effect on the management of chronic HCV. Response to therapy is increased by decreasing insulin resistance by weight loss or the use of thiazolidenediones or metformin. The underlying mechanisms of this complex interaction are not fully understood. A direct cytopathic effect of HCV has been suggested. The genomic structure of HCV (suggesting that some viral sequences are involved in the intracellular accumulation of triglycerides), lipid metabolism, the molecular links between the HCV core protein and lipid droplets (the core protein of HCV and its transcriptional regulatory function which induce a triglyceride accumulation in hepatocytes) and increased neolipogenesis and inhibited fatty acid degradation in mitochondria have been investigated.
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