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Strauhs-Nitsch L, Campiolo MF, Morsoletto DBG, Pissaia Junior A, Ivantes CAP. CURING HEPATITIS C WITH THE NEW DIRECT ACTING ANTIVIRALS DID NOT IMPROVE INSULIN RESISTANCE AFTER ONE YEAR. ARQUIVOS DE GASTROENTEROLOGIA 2021; 57:267-271. [PMID: 33027477 DOI: 10.1590/s0004-2803.202000000-50] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Accepted: 06/30/2020] [Indexed: 01/10/2023]
Abstract
BACKGROUND Chronic hepatitis C still figures as an important cause of morbidity among the Brazilian population, and is closely associated with metabolic disturbances, including insulin resistance (IR), which can be evaluated by the Homeostatic Model Assessment (HOMA-IR). IR may entail lower sustained virologic response (SVR) on certain therapeutic regimens and faster progression to advanced hepatic fibrosis. With the arrival of the direct acting agents (DAA) in hepatitis C treatment, there is an increased need in observing the impact in patients' IR profile while using such therapies. OBJECTIVE - 1) To compare the results of HOMA-IR in patients affected by chronic hepatitis C before treatment with DAA and 12 months after finishing it with SVR. 2) To evaluate the evolution of weight after curing chronic hepatitis C. METHODS We included patients older than 18 from two tertiary care in Curitiba - PR, of both sexes, with chronic hepatitis C, treated with DAA, from July 2015 to September 2017. We also evaluated the patients' levels of fasting insulin, fasting glucose and glycated hemoglobin before starting treatment and 12 months after finishing it. We also used epidemiologic data, such as age, sex, hepatic fibrosis degree, body mass index, abdominal circumference, viral genotype and the presence of diabetes mellitus before and after treatment. IR was assessed before and after treatment and calculated by the HOMA-IR score. Insulin resistance was defined by a HOMA-IR greater than 2.5. We excluded patients who lost follow-up, those who did not achieve SRV and those who did not have a laboratory profile. The results of quantitative variables were described by means, medians, and standard deviations. P values <0.05 indicated statistical significance. RESULTS We included 75 patients in this study, with a mean age of 55.2 years and 60% of males. Forty-three patients had advanced fibrosis. Twenty one (28%) had a previous diabetes mellitus diagnosis. We identified 31 (41.3%) patients with IR before antiviral treatment, and this number increased to 39 (52%) after 12 months of finishing treatment, according to HOMA-IR. There was no statistic difference between insulin, glucose and HOMA-IR measurements before and after curing hepatitis C. We observed a weight gain in patients shortly after curing hepatitis C, but this did not persist at the end of the study. We also had no significant difference in IR prevalence when viral genotype was concerned. CONCLUSION In this study, there was no statistically significant difference between HOMA-IR results in patients before and 12 months after treatment for hepatitis C. Even though patients gained weight after the cure, this was not statistically significant after a year (P=0.131).
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Affiliation(s)
- Lohanna Strauhs-Nitsch
- Hospital Nossa Senhora das Graças, Departamento de Gastroenterologia e Hepatologia, Curitiba, PR, Brasil
| | - Marcela Ferro Campiolo
- Hospital Nossa Senhora das Graças, Departamento de Gastroenterologia e Hepatologia, Curitiba, PR, Brasil
| | | | - Alcindo Pissaia Junior
- Hospital Nossa Senhora das Graças, Departamento de Gastroenterologia e Hepatologia, Curitiba, PR, Brasil
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Saleh P, Infectious and Tropical Disease Research Center, Department of Infectious and Tropical Disease, Tabriz University of Medical Sciences, Tabriz, Iran, Sheikholeslami A, Infectious and Tropical Disease Research Center, Department of Infectious and Tropical Disease, Tabriz University of Medical Sciences, Tabriz, Iran, Salman Mohajer A, Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran, Babapour S, Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran, Hosseini MS, Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran. Association between Different Hepatitis C Virus Genotypes Infection and Type-2 Diabetes Mellitus: A Descriptive-Analytical Study from the Northwest of Iran. JOURNAL OF MEDICAL MICROBIOLOGY AND INFECTIOUS DISEASES 2020; 8:137-142. [DOI: 10.29252/jommid.8.4.137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
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Ndako JA, Owolabi AO, Olisa JA, Akinwumi JA, Dojumo VT, Olatinsu O, Adebayo BA. Studies on the prevalence of Hepatitis C virus infection in diabetic patients attending a tertiary health-care facility South-west Nigeria. BMC Infect Dis 2020; 20:664. [PMID: 32907538 PMCID: PMC7488326 DOI: 10.1186/s12879-020-05388-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Accepted: 08/31/2020] [Indexed: 02/08/2023] Open
Abstract
Background Hepatitis C virus (HCV) infection and type 2 diabetes mellitus (T2DM) are two major public health problems associated with increasing complications and mortality rates worldwide. The objective of this study is to evaluate the prevalence of hepatitis C virus (HCV) infection in diabetic patients and to investigate the influence of several epidemiological and clinical factors on HCV infection. Method A total number of one hundred and eighty diabetic patients were recruited for this study. Consented subjects made up of 71(39.4%) males and 109(60.56%) females were recruited for the study. While one-Hundred (100) Non-Diabetics (Controls) were also recruited for the study. Structured questionnaires were administered to the consented participants to obtain relevant data. Sera samples were assayed for antibodies to HCV using an enzyme linked immunosorbent assay [Inteco Diagnostic Limited]. ELISA technique. Result Overall prevalence of HCV infection among diabetes patients assayed was 13.3% out of which 8(11.3%) was obtained from the male subjects compared to 16 (14.7%) seropositivity recorded among the females (P = 0.511; P > 0.05). Considering age distribution, Subjects aged 41–50 years recorded, 9 (22.5%) positivity (P = 0.238; P > 0.05).Considering educational status of subjects screened, 22 (14.9%) positivity was rescored among subjects who have attained tertiary status of education.(P = 0.574;P > 0.05).Risk factors considered showed that, 7 (18.9%) seropositive subject were alcoholic consumers(P value = 0.2621;P > 0.05) while 5 (8.9%) recorded history of sharing sharp objects P = 0.2427;P > 0.05). Conclusion Our study shows a slightly higher prevalence of hepatitis C infection in type 2 diabetics. This call for urgent routine screening exercise among diabetic patients for HCV infection. This study also emphasizes the need for public enlightenment on the association between HCV infection and T2DM, to avert possible complications among diabetic patients.
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Affiliation(s)
- James A Ndako
- Department of Microbiology, Landmark University, Omu-aran, Nigeria.
| | | | - Joseph A Olisa
- Department of Medical Services, Landmark University Medical Center, LMU, Omu-aran, Nigeria
| | - Jeremiah A Akinwumi
- Department of Medical Laboratory Services, Landmark University Medical Center, LMU, Omu-aran, Nigeria
| | - Victor T Dojumo
- Department of Medical Laboratory Services, Landmark University Medical Center, LMU, Omu-aran, Nigeria
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Muñoz Díaz HA, Lúquez Mindiola AJ, Gómez Aldana AJ. Fisiopatología de la hepatitis C y diabetes mellitus. Hacia la cura de dos epidemias en el siglo XXI. REVISTA COLOMBIANA DE GASTROENTEROLOGÍA 2019; 34:277-287. [DOI: 10.22516/25007440.322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/01/2024]
Abstract
La infección crónica por virus de la hepatitis C (VHC) y la diabetes mellitus (DM) son dos problemas de salud pública que impactan los sistemas de salud, con una alta carga económica global. La infección por VHC produce manifestaciones hepáticas tales como hepatitis, cirrosis y carcinoma hepatocelular; asimismo, se ha involucrado en la patogénesis de manifestaciones extrahepáticas, entre las cuales se ha asociado con alteraciones metabólicas como la DM. Estudios longitudinales y transversales han reportado mayor incidencia y prevalencia de DM en pacientes con infección crónica por VHC. La DM acelera la progresión histológica y clínica en pacientes con infección crónica por VHC y las complicaciones cardiovasculares. Recientemente se ha avanzado en el tratamiento y la introducción de nuevos medicamentos como los antivirales de acción directa, que mejoran el control glucémico en estos pacientes.
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Juttada U, Smina TP, Kumpatla S, Viswanathan V. Seroprevalence and risk factors associated with HBV and HCV infection among subjects with type 2 diabetes from South India. Diabetes Res Clin Pract 2019; 153:133-137. [PMID: 31189089 DOI: 10.1016/j.diabres.2019.06.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2019] [Revised: 05/28/2019] [Accepted: 06/07/2019] [Indexed: 12/26/2022]
Abstract
This is a brief summary of the prevalence on Hepatitis C (HCV) and Hepatitis B (HBV) viral infections and associated risk factors in Type 2 diabetes subjects. Prevalence of HBV (9%) was higher compared to HCV (2%) infection in the screened 388 subjects. Results showed that these infections are independent of the liver damage. Risk factors prominently observed among positive HCV and HBV cases were longer duration of diabetes, hospital admission, history of jaundice and history of surgeries which enlightened the importance of hepatitis vaccination once the subject is diagnosed with diabetes.
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Affiliation(s)
- Udyama Juttada
- M.V. Hospital for Diabetes and Prof. M. Viswanathan Diabetes Research Center [WHO Collaborating Center for Research Education and Training in Diabetes], Royapuram, Chennai, Tamil Nadu, India
| | - T P Smina
- M.V. Hospital for Diabetes and Prof. M. Viswanathan Diabetes Research Center [WHO Collaborating Center for Research Education and Training in Diabetes], Royapuram, Chennai, Tamil Nadu, India
| | - Satyavani Kumpatla
- M.V. Hospital for Diabetes and Prof. M. Viswanathan Diabetes Research Center [WHO Collaborating Center for Research Education and Training in Diabetes], Royapuram, Chennai, Tamil Nadu, India
| | - Vijay Viswanathan
- M.V. Hospital for Diabetes and Prof. M. Viswanathan Diabetes Research Center [WHO Collaborating Center for Research Education and Training in Diabetes], Royapuram, Chennai, Tamil Nadu, India.
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Barbato GM, Cadamuro M, Fabris L. Incretin-based treatment in type 2 diabetes mellitus and risk of cholangiocarcinoma: Is it only adverse drug effect? Clin Res Hepatol Gastroenterol 2019; 43:232-235. [PMID: 30833185 DOI: 10.1016/j.clinre.2019.01.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2019] [Accepted: 01/29/2019] [Indexed: 02/04/2023]
Affiliation(s)
| | | | - Luca Fabris
- Division of General Medicine, University-Hospital, Padua, Italy; Department of Molecular Medicine, University of Padua, Italy; Department of Internal Medicine, Digestive Disease Section, Yale University, New Haven, USA.
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Frequency and factors associated with hepatitis C virus infection among patients with diabetes, Dammam, KSA. J Egypt Public Health Assoc 2017; 91:53-8. [PMID: 27455081 DOI: 10.1097/01.epx.0000483164.17996.b8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV) infection and diabetes mellitus (DM) are main causes of morbidity and mortality worldwide. There is an increasing evidence of association between HCV and type 2 DM. Comorbidity will cause devastating health and financial burdens. Early detection may help proper management and better prognosis. OBJECTIVE The aim of this study was to examine the frequency and risk factors of HCV among Saudi patients with diabetes. PATIENTS AND METHODS In this cross-sectional study, 1054 Saudi patients with diabetes type 1 and type 2 were randomly selected, interviewed, and tested for HCV in Dammam Medical Complex, KSA (2011), using the HCV Rapid Test. Positive cases were later confirmed using the INNO-LIA HCV score line immunoassay. RESULTS Seropositivity of HCV was 1.9%. Regression analysis revealed the following independent predictors: sharing articles, elevated liver enzymes, exposure to blood or blood products in occupational setting, disease duration more than 5 years, tattooing, blood transfusion, and hospitalization more than two times. CONCLUSION AND RECOMMENDATIONS The study confirmed a positive association between HCV and DM. The frequency of HCV among patients with diabetes was 1.9%. Predictors of HCV among DM patients were sharing articles, elevated transaminases, occupational exposure to blood or its products, disease duration more than 5 years, tattooing, blood transfusion, and hospitalization more than two times. We recommend screening for HCV among DM patients with elevated serum transaminases and those having the disease for more than 5 years and education of patients with diabetes as regards their high risk for HCV and how to avoid infection.
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Hepatitis B and C seroprevalence in patients with diabetes mellitus and its relationship with microvascular complications. GASTROENTEROLOGY REVIEW 2016; 12:105-110. [PMID: 28702098 PMCID: PMC5497127 DOI: 10.5114/pg.2016.64748] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 08/28/2015] [Accepted: 01/12/2016] [Indexed: 11/23/2022]
Abstract
Introduction Diabetic patients are susceptible to bacterial, viral and fungal infections because of various deficiencies in the immune system. Aim To investigate a possible link between hepatitis B/C prevalence and microvascular complications as well as duration of diabetes. Material and methods In total 1263 diabetic patients (1149 type 2, 114 type 1) were enrolled in the study. The control group consisted of 1482 healthy blood donors who were over 40 years old. All diabetic patients were tested for HBsAg, anti-HBs and anti-HCV beside routine laboratory tests. Diabetic patients were divided into three groups according to their diabetes duration, and all of the patients were scanned for microvascular complications. Demographic data of all patients were recorded. Results HBsAg seropositivity was 3.7% in diabetic patients and 1.08% in the control group; this difference was statistically significant (p < 0.001). HBsAg positivity rates in type 1 and type 2 diabetics were 0.8% and 4%, respectively (p = 0.09). HCV seropositivity was 2.2% for diabetics and 0.5% for the control group; this difference was statistically significant (p < 0.001). Anti-HCV seropositivity in type 1 and type 2 diabetics was 1.75% and 2.26%, respectively. There was no relationship between diabetes duration and hepatitis B-C prevalence (p > 0.05). Also, no relationship was found between microvascular complications of diabetes and hepatitis B/C seropositivity. Conclusions Hepatitis B and C seroprevalence was found to be increased in diabetes mellitus; however, there was no relationship between hepatitis seroprevalence and the duration or microvascular complications of diabetes.
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Ba-Essa EM, Mobarak EI, Al-Daghri NM. Hepatitis C virus infection among patients with diabetes mellitus in Dammam, Saudi Arabia. BMC Health Serv Res 2016; 16:313. [PMID: 27464785 PMCID: PMC4963943 DOI: 10.1186/s12913-016-1578-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2015] [Accepted: 07/21/2016] [Indexed: 01/06/2023] Open
Abstract
Background Data regarding comorbidities of hepatitis C virus infection (HCV) in the kingdom of Saudi Arabia (KSA) are lacking. The present study aimed to determine the prevalence and risk factors of HCV among Saudi patients with diabetes mellitus (DM) in Dammam, KSA. Methods In this cross-sectional study done in 2011, a total of 1054 Saudi DM patients were randomly selected from the Diabetes Center in Dammam Medical Complex, KSA, for interview and HCV screening using the HCV Rapid Test. Positive cases were later confirmed via INNO-LIA HCV score line immune assay. Results Seropositivity of HCV was 1.9 %. DM duration of >5 years increased the probability of HCV risk to 3.7 fold while insulin users were 3.2 times more likely to have HCV infection. Increased hospital admission (3–4 times) also increased HCV risk by 11.5 times and 13.6 times among patients with ≥5 admissions. Similarly, having 3–4 surgical procedures increased HCV risk by 8.6 times and 39.3 times with ≥5 procedures. HCV transmission is 4 times more likely by blood transfusion. Those who shared personal items were 8.5 times more likely to have HCV. Tattooing increased HCV risk by 6.7 times. The likelihood of HCV infection was also higher among DM patients with liver diseases and elevated liver enzymes. Conclusion The study confirmed a significant association between HCV risk and DM. Frequency of HCV among DM Saudis was 1.9 %. Predictors of HCV among DM patients were sharing personal items, occupational exposure to blood or its products, elevated transaminases, tattooing, disease duration > 5 years, increased hospital admission and blood transfusion.
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Affiliation(s)
| | - Eman I Mobarak
- Community Medicine Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Nasser M Al-Daghri
- Prince Mutaib Chair for Biomarkers of Osteoporosis, Biochemistry Department, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia. .,Biomarkers Research Program, Biochemistry Department, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia.
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Affiliation(s)
- Gautam Das
- Prince Charles Hospital, Cwm Taf University Health Board; Merthyr Tydfil UK
| | - Hemanth Bolusani
- University Hospital of Wales, Cardiff and Vale University Health Board; Cardiff UK
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Byrd KK, Mehal JM, Schillie SF, Holman RC, Haberling D, Murphy T. Chronic Liver Disease-Associated Hospitalizations Among Adults with Diabetes, National Inpatient Sample, 2001-2012. Public Health Rep 2016; 130:693-703. [PMID: 26556941 DOI: 10.1177/003335491513000619] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
OBJECTIVE Many people with diabetes have a variety of diabetes-related complications. Among the variety of conditions associated with diabetes, however, liver diseases are less well recognized. As such, we aimed to describe chronic liver disease (CLD)-associated hospitalization rates among U.S. adults with diabetes from 2001-2012. METHODS We used a nationally representative database of hospitalizations, the National Inpatient Sample, to determine CLD-associated hospitalization rates among U.S. adults aged ≥ 18 years with and without diabetes, from 2001-2012. Hospitalizations listing an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code for CLD on the discharge record were selected for analysis and were further classified by diabetes status based on concurrent presence of a diabetes ICD-9-CM code. We calculated average annual age-adjusted hospitalization rates and 95% confidence intervals (CIs), and conducted a test for trend. RESULTS For 2001-2012, the total age-adjusted CLD-associated hospitalization rate among adults with diabetes (1,680.9 per 100,000 population; 95% CI 1,577.2, 1,784.6) was approximately four times the rate of adults without diabetes (424.2 per 100,000 population; 95% CI 413.4, 435.1). Total age-adjusted hospitalization rates of adults with and without diabetes increased 59% and 48%, respectively, from 2001-2002 to 2011-2012 (p<0.001). Hepatitis C- and chronic hepatitis and cirrhosis-associated hospitalizations comprised the largest proportion of total CLD-associated hospitalizations among adults with and without diabetes. CONCLUSION Providers should be aware of the potential existence of CLD among adults with diabetes and counsel patients on preventive methods to avoid progressive liver damage.
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Affiliation(s)
- Kathy K Byrd
- Centers for Disease Control and Prevention, Division of Viral Hepatitis, Atlanta, GA ; Current affiliation: Centers for Disease Control and Prevention, Division of HIV/AIDS Prevention, Atlanta, GA
| | - Jason M Mehal
- Centers for Disease Control and Prevention, Division of High-Consequence Pathogens and Pathology, Atlanta, GA
| | - Sarah F Schillie
- Centers for Disease Control and Prevention, Division of Viral Hepatitis, Atlanta, GA
| | - Robert C Holman
- Centers for Disease Control and Prevention, Division of High-Consequence Pathogens and Pathology, Atlanta, GA
| | - Dana Haberling
- Centers for Disease Control and Prevention, Division of High-Consequence Pathogens and Pathology, Atlanta, GA
| | - Trudy Murphy
- Centers for Disease Control and Prevention, Division of Viral Hepatitis, Atlanta, GA
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Assessment of evidence for positive association and seroprevalence of hepatitis B and C in diabetic patients in a developing country. J Investig Med 2015; 63:251-7. [PMID: 25415060 DOI: 10.1097/jim.0000000000000126] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND AIM The data related to the association between hepatitis virus infections and diabetes mellitus (DM) are conflicting. The aim of this study was to investigate the seroprevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) and to determine the risk factors affecting the prevalence in Turkish patients with type 1 DM and type 2 DM. METHODS The study consisted of 736 diabetic and 505 nondiabetic patients. Serological investigation for the hepatitis B surface antigen (HBsAg) and the HCV antibody (anti-HCV) was performed with a third-generation commercial chemiluminescence assay. The presence of HBsAg was considered as indicator of HBV infection. The HCV infection in the patients with positive anti-HCV was confirmed by a real-time polymerase chain reaction assay. The patients were divided according to their HBV and HCV infection status, and their demographic features, diabetes properties, general risk factors, and aminotransferase levels were analyzed. RESULTS There was no significant difference in the seropositivity rate for the HBsAg (3.8% vs 3.0%, P > 0.43; odds ratio, 1.292; 95% confidence interval, 0.683-2.444). However, anti-HCV seropositivity was significantly increased in the DM group (3.3% vs 1.8%, P < 0.03; odds ratio, 2.398; 95% confidence interval, 1.025-5.609). Increased aminotransferase levels and a history of blood transfusions were positively correlated with both HBV and HCV infection. Moreover, a history of surgical procedures and high glycated hemoglobin A1c levels were positively associated with HBsAg antigen seropositivity. CONCLUSIONS Although no significant difference in the seropositivity of the HBsAg was determined, a high prevalence of HCV infection was detected in the DM patients compared to healthy controls.
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Laloo D, Walke P, Bhimo T, Prasad L, Ranabir S. Seroprevalence of hepatitis C infection in type 2 diabetes mellitus. Indian J Endocrinol Metab 2015; 19:296-299. [PMID: 25729696 PMCID: PMC4319274 DOI: 10.4103/2230-8210.149325] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
INTRODUCTION Hepatitis C is an emerging disease with different studies showing varying prevalence rates across India. In several studies, prevalence of hepatitis C infection was found to be higher in diabetics than nondiabetics. However, none has been reported from India. OBJECTIVES The aim was to determine the sero-prevalence of hepatitis C infection in type 2 diabetes mellitus (T2DM). SETTINGS AND DESIGN Cross-sectional study of all T2DM patients attending endocrine clinic in Regional Institute of Medical Sciences, Imphal from October 2011 to September 2013. SUBJECTS AND METHODS All T2DM patients included and exclusion criteria are patients with other forms of diabetes, liver failure, renal failure, malignancy or other chronic illness. Patient's age, sex, height, weight, body mass index, history of risk factors, etc., collected and investigated for blood glucose fasting and prandial levels, transaminases levels, hepatitis C virus (HCV) screening, etc.. STATISTICAL ANALYSIS Statistical analysis was performed using Statistical Package for the Social Sciences version 20; appropriate test used where applicable. RESULTS Out of the 192 T2DM patients screened, prevalence rate of HCV sero-positivity is found to be 5.7% (11/192), higher in males. History of jaundice in the past was the only significant history among sero-positive patients. Transaminases levels are significantly higher in sero-postive cases. They had higher fasting and postprandial blood glucose, fasting glucose levels being significantly higher. CONCLUSION Our study shows a slightly higher prevalence of hepatitis C infection in type 2 diabetics.
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Affiliation(s)
- Demitrost Laloo
- Department of Medicine, Regional Institute of Medical Sciences, Imphal, Manipur, India
| | - Prashant Walke
- Department of Medicine, Regional Institute of Medical Sciences, Imphal, Manipur, India
| | - Thongam Bhimo
- Department of Medicine, Regional Institute of Medical Sciences, Imphal, Manipur, India
| | - Lallan Prasad
- Department of Medicine, Regional Institute of Medical Sciences, Imphal, Manipur, India
| | - Salam Ranabir
- Department of Medicine, Regional Institute of Medical Sciences, Imphal, Manipur, India
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Cacoub P, Gragnani L, Comarmond C, Zignego AL. Extrahepatic manifestations of chronic hepatitis C virus infection. Dig Liver Dis 2014; 46 Suppl 5:S165-73. [PMID: 25458776 DOI: 10.1016/j.dld.2014.10.005] [Citation(s) in RCA: 190] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2014] [Accepted: 10/03/2014] [Indexed: 02/09/2023]
Abstract
Hepatitis C virus (HCV) infected patients are known to be at risk of developing liver complications i.e. cirrhosis and liver cancer. However, the risks of morbidity and mortality are underestimated because they do not take into account non-liver consequences of chronic hepatitis C virus infection. Numerous extrahepatic manifestations have been reported in up to 74% of patients, from perceived to disabling conditions. The majority of data concern hepatitis C virus-related autoimmune and/or lymphoproliferative disorders, from mixed cryoglobulinaemia vasculitis to frank lymphomas. More recently, other hepatitis C virus-associated disorders have been reported including cardiovascular, renal, metabolic, and central nervous system diseases. This review aims to outline most of the extrahepatic manifestations that are currently being investigated, including some of autoimmune and/or lymphoproliferative nature, and others in which the role of immune mechanisms appears less clear. Beyond the liver, hepatitis C virus chronic infection should be analyzed as a multifaceted systemic disease leading to heavy direct and indirect costs. The accurate consideration of extrahepatic consequences of such a systemic infection significantly increases the weight of its pathological burden. The need for effective viral eradication measures is underlined.
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Affiliation(s)
- Patrice Cacoub
- Sorbonne University, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR_S 959, Paris, France; CNRS, FRE3632, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France.
| | - Laura Gragnani
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Cloe Comarmond
- Sorbonne University, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR_S 959, Paris, France; CNRS, FRE3632, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
| | - Anna Linda Zignego
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
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Antonelli A, Ferrari SM, Giuggioli D, Di Domenicantonio A, Ruffilli I, Corrado A, Fabiani S, Marchi S, Ferri C, Ferrannini E, Fallahi P. Hepatitis C virus infection and type 1 and type 2 diabetes mellitus. World J Diabetes 2014; 5:586-600. [PMID: 25317237 PMCID: PMC4138583 DOI: 10.4239/wjd.v5.i5.586] [Citation(s) in RCA: 71] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2013] [Revised: 04/10/2014] [Accepted: 07/12/2014] [Indexed: 02/05/2023] Open
Abstract
Hepatitis C virus (HCV) infection and diabetes mellitus are two major public health problems that cause devastating health and financial burdens worldwide. Diabetes can be classified into two major types: type 1 diabetes mellitus (T1DM) and T2DM. T2DM is a common endocrine disorder that encompasses multifactorial mechanisms, and T1DM is an immunologically mediated disease. Many epidemiological studies have shown an association between T2DM and chronic hepatitis C (CHC) infection. The processes through which CHC is associated with T2DM seem to involve direct viral effects, insulin resistance, proinflammatory cytokines, chemokines, and other immune-mediated mechanisms. Few data have been reported on the association of CHC and T1DM and reports on the potential association between T1DM and acute HCV infection are even rarer. A small number of studies indicate that interferon-α therapy can stimulate pancreatic autoimmunity and in certain cases lead to the development of T1DM. Diabetes and CHC have important interactions. Diabetic CHC patients have an increased risk of developing cirrhosis and hepatocellular carcinoma compared with non-diabetic CHC subjects. However, clinical trials on HCV-positive patients have reported improvements in glucose metabolism after antiviral treatment. Further studies are needed to improve prevention policies and to foster adequate and cost-effective programmes for the surveillance and treatment of diabetic CHC patients.
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Ahmadieh H, Azar ST. Liver disease and diabetes: association, pathophysiology, and management. Diabetes Res Clin Pract 2014; 104:53-62. [PMID: 24485856 DOI: 10.1016/j.diabres.2014.01.003] [Citation(s) in RCA: 67] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2013] [Revised: 06/20/2013] [Accepted: 01/01/2014] [Indexed: 12/19/2022]
Abstract
Diabetes is associated with a spectrum of liver diseases including nonalcoholic liver disease, steatohepatitis, and liver cirrhosis with their increased complications and mortality. Hepatitis C virus (HCV) and its associated liver cirrhosis has been associated with diabetes through insulin resistance. Cryptogenic diabetes occurs as a consequence of liver cirrhosis with the pathophysiology being complex, but mostly attributed to the increased insulin resistance in muscle, liver, and adipose tissue. As for the management of diabetes in patients with liver disease, lifestyle modification plays an important role. Oral diabetic medications are contraindicated in patients with advanced liver diseases with associated cirrhosis, ascites, or encephalopathy. As for stable liver disease, metformin and thiazolenediones have shown mixed results, with some showing them to be effective in improving liver transaminases in addition to histological improvement in steatosis and inflammation. α-glucosidase inhibitors may be helpful in decreasing hepatic encephalopathy. Upregulation of Dipeptidyl peptidase-4 (DPP-4) has been suggested as a possible pathogenetic mechanism for HCV-related insulin resistance, and treatment with DPP-4 inhibitors could improve insulin sensitivity in diabetic patients with liver disease. Patients with impaired liver function with associated insulin resistance may need increased insulin requirements. On the other hand patients with altered liver metabolism might need decreased insulin requirements.
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Affiliation(s)
- Hala Ahmadieh
- Department of Internal Medicine, Division of Endocrinology, American University of Beirut-Medical Center, New York, NY 10017 USA
| | - Sami T Azar
- Department of Internal Medicine, Division of Endocrinology, American University of Beirut-Medical Center, New York, NY 10017 USA.
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Ladep NG, Khan SA, Crossey MME, Thillainayagam AV, Taylor-Robinson SD, Toledano MB. Incidence and mortality of primary liver cancer in England and Wales: Changing patterns and ethnic variations. World J Gastroenterol 2014; 20:1544-1553. [PMID: 24587630 PMCID: PMC3925863 DOI: 10.3748/wjg.v20.i6.1544] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2013] [Revised: 11/18/2013] [Accepted: 12/04/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To explore recent trends, modes of diagnosis, ethnic distribution and the mortality to incidence ratio of primary liver cancer by subtypes in England and Wales.
METHODS: We obtained incidence (1979-2008) and mortality (1968-2008) data for primary liver cancer for England and Wales and calculated age-standardised incidence and mortality rates. Trends in age-standardised mortality (ASMR) and incidence (ASIR) rates and basis of diagnosis of primary liver cancer and subcategories: hepatocellular carcinoma, intrahepatic bile duct and unspecified liver tumours, were analysed over the study period. Changes in guidelines for the diagnosis of primary liver cancer (PLC) may impact changing trends in the rates that may be obtained. We thus explored changes in the mode of diagnosis as reported to cancer registries. Furthermore, we examined the distribution of these tumours by ethnicity. Most of the statistical manipulations of these data was carried out in Microsoft excel® (Seattle, Washington, United Sttaes). Additional epidemiological statistics were done in Epi Info software (Atlanta, GA, United Sttaes). To define patterns of change over time, we evaluated trends in ASMR and ASIR of PLC and intrahepatic bile duct carcinoma (IHBD) using a least squares regression line fitted to the natural logarithm of the mortality and incidence rates. We estimated the patterns of survival over subsequent 5 and 10 years using complement of mortality to incidence ratio (1-MIR).
RESULTS: Age-standardised mortality rate of primary liver cancer increased in both sexes: from 2.56 and 1.29/100000 in 1968 to 5.10 and 2.63/100000 in 2008 for men and women respectively. The use of histology for diagnostic confirmation of primary liver cancer increased from 35.7% of registered cases in 1993 to plateau at about 50% during 2005 to 2008. Reliance on cytology as a basis of diagnosis has maintained a downward trend throughout the study period. Although approximately 30% of the PLC registrations had information on ethnicity, there was a relatively higher registration of the major tumour subtypes in patients whose ethnic backgrounds were from high incident regions of the world. Survival from PLC is estimated to get poorer in 10 years (2018) relative to 2008, particularly as a result of IHBD.
CONCLUSION: Incidence and mortality of PLC, and particularly IHBD, have continued to rise in England and Wales. Changes in the modes of diagnosis may be contributing.
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Type 2 diabetes mellitus and the risk of hepatitis C virus infection: a systematic review. Sci Rep 2013; 3:2981. [PMID: 25671325 PMCID: PMC6506455 DOI: 10.1038/srep02981] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2013] [Accepted: 09/24/2013] [Indexed: 02/05/2023] Open
Abstract
The aim of this study was to evaluate the relationship between type 2 diabetes mellitus (T2DM) and hepatitis C virus (HCV) infection and to examine whether T2DM enhances the risk of HCV infection compared with the risk in the general population. We followed standard guidelines to perform a meta-analysis. The associated literature was selected based on the established inclusion criteria. The summary odds ratio (OR) and 95% confidence interval (95% CI) were used to investigate the strength of the association. Through electronic database and manual searching, 22 studies were identified for the final analysis, which included a total of 78,051 individuals. Based on the random effects model, the meta-analysis results showed that patients with T2DM were at a higher risk of acquiring HCV infection than non-T2DM patients (summary OR = 3.50, 95% CI = 2.54–4.82, I2 = 82.3%). Based on the current limited evidence, this study suggests that T2DM is associated with increased susceptibility to HCV infection.
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Association of Hepatitis C Virus Infection with Type II Diabetes in Ethiopia: A Hospital-Based Case-Control Study. Interdiscip Perspect Infect Dis 2012; 2012:354656. [PMID: 23049551 PMCID: PMC3461610 DOI: 10.1155/2012/354656] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2012] [Accepted: 08/22/2012] [Indexed: 02/07/2023] Open
Abstract
Background. Chronic hepatitis C virus (HCV) has become the global “epidemic” with an estimated 123 million people currently infected worldwide. As the same time diabetes is also rapidly emerging as a global health care problem that threatens to reach pandemic levels by 2030. Objective. To investigate the magnitude of HCV infection in type II diabetes as compared to controls. Methodology. A case control study design was conducted at Jimma University Specialized Hospital from May to June 2010. A total of 604 study subjects were included in this study. Sociodemographic and risk factor data were collected by questionnaire. From serum sample, HCVAb screening was done by rapid antibody screening test. Liver functioning tests and total cholesterol tests were done by Dr. Lange LP 800 spectrophotometer.
Results. The prevalence of HCV in type II diabetes and nondiabetic controls was 9.9% and 3.3%, respectively. In multivariate analysis, HCV seropositives have high risk of developing diabetes as compared with seronegatives (AOR = 2.997, 95% CI: (1.08, 8.315)). Conclusion. In this study, we found a positive association between past HCV infection and type II diabetes. As we did not perform HCV RNA test, we could not assess the association with HCV viremia.
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Harrison SA, Hamzeh FM, Han J, Pandya PK, Sheikh MY, Vierling JM. Chronic hepatitis C genotype 1 patients with insulin resistance treated with pioglitazone and peginterferon alpha-2a plus ribavirin. Hepatology 2012; 56:464-73. [PMID: 22334369 DOI: 10.1002/hep.25661] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2011] [Revised: 01/24/2012] [Accepted: 02/07/2012] [Indexed: 12/14/2022]
Abstract
UNLABELLED Patients with chronic hepatitis C and insulin resistance are less likely to respond to anti-hepatitis C virus (HCV) therapy and are at risk for more rapid fibrosis progression. Coadministration of pioglitazone with peginterferon/ribavirin improves insulin sensitivity and increases virologic response rates in insulin-resistant HCV genotype 4 patients, but it is unclear whether this finding applies to genotype 1 patients. For this reason we randomized treatment-naive HCV genotype 1 patients with insulin resistance to receive either standard care (peginterferon alpha-2a plus ribavirin for 48 weeks, n = 73) or pioglitazone 30-45 mg/day plus standard care (n = 77) in an open-label multicenter trial. Patients randomized to pioglitazone received the drug during a 16-week run-in phase, the 48-week standard-care phase, and the 24-week untreated follow-up phase. Pioglitazone treatment improved hemoglobin A1c (HbA1c), plasma glucose, insulin levels, and homeostasis model assessment of insulin resistance score and increased serum adiponectin levels during the 16-week run-in phase and maintained these improvements during the standard-care phase. However, we observed no statistically significant difference between the two groups in the primary efficacy endpoint, the decrease from baseline to Week 12 of peginterferon alpha-2a/ribavirin treatment in mean log(10) HCV RNA titer (-3.5 ± 1.71 and -3.7 ± 1.62 IU/mL in the pioglitazone and standard-care groups, respectively, Δ = 0.21 IU/mL, P = 0.4394). CONCLUSION Treatment with pioglitazone before and during treatment with peginterferon alpha-2a plus ribavirin improved several indices of glycemic control in patients with chronic hepatitis C and insulin resistance, but did not improve virologic response rates compared with peginterferon alpha-2a plus ribavirin alone.
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Affiliation(s)
- Stephen A Harrison
- Division of Gastroenterology and Hepatology, Department of Medicine, Brooke Army Medical Center, Fort Sam Houston, TX 78234, USA.
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Hepatitis C virus activates the mTOR/S6K1 signaling pathway in inhibiting IRS-1 function for insulin resistance. J Virol 2012; 86:6315-22. [PMID: 22457523 DOI: 10.1128/jvi.00050-12] [Citation(s) in RCA: 102] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infection significantly increases the prevalence of type 2 diabetes mellitus (T2DM). Insulin receptor substrate 1 (IRS-1) plays a key role in insulin signaling, thus enabling metabolic regulation in mammalian cells. We have previously shown that HCV infection modulates phosphorylation of Akt, a downstream target of IRS-1. In this study, we further examined the status of total IRS-1 and the downstream regulation of the Akt pathway in understanding mTOR/S6K1 signaling using HCV genotype 2a (clone JFH1)-infected hepatocytes. Inhibition of IRS-1 expression was observed in HCV-infected hepatocytes compared to that in a mock-infected control. The status of the tuberous sclerosis complex (TSC-1/TSC-2) was significantly decreased after HCV infection of human hepatocytes, showing a modulation of the downstream Akt pathway. Subsequent study indicated an increased level of Rheb and mTOR expression in HCV-infected hepatocytes. Interestingly, the phosphoS6K1 level was higher in HCV-infected hepatocytes, suggesting a novel mechanism for IRS-1 inhibition. Ectopic expression of TSC-1/TSC-2 significantly recovered the IRS-1 protein expression level in HCV-infected hepatocytes. Further analyses indicated that HCV core protein plays a significant role in modulating the mTOR/S6K1 signaling pathway. Proteasome inhibitor MG 132 recovered IRS-1 and TSC1/2 expression, suggesting that degradation occurred via the ubiquitin proteasome pathway. A functional consequence of IRS-1 inhibition was reflected in a decrease in GLUT4 protein expression and upregulation of the gluconeogenic enzyme PCK2 in HCV-infected hepatocytes. Together, these observations suggested that HCV infection activates the mTOR/S6K1 pathway in inhibiting IRS-1 function and perturbs glucose metabolism via downregulation of GLUT4 and upregulation of PCK2 for insulin resistance.
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Greca LF, Pinto LC, Rados DR, Canani LH, Gross JL. Clinical features of patients with type 2 diabetes mellitus and hepatitis C infection. Braz J Med Biol Res 2012; 45:284-90. [PMID: 22286533 PMCID: PMC3854195 DOI: 10.1590/s0100-879x2012007500013] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2011] [Accepted: 10/06/2011] [Indexed: 02/07/2023] Open
Abstract
The objective of the present cross-sectional study was to assess the prevalence and the clinical and laboratory features of hepatitis C virus (HCV)-positive patients with type 2 diabetes mellitus (DM) attending either an outpatient clinic or hemodialysis units. Serologic-HCV testing was performed in 489 type 2 DM patients (303 outpatients and 186 on dialysis). A structured assessment of clinical, laboratory and DM-related complications was performed and the patients were then compared according to HCV infection status. Mean patient age was 60 years; HCV positivity (HCV+) was observed in 39 of 303 (12.9%) outpatients and in 34 of 186 (18.7%) dialysis patients. Among HCV+ patients, 32 were men (43.8%). HCV+ patients had higher serum levels of aspartate aminotransferase (0.90 ± 0.83 vs 0.35 ± 0.13 μKat/L), alanine aminotransferase (0.88 ± 0.93 vs 0.38 ± 0.19 μKat/L), gamma-glutamyl transferase (1.57 ± 2.52 vs 0.62 ± 0.87 μKat/L; P < 0.001), and serum iron (17.65 ± 6.68 vs 14.96 ± 4.72 μM; P = 0.011), and lower leukocyte and platelet counts (P = 0.010 and P < 0.001, respectively) than HCV-negative (HCV-) patients. HCV+ dialysis patients had higher diastolic blood pressure than HCV- patients (87.5 ± 6.7 vs 81.5 ± 6.0 mmHg; P = 0.005) and a lower prevalence of diabetic retinopathy (75 vs 92.7%; P = 0.007). In conclusion, our study showed that HCV is common among subjects with type 2 DM but is not associated with a higher prevalence of chronic diabetic complications.
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Affiliation(s)
- L F Greca
- Serviço de Endocrinologia, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2350, Porto Alegre, RS, Brazil
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23
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Samantray J, Zambare S, Seyoum B, Abou-Samra AB. Glucose control and lipid metabolism in African American patients with type 2 diabetes mellitus and chronic hepatitis C viral infection. Endocr Pract 2011; 17:363-8. [PMID: 21134881 DOI: 10.4158/ep10175.or] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To compare lipid profiles and glucose control in African American patients with type 2 diabetes mellitus with and without chronic hepatitis C viral (HCV) infection. METHODS This retrospective study conducted in an academic outpatient setting included African American patients with both type 2 diabetes and HCV, patients with HVC only, and patients with type 2 diabetes only. Serum total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglyceride values were compared among all 3 patient groups. RESULTS The study population included 283 patients, of whom 111 had type 2 diabetes and HCV, 68 had HCV only, and 104 had type 2 diabetes only. Chronic HCV was associated with lower total cholesterol and LDL-cholesterol levels in patients with or without type 2 diabetes. In contrast, elevated serum triglyceride levels associated with diabetes were not reduced in patients with chronic HCV, although diabetes control was better in the diabetes group with HCV than in the diabetes group without HCV (mean hemoglobin A1c [standard error of the mean]: 7.1% [1.8%]vs 8.8% [2.1%], P<.001). HDL cholesterol was higher in the patients with earlier stages of HCV when compared with HDL cholesterol in the other 2 groups. CONCLUSIONS Chronic HCV infection in type 2 diabetic patients decreases serum levels of total and LDL cholesterol, but has no such protective effect on triglyceride levels. HCV infection may alter the cellular pathways of cholesterol and triglyceride metabolism in patients with type 2 diabetes.
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Affiliation(s)
- Julie Samantray
- Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI, USA.
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Kaddai V, Negro F. Current understanding of insulin resistance in hepatitis C. Expert Rev Gastroenterol Hepatol 2011; 5:503-16. [PMID: 21780897 DOI: 10.1586/egh.11.43] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Important breakthroughs have been made in recent years into understanding the close interaction between hepatitis C virus (HCV) infection and glucose homeostasis. Both cross-sectional and longitudinal studies have demonstrated that infection with HCV is associated with an increased risk of developing insulin resistance and Type 2 diabetes. A direct effect of HCV on hepatocyte insulin signaling has been shown in experimental models. Some preliminary observations seem to suggest that indirect mechanisms involving extrahepatic organs might also play a role. The interaction between HCV and glucose metabolism has significant clinical consequences. Insulin resistance and Type 2 diabetes not only accelerate the histological and clinical progression of chronic hepatitis C, but also reduce the virological response to IFN-α-based therapy. Thus, understanding the mechanisms underlying HCV-associated glucose metabolism derangements is of paramount interest in order to improve the clinical management of chronic hepatitis C. This article will focus on the studies that consistently argue in favor of an interrelation between HCV and insulin resistance and will highlight the latest discoveries in this field.
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Affiliation(s)
- Vincent Kaddai
- Department of Pathology and Immunology, Centre Médical Universitaire, Rue Michel-Servet 1, Geneva, Switzerland
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Chehadeh W, Kurien SS, Abdella N, Ben-Nakhi A, Al-Arouj M, Almuaili T, Al-Mutairi O, Al-Nakib W. Hepatitis C virus infection in a population with high incidence of type 2 diabetes: impact on diabetes complications. J Infect Public Health 2011; 4:200-6. [PMID: 22000848 DOI: 10.1016/j.jiph.2011.05.004] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2011] [Revised: 05/25/2011] [Accepted: 05/26/2011] [Indexed: 02/08/2023] Open
Abstract
A growing number of reports suggest a connection between hepatitis C virus (HCV) infection and type 2 diabetes (T2D). However, the association of HCV infection with diabetes-related complications has not yet been clarified. The aim of this study was to determine the prevalence of HCV infection in T2D-patients in Kuwait which has a high incidence of type 2 diabetes, and to investigate the association between HCV viremia and diabetes-related complications. A total of 438 patients with T2D (325 Kuwaitis and 113 Egyptians), and 440 control subjects, were enrolled for this study. HCV infection was assessed by testing for serum HCV-specific antibodies, and by detection of HCV RNA. HCV viral load and hemoglobin A1c (HbA1c) levels were assessed in patients with and without diabetes complications. Thirty one (7%) out of 438 T2D-patients had evidence of HCV infection compared to 4 (1%) out of 440 control adults (p<0.0001). The prevalence of HCV infection in Kuwaiti and Egyptian T2D-patients was 3% and 18%, respectively. Most of the HCV sequences detected in T2D patients and control subjects were of genotype 4. The HbA1c levels in T2D-patients with HCV viremia were significantly higher than those in HCV-negative patients. HCV viremia, female sex, age, family history of diabetes were found to be independent risk factors for diabetes complications. The results suggest that T2D-patients in Kuwait have higher prevalence of HCV infection than controls, and that HCV viremia is associated with diabetes-related complications.
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Affiliation(s)
- Wassim Chehadeh
- Department of Microbiology, Faculty of Medicine, Kuwait University, Kuwait.
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Sanyal AJ. Role of insulin resistance and hepatic steatosis in the progression of fibrosis and response to treatment in hepatitis C. Liver Int 2011; 31 Suppl 1:23-8. [PMID: 21205134 DOI: 10.1111/j.1478-3231.2010.02397.x] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Hepatitis C is a common cause of chronic viral infection of the liver. It is associated with insulin resistance and the development of type 2 diabetes mellitus. It is also associated with the development of hepatic steatosis. The presence of hepatic steatosis is associated with an increased risk of having hepatic fibrosis. This is also associated with the severity of insulin resistance. These findings are specifically germane for those with genotype1 infection. Genotype 3 infection independently causes steatosis and successful treatment of the virus is followed by resolution of steatosis. In genotype 1 infection, the presence of hepatic steatosis is also a risk factor for failure to respond to pegylated interferon and ribavirin therapy. Unfortunately efforts to treat insulin resistance prior to antiviral therapy have not been very successful. Newer efforts focused on the role of specific micro RNAs in mediating the metabolic effects of hepatitis C virus infection may provide to ameliorate the metabolic risks of HCV infection.
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Affiliation(s)
- Arun J Sanyal
- Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University Medical Center, Richmond, VA 23298-0341, USA.
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Basseri B, Yamini D, Chee G, Enayati PDP, Tran T, Poordad F. Comorbidities associated with the increasing burden of hepatitis C infection. Liver Int 2010; 30:1012-8. [PMID: 20408945 DOI: 10.1111/j.1478-3231.2010.02235.x] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is implicated in an increasing number of liver transplantations, hospitalizations and healthcare costs. AIMS We present an updated assessment of comorbidities associated with HCV in comparison to the general US population. METHODS Cross-sectional retrospective review of data from 800 patients with HCV evaluated between January 1998 and November 2007. Patient data were prospectively collected using a standardized questionnaire completed at the first encounter and was compared with general US epidemiological data. Odds ratios and 95% confidence intervals (CI) are reported. RESULTS HCV conferred a 44% (CI 1.16-1.78) and 25% (CI 1.01-1.54) increased risk of diabetes (12.5 vs. 7.3-8.4%; P=0.001) and obesity (23.9 vs. 19.8-33.1%; P=0.041), respectively, compared with the US population. Human immunodeficiency virus (HIV) (5.3 vs. 0.3%; P<0.001) and end-stage renal disease (ESRD) (4.5 vs. 0.2%; P<0.001) were 16- and 13-fold more prevalent in HCV. Interestingly, HCV bestowed 90% decreased odds (CI 0.09-0.15) for hyperlipidaemia (12.3 vs. 53.2-56.1%; P<0.001). The HCV population had a higher prevalence of significant alcohol consumption (41.5 vs. 4.7%; P<0.001), current smoking (57.7 vs. 18.8-20.8%; P<0.001), drug use (46.8 vs. 14.6-15.6%; P<0.001), incarceration (6.6 vs. 2.7%; P<0.001) and tattoos (20.3 vs. 14%; P=0.011), as well as chronic fatigue (44.6 vs. 11.3-19%; P<0.001) and depression (29.3 vs. 5.0-10.3%; P<0.001). CONCLUSION HCV poses an increasing healthcare burden associated with increased prevalence of diabetes, obesity, HIV, ESRD, maladaptive lifestyle habits and poor quality of life. Practitioners should be cognizant of these trends in order to appropriately manage these comorbidities.
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Affiliation(s)
- Benjamin Basseri
- Hepatology Section, Division of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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Montano-Loza AJ, Sultan A, Falanga D, Loss G, Mason AL. Immunogenetic susceptibility to diabetes mellitus in patients with liver disease. Liver Int 2009; 29:1543-51. [PMID: 19663932 DOI: 10.1111/j.1478-3231.2009.02095.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
BACKGROUND/AIM Genetic, environmental, metabolic and infectious influences, such as hepatitis C virus (HCV) infection, are thought to impact on the development of diabetes in patients with liver disease. As specific human leucocyte antigen (HLA) alleles provide the major genetic risk factors for type 1 diabetes, our aim was to investigate whether HLA class I and II alleles constitute additional risk factors for diabetes in patients with liver disease. METHODS We evaluated two independent databases of 193 and 728 adult patients with chronic liver disease for the diagnosis of diabetes and the presence of specific HLA subtypes. RESULTS In each database, 24 and 19% of patients met criteria for diabetes. In the first database, specific class I and II alleles were observed more frequently in diabetics compared with non-diabetics: Cw7 (50 vs. 32%, P=0.04), DR51 (17 vs. 3%P=0.003) and DQ6 (37 vs. 18%, P=0.02). In the second database, DQ6 was observed in 16% of diabetics vs. 8% of non-diabetics (P=0.04). The DR2-DR51-DQ6 haplotype was higher in patients with diabetes in both databases (22 vs.7%, P=0.02 and 12 vs. 5%, P=0.02). In a subgroup analysis of patients with HCV infection, increased frequencies of Cw7, DR2/DR51, DQ6 and DR2-DR51-DQ6 were also observed to be higher in subjects with diabetes compared with those without diabetes. CONCLUSIONS Patients with chronic liver disease, especially those with HCV infection, have an immunogenetic risk for diabetes characterized by the presence of Cw7, DR51, DQ6 and DR2-DR51-DQ6.
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Affiliation(s)
- Aldo J Montano-Loza
- Department of Medicine, University of Alberta Hospital, Edmonton, AB, Canada
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Nwankiti OO, Ndako JA, Echeonwu GO, Olabode AO, Nwosuh CI, Onovoh EM, Okeke LA, Akinola JO, Duru BN, Nwagbo IO, Agada GO, Chukwuedo AA. Hepatitis C Virus infection in apparentenly healthy individuals with family history of diabetes in Vom, Plateau State Nigeria. Virol J 2009; 6:110. [PMID: 19619316 PMCID: PMC2717943 DOI: 10.1186/1743-422x-6-110] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2009] [Accepted: 07/20/2009] [Indexed: 01/14/2023] Open
Abstract
Hepatitis C virus (HCV) infection is an important public health problem worldwide. Its association with, and predisposing nature for diabetes mellitus (DM) has been long established. This research was carried out to determine the prevalence of Hepatitis C virus (HCV) amongst people with possible genetic predisposition to diabetes mellitus living in and around Vom, Plateau State, Nigeria. 188 subjects were screened after they filled a structured questionnaire to determine some of their demographic data, social habits and possible risk factors. 5 ml of blood was collected from each subject and sera separated out. Biotech's third generation ELISA Kit for HCV antibodies was used for the screening. Liver enzyme analysis was carried out on positive samples to determine their disease status. A prevalence of 14.36% was recorded with the highest seropositive group being those in the age bracket of 18 – 37 years. 13(13.40%) of males and 14(15.38%) of females were sero-positive. Liver enzyme analysis of sero-positive subjects showed increased levels which may imply early onset of liver damage. These result showed that these individuals could later suffer diabetes which may be triggered by their HCV infection if not treated. This is not over-looking the economic significance of their ill health, assuming they progress to cirrhotic HCV or develop hepatocelluar carcinoma due to HCV chronicity.
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Kaabia N, Ben Jazia E, Slim I, Fodha I, Hachfi W, Gaha R, Khalifa M, Hadj Kilani A, Trabelsi H, Abdelaziz A, Bahri F, Letaief A. Association of hepatitis C virus infection and diabetes in central Tunisia. World J Gastroenterol 2009; 15:2778-81. [PMID: 19522029 PMCID: PMC2695894 DOI: 10.3748/wjg.15.2778] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate hepatitis C virus (HCV) seroprevalence in Tunisian patients with diabetes mellitus and in a control group.
METHODS: A cross-sectional study was conducted to determine the HCV seroprevalence in 1269 patients with diabetes (452 male, 817 female) and 1315 non-diabetic patients, attending health centers in Sousse, Tunisia. HCV screening was performed in both groups using a fourth-generation enzyme immunoassay.
RESULTS: In the diabetic group, 17 (1.3%) were found to be HCV-infected compared with eight (0.6%) in the control group, although the difference was not significant (P = 0.057). Quantitative PCR was performed in 20 patients. Eleven patients were positive and showed HCV genotype 1b in all cases.
CONCLUSION: Frequency of HCV antibodies was low in patients with diabetes and in the control group in central Tunisia, with no significant difference between the groups.
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Negro F, Alaei M. Hepatitis C virus and type 2 diabetes. World J Gastroenterol 2009; 15:1537-47. [PMID: 19340895 PMCID: PMC2669937 DOI: 10.3748/wjg.15.1537] [Citation(s) in RCA: 112] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2008] [Revised: 01/21/2009] [Accepted: 01/28/2009] [Indexed: 02/06/2023] Open
Abstract
This review focuses on the relationship between hepatitis C virus (HCV) infection and glucose metabolism derangements. Cross-sectional and longitudinal studies have shown that the chronic HCV infection is associated with an increased risk of developing insulin resistance (IR) and type 2 diabetes (T2D). The direct effect of HCV on the insulin signaling has been analyzed in experimental models. Although currently available data should be considered as preliminary, HCV seems to affect glucose metabolism via mechanisms that involve cellular pathways that have been implicated in the host innate immune response. IR and T2D not only accelerate the histological and clinical progression of chronic hepatitis C, but also reduce the early and sustained virological response to interferon-alpha-based therapy. Thus, a detailed knowledge of the mechanisms underlying the HCV-associated glucose metabolism derangements is warranted, in order to improve the clinical management of chronic hepatitis C patients.
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Tsochatzis EA, Manolakopoulos S, Papatheodoridis GV, Archimandritis AJ. Insulin resistance and metabolic syndrome in chronic liver diseases: old entities with new implications. Scand J Gastroenterol 2009; 44:6-14. [PMID: 18661429 DOI: 10.1080/00365520802273058] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Insulin resistance (IR) and metabolic syndrome have recently been implicated in the pathogenesis and progression of chronic liver diseases, especially chronic hepatitis C (CHC) and non-alcoholic fatty liver disease (NAFLD). In this review, we provide current information on their deleterious effect on the liver, with particular interest in those two entities. In NAFLD, IR causes both the accumulation of fat in hepatocytes and the progression to non-alcoholic steatohepatitis (NASH). Moreover, the presence of metabolic syndrome seems to be associated with severe fibrosis in NASH patients. In CHC, IR develops early in the course of the disease and precedes steatosis. It is also independently associated with histological severity and negatively affects treatment response, irrespective of genotype. Consequently, therapies targeting IR and metabolic syndrome could indirectly ameliorate the prognosis of both NAFLD and CHC. As specific therapies do not exist, patients with metabolic syndrome and CHC and NAFLD should be counseled to lose weight and ameliorate their glycemic control and lipid profile.
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Affiliation(s)
- Emmanuel A Tsochatzis
- Second Department of Internal Medicine, Athens University Medical School, Hippokration General Hospital, Athens, Greece
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Cadranel JF, Di Martino V, Lambrey G, Mourlhon C, Nalet B, Anciaux ML, Richard C, Bigué JP, Barjon JN, Bories C, Barbare JC, Halimi C, Ribière O, Eugène C, Pauwels A, Jeanne S, Donato L, Dumouchel P, Pariente A, Duverlie G, Devergie B, Arlot S, Capron D. Prevalence of hepatitis C infection and risk factors in hospitalized diabetic patients: results of a cross-sectional study. Eur J Gastroenterol Hepatol 2008; 20:829-836. [PMID: 18794595 DOI: 10.1097/meg.0b013e3282fc73a1] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVES Although there may exist a nosocomial risk of hepatitis C virus (HCV) infection in patients with type 1 or type 2 diabetes, this risk has not been fully investigated thus far and its magnitude is unknown. The aim of this multicenter cross-sectional study was to evaluate the prevalence of, and risk factors for, hepatitis C infection in consecutive hospitalized patients with diabetes and to assess the nosocomial risk and magnitude of HCV infection in these patients. PATIENTS AND METHODS Consecutive hospitalized patients with diabetes seen in 11 French hepatogastroenterology and diabetology departments were studied. The prevalence of anti-HCV antibodies was compared with that observed in healthy blood donors and individuals seen during routine medical checkup. Diabetic patients with anti-HCV antibodies were compared with patients without anti-HCV antibodies for assessment of risk factors. RESULTS In total 1561 patients were studied. Independent risk factors for HCV infection were assessed through multivariate analysis. Thirty-three patients (2.11%) had anti-HCV antibodies and 21 (63.70%) had HCV identified risk factors. The prevalence of HCV infection was higher in patients with diabetes than in blood donors (0.08%) or healthy controls (0.20%) (P<0.001). Multivariate analysis identified four independent risk factors for HCV infection: blood transfusion before 1991 [odds ratio (OR)=2.88, P=0.033], intravenous drug use (OR=21.37, P=0.012), treatment in a hepatogastroenterology center (OR=4.17, P=0.002) and a high number (>2) of previous admissions since the onset of diabetes (OR=2.52, P=0.039). CONCLUSION A nosocomial source of HCV infection in hospitalized diabetic patients is suggested by the increased risk of HCV infection associated with the number of hospitalizations. This may account for at least 36% of cases of HCV infection.
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Abstract
As patient survival after solid organ transplantation continues to improve, comorbidites associated with chronic hyperglycemia will assume increasing importance in limiting outcomes and quality of life. New-onset diabetes mellitus commonly occurs in the posttransplant setting and is associated with multiple complications including graft loss, cardiovascular disease, infection, and death. Furthermore, recent studies have begun to highlight the very high posttransplant prevalence and the significant cardiovascular implications of the prediabetic states of impaired fasting glucose and impaired glucose tolerance, indicating that the overall burden of transplantation-associated hyperglycemia is far greater than previously appreciated. Shared and distinct pathogenic factors and clinical repercussions exist among the organ-specific transplant scenarios. Diabetogenic immunosuppressive agents are common to all organ transplant settings, whereas glucose regulation is also strained by the restoration of failed hepatic and renal function. The atherogenic properties of hyperglycemia are particularly significant in the kidney transplant population, which has a marked predisposition to cardiovascular disease, whereas accelerated cardiac allograft vasculopathy and liver fibrosis have been associated with hyperglycemia in the heart and liver transplant settings, respectively. Aggressive screening will effectively detect transplant-associated hyperglycemia, whereas risk factor modification, lifestyle intervention and, where appropriate, drug therapy, may decrease its impact. Topics of future investigation should include the use of emerging diabetes therapies and avenues for the prevention and reversal of transplant-associated hyperglycemia.
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Affiliation(s)
- Roy D Bloom
- Renal Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
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36
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Pergam SA, Wang CC, Gardella CM, Sandison TG, Phipps WT, Hawes SE. Pregnancy complications associated with hepatitis C: data from a 2003-2005 Washington state birth cohort. Am J Obstet Gynecol 2008; 199:38.e1-9. [PMID: 18486089 PMCID: PMC2517631 DOI: 10.1016/j.ajog.2008.03.052] [Citation(s) in RCA: 101] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2007] [Revised: 12/20/2007] [Accepted: 03/21/2008] [Indexed: 02/06/2023]
Abstract
OBJECTIVE The objective of the study was to determine the effect of hepatitis C virus (HCV) on selected maternal and infant birth outcomes. STUDY DESIGN This population-based cohort study using Washington state birth records from 2003 to 2005 compared a cohort of pregnant women identified as HCV positive from birth certificate data (n = 506) to randomly selected HCV-negative mothers (n = 2022) and drug-using HCV-negative mothers (n = 1439). RESULTS Infants of HCV-positive mothers were more likely to be low birthweight (odds ratio [OR], 2.17; 95% confidence interval [CI] 1.24, 3.80), to be small for gestational age (OR, 1.46; 95% CI, 1.00, 2.13), to need assisted ventilation (OR, 2.37; 95% CI, 1.46, 3.85), and to require neonatal intensive car unit (NICU) admission (OR, 2.91; 95% CI, 1.86, 4.55). HCV-positive mothers with excess weight gain also had a greater risk of gestational diabetes (OR, 2.51; 95% CI, 1.04, 6.03). Compared with the drug-using cohort, NICU admission and the need for assisted ventilation remained associated with HCV. CONCLUSION HCV-positive pregnant women appear to be at risk for adverse neonatal and maternal outcomes.
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Affiliation(s)
- Steven A Pergam
- Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
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37
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Lonardo A, Loria P, Carulli N. Dysmetabolic changes associated with HCV: a distinct syndrome? Intern Emerg Med 2008; 3:99-108. [PMID: 18274709 DOI: 10.1007/s11739-008-0127-1] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2007] [Accepted: 07/17/2007] [Indexed: 02/07/2023]
Abstract
Although not associated with the metabolic syndrome, HCV is linked with impaired insulin signalling, insulin resistance, hypocholesterolemia and steatosis which represent a distinct HCV-associated dysmetabolic syndrome. Insulin resistance affects the development of diabetes, fibrosis, impaired response to antivirals and perhaps hepatocellular carcinoma risk. HCV infection is associated with hypocholesterolemia and steatosis reversible after sustained virologic response. A "viral", and a "metabolic" steatosis exist as function of viral genotypes. Little is known about the possible role of HCV in further components of the metabolic syndrome such as atherosclerosis, obesity, arterial hypertension, hyperuricemia and thrombotic risk factors.
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Affiliation(s)
- Amedeo Lonardo
- Dipartimento Integrato di Medicina, Endocrinologia, Metabolismo e Geriatria, Università degli Studi di Modena e Reggio Emilia, Nuovo Ospedale S. Agostino Estense, Modena, Italy.
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38
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Kain K, Carter AM, Grant PJ, Scott EM. Alanine aminotransferase is associated with atherothrombotic risk factors in a British South Asian population. J Thromb Haemost 2008; 6:737-41. [PMID: 18315552 DOI: 10.1111/j.1538-7836.2008.02935.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Alanine aminotransferase (ALT) predicts the development of Type 2 diabetes mellitus and cardiovascular disease in Caucasian subjects. OBJECTIVES This study aimed to determine the incidence of an elevated ALT and its relationship to metabolic and atherothrombotic risk factors in a healthy British South Asian population. PATIENTS/METHODS One hundred and forty-three participants from the West Yorkshire community were recruited randomly from general practice registers and were grouped according to whether their ALT was above or within the normal range (cut-off 35 IU L(-1)) and examined for differences in metabolic and atherothrombotic risk factors. All participants were originally from South Asia, with their grandparents being born in India, Pakistan, or Bangladesh. RESULTS The incidence of a raised ALT was 24%. Those with a raised ALT had a more adverse metabolic profile, with significantly higher body mass index, waist/hip ratio, fasting insulin, glucose, homeostasis model assessment homeostasis model assessment insulin resistance (HOMA-IR), and triglycerides, and lower high-density lipoprotein (HDL) cholesterol. Fifty per cent had the metabolic syndrome [International Diabetes Federation (IDF) criteria]. They also had a more adverse atherothrombotic profile, with higher tissue-type plasminogen activator and plasminogen activator inhibitor-1 (PAI-1) antigen. In accordance, the group as a whole showed a positive correlation of ALT (age-adjusted) with waist/hip ratio, insulin, glucose, triglycerides, PAI-1 antigen, factor XIII B subunit, and FXII, and a negative correlation with HDL cholesterol. CONCLUSION Raised ALT is common in apparently healthy British South Asians, and is significantly associated with an adverse metabolic and atherothrombotic risk profile.
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Affiliation(s)
- K Kain
- Division of Cardiovascular and Diabetes Research, The LIGHT Laboratories, Clarendon Way, University of Leeds, Leeds, UK.
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39
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Imazeki F, Yokosuka O, Fukai K, Kanda T, Kojima H, Saisho H. Prevalence of diabetes mellitus and insulin resistance in patients with chronic hepatitis C: comparison with hepatitis B virus-infected and hepatitis C virus-cleared patients. Liver Int 2008; 28:355-62. [PMID: 18290778 DOI: 10.1111/j.1478-3231.2007.01630.x] [Citation(s) in RCA: 77] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND/AIMS Our aim was to evaluate the relationship between hepatitis C virus (HCV) infection and development of diabetes mellitus (DM) or insulin resistance (IR) in comparison with hepatitis B virus (HBV) infection and eradication of HCV infection by interferon treatment. METHODS This study consisted of 952 outpatients, including 544 HCV-infected (HCV+chronic), 286 HBV-infected (HBV+chronic) and 122 patients whose HCV was cleared by interferon treatment (HCV+cleared) (diabetes study). Among 849 without overt DM, IR was assessed in 423 patients, including 232 HCV-infected (HCV+chronic), 135 HBV-infected (HBV+chronic) and 56 HCV-eradicated patients (HCV+cleared) (IR substudy). RESULTS The prevalence of DM in the HBV+chronic, HCV+chronic and HCV+cleared groups was 6.3, 13.6 and 9.0%, respectively (HBV+chronic vs HCV+chronic, P<0.005), in the diabetes study, and the prevalence of IR in the HCV+chronic group (54.3%) was also higher than that in the HBV+chronic (36.3%) (P<0.005) and HCV+cleared groups (35.7%) (P<0.05) in the IR substudy. However, HCV infection was not shown to be independently associated with DM development [odds ratio (OR) 1.669; P=0.0936] and with IR (OR 1.531; P=0.2154) by multivariate analysis in comparison with HBV infection as control. CONCLUSIONS HCV-infected patients showed a higher prevalence of DM and IR than those with HBV infection. However, in Japan, other confounding factors appeared to be more important risk factors for the development of disturbance in glucose metabolism.
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Affiliation(s)
- Fumio Imazeki
- Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan.
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40
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Parolin MB, Réa R, Vargas RM, de Almeida ACR, Baldanzi GR, Lopes RW. [Prevalence of hepatitis C infection in patients with type 2 diabetes mellitus]. ARQUIVOS DE GASTROENTEROLOGIA 2007; 43:77-80. [PMID: 17119658 DOI: 10.1590/s0004-28032006000200003] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/27/2005] [Accepted: 10/14/2005] [Indexed: 01/28/2023]
Abstract
BACKGROUND Recently, a possible epidemiological association between hepatitis C virus infection and diabetes mellitus has been suggested and a higher prevalence of HCV antibodies has been found among type 2 diabetic when compared with normal controls. AIM To evaluate the prevalence of hepatitis C infection in diabetic patients in Curitiba, PR, Brazil. PATIENTS AND METHODS A total of 145 type 2 and 104 type 1 diabetic patients attending the outpatient diabetic unit of an university hospital were consecutively tested for anti-HCV, using a fourth-generation enzyme-linked immunosorbent assay (ELISA). The control group was constituted by 16,720 volunteer blood donors attending the blood bank of the same hospital during the period of the study. Diabetic patients were also evaluated for clinical, biochemical (aminotransferase levels) and demographic variables and previous exposure to risk factors for hepatitis C infection. RESULTS A higher prevalence of hepatitis C infection was observed in type 2 diabetic patients in comparison with blood donors. Although anti-HCV prevalence in type 2 diabetic patients was higher than found in type 1, it did not reach statistical significance. Both diabetic groups were predominantly female, and as expected, type 2 diabetic were older than type 1. Race distribution, duration of the disease, and previous exposure to hepatitis C risk factors were similar in both groups, but type 2 diabetic subjects had higher median levels of alanine aminotransferase than type 1. CONCLUSIONS A higher prevalence of hepatitis C infection was detected in type 2 diabetic patients in comparison with blood donors in our region, in accordance with study data from different populations. If all type 2 diabetic patients should undergo regular screening for hepatitis C infection remains a question.
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Affiliation(s)
- Mônica Beatriz Parolin
- Serviço de Transplante Hepático, Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, PR.
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Lonardo A, Carulli N, Loria P. HCV and diabetes. A two-question-based reappraisal. Dig Liver Dis 2007; 39:753-761. [PMID: 17611176 DOI: 10.1016/j.dld.2007.05.005] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2006] [Revised: 03/19/2007] [Accepted: 05/08/2007] [Indexed: 02/07/2023]
Abstract
We used available studies to answer two clinically relevant questions, i.e. whether those with type 2 diabetes should undergo hepatitis C virus screening and whether hepatitis C virus positive individuals should be screened for diabetes. Four reasons argue against the hypothesis of screening diabetics for hepatitis C virus. First, although it induces insulin resistance, hepatitis C virus is not directly diabetogenic. Second, the clinical phenotype of hepatitis C virus-associated type 2 diabetes might be a clue to target the specific diabetic population to be screened. Third, diabetic patients are expected to be poor responders to antivirals and evidence that this might result in recovery from type 2 diabetes is insufficient. Fourth, no econometric data are available in the specific subset of those with type 2 diabetes. Case finding of type 2 diabetes in those with hepatitis C virus infection, in contrast, might be considered in those patients with type 2 diabetes who have cirrhosis, in whom--due to increased prevalence and severity of hepatic encephalopathy--diabetes is associated with increased mortality. Preliminary evidence suggests that the prognosis of cirrhosis might benefit from improved glycemic control and thus from earlier diagnosis of type 2 diabetes. Finally, studies are needed to ascertain the most cost-effective strategy of case-finding type 2 diabetes among those who are hepatitis C virus-infected. In conclusion, available data enabled us to answer the two questions. Hepatitis C virus screening should best be restricted to those (lean) diabetic patients with (advanced) liver disease. Glucose tolerance testing should best be performed in those with hepatitis C virus-related cirrhosis. However, additional studies are needed to support the cost-effectiveness of our conclusions.
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Affiliation(s)
- A Lonardo
- University of Modena and Reggio Emilia, Department of Internal Medicine, Metabolism, Endocrinology and Geriatrics, Operating Unit Internal Medicine & Metabolism, Nuovo Ospedale Civile Estense di Baggiovara, Modena 41100, Italy.
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42
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Lao TT, Chan BCP, Leung WC, Ho LF, Tse KY. Maternal hepatitis B infection and gestational diabetes mellitus. J Hepatol 2007; 47:46-50. [PMID: 17434231 DOI: 10.1016/j.jhep.2007.02.014] [Citation(s) in RCA: 86] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2006] [Revised: 02/04/2007] [Accepted: 02/17/2007] [Indexed: 02/08/2023]
Abstract
BACKGROUND/AIMS This retrospective cohort study was performed to examine the relationship between maternal hepatitis B virus infection, as indicated by the surface antigen status, with the development of gestational diabetes mellitus in a normal-risk Chinese obstetric population. METHODS Maternal demographics, risk factors, and pregnancy outcome of 13,683 singleton pregnancies delivering in 1998-2001 were analysed according to maternal hepatitis B surface antigen status, which was routinely screened. Multiple logistic regression analysis was performed to examine the role of hepatitis B infection in the development of gestational diabetes mellitus. RESULTS The 1138 women (8.3%) with hepatitis B infection had lower mean weight and body mass index, similar prevalence of chronic medical diseases and smokers, but increased prevalence of gestational diabetes mellitus, which remained significant (odds ratio 1.24, 95% confidence interval 1.01-1.51) after adjustment for confounding variables. However, there was no difference in pregnancy outcome. CONCLUSIONS Our results confirmed the independent association between hepatitis B infection with gestational diabetes mellitus. The magnitude of chronic hepatitis B infection in the developing world and certain ethnic groups could have contributed to the high prevalence of gestational and possibly type 2 diabetes in these populations. Further studies on the long-term implications of our finding are warranted.
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Affiliation(s)
- Terence T Lao
- Department of Obstetrics and Gynaecology, The University of Hong Kong, Hong Kong, China.
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43
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Tolman KG, Fonseca V, Dalpiaz A, Tan MH. Spectrum of liver disease in type 2 diabetes and management of patients with diabetes and liver disease. Diabetes Care 2007; 30:734-43. [PMID: 17327353 DOI: 10.2337/dc06-1539] [Citation(s) in RCA: 350] [Impact Index Per Article: 19.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Affiliation(s)
- Keith G Tolman
- Division of Gastroenterology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.
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44
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Crutchlow MF, Bloom RD. Transplant-associated hyperglycemia: a new look at an old problem. Clin J Am Soc Nephrol 2007; 2:343-55. [PMID: 17699434 DOI: 10.2215/cjn.03671106] [Citation(s) in RCA: 71] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
New-onset diabetes has long been recognized as a common complication of kidney transplantation, promoting cardiovascular disease, death, and graft failure. Studies in recent years have begun to highlight the very high posttransplantation prevalence of the prediabetic states of impaired fasting glucose and impaired glucose tolerance and the significant repercussions of these states on cardiovascular health. Therefore, the overall burden of transplant-associated hyperglycemia (TAH), which encompasses new-onset diabetes and the prediabetic states, is far greater than previously appreciated. The kidney transplant population is predisposed to insulin resistance and to additional insults of hypertension and hyperlipidemia that, together with hyperglycemia, compose the metabolic syndrome and promote atherosclerosis. When recipients with an underlying, frequently nonmodifiable predisposition to glucose dysregulation encounter transplant-specific, often modifiable, diabetogenic exposures, TAH manifests. Aggressive screening will effectively detect TAH, whereas risk factor modification, lifestyle intervention, and, when appropriate, drug therapy may decrease its impact. Topics of future investigation should include the use of emerging diabetes therapies and avenues for the prevention and reversal of TAH.
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Affiliation(s)
- Michael F Crutchlow
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA
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45
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Thuluvath PJ. Is there a link between hepatitis C virus and new onset of diabetes mellitus after liver transplantation? Liver Transpl 2007; 13:5-7. [PMID: 17192890 DOI: 10.1002/lt.21024] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Abstract
The pathogenesis of liver damage associated with chronic hepatitis C virus (HCV) infection is thought to be largely immunomediated. However, some frequent histopathological features, such as steatosis, suggest a direct cytopathic effect of HCV. The direct responsibility of HCV in the pathogenesis of steatosis is shown by: (1) the association with HCV genotype 3 infection, suggesting that some viral sequences are involved in the intracellular accumulation of lipids; (2) the correlation between severity of steatosis and HCV replication levels; (3) association between response to treatment and disappearance of steatosis. Experimental studies have shown that the nucleocapsid protein of HCV (core protein) is capable and sufficient to induce lipid accumulation in hepatocytes. Moreover, the observation that chronic hepatitis C patients have reduced serum levels of ApoB suggests an interference with the very-low density lipoprotein (VLDL) assembly, although other mechanisms are possible. In patients with sustained virological response induced by antiviral therapy, such levels are normalized. Other observations suggest that the pathogenesis of steatosis in chronic hepatitis C is not solely due to HCV. The origin of the mild steatosis observed in most patients may be metabolic, since its severity correlates with body mass index and insulin resistance. Most studies have shown a correlation between presence and/or severity of steatosis and fibrosis stage, but it is unclear whether this effect is direct or mediated by the associated insulin resistance, increased susceptibility to apoptosis, or by inflammatory cytokines. Finally, steatosis negatively influences the rate of response to antiviral treatment, as confirmed by large clinical trials. Management of steatosis in chronic hepatitis C requires knowledge of its pathogenesis and may involve both life-style changes and pharmacological interventions, although the latter remain largely experimental.
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Affiliation(s)
- Francesco Negro
- Services de Gastroentérologie et d'Hépatologie et de Pathologie Clinique, Genève, Switzerland.
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47
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48
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Lecube A, Hernández C, Genescà J, Simó R. Glucose abnormalities in patients with hepatitis C virus infection: Epidemiology and pathogenesis. Diabetes Care 2006. [PMID: 16644655 DOI: 10.2337/dc05-1995] [Citation(s) in RCA: 79] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Affiliation(s)
- Albert Lecube
- Division of Endocrinology, Diabetes Research Unit, Institut de Recerca, Hospital Universitari Vall d'Hebron, Barcelona, Spain
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Abstract
BACKGROUND Many reports in the literature suggest that chronic hepatitis C virus (HCV) infection is associated with diabetes, but the results are conflicting. The aim of our study was to investigate the seroprevalence of hepatitis B virus (HBV) and HCV infections in type 2 diabetes mellitus (DM) patients. METHODS We collected 820 consecutive type 2 diabetic patients attending 2 of 5 outpatient endocrinology clinics in Far Eastern Memorial Hospital from March to July 2003. The control group consisted of 905 subjects who came for medical check-ups at the Family Medicine Department. We determined hepatitis B surface antigen (HBsAg) and anti-HCV in both groups, using third-generation microparticle enzyme immunoassay. RESULTS No significant difference was found between type 2 DM patients and the control group for seropositivity of HBsAg (13.5% versus 12.4%; odds ratio [OR] = 1.09; 95% confidence interval [CI]: 0.77-1.55; p = 0.441), but anti-HCV seropositivity was detected in 6.8% of patients and 2.6% of the control subjects (OR = 2.87; 95% CI: 1.51-5.46; p < 0.001). In anti-HCV-positive DM patients, abnormal alanine aminotransferase was observed in 61.8%, compared with only 34.2% of anti-HCV-negative DM patients (p < 0.001). We did not observe any difference in risk factors for HCV infection between anti-HCV-positive and -negative DM patients. CONCLUSION The rate of seropositive anti-HCV is 2.8 times higher in type 2 DM patients than non-diabetic control subjects.
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Affiliation(s)
- Hua-Fen Chen
- Division of Endocrinology, Department of Internal Medicine, Far-Eastern Memorial Hospital, Panchiao, Taiwan, ROC
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Abstract
Since the discovery of the hepatitis C virus (HCV) in 1989, attention has been paid to the association of chronic HCV infection and the development of diabetes. The risk factors for diabetes include older age, HCV genotype 3, severe liver fibrosis, family history of diabetes, and liver/kidney transplantation. Emerging evidence in animals and humans has shown that HCV infection induces hepatic steatosis and increases tumor necrosis factor-alpha level, both resulting in the development of insulin resistance and subsequent type 2 diabetes. It is suggested that the presence of diabetes and hepatic steatosis may enhance fibrosis progression, hepatocellular carcinoma, and atherosclerosis. Interferon is reportedly associated with improved glucose tolerance. However, interferon might enhance underlying autoimmunity against beta cells, leading to overt type 1 diabetes that is genetically predisposed or give rise to hyperglycemia, resulting in the development of type 2 diabetes. In light of the national epidemic of type 2 diabetes, the link between HCV and diabetes would be a major public health problem. Further clinical researches are awaited in order to effectively detect, prevent, and treat HCV-associated type 2 diabetes, which would also slow the progression of hepatitis C itself.
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Affiliation(s)
- Hiroshi Noto
- Division of Endocrinology and Metabolism, Department of Internal Medicine, The University of Texas Southwestern Medical Center at Dallas, TX 75390-8858, USA
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