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Liu CJ, Seto WK, Yu ML. Dual-etiology MAFLD: the interactions between viral hepatitis B, viral hepatitis C, alcohol, and MAFLD. Hepatol Int 2024; 18:897-908. [PMID: 39115632 DOI: 10.1007/s12072-024-10699-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Accepted: 05/03/2024] [Indexed: 10/05/2024]
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) and viral hepatitis due to chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection are common liver diseases worldwide. Excessive alcohol consumption and alcoholic liver disease (ALD) are also emerging health problems. Therefore, in clinical practice, we may encounter subjects with dual etiology of liver diseases such as coexisting MAFLD/HBV, MAFLD/HCV, and MAFLD/ALD. In this review, we summarize the epidemiology, clinical features, and mutual interactions of MAFLD with coexisting HBV, HCV, or ALD. The impact of MAFLD on the progression of liver diseases and treatment outcomes in patients with chronic viral hepatitis and the clinical questions to be addressed regarding dual MAFLD and ALD are also discussed.
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Affiliation(s)
- Chun-Jen Liu
- Hepatitis Research Center, National Taiwan University College of Medicine and, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan
| | - Wai Kay Seto
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Pok Fu Lam, China.
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Center of Hepatitis Research, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
- School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-Sen University, Kaohsiung, Taiwan.
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Hooshmandi H, Ghadiri-Anari A, Ranjbar AM, Fallahzadeh H, Hosseinzadeh M, Nadjarzadeh A. Effects of licorice extract in combination with a low-calorie diet on obesity indices, glycemic indices, and lipid profiles in overweight/obese women with polycystic ovary syndrome (PCOS): a randomized, double-blind, placebo-controlled trial. J Ovarian Res 2024; 17:157. [PMID: 39080737 PMCID: PMC11287987 DOI: 10.1186/s13048-024-01446-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Accepted: 05/29/2024] [Indexed: 08/03/2024] Open
Abstract
BACKGROUND Polycystic ovary syndrome (PCOS) is the most common ovarian dysfunction. Recent studies showed the effectiveness of licorice on metabolic profiles with inconsistent findings. So, we investigated the effect of licorice on obesity indices, glycemic indices, and lipid profiles in women with PCOS. METHODS This randomized, double-blind, placebo-controlled trial was performed on 66 overweight/obese women with PCOS. The participants were randomly assigned to receive either 1.5 gr/day licorice extract plus a low-calorie diet (n = 33) or placebo plus a low-calorie diet (n = 33) for 8 weeks. Participants' anthropometric indices and body composition were assessed using standard protocols. Fasting blood sugar (FBS), insulin levels, low-density lipoprotein-cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), and high-density lipoprotein-cholesterol (HDL-C) were measured using enzymatic kits. The homeostasis model assessment-insulin resistance (HOMA-IR) and HOMA of β-cell function (HOMA-B) were calculated using valid formulas. RESULTS Between-group comparisons demonstrated significant differences between the groups in terms of obesity indices (body weight, BMI, and body fat), lipid profiles (TG, TC, LDL-C, and HDL-C), FBS and insulin levels, HOMA-IR, and HOMA-B at the end of the study (P < 0.05). Supplementation with licorice plus a low-calorie diet was also more effective in improving all parameters than a low-calorie diet alone after adjusting for confounders (baseline values, age, weight changes, and physical activity changes) (P < 0.05). CONCLUSION The findings showed that licorice consumption leads to improvements in obesity indices, glucose homeostasis, and lipid profiles compared to placebo. Due to possible limitations of the study, further research is needed to confirm these findings.
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Affiliation(s)
- Hadis Hooshmandi
- Research Center for Food Hygiene and Safety, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Akram Ghadiri-Anari
- Research Center for Food Hygiene and Safety, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
- Diabetes Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Ali Mohammad Ranjbar
- Department of Pharmacognosy, Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
- Herbal Medicine Center, Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Hossein Fallahzadeh
- Department of Biostatistics and Epidemiology, Research Center of Prevention and Epidemiology of Non-Communicable Disease, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Mahdieh Hosseinzadeh
- Research Center for Food Hygiene and Safety, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Azadeh Nadjarzadeh
- Research Center for Food Hygiene and Safety, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
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Marzaban RN, AlMekhzangy HI, ElAkel W, ElBaz TM, ElShazly YM, ElSaeed K, Anees M, Said M, ElSerafy MA, Esmat GG, Doss WH. Diabetic patients with chronic hepatitis C virus response compared to non diabetics when treated with directly acting antiviral therapy. Arab J Gastroenterol 2024; 25:118-124. [PMID: 38378359 DOI: 10.1016/j.ajg.2023.12.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 11/30/2023] [Accepted: 12/30/2023] [Indexed: 02/22/2024]
Abstract
BACKGROUND AND STUDY AIMS Hepatitis C virus (HCV) impairs glucose homoestasis, thus influences its clinical picture and prognosis. This study aimed at evaluating Diabetes mellitus (DM) on Egyptian patients with chronic hepatitis C (CHC), and its impact on their virologic response when treated with directly acting antiviral (DAA) medications. PATIENTS AND METHODS Adult patients with CHC were divided into 2 groups; Diabetic patients, and Non diabetic patients serving as control group. All patients were subjected to thorough clinical evaluation, basic biochemical laboratory tests including fasting blood glucose/glycosylated haemoglobin (HbA1C), and virologic assay. They were treated with various combined DAAs, and were monitored during, at and after end of treatment. RESULTS Diabetic patients constituted 9.85 % of CHC, and had generally worse laboratory tests (significantly higher transaminases, platelet count, Fib4 and hepatic steatosis) than non diabetic patients, and a less sustained virologic response (SVR) (significantly in Sofosbuvir (SOF) + pegylated interferon (PegIFN) + ribavirin (RBV), SOF + RBV, SOF + daclatasvir (DAC)). Although DM did not play a significant influence on SVR, yet Fib4 and SOF + RBV + PEG-IFN were significant factors affecting SVR among diabetics, while female gender and viraemia were significant factors affecting SVR among non diabetics. Hepatic fibrosis and SOF/RBV significantly influenced SVR in both groups. CONCLUSIONS Diabetic patients with CHC have worse liver biochemical profile, yet DM per se did not influence the virologic response to DAAs, however, some factors played roles in affecting SVR among them.
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Affiliation(s)
- Raghda N Marzaban
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Egypt.
| | | | - Wafaa ElAkel
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Egypt.
| | - Tamer M ElBaz
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Egypt
| | - Yehia M ElShazly
- Internal Medicine, Faculty of Medicine, Ain Shams University, Egypt
| | - Kadry ElSaeed
- Tropical Medicine, Faculty of Medicine, Ain Shams University, Egypt
| | - Mahmoud Anees
- Tropical Medicine, Faculty of Medicine, Tanta University, Egypt
| | - Mohamed Said
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Egypt
| | - Magdy A ElSerafy
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Egypt
| | - Gamal G Esmat
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Egypt.
| | - Wahid H Doss
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Egypt
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Yeh ML, Huang JF, Yu ML. Fatty liver and viral hepatitis: Prevalence, risk factors, natural course, pathogenesis, and management. METABOLIC STEATOTIC LIVER DISEASE 2024:261-275. [DOI: 10.1016/b978-0-323-99649-5.00008-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Pashayee-Khamene F, Hatami B, Cheraghpour M, Yari Z. Keeping an eye on the nutrition: The importance of nutrition management on cardiometabolic risk factors in cirrhotic patients. Clin Nutr ESPEN 2023; 58:186-192. [PMID: 38057004 DOI: 10.1016/j.clnesp.2023.09.927] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Revised: 08/26/2023] [Accepted: 09/26/2023] [Indexed: 11/07/2023]
Abstract
Chronic liver diseases, especially cirrhosis, are associated with significant morbidity and mortality. Besides predisposing to chronic liver disease per se, diabetes, hypertension, and dyslipidemia worsen the prognosis of patients with cirrhosis induced by other causes. There is no standard of care in the management of these factors in patients with cirrhosis. Also, in particular, it is not known whether nutritional interventions in the modification of cardiometabolic factors can improve the course of cirrhosis or not. This narrative review aimed to investigate the clinical significance of diabetes, hypertension, and dyslipidemia and appropriate nutritional interventions in cirrhotic patients. A comprehensive literature search of the published data was performed in regard to the association of cirrhosis with cardiometabolic factors and the management of cirrhosis and its complications. There is limited evidence on the association of cirrhosis with cardiometabolic risk factors. Cirrhotic cardiometabolic abnormalities are associated with an increased risk of complications, such that the coexistence of diabetes, hypertension, and dyslipidemia increases the risk of clinical decompensation in cirrhosis. Dietary management of cirrhotic patients with risk factors such as diabetes, hypertension, or dyslipidemia does not seem to be considerably different from non-cirrhotic patients.
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Affiliation(s)
- Fereshteh Pashayee-Khamene
- Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Behzad Hatami
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Makan Cheraghpour
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Zahra Yari
- Department of Nutrition Research, National Nutrition and Food Technology Research Institute and Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Aldubaie MH, Suryavamshi PM, Irfan UM, Al-Hamed HA, Almogbel TA, Almatroudi A, Alrumaihi F, Allemailem K. Prevalence of Hepatitis C Viral Infection among Diabetes Mellitus Patients in Qassim Region, Saudi Arabia. JOURNAL OF PURE AND APPLIED MICROBIOLOGY 2023; 17:1722-1736. [DOI: 10.22207/jpam.17.3.37] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
The worldwide prevalence of Diabetes Mellitus (DM) associated with Hepatitis C Virus (HCV) infection are reported with higher rates of morbidity and mortality. The frequency of HCV is approximately 3-4 million cases each year and in parallel the incidence of DM is increasing alarmingly. World Health Organization (WHO) has specified that DM will be the 7th leading cause of mortality by 2030. The increasing association between HCV and DM has been indicated by some significant reports recently. HCV infection leads to hepatic steatosis and rapid insulin resistance, which in turn upsurges the risk factors for hepatic fibrosis and hepatocellular carcinoma. This study is designed to examine the association between HCV and DM, and different risk factors associated with HCV infection in Qassim region, Kingdom of Saudi Arabia (KSA). A total of 634 blood samples were obtained from diabetic and non-diabetic patients. These blood samples were first screened for HCV infection by enzyme-linked immunosorbent assay (ELISA) and positive samples were again confirmed by TaqMan HCV quantitative test and the viral load in different samples was estimated. The HCV prevalence was identified as 2.5% in diabetic patients with a positive association between HCV and DM (RR= 1.24, OR= 1.77) which is not significant statistically. However, the HCV prevalence among diabetic females was significantly different from males (p<0.05). The behavioural factors had no significant impact to acquire HCV infection. This study indicated a positive association between HCV and DM. Gender was an association factor in the HCV and DM status. Further studies with larger sample size is significant to properly assess the temporal relationship between HCV and DM.
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Impact of sustained virological response on metabolic disorders in diabetic chronic hepatitis C virus patients after treatment with generic sofosbuvir and daclatasvir. Eur J Gastroenterol Hepatol 2021; 33:1588-1594. [PMID: 32804853 DOI: 10.1097/meg.0000000000001903] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES To evaluate the effect of generic sofosbuvir and daclatasvir (SOF/DCV) treatment on the glycemic state and insulin resistance as well as lipid profiles of those who achieved sustained virological response (SVR) in diabetic chronic hepatitis C virus (CHC) patients. METHODS We retrospectively reviewed 114 CHC patients with evidence of type 2 diabetes that were treated with generic SOF/DCV between May 2016 and August 2017. Baseline demographic and laboratory data were recorded. At 12-week post end of therapy (SVR12), glycemic state and insulin resistance as well as lipid profiles were re-evaluated and compared with baseline. RESULTS A total of 98 diabetic CHC patients were finally included and were responders. A significant decline in the glycemic state as well as Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) values (P ≤ 0.0001) was observed, but HOMA-S showed a statistically significant increase (P ≤ 0.0001) at SVR12 in comparison to baseline values. Also, a significant increase in serum total cholesterol, low-density lipoprotein (LDL)-cholesterol, and high-density lipoprotein (HDL)-cholesterol levels was observed at SVR12 compared to baseline, but serum triglycerides levels showed a significant decrease. Logistic regression showed that the higher baseline HOMA-IR was a significant predictive variable of a decrease ≥20% of HOMA-IR, while higher baseline HOMA-IR and baseline triglycerides emerged as the only significant predictors of the Δ increase LDL-C level at SVR12. CONCLUSION SOF/DCV-based therapy led to an improvement of glycemic state associated with a global worsening of lipid profile. Further studies are strongly warranted to evaluate the cardiovascular balance between amelioration of insulin resistance and negative changes of the lipid profile.
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Urganci N, Kalyoncu D, Geylani-Gulec S. Insulin resistance in children with chronic hepatitis C and its association with response to IFN-alpha and ribavirin. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2021; 86:140-144. [PMID: 32839082 DOI: 10.1016/j.rgmx.2020.07.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Revised: 07/15/2020] [Accepted: 07/15/2020] [Indexed: 06/11/2023]
Abstract
OBJECTIVE The aim of our study was to evaluate the association between insulin resistance and the response to IFN-alpha and ribavirin in pediatric patients with chronic hepatitis C. METHODS Twenty-six patients with chronic hepatitis C (mean age: 12.5 ± 1.96 years, M/F:3.33) were included in the study. Fasting glucose, insulin, and C-peptide levels, together with HOMA-IR, HOMA-B, and QUICKI values, were assessed. The association between those parameters and treatment response was determined. RESULTS Five (19.2%) of the 26 patients analyzed (2 [21.4%] with treatment response and 3 [16.6%] with no treatment response) had insulin resistance (p=1.00). There were no significant differences between the patients with and without treatment response with respect to fasting glucose, insulin, and C-peptide levels or HOMA-IR, HOMA-B, and QUICKI values (p>0.05). CONCLUSIONS No significant association was establihed between insulin resistance and response to IFN-alpha and ribavirin, in children with chronic hepatitis C.
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Affiliation(s)
- N Urganci
- Hospital Universitario y de Investigación Sisli Hamidiye Etfal, División de Gastroenterología Pediátrica, Estambul, Turquía
| | - D Kalyoncu
- Hospital Universitario y de Investigación Sisli Hamidiye Etfal, Departamento de Pediatría, Estambul, Turquía; Hospital Estatal de İstinye, Pediatría, Estambul, Turquía.
| | - S Geylani-Gulec
- Hospital Universitario y de Investigación Sisli Hamidiye Etfal, Departamento de Pediatría, Estambul, Turquía
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Urganci N, Kalyoncu D, Geylani-Gulec S. Insulin resistance in children with chronic hepatitis C and its association with response to IFN-alpha and ribavirin. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2021. [DOI: 10.1016/j.rgmxen.2020.07.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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Lee DY, Nam SM. Association between restrictive pulmonary disease and type 2 diabetes in Koreans: A cross-sectional study. World J Diabetes 2020; 11:425-434. [PMID: 33133390 PMCID: PMC7582118 DOI: 10.4239/wjd.v11.i10.425] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Revised: 08/11/2020] [Accepted: 08/31/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Diabetes is a progressive disease that increases glucose levels in the blood. While studies have shown that patients with pulmonary disease (both obstructive and restrictive pulmonary disease) have a higher prevalence of type 2 diabetes mellitus (T2DM), there have been more studies on restrictive patterns than chronic obstructive pulmonary disease.
AIM To assess whether restrictive and obstructive pulmonary diseases are associated with T2DM in Koreans.
METHODS For our analysis, we used data from the Korea National Health and Nutrition Examination Survey. A total of 2830 subjects were included in this study. Spirometry results were categorized into three patterns: Normal, restrictive pulmonary disease (RPD), and obstructive pulmonary disease (OPD).
RESULTS The factors used as diabetic indicators (i.e. homeostatic model assessment of insulin resistance, homeostatic model assessment of beta-cell function, glycated hemoglobin, and fasting insulin) were among the highest in RPD but not in OPD. Based on multivariate logistic regression analysis, subjects with RPD were found with an increased odds ratio [OR: 1.907, 95% confidence interval (CI): 1.110-3.277] for T2DM compared with subjects with normal pulmonary function, whereas in patients with OPD, the OR had not increased. Model 4, which adjusted for the variables that could affect diabetes and pulmonary disease, showed a significant increase in the T2DM OR to RPD (OR: 2.025, 95%CI: 1.264-3.244). On the other hand, no statistically significant difference was shown in OPD (OR: 0.982, 95%CI: 0.634-1.519).
CONCLUSION RPD, not OPD, is highly associated with T2DM regardless of the risk factors of various T2DMs that can be confounds.
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Affiliation(s)
- Do Y Lee
- Department of Physical Therapy, Daegu University, Gyeongsan-si 38453, South Korea
| | - Seung M Nam
- Department of Physical Therapy, Daegu University, Gyeongsan-si 38453, South Korea
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Özdoğan O, Yaraş S, Ateş F, Üçbilek E, Sezgin O, Altıntaş E. The impact of direct-acting antiviral treatment on lipid metabolism and insulin resistance in chronic hepatitis C patients: temporary? permanent? TURKISH JOURNAL OF GASTROENTEROLOGY 2020; 31:384-392. [PMID: 32519958 DOI: 10.5152/tjg.2020.19273] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND/AIMS In previous studies that investigated the impact of direct-acting antiviral (DAA) treatment on lipid metabolism and insulin resistance in chronic hepatitis C patients have been compared to baseline values with either end of treatment or post-treatment values. The results are inconsistent. We evaluated patients throughout the treatment and after treatment. MATERIALS AND METHODS 121 patients were included in the study. 93 patients were treated with sofosbuvir/ledipasvir±Ribavirin (RBV), and 28 patients were treated with ombitasvir/paritaprevir/ritonavir+dasabuvir±RBV. Total cholesterol (TC), low-density lipoprotein (LDL), triglycerides (TG) and homeostatic model assessment-insulin resistance (HOMA-IR) levels were measured at the onset of treatment, after the1st month of treatment, at the end of treatment, and 6 and 12 months after the end of treatment. RESULTS 117 patients were genotype 1. Sustained virological response was 98.4%. HOMA-IR values during treatment were significantly higher than at the beginning of treatment (p=0.0001). At 12 months there was a decrease in HOMA-IR, but this was not statistically significant (p=0.2048). TC and LDL levels were significantly increased in the first month of treatment (TC; 159±30, 180±34 mg/dl; LDL; 84±28, 100±30 mg/dl, respectively) (p<0.0001) and this increase was present during and after treatment. There was no statistically significant increase in TG (p=0120). Both treatment regimens showed similar effects on HOMA-IR, TC, and LDL. CONCLUSION Patients with HCV treated with DAAs drugs showed increased IR, TC, and LDL cholesterol levels during treatment. After the end of treatment, IR goes back to normal, while the elevated TC and LDL levels persist indefinitely.
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Affiliation(s)
- Osman Özdoğan
- Department of Gastroenterology, Mersin University School of Medicine, Mersin, Turkey
| | - Serkan Yaraş
- Department of Gastroenterology, Mersin University School of Medicine, Mersin, Turkey
| | - Fehmi Ateş
- Department of Gastroenterology, Mersin University School of Medicine, Mersin, Turkey
| | - Enver Üçbilek
- Department of Gastroenterology, Mersin University School of Medicine, Mersin, Turkey
| | - Orhan Sezgin
- Department of Gastroenterology, Mersin University School of Medicine, Mersin, Turkey
| | - Engin Altıntaş
- Department of Gastroenterology, Mersin University School of Medicine, Mersin, Turkey
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Abudawood M. Diabetes and cancer: A comprehensive review. JOURNAL OF RESEARCH IN MEDICAL SCIENCES 2019; 24:94. [PMID: 31741666 PMCID: PMC6856544 DOI: 10.4103/jrms.jrms_242_19] [Citation(s) in RCA: 74] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/10/2019] [Revised: 06/30/2019] [Accepted: 08/26/2019] [Indexed: 02/06/2023]
Abstract
Diabetes mellitus (DM) is a common worldwide endocrine disorder characterized by hyperglycemia resulting from defects in insulin secretion and insulin action or both. A number of clinical studies have investigated diabetes and its causal relation with neoplasm. Several epidemiological studies have found that diabetic patients have an increased risk of different types of cancers, for example liver, pancreas, gastric (stomach), colorectum, kidney, and breast, and it is predicted that hyperglycemic state observed in diabetic milieu enhances the cancer risk in prediabetic and diabetic individuals. To explore the strength of evidence and biases in the claimed associations between type 2 DM (T2DM) and risk of developing cancer, an umbrella review of the evidence across published meta-analyses or systematic reviews is performed. The concurrence of T2DM with the growing burden of cancer globally has generated interest in defining the epidemiological and biological relationships between these medical conditions. Through this review, it was found that diabetes could be related to cancer. Yet, the results from most of the studies are obscure and conflicting and need a robust research so that the link between diabetes and cancer could be firmly and impeccably documented.
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Affiliation(s)
- Manal Abudawood
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, KSA
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Saleh M, Rüschenbaum S, Welsch C, Zeuzem S, Moradpour D, Gouttenoire J, Lange CM. Glycogen Synthase Kinase 3β Enhances Hepatitis C Virus Replication by Supporting miR-122. Front Microbiol 2018; 9:2949. [PMID: 30542341 PMCID: PMC6278592 DOI: 10.3389/fmicb.2018.02949] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2018] [Accepted: 11/16/2018] [Indexed: 12/13/2022] Open
Abstract
Hepatitis C virus (HCV) infection is associated with alterations in host lipid and insulin signaling cascades, which are partially explained by a dependence of the HCV life cycle on key molecules in these metabolic pathways. Yet, little is known on the role in the HCV life cycle of glycogen synthase kinase 3 (GSK3), one of the most important kinases in cellular metabolism. Therefore, the impact of GSK3 on the HCV life cycle was assessed in human hepatoma cell lines harboring subgenomic genotype 1b and 2a replicons or producing cell culture-derived HCV genotype 2a by exposure to synthetic GSK3 inhibitors, GSK3 gene silencing, overexpression of GSK3 constructs and immunofluorescence analyses. In addition, the role of GSK3 in hepatitis E virus (HEV) replication was investigated to assess virus specificity of the observed findings. We found that both inhibition of GSK3 function by synthetic inhibitors as well as silencing of GSK3β gene expression resulted in a decrease of HCV replication and infectious particle production, whereas silencing of the GSK3α isoform had no relevant effect on the HCV life cycle. Conversely, overexpression of GSK3β resulted in enhanced HCV replication. In contrast, GSK3β had no effect on replication of subgenomic HEV replicon. The pro-viral effect of GSK3β on HCV replication was mediated by supporting expression of microRNA-122 (miR-122), a micro-RNA which is mandatory for wild-type HCV replication, as GSK3 inhibitors suppressed miR-122 levels and as inhibitors of GSK3 had no antiviral effect on a miR-122-independent HCV mutant. In conclusion, we have identified GSK3β is a novel host factor supporting HCV replication by maintaining high levels of hepatic miR-122 expression.
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Affiliation(s)
- Maged Saleh
- Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt, Germany
| | - Sabrina Rüschenbaum
- Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt, Germany
| | - Christoph Welsch
- Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt, Germany
| | - Stefan Zeuzem
- Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt, Germany
| | - Darius Moradpour
- Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland
| | - Jérôme Gouttenoire
- Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland
| | - Christian M Lange
- Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt, Germany
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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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15
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Laurito MP, Silva GF, Cheinquer H, Sharma R, Verna E, Parise ER. DOES INSULIN RESISTANCE IMPAIR THE VIROLOGICAL RESPONSE TO PEGINTERFERON/RIBAVIRIN IN CHRONIC HEPATITIS C GENOTYPE 3 PATIENTS? ARQUIVOS DE GASTROENTEROLOGIA 2018; 55:179-183. [PMID: 30043870 DOI: 10.1590/s0004-2803.201800000-32] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/11/2017] [Accepted: 12/11/2017] [Indexed: 02/23/2023]
Abstract
BACKGROUND Insulin resistance and diabetes mellitus are common extrahepatic manifestations of chronic hepatitis C (HCV). Insulin resistance assessed by HOMA-IR is associated with low rates of sustained virological response, especially in HCV genotype 1 positive patients treated with peginterferon/ribavirin. The effect of insulin resistance on sustained virologic response in HCV genotype 3 positive patients who were treated with peginterferon/ribavirin still remains unclear. OBJECTIVE To evaluate the impact of insulin resistance on sustained virological response in HCV genotype 3 patients treated with peginterferon/ribavirin. METHODS A retrospective multicenter study was performed to evaluate the impact of insulin resistance on sustained virological response in non-diabetic HCV genotype 3 positive patients treated with peginterferon and ribavirin. A total of 200 HCV genotype 3 positive patients were enrolled in the study. All patients were non-diabetic. Each patient had a HOMA-IR value measured before the initiation of HCV treatment with peginterferon/ribavirin. The treatment duration was at least 24 weeks. The HOMA-IR cut-off was defined in the study as ≥2.5 due to the coefficient of correlation with sustained virological response of 0.202 (P=0.004). RESULTS Univariate analysis showed that age, aspartate aminotransferase, platelets, stage of fibrosis and HOMA-IR were predictors of sustained virological response. However multivariate analysis showed advanced fibrosis [OR=2.01 (95%CI: 0.986-4.119) P=0.05] and age [OR=1.06 (95%CI: 1.022-1.110) P=0.002] as negative predictors of sustained virological response. CONCLUSION In this retrospective multicenter study of non-diabetic HCV genotype 3 positive patients, insulin resistance was not associated with the sustained virological response in patients who were treated with peginterferon/ribavirin.
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Affiliation(s)
- Marcela Pezzoto Laurito
- Universidade Federal de São Paulo, Disciplina de Gastroenterologia, SP, Brasil.,Columbia University Medical Center, Center for Liver Disease and Transplantation, New York, NY, USA
| | | | - Hugo Cheinquer
- Hospital de Clínicas de Porto Alegre, Departamento de Gastroenterologia, RS, Brasil
| | - Rajani Sharma
- Columbia University Medical Center, Center for Liver Disease and Transplantation, New York, NY, USA
| | - Elizabeth Verna
- Columbia University Medical Center, Center for Liver Disease and Transplantation, New York, NY, USA
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16
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Shahnazarian V, Ramai D, Reddy M, Mohanty S. Hepatitis C virus genotype 3: clinical features, current and emerging viral inhibitors, future challenges. Ann Gastroenterol 2018; 31:541-551. [PMID: 30174390 PMCID: PMC6102453 DOI: 10.20524/aog.2018.0281] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2018] [Accepted: 04/18/2018] [Indexed: 12/14/2022] Open
Abstract
Hepatitis C virus (HCV) represents a global burden on healthcare that affects over 150 million people worldwide. In the past, HCV genotype 3 was considered difficult to treat relative to other genotypes. Genotype 3 has been associated with a higher rate of complications, including fatty liver disease, fibrosis, hepatocellular carcinoma and mortality. However, with the advent of first- and second-generation direct-acting antivirals, genotype 3 can be treated effectively. Additionally, these new drugs are well tolerated by patients and have significantly fewer side effects compared to ribavirin and interferon-based regimens. However, while great strides have been made in overcoming biological barriers, our next challenge lies in overcoming economic and financial obstacles if we are to eradicate HCV genotype 3. Herein, we review the clinical features associated with HCV genotype 3, current and emerging treatment regimens, and challenges associated with treatment.
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Affiliation(s)
- Vahe Shahnazarian
- Division of Gastroenterology, Hepatology, and Advanced Endoscopy, The Brooklyn Hospital Center, Academic Affiliate of The Icahn School of Medicine at Mount Sinai, Clinical Affiliate of The Mount Sinai Hospital, Brooklyn, NY (Vahe Shahnazarian, Daryl Ramai, Madhavi Reddy), USA
| | - Daryl Ramai
- Division of Gastroenterology, Hepatology, and Advanced Endoscopy, The Brooklyn Hospital Center, Academic Affiliate of The Icahn School of Medicine at Mount Sinai, Clinical Affiliate of The Mount Sinai Hospital, Brooklyn, NY (Vahe Shahnazarian, Daryl Ramai, Madhavi Reddy), USA
- School of Medicine, St George’s University, True Blue, Grenada, WI (Daryl Ramai), USA
| | - Madhavi Reddy
- Division of Gastroenterology, Hepatology, and Advanced Endoscopy, The Brooklyn Hospital Center, Academic Affiliate of The Icahn School of Medicine at Mount Sinai, Clinical Affiliate of The Mount Sinai Hospital, Brooklyn, NY (Vahe Shahnazarian, Daryl Ramai, Madhavi Reddy), USA
| | - Smruti Mohanty
- Division of Gastroenterology and Hepatology, New York Presbyterian Brooklyn Methodist Hospital, Clinical Affiliate of Weill Cornell Medicine, Brooklyn, NY (Smruti Mohanty), USA
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17
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Li J, Zhang T, Gordon SC, Rupp LB, Trudeau S, Holmberg SD, Moorman AC, Spradling PR, Teshale EH, Boscarino JA, Schmidt MA, Daida YG, Lu M. Impact of sustained virologic response on risk of type 2 diabetes among hepatitis C patients in the United States. J Viral Hepat 2018; 25:952-958. [PMID: 29478263 PMCID: PMC6205163 DOI: 10.1111/jvh.12887] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2017] [Accepted: 01/16/2018] [Indexed: 12/27/2022]
Abstract
Data regarding the impact of hepatitis C (HCV) therapy on incidence of type 2 diabetes mellitus are limited. We used the data from the longitudinal Chronic Hepatitis Cohort Study-drawn from four large US health systems-to investigate how response to HCV treatment impacts the risk of subsequent diabetes. Among HCV patients without a history of type 2 diabetes mellitus or hepatitis B, we investigated the incidence of type 2 diabetes from 12 weeks post-HCV treatment through December 2015. Cox proportional hazards models were used to test the effect of treatment status (sustained virologic response [SVR] or treatment failure) and baseline risk factors on the development of diabetes, considering any possible risk factor-by-SVR interactions, and death as a competing risk. Among 5127 patients with an average follow-up of 3.7 years, diabetes incidence was significantly lower among patients who achieved SVR (231/3748; 6.2%) than among patients with treatment failure (299/1379; 21.7%; adjusted hazard ratio [aHR] = 0.79; 95% CI: 0.65-0.96). Risk of diabetes was higher among African American and Asian American patients than White patients (aHR = 1.82 and 1.75, respectively; P < .05), and among Hispanic patients than non-Hispanics (aHR = 1.86). Patients with BMI ≥ 30 and 25-30 (demonstrated higher risk of diabetes aHR = 3.62 and 1.72, respectively; P < .05) than those with BMI < 25; patients with cirrhosis at baseline had higher risk than those without cirrhosis (aHR = 1.47). Among a large US cohort of patients treated for HCV, patients who achieved SVR demonstrated a substantially lower risk for the development of type 2 diabetes mellitus than patients with treatment failure.
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Affiliation(s)
- J. Li
- Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA
| | - T. Zhang
- Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA
| | - S. C. Gordon
- Division of Gastroenterology and Hepatology, Henry Ford Health System, Detroit, MI, USA
| | - L. B. Rupp
- Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, MI, USA
| | - S. Trudeau
- Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA
| | - S. D. Holmberg
- Division of Viral Hepatitis, National Center for HIV, Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - A. C. Moorman
- Division of Viral Hepatitis, National Center for HIV, Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - P. R. Spradling
- Division of Viral Hepatitis, National Center for HIV, Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - E. H. Teshale
- Division of Viral Hepatitis, National Center for HIV, Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - J. A. Boscarino
- Department of Epidemiology and Health Services Research, Geisinger Clinic, Danville, PA, USA
| | - M. A. Schmidt
- Center for Health Research, Kaiser Permanente–Northwest, Portland, OR, USAs
| | - Y. G. Daida
- Center for Health Research, Kaiser Permanente–Hawaii, Honolulu, HI, USA
| | - M. Lu
- Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA
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18
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Alizadeh M, Namazi N, Mirtaheri E, Sargheini N, Kheirouri S. Changes of Insulin Resistance and Adipokines Following Supplementation with Glycyrrhiza Glabra L. Extract in Combination with a Low-Calorie Diet in Overweight and Obese Subjects: a Randomized Double Blind Clinical Trial. Adv Pharm Bull 2018; 8:123-130. [PMID: 29670847 PMCID: PMC5896387 DOI: 10.15171/apb.2018.015] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2017] [Revised: 02/18/2018] [Accepted: 02/20/2018] [Indexed: 11/25/2022] Open
Abstract
Purpose: Adipose tissue is a highly active endocrine organ which plays a key role in energy homeostasis. The aim of this study was to determine the effects of dried licorice extract along with a calorie restricted diet on body composition, insulin resistance and adipokines in overweight and obese subjects. Methods: Sixty-four overweight and obese volunteers (27 men, 37 women) were recruited into this double-blind, placebo-controlled, randomized, clinical trial. Participants were randomly allocated to the Licorice (n=32) or the placebo group (n=32), and each group received a low-calorie diet with either 1.5 g/day of Licorice extract or placebo for 8 weeks. Biochemical parameters, anthropometric indices, body composition and dietary intake were measured at baseline and at the end of the study. Results: A total of 58 subjects completed the trial. No side effects were observed following licorice supplementation. At the end of the study, waist circumference, fat mass, serum levels of vaspin, zinc-α2 glycoprotein, insulin and HOMA-IR were significantly decreased in the intervention group, but only the reduction in serum vaspin levels in the licorice group was significant when compared to the placebo group (p<0.01). Conclusion: Supplementation with dried licorice extract plus a low-calorie diet can increase vaspin levels in obese subjects. However, the anti-obesity effects of the intervention were not stronger than a low-calorie diet alone in the management of obesity.
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Affiliation(s)
- Mohammad Alizadeh
- Nutrition Research Center, Faculty of Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Nazli Namazi
- Nutrition Research Center, Faculty of Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran.,Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Elham Mirtaheri
- Nutrition Research Center, Faculty of Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Sorayya Kheirouri
- Department of Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran
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19
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Diabetes Mellitus and Risk of Hepatocellular Carcinoma. BIOMED RESEARCH INTERNATIONAL 2017; 2017:5202684. [PMID: 29379799 PMCID: PMC5742888 DOI: 10.1155/2017/5202684] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/25/2017] [Accepted: 11/22/2017] [Indexed: 02/06/2023]
Abstract
The occurrence of hepatocellular carcinoma (HCC) is two to three times higher in patients with diabetes mellitus (DM), the prevalence of which is increasing sharply worldwide. The purpose of this review was to describe clinical links between DM and HCC and potential biological mechanisms that may account for this association. We evaluated the role of potential pathways that could account for the development of HCC with different etiologies in the presence of DM. In addition, we also briefly discuss the potential effect of other factors such as type and dosage of antidiabetic medicines and duration of DM on HCC risk.
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20
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Oh IS, Won JW, Kim HJ, Lee HW. Clinical implication of serum uric acid level in pegylated interferon and ribavirin combination therapy for chronic hepatitis C infection. Korean J Intern Med 2017; 32:1010-1017. [PMID: 28797159 PMCID: PMC5668402 DOI: 10.3904/kjim.2016.405] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2016] [Revised: 02/08/2017] [Accepted: 05/22/2017] [Indexed: 01/15/2023] Open
Abstract
BACKGROUND/AIMS Combined treatment of pegylated interferon-α (PEG-IFN) and ribavirin (RBV) has long been accepted as the standard treatment for chronic hepatitis C virus (HCV) infection. Many predictive factors for treatment response have been identified. The aim of this study was to evaluate the efficacy and safety of combined PEG-IFN plus RBV and to examine the value of serum uric acid as a predictive factor in the treatment of chronic hepatitis C. METHODS A total of 74 patients chronically infected with HCV were enrolled between December 2004 and June 2009. Patients received subcutaneous PEG-IFN (α-2a: 180 μg once a week) in combination with RBV (1,000 to 1,200 mg daily depending on body weight). We evaluated treatment responses represented by early virologic response (EVR), end-of-treatment response (ETR), sustained virologic response (SVR), and relapse, as well as diverse adverse events. Various viral and host features were also assessed to clarify factors associated with treatment response. RESULTS During treatment, EVR was achieved in 26 patients (26/33, 78.8%) with HCV genotype 1. ETR and SVR were achieved in 59 (77.6%) and 56 patients (73.6%), respectively, across all genotypes. Genotype 2/3, lower HCV RNA, and lower uric acid were associated with higher SVR. CONCLUSIONS The treatment response to combination therapy with PEG-IFN plus RBV was effective, especially in genotype 2/3. Uric acid might be useful as a predictive factor for response to therapy for chronic hepatitis.
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Affiliation(s)
| | | | | | - Hyun Woong Lee
- Correspondence to Hyun Woong Lee, M.D. Department of Internal Medicine, Chung-Ang University College of Medicine, 102 Heukseok-ro, Dongjak-gu, Seoul 06973, Korea Tel: +82-2-6299-1417 Fax: +82-2-6299-1137 E-mail:
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21
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Li X, Gao Y, Xu H, Hou J, Gao P. Diabetes mellitus is a significant risk factor for the development of liver cirrhosis in chronic hepatitis C patients. Sci Rep 2017; 7:9087. [PMID: 28831144 PMCID: PMC5567219 DOI: 10.1038/s41598-017-09825-7] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2017] [Accepted: 07/31/2017] [Indexed: 12/21/2022] Open
Abstract
We explored the association between diabetes mellitus (DM) and the risk of hepatitis C virus (HCV)-related liver cirrhosis in Chinese patients with chronic hepatitis C (CHC). To examine the link between DM and liver cirrhosis, we conducted a case-control study of 210 Chinese CHC patients diagnosed with liver cirrhosis, comparing them to an age- and sex-matched control group of 431 CHC patients without liver cirrhosis. We conducted logistic regression analyses adjusting for demographic features and liver cirrhosis risk factors, and found that DM increased the risk of developing liver cirrhosis 2-fold [adjusted odds ratio (AOR), 2.132; 95% confidence interval (CI), 1.344–3.382]. Furthermore, the proportion of liver cirrhosis patients and CHC-only patients with elevated serum triglycerides (>1.8 mmol/L) were 5.2% and 17.4%, respectively, yielding an AOR of 0.264 (95% CI, 0.135–0.517). Multivariate analyses that stratified the risk of developing HCV-related liver cirrhosis in DM patients by gender revealed that the estimated AOR (95% CI) for males was 0.415 (0.178–0.969). In conclusion, DM was associated with an increased risk of developing liver cirrhosis in CHC patients in China. Furthermore, among patients diagnosed with both CHC and DM, females had an increased risk of liver cirrhosis development.
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Affiliation(s)
- Xu Li
- Department of Hepatology, The First Hospital of Jilin University, Jilin University, No. 71 Xinmin Street, Changchun, 130021, China
| | - Yang Gao
- Department of Neurology, The First Hospital of Jilin University, Jilin University, No. 71 Xinmin Street, Changchun, 130021, China
| | - Hongqin Xu
- Department of Hepatology, The First Hospital of Jilin University, Jilin University, No. 71 Xinmin Street, Changchun, 130021, China.,Jilin Province Key Laboratory of Infectious Disease, Laboratory of Molecular Virology, Changchun, 130021, China
| | - Jie Hou
- Department of Nephrology, The First Hospital of Jilin University, Jilin University, No. 71 Xinmin Street, Changchun, 130021, China
| | - Pujun Gao
- Department of Hepatology, The First Hospital of Jilin University, Jilin University, No. 71 Xinmin Street, Changchun, 130021, China.
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22
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Tsai WL, Chang TH, Sun WC, Chan HH, Wu CC, Hsu PI, Cheng JS, Yu ML. Metformin activates type I interferon signaling against HCV via activation of adenosine monophosphate-activated protein kinase. Oncotarget 2017; 8:91928-91937. [PMID: 29190886 PMCID: PMC5696152 DOI: 10.18632/oncotarget.20248] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2017] [Accepted: 07/12/2017] [Indexed: 12/25/2022] Open
Abstract
Activation of the type I interferon (IFN) signaling pathway is essential for the eradication of hepatitis C virus (HCV). Metformin can activate adenosine monophosphate-activated protein kinase (AMPK) to reduce insulin resistance. Cross talks between AMPK and IFN signaling remain unclear. To understand the influence of metformin on the type I IFN signaling pathway and HCV infection, the full-length HCV replicon OR6 cells and the infectious HCV clones JFH1 were used to assess the anti-HCV effect of the insulin sensitizers, metformin and pioglitazone. Immunofluorescence staining and the immunoblotting of HCV viral protein demonstrated that metformin, but not pioglitazone, inhibited HCV replication in OR-6 and JFH-1-infected Huh 7.5.1 cells. Immunoblotting data showed that metformin activated the phosphorylation of STAT-1 and STAT-2 in OR-6 and JFH-1 infected Huh 7.5.1 cells. Metformin enhanced the phosphorylation of AMPK, and the metformin-activated IFN signaling was down-regulated by AMPK inhibitor. After treatment of AMPK inhibitor, the level of HCV core protein decreased by metformin can be rescued. In conclusion, metformin activates type I interferon signaling and inhibits the replication of HCV via activation of AMPK.
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Affiliation(s)
- Wei-Lun Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Tsung-Hsien Chang
- Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.,Department of Medical Laboratory Science and Biotechnology, Chung Hwa University of Medical Technology, Tainan, Taiwan
| | - Wei-Chi Sun
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Hoi-Hung Chan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Chun-Ching Wu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Ping-I Hsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Jin-Shiung Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan.,Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan
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23
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Huang JF, Huang CF, Yeh ML, Dai CY, Hsieh MH, Yang JF, Huang CI, Lin YH, Liang PC, Lin ZY, Chen SC, Yu ML, Chuang WL. The outcomes of glucose abnormalities in chronic hepatitis C patients receiving interferon-free direct antiviral agents. Kaohsiung J Med Sci 2017; 33:567-571. [PMID: 29050674 DOI: 10.1016/j.kjms.2017.07.003] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2017] [Revised: 05/23/2017] [Accepted: 07/05/2017] [Indexed: 12/11/2022] Open
Abstract
Direct-acting antiviral agents (DAAs) have been widely used for chronic hepatitis C (CHC) treatment recently. The characteristics of glucose abnormalities after DAAs therapy however, remain elusive. We aimed to elucidate the mutual impact between treatment response and parameters of glucose abnormalities after DAAs therapy in CHC patients. CHC patients who received DAAs therapy were recruited. The primary outcome measurements were their insulin resistance (IR) and beta-cell function assessed by the homeostasis model assessment (HOMA) method before treatment and at end-of-follow-up (EOF). Sixty-five CHC patients (19 males, mean age = 59.8 ± 10.3 years) were consecutively enrolled. They included 47 (72.3%) patients of genotype-1 infection. The treatment regimens among patients were sofosbuvir in 30 patients, paritaprevir-ritonavir/ombitasvir/dasabuvir in 23 patients, and asunaprevir/daclatasvir in 12 patients respectively. The overall sustained virological response rate was 98.5%. The mean IR at EOF was 2.6 ± 1.8, which was not significantly different from baseline level (2.7 ± 2.9, P = 0.75). There was a significant improvement of beta-cell function at EOF compared to baseline (107.7 ± 86.8 to 86.7 ± 44.5, P = 0.05). The amelioration of beta-cell function at EOF was significantly observed among 23 patients of high baseline IR (166.7 ± 111.3 of baseline vs 105.7 ± 48.2 of EOF, P = 0.04). Six (60%) of the 10 pre-diabetic patients at baseline achieved a normoglycemic state at EOF. Successful eradication of HCV by DAAs might improve glucose abnormalities in CHC patients, particularly among those who had high IR.
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Affiliation(s)
- Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Meng-Hsuan Hsieh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jeng-Fu Yang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ching-I Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Yi-Hung Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Po-Cheng Liang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Zu-Yau Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shinn-Chern Chen
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
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Lack of Association between Hepatitis C Virus core Gene Variation 70/91aa and Insulin Resistance. Int J Mol Sci 2017; 18:ijms18071444. [PMID: 28753979 PMCID: PMC5535935 DOI: 10.3390/ijms18071444] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2017] [Revised: 05/17/2017] [Accepted: 05/24/2017] [Indexed: 01/08/2023] Open
Abstract
The role of hepatitis C virus (HCV) in insulin resistance (IR) is not fully understood. The aim of this study was to determine the impact of amino acid (aa) substitutions in the core region of HCV according to IR and to identify clinical and laboratory associations. Ninety-two treatment-naive HCV patients were recruited to determine laboratory data and blood cell count. IR was determined using Homeostasis Model Assessment (HOMA) index where IR was defined as HOMA ≥2. HCV RNA load and genotype were determined by Abbott Real time HCV. HCV core region was determined by direct nucleotide sequencing. Bivariate analysis was conducted using HOMA IR ≥2 as a dependent factor. IR prevalence was 43.5% (n = 40), vitamin D sufficiency was found in 76.1% (n = 70) and 72.8% (n = 67) had advanced liver fibrosis. In the bivariate analyses, elevated values of γGT (p = 0.024) and fibrosis staging (p = 0.004) were associated with IR, but IR was not related to core mutations. The presence of glutamine in position 70 was associated with low vitamin D concentration (p = 0.005). In the multivariate analysis, no variable was independently associated with HOMA-IR. In conclusion, lack of association between IR and HCV core mutations in positions 70 and 91 suggests that genetic variability of this region has little impact on IR.
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Hsiao CY, Hsu CS. Serum proteome and hepatitis C virus: Further issues to be discussed. J Formos Med Assoc 2017; 116:328. [PMID: 28010913 DOI: 10.1016/j.jfma.2016.11.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2016] [Accepted: 11/28/2016] [Indexed: 11/30/2022] Open
Affiliation(s)
- Chao-Yang Hsiao
- Division of Chinese internal medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23142, Taiwan
| | - Ching-Sheng Hsu
- Liver Diseases Research Center, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23142, Taiwan; School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien 97002, Taiwan.
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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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Li X, Xu H, Gao Y, Pan M, Wang L, Gao P. Diabetes mellitus increases the risk of hepatocellular carcinoma in treatment-naïve chronic hepatitis C patients in China. Medicine (Baltimore) 2017; 96:e6508. [PMID: 28353605 PMCID: PMC5380289 DOI: 10.1097/md.0000000000006508] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
We investigated the link between diabetes mellitus (DM) and hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) risk in treatment-naïve chronic hepatitis C (CHC) patients in China.To examine the association between DM and HCC, we conducted a case-control study of 300 Chinese CHC patients with HCC, compared to an age- and sex-matched control group of 517 CHC patients not diagnosed with HCC.We found that DM was more prevalent in the HCC patient group (18.7%) than in the CHC-only patient group (10.8%). We conducted logistic regression analyses adjusting for demographics features and other HCC risk factors and found that DM increased the risk of HCC development nearly 2-fold [adjusted odds ratio (AOR), 95% confidence interval (95% CI), 1.80 (1.17-2.75)]. Meanwhile, the proportion of HCC patients and CHC-only patients with liver cirrhosis were 79.3% and 46.2%, respectively, yielding an AOR of 4.62 (95% CI, 3.31-6.46). Multivariate analyses comparing the risk of HCV-related HCC development in DM patients with and without liver cirrhosis revealed that the estimated AOR (95% CI) for those with liver cirrhosis was 5.60 (2.25-13.96). However, the HCC risk decreased significantly with a later age of diabetes onset (AOR [95% CI], 0.94 [0.89-0.99]).DM was associated with an increased risk for HCC development in treatment-naïve CHC patients in China. Furthermore, liver cirrhosis and an early DM diagnoses further increased the risks of HCC development in patients diagnosed with both CHC and DM.
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Affiliation(s)
- Xu Li
- Department of Hepatology, The First Hospital of Jilin University, Jilin University
| | - Hongqin Xu
- Department of Hepatology, The First Hospital of Jilin University, Jilin University
- Jilin Province Key Laboratory of Infectious Disease, Laboratory of Molecular Virology
| | - Yang Gao
- Department of Neurology, The First Hospital of Jilin University, Jilin University, Changchun, China
| | - Meng Pan
- Department of Hepatology, The First Hospital of Jilin University, Jilin University
| | - Le Wang
- Department of Hepatology, The First Hospital of Jilin University, Jilin University
| | - Pujun Gao
- Department of Hepatology, The First Hospital of Jilin University, Jilin University
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Chang ML, Lin YS, Pao LH, Huang HC, Chiu CT. Link between plasminogen activator inhibitor-1 and cardiovascular risk in chronic hepatitis C after viral clearance. Sci Rep 2017; 7:42503. [PMID: 28211910 PMCID: PMC5304196 DOI: 10.1038/srep42503] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2016] [Accepted: 01/11/2017] [Indexed: 12/15/2022] Open
Abstract
The pathophysiological implications of plasminogen activator inhibitor-1 (PAI-1) in HCV infection remain obscure. This prospective study evaluated 669 HCV patients, of whom 536 had completed a course of anti-HCV therapy and had pre-, peri- and post-therapy measurements of various profiles, including PAI-1 levels. Multivariate analysis demonstrated, before anti-HCV-therapy, platelet count and PAI-1-rs1799889 genotype were associated with PAI-1 levels. Among patients with a sustained virological response (SVR, n = 445), platelet count was associated with PAI-1 level at 24 weeks post-therapy. GEE analysis showed that PAI-1-rs-1799889 and interferon-λ3-rs12979860 genotypes affected PAI-1 levels early and late in therapy, respectively. At 24 weeks post-therapy, higher lipid, brain natriuretic peptide, homocysteine and PAI-1 levels and PAI-1 activity were noted only in SVR patients compared with pre-therapy levels. Within 24 weeks post-therapy, 2.2% of the SVR (mean age: 57.8 yr; 8 smoking males; the 2 females had pre-therapy hypercholesteremia or cardiovascular family history of disease) and 0% of the non-SVR patients experienced a new cardiovascular event. Platelet counts consistently correlated with PAI-1 levels regardless of HCV infection. PAI-1-rs-1799889 and interferon-λ3-rs12979860 genotypes mainly affected PAI-1 levels longitudinally. Within 24 weeks post-anti-HCV therapy, the SVR patients showed increasing PAI-1 levels with accelerating cardiovascular risk, especially the vulnerable cases.
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Affiliation(s)
- Ming-Ling Chang
- Liver Research Center, Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.,Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Yu-Sheng Lin
- Department of Cardiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.,Healthcare center, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Li-Heng Pao
- Graduate Institute of Health-Industry Technology, Chang Gung University of Science and Technology, Taoyuan, Taiwan.,Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan
| | - Hsin-Chih Huang
- Liver Research Center, Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Cheng-Tang Chiu
- Liver Research Center, Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
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Shiffman ML, Gunn NT. Impact of hepatitis C virus therapy on metabolism and public health. Liver Int 2017; 37 Suppl 1:13-18. [PMID: 28052632 DOI: 10.1111/liv.13282] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2016] [Accepted: 10/20/2016] [Indexed: 12/22/2022]
Abstract
Chronic hepatitis C virus (HCV) is associated with insulin resistance (IR) and leads to type 2 diabetes mellitus (T2DM) and hepatic steatosis in many patients. These metabolic complications of HCV have been shown to accelerate the progression of fibrosis to cirrhosis and increase the risk of hepatocellular carcinoma. The metabolic syndrome is a common disorder that also includes IR, T2DM and hepatic steatosis. Approximately 20%-30% of patients with chronic HCV also have co-existent metabolic syndrome. The cause of steatosis in patients with the features of both the metabolic syndrome and chronic HCV is sometime difficult to determine. Patients with metabolic syndrome and chronic HCV are also at risk of developing renal, cardiovascular and cerebrovascular disease. Recent data suggest that HCV is an independent risk factor for renal, coronary and cerebral vascular disease, and may increase mortality associated with these disorders. The treatment of HCV can now result in a sustained virological response and cure nearly all patients with chronic HCV. The eradication of HCV reduces the risk of developing IR and T2DM, improves IR and 2TDM, reduces the risk of developing chronic kidney disease, end-stage renal disease, acute cardiac syndrome and stroke in patients with 2TDM. Thus, treatment of chronic HCV can provide a significant public health benefit, but only if all patients with chronic HCV are identified and universally treated.
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Affiliation(s)
- Mitchell L Shiffman
- Liver Institute of Virginia, Bon Secours Health System, Richmond and Newport News, VA, USA
| | - Nadege T Gunn
- Liver Institute of Virginia, Bon Secours Health System, Richmond and Newport News, VA, USA
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Stine JG, Wynter JA, Niccum B, Kelly V, Caldwell SH, Shah NL, Marquez V. Effect of Treatment with Direct Acting Antiviral on Glycemic Control in Patients with Diabetes Mellitus and Chronic Hepatitis C. Ann Hepatol 2017; 16:215-220. [PMID: 31153414 PMCID: PMC6600819 DOI: 10.5604/16652681.1231581] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2016] [Accepted: 07/17/2017] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND AIM The effect of the new direct acting antiviral drugs (DAAs) for chronic hepatitis C (HCV) on glycemic control is unknown. MATERIALS AND METHODS We conducted a retrospective cohort study of patients who were treated for chronic HCV with direct-acting antiviral medications at a single academic institution between May 2013 and April 2016. Univariate analysis was performed comparing subjects pre- and post-treatment. RESULTS One hundred seventy-five consecutive adult patients were treated for chronic HCV and met enrollment criteria. The majority (80.8%) were genotype 1 and overall cohort sustained virologic response at week 12 (SVR12) was 97.8%. Thirty-one (18.5%) had diabetes mellitus (DM); twenty-six had pre- and post-treatment HbA1c values. Of these, 76.9% were male and 61.5% had cirrhosis. Ninety-six percent were prescribed sofosbuvir-based therapy and all but one (96.8%) achieved SVR12. Three patients were started on treatment despite meeting the definition for poorly controlled DM (HbA1c > 9 mg/dL). There was no significant difference when comparing pre-treatment (7.36 mg/dL, 95% CI 6.55-8.16) to post-treatment HbA1c (7.11 mg/dL, 95% CI 6.34-7.88, p = 0.268). Thirty-one percent of subjects required dose escalation or the initiation of insulin based therapy during treatment. DISCUSSION Although chronic HCV is associated with exacerbation of insulin resistance, our results showed HbA1c to be unaffected by eradication of chronic HCV with DAA in diabetic patients with and without cirrhosis. Paradoxically, almost 1/3 of patients required escalation of anti-diabetic therapy during treatment. Long-term studies are warranted to understand the relationship between HCV viral eradication and insulin metabolism.
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Affiliation(s)
- Jonathan G. Stine
- Division of Gastroenterology & Hepatology, University of Virginia, Charlottesville, Virginia, United States
| | - Javelle A. Wynter
- Department of Medicine, University of Virginia, Charlottesville, Virginia, United States
| | - Blake Niccum
- School of Medicine, University of Virginia, Charlottesville, Virginia, United States
| | - Virginia Kelly
- Division of Gastroenterology & Hepatology, University of Virginia, Charlottesville, Virginia, United States
| | - Stephen H. Caldwell
- Division of Gastroenterology & Hepatology, University of Virginia, Charlottesville, Virginia, United States
| | - Neeral L. Shah
- Division of Gastroenterology & Hepatology, University of Virginia, Charlottesville, Virginia, United States
| | - Vladimir Marquez
- Division of Gastroenterology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada
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Morales AL, Junga Z, Singla MB, Sjogren M, Torres D. Hepatitis C eradication with sofosbuvir leads to significant metabolic changes. World J Hepatol 2016; 8:1557-1563. [PMID: 28050236 PMCID: PMC5165269 DOI: 10.4254/wjh.v8.i35.1557] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2016] [Revised: 09/20/2016] [Accepted: 10/24/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To assess the effect of sofosbuvir (SOF) based regimens on glycemic and lipid control.
METHODS This is a retrospective analysis of hepatitis C virus (HCV)-infected patients treated and cured with a SOF regimen [SOF/ribavirin/interferon, SOF/simeprevir, or SOF/ledipasvir (LDV) ± ribavirin] from January 2014 to March 2015. Patients with hemoglobin A1C (HbA1C) and lipid panels within six months before and six months after therapy were identified and included in our study. Due to the known hemolytic effect of ribavirin, HbA1C was obtained a minimum of three months post-treatment for the patients treated with a ribavirin regimen. Medical history, demographics, HCV genotype, pre-therapy RNA, and liver biopsies were included in our analysis. The patients who started a new medication or had an adjustment of baseline medical management for hyperlipidemia or diabetes mellitus (DM) were excluded from our analysis.
RESULTS Two hundred and thirty-four patients were reviewed, of which 60 patients met inclusion criteria. Sixty-three point three percent were male, 26.7% were Caucasian, 41.7% were African American and 91.7% were infected with hepatitis C genotype 1. Mean age was 60.6 ± 6.7 years. Thirty-nine patients had HbA1C checked before and after treatment, of which 22 had the diagnosis of DM type 2. HbA1C significantly decreased with treatment of HCV (pretreatment 6.66% ± 0.95% vs post-treatment 6.14% ± 0.65%, P < 0.005). Those treated with SOF/LDV had a lower HbA1C response than those treated with other regimens (0.26% ± 0.53% vs 0.71% ± 0.83%, P = 0.070). Fifty-two patients had pre- and post-treatment lipid panels; there was a significant increase in low-density lipoprotein (LDL) and total cholesterol (TC) after treatment (LDL: 99.5 ± 28.9 mg/dL vs 128.3 ± 34.9 mg/dL, P < 0.001; TC: 171.6 ± 32.5 mg/dL vs 199.7 ± 40.0 mg/dL, P < 0.001). Pre-treatment body-mass index (BMI) did not differ from post-treatment BMI (P = 0.684).
CONCLUSION Eradication of HCV with a SOF regimen resulted in a significant drop in HbA1C and an increase in LDL and TC post therapy.
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Lonardo A, Ballestri S, Guaraldi G, Nascimbeni F, Romagnoli D, Zona S, Targher G. Fatty liver is associated with an increased risk of diabetes and cardiovascular disease - Evidence from three different disease models: NAFLD, HCV and HIV. World J Gastroenterol 2016; 22:9674-9693. [PMID: 27956792 PMCID: PMC5124973 DOI: 10.3748/wjg.v22.i44.9674] [Citation(s) in RCA: 91] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2016] [Revised: 09/29/2016] [Accepted: 10/31/2016] [Indexed: 02/06/2023] Open
Abstract
Fatty liver, which frequently coexists with necro-inflammatory and fibrotic changes, may occur in the setting of nonalcoholic fatty liver disease (NAFLD) and chronic infections due to either hepatitis C virus (HCV) or human immunodeficiency virus (HIV). These three pathologic conditions are associated with an increased prevalence and incidence of cardiovascular disease (CVD) and type 2 diabetes (T2D). In this multidisciplinary clinical review, we aim to discuss the ever-expanding wealth of clinical and epidemiological evidence supporting a key role of fatty liver in the development of T2D and CVD in patients with NAFLD and in those with HCV or HIV infections. For each of these three common diseases, the epidemiological features, pathophysiologic mechanisms and clinical implications of the presence of fatty liver in predicting the risk of incident T2D and CVD are examined in depth. Collectively, the data discussed in this updated review, which follows an innovative comparative approach, further reinforce the conclusion that the presence of fatty/inflamed/fibrotic liver might be a shared important determinant for the development of T2D and CVD in patients with NAFLD, HCV or HIV. This review may also open new avenues in the clinical and research arenas and paves the way for the planning of future, well-designed prospective and intervention studies.
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Huang CF, Yeh ML, Huang CY, Tsai PC, Ko YM, Chen KY, Lin ZY, Chen SC, Dai CY, Chuang WL, Huang JF, Yu ML. Pretreatment glucose status determines HCC development in HCV patients with mild liver disease after curative antiviral therapy. Medicine (Baltimore) 2016; 95:e4157. [PMID: 27399135 PMCID: PMC5058864 DOI: 10.1097/md.0000000000004157] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2016] [Revised: 06/03/2016] [Accepted: 06/14/2016] [Indexed: 12/15/2022] Open
Abstract
Although diabetes mellitus (DM) is known to increase the risk of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC), the impact of dynamic glucose status on HCC occurrence in chronic hepatitis C (CHC) patients receiving antiviral therapy is unclear. In total, 1112 biopsy-proven patients treated with peginterferon/ribavirin were enrolled in this study. Both pretreatment and post-treatment glucose status, including 75 g oral glucose tolerance test (OGTT), were measured to evaluate the association between glucose status and the development of HCC. Of the 1112 patients evaluated, 93 (8.4%) developed HCC >5183.8 person-years of follow-up (annual incidence rate: 1.79%). DM only influenced the risk of developing CC in patients with mild liver disease (F0-2) and a sustained virological response (SVR) but not in other patient subpopulations. Cox-regression analysis demonstrated that the strongest factor associated with HCC in patients with mild liver disease and SVR was the presence of DM (hazard ratio [HR]/95 % confidence intervals [CI]: 3.79/1.420-10.136, P = 0.008), followed by age (HR/CI: 1.06/1.001-1.117, P = 0.046) and platelet count (HR/CI: 0.989/0.979-1.000, P = 0.05). The percentages of SVR patients with F0-2 with normoglycemia, pre-DM, sub-DM (pre-sDM), and DM before treatment were 45.3% (n = 267), 29.9% (n = 176), 15.6% (n = 92), and 9.2% (n = 54), respectively. The percentages of HCC in patients with normoglycemia, pre-sDM, and DM were 1.1%, 3.7%, and 11.1%, respectively (trend P < 0.001). Sixteen of the 19 (84.2 %) HCC patients possessed glucose abnormality (including 6 patients with DM and 10 patients with pre-sDM) before antiviral therapy. Compared to patients with normoglycemia, the incidence of HCC increased gradually from pre-sDM (HR: 3.6, P = 0.05) to DM (HR: 11.6, P = 0.001) (adjusted trend P = 0.004). We concluded that DM is a critical determinant for the development of HCC in SVR patients with mild liver disease. Pre-sDM status carried an additional risk for HCC, and these patients should also be carefully monitored for HCC after viral eradication.
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Affiliation(s)
- Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Occupational Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Health Management Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Cing-Yi Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Pei-Chien Tsai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yu-Min Ko
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Kuan-Yu Chen
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Zu-Yau Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shinn-Cherng Chen
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Health Management Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Occupational Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Institute of Biomedical Sciences, National Sun Yat-Sen University
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Abstract
GOALS To elucidate impact of insulin resistance (IR) on the response to interferon-α (IFN-α) therapy in chronic hepatitis B (CHB) patients. BACKGROUND Metabolic factors influencing the virological response of CHB patients on IFN-α treatment are still unexplored. STUDY Eighty CHB patients were treated with IFN-α for 48 weeks. The IR was evaluated by homeostasis model assessment of IR (HOMA-IR) before treatment. Viral load and biochemical parameters were measured at 12, 24, and 48 weeks after starting treatment, and then 24 weeks after the end of treatment. IFN-γ and tumor necrosis factor-α were tested at baseline and 12 weeks of treatment. RESULTS Pretreatment HOMA-IR proved to be the only independent predictor of primary nonresponse, as well as the pretreatment HOMA-IR, viral load and primary nonresponse were independently associated with virological response at 24, 48 weeks of treatment and at the follow-up endpoint. The significant higher virological relapse rate in patients with IR was observed in patients with virological response at 48 weeks of treatment. The mean HOMA-IR was significantly lower in virological responders than in virological nonresponders. The secretion of IFN-γ and tumor necrosis factor-α was not induced in patients with IR at 12 weeks after IFN-α treatment. CONCLUSIONS Our data suggest that IR is strongly associated with virological response, thus reflecting the important role played by metabolic factors in the viral kinetics during IFN-α treatment. These findings suggested clinical application of pretreatment HOMA-IR could enable treatment outcome to be predicted and treatment regimens to be determined.
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Tseng CH, Hsu YC, Chang CY, Lin CW, Lin JT, Mo LR. Change in insulin resistance according to virological response during antiviral treatment for hepatitis C virus infection. ADVANCES IN DIGESTIVE MEDICINE 2016. [DOI: 10.1016/j.aidm.2014.12.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
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Dai CY. Insulin resistance and anti-hepatitis C virus therapy. ADVANCES IN DIGESTIVE MEDICINE 2016. [DOI: 10.1016/j.aidm.2016.03.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Ranjbari A, Azarbayjani MA, Yusof A, Halim Mokhtar A, Akbarzadeh S, Ibrahim MY, Tarverdizadeh B, Farzadinia P, Hajiaghaee R, Dehghan F. In vivo and in vitro evaluation of the effects of Urtica dioica and swimming activity on diabetic factors and pancreatic beta cells. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 2016; 16:101. [PMID: 26980377 PMCID: PMC4791772 DOI: 10.1186/s12906-016-1064-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/29/2015] [Accepted: 02/23/2016] [Indexed: 11/10/2022]
Abstract
BACKGROUND Urtica dioica (UD) has been identified as a traditional herbal medicine. This study aimed to investigate the effect of UD extract and swimming activity on diabetic parameters through in vivo and in vitro experiments. METHODS Adult WKY male rats were randomly distributed in nine groups: intact control, diabetic control, diabetic + 625 mg/kg, 1.25 g/kg UD, diabetic + 100 mg/kg Metformin, diabetic + swimming, diabetic + swimming 625 mg/kg, 1.25 g/kg UD, and diabetic +100 mg/kg Metformin + swimming. The hearts of the animals were punctured, and blood samples were collected for biochemical analysis. The entire pancreas was exposed for histologic examination. The effect of UD on insulin secretion by RIN-5F cells in 6.25 or 12.5 mM glucose dose was examined. Glucose uptake by cultured L6 myotubes was determined. RESULTS The serum glucose concentration decreased, the insulin resistance and insulin sensitivity significantly increased in treated groups. These changes were more pronounced in the group that received UD extract and swimming training. Regeneration and less beta cell damage of Langerhans islets were observed in the treated groups. UD treatment increased insulin secretion in the RIN-5F cells and glucose uptake in the L6 myotubes cells. CONCLUSIONS Swimming exercises accompanied by consuming UD aqueous extracts effectively improved diabetic parameters, repaired pancreatic tissues in streptozotocin-induced diabetics in vivo, and increased glucose uptake or insulin in UD-treated cells in vitro.
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Affiliation(s)
- Abbas Ranjbari
- />Department of Physical Education, Sanandaj Farhangyan University, Sanandaj, Iran
| | - Mohammad Ali Azarbayjani
- />Exercise Physiology Department, Faculty of Physical Education, Islamic Azad University, Central Tehran Branch, Tehran, Iran
| | - Ashril Yusof
- />Department of Exercise Science, Sports Centre, University Malaya, 50603 Kuala Lumpur, Malaysia
| | - Abdul Halim Mokhtar
- />Department of Sport Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
| | - Samad Akbarzadeh
- />Biochemistry Department, Faculty of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Mohamed Yousif Ibrahim
- />Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
| | - Bahman Tarverdizadeh
- />Exercise Physiology Department, Faculty of Physical Education, Islamic Azad University, Bushehr Branch, Bushehr, Iran
| | - Parviz Farzadinia
- />Biology and Anatomical Sciences, Faculty of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Reza Hajiaghaee
- />Pharmacognosy and Pharmaceutic Department of Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Karaj, Iran
| | - Firouzeh Dehghan
- />Department of Exercise Science, Sports Centre, University Malaya, 50603 Kuala Lumpur, Malaysia
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Chou WW, Huang CF, Yeh ML, Tsai YS, Hsieh MY, Huang CI, Huang JF, Tsai PC, Hsi E, Juo SHH, Tsai WL, Chuang WL, Yu ML, Dai CY. MicroRNA let-7g cooperates with interferon/ribavirin to repress hepatitis C virus replication. J Mol Med (Berl) 2016; 94:311-320. [PMID: 26489607 DOI: 10.1007/s00109-015-1348-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2015] [Revised: 08/18/2015] [Accepted: 09/21/2015] [Indexed: 01/19/2023]
Abstract
MicroRNAs (miRNA) have been implicated in HCV infection. The present study analyzed the effects of let-7g on HCV infection in vitro, in clinical tissue and serum samples. Here, we show that the expression of let-7g in serum and liver tissue is significantly higher in patients with sustained virologic response (SVR). We show that interferon (IFN)/ribavirin (RBV) induces let-7g expression through p38/AP-1 signaling. Overexpression of let-7g reduced HCV gene or core protein level and inhibited the HCV viral load. The let-7g and IFN/RBV have additively inhibitory effect on HCV replication. These data implicate let-7g as a new therapeutic drug to additively cooperate with IFN/RBV to repress HCV replication. Key messages: let-7g expression is increased in serum and liver tissue of patients with SVR. Interferon/ribavirin induces let-7g expression through p38/AP-1 signaling. Overexpression of let-7g can repress HCV replication. Let-7g additively cooperates with interferon/ribavirin to repress HCV replication. Lin28B silencing can reverse let-7g expression and repress HCV replication.
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Affiliation(s)
- Wen-Wen Chou
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yi-Shan Tsai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan
| | - Ming-Yen Hsieh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan
| | - Ching-I Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Pei-Chien Tsai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan
| | - Edward Hsi
- Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Genome Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Suh-Hang Hank Juo
- Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Genome Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wei-Lun Tsai
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- School of Medicine, National Yang Ming University, Taipei, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center for Infectious Disease and Cancer Research, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center for Lipid Science and Aging Research, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center for Infectious Disease and Cancer Research, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center for Lipid Science and Aging Research, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan.
- Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
- Center for Infectious Disease and Cancer Research, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
- Center for Lipid Science and Aging Research, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
- Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
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Dorna MDS, Santos LAA, Gondo FF, Augusti L, de Campos Franzoni L, Sassaki LY, Romeiro FG, de Paiva SAR, Minicucci MF, Silva GF. Phase angle is associated with advanced fibrosis in patients chronically infected with hepatitis C virus. Life Sci 2016; 154:30-3. [PMID: 26896689 DOI: 10.1016/j.lfs.2016.02.061] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2015] [Revised: 11/05/2015] [Accepted: 02/15/2016] [Indexed: 12/13/2022]
Abstract
AIMS The objective of this study was to evaluate the association of phase angle (PhA) with advanced liver fibrosis in patients chronically infected with hepatitis C virus (HCV). MAIN METHODS One hundred sixty consecutive patients chronically infected with HCV were treated at the Hepatitis C outpatient care setting of our hospital from April 2010 to May 2011 and prospectively evaluated. Bioelectrical impedance analysis measurements were performed during the first hospital visit. Biochemical measurements and liver biopsy data were collected from the patients' medical records and included in the analysis only if they were performed within three months of the inclusion of the patient in the study. KEY FINDINGS One hundred sixty consecutive patients were evaluated and 25 patients were excluded. A total of 135 patients with 49.8±11.4years old were studied. Among these patients, 60% were male and the PhA was 6.5±0.8°. Regarding the stage of fibrosis, patients with advanced fibrosis were older and had more insulin resistance and more inflammation compared with patients that had mild fibrosis. Logistic regression analysis revealed that PhA was a predictor of advanced fibrosis even when adjusted for gender, age, HOMA-IR, HDL-cholesterol and AST (OR: 0.227; CI 95%: 0.090-0.569; p: 0.013). The best PhA cut-off points associated with advanced fibrosis for the combined data, for females and for males were 6.43°, 5.94° and 6.72°, respectively. SIGNIFICANCE PhA was predictor of advanced liver fibrosis in patients chronically infected with HCV. In the sample evaluated, for each one-degree decrease in PhA, the risk of advanced fibrosis increased more than four-fold.
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Affiliation(s)
- Mariana de Souza Dorna
- Department of Internal Medicine, Botucatu Medical School, UNESP - Univ Estadual Paulista, Botucatu, Brazil.
| | - Livia Alves Amaral Santos
- Department of Internal Medicine, Botucatu Medical School, UNESP - Univ Estadual Paulista, Botucatu, Brazil
| | - Fernanda Futino Gondo
- Department of Internal Medicine, Botucatu Medical School, UNESP - Univ Estadual Paulista, Botucatu, Brazil
| | - Lais Augusti
- Department of Internal Medicine, Botucatu Medical School, UNESP - Univ Estadual Paulista, Botucatu, Brazil
| | - Letícia de Campos Franzoni
- Department of Internal Medicine, Botucatu Medical School, UNESP - Univ Estadual Paulista, Botucatu, Brazil
| | - Ligia Yukie Sassaki
- Department of Internal Medicine, Botucatu Medical School, UNESP - Univ Estadual Paulista, Botucatu, Brazil
| | - Fernando Gomes Romeiro
- Department of Internal Medicine, Botucatu Medical School, UNESP - Univ Estadual Paulista, Botucatu, Brazil
| | | | - Marcos Ferreira Minicucci
- Department of Internal Medicine, Botucatu Medical School, UNESP - Univ Estadual Paulista, Botucatu, Brazil
| | - Giovanni Faria Silva
- Department of Internal Medicine, Botucatu Medical School, UNESP - Univ Estadual Paulista, Botucatu, Brazil
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Chang ML. Metabolic alterations and hepatitis C: From bench to bedside. World J Gastroenterol 2016; 22:1461-1476. [PMID: 26819514 PMCID: PMC4721980 DOI: 10.3748/wjg.v22.i4.1461] [Citation(s) in RCA: 93] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2015] [Revised: 08/14/2015] [Accepted: 10/26/2015] [Indexed: 02/06/2023] Open
Abstract
In addition to causing cirrhosis and hepatocellular carcinoma, hepatitis C virus (HCV) is thought to cause hypolipidemia, hepatic steatosis, insulin resistance, metabolic syndrome, and diabetes. The viral life cycle of HCV depends on cholesterol metabolism in host cells. HCV core protein and nonstructural protein 5A perturb crucial lipid and glucose pathways, such as the sterol regulatory element-binding protein pathway and the protein kinase B/mammalian target of rapamycin/S6 kinase 1 pathway. Although several lines of transgenic mice expressing core or full HCV proteins exhibit hepatic steatosis and/or dyslipidemia, whether they completely reflect the metabolic alterations in humans with HCV infection remains unknown. Many cross-sectional studies have demonstrated increased prevalences of metabolic alterations and cardiovascular events in patients with chronic hepatitis C (CHC); however, conflicting results exist, primarily due to unavoidable individual variations. Utilizing anti-HCV therapy, most longitudinal cohort studies of CHC patients have demonstrated the favorable effects of viral clearance in attenuating metabolic alterations and cardiovascular risks. To determine the risks of HCV-associated metabolic alterations and associated complications in patients with CHC, it is necessary to adjust for crucial confounders, such as HCV genotype and host baseline glucose metabolism, for a long follow-up period after anti-HCV treatment. Adipose tissue is an important endocrine organ due to its release of adipocytokines, which regulate lipid and glucose metabolism. However, most data on HCV infection and adipocytokine alteration are inconclusive. A comprehensive overview of HCV-associated metabolic and adipocytokine alterations, from bench to bedside, is presented in this topic highlight.
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Gürbüz Y, Tülek NE, Tütüncü EE, Koruk ST, Aygen B, Demirtürk N, Kınıklı S, Kaya A, Yıldırmak T, Süer K, Korkmaz F, Ural O, Akhan S, Günal Ö, Tuna N, Köse Ş, Gönen İ, Örmen B, Türker N, Saltoğlu N, Batırel A, Tuncer G, Bulut C, Sırmatel F, Ulçay A, Karagöz E, Tosun D, Şener A, Aynıoğlu A, Altunok ES. Evaluation of Dual Therapy in Real Life Setting in Treatment-Naïve Turkish Patients with HCV Infection: A Multicenter, Retrospective Study. Balkan Med J 2016; 33:18-26. [PMID: 26966614 PMCID: PMC4767305 DOI: 10.5152/balkanmedj.2015.15859] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2015] [Accepted: 09/30/2015] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Before the introduction of direct-acting antivirals in the treatment of chronic hepatitis C patients, the combination of peginterferon alpha and ribavirin was the standard therapy. Observational studies that investigated sustained virological response (SVR) rates by these drugs yielded different outcomes. AIMS The goal of the study was to demonstrate real life data concerning SVR rate achieved by peginterferon alpha plus ribavirin in patients who were treatment-naïve. STUDY DESIGN A multicenter, retrospective observational study. METHODS The study was conducted retrospectively on 1214 treatment naïve-patients, being treated with peginterferon alpha-2a or 2b plus ribavirin in respect of the current guidelines between 2005 and 2013. The patients' data were collected from 22 centers via a standard form, which has been prepared for this study. The data included demographic and clinical characteristics (gender, age, body weight, initial Hepatitis C virus RNA (HCV RNA) level, disease staging) as well as course of treatment (duration of treatment, outcomes, discontinuations and adverse events). Renal insufficiency, decompensated liver disease, history of transplantation, immunosuppressive therapy or autoimmune liver disease were exclusion criteria for the study. Treatment efficacy was assessed according to the patient's demographic characteristics, baseline viral load, genotype, and fibrosis scores. RESULTS The mean age of the patients was 50.74 (±0.64) years. Most of them were infected with genotype 1 (91.8%). SVR was achieved in 761 (62.7%) patients. SVR rate was 59.1% in genotype 1, 89.4% in genotype 2, 93.8% in genotype 3, and 33.3% in genotype 4 patients. Patients with lower viral load yielded higher SVR (65.8% vs. 58.4%, p=0.09). SVR rates according to histologic severity were found to be 69.3%, 66.3%, 59.9%, 47.3%, and 45.5% in patients with fibrosis stage 0, 1, 2, 3 and 4, respectively. The predictors of SVR were male gender, genotype 2/3, age less than 45 years, low fibrosis stage, low baseline viral load and presence of early virological response. SVR rates to each peginterferon were found to be similar in genotype 1/4 although SVR rates were found to be higher for peginterferon alpha-2b in patients with genotype 2/3. The number of patients who failed to complete treatment due to adverse effects was 33 (2.7%). The number of patients failed to complete treatment due to adverse effects was 33 (2.7%). CONCLUSION Our findings showed that the rate of SVR to dual therapy was higher in treatment-naïve Turkish patients than that reported in randomized controlled trials. Also peginterferon alpha-2a and alpha-2b were found to be similar in terms of SVR in genotype 1 patients.
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Affiliation(s)
- Yunus Gürbüz
- Department of Infectious Diseases and Clinical Microbiology, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Ankara, Turkey
| | - Necla Eren Tülek
- Department of Infectious Diseases and Clinical Microbiology, Ankara Training and Research Hospital, Ankara, Turkey
| | - Emin Ediz Tütüncü
- Department of Infectious Diseases and Clinical Microbiology, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Ankara, Turkey
| | - Süda Tekin Koruk
- Department of Infectious Diseases and Clinical Microbiology, Harran University Faculty of Medicine, Şanlıurfa, Turkey
| | - Bilgehan Aygen
- Department of Infectious Diseases and Clinical Microbiology, Erciyes University Faculty of Medicine, Kayseri, Turkey
| | - Neşe Demirtürk
- Department of Infectious Diseases and Clinical Microbiology, Afyon Kocatepe University Faculty of Medicine, Afyonkarahisar, Turkey
| | - Sami Kınıklı
- Department of Infectious Diseases and Clinical Microbiology, Ankara Training and Research Hospital, Ankara, Turkey
| | - Ali Kaya
- Department of Infectious Diseases and Clinical Microbiology, Mersin University Faculty of Medicine, Mersin, Turkey
| | - Taner Yıldırmak
- Department of Infectious Diseases and Clinical Microbiology, Okmeydanı Training and Research Hospital, İstanbul, Turkey
| | - Kaya Süer
- Department of Infectious Diseases and Clinical Microbiology, Near East University Faculty of Medicine, Nicosia, North Cyprus
| | - Fatime Korkmaz
- Department of Infectious Diseases and Clinical Microbiology, Konya Training and Research Hospital, Konya, Turkey
| | - Onur Ural
- Department of Infectious Diseases and Clinical Microbiology, Selçuk University Faculty of Medicine, Konya, Turkey
| | - Sıla Akhan
- Department of Infectious Diseases and Clinical Microbiology, Kocaeli University Faculty of Medicine, Kocaeli, Turkey
| | - Özgür Günal
- Department of Infectious Diseases and Clinical Microbiology, Gaziosmanpaşa University Faculty of Medicine, Tokat, Turkey
| | - Nazan Tuna
- Department of Infectious Diseases and Clinical Microbiology, Sakarya University Faculty of Medicine, Sakarya, Turkey
| | - Şükran Köse
- Department of Infectious Diseases and Clinical Microbiology, Tepecik Training and Research Hospital, İzmir, Turkey
| | - İbak Gönen
- Department of Infectious Diseases and Clinical Microbiology, Süleyman Demirel University Faculty of Medicine, Isparta, Turkey
| | - Bahar Örmen
- Department of Infectious Diseases and Clinical Microbiology, İzmir Katip Çelebi University Atatürk Training and Research Hospital, İzmir, Turkey
| | - Nesrin Türker
- Department of Infectious Diseases and Clinical Microbiology, İzmir Katip Çelebi University Atatürk Training and Research Hospital, İzmir, Turkey
| | - Neşe Saltoğlu
- Department of Infectious Diseases and Clinical Microbiology, İstanbul University Cerrahpaşa Faculty of Medicine, İstanbul, Turkey
| | - Ayşe Batırel
- Department of Infectious Diseases and Clinical Microbiology, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul, Turkey
| | - Günay Tuncer
- Department of Infectious Diseases and Clinical Microbiology, Ankara Training and Research Hospital, Ankara, Turkey
| | - Cemal Bulut
- Department of Infectious Diseases and Clinical Microbiology, Ankara Training and Research Hospital, Ankara, Turkey
| | - Fatma Sırmatel
- Department of Infectious Diseases and Clinical Microbiology, Abant İzzet Baysal University Faculty of Medicine, Bolu, Turkey
| | - Asım Ulçay
- Department of Infectious Diseases and Clinical Microbiology, GATA Haydarpaşa Training and Research Hospital, İstanbul, Turkey
| | - Ergenekon Karagöz
- Department of Infectious Diseases and Clinical Microbiology, GATA Haydarpaşa Training and Research Hospital, İstanbul, Turkey
| | - Derviş Tosun
- Department of Infectious Diseases and Clinical Microbiology, Ulus State Hospital, Ankara, Turkey
| | - Alper Şener
- Department of Infectious Diseases and Clinical Microbiology, Çanakkale Onsekiz Mart University Faculty of Medicine, Çanakkale, Turkey
| | - Aynur Aynıoğlu
- Department of Infectious Diseases and Clinical Microbiology, Kocaeli University Faculty of Medicine, Kocaeli, Turkey
| | - Elif Sargın Altunok
- Department of Infectious Diseases and Clinical Microbiology, Kocaeli University Faculty of Medicine, Kocaeli, Turkey
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Huang JF, Yeh ML, Yu ML, Huang CF, Dai CY, Hsieh MY, Hsieh MH, Huang CI, Lin ZY, Chen SC, Hsiao PJ, Shin SJ, Chuang WL. Hyperuricemia Inversely Correlates with Disease Severity in Taiwanese Nonalcoholic Steatohepatitis Patients. PLoS One 2015; 10:e0139796. [PMID: 26441244 PMCID: PMC4595446 DOI: 10.1371/journal.pone.0139796] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2015] [Accepted: 09/16/2015] [Indexed: 02/07/2023] Open
Abstract
Background & Aims Asians are more susceptible to non-alcoholic steatohepatitis (NASH) as well as metabolic disorder than other ethnicities. We aimed to assess the interaction between metabolic factors and fibrosis in Taiwanese NASH patients. Methods A total of 130 biopsy-proven Taiwanese NASH patients (94 males, age = 43.0 ± 13.0 years) were consecutively enrolled. Their demographic, metabolic profiles and histopathological manifestations were analyzed. Results Twenty-four (18.5%) NASH patients were non-obese. Thirty-three (25.4%) patients had significant fibrosis (F2) or more: 22 (16.9%) patients were of F2, whilst 11 (8.5%) patients were of advanced fibrosis (F3-4). The prevalence of metabolic syndrome, diabetes and hypertension were 60.8%, 39.4%, and 61.5%, respectively. There was a significant inverse correlation between hyperuricemia and fibrosis stages, ranging from 48.4% of F0-1, 33.3% of F2, and 9.1% of F3-4, respectively (P = 0.01, linear trend). Multivariate logistic regression analysis showed that a decreased serum albumin level (OR = 40.0, 95% CI = 4.5–300, P = 0.001) and normal uric acid level (OR = 5.6, 95% CI = 1.5–21.7, P = 0.01) were the significant factors associated with significant fibrosis. Conclusions Hyperuricemia inversely predicts fibrosis stages. Females might carry a more disease severity than males in Taiwanese NASH patients.
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Affiliation(s)
- Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Yen Hsieh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Meng-Hsuan Hsieh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ching-I Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Zu-Yau Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shinn-Chern Chen
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Pi-Jung Hsiao
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Endocrine Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Shyi-Jang Shin
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Endocrine Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- * E-mail: ;
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Yeh ML, Hsieh MY, Huang CI, Huang CF, Hsieh MH, Liang PC, Lin YH, Hou NJ, Lin ZY, Chen SC, Huang JF, Dai CY, Chuang WL, Yu ML. Personalized Therapy of Chronic Hepatitis C and B Dually Infected Patients With Pegylated Interferon Plus Ribavirin: A Randomized Study. Medicine (Baltimore) 2015; 94:e1837. [PMID: 26496327 PMCID: PMC4620800 DOI: 10.1097/md.0000000000001837] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2015] [Revised: 09/19/2015] [Accepted: 09/23/2015] [Indexed: 12/18/2022] Open
Abstract
We aimed to investigate whether response-guided therapy (RGT) with peginterferon-alpha plus ribavirin by using hepatitis C virus (HCV) genotype, pretreatment HCV RNA levels, and rapid virological response (RVR, undetectable HCV RNA at treatment week 4) could be applied for active HCV/hepatitis B virus (HBV) dually infected patients, without compromised the treatment efficacy.A total of 203 patients, seropositive of HCV antibody, HCV RNA and HBV surface antigen (HBsAg), and seronegative for HBV e antigen for >6 months, were randomized to receive peginterferon-alpha/ribavirin by either genotype-guided therapy (GGT, n = 102: HCV genotype 1 [HCV-1], 48 weeks; HCV-2/3, 24 weeks) or RGT (n = 101: HCV-1, 48 or 24 weeks if patients with baseline VL <400,000 IU/mL and RVR; HCV-2/3, 24 or 16 weeks if patients with RVR). The primary endpoint was HCV-sustained virological response (SVR).The HCV SVR rate was comparable between the GGT (77.5%, 79/102) and RGT groups (70.3%, 71/101, P = 0.267), either among HCV-1/HBV (69.4% [43/62] vs 63.5% [40/63], P = 0.571) or among HCV-2/3/HBV (90.0% [36/40] vs 81.6% [31/38], P = 0.342) dually infected patients based on intention-to-treat analysis. In HCV-1/HBV dually infected patients, RVR (odds ratio [OR]: 6.05; 95% confidence intervals [CI]: 2.148-17.025, P = 0.001) and lower pretreatment blood glucose levels (OR: 0.97; CI: 0.944-0.989, P = 0.003) were independent predictors of HCV SVR. Although RVR (OR: 10.68; CI: 1.948-58.514, P = 0.006) was the only significant factor associated with HCV SVR in HCV-2/3/HBV dually infected patients. HBsAg loss at 1 year posttreatment was observed in 17 of 185 (9.2%) patients. The rates of discontinuation and adverse events were similar between the 2 groups.RGT with peginterferon-alpha/RBV may be considered for HBeAg-negative HBV/HCV dually infected patients.
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Affiliation(s)
- Ming-Lun Yeh
- From the Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital (M-LYeh, M-YH, C-FH, P-CL, Y-HL, Z-YL, S-CC, J-FH, C-YD, W-LC, M-LYu), Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University (M-LYeh, C-FH, M-HH, Z-YL, S-CC, J-FH, C-YD, W-LC; M-LYu), Institute of Biomedical Sciences, National Sun Yat-Sen University (M-LYu), Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital (C-IH, N-JH), Department of Occupational Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University (C-FH), Department of Preventive Medicine, Kaohsiung Medical University Hospital (M-HH), Graduate Institute of Medicine, College of Medicine (M-LYeh, C-YD), Center for Infectious Disease and Cancer Research; and Center for Lipid Science and Aging Research, Kaohsiung Medical University, Kaohsiung, Taiwan (C-YD, W-LC, M-LYu)
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Chien CH, Lin CL, Hu CC, Chang JJ, Chien RN. Clearance of Hepatitis C Virus Improves Insulin Resistance During and After Peginterferon and Ribavirin Therapy. J Interferon Cytokine Res 2015; 35:981-9. [PMID: 26308911 DOI: 10.1089/jir.2014.0200] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Patients with chronic hepatitis C virus (HCV) infection are at a greater risk of developing insulin resistance (IR). However, little is known about when insulin sensitivity may improve during or after treatment for hepatitis C. In this study, we examined the effect of combination therapy with pegylated interferon-α and ribavirin on IR in patients with chronic HCV infection. We also analyzed factors associated with changes in insulin sensitivity. IR was estimated by homeostasis model assessment (HOMA-IR). HOMA-IR was measured before therapy, during therapy (12 and 24 weeks), and at the end of therapy (EOT; 24 or 48 weeks). We analyzed 78 HCV patients receiving combination therapy. Twenty-two patients (28.2%) exhibited pretreatment IR (HOMA-IR >2.5). In all patients, HOMA-IR was not significantly different from baseline values at 12 weeks (P = 0.823), 24 weeks (P = 0.417), or at EOT (P = 0.158). In patients with pretreatment IR, a significant decrease in HOMA-IR was observed at 12 weeks (P = 0.023), 24 weeks (P = 0.008), and at EOT (P = 0.002). Multivariate analysis using a logistic regression model showed that baseline HOMA-IR is the only factor associated with the decline in HOMA-IR during and after therapy. The eradication of HCV infection was associated with improved insulin sensitivity among patients with pretreatment IR. This significant improvement in insulin sensitivity may occur as early as 12 weeks after the initiation of antiviral therapy.
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Affiliation(s)
- Cheng-Hung Chien
- Liver Research Unit, College of Medicine, Chang Gung Memorial Hospital, Chang Gung University , Keelung, Taiwan
| | - Chih-Lang Lin
- Liver Research Unit, College of Medicine, Chang Gung Memorial Hospital, Chang Gung University , Keelung, Taiwan
| | - Ching-Chih Hu
- Liver Research Unit, College of Medicine, Chang Gung Memorial Hospital, Chang Gung University , Keelung, Taiwan
| | - Jia-Jang Chang
- Liver Research Unit, College of Medicine, Chang Gung Memorial Hospital, Chang Gung University , Keelung, Taiwan
| | - Rong-Nan Chien
- Liver Research Unit, College of Medicine, Chang Gung Memorial Hospital, Chang Gung University , Keelung, Taiwan
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Naing C, Sitt T, Aung AT, Aung K. Sustained Virologic Response to a Dual Peginterferon alfa-2a and Ribavirin in Treating Chronic hepatitis C Infection: A Retrospective Cohort Study. Medicine (Baltimore) 2015; 94:e1234. [PMID: 26222859 PMCID: PMC4554122 DOI: 10.1097/md.0000000000001234] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
In Myanmar, hepatitis C virus (HCV) infection prevalence is 2%. A combination therapy of pegylated interferon alfa-2a and ribavirin (PEG-IFNa/RBV) is a standard treatment, but the effect of this antiviral therapy needs evaluation as to determine the efficacy and safety of dual PEG-IFNa/RBV therapy in treating patients infected with HCV in Myanmar.This was a retrospective analysis of data from a single clinic exclusively for gastrointestinal diseases in Yangon, Myanmar. We assessed treatment responses at the defined time points and stratified by genotypes of HCV. We also determined incidences of adverse events (AEs). We investigated independent predictors of sustained virologic response (SVR) in the participants.A total of 362 HCV-infected cases were included in this study. The majority were females (51.7%) with mean age of 47.12 years (±11.6) and noncirrhosis patients (82%). Rapid virologic response (RVR), early virologic response (EVR), end of treatment response (ETR), and SVR 24 weeks after completion of the dual treatment were 50.3% (178/362), 88% (314/357), 80.1% (286/357), and 85.6% (167/195), respectively. The most frequently reported AEs were nausea/anorexia (72.8%) and flu-like symptoms (62.4%). In multivariate analysis, 4 factors were independently associated with SVR; SVR to genotype 3 (odds ratio [OR] 2.4, 95% CI: 1.24-4.62), EVR (OR 0.54, 95% CI: 0.3-0.95), and duration of treatment (OR 1.52, 95% CI: 1.18-1.98). Study limitations were acknowledged.The efficacy and safety of the dual therapy in treating HCV-infected patient in Myanmar was acceptable. We recommend a prospective randomized control trial looking at duration of therapy and rates of achieving SVR, which could significantly impact the care of HCV-infected patients in Myanmar and perhaps other countries as well.
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Affiliation(s)
- Cho Naing
- From the Institute for Research, Development and Innovation (IRDI), International Medical University (IMU), Kuala Lumpur, Malaysia (CN); Option Endoscopy Centre (OEC) Specialist Clinic, Yangon, Myanmar (TS, ATA); and School of Medicine, IMU, Kuala Lumpur, Malaysia (KA)
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Warriner AH, Burkholder GA, Overton ET. HIV-related metabolic comorbidities in the current ART era. Infect Dis Clin North Am 2015; 28:457-76. [PMID: 25151566 DOI: 10.1016/j.idc.2014.05.003] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Despite effective antiretroviral therapy (ART), HIV-infected individuals have residual chronic immune activation that contributes to the pathogenesis of HIV infection. This immune system dysregulation is a pathogenic state manifested by very low naïve T-cell numbers and increased terminally differentiated effector cells that generate excessive proinflammatory cytokines with limited functionality. Immune exhaustion leaves an individual at risk for accelerated aging-related diseases, including renal dysfunction, atherosclerosis, diabetes mellitus, and osteoporosis. We highlight research that clarifies the role of HIV, ART, and other factors that contribute to the development of these diseases among HIV-infected persons.
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Affiliation(s)
- Amy H Warriner
- Department of Medicine, University of Alabama at Birmingham School of Medicine, 908 20th Street South, CCB Room 330A, Birmingham, AL 35294, USA
| | - Greer A Burkholder
- Department of Medicine, University of Alabama at Birmingham School of Medicine, 908 20th Street South, CCB Room 330A, Birmingham, AL 35294, USA
| | - Edgar Turner Overton
- Department of Medicine, University of Alabama at Birmingham School of Medicine, 908 20th Street South, CCB Room 330A, Birmingham, AL 35294, USA.
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Hsu YC, Wu CY, Lin JT. Hepatitis C Virus Infection, Antiviral Therapy, and Risk of Hepatocellular Carcinoma. Semin Oncol 2015; 42:329-38. [PMID: 25843737 DOI: 10.1053/j.seminoncol.2014.12.023] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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Abstract
The efficacy of antiviral treatment depends on which of the seven genotypes (G1-G7) of hepatitis C virus (HCV) has infected the patient. Conventionally, clinicians regarded G2 and G3 infections as 'easy-to-treat': dual therapy with pegylated interferon and ribavirin produces a sustained virologic response in approximately 40-50% of patients with G1 infection, compared with 80% when analyses report combined data for G2 and G3 patients, which is standard practice in many clinical studies. However, sustained virologic response rates appear to be lower in certain subgroups of people infected with G3 compared with those with G2 or the general HCV-infected population. This review examines the growing evidence that factors related to the virus (e.g., baseline viral load and a rapid virologic response) and host characteristics (e.g., steatosis and fibrosis, metabolic syndrome, host polymorphisms and ethnicity) contribute to variations in therapeutic success in G3 HCV.
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Affiliation(s)
- Maria Buti
- Liver Unit, Hospital Universitario Valle Hebron and Ciberehd del Instituto, Carlos III Paseo Valle Hebron 119, Barcelona 08035, Spain
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Abd El-Wahab EW, Mikheal A, Sidkey F, Shatat HZ. Insulin resistance as a predictor of early virologic response to HCV therapy among chronic HCV Egyptian patients. J Med Virol 2015; 87:428-40. [PMID: 25583244 DOI: 10.1002/jmv.24092] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/01/2014] [Indexed: 12/19/2022]
Abstract
Prior assessment of insulin resistance by HOMA-IR is emerging as an important milestone in the treatment of patients with chronic hepatitis C. This cost-effective tool is recommended to individualize treatment duration, or to exclude those with low insulin sensitivity from being treated until ameliorating their state of insulin resistance (IR). The present work aims to elucidate further the effect IR state on early viral kinetic response to Chronic hepatitis C virus (HCV) therapy and the impact of HCV treatment and viral eradication on insulin sensitivity. Insulin sensitivity was assessed using the HOMA-IR method. All enrolled patients were treated with a dual therapy (pegylated interferon-alpha plus ribavirin) for 48 weeks and evaluated using qRT-PCR for early virologic response as well as the impact of treatment on insulin sensitivity throughout the early period of therapy. Of a total 392 chronic HCV cases, early virologic response was achieved by 318 (81.1%). IR was detected in 241 (61.5%) chronic HCV patient of which 73.4% responded to treatment. Early virologic response among patients with > 2.18 HOMA-IR value were significantly lower than those with HOMA-IR values ≤2.18 (P < 0.0001). IR was significantly associated with high baseline BMI. Steatosis and fibrosis correlated with IR but neither independently predicted early virologic response. Pretreatment IR < 2.18, low fasting blood glucose, low and intermediate HCV viral load, normal BMI, and non-smoking were independent factors associated with early virologic response. IR interferes with early virologic response to the antiviral care. Clinical application of pretreatment HOMA-IR assessment could help in predicting early treatment outcome and thus enable treatment regimens to be optimized and individually tailored.
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Affiliation(s)
- Ekram W Abd El-Wahab
- Tropical Health Department, High Institute of Public Health, Alexandria University, Egypt
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