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Fernandez CJ, Alkhalifah M, Afsar H, Pappachan JM. Metabolic Dysfunction-Associated Fatty Liver Disease and Chronic Viral Hepatitis: The Interlink. Pathogens 2024; 13:68. [PMID: 38251375 PMCID: PMC10821334 DOI: 10.3390/pathogens13010068] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 01/05/2024] [Accepted: 01/07/2024] [Indexed: 01/23/2024] Open
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) has now affected nearly one-third of the global population and has become the number one cause of chronic liver disease in the world because of the obesity pandemic. Chronic hepatitis resulting from hepatitis B virus (HBV) and hepatitis C virus (HCV) remain significant challenges to liver health even in the 21st century. The co-existence of MAFLD and chronic viral hepatitis can markedly alter the disease course of individual diseases and can complicate the management of each of these disorders. A thorough understanding of the pathobiological interactions between MAFLD and these two chronic viral infections is crucial for appropriately managing these patients. In this comprehensive clinical review, we discuss the various mechanisms of chronic viral hepatitis-mediated metabolic dysfunction and the impact of MAFLD on the progression of liver disease.
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Affiliation(s)
- Cornelius J. Fernandez
- Department of Endocrinology and Metabolism, Pilgrim Hospital, United Lincolnshire Hospitals NHS Trust, Boston PE21 9QS, UK;
| | - Mohammed Alkhalifah
- Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust, Royal Preston Hospital, Sharoe Green Lane, Preston PR2 9HT, UK; (M.A.); (H.A.)
- Department of Family Medicine and Polyclinics, King Faisal Specialist Hospital & Research Centre, Riyadh 11211, Saudi Arabia
- University Diabetes Center, King Saud University Medical City, King Saud University, Riyadh 11411, Saudi Arabia
| | - Hafsa Afsar
- Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust, Royal Preston Hospital, Sharoe Green Lane, Preston PR2 9HT, UK; (M.A.); (H.A.)
| | - Joseph M. Pappachan
- Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust, Royal Preston Hospital, Sharoe Green Lane, Preston PR2 9HT, UK; (M.A.); (H.A.)
- Faculty of Science, Manchester Metropolitan University, Manchester M15 6BH, UK
- Faculty of Biology, Medicine & Health, The University of Manchester, Manchester M13 9PL, UK
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Sofosbuvir-based direct-acting antivirals and changes in cholesterol and low density lipoprotein-cholesterol. Sci Rep 2022; 12:9942. [PMID: 35705594 PMCID: PMC9200852 DOI: 10.1038/s41598-022-13657-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Accepted: 05/05/2022] [Indexed: 11/19/2022] Open
Abstract
Worsened lipid profiles were observed in chronic hepatitis C (CHC) patients during direct-acting antivirals (DAAs) treatment, among which combination drugs confounded the effect of individual ingredient on lipid. Tenofovir alafenamide (TAF) also worsened lipid profiles in HIV patients. Structural similarity between sofosbuvir (SOF) and TAF prompted us to investigate rapid increase in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in CHC patients treated with SOF-based DAAs. A retrospective study was performed to analyze 487 CHC patients receiving DAAs with SVR12. Relative risks on elevating TC and LDL-C were analyzed by logistic regression to determine SOF-based over non-SOF-based regimens. TC or LDL-C levels at baseline, week-4 and SVR12 were compared by Wilcoxon matched-pairs signed rank test. Week 4 or SVR12 to baseline ratios of serum TC or LDL-C between regimens were compared by Mann–Whitney's test. 487 patients were treated with Harvoni (SOF-based, 206 patients), Epclusa (SOF-based, 124 patients), Maviret (non-SOF-based, 122 patients), or Zepatier (non-SOF-based, 35 patients). At week 4 during drug treatment, Harvoni, Epclusa, and Maviret induced statistically significant elevation of TC and LDL-C, but Zepatier did not. SOF-based regimens had 2.72-fold higher relative risk (RR) causing 10% elevation of TC (95% CI 1.84–4.02, p < 0.001) and 2.04-fold higher RR causing 10% elevation of LDL-C (95% CI 1.39–3.01, p < 0.001) than non-SOF-based DAAs. SOF-based DAAs were associated with significantly larger amplitude of increases in TC and LDL-C than non-SOF-based DAAs during the initial 4 weeks of treatment, but the increases were not sustained to SVR12.
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El-Kassas M, Awad A. Metabolic aspects of hepatitis C virus. World J Gastroenterol 2022; 28:2429-2436. [PMID: 35979265 PMCID: PMC9258278 DOI: 10.3748/wjg.v28.i22.2429] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 03/18/2022] [Accepted: 04/22/2022] [Indexed: 02/06/2023] Open
Abstract
Many metabolic factors are associated with chronic hepatitis C virus (HCV) infection and can influence the course of the illness and impact the progression of liver and non-liver-related diseases through complex interactions. Several of these factors impact the course of chronic HCV (CHC) and result in the conceptual translation of CHC from a localized to systemic disease. Besides the traditional liver manifestations associated with CHC infection, such as cirrhosis and hepatocellular carcinoma, various extrahepatic disorders are associated with HCV infection, including atherosclerosis, glucose and lipid metabolic disturbances, alterations in the iron metabolic pathways, and lymphoproliferative diseases. The coexistence of metabolic disorders and CHC is known to influence the chronicity and virulence of HCV and accelerates the progression to liver fibrosis and hepatocellular carcinoma. Insulin resistance is one of the key factors that have a tremendous metabolic impact on CHC. Therefore, there is a great need to properly evaluate patients with CHC infection and correct the modifiable metabolic risk factors. Furthermore, patients with HCV who achieved a sustained virological response showed an overall improvement in glucose metabolism, but the exact evidence still requires further studies with long-term follow-up. This review delineates the most recent evidence on the main metabolic factors associated with CHC and the possible influence of chronic HCV infection on metabolic features.
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Affiliation(s)
- Mohamed El-Kassas
- Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo 11795, Egypt
| | - Abeer Awad
- Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo 11566, Egypt
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El-Kassas M, El-Folly R, Aboromia M, Aly H, Bahgat M, Hamed M. Effect of achieving sustained virological response with direct-acting antiviral agents on glycemic control in diabetic patients with chronic hepatitis C infection. EGYPTIAN LIVER JOURNAL 2022. [DOI: 10.1186/s43066-022-00190-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/07/2022] Open
Abstract
Abstract
Background
Hepatitis C virus (HCV) is a significant cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma worldwide. Liver disease is not the only problem caused by chronic HCV infection; many extrahepatic complications, such as insulin resistance, can be associated with HCV infection. The aim of this study was to assess the effect of achieving a sustained virological response after treatment with directly acting antiviral drugs on insulin resistance in patients with chronic HCV infection.
Results
This prospective study was conducted on 46 HCV patients with type 2 diabetes mellitus who received directly acting antiviral drugs for HCV infections. Fasting insulin, fasting blood glucose, and lipid profiles were assessed in all patients at three time points: before treatment, at the end of treatment, and 12 weeks after the end of treatment. Despite using three different directly acting antiviral drug regimens, all patients achieved a sustained viral response, regardless of the regimen used. the Homeostatic Model Assessment for Insulin Resistance decreased significantly at the end of treatment; however, when recalculated at week 12 after end of treatment, the reduction of the Homeostatic Model Assessment for Insulin Resistance was not significant compared to the baseline levels. Total cholesterol and low-density lipoproteins increased at the end of treatment and continued to increase for 12 weeks after the end of treatment.
Conclusions
Improvements in insulin resistance and glycemic control were noted in HCV patients at the end of treatment with directly acting antiviral drugs; this effect was also apparent after 12 weeks. An increase in the levels of total cholesterol and low-density lipoprotein can be expected after treatment with directly acting antiviral drugs.
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Wang YW, Lee WP, Huang YH, Hou MC, Lan KH. Effect of sofosbuvir-based DAAs on changes in lower-density lipoprotein in HCV patients: a systematic review and meta-analysis. BMC Infect Dis 2021; 21:984. [PMID: 34548026 PMCID: PMC8454153 DOI: 10.1186/s12879-021-06657-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Accepted: 09/04/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Previous studies reported worsened lipid profiles in patients infected with hepatitis C virus (HCV) during direct-acting antivirals (DAAs) treatment. This study aimed to investigate the effect of sofosbuvir (SOF)-based DAAs on changes in low-density lipoprotein (LDL) in HCV patients. METHODS A systematic review of articles published before 31 May 2021 was conducted by searching MEDLINE, Cochrane Library, EMBASE, and CINAHL Plus. Eligible studies were those comparing SOF-based DAAs and non-SOF DAAs for HCV patients and providing numerical data for changes in LDL. Risk of Bias in Non-randomized Studies- of Interventions was used for assessing risk of bias, and meta-analysis was performed for changes in LDL. RESULTS Six studies comprising 1248 patients were included, 848 patients treated with SOF-based DAAs and 400 patients with non-SOF DAAs vs. SOF-based DAAs group had significantly greater increases in LDL from baseline to week 4 than non-SOF DAAs group (P = 0.001). However, changes in LDL from baseline to the end of treatment (P = 0.060), to post-treatment week 12 (P = 0.263), and to post-treatment week 24 (P = 0.319) did not significantly differ between the two groups. Further comparison of SOF/ledipasvir with asunaprevir/daclatasvir revealed a similar trend in changes in LDL. CONCLUSIONS For HCV patients, SOF-based DAA regimens were associated with rapid and significant increases in LDL during the initial 4 weeks of treatment, and the changes did not sustain after the end of treatment. Potential mechanism might be related to the phosphoramidate side chain of SOF.
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Affiliation(s)
- Ying-Wen Wang
- Healthcare and Management Center, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Wei-Ping Lee
- Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Institute of Biochemistry and Molecular Biology, College of Life Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, 201, Section 2, Shi-Pai Road, Taipei, 112 Taiwan, ROC
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Institute of Clinical Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, 201, Section 2, Shi-Pai Road, Taipei, 112 Taiwan, ROC
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Keng-Hsin Lan
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, 201, Section 2, Shi-Pai Road, Taipei, 112 Taiwan, ROC
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Institute of Pharmacology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
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Impact of DAA-Based Regimens on HCV-Related Extra-Hepatic Damage: A Narrative Review. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1323:115-147. [PMID: 33326112 DOI: 10.1007/5584_2020_604] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Two-third of patients with chronic hepatitis C show extrahepatic manifestations due to HCV infection of B lymphocytes, such as mixed cryoglobulinemia and non-Hodgkin B-cell lymphoma, or develop a chronic inflammatory status that may favor the development of adverse cardiovascular events, kidney diseases or metabolic abnormalities.DAAs treatments induce HCV eradication in 95% of treated patients, which also improves the clinical course of extrahepatic manifestations, but with some limitations. After HCV eradication a good compensation of T2DM has been observed, but doubts persist about the possibility of obtaining a stable reduction in fasting glucose and HbA1c levels.Chronic HCV infection is associated with low total and LDL cholesterol serum levels, which however increase significantly after HCV elimination, possibly due to the disruption of HCV/lipid metabolism interaction. Despite this adverse effect, HCV eradication exerts a favorable action on cardiovascular system, possibly by eliminating numerous other harmful effects exerted by HCV on this system.DAA treatment is also indicated for the treatment of patients with mixed cryoglobulinemia syndrome, since HCV eradication results in symptom reduction and, in particular, is effective in cryoglobulinemic vasculitis. Furthermore, HCV eradication exerts a favorable action on HCV-related lymphoproliferative disorders, with frequent remission or reduction of clinical manifestations.There is also evidence that HCV clearance may improve impaired renal functions, but same conflicting data persist on the effect of some DAAs on eGFR.
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Chaudhari R, Fouda S, Sainu A, Pappachan JM. Metabolic complications of hepatitis C virus infection. World J Gastroenterol 2021; 27:1267-1282. [PMID: 33833481 PMCID: PMC8015302 DOI: 10.3748/wjg.v27.i13.1267] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2021] [Revised: 02/10/2021] [Accepted: 03/12/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infection is a systemic disease that is implicated in multiple extrahepatic organ dysfunction contributing to its protean manifestations. HCV is associated with diverse extrahepatic disorders including atherosclerosis, glucose and lipid metabolic disturbances, alterations in the iron metabolic pathways, and lymphoproliferative diseases over and above the traditional liver manifestations of cirrhosis and hepatocellular carcinoma. The orchestration between HCV major proteins and the liver-muscle-adipose axis, poses a major burden on the global health of human body organs, if not adequately addressed. The close and inseparable associations between chronic HCV infection, metabolic disease, and cardiovascular disorders are specifically important considering the increasing prevalence of obesity and metabolic syndrome, and their economic burden to patients, the healthcare systems, and society. Cellular and molecular mechanisms governing the interplay of these organs and tissues in health and disease are therefore of significant interest. The coexistence of metabolic disorders and chronic hepatitis C infection also enhances the progression to liver fibrosis and hepatocellular carcinoma. The presence of metabolic disorders is believed to influence the chronicity and virulence of HCV leading to liver disease progression. This comprehensive review highlights current knowledge on the metabolic manifestations of hepatitis C and the potential pathways in which these metabolic changes can influence the natural history of the disease.
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Affiliation(s)
- Rahul Chaudhari
- Department of Medicine, Pennsylvania Hospital of the University of Pennsylvania, Pennsylvania, PA 19104, United States
| | - Sherouk Fouda
- School of Health and Biomedical Sciences, RMIT University, Melbourne VIC 3000, Australia
| | - Ashik Sainu
- Department of Gastroenterology and Hepatology, Aster Oman Hospital, Al Ghubra, Muscat OM 133, Oman
| | - Joseph M Pappachan
- Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust, Preston PR2 9HT, United Kingdom
- Faculty of Science, Manchester Metropolitan University, Manchester M15 6BH, United Kingdom
- Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, United Kingdom
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The association between metabolic syndrome and Hepatitis C virus infection in the United States. Cancer Causes Control 2020; 31:569-581. [PMID: 32300943 DOI: 10.1007/s10552-020-01300-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2019] [Accepted: 04/07/2020] [Indexed: 12/19/2022]
Abstract
PURPOSE Hepatitis C virus (HCV) infection is the prevalent risk factor for chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC) worldwide. The association between metabolic syndrome (MetS) and HCV infection has not been studied effectively, particularly among different ethnic/racial groups in the US. METHODS A retrospective cross-sectional study was conducted using data from the National Health and Nutrition Examination Survey (1999-2014). Unadjusted and adjusted associations were summarized using the prevalence ratio (PR) and 95% confidence interval (CI) after exploring possible interactions. RESULTS In the overall population, MetS was significantly associated with HCV infection with an interaction of age. After adjusting for all potential confounders, MetS was found to be significantly associated with HCV among non-obese and younger adults of age less than 60 years (PR 1.67, 95% CI 1.21-2.30, p = 0.002). MetS was also associated with an increased prevalence of HCV in each racial/ethnic group, while the association was strongly modified by age and obesity status of the subjects in different ethnic/racial groups. CONCLUSIONS MetS or its components are associated with an increased prevalence of HCV in some sub-populations of all ethnic/racial groups in the US. A better understanding of the pathophysiology of MetS associated with HCV is important as MetS may have a role in HCV infection treatment outcomes.
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Carvalho JR, Velosa J, Serejo F. Lipids, glucose and iron metabolic alterations in chronic hepatitis C after viral eradication - comparison of the new direct-acting antiviral agents with the old regimens. Scand J Gastroenterol 2018; 53:857-863. [PMID: 29779403 DOI: 10.1080/00365521.2018.1473486] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Hepatitis C virus (HCV) is a unique virus which interacts with cholesterol, iron and insulin metabolism. There is limited data on the effects of direct-acting antiviral agents (DAAs) on metabolic profiles. We aimed at evaluating the behavior of metabolic risk factors of chronically HCV-infected patients after sustained virologic response (SVR), comparing the outcomes with the new DAAs versus the old treatment regimen Peg-interferon ± ribavirin. METHODS A total of 178 patients who achieved SVR and completed one year of follow-up were prospectively included in this study: group 1 with 105 patients treated with DAAs and group 2 with 73 patients treated with old regimens. Outcomes included lipid, glucose and iron metabolism variation after SVR. RESULTS There was a significant increase in total cholesterol in both groups (group 1: p < .001, 95% CI: 0.41-0.78; group 2: p < .001, 95% CI: 0.24-0.69). Triglyceride levels significantly decreased (p = .015, 95% CI: -0.33-0.04) in group 1 and increased (p = .014, 95% CI: 0.07-0.59) in group 2. LDL levels increased in group 1 (p = .029, 95% CI: 0.05-0.88), but no significant variation was found in group 2. No significant variation in HDL, fast glucose and iron was seen in both groups. There was a significant increase of HOMA (p = .002, 95% CI: 0.17592-0.72317) only in group 2. Ferritin serum levels significantly decreased (p < .001, 95% CI:-138.3-74.4) in group 1 but no significant variation was found in group 2. CONCLUSION Patients who have achieved SVR may have increased risk of cardiovascular outcomes due to development of hyperlipidemia and insulin resistance.
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Affiliation(s)
- Joana Rita Carvalho
- a Department of Gastroenterology and Hepatology , North Lisbon Hospital Center, University of Lisbon , Lisboa , Portugal
| | - José Velosa
- a Department of Gastroenterology and Hepatology , North Lisbon Hospital Center, University of Lisbon , Lisboa , Portugal
| | - Fátima Serejo
- a Department of Gastroenterology and Hepatology , North Lisbon Hospital Center, University of Lisbon , Lisboa , Portugal
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Drazilova S, Gazda J, Janicko M, Jarcuska P. Chronic Hepatitis C Association with Diabetes Mellitus and Cardiovascular Risk in the Era of DAA Therapy. Can J Gastroenterol Hepatol 2018; 2018:6150861. [PMID: 30186821 PMCID: PMC6110000 DOI: 10.1155/2018/6150861] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2018] [Accepted: 07/31/2018] [Indexed: 12/15/2022] Open
Abstract
Patients with chronic hepatitis C have both higher prevalence of diabetes mellitus type 2 (T2DM) and increased cardiovascular risk compared to never infected people. Sustained viral response (SVR) achievement led to decreasing incidence and prevalence of T2DM during the interferon era of HCV treatment. Currently, direct-acting antiviral drugs (DAA) are the gold standard for treating HCV infection, while yielding SVR in nearly all patients. In chronic HCV patients with T2DM (prediabetes most likely too), DAA therapy is associated with both better fasting glucose and glycated hemoglobin (HbA1C) controls; thus reducing pharmacotherapy in a certain part of patients is possible. Papers mentioned in the review confirmed DAA role in both total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) increase. This alteration was accompanied by an increase in high-density lipoprotein cholesterol (HDL-C) and a decrease in triglycerides (TG) verified by most of the studies. However, the clinical significance of lipoprotein alterations caused by DAA therapy has not been explained yet. Moreover, DAA treatment of chronic hepatitis C improves hypertension control and atherosclerotic plaques. It is very likely that DAA therapeutic regimens will decrease both T2DM prevalence and cardiovascular risk in chronic hepatitis C patients; further research, however, is needed.
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Affiliation(s)
- Sylvia Drazilova
- Department of Internal Medicine, Hospital Poprad, Poprad, Slovakia
| | - Jakub Gazda
- 1st Department of Internal Medicine, PJ Safarik University, Faculty of Medicine and L Pasteur University Hospital, Kosice, Slovakia
| | - Martin Janicko
- 1st Department of Internal Medicine, PJ Safarik University, Faculty of Medicine and L Pasteur University Hospital, Kosice, Slovakia
| | - Peter Jarcuska
- 1st Department of Internal Medicine, PJ Safarik University, Faculty of Medicine and L Pasteur University Hospital, Kosice, Slovakia
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Gadallah M, Kandil S, Mohsen A. Association between hepatitis C infection and cerebro-cardiovascular disease: analysis of a national population-based survey in Egypt. Trop Med Int Health 2018; 23:738-747. [PMID: 29723920 DOI: 10.1111/tmi.13068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVES To examine the association between hepatitis C virus (HCV) infection, cardiovascular risk factors and cerebro-cardiovascular (CCV) disease. METHODS The source of data was the Egypt Health Issues Survey conducted in 2015. Participants were 11 256 individuals with complete HCV testing, age 25-59 years. Data on demographics, cardiovascular risk factors, CCV disease (myocardial infarction and/or cerebral stroke) and HCV infection were retrieved. Descriptive, bivariate, multivariable logistic regression and sensitivity analyses were performed to determine the independent association of past HCV exposure or chronic infection with diabetes, hypertension and CCV disease. RESULTS 3.9% of participants were antibody positive/RNA negative and considered to have past HCV exposure; 7.9% had detectable HCV-RNA and were considered to have chronic infection. Participants with negative antibodies and no history of liver disease (n = 9928) were the control group. In addition to the previously known risk factors, multivariable analyses revealed that diabetes was independently associated with past HCV exposure (OR = 1.71, 95% CI: 1.27-2.32) and HCV chronic infection (OR = 1.56, 95% CI: 1.23-1.97), whereas CCV disease was independently associated with past exposure (OR = 2.69, 95% CI: 1.62-4.46) and not with chronic infection. No evidence of an association between hypertension and either HCV status was found. CONCLUSION The association of both past HCV exposure and chronic infection with diabetes and that of past HCV exposure with CCV disease may suggest targeting HCV-positive reactors for preventive and curative programmes addressing extrahepatic complications.
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Affiliation(s)
- Mohsen Gadallah
- Department of Community, Environmental and Occupational Medicine, Ain Shams University, Cairo, Egypt
| | - Sahar Kandil
- Department of Community, Environmental and Occupational Medicine, Ain Shams University, Cairo, Egypt
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Harada R, Kimura M, Sato Y, Taniguchi T, Tomonari T, Tanaka T, Tanaka H, Muguruma N, Shinomiya H, Honda H, Imoto I, Sogabe M, Okahisa T, Takayama T. APOB codon 4311 polymorphism is associated with hepatitis C virus infection through altered lipid metabolism. BMC Gastroenterol 2018; 18:24. [PMID: 29382324 PMCID: PMC5791310 DOI: 10.1186/s12876-018-0747-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2017] [Accepted: 01/18/2018] [Indexed: 01/01/2023] Open
Abstract
Background It has been reported that some single-nucleotide polymorphisms (SNPs) in lipid regulators such as apolipoproteins and cell surface molecules for hepatitis C virus (HCV) entry into hepatocytes are associated with HCV infection. However, it is unknown how HCV infection is affected by altered lipid metabolism resulting from the SNPs. We investigated the relationship between these SNPs and HCV infection status, and also analyzed the mechanism by which these SNPs mediate HCV infection via lipid metabolism alterations. Methods Serum lipid and apolipoprotein profiles were tested in 158 HCV-positive and 220 HCV-negative subjects. We selected 22 SNPs in five lipid regulator genes which were related to HCV entry into hepatocytes and to lipid metabolism (APOA1, APOB, SR-B1, LDLR, and APOE), and their polymorphisms were analyzed using the PCR-sequence-specific oligonucleotide probe-Luminex method. Results An APOB N4311S (g.41553a > g) SNP, rs1042034, was significantly associated with HCV positivity; the HCV positivity rate for the minor allele AA genotype was significantly higher than for genotype AG + GG (P = 0.016). Other SNPs except for APOB P2712L SNP rs676210, which is in linkage disequilibrium with rs1042034, showed no significant difference in genotype distribution. The serum level of low density lipoprotein-cholesterol (LDL-C) in the genotype AA group was significantly lower than in the genotype non-AA group (P = 0.032), whereas the triglyceride (TG) level was significantly higher (P = 0.007). Conclusion An APOB SNP, rs1042034, is closely associated with HCV infection through lipid metabolism alteration. The minor allele AA genotype might contribute to facilitating serum LDL uptake into hepatocytes via LDLR by modifying their affinity and interaction and may have an influence on HCV infection by their entry to the liver through the LDLR.
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Affiliation(s)
- Rie Harada
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Masako Kimura
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Yasushi Sato
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Tatsuya Taniguchi
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Tetsu Tomonari
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Takahiro Tanaka
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Hironori Tanaka
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Naoki Muguruma
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Hirohiko Shinomiya
- Department of Gastroenterology, Yoshinogawa Medical Center, Yoshinogawa, Tokushima, 776-8511, Japan
| | - Hirohito Honda
- Department of Internal Medicine, Tokushima Health Screening Center, 1-10-3, Kuramoto-cho, Tokushima, 770-0042, Japan
| | - Issei Imoto
- Department of Human Genetics, Tokushima University Graduate School of Biomedical Sciences, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Masahiro Sogabe
- Department of General Medicine and Community Health Science, Tokushima University Graduate School of Biomedical Sciences, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Toshiya Okahisa
- Department of General Medicine and Community Health Science, Tokushima University Graduate School of Biomedical Sciences, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Tetsuji Takayama
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.
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13
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Kuo SH, Hung WT, Tang PL, Huang WC, Yang JS, Lin HC, Mar GY, Chang HT, Liu CP. Impact of hepatitis C virus infection on long-term mortality after acute myocardial infarction: a nationwide population-based, propensity-matched cohort study in Taiwan. BMJ Open 2018; 8:e017412. [PMID: 29374659 PMCID: PMC5829782 DOI: 10.1136/bmjopen-2017-017412] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION The influence of hepatitis C virus (HCV) infection on long-term outcomes of patients with acute myocardial infarction (AMI) is unclear. Therefore, this study aimed to analyse the impact of HCV infection on 12-year mortality rates after AMI using data from the Taiwan National Health Insurance Research Database (NHIRD). METHODS NHIRD data for approximately 23 000 000 patients between January 2000 and December 2012 were analysed. A total of 186 112 cases of first AMI admission were identified. A total of 4659 patients with HCV infection not receiving interferon therapy were enrolled and divided into those with (n=107) or without (n=4552) cirrhosis. Using one-to-one matching, 4552 matched controls were included in the final analysis. RESULTS The 12-year mortality rate was significantly higher in patients with AMI with HCV infection and cirrhosis than in those with HCV infection but without cirrhosis (P<0.0001) or controls (P<0.0001). Patients with HCV infection but without cirrhosis had significantly higher long-term mortality rates than the matched controls (P<0.0001). The HR for mortality was higher in patients with HCV infection (HR 1.12; 95% CI 1.06 to 1.18). HCV influenced outcomes among the subgroups of patients who were male (HR 1.15) and those who had hypertension (HR 1.14). CONCLUSIONS HCV infection influenced the 12-year mortality rates of patients with AMI, especially those who were male and those who had hypertension. Cirrhosis further increased the long-term mortality rates of patients with AMI with HCV infection.
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Affiliation(s)
- Shu-Hung Kuo
- Critical Care Center and Cardiovascular Medical Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Wang-Ting Hung
- Critical Care Center and Cardiovascular Medical Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Pei-Ling Tang
- Critical Care Center and Cardiovascular Medical Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Wei-Chun Huang
- Critical Care Center and Cardiovascular Medical Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- Department of Physical Therapy, Fooyin University, Kaohsiung, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Jin-Shiou Yang
- Department of Physical Therapy, Fooyin University, Kaohsiung, Taiwan
| | - Hsiao-Chin Lin
- Critical Care Center and Cardiovascular Medical Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Guang-Yuan Mar
- Critical Care Center and Cardiovascular Medical Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Hong-Tai Chang
- Critical Care Center and Cardiovascular Medical Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Chun-Peng Liu
- Critical Care Center and Cardiovascular Medical Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
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14
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Gomaa HE, Mahmoud M, Saad NE, Saad-Hussein A, Ismail S, Thabet EH, Farouk H, Kandil D, Heiba A, Hafez W. Impact of Apo E gene polymorphism on HCV therapy related outcome in a cohort of HCV Egyptian patients. J Genet Eng Biotechnol 2017; 16:47-51. [PMID: 30647703 PMCID: PMC6296613 DOI: 10.1016/j.jgeb.2017.10.008] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2017] [Revised: 09/18/2017] [Accepted: 10/05/2017] [Indexed: 02/07/2023]
Abstract
The functional apolipoprotein E (Apo E) gene polymorphism could be used as a determinant of outcome of HCV infection. This study aimed to demonstrate the impact of Apo E genotype on the response to HCV combined therapy. MATERIAL AND METHODS The study has been implemented on 125 individuals with persistent HCV infection and 120 cases with sustained virologic response (SVR). All participants were genotyped for ApoE gene polymorphism by a real-time quantitative PCR (qPCR). RESULTS Statistically significant differences were demonstrated regarding the Apo E genotypes between the two groups (P-value < .001) where the frequency of E3E3 was significantly higher among the chronic HCV-patients while E3E4 and E4E4 genotypes frequencies were higher among the SVR-subjects group and E3E3 genotype was associated with increased risk of chronicity (OR 4.7; 95% CI 1.9-12.1, P-value < .001). Moreover, There were statically significant differences regarding E3 and E4 alleles frequencies, where E3 allele display a higher frequency among the chronic HCV-patient group while the SVR-subjects group showed higher frequency of E4 allele and the carriers of E3 allele have 1.4 times more risk to develop chronicity than those with E4 allele (OR 1.4; 95% CI 1.0-2.0, P-value < .05). Meanwhile the protective E2 allele was absent in all infected participants. CONCLUSION This study supports the hypothesis of the protective impact of Apo E4 allele that favors viral clearance of HCV infection and its recovery after combined therapy, while the Apo E3 allele is considered as a particular risk factor for the chronicity in HCV patients and resistance to therapy. Whereas the Apo E2 allele confers a resistance to HCV infection at a time of exposure.
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Affiliation(s)
- Howayda E Gomaa
- Clinical Pathology Department, National Research Centre, El-Behoos Street, Giza, Egypt
| | - Mohamed Mahmoud
- Internal Medicine Department, National Research Centre, Egypt
| | - Nevine E Saad
- Clinical Pathology Department, National Research Centre, El-Behoos Street, Giza, Egypt
| | - Amal Saad-Hussein
- Environmental and Occupational Medicine Department, National Research Centre, Egypt
| | - Somaia Ismail
- Medical Molecular Genetics Department, National Research Centre, Egypt
| | - Eman H Thabet
- Clinical Pathology Department, National Research Centre, El-Behoos Street, Giza, Egypt
| | - Hebatallah Farouk
- Clinical Pathology Department, National Research Centre, El-Behoos Street, Giza, Egypt
| | - Dina Kandil
- Clinical Pathology Department, National Research Centre, El-Behoos Street, Giza, Egypt
| | - Ahmed Heiba
- Internal Medicine Department, National Research Centre, Egypt
| | - Wael Hafez
- Internal Medicine Department, National Research Centre, Egypt
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Abstract
OPINION STATEMENT The long-term survival in liver transplant recipients (LTRs) is currently at an historical high level stemming from improvement in perioperative care, infection control, and immunosuppression medications. However, compared to the general population, LTRs have decreased survival. Metabolic diseases like hypertension, dyslipidemia, type 2 diabetes, and obesity are key determinants of long-term mortality in LTRs. The incidence and prevalence of these metabolic comorbidities is considerably higher in LTRs and likely results from a combination of factors including exposure to chronic immunosuppression, weight gain, and recurrence of chronic liver disease after liver transplantation (LT). Although there is currently little guidance in managing these metabolic conditions post-LT, recommendations are often extrapolated from non-transplant cohorts. In the current review, we explore the relationship between metabolic syndrome and its comorbidities in LTRs.
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16
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Desbois AC, Cacoub P. Diabetes mellitus, insulin resistance and hepatitis C virus infection: A contemporary review. World J Gastroenterol 2017; 23:1697-1711. [PMID: 28321170 PMCID: PMC5340821 DOI: 10.3748/wjg.v23.i9.1697] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2016] [Revised: 11/10/2016] [Accepted: 02/08/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To summarise the literature data on hepatitis C virus (HCV)-infected patients concerning the prevalence of glucose abnormalities and associated risk.
METHODS We conducted a PubMed search and selected all studies found with the key words "HCV" or "hepatitis C virus" and "diabetes" or "insulin resistance". We included only comparative studies written in English or in French, published from January 2000 to April 2015. We collected the literature data on HCV-infected patients concerning the prevalence of glucose abnormalities [diabetes mellitus (DM) and insulin resistance (IR)] and associated risk [i.e., severe liver fibrosis, response to antivirals, and the occurrence of hepatocellular carcinoma (HCC)].
RESULTS HCV infection is significantly associated with DM/IR compared with healthy volunteers and patients with hepatitis B virus infection. Glucose abnormalities were associated with advanced liver fibrosis, lack of sustained virologic response to interferon alfa-based treatment and with a higher risk of HCC development. As new antiviral therapies may offer a cure for HCV infection, such data should be taken into account, from a therapeutic and preventive point of view, for liver and non-liver consequences of HCV disease. The efficacy of antidiabetic treatment in improving the response to antiviral treatment and in decreasing the risk of HCC has been reported by some studies but not by others. Thus, the effects of glucose abnormalities correction in reducing liver events need further studies.
CONCLUSION Glucose abnormalities are strongly associated with HCV infection and show a negative impact on the main liver related outcomes.
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Barr AL, Young EH, Smeeth L, Newton R, Seeley J, Ripullone K, Hird TR, Thornton JRM, Nyirenda MJ, Kapiga S, Adebamowo CA, Amoah AG, Wareham N, Rotimi CN, Levitt NS, Ramaiya K, Hennig BJ, Mbanya JC, Tollman S, Motala AA, Kaleebu P, Sandhu MS. The need for an integrated approach for chronic disease research and care in Africa. Glob Health Epidemiol Genom 2016; 1:e19. [PMID: 29868211 PMCID: PMC5870416 DOI: 10.1017/gheg.2016.16] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2016] [Revised: 08/09/2016] [Accepted: 09/11/2016] [Indexed: 02/06/2023] Open
Abstract
With the changing distribution of infectious diseases, and an increase in the burden of non-communicable diseases, low- and middle-income countries, including those in Africa, will need to expand their health care capacities to effectively respond to these epidemiological transitions. The interrelated risk factors for chronic infectious and non-communicable diseases and the need for long-term disease management, argue for combined strategies to understand their underlying causes and to design strategies for effective prevention and long-term care. Through multidisciplinary research and implementation partnerships, we advocate an integrated approach for research and healthcare for chronic diseases in Africa.
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Affiliation(s)
- A. L. Barr
- Department of Medicine, University of Cambridge, Cambridge, UK
- Wellcome Trust Sanger Institute, Genome Campus, Hinxton, UK
| | - E. H. Young
- Department of Medicine, University of Cambridge, Cambridge, UK
- Wellcome Trust Sanger Institute, Genome Campus, Hinxton, UK
| | - L. Smeeth
- Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK
| | - R. Newton
- Medical Research Council/Uganda Virus Research Institute (MRC/UVRI), Uganda Research Unit on AIDS, Entebbe, Uganda
| | - J. Seeley
- Medical Research Council/Uganda Virus Research Institute (MRC/UVRI), Uganda Research Unit on AIDS, Entebbe, Uganda
- Global Health and Development, London School of Hygiene & Tropical Medicine, London, UK
| | - K. Ripullone
- Department of Medicine, University of Cambridge, Cambridge, UK
- Wellcome Trust Sanger Institute, Genome Campus, Hinxton, UK
| | - T. R. Hird
- Department of Medicine, University of Cambridge, Cambridge, UK
- Wellcome Trust Sanger Institute, Genome Campus, Hinxton, UK
| | - J. R. M. Thornton
- Department of Medicine, University of Cambridge, Cambridge, UK
- Wellcome Trust Sanger Institute, Genome Campus, Hinxton, UK
| | - M. J. Nyirenda
- Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK
- Malawi Epidemiology and Intervention Research Unit, Lilongwe, Malawi
| | - S. Kapiga
- Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK
- Mwanza Intervention Trials Unit, National Institute for Medical Research, Mwanza, Tanzania
| | - C. A. Adebamowo
- Department of Epidemiology and Public Health, Greenebaum Comprehensive Cancer Center and Institute of Human Virology, University of Maryland School of Medicine, Baltimore MD 21201 USA
- Institute of Human Virology, Nigeria
| | - A. G. Amoah
- Department of Medicine, University of Ghana Medical School, Korlebu, Ghana
| | - N. Wareham
- MRC Epidemiology Unit, University of Cambridge, Cambridge, UK
| | - C. N. Rotimi
- Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, USA
| | - N. S. Levitt
- Division of Diabetic Medicine and Endocrinology, Department of Medicine, University of Cape Town, Cape Town, South Africa
| | - K. Ramaiya
- Shree Hindu Mandal Hospital, Dar es Salaam, Tanzania
| | - B. J. Hennig
- MRC Unit, The Gambia, Fajara, The Gambia
- MRC International Nutrition Group, London School of Hygiene & Tropical Medicine, London, UK
| | - J. C. Mbanya
- Department of Internal Medicine and Specialties, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon
| | - S. Tollman
- MRC/Wits Rural Public Health and Health Transitions Research Unit, School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
- INDEPTH Network, Accra, Ghana
| | - A. A. Motala
- Department of Diabetes and Endocrinology, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa
| | - P. Kaleebu
- Medical Research Council/Uganda Virus Research Institute (MRC/UVRI), Uganda Research Unit on AIDS, Entebbe, Uganda
| | - M. S. Sandhu
- Department of Medicine, University of Cambridge, Cambridge, UK
- Wellcome Trust Sanger Institute, Genome Campus, Hinxton, UK
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Wong RJ, Gish RG. Metabolic Manifestations and Complications Associated With Chronic Hepatitis C Virus Infection. Gastroenterol Hepatol (N Y) 2016; 12:293-299. [PMID: 27499712 PMCID: PMC4973560] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
Chronic hepatitis C virus (HCV) infection is associated with many extrahepatic manifestations that contribute to morbidity and mortality. It is especially important to be aware of metabolic manifestations and serious complications that affect other organs and cancer risks. Chronic HCV infection itself contributes to de novo development of insulin resistance and hepatic steatosis, both of which increase the risk of cardiovascular diseases. Through these metabolic pathways (as well as through other hypothesized mechanisms that involve lipid metabolism, systemic inflammatory signals, and endothelial dysfunction), chronic HCV infection also contributes to significant systemic cardiovascular morbidity and mortality. While chronic HCV infection contributes to incident development of metabolic complications, the presence of concurrent metabolic diseases also contributes to disease progression, such as higher risks of hepatocellular carcinoma and progression to advanced fibrosis, among patients with chronic HCV infection. The implications of these observations are particularly important given the rising prevalence of obesity and metabolic syndrome in the United States and worldwide. Furthermore, concurrent nonalcoholic fatty liver disease, either as a result of underlying metabolic syndrome or as a direct result of HCV-induced fatty liver disease, further complicates the management of chronic HCV-infected patients. Greater awareness is needed toward the systemic manifestations of chronic HCV infection, with focused attention on the associated metabolic manifestations and complications. Successful treatment and cure of chronic HCV infection with the currently available, highly effective antiviral therapies will significantly improve long-term outcomes among these patients. It is also important to recognize and address the associated metabolic manifestations and complications to reduce cardiovascular-related morbidity and mortality.
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Affiliation(s)
- Robert J Wong
- Dr Wong is an assistant clinical professor of medicine at the University of California, San Francisco in San Francisco, California, and the director of research and education in the Division of Gastroenterology and Hepatology at Highland Hospital in Oakland, California. Dr Gish is a professor consultant in the Department of Medicine in the Division of Gastroenterology and Hepatology at Stanford University in Stanford, California; principal of Robert G. Gish Consultants, LLC, in San Diego, California; and senior medical director at St Joseph's Hospital and Medical Center in Phoenix, Arizona
| | - Robert G Gish
- Dr Wong is an assistant clinical professor of medicine at the University of California, San Francisco in San Francisco, California, and the director of research and education in the Division of Gastroenterology and Hepatology at Highland Hospital in Oakland, California. Dr Gish is a professor consultant in the Department of Medicine in the Division of Gastroenterology and Hepatology at Stanford University in Stanford, California; principal of Robert G. Gish Consultants, LLC, in San Diego, California; and senior medical director at St Joseph's Hospital and Medical Center in Phoenix, Arizona
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19
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Tabll AA, Kodous MA, Abbas AT, Omran MM, Elsayed EH. Association between serum aminotransferase enzymes–lipid profile ratio and spontaneous HCV clearance in blood donors. Future Virol 2016. [DOI: 10.2217/fvl.15.103] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Aim: Study the role of the aminotransferase lipid profile ratio in the spontaneous clearance of HCV. Materials & methods: Blood samples from 68 blood donors were classified into three groups: negative for HCV antibodies (control group I), positive anti-HCV with negative HCV-RNA, (group II) and positive anti-HCV with positive HCV-RNA (group III). Results: A significant linear correlation was observed between the HCV-RNA levels and aminotransferase enzymes–lipid profile ratio as indicated by the values of (AST)/triglycerides (r = 0.577; p = 0.003) and ALT/triglycerides (r = 0.508; p < 0.009). AST/high-density lipoprotein had an area under the receiver operating characteristic curve of 0.72 for discriminating between nonspontaneous HCV-clearance from spontaneous HCV-clearance patients. Conclusion: AST/high-density lipoprotein can be used for the prediction of HCV clearance without treatment.
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Affiliation(s)
- Ashraf A Tabll
- Microbial Biotechnology Department, National Research Centre, Giza, Egypt
| | - Marwa A Kodous
- Chemistry Department, Faculty of Science, Port-Said University, Port-Said, Egypt
| | - Ayman T Abbas
- Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdul-Aziz University, Jeddah, Saudi Arabia
- Biotechnology Research Laboratories, Gastroenterology Surgery Center, Mansoura University, Mansoura, Egypt
| | - Mohamed M Omran
- Chemistry Department, Faculty of Science, Helwan University, Cairo, Egypt
| | - Elsherbeny H Elsayed
- Chemistry Department, Faculty of Science, Port-Said University, Port-Said, Egypt
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20
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Arisar FAQ, Khan SB, Umar A, Shaikh NUS, Choudhry F. Changes in Serum Lipid Profile among Patients Suffering from Chronic Liver Disease Secondary to Hepatitis C. OPEN JOURNAL OF GASTROENTEROLOGY 2016; 06:333-342. [DOI: 10.4236/ojgas.2016.611036] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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Abstract
Patients with chronic hepatitis C virus (HCV) infection frequently present with extrahepatic manifestations covering a large spectrum, involving different organ systems leading to the concept of systemic HCV infection. These manifestations include autoimmune phenomena and frank autoimmune and/or rheumatic diseases and may dominate the course of chronic HCV infection. Chronic HCV infection causes liver inflammation affecting the development of hepatic diseases. HCV is also a lymphotropic virus that triggers B cells and promotes favorable conditions for B lymphocyte proliferation, including mixed cryoglobulinemia (MC) and MC vasculitis, which is the most prominent extrahepatic manifestation of chronic HCV infection. HCV may also promote a low-grade chronic systemic inflammation that may affect the development of some extrahepatic manifestations, particularly cardiovascular and cerebral vascular diseases. Recognition of extrahepatic symptoms of HCV infection could facilitate early diagnosis and treatment. The development of direct-acting antiviral agents (DDAs) has revolutionized HCV treatment. DDAs, as well as new B-cell-depleting or B-cell-modulating monoclonal antibodies, will expand the panorama of treatment options for HCV-related extrahepatic manifestations including cryoglobulinemic vasculitis. In this context, a proactive, integrated approach to HCV therapy should maximize the benefits of HCV therapy, even when liver disease is mild.
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Affiliation(s)
- E Rosenthal
- Service de Médecine Interne, Hôpital de l'Archet, CHU de Nice, Nice; Université de Nice-Sophia Antipolis, Nice, France COREVIH PACA EST, CHU de Nice, France
| | - P Cacoub
- Sorbonne Universités, 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
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22
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Butt AA, Yan P, Simon TG, Chung RT, Abou-Samra AB. Changes in circulating lipids level over time after acquiring HCV infection: results from ERCHIVES. BMC Infect Dis 2015; 15:510. [PMID: 26558512 PMCID: PMC4642733 DOI: 10.1186/s12879-015-1268-2] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2015] [Accepted: 11/05/2015] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Changes in lipid levels over time after acquiring HCV infection, and how they differ from HCV-uninfected persons are unknown. METHODS We used ERCHIVES to identify those with a known HCV seroconversion window and persistently negative controls. We excluded subjects with HIV and hepatitis B and those who received lipid lowering agents. Total Cholesterol (TC), low-density lipoproteins (LDL), high-density lipoproteins (HDL), triglycerides (TG) and non-HDL cholesterol were retrieved at yearly intervals and plotted over time. RESULTS Among 1,270 HCV+ and 5,070 HCV- subjects, median age [IQR] was 47[37,53] for HCV+ and 52[47,57] for the HCV- group; 69% were White and 91% were males in each group. Mean BMI [SD] was 26.94[6.73] in the HCV+ and 28.15 [5.98] in the HCV- group (P < 0.001). Over a 10-year follow-up period among HCV+ persons, TC decreased by (mean (SD) mg/dL) 12.06(36.95), LDL by 9.22(31.44), TG by 13.58(87.01) and non-HDL-C by 12.55(35.14). Among HCV- persons, TC cholesterol decreased by 4.15(31.21), LDL by 4.16(26.51); TG by 4.42(82.34) and non-HDL-C by 5.78(30.17). CONCLUSIONS After HCV acquisition, TC, LDL, TG and non-HDL-C progressively decline over time independent of BMI and liver fibrosis. Consequences of lipid changes and the need and optimal timing of lipid lowering therapy in HCV+ persons require further study.
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Affiliation(s)
- Adeel A Butt
- VA Pittsburgh Healthcare System, 3601 Fifth Avenue, Suite 3A, Pittsburgh, PA, 15213, USA. .,University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. .,Hamad Healthcare Quality Institute, Doha, Qatar. .,Hamad Medical Corporation, Doha, Qatar.
| | - Peng Yan
- VA Pittsburgh Healthcare System, 3601 Fifth Avenue, Suite 3A, Pittsburgh, PA, 15213, USA.
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Negro F, Forton D, Craxì A, Sulkowski MS, Feld JJ, Manns MP. Extrahepatic morbidity and mortality of chronic hepatitis C. Gastroenterology 2015; 149:1345-60. [PMID: 26319013 DOI: 10.1053/j.gastro.2015.08.035] [Citation(s) in RCA: 271] [Impact Index Per Article: 27.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2014] [Revised: 08/14/2015] [Accepted: 08/17/2015] [Indexed: 12/17/2022]
Abstract
Chronic hepatitis C virus (HCV) infection is associated with several extrahepatic manifestations. Patients with HCV may develop mixed cryoglobulinemia and its sequelae, ranging from cutaneous and visceral vasculitis to glomerulonephritis and B-cell non-Hodgkin lymphoma. HCV-infected patients have increased rates of insulin resistance, diabetes, and atherosclerosis, which may lead to increased cardiovascular morbidity and mortality. Neurological manifestations of HCV infection include fatigue and cognitive impairment. The mechanisms causing the extrahepatic effects of HCV infection are likely multifactorial and may include endocrine effects, HCV replication in extrahepatic cells, or a heightened immune reaction with systemic effects. Successful eradication of HCV with interferon alfa and ribavirin was shown to improve some of these extrahepatic effects; sustained virological response is associated with resolution of complications of cryoglobulinemia, reduced levels of insulin resistance, reduced incidence of diabetes and stroke, and improved fatigue and cognitive functioning. The availability of new interferon-free, well-tolerated anti-HCV treatment regimens is broadening the spectrum of patients available for therapy, including those in whom interferon was contraindicated, and will likely result in greater improvements in the extrahepatic manifestations of HCV. If these regimens are shown to confer significant benefit in the metabolic, cardiovascular, or neuropsychiatric conditions associated with HCV infection, extrahepatic manifestations of HCV may become a major indication for treatment even in the absence of liver disease.
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Affiliation(s)
- Francesco Negro
- Division of Gastroenterology and Hepatology and Division of Clinical Pathology, University Hospital, Geneva, Switzerland
| | - Daniel Forton
- Department of Gastroenterology and Hepatology, St George's Hospital, London, England
| | - Antonio Craxì
- Gastroenterology and Internal Medicine, University of Palermo, Palermo, Italy
| | - Mark S Sulkowski
- Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Jordan J Feld
- Toronto Centre for Liver Disease, Sandra Rotman Centre for Global Health, University of Toronto, Toronto, Ontario, Canada
| | - Michael P Manns
- Department of Gastroenterology, Hepatology and Endocrinology, Medical School of Hannover, Hannover, Germany.
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Cuadros DF, Miller FD, Nagelkerke N, Abu-Raddad LJ. Association between HCV infection and diabetes type 2 in Egypt: is it time to split up? Ann Epidemiol 2015; 25:918-23. [PMID: 26499381 DOI: 10.1016/j.annepidem.2015.09.005] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2015] [Revised: 09/06/2015] [Accepted: 09/07/2015] [Indexed: 12/15/2022]
Abstract
PURPOSE There is a conflicting evidence about the association between hepatitis C virus (HCV) infection and diabetes mellitus. The objective of this study was to assess this association in Egypt, the country with the highest HCV prevalence in the world. METHODS The source of data was from the Egypt Demographic and Health Survey conducted in 2008. Using multivariable logistic regression analyses to account for known confounders, the association was investigated at two levels']: (1) HCV exposure (HCV antibody status) and diabetes mellitus and (2) diabetes mellitus and chronic HCV infection (HCV RNA status) among HCV-exposed individuals. RESULTS We found no evidence for an association between HCV antibody status and diabetes (adjusted odds ratio [OR] = 0.87; 95% confidence interval [CI], 0.63-1.19). However, among HCV-exposed individuals, we found an evidence for an association between diabetes and active HCV infection (adjusted OR = 2.44, 95% CI, 1.30-4.57). CONCLUSIONS Although it does not appear that HCV exposure and diabetes are linked, there might be an association between diabetes and chronic HCV infection. The HCV-diabetes relationship may be more complex than previously anticipated. Therefore, a call for an "amicable divorce" to the HCV-diabetes relationship could be premature.
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Affiliation(s)
- Diego F Cuadros
- Infectious Disease Epidemiology Group, Weill Cornell Medical College-Qatar, Cornell University, Qatar Foundation-Education City, Doha, Qatar; Department of Healthcare Policy and Research, Weill Cornell Medical College, Cornell University, New York, NY.
| | - F DeWolfe Miller
- Department of Tropical Medicine and Medical Microbiology and Pharmacology, University of Hawaii, Honolulu
| | - Nico Nagelkerke
- Department of Public Health, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Laith J Abu-Raddad
- Infectious Disease Epidemiology Group, Weill Cornell Medical College-Qatar, Cornell University, Qatar Foundation-Education City, Doha, Qatar; Department of Healthcare Policy and Research, Weill Cornell Medical College, Cornell University, New York, NY; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA
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Ciccone MM, Principi M, Ierardi E, Di Leo A, Ricci G, Carbonara S, Gesualdo M, Devito F, Zito A, Cortese F, Scicchitano P. Inflammatory bowel disease, liver diseases and endothelial function: is there a linkage? J Cardiovasc Med (Hagerstown) 2015; 16:11-21. [PMID: 25427048 DOI: 10.2459/jcm.0000000000000149] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Atherosclerosis is a systemic inflammatory disease able to deeply worsen the outcome of patients because of its serious clinical consequences. The complex inflammatory background underlining such a disease makes atherosclerosis linked to several systemic inflammatory conditions able to impair endothelial function and morphology. Inflammatory bowel diseases are a group of gastrointestinal diseases including Crohn's disease and ulcerative colitis, that is, syndromes characterized by changes in mucosal immunity and gastrointestinal physiology, which could negatively influence the vascular endothelial function and structure. Hepatitis (i.e. inflammatory diseases of the liver mainly due to viral infections) and nonalcoholic fatty liver disease could be aligned to inflammatory bowel disease in such an induction of atherosclerosis disease.Many studies tried to point out the relationship between bowel and liver inflammatory diseases and early vascular changes, considered the first step for atherosclerosis development.The aim of such a narrative review is to explain the relationship between inflammatory bowel disease, hepatitis and nonalcoholic fatty liver disease and their role in increasing cardiovascular risk profile due to early impairment in vascular function and morphology.
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Affiliation(s)
- Marco Matteo Ciccone
- aDepartment of Emergency and Organ Transplantation (DETO) bUniversity of Bari, Bari cDepartment of Medical Sciences, Section of Gastroenterology, University of Foggia, Foggia, Italy
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Simon TG, Butt AA. Lipid dysregulation in hepatitis C virus, and impact of statin therapy upon clinical outcomes. World J Gastroenterol 2015; 21:8293-8303. [PMID: 26217081 PMCID: PMC4507099 DOI: 10.3748/wjg.v21.i27.8293] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2015] [Revised: 04/17/2015] [Accepted: 06/10/2015] [Indexed: 02/06/2023] Open
Abstract
The hepatitis C virus (HCV) is one of the most common causes of chronic liver disease and the leading indication for liver transplantation worldwide. Every aspect of the HCV life cycle is closely tied to human lipid metabolism. The virus circulates as a lipid-rich particle, utilizing lipoprotein cell receptors to gain entry into the hepatocyte. It has also been shown to upregulate lipid biosynthesis and impair lipid degradation, resulting in significant intracellular lipid accumulation and circulating hypocholesterolemia. Patients with chronic hepatitis C (CHC) are at increased risk of hepatic steatosis, fibrosis, and cardiovascular disease including accelerated atherosclerosis. HMG CoA Reductase inhibitors, or statins, have been shown to play an important role in the modulation of hepatic steatosis and fibrosis, and recent attention has focused upon their potential therapeutic role in CHC. This article reviews the hepatitis C viral life cycle as it impacts host lipoproteins and lipid metabolism. It then describes the pathogenesis of HCV-related hepatic steatosis, hypocholesterolemia and atherosclerosis, and finally describes the promising anti-viral and anti-fibrotic effects of statins, for the treatment of CHC.
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Dai CY, Yeh ML, Huang CF, Hou CH, Hsieh MY, Huang JF, Lin IL, Lin ZY, Chen SC, Wang LY, Chuang WL, Yu ML, Tung HD. Chronic hepatitis C infection is associated with insulin resistance and lipid profiles. J Gastroenterol Hepatol 2015; 30:879-84. [PMID: 23808794 DOI: 10.1111/jgh.12313] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/12/2013] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIM Chronic hepatitis C virus (HCV) infection has been suggested to be associated with non-insulin-dependent diabetes mellitus and lipid profiles. This study aimed to investigate the possible relationships of insulin resistance (IR) and lipid profiles with chronic hepatitis C (CHC) patients in Taiwan. METHODS We enrolled 160 hospital-based CHC patients with liver biopsy and the 480 controlled individuals without CHC and chronic hepatitis B from communities without known history of non-insulin-dependent diabetes mellitus. Fasting plasma glucose, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), alanine aminotransferase, and serum insulin levels, and homeostasis model assessment (HOMA-IR) were tested. RESULTS When comparing factors between CHC patients, and sex- and age-matched controls who had no HCV infection, patients with HCV infection had a significantly higher alanine aminotransferase level, fasting plasma glucose level, insulin level, and HOMA-IR (P < 0.001, P = 0.023, P = 0.017, and P = 0.011, respectively), and significantly lower TG level (P = 0.023), total cholesterol, and HDL-C and LDL-C levels (all P < 0.001) than 480 controls. In multivariate logistic regression analyses, a low total cholesterol, a low TGs, and a high HOMA-IR are independent factors significantly associated with chronic HCV infection. In the 160 CHC patients (41 patients with high HOMA-IR [> 2.5]), a high body mass index, TGs, and HCV RNA level are independent factors significantly associated with high HOMA-IR in multivariate logistic analyses. CONCLUSIONS Chronic HCV infection was associated with metabolic characteristics including IR and lipid profile. IR was also associated with virological characteristics.
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Affiliation(s)
- Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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Vercauteren K, Mesalam AA, Leroux-Roels G, Meuleman P. Impact of lipids and lipoproteins on hepatitis C virus infection and virus neutralization. World J Gastroenterol 2014; 20:15975-91. [PMID: 25473151 PMCID: PMC4239485 DOI: 10.3748/wjg.v20.i43.15975] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2014] [Revised: 07/09/2014] [Accepted: 09/05/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infections represent a major global health problem. End-stage liver disease caused by chronic HCV infection is a major indication for liver transplantation. However, after transplantation the engrafted liver inevitably becomes infected by the circulating virus. Direct acting antivirals are not yet approved for use in liver transplant patients, and limited efficacy and severe side effects hamper the use of pegylated interferon combined with ribavirin in a post-transplant setting. Therefore, alternative therapeutic options need to be explored. Viral entry represents an attractive target for such therapeutic intervention. Understanding the mechanisms of viral entry is essential to define the viral and cellular factors involved. The HCV life cycle is dependent of and associated with lipoprotein physiology and the presence of lipoproteins has been correlated with altered antiviral efficacy of entry inhibitors. In this review, we summarise the current knowledge on how lipoprotein physiology influences the HCV life cycle. We focus especially on the influence of lipoproteins on antibodies that target HCV envelope proteins or antibodies that target the cellular receptors of the virus. This information can be particularly relevant for the prevention of HCV re-infection after liver transplantation.
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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: 67] [Impact Index Per Article: 6.1] [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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Arain SA, Kazi TG, Afridi HI, Talpur FN, Mughal MA, Shah F, Arain SS, Panhwar AH. Estimation of copper and iron burden in biological samples of various stages of hepatitis C and liver cirrhosis patients. Biol Trace Elem Res 2014; 160:197-205. [PMID: 24973874 DOI: 10.1007/s12011-014-0058-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2014] [Accepted: 06/22/2014] [Indexed: 01/19/2023]
Abstract
There is accumulative evidence that the metabolism of iron (Fe) and copper (Cu) is altered in human due to infections, indicating that both elements have roles in pathogenesis and progress of viral diseases. In the present study, the correlation of Cu and Fe was evaluate in biological samples (serum and scalp hair) of hepatitis C (hepatitis C virus (HCV)) patients of both genders at different stages. For comparative study, the scalp hair and serum samples of healthy individuals of same age group (30-50 years) and socioeconomic status were collected. The biological samples were analyzed for Fe and Cu by atomic absorption spectroscopy after microwave-assisted acid digestion. The validity and accuracy of methodology were checked by certified reference materials of same matrixes. The levels of Cu and Fe in biological samples were enhanced in hepatic disorder patients, including acute (after diagnosis test, anti-HCV sero-positive) hepatic fibrosis and liver cirrhosis as compared to healthy referents. The difference was significant (p < 0.01) in the case of liver cirrhotic patients. It was observed that the data of Cu and Fe in referents and patients of both genders had normal distributions. The inter-elemental correlation (r) among Cu vs Fe in serum and scalp hair samples of referents and patients were not significant in both genders (p > 0.1) except in the first stage of HCV (p < 0.1). It was concluded that the increase of Cu and Fe content in human body seems to contribute to the development of cirrhosis in patients with viral hepatitis C.
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Affiliation(s)
- Salma Aslam Arain
- National Centre of Excellence in Analytical Chemistry, University of Sindh, Jamshoro, Pakistan,
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31
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Wong RJ, Kanwal F, Younossi ZM, Ahmed A. Hepatitis C virus infection and coronary artery disease risk: a systematic review of the literature. Dig Dis Sci 2014; 59:1586-93. [PMID: 24894512 DOI: 10.1007/s10620-014-3222-3] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2014] [Accepted: 05/18/2014] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND AIMS While hepatitis C virus (HCV) infection has been implicated in increasing the risk of coronary artery disease (CAD), conflicting reports exist regarding this association. We performed a systematic review to further investigate this association. METHODS We conducted a PubMed search of original research articles from January 1, 1995 to June 30, 2013 to identify case-control and cohort studies evaluating the association between HCV and CAD using keyword terms ["hepatitis c" or "HCV"] and ["coronary artery disease" or "heart disease" or "atherosclerosis."] The primary CAD-related endpoints included myocardial infarction, congestive heart failure, need for coronary artery bypass grafting, or transluminal percutaneous coronary angioplasty. Binary outcomes are reported as odds ratios (OR) with 95 % confidence interval (CI). RESULTS We identified five studies (four cohort studies and one case-control study) that met our inclusion criteria. A significant association between HCV and CAD was demonstrated in one cohort study (adjusted HR 1.27; 95 % CI 1.22-1.31). One cohort study demonstrated a decreased risk of CAD associated with HCV (adjusted OR 0.74; 95 % CI 0.71-0.76). The remaining studies did not find a significant association between HCV and risk of CAD. CONCLUSIONS The current systematic review demonstrates that the association between HCV and CAD remains unclear. We need more large, long-term cohort studies with clear definitions of patient population and endpoints to better ascertain the association between HCV and CAD.
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Affiliation(s)
- Robert J Wong
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA,
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The adiponutrin I148M variant is a risk factor for HCV-associated liver cancer in North-African patients. INFECTION GENETICS AND EVOLUTION 2013; 21:179-83. [PMID: 24269995 DOI: 10.1016/j.meegid.2013.11.005] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/12/2013] [Revised: 10/25/2013] [Accepted: 11/01/2013] [Indexed: 01/04/2023]
Abstract
Recent reports revealed an association between variation in the PNPLA3 gene and alcohol-induced hepatocellular carcinoma among Europeans. We have assessed whether the PNPLA3 rs738409 (I148M) polymorphism may also affect the resolution and/or the progression of hepatitis C in a Moroccan cohort. Genotype and allele frequencies at rs738409 were determined using a TaqMan 5' allelic discrimination assay in 437 individuals. Among them, 230 patients had a persistent infection with hepatitis C virus (HCV) with 129 patients affected by a chronic hepatitis and 101 patients by a hepatocellular carcinoma (HCC). In addition, we analyzed 75 individuals who naturally cleared HCV and 132 healthy subjects. Variation at rs738409 was not associated with significant changes in resolution rate of hepatitis C. By contrast, M/M genotype, present at higher frequencies (22.8%) in HCC patients than in patients with chronic hepatitis C (8.5%, P = 0.004) or control individuals (9.1%, P = 0.005) was associated with a 3-fold increase of liver cancer risk. In North African subjects, the PNPLA3 I148M variant apparently stimulates liver cancer development without interfering on the HCV clearance process. This polymorphism may, therefore, represent a valuable genetic marker to monitor liver cancer risk in populations from the Southern bank of the Mediterranean.
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Arain SA, Afridi HI, Kazi TG, Talpur FN, Shah F, Arain SS, Panhwar AH, Brahman KD. Investigation of Alteration in the Levels of Iron and Copper in Scalp Hair Samples of Patients Having Different Types of Viral Hepatitis. Biol Trace Elem Res 2013; 156:5-11. [PMID: 24122058 DOI: 10.1007/s12011-013-9832-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2013] [Accepted: 09/18/2013] [Indexed: 12/20/2022]
Abstract
The aim of this study was to measure the alterations of copper and iron contents in scalp hair samples of hepatitis A-E patients of both genders, same age group, and socioeconomic status. For comparative study, the scalp hair samples of healthy individuals of the same age and socioeconomic status were collected. The concentrations of copper and iron were measured using an atomic absorption spectrophotometer, after microwave-assisted acid digestion. The validity and accuracy of methodology was checked using a certified reference material. The results of this study showed that the mean values of copper and iron were higher in scalp hair samples of hepatitis patients than those of age-matched control subjects, while the difference was significant in the cases of patients having viral hepatitis B, C, and D as compared to those who have viral hepatitis A and E (p < 0.001). It was concluded that the overload of copper and iron in the human body may cause lipid peroxidation and eventually damage the hepatic system.
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Affiliation(s)
- Salma Aslam Arain
- National Centre of Excellence in Analytical Chemistry, University of Sindh, Jamshoro, 76080, Pakistan,
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Kutikhin A, Brusina E, Yuzhalin AE. Hepatitis Viruses, Atherosclerosis, and Related Diseases. ACTA ACUST UNITED AC 2013. [DOI: 10.1007/978-1-4614-8863-7_5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
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Hejazi N, Rajikan R, Choong CLK, Sahar S. Metabolic abnormalities in adult HIV infected population on antiretroviral medication in Malaysia: a cross-sectional survey. BMC Public Health 2013; 13:758. [PMID: 23947428 PMCID: PMC3844340 DOI: 10.1186/1471-2458-13-758] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2013] [Accepted: 07/31/2013] [Indexed: 12/11/2022] Open
Abstract
Background In the current two decades, dyslipidemia and increased blood glucose as metabolic abnormalities are the most common health threats with a high incidence among HIV/AIDS patients on antiretroviral (ARV) treatment. Scientific investigations and reports on lipid and glucose disorders among HIV infected communities are inadequate especially in those developing such as Malaysia. This cross-sectional survey was mainly aimed to evaluate the prevalence of metabolic abnormalities and associated risk factors among HIV infected population patients on ARV medication. Methods In a single reference health center in Malaysia, 2739 adult HIV positive patients on antiretroviral therapy (ART) were studied cross-sectionally using medical records. Besides demographic variables and associated health disorders, those factors which can change the lipid and glucose levels were collected. Logistic Regression was used to find the potential risk factors (p < 0.05). Results Majority of the studied population were male (81.1%) and aged between 30–49 (68.6%). Mean CD4 count was 474.25 (cells/mm3) while undetectable RNA viral load was common among 83.3 (%) of subjects. Among 1,583 patients with the recent blood lipid and glucose tests, increased levels of triglyceride (TG) and total cholesterol (TC) were frequently prevalent in half of the population as 59 (%) and 54.2 (%) while 28.7 (%), 35.1 (%) and 38.2 (%) had declined level of high-density lipoprotein (HDL), raised low-density lipoprotein (LDL) and fasting plasma glucose (FPG) which were less common. Dyslipidemia was common in 82.3 (%) of the subjects. Notably, medication with protease inhibitor (PI) was a potential risk for elevated triglyceride (odds ratio (OR) = 2.309, 95% confidence interval (CI) = 1.605–3.324, P = 0.001), high TC (OR = 1.561, 95% CI = 1.123–2.169, P = 0.008) and low HDL (OR = 1.449, 95% CI = 1.037–2.024, P = 0.029). As lifestyle factor, alcohol consumption results as significant risk factor for raised TG (OR = 2.653, 95% CI = 1.353–5.202, P = 0.004). Also having hepatitis raised risk of high FPG level (OR = 1.630, 95% CI = 1.197-2.220, P = 0.002) in this sample population. Conclusions Dyslipidemia is highly common in Malaysian HIV subjects receiving ARV medication. Lifestyle modification, changing PI and switch to other ARV regimen can help in reduction of these abnormalities. Also suitable strategies and plans are necessary to prevent cardiovascular diseases in future.
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Affiliation(s)
- Nazisa Hejazi
- Dietetics Program, School of Health Sciences, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur, 50300, Malaysia.
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Metabolic factors and chronic hepatitis C: a complex interplay. BIOMED RESEARCH INTERNATIONAL 2013; 2013:564645. [PMID: 23956991 PMCID: PMC3730187 DOI: 10.1155/2013/564645] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/29/2013] [Accepted: 06/29/2013] [Indexed: 12/15/2022]
Abstract
In the last years, several lines of evidence showed how metabolic factors may influence the natural history of patients with chronic hepatitis C. Chronic HCV infection is able to perturb the metabolic homeostasis of the host, in a context of complex interactions where pre-existent metabolic status and genetic background play an important role, allowing us to state that HCV infection is a systemic disease. In this review, we discuss the most recent lines of evidence on the main metabolic factors that are known to be associated with CHC, namely, insulin resistance/type 2 diabetes, steatosis, visceral obesity, atherosclerosis, vitamin D, menopause, fructose and coffee intake, lipoproteins, methylenetetrahydrofolate reductase status, and hyperuricaemia. In particular, we focus on the pathophysiological mechanisms underlying the correlation between HCV infection and metabolic disorders, the impact of metabolic factors on the progression of liver and non-liver-related diseases, and, on the contrary, the possible influence of chronic HCV infection on metabolic features. In this setting, the importance of a multifaceted evaluation of CHC patients and a prompt correction of modifiable metabolic risk factors should be emphasized.
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Hepatitis C virus, cholesterol and lipoproteins--impact for the viral life cycle and pathogenesis of liver disease. Viruses 2013; 5:1292-324. [PMID: 23698400 PMCID: PMC3712309 DOI: 10.3390/v5051292] [Citation(s) in RCA: 108] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2013] [Revised: 04/10/2013] [Accepted: 04/27/2013] [Indexed: 02/07/2023] Open
Abstract
Hepatitis C virus (HCV) is a leading cause of chronic liver disease, including chronic hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Hepatitis C infection associates with lipid and lipoprotein metabolism disorders such as hepatic steatosis, hypobetalipoproteinemia, and hypocholesterolemia. Furthermore, virus production is dependent on hepatic very-low-density lipoprotein (VLDL) assembly, and circulating virions are physically associated with lipoproteins in complexes termed lipoviral particles. Evidence has indicated several functional roles for the formation of these complexes, including co-opting of lipoprotein receptors for attachment and entry, concealing epitopes to facilitate immune escape, and hijacking host factors for HCV maturation and secretion. Here, we review the evidence surrounding pathogenesis of the hepatitis C infection regarding lipoprotein engagement, cholesterol and triglyceride regulation, and the molecular mechanisms underlying these effects.
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Kim DY, Kim IH, Jeong SH, Cho YK, Lee JH, Jin YJ, Lee D, Suh DJ, Han KH, Park NH, Kang HY, Jung YK, Kim YS, Kim KA, Lee YJ, Lee BS, Yim HJ, Lee HJ, Baik SK, Tak WY, Lee SJ, Chung WJ, Choi SK, Cho EY, Heo J, Kim DJ, Song BC, Kim MW, Lee J, Chae HB, Choi DH, Choi HY, Ki M. A nationwide seroepidemiology of hepatitis C virus infection in South Korea. Liver Int 2013; 33:586-94. [PMID: 23356674 DOI: 10.1111/liv.12108] [Citation(s) in RCA: 75] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2012] [Accepted: 12/19/2012] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS The aim of this study was to reveal nationwide seroprevalence of HCV infection in South Korea by a large-scale survey. METHODS From January to December 2009, a total of 291 314 adults underwent health check-up in 29 centres nationwide. The data concerning anti-HCV antibody and biochemical tests were obtained from all participants. Among subjects with positive anti-HCV, such data as HCV RNA, genotypes and treatment detail were additionally analysed. RESULTS Using an estimated 2009 population of Korea, the age, sex and area-adjusted anti-HCV positive rate was 0.78%. Anti-HCV prevalence in female patients (0.83%) was higher than that in male patients (0.75%). Gradual increase in anti-HCV positivity was observed, from 0.34% in those aged 20-29 years to 2.31% in those >70 years. The age- and sex-adjusted anti-HCV prevalence varied in different areas, being higher in Busan and Jeonnam (1.53-2.07%), mid-level in Seoul and surrounding districts (0.50-0.61%) and lower in Jeju (0.23%). The comparative analysis of laboratory variables between anti-HCV (+) and anti-HCV (-) group revealed significantly higher levels of alanine aminotransferase and lower levels of serum lipids in anti-HCV (+) group. Among 1 718 anti-HCV positive subjects, serum HCV RNA was measured only in 478 people, of whom 268 (56.1%) patients had detectable HCV RNA in serum. Among 50 patients for whom assessment of response to antiviral therapy was feasible, overall sustained virological response was achieved in 84% of patients. CONCLUSION The prevalence of HCV infection is low in South Korea. Studies to analyse risk factors are warranted to reduce HCV infection.
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Affiliation(s)
- Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
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Saleh O, Baiomy AA, El-desouky A, Zaghloul H, El-Arman M, Dahab GM, Abdel-Rahman MS. Hepatitis C virus genotype distribution in Egyptian diabetic patients: a preliminary study. Arab J Gastroenterol 2013; 14:14-19. [PMID: 23622804 DOI: 10.1016/j.ajg.2013.01.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2011] [Revised: 09/04/2012] [Accepted: 12/29/2012] [Indexed: 12/22/2022]
Abstract
BACKGROUND AND STUDY AIMS There is controversy regarding whether a specific hepatitis C virus (HCV) genotype is associated with diabetes mellitus. This study aimed to investigate HCV genotype distribution in diabetics and its relation to some clinical and laboratory variables in HCV-positive diabetic versus non-diabetic Egyptians in East Delta. PATIENTS AND METHODS The study included 100 HCV-positive patients of which 66 were diabetic in addition to 35 healthy adults as a control group. Clinical assessment, laboratory measurements of plasma glucose, insulin, C-peptide, C-reactive protein (CRP), tumour necrosis factor-α (TNF-α) and liver functions (alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT)) as well as HCV genotype determination were done, and AST/platelet ratio index (APRI) and Homoeostasis Model of Assessment-Insulin Resistance (HOMA-IR) were calculated. RESULTS The main results were the presence of HCV genotype 3, in 31.8% of the diabetic group and in 26.5% of the non-diabetic group, while the remainder of cases had genotype 4, the predominant genotype in Egypt. This is the first report of the presence of HCV genotype 3 in about 30% of an Egyptian cohort. However, there was no significant difference in genotype distribution between both groups. Further, there were significantly higher values of HOMA-IR, insulin and C-peptide in HCV-positive groups in comparison to the control group, while TNF-α was significantly higher in the HCV-positive diabetic group. However, there were no significant differences between both genotypes regarding these parameters. CONCLUSION Although this study reveals for the first time the presence of HCV genotype 3 in a significant percentage of a group of Egyptian patients, where the majority were diabetic, the association between diabetes and certain HCV genotypes could not be confirmed on the basis of our findings. Hence, taking into consideration the impact of such a finding on the treatment decisions of those patients, further studies are warranted to explore these findings to a greater extent.
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Affiliation(s)
- Omayma Saleh
- Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura City, Egypt.
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Chiba-Falek O, Linnertz C, Guyton J, Gardner SD, Roses AD, McCarthy JJ, Patel K. Pleiotropy and allelic heterogeneity in the TOMM40-APOE genomic region related to clinical and metabolic features of hepatitis C infection. Hum Genet 2012; 131:1911-20. [PMID: 22898894 DOI: 10.1007/s00439-012-1220-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2012] [Accepted: 08/08/2012] [Indexed: 12/11/2022]
Abstract
Hepatitis C virus (HCV) modulates host lipid metabolism as part of its lifecycle and is dependent upon VLDL for co-assembly and secretion. HCV dyslipidemia is associated with steatosis, insulin resistance, IL28B genotype and disease progression. Apolipoprotein E (ApoE) is an important lipid transport protein, a key constituent of VLDL, and is involved in immunomodulation. Our aims were to determine the role of APOE regional polymorphisms on host lipids, IL28B genotype and disease severity in chronic HCV (CHC) patients. The study cohort included 732 CHC patients with available DNA for genotype determination of four polymorphisms in the chromosome 19 region that encompasses the TOMM40, APOE and APOC1 genes. Serum lipid analysis and apolipoproteins levels were measured using an immunoturbidimetric assay. APOE rs7412 polymorphism (capturing the ε2 isoform) was significantly associated with serum ApoE levels in both Caucasians and African-American patients (p = 2.3 × 10(-11)) and explained 7 % of variance in serum ApoE. Among IL28B-CC patients (n = 196), the rs429358 (defines ε4 isoform) and TOMM40 '523' S polymorphisms were associated with 12 % of variance in ApoB levels. Patients homozygous for the APOE ε3 isoform had a greater than twofold increased odds of F2-F4 fibrosis (p = 1.8 × 10(-5)), independent of serum lipid and lipoprotein levels. There were no associations between APOE polymorphisms and serum HDL-C, APO-CIII and triglycerides. In CHC patients, genetic heterogeneity in the APOE/TOMM40 genomic region is significantly associated with variation in serum ApoE and ApoB levels, and also with fibrosis suggesting a pleiotropic attribute of this genomic region.
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Affiliation(s)
- Ornit Chiba-Falek
- Division of Neurology, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
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Roed T, Lebech AM, Kjaer A, Weis N. Hepatitis C virus infection and risk of coronary artery disease: a systematic review of the literature. Clin Physiol Funct Imaging 2012; 32:421-30. [PMID: 23031062 DOI: 10.1111/j.1475-097x.2012.01152.x] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2012] [Accepted: 06/25/2012] [Indexed: 02/06/2023]
Abstract
BACKGROUND Several chronic infections have been associated with cardiovascular diseases, including Chlamydia pneumoniae, human immunodeficiency virus and viral hepatitis. This review evaluates the literature on the association between chronic hepatitis C virus (HCV) infection and the risk of coronary artery disease (CAD). METHODS Studies were identified using several databases. Only studies on CAD in patients with HCV infection were included. A set of criteria for evaluating potential biases was made, based on known confounders and biases in observational research. Data were not synthesized because of the large heterogeneity in the included studies. RESULTS Twelve eligible references were identified. Nine did not comply with our criteria of minimizing bias, and six studies were evaluated as potentially heavily biased. The studies of the highest quality showed a trend towards association of HCV with CAD. Five studies showed this association (three studies significantly), while one showed that HCV was a protective factor against CAD. CONCLUSION Our findings suggest an increased risk of CAD in HCV-infected individuals. Further studies are needed to confirm this and to evaluate the magnitude of the association. Clinicians should be aware of this and strive to reduce CAD risk factors in patients with chronic HCV infection.
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Affiliation(s)
- Torsten Roed
- Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark.
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Petta S, Torres D, Fazio G, Cammà C, Cabibi D, Di Marco V, Licata A, Marchesini G, Mazzola A, Parrinello G, Novo S, Licata G, Craxì A. Carotid atherosclerosis and chronic hepatitis C: a prospective study of risk associations. Hepatology 2012; 55:1317-23. [PMID: 22135089 DOI: 10.1002/hep.25508] [Citation(s) in RCA: 106] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2011] [Accepted: 11/17/2011] [Indexed: 12/14/2022]
Abstract
UNLABELLED There are contrasting results in studies of cardiovascular risk in patients with genotype 1 chronic hepatitis C (G1 CHC). We evaluated the prevalence of carotid atherosclerosis compared with a control population in order to assess the potential association between atherosclerosis, host and viral factors, and liver histological features. In all, 174 consecutive biopsy-proven G1 CHC patients were evaluated by anthropometric and metabolic measurements and 174 patients attending an outpatient cardiology unit were used as controls. Intima-media thickness (IMT) and carotid plaques, defined as focal thickening of >1.3 mm at the level of common carotid, were evaluated using ultrasonography. All G1 CHC biopsies were scored by one pathologist for staging and grading, and graded for steatosis. Carotid plaques were found in 73 (41.9%) G1 CHC patients compared with 40 (22.9%) control patients (P < 0.001). Similarly, G1 CHC patients had a greater IMT compared with control patients (1.04 ± 0.21 versus 0.90 ± 0.16; P < 0.001). Multivariate logistic regression analysis showed that older age (odds ratio [OR] 1.047, 95% confidence interval [CI]: 1.014-1.082, P = 0.005), and severe hepatic fibrosis (OR 2.177, 95% CI: 1.043-4.542, P = 0.03), were independently linked to the presence of carotid plaques. In patients ≤55 years, 15/67 cases with F0-F2 fibrosis (22.3%) had carotid plaques, compared with 11/21 (52.3%) with F3-F4 fibrosis (P = 0.008). By contrast, in patients >55 years the prevalence of carotid plaques was similar in those with or without severe fibrosis (25/43, 58.1% versus 22/43, 51.1%; P = 0.51). CONCLUSION Severe hepatic fibrosis is associated with a high risk of early carotid atherosclerosis in G1 CHC patients.
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Affiliation(s)
- Salvatore Petta
- Sezione di Gastroenterologia, Di.Bi.M.I.S, Università di Palermo, Italia.
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Insulin resistance and diabetes mellitus in patients with chronic hepatitis C: spectators or actors? Dig Liver Dis 2012; 44:359-60. [PMID: 22418268 DOI: 10.1016/j.dld.2012.02.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2012] [Accepted: 02/03/2012] [Indexed: 12/11/2022]
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Naing C, Mak JW, Ahmed SI, Maung M. Relationship between hepatitis C virus infection and type 2 diabetes mellitus: meta-analysis. World J Gastroenterol 2012; 18:1642-51. [PMID: 22529694 PMCID: PMC3325531 DOI: 10.3748/wjg.v18.i14.1642] [Citation(s) in RCA: 105] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2011] [Revised: 12/04/2011] [Accepted: 01/18/2012] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the association between hepatitis C infection and type 2 diabetes mellitus. METHODS Observational studies assessing the relationship between hepatitis C infection and type 2 diabetes mellitus were identified via electronic and hand searches. Studies published between 1988 to March 2011 were screened, according to the inclusion criteria set for the present analysis. Authors performed separate analyses for the comparisons between hepatitis C virus (HCV) infected and not infected, and HCV infected and hepatitis B virus infected. The included studies were further subgrouped according to the study design. Heterogenity was assessed using I(2) statistics. The summary odds ratios with their corresponding 95% CIs were calculated based on a random-effects model. The included studies were subgrouped according to the study design. To assess any factor that could potentially affect the outcome, results were further stratified by age group (proportion of ≥ 40 years), gender (proportion of male gender), body mass index (BMI) (proportion of BMI ≥ 27), and family history of diabetes (i.e., self reported). For stability of results, a sensitivity analysis was conducted including only prospective studies. RESULTS Combining the electronic database and hand searches, a total of 35 observational studies (in 31 articles) were identified for the final analysis. Based on random-effects model, 17 studies (n = 286,084) compared hepatitis C-infected patients with those who were uninfected [summary odds ratio (OR): 1.68, 95% CI: 1.15-2.45]. Of these 17 studies, 7 were both a cross-sectional design (41.2%) and cohort design (41.2%), while 3 were case-control studies (17.6%). Nineteen studies (n = 51,156) compared hepatitis C-infected participants with hepatitis B-infected (summary OR: 1.92, 95% CI: 1.41-2.62). Of these 19 studies, 4 (21.1%), 6 (31.6%) and 9 (47.4%) were cross-sectional, cohort and case-control studies, respectively. A sensitivity analysis with 3 prospective studies indicated that hepatitis C-infected patients had a higher risk of developing type 2 diabetes compared with uninfected controls (summary odds ratio: 1.41, 95% CI: 1.17-1.7; I(2) = 0%). Among hepatitis C-infected patients, male patients (OR: 1.26, 95% CI: 1.03-1.54) with age over 40 years (summary OR: 7.39, 95% CI: 3.82-9.38) had an increased frequency of type 2 diabetes. Some caution must be taken in the interpretation of these results because there may be unmeasured confounding factors which may introduce bias. CONCLUSION The findings support the association between hepatitis C infection and type 2 diabetes mellitus. The direction of association remains to be determined, however. Prospective studies with adequate sample sizes are recommended.
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Affiliation(s)
- Cho Naing
- Faculty of Medicine and Health, International Medical University, Kuala Lumpur 57000, Malaysia.
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Forde KA, Haynes K, Troxel AB, Trooskin S, Osterman MT, Kimmel SE, Lewis JD, Lo Re V. Risk of myocardial infarction associated with chronic hepatitis C virus infection: a population-based cohort study. J Viral Hepat 2012. [PMID: 22404725 DOI: 10.1111/j.1365-2893.2011.01545] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Hepatitis C virus (HCV) infection is associated with systemic inflammation and metabolic complications that might predispose patients to atherosclerosis. However, it remains unclear if HCV infection increases the risk of acute myocardial infarction (MI). To determine whether HCV infection is an independent risk factor for acute MI among adults followed in general practices in the United Kingdom (UK), a retrospective cohort study was conducted in The Health Improvement Network, from 1996 through 2008. Patients ≥18 years of age with at least 6 months of follow-up and without a prior history of MI were eligible for study inclusion. HCV-infected individuals, identified with previously validated HCV diagnostic codes (n = 4809), were matched on age, sex and practice with up to 15 randomly selected patients without HCV (n = 71 668). Rates of incident MI among patients with and without a diagnosis of HCV infection were calculated. Adjusted hazard ratios were estimated using Cox proportional hazards regression, controlling for established cardiovascular risk factors. During a median follow-up of 3.2 years, there was no difference in the incidence rates of MI between HCV-infected and -uninfected patients (1.02 vs 0.92 events per 1000 person-years; P = 0.7). HCV infection was not associated with an increased risk of incident MI (adjusted HR, 1.10; 95% confidence interval [CI], 0.67-1.83). Sensitivity analyses including the exploration of a composite outcome of acute MI and coronary interventions yielded similar results (adjusted HR, 1.16; 95% CI, 0.77-1.74). In conclusion, HCV infection was not associated with an increased risk of incident MI.
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Affiliation(s)
- K A Forde
- Division of Gastroenterology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
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Forde KA, Haynes K, Troxel AB, Trooskin S, Osterman MT, Kimmel SE, Lewis JD, Lo Re V. Risk of myocardial infarction associated with chronic hepatitis C virus infection: a population-based cohort study. J Viral Hepat 2012; 19:271-7. [PMID: 22404725 PMCID: PMC3636529 DOI: 10.1111/j.1365-2893.2011.01545.x] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Hepatitis C virus (HCV) infection is associated with systemic inflammation and metabolic complications that might predispose patients to atherosclerosis. However, it remains unclear if HCV infection increases the risk of acute myocardial infarction (MI). To determine whether HCV infection is an independent risk factor for acute MI among adults followed in general practices in the United Kingdom (UK), a retrospective cohort study was conducted in The Health Improvement Network, from 1996 through 2008. Patients ≥18 years of age with at least 6 months of follow-up and without a prior history of MI were eligible for study inclusion. HCV-infected individuals, identified with previously validated HCV diagnostic codes (n = 4809), were matched on age, sex and practice with up to 15 randomly selected patients without HCV (n = 71 668). Rates of incident MI among patients with and without a diagnosis of HCV infection were calculated. Adjusted hazard ratios were estimated using Cox proportional hazards regression, controlling for established cardiovascular risk factors. During a median follow-up of 3.2 years, there was no difference in the incidence rates of MI between HCV-infected and -uninfected patients (1.02 vs 0.92 events per 1000 person-years; P = 0.7). HCV infection was not associated with an increased risk of incident MI (adjusted HR, 1.10; 95% confidence interval [CI], 0.67-1.83). Sensitivity analyses including the exploration of a composite outcome of acute MI and coronary interventions yielded similar results (adjusted HR, 1.16; 95% CI, 0.77-1.74). In conclusion, HCV infection was not associated with an increased risk of incident MI.
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Affiliation(s)
- Kimberly A. Forde
- Division of Gastroenterology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA,Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA,Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA
| | - Kevin Haynes
- Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA,Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA
| | - Andrea B. Troxel
- Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA,Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA
| | - Stacey Trooskin
- Division of Infectious Diseases, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA
| | - Mark T. Osterman
- Division of Gastroenterology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA,Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA,Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA
| | - Stephen E. Kimmel
- Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA,Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA,Division of Cardiovascular Medicine, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA
| | - James D. Lewis
- Division of Gastroenterology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA,Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA,Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA
| | - Vincent Lo Re
- Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA,Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA,Division of Infectious Diseases, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA
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Khattab MA, Eslam M, Aly MM, Shatat M, Mousa YI, Abd-Aalhalim H, Aly H, Shaker Y. Serum lipids and chronic hepatitis C genotype 4: interaction and significance. Ann Hepatol 2012; 11:37-46. [PMID: 22166559 DOI: 10.1016/s1665-2681(19)31484-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/29/2023]
Abstract
BACKGROUND & AIM Metabolic abnormalities are common in chronic hepatitis C infection (CHC). However, the genotypic differences of these disarrangements in patients infected with CHC genotype 4 (HCV-4) and its association with liver histology and viral loads remain unknown. MATERIAL AND METHODS We consecutively enrolled 183 HCV-4 patients and 106 healthy matched controls; to compare metabolic profiles and assess pattern of association of HCV RNA levels as well as histological factors with the serum lipid profile. RESULTS HCV-4 infection is associated with higher homeostasis model assessment of insulin resistance (HOMA-IR) index, despite that, a favourable lipid pattern, consisting of an elevation in HDL- C and a reduction in serum cholesterol (TC), LDL-C and triglyceride (TG) levels, in comparison with normal matched adults. Significant fibrosis was independently associated with HOMA-IR, portal/periportal inflammation grade, serum cholesterol and age. Univariate association was elucidated between lower LDL-C and TC and Metavir activity score and between higher TG and TC and steatosis. In multivariate analysis, severe hepatitis activity, milder hepatic fibrosis, and triglyceride levels are associated with higher HCV RNA levels. CONCLUSION HCV-4 is associated with wide metabolic changes. A proportional relationship is found between serum lipid profiles and hepatitis C viral load and liver histology in patients with HCV-4.
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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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Kolachi NF, Kazi TG, Afridi HI, Kazi N, Kandhro GA, Shah AQ, Baig JA, Wadhwa SK, Khan S, Shah F, Jamali MK, Arain MB. Distribution of copper, iron, and zinc in biological samples (scalp hair, serum, blood, and urine) of Pakistani viral hepatitis (A-E) patients and controls. Biol Trace Elem Res 2011; 143:116-30. [PMID: 20872092 DOI: 10.1007/s12011-010-8852-5] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2010] [Accepted: 09/09/2010] [Indexed: 12/17/2022]
Abstract
The aim of the present study was to compare the level of copper (Cu), iron (Fe) and zinc (Zn) in biological samples (serum, blood, urine, and scalp hair) of patients suffering from different viral hepatitis (A, B, C, D, and E; n = 521) of both gender age ranged 31-45 years. For comparative study, 255 age-matched control subjects, of both genders residing in the same city were selected as referents. The elements in the biological samples were analyzed by flame atomic absorption spectrophotometry, prior to microwave-assisted acid digestion. The validity and accuracy of the methodology was checked by using certified reference materials (CRMs) and with those values obtained by conventional wet acid digestion method on same CRMs. The results of this study showed that the mean values of Cu and Fe were higher in blood, sera, and scalp hair samples of hepatitis patients, while Zn level was found to be lower than age-matched control subjects. The urinary levels of these elements were found to be higher in the hepatitis patients than in the age-matched healthy controls (p < 0.05). These results are consistent with literature-reported data, confirming that the deficiency of zinc and hepatic iron and copper overload can directly cause lipid peroxidation and eventually hepatic damage.
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Affiliation(s)
- Nida Fatima Kolachi
- National Center of Excellence in Analytical Chemistry, University of Sindh, Jamshoro, 76080 Sindh, Pakistan
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