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Jain N, Garg R, Singh GP, Kaur S, Chawla SPS, Padda P. Assessment of factors affecting response of direct-acting antivirals in chronic hepatitis C patients. Ann Afr Med 2023; 22:456-464. [PMID: 38358146 PMCID: PMC10775945 DOI: 10.4103/aam.aam_183_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Revised: 03/12/2023] [Accepted: 03/20/2023] [Indexed: 02/16/2024] Open
Abstract
Background Hepatitis C virus (HCV) is a universally prevalent pathogen and a major cause of liver-related morbidity and mortality worldwide. The evolution of antiviral therapy for HCV has rapidly progressed from interferon (IFN)-based therapies to IFN-free combinations of direct-acting antivirals (DAAs). Aims This study aims to assess the response of DAAs in chronic hepatitis C (CHC) patients and to study the various factors affecting the response of DAAs in CHC. Settings and Design This longitudinal observational study spanning over a year was conducted in the Medicine department of a tertiary care teaching hospital. Materials and Methods The study was conducted on 400 adult CHC patients, diagnosed by a positive anti-HCV antibody test and a detectable viral load (HCV RNA) by real time polymerase chain reaction (RT-PCR), registered for treatment with DAAs. The first 400 patients satisfying the eligibility criteria were enrolled by non-probability consecutive sampling. All the participants were treated as per the National Viral Hepatitis Control Programme (NVHCP) guidelines. Repeat HCV viral load was done at or after 12 weeks of completion of anti-viral therapy to ascertain sustained virological response (SVR). Various factors which might predict treatment response were analyzed. Statistical Analysis Used The continuous variables were expressed as mean and standard deviation, while the categorical variables were summarized as frequencies and percentages. The Student's independent t-test was employed for the comparison of continuous variables. The Chi-square or Fisher's exact test, whichever is appropriate, was employed for the comparison of categorical variables. Multivariate Logistic Regression was used to identify the independent predictors of treatment nonresponse. A P < 0.05 was considered statistically significant. Results The mean age of the subjects was 42.3 ± 15.23 years with a male-to-female ratio of 1.96:1. Most of the patients (80.5%) were non-cirrhotic; among 19.5% cirrhotic, 13% were compensated while 6.5% were decompensated cirrhotic. The overall SVR done at or after 12 weeks of completion of treatment was 88.75%. Age, gender distribution, occupation, socioeconomic status, educational status, body mass index, treatment regimen, duration of treatment, and baseline viral load did not alter the treatment response. Among comorbidities, only diabetes mellitus (DM) and human immunodeficiency virus (HIV) co-infection adversely affected the treatment response (P = 0.009 and P < 0.001, respectively). Intravenous (IV) drug abuse was significantly associated with treatment failure (P < 0.001). The presence of liver cirrhosis (P < 0.001), thrombocytopenia (P < 0.001), elevated transaminases (alanine transaminase: P = 0.021, aspartate transaminase: P < 0.001), and previous treatment experience (P = 0.038) were other significant predictors of treatment failure. Conclusions DAAs are highly efficacious drugs in the treatment of CHC with a high rate of treatment response. Significant predictors of CHC treatment failure included comorbidities especially DM and HIV co-infection, IV drug abuse, presence of liver cirrhosis, thrombocytopenia, elevated transaminases, and previous treatment experience. However, independent predictors of treatment nonresponse observed in this study were thrombocytopenia, IV drug abuse, and liver cirrhosis.
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Affiliation(s)
- Nipun Jain
- Department of Medicine, Guru Gobind Singh Medical College and Hospital, Faridkot, Punjab, India
| | - Ravinder Garg
- Department of Medicine, Guru Gobind Singh Medical College and Hospital, Faridkot, Punjab, India
| | - Gagan Preet Singh
- Department of Community Medicine, Guru Gobind Singh Medical College and Hospital, Faridkot, Punjab, India
| | - Sarabjot Kaur
- Department of Medicine, Guru Gobind Singh Medical College and Hospital, Faridkot, Punjab, India
| | - Sumit Pal Singh Chawla
- Department of Medicine, Guru Gobind Singh Medical College and Hospital, Faridkot, Punjab, India
| | - Preeti Padda
- Department of Community Medicine, Government Medical College, Amritsar, Punjab, India
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Popescu MS, Firu DM, Pădureanu V, Mărginean CM, Mitruț R, Arsene AL, Mărgăritescu DN, Calina D, Docea AO, Mitruț P. Effects of Achieving Sustained Virologic Response after Direct-Acting Antiviral Agents on Long-Term Liver Fibrosis in Diabetics vs. in Non-Diabetic Patients with Chronic Hepatitis C Infection. Biomedicines 2022; 10:2093. [PMID: 36140194 PMCID: PMC9495608 DOI: 10.3390/biomedicines10092093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 08/22/2022] [Accepted: 08/24/2022] [Indexed: 12/15/2022] Open
Abstract
Because of the prevalence of HCV worldwide as well as its undiagnosed population due to a lack of screening, HCV can be considered a modern pandemic disease. In 2016, the World Health Organization (WHO) set goals for HCV's elimination that included a 65 percent reduction in mortality and an 80 percent reduction in newly infected cases by 2030. This study is a follow-up evaluation of 80 patients who received interferon-free treatment with direct-acting agents (DAA) for chronic HCV infection between the second half of 2017 and the end of 2018. They were assessed using a FibroMax test prior to DAA administration. Two pills/day of Ombitasvir 12.5 mg/Paritaprevir 75 mg/Ritonavir 50 mg and two pills/day of Dasabuvir 250 mg were given to the patients for 8 weeks. After treatment, all 80 patients in this study achieved an SVR (sustained virologic response), and the FibroMax test was performed three years later. Our study found that successfully treating HCV infection can play a significant role in reducing fibrosis in T2DM patients. In comparison to those of ActiTest and SteatoTest, FibroMax scores showed a significantly greater reduction in T2DM patients than in treatment-naive patients.
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Affiliation(s)
- Marian-Sorin Popescu
- Department of Medical Semiology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Dan-Mihai Firu
- Department of Medical Semiology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Vlad Pădureanu
- Department of Medical Semiology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Cristina Maria Mărginean
- Department of Medical Semiology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Radu Mitruț
- Department of Cardiology, University and Emergency Hospital, 050098 Bucharest, Romania
| | - Andreea Letitia Arsene
- Department of Microbiology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | | | - Daniela Calina
- Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Anca Oana Docea
- Department of Toxicology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Paul Mitruț
- Department of Medical Semiology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
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Alzahrani N. Hepatitis C Virus, Insulin Resistance, and Diabetes: A Review. Microbiol Immunol 2022; 66:453-459. [PMID: 35941761 DOI: 10.1111/1348-0421.13023] [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: 01/25/2022] [Revised: 07/19/2022] [Accepted: 08/03/2022] [Indexed: 12/15/2022]
Abstract
Hepatitis C virus (HCV) infection and diabetes mellitus (DM) are two chronic diseases that are a cause of significant health and economic burdens worldwide. HCV is associated with the development of insulin resistance (IR) and diabetes mellitus (DM). The mechanisms through which HCV induces IR and DM include direct viral effects, pro-inflammatory cytokines and other immune-mediated processes. Type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) are both chronic diseases that involve impaired glucose homeostasis, albeit through different mechanisms. T1DM is an autoimmune disease that leads to the destruction of pancreatic beta cells resulting in insulin deficiency. In T2DM, a combination of peripheral insulin resistance and irregular production of insulin eventually lead to beta cell destruction and insulin insufficiency. Both type 1 and type 2 DM etiologies involve a combination of genetic and environmental factors. The data on HCV and T1DM association is limited, unlike T2DM, where a large body of evidence linking HCV to T2DM is available. Here, we intend to outline the current state of knowledge on HCV, IR, and DM. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Nabeel Alzahrani
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud bin Abdulaziz University for Health Sciences, Riyadh, 14611, Saudi Arabia
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Hagag RY, Selim AF, Darrag OM, Zied H, Aboelnasr MS. Does Hepatitis C Virus Treatment by Directly Acting Antivirals Obligate Shifting Patients with Type 2 Diabetes from Oral Hypoglycemic Drugs to Insulin Therapy? Diabetes Metab Syndr Obes 2022; 15:1261-1268. [PMID: 35502409 PMCID: PMC9056022 DOI: 10.2147/dmso.s354023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2021] [Accepted: 04/06/2022] [Indexed: 12/15/2022] Open
Abstract
PURPOSE The aim of the present work was to investigate whether hepatitis C virus treatment by directly acting antivirals obligate shifting patients with type 2 diabetes from oral hypoglycemic drugs to insulin therapy. METHODS This was a prospective study including 92 treatment-naïve patients with chronic hepatitis C virus infection and type 2 diabetes who were eligible for treatment with directly acting antivirals (sofosbuvir + daclatasvir ± ribavirin). Patients in the study were divided into two groups; group 1 included 22 patients on insulin therapy and group 2 included 70 patients on oral antidiabetic medications. Patients were advised to keep on their anti-diabetic treatment. RESULTS All our patients achieved sustained virologic response with significantly lower HbA1c 12 weeks after the end of therapy (p. values 0.001 for group 1 and group 2). There was no statistically significant difference in HbA1c level post-treatment between both groups (p. value 0.352). CONCLUSION Achievement of sustained virologic response using interferon free, directly acting antivirals-based regimen was associated with significantly lower HbA1c 12 weeks after the end of therapy. The type of treatment used for type 2 diabetes (oral drugs or insulin) did not affect improved glycemic control observed after achieving sustained virologic response.
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Affiliation(s)
- Rasha Youssef Hagag
- Department of internal medicine, Faculty of medicine, Tanta University, Tanta, Egypt
| | - Ahmed Fawzy Selim
- Department of internal medicine, Faculty of medicine, Tanta University, Tanta, Egypt
| | - Omneya Mohamed Darrag
- Department of internal medicine, Faculty of medicine, Tanta University, Tanta, Egypt
| | - Hassan Zied
- Kafr-Elsheikh Liver Institute, Kafr-Elsheikh, Egypt
| | - Mohamed Sabry Aboelnasr
- Department of internal medicine, Faculty of medicine, Tanta University, Tanta, Egypt
- Correspondence: Mohamed Sabry Aboelnasr, Elgeish Street, Aboelelasorour Building, Floor 6, Kafrelzayat, Gharbia Governorate, 31611, Egypt, Tel +20 1066276267, Email ;
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Chen G, Zhang W, Ben Y. Identification of Key Regulators of Hepatitis C Virus-Induced Hepatocellular Carcinoma by Integrating Whole-Genome and Transcriptome Sequencing Data. Front Genet 2021; 12:741608. [PMID: 34567091 PMCID: PMC8460086 DOI: 10.3389/fgene.2021.741608] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Accepted: 08/12/2021] [Indexed: 12/23/2022] Open
Abstract
Background: Hepatitis C virus (HCV) infection is a major cause of cirrhosis and hepatocellular carcinoma (HCC). Despite recent advances in the understanding of the biological basis of HCC development, the molecular mechanisms underlying HCV-induced HCC (HCC-HCV) remain unclear. The carcinogenic potential of HCV varies according to the genotype and mutation in its viral sequence. Moreover, regulatory pathways play important roles in many pathogenic processes. Therefore, identifying the pathways by which HCV induces HCC may enable improved HCC diagnosis and treatment. Methods: We employed a systematic approach to identify an important regulatory module in the process of HCV-HCC development to find the important regulators. First, an HCV-related HCC subnetwork was constructed based on the gene expression in HCC-HCV patients and HCC patients. A priority algorithm was then used to extract the module from the subnetworks, and all the regulatory relationships of the core genes of the network were extracted. Integrating the significantly highly mutated genes involved in the HCC-HCV patients, core regulatory modules and key regulators related to disease prognosis and progression were identified. Result: The key regulatory genes including EXO1, VCAN, KIT, and hsa-miR-200c-5p were found to play vital roles in HCV-HCC development. Based on the statistics analysis, EXO1, VCAN, and KIT mutations are potential biomarkers for HCV–HCC prognosis at the genomic level, whereas has-miR-200c-5P is a potential biomarker for HCV–HCC prognosis at the expression level. Conclusion: We identified three significantly mutated genes and one differentially expressed miRNA, all related to HCC prognosis. As potential pathogenic factors of HCC, these genes and the miRNA could be new biomarkers for HCV-HCC diagnosis.
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Affiliation(s)
- Guolin Chen
- Department of Infectious Diseases, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Wei Zhang
- Department of Infectious Diseases, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Yiran Ben
- Department of Infectious Diseases, The First Affiliated Hospital of Harbin Medical University, Harbin, China
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Lapumnuaypol K, Pisarcik D, Putthapiban P, Sukhumthammarat W, Wijarnpreecha K, Thongprayoon C, Ungprasert P. Direct-acting antiviral agents decrease haemoglobin A1c level in patients with diabetes infected with hepatitis C virus: A systematic review & meta-analysis. Indian J Med Res 2021; 152:562-567. [PMID: 34145095 PMCID: PMC8224154 DOI: 10.4103/ijmr.ijmr_1088_18] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/09/2022] Open
Abstract
Background & objectives: Several epidemiologic studies have demonstrated that type 2 diabetes mellitus (T2DM) is more prevalent in patients infected with hepatitis C virus (HCV), and the eradication of HCV has been shown to decrease the risk of T2DM. This meta-analysis was undertaken to see if treatment with direct-acting antiviral (DAA) agents would improve glycaemic control among HCV-infected patients with T2DM . Methods: A systematic review was conducted using MEDLINE and EMBASE databases since inception to February 2018. Eligible studies must be cohort studies that recruited HCV-infected patients with T2DM and received DAA therapy. The studies must report the change of haemoglobin A1c (HbA1c) level (before vs. after DAA therapy). Patients who achieved sustained virologic response (SVR) were included in the meta-analysis. The mean HbA1c level and standard deviation of participants were extracted from each study to calculate the mean difference (MD). Pooled MD was then calculated using the random effects model. Results: Four cohort studies with 2648 patients were included. Among HCV-infected T2DM patients who achieved SVR with DAA agents, the mean HbA1c level after treatment was significantly lower than the mean HbA1c level before treatment, with the pooled MD of −0.50 per cent (95% confidence interval, −0.66 to −0.34, I2 = 77%). The main limitation of this study was the lack of comparison groups. Therefore, it could not be concluded that the observed decreased HbA1c level was a direct result of DAA therapy. Interpretation & conclusions: Treatment with DAA agents was found to be associated with a significant reduction of post-treatment HbA1c level compared with pre-treatment HbA1c level among T2DM patients who achieved SVR.
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Affiliation(s)
| | - David Pisarcik
- Department of Internal Medicine, Philadelphia College of Osteopathic Medicine, PA, USA
| | | | | | - Karn Wijarnpreecha
- Department of Gastroenterology, Mayo Clinic Hospital, Gastroenterology - Jacksonville, FL, USA
| | - Charat Thongprayoon
- Department of Nephrology, Mayo Clinic, Nephrology & Hypertension Rochester, MN, USA
| | - Patompong Ungprasert
- Department of Research & Development, Division of Clinical Epidemiology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
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Narayanamurthy V, Jeroish ZE, Bhuvaneshwari KS, Samsuri F. Hepatitis C virus (HCV) diagnosis via microfluidics. ANALYTICAL METHODS : ADVANCING METHODS AND APPLICATIONS 2021; 13:740-763. [PMID: 33511975 DOI: 10.1039/d0ay02045a] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
Humans are subjected to various diseases; hence, proper diagnosis helps avoid further disease consequences. One such severe issue that could cause significant damage to the human liver is the hepatitis C virus (HCV). Several techniques are available to detect HCV under various categories, such as detection through antibodies, antigens, and RNA. Although immunoassays play a significant role in discovering hepatitis viruses, there is a need for point-of-care tests (POCT). Some developing strategies are required to ensure the appropriate selection of POCT for HCV detection, initiate appropriate antiviral therapy, and define associated risks, which will be critical in achieving optimal outcomes. Though molecular assays are precise, reproducible, sensitive, and specific, alternative strategies are required to enhance HCV diagnosis among the infected population. Herein, we described and assessed the potential of various microfluidic detection techniques and confirmatory approaches used in present communities. In addition, current key market players in HCV chip-based diagnosis and the future perspectives on the basis of which the diagnosis can be made easier are presented in the present review.
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Affiliation(s)
- Vigneswaran Narayanamurthy
- Fakulti Teknologi Kejuruteraan Elektrik dan Elektronik, Universiti Teknikal Malaysia Melaka, Hang Tuah Jaya, 76100 Durian Tunggal, Melaka, Malaysia.
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Losurdo G, Iannone A, Contaldo A, Barone M, Ierardi E, Di Leo A, Principi M. Chronic Viral Hepatitis in a Cohort of Inflammatory Bowel Disease Patients from Southern Italy: A Case-Control Study. Pathogens 2020; 9:870. [PMID: 33113974 PMCID: PMC7690684 DOI: 10.3390/pathogens9110870] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Revised: 10/20/2020] [Accepted: 10/21/2020] [Indexed: 02/07/2023] Open
Abstract
We performed an epidemiologic study to assess the prevalence of chronic viral hepatitis in inflammatory bowel disease (IBD) and to detect their possible relationships. Methods: It was a single centre cohort cross-sectional study, during October 2016 and October 2017. Consecutive IBD adult patients and a control group of non-IBD subjects were recruited. All patients underwent laboratory investigations to detect chronic hepatitis B (HBV) and C (HCV) infection. Parameters of liver function, elastography and IBD features were collected. Univariate analysis was performed by Student's t or chi-square test. Multivariate analysis was performed by binomial logistic regression and odds ratios (ORs) were calculated. We enrolled 807 IBD patients and 189 controls. Thirty-five (4.3%) had chronic viral hepatitis: 28 HCV (3.4%, versus 5.3% in controls, p = 0.24) and 7 HBV (0.9% versus 0.5% in controls, p = 0.64). More men were observed in the IBD-hepatitis group (71.2% versus 58.2%, p < 0.001). Patients with IBD and chronic viral hepatitis had a higher mean age and showed a higher frequency of diabetes, hypertension and wider waist circumference. They suffered more frequently from ulcerative colitis. Liver stiffness was greater in subjects with IBD and chronic viral hepatitis (7.0 ± 4.4 versus 5.0 ± 1.2 KPa; p < 0.001). At multivariate analysis, only old age directly correlated with viral hepatitis risk (OR = 1.05, 95%CI 1.02-1.08, p < 0.001). In conclusion, the prevalence of HBV/HCV in IBD is low in our region. Age may be the only independent factor of viral hepatitis-IBD association. Finally, this study firstly measured liver stiffness in a large scale, showing higher values in subjects with both diseases.
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Affiliation(s)
- Giuseppe Losurdo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy; (G.L.); (A.I.); (A.C.); (M.B.); (E.I.); (M.P.)
| | - Andrea Iannone
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy; (G.L.); (A.I.); (A.C.); (M.B.); (E.I.); (M.P.)
| | - Antonella Contaldo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy; (G.L.); (A.I.); (A.C.); (M.B.); (E.I.); (M.P.)
| | - Michele Barone
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy; (G.L.); (A.I.); (A.C.); (M.B.); (E.I.); (M.P.)
| | - Enzo Ierardi
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy; (G.L.); (A.I.); (A.C.); (M.B.); (E.I.); (M.P.)
| | - Alfredo Di Leo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy; (G.L.); (A.I.); (A.C.); (M.B.); (E.I.); (M.P.)
| | - Mariabeatrice Principi
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy; (G.L.); (A.I.); (A.C.); (M.B.); (E.I.); (M.P.)
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Saleh P, Sheikholeslami A, Salman Mohajer A, Babapour S, Hosseini MS. 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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Marei ES, Gabr HM, Shaheen DS. Potential role of vaspin and apelin in chronic hepatitis C virus patients with and without diabetes. JOURNAL OF RADIATION RESEARCH AND APPLIED SCIENCES 2020. [DOI: 10.1080/16878507.2020.1715556] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Liu Y, Ye S, Xiao X, Zhou T, Yang S, Wang G, Sun C, Zhang B, Wang G. Association of diabetes mellitus with hepatitis B and hepatitis C virus infection: evidence from an epidemiological study. Infect Drug Resist 2019; 12:2875-2883. [PMID: 31686868 PMCID: PMC6751765 DOI: 10.2147/idr.s218536] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2019] [Accepted: 09/02/2019] [Indexed: 12/17/2022] Open
Abstract
Objective To study the association between glucose metabolism disorders and hepatotropic virus infection. Methods A cross-sectional analysis was performed using data from the REACTION study (Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal Study). Outcomes of the analysis were test results of kidney function, liver function, lipid metabolism, and the prevalence of hepatitis B virus (HBV) infection and potential hepatitis C virus (HCV) infection (positive hepatitis C virus antibody) among individuals with and without diabetes mellitus (DM) or pre-diabetes mellitus (pre-DM). Results Of the 10,080 patients who participated in the study, 7665 eligible subjects were included in the analysis. There was no significant difference in the prevalence of HBV infection between DM and normal subjects, pre-DM and normal subjects, and DM or pre-DM and normal subjects (p-values of 0.9180, 0.8154, and 0.6448, respectively). There was also no significant difference in the prevalence of potential HCV infection between DM and normal subjects, pre-DM and normal subjects, and DM or pre-DM and normal subjects (p-values of 0.1190, 0.0591, and 0.5591, respectively). Lipid metabolism showed a significant difference between DM or pre-DM subjects and normal subjects (p-values were less than 0.0221 in all cases). Multiple logistic regression analysis revealed hypertension as the leading significant variable associated with DM, pre-DM, and both. Other significant factors included gender, body mass index, age, and alanine aminotransferase. Conclusion No significant association was detected between DM or pre-DM and HBV or potential HCV infection. Significant association was detected between lipid metabolism disorders and DM, but this association was absent in pre-DM patients when adjusting for other factors.
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Affiliation(s)
- Yujia Liu
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin, People's Republic of China
| | - Shangyuan Ye
- Department of Population and Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, MA, USA
| | - Xianchao Xiao
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin, People's Republic of China
| | - Tong Zhou
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin, People's Republic of China
| | - Shuo Yang
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin, People's Republic of China
| | - Gang Wang
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin, People's Republic of China
| | - Chenglin Sun
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin, People's Republic of China
| | - Bo Zhang
- Department of Population and Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, MA, USA
| | - Guixia Wang
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin, People's Republic of China
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Lapumnuaypol K, Thongprayoon C, Wijarnpreecha K, Cheungpasitporn W. Impact of hepatitis C sustained viral response on cardiovascular diseases: a meta-analysis. Hosp Pract (1995) 2019; 47:105-110. [PMID: 31018721 DOI: 10.1080/21548331.2019.1612066] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Background: Hepatitis C virus-infected patients are found to have increased risks of cardiovascular disease (CVD)-related morbidity and mortality. However, the effect of treatment on cardiovascular risk remains unknown. We performed a systematic review and meta-analysis to assess the effect of Sustained Virologic Response (SVR) on cardiovascular outcome in chronic HCV-infected patients. Methods: A systematic review was conducted in MEDLINE, EMBASE, Cochrane databases from inception through November 2018 to identify studies that assessed the effect of SVR on CVDs. Effect estimates from the individual study were extracted and combined using random-effect, generic inverse variance method of DerSimonian and Laird. Results: Seven cohort studies with a total of 53,841 HCV-infected patients with average follow-up time of 5 years were enrolled. When compared with HCV-infected patients who do not achieve SVR, patients with SVR have a reduced risk of overall CVDs with the pooled hazard ratio of 0.76 (95% confidence interval 0.61-0.94). Egger's regression asymmetry test was performed and showed no publication bias. Conclusions: Our study demonstrates a significant association between SVR after HCV treatment and reduced risk of overall CVDs.
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Affiliation(s)
- Kamolyut Lapumnuaypol
- Department of Internal Medicine, Albert Einstein Medical Center , Philadelphia , PA , USA
| | - Charat Thongprayoon
- Department of Nephrology and Hypertension, Mayo Clinic , Rochester , MN , USA
| | - Karn Wijarnpreecha
- Department of Gastroenterology, Mayo Clinic Hospital , Jacksonville , FL , USA
| | - Wisit Cheungpasitporn
- Division of Nephrology, Department of Medicine, University of Mississippi Medical Center , Jackson , MS , USA
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Santos TPS, Pereira MDM, Schinoni MI, Sampaio GP, Aras R, Atta MLS, Atta AM. Atherogenic cytokines and chemokines in chronic hepatitis C are not associated with the presence of cardiovascular diseases. Cytokine 2019; 115:24-31. [PMID: 30771700 DOI: 10.1016/j.cyto.2018.12.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2018] [Revised: 11/26/2018] [Accepted: 12/05/2018] [Indexed: 12/27/2022]
Abstract
There appears to be an associative link between chronic hepatitis C (CHC) and cardiovascular diseases (CVDs). However, the exact nature of the relationship between CHC and CVDs has not been elucidated. We investigated the presence of CVDs and the clinical and laboratory alterations associated with these diseases in CHC patients. Twenty-six CHC patients, 35 individuals with atherosclerosis (Athero) and 27 healthy individuals were examined for risk factors for CVD, lipid profile, atherogenic risk indexes, and insulin resistance (IR). Cardiac biomarkers and the chemokines and cytokines involved in atherosclerosis were also evaluated. A higher prevalence of prior acute myocardial infarction was found in the Athero group. Most CHC patients were infected with the hepatitis C virus genotype 1 and exhibited either no hepatic fibrosis or a mild to moderate liver fibrosis. The apolipoprotein B/apolipoprotein A-I and triglyceride/high-density lipoprotein cholesterol ratios and C-reactive protein levels were lower in CHC patients than in the Athero group. Further, IR was elevated in the CHC group and associated with the waist circumference. High GDF-15 levels were observed in the CHC group, which were inversely correlated with APOB levels. Peripheral blood mononuclear cells from CHC patients produced more IFN-γ, TNF-α and IL-6 than CAD PBMC but the production of IL-10 and IL-1β was similar. CHC and CAD groups presented similar levels of IL-8, MCP-1 and LAP-TGF-β1. Increased IR, elevated levels of GDF-15, and high production of atherogenic cytokines can be observed in Brazilian CHC patients without association with diabetes and clinical manifestation of cardiovascular diseases.
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Affiliation(s)
| | | | | | | | - Roque Aras
- Hospital Universitário Prof. Edgard Santos, Universidade Federal da Bahia, Brazil
| | - Maria Luiza Sousa Atta
- Faculdade de Farmácia, Laboratório de Pesquisa em Imunologia, Universidade Federal da Bahia, Brazil
| | - Ajax M Atta
- Faculdade de Farmácia, Laboratório de Pesquisa em Imunologia, Universidade Federal da Bahia, Brazil.
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14
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Jepson C, Hsu JY, Fischer MJ, Kusek JW, Lash JP, Ricardo AC, Schelling JR, Feldman HI. Incident Type 2 Diabetes Among Individuals With CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study. Am J Kidney Dis 2019; 73:72-81. [PMID: 30177484 PMCID: PMC6309655 DOI: 10.1053/j.ajkd.2018.06.017] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2018] [Accepted: 06/12/2018] [Indexed: 01/15/2023]
Abstract
RATIONALE & OBJECTIVE Few studies have examined incident type 2 diabetes mellitus (T2DM) in chronic kidney disease (CKD). Our objective was to examine rates of and risk factors for T2DM in CKD, using several alternative measures of glycemic control. STUDY DESIGN Prospective cohort study. SETTING & PARTICIPANTS 1,713 participants with reduced glomerular filtration rates and without diabetes at baseline, enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. PREDICTORS Measures of kidney function and damage, fasting blood glucose, hemoglobin A1c (HbA1c), HOMA-IR (homeostatic model assessment of insulin resistance), demographics, family history of diabetes mellitus (DM), smoking status, medication use, systolic blood pressure, triglyceride level, high-density lipoprotein cholesterol level, body mass index, and physical activity. OUTCOME Incident T2DM (defined as fasting blood glucose ≥ 126mg/dL or prescription of insulin or oral hypoglycemic agents). ANALYTICAL APPROACH Concordance between fasting blood glucose and HbA1c levels was assessed using κ. Cause-specific hazards modeling, treating death and end-stage kidney disease as competing events, was used to predict incident T2DM. RESULTS Overall T2DM incidence rate was 17.81 cases/1,000 person-years. Concordance between fasting blood glucose and HbA1c levels was low (κ for categorical versions of fasting blood glucose and HbA1c = 13%). Unadjusted associations of measures of kidney function and damage with incident T2DM were nonsignificant (P ≥ 0.4). In multivariable models, T2DM was significantly associated with fasting blood glucose level (P = 0.002) and family history of DM (P = 0.03). The adjusted association of HOMA-IR with T2DM was comparable to that of fasting blood glucose level; the association of HbA1c level was nonsignificant (P ≥ 0.1). Harrell's C for the models ranged from 0.62 to 0.68. LIMITATIONS Limited number of outcome events; predictors limited to measures taken at baseline. CONCLUSIONS The T2DM incidence rate among individuals with CKD is markedly higher than in the general population, supporting the need for greater vigilance in this population. Measures of glycemic control and family history of DM were independently associated with incident T2DM.
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Affiliation(s)
- Christopher Jepson
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA.
| | - Jesse Y Hsu
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA
| | - Michael J Fischer
- Department of Medicine, University of Illinois College of Medicine, Chicago, IL; Center of Innovation for Complex Chronic Healthcare, Edward Hines Jr VA Hospital, Hines, and Jesse Brown VAMC, Chicago, IL
| | - John W Kusek
- Division of Kidney, Urologic and Hematologic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD
| | - James P Lash
- Department of Medicine, University of Illinois College of Medicine, Chicago, IL
| | - Ana C Ricardo
- Department of Medicine, University of Illinois College of Medicine, Chicago, IL
| | - Jeffrey R Schelling
- Division of Nephrology and Hypertension, Case Western Reserve University, Cleveland, OH
| | - Harold I Feldman
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA
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15
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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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16
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Cao LH, Lu FM, Lu XJ, Zhu LY. Study on the relationship between insulin growth factor 1 and liver fibrosis in patients with chronic hepatitis C with type 2 diabetes mellitus. J Cell Biochem 2018; 119:9513-9518. [PMID: 30105830 DOI: 10.1002/jcb.27267] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2018] [Accepted: 06/22/2018] [Indexed: 02/06/2023]
Abstract
OBJECTIVE To investigate the correlation between serum protein level of insulin growth factor 1 (IGF-1) and the degree of liver fibrosis in patients with chronic hepatitis C (CHC) combined with type 2 diabetes mellitus (T2DM). METHODS The cases are divided into four groups. Then serum levels of IFG-1, alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatitis C virus (HCV) RNA, and HCV genotypes were detected simultaneously in patients with hepatitis C, liver stiffness measurement (LSM) was measured by transient elastography, and aspartate aminotransferase platelet ratio (APRI) score was determined. RESULTS There was no significant difference between CHC with T2DM group and CHC group in diabetes family history (P > 0.05), but the difference between the two groups were significantly lower than that of T2DM group ( P < 0.05). The levels of fasting insulin and homeostatic model assessment of insulin resistance (HOMA-IR) in CHC group with T2DM group were significantly higher than those in the other two groups ( P < 0.05), while the IGF-1 RNA and the serum protein level in the two groups were significantly lower than those in the CHC group, and were lower than those in the control group ( P < 0.05). The level of serum IGF-1 was negatively correlated with HOMA-IR, LSM, and APRI score in CHC with T2DM group ( r = -0.71, -0.75, and -0.69; P < 0.01). CONCLUSION The degree of hepatic fibrosis in patients with CHC combined with T2DM was higher than that in non-T2DM patients with CHC, which was mainly related to insulin resistance (IR) induced by 1b genotype HCV infection. IR can lead to impaired synthesis of IGF-1, and the degree of damage has a corresponding relationship with hepatic fibrosis.
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Affiliation(s)
- Li-Hua Cao
- Liver Disease Center, The Third Hospital of Qinhuangdao City, Qinhuangdao, China
| | - Feng-Min Lu
- Department of Microbiology and Infectious Disease Center, Peking University Health Science Center, Beijing, China
| | - Xiao-Jie Lu
- Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Li-Yao Zhu
- Department of Hepatology, The Fourth People's Hospital of Huai'an, Huai'an, China
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17
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Plasma β-amyloid 1–42 reference values in cognitively normal subjects. J Neurol Sci 2018; 391:120-126. [DOI: 10.1016/j.jns.2018.06.006] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2018] [Revised: 05/18/2018] [Accepted: 06/12/2018] [Indexed: 12/17/2022]
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18
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Li J, Zhang T, Gordon SC, Rupp LB, Trudeau S, Holmberg SD, Moorman AC, Spradling PR, Teshale EH, Boscarino JA, Schmidt MA, Daida YG, Lu M. Impact of sustained virologic response on risk of type 2 diabetes among hepatitis C patients in the United States. J Viral Hepat 2018; 25:952-958. [PMID: 29478263 PMCID: PMC6205163 DOI: 10.1111/jvh.12887] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2017] [Accepted: 01/16/2018] [Indexed: 12/27/2022]
Abstract
Data regarding the impact of hepatitis C (HCV) therapy on incidence of type 2 diabetes mellitus are limited. We used the data from the longitudinal Chronic Hepatitis Cohort Study-drawn from four large US health systems-to investigate how response to HCV treatment impacts the risk of subsequent diabetes. Among HCV patients without a history of type 2 diabetes mellitus or hepatitis B, we investigated the incidence of type 2 diabetes from 12 weeks post-HCV treatment through December 2015. Cox proportional hazards models were used to test the effect of treatment status (sustained virologic response [SVR] or treatment failure) and baseline risk factors on the development of diabetes, considering any possible risk factor-by-SVR interactions, and death as a competing risk. Among 5127 patients with an average follow-up of 3.7 years, diabetes incidence was significantly lower among patients who achieved SVR (231/3748; 6.2%) than among patients with treatment failure (299/1379; 21.7%; adjusted hazard ratio [aHR] = 0.79; 95% CI: 0.65-0.96). Risk of diabetes was higher among African American and Asian American patients than White patients (aHR = 1.82 and 1.75, respectively; P < .05), and among Hispanic patients than non-Hispanics (aHR = 1.86). Patients with BMI ≥ 30 and 25-30 (demonstrated higher risk of diabetes aHR = 3.62 and 1.72, respectively; P < .05) than those with BMI < 25; patients with cirrhosis at baseline had higher risk than those without cirrhosis (aHR = 1.47). Among a large US cohort of patients treated for HCV, patients who achieved SVR demonstrated a substantially lower risk for the development of type 2 diabetes mellitus than patients with treatment failure.
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Affiliation(s)
- J. Li
- Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA
| | - T. Zhang
- Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA
| | - S. C. Gordon
- Division of Gastroenterology and Hepatology, Henry Ford Health System, Detroit, MI, USA
| | - L. B. Rupp
- Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, MI, USA
| | - S. Trudeau
- Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA
| | - S. D. Holmberg
- Division of Viral Hepatitis, National Center for HIV, Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - A. C. Moorman
- Division of Viral Hepatitis, National Center for HIV, Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - P. R. Spradling
- Division of Viral Hepatitis, National Center for HIV, Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - E. H. Teshale
- Division of Viral Hepatitis, National Center for HIV, Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - J. A. Boscarino
- Department of Epidemiology and Health Services Research, Geisinger Clinic, Danville, PA, USA
| | - M. A. Schmidt
- Center for Health Research, Kaiser Permanente–Northwest, Portland, OR, USAs
| | - Y. G. Daida
- Center for Health Research, Kaiser Permanente–Hawaii, Honolulu, HI, USA
| | - M. Lu
- Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA
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19
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Provoost A, Dramé M, Cotte L, Cuzin L, Garraffo R, Rey D, Raffi F, Poizot-Martin I, Pugliese P, Bani-Sadr F. Risk of diabetes in HIV-infected patients is associated with cirrhosis but not with chronic HCV coinfection in a French nationwide HIV cohort. Aliment Pharmacol Ther 2018; 48:281-289. [PMID: 29901821 DOI: 10.1111/apt.14812] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2018] [Revised: 02/12/2018] [Accepted: 04/29/2018] [Indexed: 12/20/2022]
Abstract
BACKGROUND Both human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections have been reportedly associated with a higher risk of diabetes mellitus (DM) but results are conflicting. AIMS To determine whether there is an association between chronic HCV and the incidence of DM, and to study the role of factors such as cirrhosis, IFN-based HCV therapy, sustained virologic response (SVR) and chronic HBV infection among patients living with HIV (PLHIV) followed in a large French multicentre cohort in the combination antiretroviral therapy (cART) era. METHODS All PLHIV followed up in the Dat'AIDS cohort were eligible. Cox models for survival analysis were used to study the time to occurrence of DM. RESULTS Among 28 699 PLHIV, 4004 patients had chronic HCV infection. The mean duration of HCV follow-up was 12.5 ± 8.1 years. The rate ratio of DM was 2.74 per 1000 person-years. By multivariate analysis, increasing age, body mass index>25, AIDS status, nadir CD4 cell count ≤200/mm3 , detectable HIV viral load and cirrhosis (HR 2.26 95% CI 1.14-1.18; P < 0.0001) were predictors of DM, whereas longer cART duration was associated with a lower risk of DM. Chronic HCV and HBV infection and IFN-based HCV therapy were not associated with DM. In a subanalysis among HCV-infected patients, SVR was not related to DM. CONCLUSIONS Our study shows that in the HIV population, cirrhosis is associated with an increased occurrence of DM, but not chronic HCV infection or duration of HCV infection.
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20
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Provoost A, Dramé M, Bani-Sadr F. Editorial: diabetes in HIV-infected patients-do not blame the usual suspect! Authors' reply. Aliment Pharmacol Ther 2018; 48:482-483. [PMID: 30588690 DOI: 10.1111/apt.14892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/08/2022]
Affiliation(s)
- A Provoost
- Department of Research and Public Health, Reims Teaching Hospitals, Robert Debré Hospital, Reims, France
| | - M Dramé
- Department of Research and Public Health, Reims Teaching Hospitals, Robert Debré Hospital, Reims, France
| | - F Bani-Sadr
- Department of Internal Medicine, Infectious Diseases, and Clinical Immunology, University of Reims Champagne-Ardenne, Reims, France
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21
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Shen X, Cai J, Gao J, Vaidya A, Liu X, Li W, Chen S, Zhou Y, Li Y, Zhang Y, Zhao J, Hu FB, Wu S, Gao X. Nonalcoholic Fatty Liver Disease and Risk of Diabetes: A Prospective Study in China. Endocr Pract 2018; 24:823-832. [PMID: 29975579 DOI: 10.4158/ep-2018-0098] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVE We aimed to investigate whether liver steatosis severity affects the risk of developing diabetes in a large cohort study. METHODS We prospectively examined the association in 41,650 Chinese adults with negative hepatitis-B surface antigen who were free of alcohol consumption, diabetes, and liver cirrhosis at baseline. Cox proportional models were used to estimate the risk of diabetes after a mean of 3.6 years of follow-up. Nonalcoholic fatty liver disease (NAFLD) was assessed with hepatic ultrasonography. Elevated alanine transaminase (ALT) was defined as ALT concentrations >19 and >30 U/L in females and males, respectively. Diabetes was defined as a fasting glucose 37.0 mmol/L or treatment with hypoglycemic medication. RESULTS Liver steatosis severity was significantly associated with higher risks of developing diabetes (adjusted hazard ratio [HR] for severe vs. without NAFLD = 2.66, 95% confidence interval [CI]: 2.17-3.25, P-trend<.001) and impaired fasting glucose (fasting glucose between 5.6 and 6.9 mmol/L, adjusted HR = 1.36, 95% CI: 1.16-1.59, P-trend<.001), as well as a faster increase rate of fasting glucose concentrations ( P-trend<.001), during 3.6 years of follow-up. Elevated ALT was also associated with incident diabetes (HR = 1.12, 95% CI: 1.02-1.22), adjusting for NAFLD and other covariates. CONCLUSION We observed a dose-response relationship between liver steatosis severity and increased diabetes risk, and ALT may predict incident diabetes independently of NAFLD. ABBREVIATIONS ALT = alanine transaminase; BP = blood pressure; CI = confidence interval; HCV = hepatitis C virus; HR = hazard ratio; IFG = impaired fasting glucose; NAFLD = nonalcoholic fatty liver disease; ULN = upper limit of normal.
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22
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Puchades Renau L, Berenguer M. Introduction to hepatitis C virus infection: Overview and history of hepatitis C virus therapies. Hemodial Int 2018; 22 Suppl 1:S8-S21. [DOI: 10.1111/hdi.12647] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Lorena Puchades Renau
- Department of Gastroenterology, Hepatology Unit & Instituto de Investigación La Fe; Hospital Universitari i Politècnic La Fe; Valencia Spain
| | - Marina Berenguer
- Department of Gastroenterology, Hepatology Unit & Instituto de Investigación La Fe; Hospital Universitari i Politècnic La Fe; Valencia Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd); Valencia Spain
- School of Medicine; University of Valencia; Valencia Spain
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23
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Salmon D, Mondelli MU, Maticic M, Arends JE. The benefits of hepatitis C virus cure: Every rose has thorns. J Viral Hepat 2018; 25:320-328. [PMID: 29112304 DOI: 10.1111/jvh.12823] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2017] [Accepted: 09/19/2017] [Indexed: 02/06/2023]
Abstract
To examine mid-term benefits on hepatic complications, extrahepatic clinical syndromes and quality of life associated with HCV cure; to review the few safety issues linked to oral direct-acting antivirals (DAAs); and to discuss the potential population benefits of reducing the burden of HCV infection. DAAs cure HCV infection in more than 95% of patients. The halting of liver inflammation and fibrosis progression translates into both hepatic and extrahepatic benefits and reduces the need for liver transplantation. A reduction in the frequency of extrahepatic manifestations such as mixed cryoglobulinaemia and vasculitis and improvements in quality of life and fatigue have also been described. A few safety issues linked to DAAs such as the potential recurrence of aggressive HCC, the flares of hepatitis B virus in patients with overt or occult HBV infection are been discussed. Curing HCV infection also has a high potential to reduce the burden of HCV infection at the population level. With widespread scaling up of HCV treatment, several modeling studies suggest that major reductions in HCV prevalence and incidence are possible, and that elimination of viral hepatitis is an achievable target by 2030.
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Affiliation(s)
- D Salmon
- Division of Infectious Diseases and Immunology, Center for Diagnosis, Paris Centre University Hospitals, APHP, Paris Descartes University, Paris, France
| | - M U Mondelli
- Division of Infectious Diseases and Immunology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - M Maticic
- Faculty of Medicine, Clinic for Infectious Diseases and Febrile Illnesses, University Medical Centre Ljubljana, University of Ljubljana, Ljubljana, Slovenia
| | - J E Arends
- Department of Internal Medicine, Infectious diseases section, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands
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24
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Mahale P, Engels EA, Li R, Torres HA, Hwang LY, Brown EL, Kramer JR. The effect of sustained virological response on the risk of extrahepatic manifestations of hepatitis C virus infection. Gut 2018; 67. [PMID: 28634198 PMCID: PMC6292199 DOI: 10.1136/gutjnl-2017-313983] [Citation(s) in RCA: 92] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM Chronic HCV infection is associated with several extrahepatic manifestations (EHMs). Data on the effect of sustained virological response (SVR) on the risk of EHMs are limited. METHODS We conducted a retrospective cohort study using data of patients from the US Veterans Affairs HCV Clinical Case Registry who had a positive HCV RNA test (10/1999-08/2009). Patients receiving interferon-based antiviral therapy (AVT) were identified. SVR was defined as negative HCV RNA at least 12 weeks after end of AVT. Risks of eight incident EHMs were evaluated in Cox regression models. RESULTS Of the 160 875 HCV-infected veterans, 31 143 (19.4%) received AVT, of whom 10 575 (33.9%) experienced SVR. EHM risk was reduced in the SVR group compared with untreated patients for mixed cryoglobulinaemia (adjusted HR (aHR)=0.61; 95% CI 0.39 to 0.94), glomerulonephritis (aHR=0.62; 95% CI 0.48 to 0.79), porphyria cutanea tarda (PCT) (aHR=0.41; 95% CI 0.20 to 0.83), non-Hodgkin's lymphoma (NHL) (aHR=0.64; 95% CI 0.43 to 0.95), diabetes (aHR=0.82; 95% CI 0.76 to 0.88) and stroke (aHR=0.84; 95% CI 0.74 to 0.94), but not for lichen planus (aHR=1.11; 95% CI 0.78 to 1.56) or coronary heart disease (aHR=1.12; 95% CI 0.81 to 1.56). Risk reductions were also observed when patients with SVR were compared with treated patients without SVR for mixed cryoglobulinaemia, glomerulonephritis, PCT and diabetes. Significant reductions in the magnitude of aHRs towards the null with increasing time to initiation of AVT after HCV diagnosis were observed for glomerulonephritis, NHL and stroke. CONCLUSIONS Risks of several EHMs of HCV infection are reduced after AVT with SVR. However, early initiation of AVT may be required to reduce the risk of glomerulonephritis, NHL and stroke.
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Affiliation(s)
- Parag Mahale
- Department of Epidemiology, Human Genetics, and Environmental Sciences, The University of Texas School of Public Health, Houston, Texas,Center for Innovations in Quality, Effectiveness, and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas,Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland
| | - Eric A. Engels
- Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland
| | - Ruosha Li
- Department of Biostatistics, The University of Texas School of Public Health, Houston, Texas
| | - Harrys A. Torres
- Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Lu-Yu Hwang
- Department of Epidemiology, Human Genetics, and Environmental Sciences, The University of Texas School of Public Health, Houston, Texas
| | - Eric L. Brown
- Department of Epidemiology, Human Genetics, and Environmental Sciences, The University of Texas School of Public Health, Houston, Texas
| | - Jennifer R. Kramer
- Department of Epidemiology, Human Genetics, and Environmental Sciences, The University of Texas School of Public Health, Houston, Texas,Center for Innovations in Quality, Effectiveness, and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas,Department of Medicine, Section of Health Services Research, Baylor College of Medicine, Houston, Texas
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25
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Data mining of routine laboratory tests can predict liver disease progression in Egyptian diabetic patients with hepatitis C virus (G4) infection: a cohort study of 71 806 patients. Eur J Gastroenterol Hepatol 2018; 30:201-206. [PMID: 29099423 DOI: 10.1097/meg.0000000000001008] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVES Hepatitis C virus (HCV) and diabetes mellitus (DM) are prevalent diseases worldwide, associated with significant morbidity, mortality, and mutual association. The aims of this study were as follows: (i) find the prevalence of DM among 71 806 Egyptian patients with chronic HCV infection and its effect on liver disease progression and (ii) using data mining of routine tests to predict hepatic fibrosis in diabetic patients with HCV infection. PATIENTS AND METHODS A retrospective multicentered study included laboratory and histopathological data of 71 806 patients with HCV infection collected by Egyptian National Committee for control of viral hepatitis. Using data mining analysis, we constructed decision tree algorithm to assess predictors of fibrosis progression in diabetic patients with HCV. RESULTS Overall, 12 018 (16.8%) patients were diagnosed as having diabetes [6428: fasting blood glucose ≥126 mg/dl (9%) and 5590: fasting blood glucose ≥110-126 mg/dl (7.8%)]. DM was significantly associated with advanced age, high BMI and α-fetoprotein (AFP), and low platelets and serum albumin (P≤0.001). Advanced liver fibrosis (F3-F4) was significantly correlated with DM (P≤0.001) irrespective of age. Of 16 attributes, decision tree model for fibrosis showed AFP was most decisive with cutoff of 5.25 ng/ml as starting point of fibrosis. AFP level greater than cutoff in patients was the first important splitting attribute; age and platelet count were second important splitting attributes. CONCLUSION (i) Chronic HCV is significantly associated with DM (16.8%). (ii) Advanced age, high BMI and AFP, low platelets count and albumin show significant association with DM in HCV. (iii) AFP cutoff of 5.25 is a starting point of fibrosis development and integrated into mathematical model to predict development of liver fibrosis in diabetics with HCV (G4) infection.
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Ambachew S, Eshetie S, Geremew D, Endalamaw A, Melku M. Prevalence of Type 2 Diabetes Mellitus among Hepatitis C Virus-Infected Patients: A Systematic Review and Meta-Analysis. DUBAI DIABETES AND ENDOCRINOLOGY JOURNAL 2018. [DOI: 10.1159/000493945] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
<b><i>Background:</i></b> The ever-increasing global prevalence of hepatitis C infection is fueling the burden of diabetes mellitus, which exacerbates various complications and may be a cause of death of millions of people. Several studies have reported that hepatitis C virus infection is an important risk factor for the development of diabetes mellitus. However, fragmented studies have reported variable and inconsistent findings regarding the prevalence of type 2 diabetes mellitus among hepatitis C virus-infected patients. Therefore, this meta-analysis aimed to estimate the overall prevalence of type 2 diabetes mellitus among patients infected with hepatitis C virus. <b><i>Methods:</i></b> This systematic review and meta-analysis includes original articles reporting on cohort and cross-sectional studies. A systematic search was performed in PubMed, ScienceDirect, and Google Scholar. A random-effects meta-analysis model was used to estimate the global pooled prevalence of type 2 diabetes mellitus among hepatitis C-infected patients. A sensitivity analysis was conducted to check the stability of the summary estimate. Heterogeneity was assessed using the <i>I</i><sup>2</sup> statistic. A subgroup analysis was also conducted based on geographical region. Funnel plots were used to spot publication bias. <b><i>Results:</i></b> A total of 40 eligible articles reporting data on 14,765 study participants were included in this meta-analysis. The pooled prevalence of type 2 diabetes mellitus among hepatitis C virus-infected patients was 19.67% (95% CI: 17.25, 22.09). The subgroup analysis showed a pooled prevalence of 27.72% (95% CI: 20.79, 34.65) in Africa, 20.73% (95% CI: 17.57, 23.90) in Asia, 16.64% (95% CI: 6.79, 26.49) in North America, and 15.02% (95% CI: 10.66, 19.38) in Europe. <b><i>Conclusions:</i></b> The overall prevalence of type 2 diabetes mellitus among hepatitis C virus-infected patients was considerably higher than in the general population in a global perspective. The highest prevalence was noted in Africa and Asia, followed by North America and Europe. Therefore, early intervention is needed (prevention and early treatment of hepatitis C virus infection) to prevent the development of type 2 diabetes mellitus.
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Abstract
Metabolic disorders are common in patients with chronic hepatitis C virus (HCV) infection. Epidemiologic and clinical data indicate an overprevalence of lipids abnormalite, steatosis, insuline resistance (IR) and diabetes mellitus in HCV patients, suggesting that HCV itself may interact with glucido-lipidic metabolism. HCV interacts with the host lipid metabolism by several mechanisms leading to hepatic steatosis and hypolipidemia which are reversible after viral eradication. Liver and peripheral IR are HCV genotype/viral load dependent and improved after viral eradication. This article examines examine the relationship between HCV, lipid abnormalities, steatosis, IR, and diabetes and the pathogenic mechanisms accounting for these events in HCV-infected patients.
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Affiliation(s)
- Lawrence Serfaty
- Hepatology Department, INSERM UMR_S 938, APHP, Saint-Antoine Hospital, UPMC Univ Paris 06, Paris, France.
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28
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Desbois AC, Cacoub P. Diabetes mellitus, insulin resistance and hepatitis C virus infection: A contemporary review. World J Gastroenterol 2017; 23:1697-1711. [PMID: 28321170 PMCID: PMC5340821 DOI: 10.3748/wjg.v23.i9.1697] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2016] [Revised: 11/10/2016] [Accepted: 02/08/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To summarise the literature data on hepatitis C virus (HCV)-infected patients concerning the prevalence of glucose abnormalities and associated risk.
METHODS We conducted a PubMed search and selected all studies found with the key words "HCV" or "hepatitis C virus" and "diabetes" or "insulin resistance". We included only comparative studies written in English or in French, published from January 2000 to April 2015. We collected the literature data on HCV-infected patients concerning the prevalence of glucose abnormalities [diabetes mellitus (DM) and insulin resistance (IR)] and associated risk [i.e., severe liver fibrosis, response to antivirals, and the occurrence of hepatocellular carcinoma (HCC)].
RESULTS HCV infection is significantly associated with DM/IR compared with healthy volunteers and patients with hepatitis B virus infection. Glucose abnormalities were associated with advanced liver fibrosis, lack of sustained virologic response to interferon alfa-based treatment and with a higher risk of HCC development. As new antiviral therapies may offer a cure for HCV infection, such data should be taken into account, from a therapeutic and preventive point of view, for liver and non-liver consequences of HCV disease. The efficacy of antidiabetic treatment in improving the response to antiviral treatment and in decreasing the risk of HCC has been reported by some studies but not by others. Thus, the effects of glucose abnormalities correction in reducing liver events need further studies.
CONCLUSION Glucose abnormalities are strongly associated with HCV infection and show a negative impact on the main liver related outcomes.
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Saeed MJ, Olsen MA, Powderly WG, Presti RM. Diabetes Mellitus is Associated With Higher Risk of Developing Decompensated Cirrhosis in Chronic Hepatitis C Patients. J Clin Gastroenterol 2017; 51:70-76. [PMID: 27306942 PMCID: PMC5154898 DOI: 10.1097/mcg.0000000000000566] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
GOALS To investigate the association of diabetes with risk of decompensated cirrhosis in patients with chronic hepatitis C (CHC). BACKGROUND Direct-acting antivirals are highly effective in treating CHC but very expensive. CHC patients at high risk of progression to symptomatic liver disease may benefit most from early treatment. STUDY We conducted a retrospective cohort study using the 2006 to 2013 Truven Health Analytics MarketScan Commercial Claims and Encounters database including inpatient, outpatient, and pharmacy claims from private insurers. CHC and cirrhosis were identified using ICD-9-CM diagnosis codes; baseline diabetes was identified by diagnosis codes or antidiabetic medications. CHC patients were followed to identify decompensated cirrhosis. Multivariable Cox proportional hazards regression was used to model the risk of decompensated cirrhosis by baseline cirrhosis. RESULTS There were 75,805 CHC patients with median 1.9 years follow-up. A total of 10,317 (13.6%) of the CHC population had diabetes. The rates of decompensated cirrhosis per 1000 person-years were: 185.5 for persons with baseline cirrhosis and diabetes, 119.8 for persons with cirrhosis and no diabetes, 35.3 for persons with no cirrhosis and diabetes, and 17.1 for persons with no cirrhosis and no diabetes. Diabetes was associated with increased risk of decompensated cirrhosis in persons with baseline cirrhosis (adjusted hazard ratio=1.4; 95% confidence interval, 1.3-1.6) and in persons without baseline cirrhosis (adjusted hazard ratio=1.9; 95% confidence interval, 1.7-2.1). CONCLUSIONS In a privately insured US population with CHC, the adjusted risk of decompensated cirrhosis was higher in diabetic compared with nondiabetic patients. Diabetes status should be included in prioritization of antiviral treatment.
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Affiliation(s)
- Mohammed J Saeed
- Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Margaret A Olsen
- Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA
| | - William G Powderly
- Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Rachel M Presti
- Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
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30
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Schnier C, Wild S, Kurdi Z, Povey C, Goldberg DJ, Hutchinson SJ. Matched population-based study examining the risk of type 2 diabetes in people with and without diagnosed hepatitis C virus infection. J Viral Hepat 2016; 23:596-605. [PMID: 26910297 DOI: 10.1111/jvh.12520] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2015] [Accepted: 01/14/2016] [Indexed: 01/03/2023]
Abstract
Meta-analyses have found hepatitis C virus (HCV) infection to be associated with an increased risk of type 2 diabetes mellitus (T2DM). Here, we examine this association within a large population-based study, according to HCV RNA status. A data-linkage approach was used to examine the excess risk of diagnosed T2DM in people diagnosed with antibodies to HCV (anti-HCV) in Scotland (21 929 anti-HCV(+ves) ; involving 15 827 HCV RNA(+ves) , 3927 HCV RNA(-ves) and 2175 with unknown RNA-status) compared to that of a threefold larger general population sample matched for gender, age and postcode (65 074 anti-HCV(-ves) ). To investigate effects of ascertainment bias the following periods were studied: up to 1 year before (pre-HCV)/within 1 year of (peri-HCV)/more than 1 year post (post-HCV) the date of HCV-diagnosis. T2DM had been diagnosed in 2.9% of anti-HCV(+ves) (including 3.2% of HCV RNA(+ves) and 2.3% of HCV RNA(-ves) ) and 2.7% of anti-HCV(-ves) . A higher proportion of T2DM was diagnosed in the peri-HCV period (i.e. around the time of HCV-diagnosis) for the anti-HCV(+ves) (22%) compared to anti-HCV(-ves) (10%). In both the pre-HCV and post-HCV periods, only those anti-HCV(+ves) living in less deprived areas (13% of the cohort) were found to have a significant excess risk of T2DM compared to anti-HCV(-ves) (adjusted odds ratio in the pre-HCV period: 4.0 for females and 2.3 for males; adjusted hazard ratio in the post-HCV period: 1.5). These findings were similarly observed for both HCV RNA(+ves) (chronic) and HCV RNA(-ves) (resolved). In the largest study of T2DM among chronic HCV-infected individuals to date, there was no evidence to indicate that infection conveyed an appreciable excess risk of T2DM at the population level.
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Affiliation(s)
- C Schnier
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK.,Health Protection Scotland, Glasgow, UK
| | - S Wild
- Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK
| | - Z Kurdi
- Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK
| | - C Povey
- Information Services Division, NHS National Services Scotland, Edinburgh, UK
| | - D J Goldberg
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK.,Health Protection Scotland, Glasgow, UK
| | - S J Hutchinson
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK.,Health Protection Scotland, Glasgow, UK
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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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Negro F, Forton D, Craxì A, Sulkowski MS, Feld JJ, Manns MP. Extrahepatic morbidity and mortality of chronic hepatitis C. Gastroenterology 2015; 149:1345-60. [PMID: 26319013 DOI: 10.1053/j.gastro.2015.08.035] [Citation(s) in RCA: 271] [Impact Index Per Article: 27.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2014] [Revised: 08/14/2015] [Accepted: 08/17/2015] [Indexed: 12/17/2022]
Abstract
Chronic hepatitis C virus (HCV) infection is associated with several extrahepatic manifestations. Patients with HCV may develop mixed cryoglobulinemia and its sequelae, ranging from cutaneous and visceral vasculitis to glomerulonephritis and B-cell non-Hodgkin lymphoma. HCV-infected patients have increased rates of insulin resistance, diabetes, and atherosclerosis, which may lead to increased cardiovascular morbidity and mortality. Neurological manifestations of HCV infection include fatigue and cognitive impairment. The mechanisms causing the extrahepatic effects of HCV infection are likely multifactorial and may include endocrine effects, HCV replication in extrahepatic cells, or a heightened immune reaction with systemic effects. Successful eradication of HCV with interferon alfa and ribavirin was shown to improve some of these extrahepatic effects; sustained virological response is associated with resolution of complications of cryoglobulinemia, reduced levels of insulin resistance, reduced incidence of diabetes and stroke, and improved fatigue and cognitive functioning. The availability of new interferon-free, well-tolerated anti-HCV treatment regimens is broadening the spectrum of patients available for therapy, including those in whom interferon was contraindicated, and will likely result in greater improvements in the extrahepatic manifestations of HCV. If these regimens are shown to confer significant benefit in the metabolic, cardiovascular, or neuropsychiatric conditions associated with HCV infection, extrahepatic manifestations of HCV may become a major indication for treatment even in the absence of liver disease.
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Affiliation(s)
- Francesco Negro
- Division of Gastroenterology and Hepatology and Division of Clinical Pathology, University Hospital, Geneva, Switzerland
| | - Daniel Forton
- Department of Gastroenterology and Hepatology, St George's Hospital, London, England
| | - Antonio Craxì
- Gastroenterology and Internal Medicine, University of Palermo, Palermo, Italy
| | - Mark S Sulkowski
- Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Jordan J Feld
- Toronto Centre for Liver Disease, Sandra Rotman Centre for Global Health, University of Toronto, Toronto, Ontario, Canada
| | - Michael P Manns
- Department of Gastroenterology, Hepatology and Endocrinology, Medical School of Hannover, Hannover, Germany.
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Ramos-Prol A, Hervás-Marín D, Rodríguez-Medina B, Campos-Alborg V, Berenguer M, Moya-Herraiz Á, Merino-Torres JF. Alterations in carbohydrate metabolism in cirrhotic patients before and after liver transplant. Diabetes Res Clin Pract 2015; 110:123-8. [PMID: 26506435 DOI: 10.1016/j.diabres.2015.10.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2015] [Revised: 09/06/2015] [Accepted: 10/01/2015] [Indexed: 12/15/2022]
Abstract
AIM The main objective of this study is to demonstrate whether carbohydrate metabolism alterations identified in patients with advanced cirrhosis show any improvement after liver transplant. METHODS The study included 86 patients who underwent liver transplant between March 2010 and February 2011. An oral glucose tolerance test was performed before the liver transplant, and 6 and 12 months after. Beta cell function and insulin resistance were also calculated, applying formulae that use basal plasma glycaemia and insulin, and plasma glycaemia and insulin during an oral glucose tolerance test. Risk factors for pre- and post-transplant diabetes were also studied. The diagnosis of diabetes was based on an OGTT. RESULTS The proportion of patients with diabetes before transplant, and at month 6 and 12 after transplant were 70.9%, 48.8% and 39.2%, respectively. Compared to baseline, at month 6 the odds ratio of having diabetes was 0.39 (IC 95% [0.21, 0.73]) and at month 12 it was 0.26 (IC 95% [0.14, 0.50]). The composite insulin sensitivity index values at 6 and 12 months were 1.72 units higher (IC 95% [0.84, 2.58]) and 1.58 units higher (IC 95% [0.68, 2.44)] than baseline. A statistically significant association was found between high MELD values and high body mass index, and risk of pre-transplant diabetes (p=0.001 and p=0.033, respectively). Cirrhosis aetiology did not influence the risk of diabetes. CONCLUSIONS In this study, we were able to ascertain that alterations in carbohydrate metabolism typical of advanced cirrhosis improve after liver transplant. This improvement is mainly due to an improvement in insulin resistance.
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Affiliation(s)
- Agustín Ramos-Prol
- Endocrinology and Nutrition Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain; Instituto de Investigación Sanitaria La Fe (Health Research Institute La Fe), Valencia, Spain
| | | | - Beatriz Rodríguez-Medina
- Liver Transplantation and Hepatology Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain
| | - Vicente Campos-Alborg
- Endocrinology and Nutrition Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain
| | - Marina Berenguer
- Liver Transplantation and Hepatology Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain
| | - Ángel Moya-Herraiz
- Liver Transplantation and Hepatology Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain
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Cuadros DF, Miller FD, Nagelkerke N, Abu-Raddad LJ. Association between HCV infection and diabetes type 2 in Egypt: is it time to split up? Ann Epidemiol 2015; 25:918-23. [PMID: 26499381 DOI: 10.1016/j.annepidem.2015.09.005] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2015] [Revised: 09/06/2015] [Accepted: 09/07/2015] [Indexed: 12/15/2022]
Abstract
PURPOSE There is a conflicting evidence about the association between hepatitis C virus (HCV) infection and diabetes mellitus. The objective of this study was to assess this association in Egypt, the country with the highest HCV prevalence in the world. METHODS The source of data was from the Egypt Demographic and Health Survey conducted in 2008. Using multivariable logistic regression analyses to account for known confounders, the association was investigated at two levels']: (1) HCV exposure (HCV antibody status) and diabetes mellitus and (2) diabetes mellitus and chronic HCV infection (HCV RNA status) among HCV-exposed individuals. RESULTS We found no evidence for an association between HCV antibody status and diabetes (adjusted odds ratio [OR] = 0.87; 95% confidence interval [CI], 0.63-1.19). However, among HCV-exposed individuals, we found an evidence for an association between diabetes and active HCV infection (adjusted OR = 2.44, 95% CI, 1.30-4.57). CONCLUSIONS Although it does not appear that HCV exposure and diabetes are linked, there might be an association between diabetes and chronic HCV infection. The HCV-diabetes relationship may be more complex than previously anticipated. Therefore, a call for an "amicable divorce" to the HCV-diabetes relationship could be premature.
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Affiliation(s)
- Diego F Cuadros
- Infectious Disease Epidemiology Group, Weill Cornell Medical College-Qatar, Cornell University, Qatar Foundation-Education City, Doha, Qatar; Department of Healthcare Policy and Research, Weill Cornell Medical College, Cornell University, New York, NY.
| | - F DeWolfe Miller
- Department of Tropical Medicine and Medical Microbiology and Pharmacology, University of Hawaii, Honolulu
| | - Nico Nagelkerke
- Department of Public Health, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Laith J Abu-Raddad
- Infectious Disease Epidemiology Group, Weill Cornell Medical College-Qatar, Cornell University, Qatar Foundation-Education City, Doha, Qatar; Department of Healthcare Policy and Research, Weill Cornell Medical College, Cornell University, New York, NY; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA
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35
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Li HC, Lo SY. Hepatitis C virus: Virology, diagnosis and treatment. World J Hepatol 2015; 7:1377-1389. [PMID: 26052383 PMCID: PMC4450201 DOI: 10.4254/wjh.v7.i10.1377] [Citation(s) in RCA: 103] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2014] [Revised: 12/22/2014] [Accepted: 04/02/2015] [Indexed: 02/06/2023] Open
Abstract
More than twenty years of study has provided a better understanding of hepatitis C virus (HCV) life cycle, including the general properties of viral RNA and proteins. This effort facilitates the development of sensitive diagnostic tools and effective antiviral treatments. At present, serologic screening test is recommended to perform on individuals in the high risk groups and nucleic acid tests are recommended to confirm the active HCV infections. Quantization and genotyping of HCV RNAs are important to determine the optimal duration of anti-viral therapy and predict the likelihood of response. In the early 2000s, pegylated interferon plus ribavirin became the standard anti-HCV treatment. However, this therapy is not ideal. To 2014, boceprevir, telaprevir, simeprevir, sofosbuvir and Harvoni are approved by Food and Drug Administration for the treat of HCV infections. It is likely that the new all-oral, interferon-free, pan-genotyping anti-HCV therapy will be available within the next few years. Majority of HCV infections will be cured by these anti-viral treatments. However, not all patients are expected to be cured due to viral resistance and the high cost of antiviral treatments. Thus, an efficient prophylactic vaccine will be the next challenge in the fight against HCV infection.
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Vukotic R, Gamal N, Andreone P. Prospective, observational real-life study on eligibility for and outcomes of antiviral treatment with peginterferon α plus ribavirin in chronic hepatitis C. Dig Liver Dis 2015; 47:151-156. [PMID: 25483909 DOI: 10.1016/j.dld.2014.11.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2014] [Revised: 10/30/2014] [Accepted: 11/04/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND We aimed to investigate eligibility, reasons for treatment discontinuation and characteristics of chronic hepatitis C patients with treatment failure to peginterferon/ribavirin in clinical practice. METHODS 1128 chronic hepatitis C patients, from 45 Italian Hepatology centres, were enrolled in this phase-4, prospective, observational study from January 2009 to February 2010. RESULTS 687/1118 patients (61.4%) were eligible for antiviral treatment, of which 598 (87.0%) agreed with the physician's decision. Outcome information was available in 500/598 patients, among whom 348 (69.6%) completed treatment. Treatment was discontinued in 152 patients due to: lack of response (28.9%), personal reasons (29.6%), adverse events (38.2%), and decompensation (1.3%). Sustained virological response was obtained in 263/500 (52.6%), 71 (14.2%) relapsed and 61 (12.2%) were non-responders. Treatment outcome was not available in 105 (21%): lost while receiving treatment (33.3%), lost during follow-up (25.7%), withdrawn for adverse events (19.1%) or for administrative reasons (21.9%). CONCLUSION In clinical practice, only 61% of chronic hepatitis C patients are considered eligible for peginterferon/ribavirin. Of these, 13% refuse treatment. Approximately 30% do not complete the scheduled treatment and, despite this, the sustained virological response rate is similar to that of randomized-controlled trials. In the era of new antiviral combinations, these findings have important implications for assessing eligibility and estimating drop-out rates.
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Affiliation(s)
- Ranka Vukotic
- Department of Medical and Surgical Sciences, Bologna University, Bologna, Italy
| | - Nesrine Gamal
- Department of Medical and Surgical Sciences, Bologna University, Bologna, Italy
| | - Pietro Andreone
- Department of Medical and Surgical Sciences, Bologna University, Bologna, Italy.
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Burman BE, Bacchetti P, Ayala CE, Gelman N, Melgar J, Khalili M. Liver inflammation is a risk factor for prediabetes in at-risk latinos with and without hepatitis C infection. Liver Int 2015; 35:101-7. [PMID: 25156890 PMCID: PMC4293255 DOI: 10.1111/liv.12676] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2014] [Accepted: 08/19/2014] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS Early recognition of prediabetes can lead to timely clinical interventions to prevent type 2 diabetes. Both Latino ethnicity and chronic hepatitis C (HCV) have been identified as diabetic risk factors. We aimed to investigate predictors of impaired fasting glucose (IFG), a common prediabetic state, among Latinos with and without HCV. METHODS One hundred Latino adults with no history of diabetes or cirrhosis underwent clinical, laboratory, and metabolic evaluation, including oral glucose tolerance testing (OGTT) and insulin suppression testing to quantify directly measured insulin resistance (IR). Isolated IFG was defined as fasting glucose ≥100 mg/dl and <140 mg/dl at 2 h during normal glucose tolerance during OGTT. RESULTS Overall subject characteristics included median age 44 years, 64% male, 40% HCV-positive and 32% with isolated IFG. Factors associated with isolated IFG included subject age (OR 2.42 per decade, 95%CI 1.40-3.90, P = 0.001), HCV infection (OR 4.0, 95%CI 1.71-9.72, P = 0.002) and alanine aminotransferase (ALT) (OR 2.35 per doubling, 95%CI 1.46-3.77, P < 0.0001). Multipredictor logistic regression analysis identified ALT (OR 2.05 per doubling, P = 0.005, 95% CI 1.24-3.40) and age (OR 2.20 per 10 years, P = 0.005, 95%CI 1.27-3.80) as factors independently associated with IFG. While HCV was associated with 4-fold higher odds of IFG, this entire effect was mediated by ALT. CONCLUSIONS We found strong evidence that liver inflammation is a risk factor for prediabetes among Latinos with and without HCV. Among HCV-infected individuals, early antiviral therapy could mitigate the effect of inflammation and represent an important intervention to prevent diabetes in this at-risk population.
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Affiliation(s)
- Blaire E Burman
- Department of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Peter Bacchetti
- Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA
| | - Claudia E. Ayala
- Department of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Nicholas Gelman
- Department of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Jennifer Melgar
- Department of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Mandana Khalili
- Department of Medicine, University of California San Francisco, San Francisco, CA, USA,Liver Center, University of California San Francisco, San Francisco, CA, USA
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Hammerstad SS, Grock SF, Lee HJ, Hasham A, Sundaram N, Tomer Y. Diabetes and Hepatitis C: A Two-Way Association. Front Endocrinol (Lausanne) 2015; 6:134. [PMID: 26441826 PMCID: PMC4568414 DOI: 10.3389/fendo.2015.00134] [Citation(s) in RCA: 79] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2015] [Accepted: 08/17/2015] [Indexed: 12/15/2022] Open
Abstract
Diabetes and hepatitis C infection are both prevalent diseases worldwide, and are associated with increased morbidity and mortality. Most studies, but not all, have shown that patients with chronic hepatitis C are more prone to develop type 2 diabetes (T2D) compared to healthy controls, as well as when compared to patients with other liver diseases, including hepatitis B. Furthermore, epidemiological studies have revealed that patients with T2D may also be at higher risk for worse outcomes of their hepatitis C infection, including reduced rate of sustained virological response, progression to fibrosis and cirrhosis, and higher risk for development of hepatocellular carcinoma. Moreover, hepatitis C infection and mainly its treatment, interferon α, can trigger the development of type 1 diabetes. In this review, we discuss the existing data on this two-way association between diabetes and hepatitis C infection with emphasis on possible mechanisms. It remains to be determined whether the new curative therapies for chronic hepatitis C will improve outcomes in diabetic hepatitis C patients, and conversely whether treatment with Metformin will reduce complications from hepatitis C virus infection. We propose an algorithm for diabetes screening and follow-up in hepatitis C patients.
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Affiliation(s)
- Sara Salehi Hammerstad
- Department of Medicine, Division of Endocrinology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Department of Pediatrics, Oslo University Hospital Ullevål, Oslo, Norway
| | - Shira Frankel Grock
- Department of Medicine, Division of Endocrinology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Hanna J. Lee
- Department of Medicine, Division of Endocrinology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Alia Hasham
- Department of Medicine, Division of Endocrinology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Nina Sundaram
- Department of Medicine, Division of Endocrinology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Yaron Tomer
- Department of Medicine, Division of Endocrinology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- James J. Peters VA Medical Center, Bronx, NY, USA
- *Correspondence: Yaron Tomer, Division of Endocrinology, Icahn School of Medicine at Mount Sinai, Box 1055, One Gustave L. Levy Place, New York, NY 10029, USA,
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Ruhl CE, Menke A, Cowie CC, Everhart JE. Relationship of hepatitis C virus infection with diabetes in the U.S. population. Hepatology 2014; 60:1139-49. [PMID: 24500979 PMCID: PMC4122643 DOI: 10.1002/hep.27047] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2013] [Accepted: 01/31/2014] [Indexed: 12/16/2022]
Abstract
UNLABELLED An association of hepatitis C virus (HCV) infection with diabetes has been reported in many studies, but few have been population based and applied standard criteria for diabetes diagnosis. We examined this relationship using recent population-based data from the U.S. National Health and Nutrition Examination Survey. Adult participants (15,128) in the 1999-2010 surveys had data on diabetes status and serum HCV antibody (anti-HCV) or HCV RNA. Using American Diabetes Association criteria, diabetes was defined as a health care provider diagnosis, serum hemoglobin A1C (A1C) ≥6.5%, or fasting plasma glucose (FPG) ≥126 mg/dL, prediabetes as A1C 5.7%-<6.5% or FPG 100-<126 mg/dL, and normal glucose as A1C <5.7% and FPG <100 mg/dL. Odds ratios (ORs) for diabetes and prediabetes, comparing persons with HCV infection to those without, were adjusted for demographics, BMI, C-reactive protein, smoking, drinking, and blood transfusion before 1992. Among participants without diabetes, we compared mean insulin resistance (IR), estimated using homeostasis model assessment (HOMA-IR), by HCV status. The overall prevalence of anti-HCV+ was 1.7%, of HCV RNA(+) 1.1%, of diabetes 10.5%, and of prediabetes 32.8%. The prevalence of diabetes and prediabetes did not differ by HCV status. In multivariate-adjusted analysis, diabetes remained unassociated with anti-HCV (OR, 1.0; 95% confidence interval [CI]: 0.6-1.7) or with HCV RNA (OR, 1.1; 95% CI: 0.6-1.9). In contrast, elevated alanine aminotransferase and gamma glutamyltransferase activities were associated with diabetes regardless of HCV status. HOMA-IR was not associated with HCV markers in unadjusted or multivariate-adjusted analyses (P > 0.05). CONCLUSION In the U.S. population, HCV was not associated with diabetes or with IR among persons with normal glucose. Previously reported relationships of HCV with diabetes were possibly attributable to the effect of elevated liver enzymes.
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Affiliation(s)
- Constance E. Ruhl
- Social & Scientific Systems, Inc., 8757 Georgia Avenue, 12floor, Silver Spring, MD 20910, 301-628-3272 (phone), 301-628-3201 (fax)
| | - Andy Menke
- Social & Scientific Systems, Inc., 8757 Georgia Avenue, 12floor, Silver Spring, MD 20910
| | - Catherine C. Cowie
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, 2 Democracy Plaza, Room 691, 6707 Democracy Boulevard MSC 5460, Bethesda, MD 20892-5450
| | - James E. Everhart
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, 2 Democracy Plaza, Room 642F, 6707 Democracy Boulevard MSC 5450, Bethesda, MD 20892-5450
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Li HC, Ma HC, Yang CH, Lo SY. Production and pathogenicity of hepatitis C virus core gene products. World J Gastroenterol 2014; 20:7104-7122. [PMID: 24966583 PMCID: PMC4064058 DOI: 10.3748/wjg.v20.i23.7104] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2013] [Revised: 12/05/2013] [Accepted: 04/03/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) is a major cause of chronic liver diseases, including steatosis, cirrhosis and hepatocellular carcinoma, and its infection is also associated with insulin resistance and type 2 diabetes mellitus. HCV, belonging to the Flaviviridae family, is a small enveloped virus whose positive-stranded RNA genome encoding a polyprotein. The HCV core protein is cleaved first at residue 191 by the host signal peptidase and further cleaved by the host signal peptide peptidase at about residue 177 to generate the mature core protein (a.a. 1-177) and the cleaved peptide (a.a. 178-191). Core protein could induce insulin resistance, steatosis and even hepatocellular carcinoma through various mechanisms. The peptide (a.a. 178-191) may play a role in the immune response. The polymorphism of this peptide is associated with the cellular lipid drop accumulation, contributing to steatosis development. In addition to the conventional open reading frame (ORF), in the +1 frame, an ORF overlaps with the core protein-coding sequence and encodes the alternative reading frame proteins (ARFP or core+1). ARFP/core+1/F protein could enhance hepatocyte growth and may regulate iron metabolism. In this review, we briefly summarized the current knowledge regarding the production of different core gene products and their roles in viral pathogenesis.
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Abstract
The metabolic syndrome and the hepatitis C virus (HCV) infection are 2 global health care challenges with a complex interaction. Insulin resistance, a central component of the metabolic syndrome, is epidemiologically and pathophysiologically intrinsically linked to HCV infection. Insulin resistance and diabetes affect clinical outcomes in patients with liver disease related to HCV, namely, incidence of hepatocellular carcinoma, liver-related mortality, fibrosis progression rate, response to antiviral therapy, and possibly the incidence of cardiovascular events. Viral and metabolic steatosis and its interactions with HCV and the metabolic syndrome are discussed. Management and the need for further research conclude the article.
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Affiliation(s)
- Nicolas Goossens
- Division of Gastroenterology and Hepatology, Geneva University Hospital, 4 rue Gabrielle-Perret-Gentil, 1211 Geneva 4, Switzerland
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Manickam P, Muthusamy AK, Cappell MS. Association of chronic hepatitis C and diabetes: is there a gender difference? Am J Gastroenterol 2013; 108:1804. [PMID: 24192951 DOI: 10.1038/ajg.2013.308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Palaniappan Manickam
- 1] Division of Gastroenterology, Department of Medicine, William Beaumont Hospital, Royal Oak, Michigan, USA [2] Oakland University William Beaumont School of Medicine, Royal Oak, Michigan, USA
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Response to Cappell et al. Am J Gastroenterol 2013; 108:1804-5. [PMID: 24192950 DOI: 10.1038/ajg.2013.310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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