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Giannini EG, Mangia A, Morisco F, Toniutto P, Avogaro A, Fagiuoli S, Borghi C, Frigerio F, Nugnes M, Veronesi C, Cappuccilli M, Andretta M, Bacca M, Barbieri A, Bartolini F, Chinellato G, Ciaccia A, Lombardi R, Mancini D, Pagliaro R, Ubertazzo L, Degli Esposti L, Ponziani FR. A Real-World Analysis of the Population with Hepatitis C Virus Infection Affected by Type 2 Diabetes in Italy: Patients' Characteristics, Comorbidity Profiles and Treatment Patterns. MEDICINA (KAUNAS, LITHUANIA) 2025; 61:614. [PMID: 40282905 PMCID: PMC12028345 DOI: 10.3390/medicina61040614] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/28/2025] [Revised: 03/23/2025] [Accepted: 03/24/2025] [Indexed: 04/29/2025]
Abstract
Background and Objectives: HCV infection represents a main risk factor for type 2 diabetes (T2D). This real-world analysis investigated the HCV-positive (HCV+) population with a T2D co-diagnosis in Italy. Methods: From 2017 to 2021, HCV+ patients were identified from administrative databases and stratified into T2D-HCV+ and HCV+-only cohorts in the presence/absence of a T2D diagnosis. Both cohorts were further divided by treatment with direct-acting antivirals (DAAs). The subgroups were compared for demographic variables, comorbidity profiles, most frequent hospitalizations, and drug prescriptions before inclusion. A sensitivity analysis was performed on patients included after 2019, the year of widespread use of pangenotypic DAAs. Results: Considering HCV+ patients aged ≥55 years, T2D-HCV+ patients (N = 1277) were significantly (p < 0.001) older than HCV+-only (N = 6576) ones and burdened by a worse comorbidity profile (average Charlson index: 1.4 vs. 0.3, p < 0.05). Moreover, regardless of T2D presence, DAA-treated patients were older (p < 0.001) and had a worse Charlson index than the untreated ones. T2D-HCV+ patients showed tendentially higher hospitalization rates and co-medication prescriptions compared to the HCV+-only patients. After 2019, a trend towards reduced co-medication use in DAA-treated patients was noticed, especially antibiotics and cardiovascular drugs. Conclusions: The co-presence of T2D in HCV+ patients resulted in a worse clinical status, as confirmed by the more frequent requirement of hospitalizations and complex polypharmacy regimens.
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Affiliation(s)
| | - Alessandra Mangia
- Liver Unit, Department of Medical Sciences, Fondazione “Casa Sollievo della Sofferenza” IRCCS, 71013 San Giovanni Rotondo, Italy;
| | - Filomena Morisco
- Gastroenterology Unit, Department of Clinical Medicine and Surgery, University of Naples “Federico II”, 80138 Naples, Italy;
| | - Pierluigi Toniutto
- Hepatology and Liver Transplantation Unit, University of Udine, 33100 Udine, Italy;
| | - Angelo Avogaro
- Department of Medicine, Section of Diabetes and Metabolic Diseases, University of Padova, 35128 Padua, Italy;
| | - Stefano Fagiuoli
- Gastroenterology Hepatology and Transplantation Unit, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy;
- Gastroenterology, Department of Medicine, University of Milan Bicocca, 20126 Milan, Italy
| | - Claudio Borghi
- Department of Medical and Surgical Sciences, IRCCS AOU S. Orsola di Bologna, 40138 Bologna, Italy;
| | | | - Marta Nugnes
- CliCon S.r.l. Società Benefit, Health, Economics & Outcomes Research, 40137 Bologna, Italy; (M.N.); (C.V.); (M.C.); (L.D.E.)
| | - Chiara Veronesi
- CliCon S.r.l. Società Benefit, Health, Economics & Outcomes Research, 40137 Bologna, Italy; (M.N.); (C.V.); (M.C.); (L.D.E.)
| | - Maria Cappuccilli
- CliCon S.r.l. Società Benefit, Health, Economics & Outcomes Research, 40137 Bologna, Italy; (M.N.); (C.V.); (M.C.); (L.D.E.)
| | - Margherita Andretta
- UOC Assistenza Farmaceutica Territoriale, Azienda ULSS 8 Berica, 36100 Vicenza, Italy; (M.A.); (G.C.)
| | - Marcello Bacca
- Programmazione e Controllo di Gestione, ASL Brindisi, 72100 Brindisi, Italy;
| | - Antonella Barbieri
- SC Farmaceutica Territoriale, Azienda Sanitaria Locale di Vercelli (ASL VC), 13100 Vercelli, Italy;
| | - Fausto Bartolini
- Dipartimento Farmaceutico USL Umbria 2, Coordinatore della Cabina di Regia Regione Umbria Sulla Governance Farmaceutica, 05100 Terni, Italy;
| | - Gianmarco Chinellato
- UOC Assistenza Farmaceutica Territoriale, Azienda ULSS 8 Berica, 36100 Vicenza, Italy; (M.A.); (G.C.)
| | - Andrea Ciaccia
- Servizio Farmaceutico Territoriale, ASL Foggia, 71100 Foggia, Italy; (A.C.); (R.L.)
| | - Renato Lombardi
- Servizio Farmaceutico Territoriale, ASL Foggia, 71100 Foggia, Italy; (A.C.); (R.L.)
| | - Daniela Mancini
- UOSD Pianificazione Acquisti Farmaci e Beni Sanitari, ASL Brindisi, 72100 Brindisi, Italy;
| | - Romina Pagliaro
- UOC Farmaceutica Territoriale, Azienda Sanitaria Locale Roma 5, 00019 Tivoli, Italy;
| | | | - Luca Degli Esposti
- CliCon S.r.l. Società Benefit, Health, Economics & Outcomes Research, 40137 Bologna, Italy; (M.N.); (C.V.); (M.C.); (L.D.E.)
| | - Francesca Romana Ponziani
- Liver Unit, CEMAD-Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
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Chang CW, Hsu WF, Tseng KC, Chen CY, Cheng PN, Hung CH, Lo CC, Bair MJ, Chen CH, Lee PL, Lin CY, Kuo HT, Chen CT, Yang CC, Huang JF, Tai CM, Hu JT, Lin CL, Su WW, Tsai WL, Huang YH, Cheng CY, Lin CL, Wang CC, Yang SS, Mo LR, Chen GY, Chang CC, Wang SJ, Huang CS, Hsieh TY, Lin CW, Lee TH, Chong LW, Huang CW, Chang SN, Tsai MC, Hsu SJ, Kao JH, Liu CJ, Liu CH, Lin HC, Tsai PC, Yeh ML, Huang CF, Dai CY, Chuang WL, Yu ML, Peng CY. Benefits of Hepatitis C Viral Eradication: A Real-World Nationwide Cohort Study in Taiwan. Dig Dis Sci 2024; 69:3501-3512. [PMID: 38965159 DOI: 10.1007/s10620-024-08512-8] [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: 04/02/2024] [Accepted: 05/25/2024] [Indexed: 07/06/2024]
Abstract
BACKGROUND Chronic hepatitis C (CHC) increases the risk of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). This nationwide cohort study assessed the effectiveness of viral eradication of CHC. METHODS The Taiwanese chronic hepatitis C cohort and Taiwan hepatitis C virus (HCV) registry are nationwide HCV registry cohorts incorporating data from 23 and 53 hospitals in Taiwan, respectively. This study included 27,577 individuals from these cohorts that were given a diagnosis of CHC and with data linked to the Taiwan National Health Insurance Research Database. Patients received either pegylated interferon and ribavirin or direct-acting antiviral agent therapy for > 4 weeks for new-onset LC and liver-related events. RESULTS Among the 27,577 analyzed patients, 25,461 (92.3%) achieved sustained virologic response (SVR). The mean follow-up duration was 51.2 ± 48.4 months, totaling 118,567 person-years. In the multivariable Cox proportional hazard analysis, the hazard ratio (HR) for incident HCC was 1.39 (95% confidence interval [CI]: 1.00-1.95, p = 0.052) among noncirrhotic patients without SVR compared with those with SVR and 1.82 (95% CI 1.34-2.48) among cirrhotic patients without SVR. The HR for liver-related events, including HCC and decompensated LC, was 1.70 (95% CI 1.30-2.24) among cirrhotic patients without SVR. Patients with SVR had a lower 10-year cumulative incidence of new-onset HCC than those without SVR did (21.7 vs. 38.7% in patients with LC, p < 0.001; 6.0 vs. 18.4% in patients without LC, p < 0.001). CONCLUSION HCV eradication reduced the incidence of HCC in patients with and without LC and reduced the incidence of liver-related events in patients with LC.
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Affiliation(s)
- Chin-Wei Chang
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, 40447, Taichung, Taiwan
| | - Wei-Fan Hsu
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, 40447, Taichung, Taiwan
- Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan
- School of Chinese Medicine, China Medical University, Taichung, Taiwan
| | - Kuo-Chih Tseng
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
| | - Chi-Yi Chen
- Division of Gastroenterology and Hepatology, Department of Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan
| | - Pin-Nan Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Ching-Chu Lo
- Division of Gastroenterology, Department of Internal Medicine, St Martin De Porres Hospital, Chiayi, Taiwan
| | - Ming-Jong Bair
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan
| | - Chien-Hung Chen
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Pei-Lun Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Liouying, Tainan, Taiwan
| | - Chun-Yen Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, New Taipei City, Taiwan
| | - Hsing-Tao Kuo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan
- School of Medicine, College of Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | - Chun-Ting Chen
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital Penghu Branch, National Defense Medical Center, Taipei, Taiwan
| | - Chi-Chieh Yang
- Department of Gastroenterology, Division of Internal Medicine, Show Chwan Memorial Hospital, Changhua, Taiwan
| | - Jee-Fu Huang
- 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
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Chi-Ming Tai
- School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Jui-Ting Hu
- Liver Center, Cathay General Hospital, Taipei, Taiwan
| | - Chih-Lang Lin
- Liver Research Unit, Department of Hepato-Gastroenterology and Community Medicine Research Center, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Wei-Wen Su
- Department of Gastroenterology and Hepatology, Changhua Christian Hospital, Changhua, Taiwan
| | - Wei-Lun Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Chien-Yu Cheng
- Division of Infectious Diseases, Department of Internal Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan
| | - Chih-Lin Lin
- Department of Gastroenterology, Renai Branch, Taipei City Hospital, Taipei, Taiwan
| | - Chia-Chi Wang
- Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Taipei, Taiwan
| | - Sheng-Shun Yang
- Division of Gastroenterology & Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Lein-Ray Mo
- Division of Gastroenterology, Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation), Tainan, Taiwan
| | - Guei-Ying Chen
- Penghu Hospital, Ministry of Health and Welfare, Magong City, Taiwan
| | - Chun-Chao Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan
| | - Szu-Jen Wang
- Division of Gastroenterology, Department of Internal Medicine, Yuan's General Hospital, Kaohsiung, Taiwan
| | - Chia-Sheng Huang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yang Ming Hospital, Chiayi, Taiwan
| | - Tsai-Yuan Hsieh
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chih-Wen Lin
- School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Tzong-Hsi Lee
- Division of Gastroenterology and Hepatology, Far Eastern Memorial Hospital, Taipei, Taiwan
| | - Lee-Won Chong
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
| | - Chien-Wei Huang
- Division of Gastroenterology, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan
| | | | - Ming-Chang Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Shih-Jer Hsu
- Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan
| | - Jia-Horng Kao
- Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan
| | - Chun-Jen Liu
- Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan
| | - Chen-Hua Liu
- Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Pei-Chien Tsai
- 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
| | - Ming-Lun Yeh
- 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
| | - Chung-Feng Huang
- 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
| | - Chia-Yen Dai
- 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
| | - Wan-Long Chuang
- 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
| | - 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.
| | - Cheng-Yuan Peng
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, 40447, Taichung, Taiwan.
- School of Medicine, China Medical University, Taichung, Taiwan.
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Pascual-Oliver A, Casas-Deza D, Yagüe-Caballero C, Arbones-Mainar JM, Bernal-Monterde V. Lipid Profile and Cardiovascular Risk Modification after Hepatitis C Virus Eradication. Pathogens 2024; 13:278. [PMID: 38668233 PMCID: PMC11054742 DOI: 10.3390/pathogens13040278] [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: 02/05/2024] [Revised: 03/18/2024] [Accepted: 03/21/2024] [Indexed: 04/29/2024] Open
Abstract
The eradication of the hepatitis C virus (HCV) has revolutionized the hepatology paradigm, halting the progression of advanced liver disease in patients with chronic infection and reducing the risk of hepatocarcinoma. In addition, treatment with direct-acting antivirals can reverse the lipid and carbohydrate abnormalities described in HCV patients. Although HCV eradication may reduce the overall risk of vascular events, it is uncertain whether altered lipid profiles increase the risk of cerebrovascular disease in certain patients. We have conducted a review on HCV and lipid and carbohydrate metabolism, as well as new scientific advances, following the advent of direct-acting antivirals.
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Affiliation(s)
- Andrea Pascual-Oliver
- Gastroenterology Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain; (A.P.-O.); (C.Y.-C.); (V.B.-M.)
| | - Diego Casas-Deza
- Gastroenterology Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain; (A.P.-O.); (C.Y.-C.); (V.B.-M.)
- Adipocyte and Fat Biology Laboratory (AdipoFat), Translational Research Unit, University Hospital Miguel Servet, 50009 Zaragoza, Spain;
- Instituto Aragones de Ciencias de la Salud (IACS), 50009 Zaragoza, Spain
- Instituto de Investigación Sanitaria (IIS) Aragon, 50009 Zaragoza, Spain
| | - Carmen Yagüe-Caballero
- Gastroenterology Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain; (A.P.-O.); (C.Y.-C.); (V.B.-M.)
- Adipocyte and Fat Biology Laboratory (AdipoFat), Translational Research Unit, University Hospital Miguel Servet, 50009 Zaragoza, Spain;
- Instituto de Investigación Sanitaria (IIS) Aragon, 50009 Zaragoza, Spain
| | - Jose M. Arbones-Mainar
- Adipocyte and Fat Biology Laboratory (AdipoFat), Translational Research Unit, University Hospital Miguel Servet, 50009 Zaragoza, Spain;
- Instituto Aragones de Ciencias de la Salud (IACS), 50009 Zaragoza, Spain
- Instituto de Investigación Sanitaria (IIS) Aragon, 50009 Zaragoza, Spain
- CIBER Fisiopatología Obesidad y Nutrición (CIBERObn), Instituto Salud Carlos III, 28029 Madrid, Spain
| | - Vanesa Bernal-Monterde
- Gastroenterology Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain; (A.P.-O.); (C.Y.-C.); (V.B.-M.)
- Adipocyte and Fat Biology Laboratory (AdipoFat), Translational Research Unit, University Hospital Miguel Servet, 50009 Zaragoza, Spain;
- Instituto Aragones de Ciencias de la Salud (IACS), 50009 Zaragoza, Spain
- Instituto de Investigación Sanitaria (IIS) Aragon, 50009 Zaragoza, Spain
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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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Abdel-Tawab MS, Mohamed MG, Doudar NA, Rateb EE, Reyad HR, Elazeem NAA. Circulating hsa-miR-221 as a possible diagnostic and prognostic biomarker of diabetic nephropathy. Mol Biol Rep 2023; 50:9793-9803. [PMID: 37831346 PMCID: PMC10676308 DOI: 10.1007/s11033-023-08846-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Accepted: 09/26/2023] [Indexed: 10/14/2023]
Abstract
BACKGROUND Diabetic nephropathy (DN), which is a chronic outcome of diabetes mellitus (DM), usually progresses to end-stage renal disease (ESRD). The DN pathophysiology, nevertheless, is not well-defined. Several miRNAs were reported to be either risk or protective factors in DN. METHODS, AND RESULTS The present study sought to inspect the potential diagnostic and prognostic value of hsa-miR-221 in DN. The study included 200 participants divided into four groups: Group 1 (50 patients with DN), Group 2 (50 diabetic patients without nephropathy), Group 3 (50 nondiabetic patients with CKD), and Group 4 (50 healthy subjects as a control group). Patients in groups 1 and 3 were further classified based on the presence of macroalbuminuria and microalbuminuria. Hsa-miR-221 expression was measured by RT- qRT-PCR. DN patients had significantly elevated serum hsa-miR-221 levels than the other groups, while diabetic patients without nephropathy exhibited elevated levels compared to both nondiabetic patients with CKD, and the control group. The DN patients with macroalbuminuria revealed significantly higher mean values of hsa-miR-221 relative to the patients with microalbuminuria. Significant positive associations were observed in the DN group between serum hsa-miR-221 and fasting insulin, fasting glucose, HOMA IR, ACR, and BMI. The ROC curve analysis of serum hsa-miR-221 in the initial diagnosis of DN in DM revealed high specificity and sensitivity. CONCLUSIONS It is concluded that hsa-miR-221 has the potential to be a useful biomarker for prognostic and diagnostic purposes in DN.
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Affiliation(s)
- Marwa Sayed Abdel-Tawab
- Medical Biochemistry Department, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt.
| | - Mohamed Gamal Mohamed
- Internal Medicine Department, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt
| | - Noha A Doudar
- Clinical and Chemical Pathology Department, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt
| | - Enas Ezzat Rateb
- Physiology Department, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt
| | - Hoda Ramadan Reyad
- Medical Biochemistry Department, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt
| | - Naglaa Adli Abd Elazeem
- Medical Biochemistry Department, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt
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Mkrtumyan AM, Markova TN, Ovchinnikova MA, Ivanova IA, Kuzmenko KV. Metformin as an activator of AMP-activated protein kinase. Known and new mechanisms of action. DIABETES MELLITUS 2023; 26:585-595. [DOI: 10.14341/dm13044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Metformin, known in the medical community as the drug of first choice for type 2 diabetes mellitus, belongs to the group of biguanides and has proven to be an effective treatment in clinical practice. Our knowledge of the pharmacodynamic properties of metformin has long been limited to the following well-known mechanisms: a decrease in hyperglycemia due to an increase in peripheral insulin sensitivity, glucose utilization by cells, inhibition of hepatic gluconeogenesis, an increase in the capacity of all types of membrane glucose transporters, activation of fibrinolysis, and a decrease in the levels of atherogenic lipoproteins. Recent studies show that the range of positive pleiotropic effects of metformin is not limited to the above, and that the molecular mechanisms of its action are more complex than previously thought. This article presents a less known, but equally important action of metformin, in particular, its anti-oncogenic, antiviral, and anti-aging effects. In our study, we highlight that the activation of 5’-adenosine monophosphate-activated protein kinase (AMPK) should be considered as the primary mechanism of action through which almost all beneficial effects are achieved. In the light of recent scientific advances in metformin pharmacology, together with the pathogenetic uncertainty of the term «biguanide», it seems fair and reasonable to apply a more relevant definition to the drugn, namely «AMPK activator».
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Affiliation(s)
- A. M. Mkrtumyan
- A.I. Yevdokimov Moscow State University of Medicine and Dentistry
| | - T. N. Markova
- A.I. Yevdokimov Moscow State University of Medicine and Dentistry;
Moscow City Clinical Hospital № 52
| | | | - I. A. Ivanova
- A.I. Yevdokimov Moscow State University of Medicine and Dentistry
| | - K. V. Kuzmenko
- A.I. Yevdokimov Moscow State University of Medicine and Dentistry
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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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Lynch EN, Russo FP. Outcomes and Follow-Up after Hepatitis C Eradication with Direct-Acting Antivirals. J Clin Med 2023; 12:2195. [PMID: 36983196 PMCID: PMC10056757 DOI: 10.3390/jcm12062195] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 02/27/2023] [Accepted: 03/10/2023] [Indexed: 03/15/2023] Open
Abstract
Treatment of hepatitis C (HCV) has been revolutionized with the introduction of direct-acting antivirals (DAAs). Patients can be treated at more advanced stages of liver disease, with a growing number of cirrhotic patients achieving sustained virological response (SVR). Long-term outcomes for cured patients and the optimal follow-up care of patients after SVR are yet to be defined, because most studies on cirrhotic patients cured with DAAs have a short follow-up period. There are many open questions related to patient management after viral eradication with DAAs, such as which could be the most reliable non-invasive tool to predict liver-related complications, or to what extent viral eradication reduces the risk of liver disease progression in the long term. Growing evidence supports the personalization of follow-up care based on individual risk. The aim of this narrative review is to analyze the impact of viral eradication with DAAs on clinically significant portal hypertension, hepatocellular carcinoma, and extrahepatic manifestations, as well as to summarize indications for optimal follow-up care of HCV patients treated with DAAs.
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Affiliation(s)
- Erica Nicola Lynch
- Department of Surgery, Oncology and Gastroenterology, University of Padua, 35122 Padova, Italy
- Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, 50134 Florence, Italy
| | - Francesco Paolo Russo
- Department of Surgery, Oncology and Gastroenterology, University of Padua, 35122 Padova, Italy
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9
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Rajsfus BF, Mohana-Borges R, Allonso D. Diabetogenic viruses: linking viruses to diabetes mellitus. Heliyon 2023; 9:e15021. [PMID: 37064445 PMCID: PMC10102442 DOI: 10.1016/j.heliyon.2023.e15021] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 03/23/2023] [Accepted: 03/24/2023] [Indexed: 03/31/2023] Open
Abstract
Diabetes Mellitus (DM) is a group of chronic metabolic diseases distinguished by elevated glycemia due to the alterations in insulin metabolism. DM is one of the most relevant diseases of the modern world, with high incidence and prevalence worldwide, associated with severe systemic complications and increased morbidity and mortality rates. Although genetic factors and lifestyle habits are two of the main factors involved in DM onset, viral infections, such as enteroviruses, cytomegalovirus, hepatitis C virus, human immunodeficiency virus, severe acute respiratory syndrome coronavirus 2, among others, have been linked as triggers of type 1 (T1DM) and type 2 (T2DM) diabetes. Over the years, various groups identified different mechanisms as to how viruses can promote these metabolic syndromes. However, this field is still poorly explored and needs further research, as millions of people live with these pathologies. Thus, this review aims to ex-plore the different processes of how viruses can induce DM and their contribution to the prevalence and incidence of DM worldwide.
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10
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Hsieh YY, Chen WM, Chang KC, Chang TS, Hung CH, Yang YH, Tung SY, Wei KL, Shen CH, Wu CS, Ding YJ, Hu JH, Huang YT, Lin MH, Lu CK, Lin YH, Lin MS. Direct-Acting Antivirals Reduce the De Novo Development of Esophageal Varices in Patients with Hepatitis C Virus Related Liver Cirrhosis. Viruses 2023; 15:252. [PMID: 36680293 PMCID: PMC9860555 DOI: 10.3390/v15010252] [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: 11/19/2022] [Revised: 01/09/2023] [Accepted: 01/12/2023] [Indexed: 01/18/2023] Open
Abstract
The real-world benefits of direct-acting antiviral (DAA)-induced sustained virologic response (SVR) on the de novo occurrence and progression of esophageal varices (EV) remain unclear in patients with hepatitis C virus (HCV)-related liver cirrhosis (LC). This is a retrospective cohort study evaluating all patients with Child-Pugh class A HCV-related LC during 2013 to 2020 in the Chang Gung Medical System. A total of 215 patients fit the inclusion criteria and were enrolled. Of them, 132 (61.4%) patients achieved DAA induced-SVR and 83 (38.6%) did not receive anti-viral treatment. During a median follow-up of 18.4 (interquartile range, 10.1−30.9) months, the 2-year incidence of de novo EV occurrence was 8 (7.0%) in the SVR group and 7 (12.7%) in the treatment-naïve group. Compared to the treatment-naïve group, the SVR group was associated with a significantly lower incidence of EV occurrence (adjusted hazard ratio [aHR]: 0.47, p = 0.030) and a significantly lower incidence of EV progression (aHR: 0.55, p = 0.033). The risk of EV progression was strongly correlated with the presence of baseline EV (p < 0.001). To the best of our knowledge, this is the first study to demonstrate that DAA-induced SVR is associated with decreased risk of de novo EV occurrence and progression in the real world.
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Affiliation(s)
- Yung-Yu Hsieh
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi 613016, Taiwan
- College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan
| | - Wei-Ming Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi 613016, Taiwan
- College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan
| | - Kao-Chi Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi 613016, Taiwan
- College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan
| | - Te-Sheng Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi 613016, Taiwan
- College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan
| | - Chao-Hung Hung
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi 613016, Taiwan
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833253, Taiwan
| | - Yao-Hsu Yang
- Health Information and Epidemiology Laboratory, Chang Gung Memorial Hospital, Chiayi 613016, Taiwan
- Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Chiayi 613016, Taiwan
- School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
| | - Shui-Yi Tung
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi 613016, Taiwan
- College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan
| | - Kuo-Liang Wei
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi 613016, Taiwan
- College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan
| | - Chen-Heng Shen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi 613016, Taiwan
| | - Cheng-Shyong Wu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi 613016, Taiwan
| | - Yuan-Jie Ding
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi 613016, Taiwan
| | - Jing-Hong Hu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Yunlin 638502, Taiwan
| | - Yu-Ting Huang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi 613016, Taiwan
| | - Meng-Hung Lin
- Health Information and Epidemiology Laboratory, Chang Gung Memorial Hospital, Chiayi 613016, Taiwan
| | - Chung-Kuang Lu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi 613016, Taiwan
| | - Yi-Hsiung Lin
- Graduate Institute of Education, Taiwan Shoufu University, Tainan 72153, Taiwan
| | - Ming-Shyan Lin
- Department of Cardiology, Chang Gung Memorial Hospital, Chiayi 613016, Taiwan
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11
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Angel M, Petrosyan Y, Doyle MA, Cooper C. HCV infection characteristics, treatment uptake and outcomes in patient with diabetes mellitus. BMC Endocr Disord 2022; 22:277. [PMID: 36371200 PMCID: PMC9652941 DOI: 10.1186/s12902-022-01198-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Accepted: 11/03/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND The interplay between HCV, DM, and DAA therapy is poorly understood. We compared HCV infection characteristics, treatment uptake, and treatment outcomes in patients with and without DM. METHODS: A retrospective cohort study was conducted using data from The Ottawa Hospital Viral Hepatitis Program. Statistical comparisons between diabetes and non-diabetes were made using χ2 and t-tests. Logistic regression analyses were performed to assess predictors of DM and SVR. RESULTS One thousand five hundred eighty-eight HCV patients were included in this analysis; 9.6% had DM. Patients with DM were older and more likely to have cirrhosis. HCC and chronic renal disease were more prevalent in the DM group. Treatment uptake and SVR were comparable between groups. Regression analysis revealed that age and employment were associated with achieving SVR. Post-SVR HCC was higher in DM group. CONCLUSION The high prevalence of DM in our HCV cohort supports screening. Further assessment is required to determine if targeted, early DAA treatment reduces DM onset, progression to cirrhosis and HCC risk. Further studies are needed to determine if optimization of glycemic control in this population can lead to improved liver outcomes.
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Affiliation(s)
- Marina Angel
- Ottawa Hospital Research Institute, G12-501 Smyth Road, Ottawa, ON, K1H 8L6, Canada
| | - Yelena Petrosyan
- Ottawa Hospital Research Institute, G12-501 Smyth Road, Ottawa, ON, K1H 8L6, Canada
| | - Mary-Anne Doyle
- Ottawa Hospital Research Institute, G12-501 Smyth Road, Ottawa, ON, K1H 8L6, Canada
- Department of Medicine, University of Ottawa, Ottawa, ON, K1H 8L6, Canada
| | - Curtis Cooper
- Ottawa Hospital Research Institute, G12-501 Smyth Road, Ottawa, ON, K1H 8L6, Canada.
- Department of Medicine, University of Ottawa, Ottawa, ON, K1H 8L6, Canada.
- School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, K1G 5Z3, Canada.
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12
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Chang SS, Hu HY, Chen YC, Yen YF, Huang N. Late hepatitis C virus diagnosis among patients with newly diagnosed hepatocellular carcinoma: a case–control study. BMC Gastroenterol 2022; 22:425. [PMID: 36115934 PMCID: PMC9482748 DOI: 10.1186/s12876-022-02504-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Accepted: 09/13/2022] [Indexed: 12/09/2022] Open
Abstract
Abstract
Background
New direct-acting antiviral therapies have revolutionized hepatitis C virus (HCV) infection therapy. Nonetheless, once liver cirrhosis is established, the risk of hepatocellular carcinoma (HCC) still exists despite virus eradication. Late HCV diagnosis hinders timely access to HCV treatment. Thus, we determined trends and risk factors associated with late HCV among patients with a diagnosis of HCC in Taiwan.
Methods
We conducted a population-based unmatched case–control study. 2008–2018 Claims data were derived from the Taiwan National Health Insurance Research Database. Individuals with an initial occurrence of liver cancer between 2012 and 2018 were included. The late HCV group were referred as individuals who were diagnosed with HCC within 3 years after HCV diagnosis. The control group were referred as individuals who were diagnosed more than 3 years after the index date. We used multivariable logistic models to explore individual- and provider-level risk factors associated with a late HCV diagnosis.
Results
A decreasing trend was observed in the prevalence of late HCV-related HCC diagnosis between 2012 and 2018 in Taiwan. On an individual level, male, elderly patients, patients with diabetes mellitus (DM), and patients with alcohol-related disease had significantly higher risks of late HCV-related HCC diagnosis. On a provider level, patients who were mainly cared for by male physicians, internists and family medicine physicians had a significantly lower risk of late diagnosis.
Conclusions
Elderly and patients who have DM and alcohol related disease should receive early HCV screening. In addition to comorbidities, physician factors also matter. HCV screening strategies shall take these higher risk patients and physician factors into consideration to avoid missing opportunities for early intervention.
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13
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Popescu MS, Firu DM, Pădureanu V, Mărginean CM, Mitruț R, Arsene AL, Mărgăritescu DN, Calina D, Docea AO, Mitruț P. Effects of Achieving Sustained Virologic Response after Direct-Acting Antiviral Agents on Long-Term Liver Fibrosis in Diabetics vs. in Non-Diabetic Patients with Chronic Hepatitis C Infection. Biomedicines 2022; 10:2093. [PMID: 36140194 PMCID: PMC9495608 DOI: 10.3390/biomedicines10092093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 08/22/2022] [Accepted: 08/24/2022] [Indexed: 12/15/2022] Open
Abstract
Because of the prevalence of HCV worldwide as well as its undiagnosed population due to a lack of screening, HCV can be considered a modern pandemic disease. In 2016, the World Health Organization (WHO) set goals for HCV's elimination that included a 65 percent reduction in mortality and an 80 percent reduction in newly infected cases by 2030. This study is a follow-up evaluation of 80 patients who received interferon-free treatment with direct-acting agents (DAA) for chronic HCV infection between the second half of 2017 and the end of 2018. They were assessed using a FibroMax test prior to DAA administration. Two pills/day of Ombitasvir 12.5 mg/Paritaprevir 75 mg/Ritonavir 50 mg and two pills/day of Dasabuvir 250 mg were given to the patients for 8 weeks. After treatment, all 80 patients in this study achieved an SVR (sustained virologic response), and the FibroMax test was performed three years later. Our study found that successfully treating HCV infection can play a significant role in reducing fibrosis in T2DM patients. In comparison to those of ActiTest and SteatoTest, FibroMax scores showed a significantly greater reduction in T2DM patients than in treatment-naive patients.
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Affiliation(s)
- Marian-Sorin Popescu
- Department of Medical Semiology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Dan-Mihai Firu
- Department of Medical Semiology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Vlad Pădureanu
- Department of Medical Semiology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Cristina Maria Mărginean
- Department of Medical Semiology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Radu Mitruț
- Department of Cardiology, University and Emergency Hospital, 050098 Bucharest, Romania
| | - Andreea Letitia Arsene
- Department of Microbiology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | | | - Daniela Calina
- Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Anca Oana Docea
- Department of Toxicology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Paul Mitruț
- Department of Medical Semiology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
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14
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Bacinschi X, Mercan-Stanciu A, Toma L, Zgura A, Bacalbasa N, Ifrim CP, Diaconu C, Iliescu L, Toma RV. Glycemic Control in Patients Undergoing Treatment With Paritaprevir/Ombitasvir/Ritonavir and Dasabuvir for Chronic Hepatitis C Infection. In Vivo 2022; 36:1438-1443. [PMID: 35478152 PMCID: PMC9087075 DOI: 10.21873/invivo.12849] [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: 03/18/2022] [Revised: 04/07/2022] [Accepted: 04/08/2022] [Indexed: 11/10/2022]
Abstract
BACKGROUND/AIM Patients with hepatitis C virus (HCV)-associated cirrhosis are more prone to developing type 2 diabetes mellitus than patients with any other etiology of cirrhosis. The main objective of this study was to evaluate the impact of all oral antiviral treatment with ritonavir-boosted paritaprevir/ombitasvir and dasabuvir (OBV/PTV/r + DSV) in patients with chronic genotype 1b HCV infection. PATIENTS AND METHODS We retrospectively evaluated 806 patients who underwent antiviral therapy between December 2015 and July 2019. The laboratory data analyzed were liver function tests, kidney function tests, HCV viremia, fasting glucose levels, and glycosylated hemoglobin. RESULTS Patients with impaired glucose metabolism were predominantly male and of older age compared to patients with normal glucose tolerance, and also had higher levels of transaminases. Proteinuria and higher creatinine levels were found in patients with impaired glucose metabolism. Overall, we found a 98.01% rate of sustained virologic response (SVR), with a non-significant difference between patients with normal and abnormal glucose metabolism. A statistically significant difference in SVR rates in patients with low degrees of fibrosis (F0-F2) versus those with advanced degrees of fibrosis (F3-F4) was found in both groups. Antiviral treatment resulted in significant decreases in fasting glucose levels and glycosylated hemoglobin levels in all patients with impaired glucose metabolism at SVR. CONCLUSION Patients with pre-diabetes, as well as diabetic patients, achieved a better glycemic control after SVR obtained by ritonavir-boosted paritaprevir/ombitasvir and dasabuvir.
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Affiliation(s)
- Xenia Bacinschi
- Department of Oncology-Radiotherapy, Prof. Dr. Alexandru Trestioreanu Institute of Oncology, Bucharest, Romania
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Adriana Mercan-Stanciu
- Department of Oncology-Radiotherapy, Prof. Dr. Alexandru Trestioreanu Institute of Oncology, Bucharest, Romania
| | - Letitia Toma
- Department of Oncology-Radiotherapy, Prof. Dr. Alexandru Trestioreanu Institute of Oncology, Bucharest, Romania
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Anca Zgura
- Department of Oncology-Radiotherapy, Prof. Dr. Alexandru Trestioreanu Institute of Oncology, Bucharest, Romania;
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Nicolae Bacalbasa
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Chen-Peng Ifrim
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Camelia Diaconu
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Department of Internal Medicine II, Fundeni Clinical Institute, Bucharest, Romania
| | - Laura Iliescu
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Department of Internal Medicine II, Fundeni Clinical Institute, Bucharest, Romania
| | - Radu Valeriu Toma
- Department of Oncology-Radiotherapy, Prof. Dr. Alexandru Trestioreanu Institute of Oncology, Bucharest, Romania
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
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15
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Ciardullo S, Mantovani A, Ciaccio A, Carbone M, Invernizzi P, Perseghin G. Hepatitis C virus infection and diabetes: A complex bidirectional relationship. Diabetes Res Clin Pract 2022; 187:109870. [PMID: 35398458 DOI: 10.1016/j.diabres.2022.109870] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Revised: 03/22/2022] [Accepted: 04/04/2022] [Indexed: 11/03/2022]
Abstract
Chronic hepatitis C (CHC) and diabetes represent two severe chronic conditions responsible for a considerable number of deaths worldwide. They have a complex, bidirectional relationship. On the one hand, several cohort studies have shown that chronic HCV infection increases both the risk of developing diabetes in non-diabetic subjects (by inducing insulin resistance and promoting β-cell dysfunction) as well as the risk of developing macro and microvascular complications in patients with known diabetes; on the other hand, diabetes is an independent risk factor for liver-related events among patients with CHC, including a higher incidence of hepatocellular carcinoma, liver-related death and transplantation. Importantly, sustained virological response, which can be obtained in the vast majority of patients with the use of direct antiviral agents, does not only lead to a lower rate of liver-related outcomes, but also to improvements of glycemic control and reduction in the rate of complications among patients with diabetes. The aim of this review is to summarize available clinical evidence on the association among CHC, diabetes and related clinical outcomes. We will also briefly discuss the biological mechanisms underpinning the association between CHC and diabetes, as well as the implications this relationship should have on everyday clinical practice.
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Affiliation(s)
- Stefano Ciardullo
- Department of Medicine and Rehabilitation, Monza Policlinico di Monza, Monza, Italy; Department of Medicine and Surgery, University of Milan Bicocca, Monza, Italy.
| | - Alessandro Mantovani
- Section of Endocrinology, Diabetes and Metabolic Diseases, Department of Medicine, University of Verona
| | - Antonio Ciaccio
- Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy
| | - Marco Carbone
- Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy
| | - Pietro Invernizzi
- Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy
| | - Gianluca Perseghin
- Department of Medicine and Rehabilitation, Monza Policlinico di Monza, Monza, Italy; Department of Medicine and Surgery, University of Milan Bicocca, Monza, Italy
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16
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Wang X, Xie Q. Metabolic Dysfunction-associated Fatty Liver Disease (MAFLD) and Viral Hepatitis. J Clin Transl Hepatol 2022; 10:128-133. [PMID: 35233381 PMCID: PMC8845159 DOI: 10.14218/jcth.2021.00200] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Revised: 08/19/2021] [Accepted: 09/07/2021] [Indexed: 12/04/2022] Open
Abstract
A new definition of metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed in 2020. The change from nonalcoholic fatty liver disease (NAFLD) to MAFLD highlights the metabolic abnormalities that accompany fatty liver. The diagnosis of MAFLD does not require exclusion of secondary causes of liver diseases and alcohol consumption. Thus, MAFLD may coexist with other types of liver diseases, such as viral hepatitis, a disease that remains the most common cause of liver disease-related death. With the increasing prevalence of MAFLD, patients with coincidental MAFLD and viral hepatitis are frequently encountered in clinical practice. In this review, we mainly summarize the mutual relationship between hepatitis B/C and systematic metabolism dysfunction related to MAFLD. We discuss the impact of MAFLD on progression of viral hepatitis and the therapies. Some unaddressed clinical problems related to concomitant MAFLD and viral hepatitis are also identified.
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Affiliation(s)
- Xiaolin Wang
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qing Xie
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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17
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Freekh DA, Helmy MW, Said M, El-Khodary NM. The effect of direct acting antiviral agents on vascular endothelial function in Egyptian patients with chronic hepatitis C virus infection. Saudi Pharm J 2021; 29:1120-1128. [PMID: 34703365 PMCID: PMC8523355 DOI: 10.1016/j.jsps.2021.08.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Accepted: 08/01/2021] [Indexed: 02/07/2023] Open
Abstract
Chronic hepatitis C virus (HCV) infection is correlated with cerebrovascular and cardiovascular disease (CVD). This study aimed to assess the effect of treatment with DAAs on vascular endothelial function in cirrhotic and non-cirrhotic HCV infected patients without any CVD risk factors. Fifty chronic HCV genotype 4 infected patients, without cardiovascular risks who have been listed to receive sofosbuvir/daclatasvir with ribavirin combination as triple therapy for 3 months were prospectively recruited. Endothelial dysfunction markers as soluble vascular cell adhesion molecule-1 (sVCAM-1) and Von willebrand factor (vWf) and inflammation marker (IL6) were estimated at baseline and 3 months post the end of therapy (SVR). All patients achieved SVR. VCAM1 level was significantly improved after HCV clearance with DAA in cirrhotic HCV patients (P = 0.002) compared to patients with mild liver fibrosis (P = 0.006). Levels of vWF also decreased significantly in cirrhosis and non-cirrhosis groups after SVR (P < 0.001 and P = 0.011, respectively). Systemic inflammatory marker (IL6) showed significant decrease in cirrhotic patients (P = 0.001). While, IL6 level did not change significantly in non-cirrhotic group (P = 0.061). Also at SVR, noninvasive liver fibrosis indices have been reduced significantly in the two groups (P < 0.001). HCV clearance by new DAA treatment improves the vascular endothelial dysfunction in Egyptian HCV infected patients with different levels of liver fibrosis and with no risk factors for endothelial dysfunction or CVD.
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Affiliation(s)
- Dalia A Freekh
- Clinical Pharmacy & Pharmacy Practice Department, Faculty of Pharmacy, Damanhour University, Damanhour City, Egypt
| | - Maged W Helmy
- Professor of Pharmacology & Toxicology, Pharmacology & Toxicology Department, Faculty of Pharmacy, Damanhour University, Damanhour City, Egypt
| | - Mohamed Said
- Professor of Endemic Medicine & Hepatology, Endemic Medicine & Hepatology Department, Cairo University, Cairo City, Egypt
| | - Noha M El-Khodary
- Lecturer of Clinical Pharmacy, Clinical Pharmacy & Pharmacy Practice Department, Faculty of Pharmacy, Damanhour University, Damanhour City, Egypt
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18
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Ahumada A, Rayón L, Usón C, Bañares R, Alonso Lopez S. Hepatocellular carcinoma risk after viral response in hepatitis C virus-advanced fibrosis: Who to screen and for how long? World J Gastroenterol 2021; 27:6737-6749. [PMID: 34790004 PMCID: PMC8567476 DOI: 10.3748/wjg.v27.i40.6737] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2021] [Revised: 06/24/2021] [Accepted: 09/19/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) chronic infection is associated with fibrosis progression, end-stage liver complications and HCC. Not surprisingly, HCV infection is a leading cause of liver-related morbidity and mortality worldwide. After sustained virological response (SVR), the risk of developing hepatocellular carcinoma is not completely eliminated in patients with established cirrhosis or with advanced fibrosis. Therefore, lifelong surveillance is currently recommended. This strategy is likely not universally cost-effective and harmless, considering that not all patients with advanced fibrosis have the same risk of developing HCC. Factors related to the severity of liver disease and its potential to improve after SVR, the molecular and epigenetic changes that occur during infection and other associated comorbidities might account for different risk levels and are likely essential for identifying patients who would benefit from screening programs after SVR. Efforts to develop predictive models and risk calculators, biomarkers and genetic panels and even deep learning models to estimate the individual risk of HCC have been made in the direct-acting antiviral agents era, when thousands of patients with advanced fibrosis and cirrhosis have reached SVR. These tools could help to identify patients with very low HCC risk in whom surveillance might not be justified. In this review, factors affecting the probability of HCC development after SVR, the benefits and risks of surveillance, suggested strategies to estimate individualized HCC risk and the current evidence to recommend lifelong surveillance are discussed.
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Affiliation(s)
- Adriana Ahumada
- Liver Unit, Hospital General Universitario Gregorio Marañón, Madrid 28007, Spain
- Liver Unit, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid 28007, Spain
| | - Laura Rayón
- Liver Unit, Hospital General Universitario Gregorio Marañón, Madrid 28007, Spain
| | - Clara Usón
- Liver Unit, Hospital General Universitario Gregorio Marañón, Madrid 28007, Spain
| | - Rafael Bañares
- Liver Unit, Hospital General Universitario Gregorio Marañón, Madrid 28007, Spain
- Liver Unit, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid 28007, Spain
- Medicine, Universidad Complutense de Madrid, Madrid 28006, Spain
- Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid 28029, Spain
| | - Sonia Alonso Lopez
- Liver Unit, Hospital General Universitario Gregorio Marañón, Madrid 28007, Spain
- Liver Unit, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid 28007, Spain
- Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid 28029, Spain
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Siphepho PY, Liu YT, Shabangu CS, Huang JF, Huang CF, Yeh ML, Yu ML, Wang SC. The Impact of Steatosis on Chronic Hepatitis C Progression and Response to Antiviral Treatments. Biomedicines 2021; 9:1491. [PMID: 34680608 PMCID: PMC8533513 DOI: 10.3390/biomedicines9101491] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 10/12/2021] [Accepted: 10/13/2021] [Indexed: 02/07/2023] Open
Abstract
Metabolic derangement is characteristic in patients with hepatitis C virus (HCV) infection. Aside from established liver injury, various extrahepatic metabolic disorders impact the natural history of the disease, clinical outcomes, and the efficacy of antiviral therapy. The presence of steatosis, recently redefined as metabolic-associated fatty liver disease (MAFLD), is a common feature in HCV-infected patients, induced by host and/or viral factors. Most chronic HCV-infected (CHC) patients have mild steatosis within the periportal region of the liver with an estimated prevalence of 40% to 86%. Indeed, this is higher than the 19% to 50% prevalence observed in patients with other chronic liver diseases such as chronic hepatitis B (CHB). The histological manifestations of HCV infection are frequently observed in genotype 3 (G-3), where relative to other genotypes, the prevalence and severity of steatosis is also increased. Steatosis may independently influence the treatment efficacy of either interferon-based or interferon-free antiviral regimens. This review aimed to provide updated evidence of the prevalence and risk factors behind HCV-associated steatosis, as well as explore the impact of steatosis on HCV-related outcomes.
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Affiliation(s)
- Phumelele Yvonne Siphepho
- Program in Tropical Medicine, Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (P.Y.S.); (M.-L.Y.)
- Center for Cancer Research, Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.S.S.); (J.-F.H.)
| | - Yi-Ting Liu
- Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan;
| | - Ciniso Sylvester Shabangu
- Center for Cancer Research, Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.S.S.); (J.-F.H.)
- Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Jee-Fu Huang
- Center for Cancer Research, Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.S.S.); (J.-F.H.)
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-F.H.); (M.-L.Y.)
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Hepatitis Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-F.H.); (M.-L.Y.)
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Hepatitis Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-F.H.); (M.-L.Y.)
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Hepatitis Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Ming-Lung Yu
- Program in Tropical Medicine, Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (P.Y.S.); (M.-L.Y.)
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-F.H.); (M.-L.Y.)
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Hepatitis Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Shu-Chi Wang
- Center for Cancer Research, Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.S.S.); (J.-F.H.)
- Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan;
- Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan
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Hepatitis C Virus Clearance by Direct-Acting Antivirals Agents Improves Endothelial Dysfunction and Subclinical Atherosclerosis: HEPCAR Study. Clin Transl Gastroenterol 2021; 11:e00203. [PMID: 32955194 PMCID: PMC7431267 DOI: 10.14309/ctg.0000000000000203] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
INTRODUCTION Hepatitis C virus (HCV) infection has been related to increased cardiovascular (CV) risk. The aim of this study was to analyze the impact of sustained virological response (SVR) on endothelial dysfunction and subclinical atherosclerosis in patients with hepatitis C virus treated with direct-acting antiviral agents. METHODS A total of 114 patients were prospectively recruited and underwent CV risk assessment including (i) endothelial dysfunction determined through laser Doppler flowmetry and (ii) subclinical atherosclerosis, elucidated by the ankle-brachial index (ABI). Atherogenic lipid profile (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides); markers of oxidative stress (oxidized low-density lipoprotein antibodies [OLAbs]), soluble markers of adhesion (vascular cell adhesion molecule [VCAM], e-selectin, and soluble markers of angiogenesis; and vascular endothelial growth factor, endothelial [EMPs] and platelet [PMPs] apoptotic microparticles, and cell-free DNA [cfDNA]) were measured. All determinations were performed at baseline, 12 weeks (SVR time), and 1 year after treatment. RESULTS In patients with endothelial dysfunction, area of hyperemia improved after virus clearance (P = 0.013) and was related to significant decrease in VCAM, e-selectin (P < 0.001), and cfDNA (P = 0.017) and to increased OLAb levels (P = 0.001). In patients with subclinical atherosclerosis at baseline, a significantly improved ABI was seen after HCV clearance (P < 0.001). Levels of both EMPs and PMPs also decreased after SVR and at follow-up (P = 0.006 and P = 0.002, respectively). DISCUSSION HCV clearance improved not only liver function but also endothelial dysfunction and subclinical atherosclerosis promoted by decrease in levels of VCAM, e-selectin, cfDNA, and PMPs and EMPs.
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21
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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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Takahashi H, Nakahara T, Kogiso T, Imajo K, Kessoku T, Kawaguchi T, Ide T, Kawanaka M, Hyogo H, Fujii H, Ono M, Kamada Y, Sumida Y, Anzai K, Shimizu M, Torimura T, Nakajima A, Tokushige K, Chayama K, Eguchi Y. Eradication of hepatitis C virus with direct-acting antivirals improves glycemic control in diabetes: A multicenter study. JGH OPEN 2020; 5:228-234. [PMID: 33553660 PMCID: PMC7857302 DOI: 10.1002/jgh3.12474] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/10/2020] [Revised: 11/29/2020] [Accepted: 11/30/2020] [Indexed: 12/19/2022]
Abstract
Background and Aim Hepatitis C virus (HCV) infection causes insulin resistance and diabetes as extrahepatic manifestations. We aimed to analyze the effect of HCV eradication by direct‐acting antiviral (DAA) agents on glucose tolerance. Methods The hemoglobin A1c (HbA1c) of 272 patients with HCV infection who achieved a sustained virologic response (SVR) was analyzed at baseline before DAA treatment, at the end of DAA therapy (ETR), and 12 weeks after therapy (Post12W). Results There were no significant differences in HbA1c between baseline, ETR, and Post12W in the overall patients. When the data were stratified according to the presence or absence of diabetes, median HbA1c significantly decreased from baseline (7.2%) to ETR (6.8%) and Post12W (6.8%) in the 55 patients with diabetes, whereas there were no significant changes in the patients without diabetes. Basal HbA1c, fasting plasma glucose, and age were independently associated with the changes in HbA1c according to multivariate analysis, and the predictive formula for changes in HbA1c was found to be ΔHbA1c (%) = 1.449–0.4* HbA1c (%) + 0.012 × Age (year). There were no changes in body mass in diabetic or nondiabetic patients. In diabetic patients taking medication, 63.4% of patients needed less medication. Conclusions Eradication of HCV improves glycemic control, indicated by a 0.4% decrease in HbA1c in diabetes.
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Affiliation(s)
- Hirokazu Takahashi
- Division of Metabolism and Endocrinology, Faculty of Medicine Saga University Saga Japan.,Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences Hiroshima University Hiroshima Japan
| | - Takashi Nakahara
- Department of Internal Medicine and Gastroenterology Tokyo Women's Medical University Tokyo Japan
| | - Tomomi Kogiso
- Department of Gastroenterology and Hepatology Yokohama City University Graduate School of Medicine Yokohama Japan
| | - Kento Imajo
- Division of Gastroenterology, Department of Medicine Kurume University School of Medicine Kurume Japan
| | - Takaomi Kessoku
- Division of Gastroenterology, Department of Medicine Kurume University School of Medicine Kurume Japan
| | - Takumi Kawaguchi
- Department of General Internal Medicine 2 General Medical Center, Kawasaki Medical School Okayama Japan
| | - Tatsuya Ide
- Department of General Internal Medicine 2 General Medical Center, Kawasaki Medical School Okayama Japan
| | - Miwa Kawanaka
- Department of Gastroenterology and Hepatology JA Hiroshima General Hospital Hiroshima Japan
| | - Hideyuki Hyogo
- Department of Gastroenterology and Hepatology Osaka City Juso Hospital Osaka Japan
| | - Hideki Fujii
- Department of Premier Preventive Medicine Osaka City University Graduate School of Medicine Osaka Japan.,Tokyo Women's Medical University Medical Center East Internal Medicine Tokyo Japan
| | - Masafumi Ono
- Department of Molecular Biochemistry and Clinical Investigation Osaka University Graduate School of Medicine Suita Japan
| | - Yoshihiro Kamada
- Division of Hepatology and Pancreatology, Department of Internal Medicine Aichi Medical University Nagakute Japan
| | - Yoshio Sumida
- Department of Gastroenterology Gifu University Graduate School of Medicine Yanagido Japan
| | - Keizo Anzai
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences Hiroshima University Hiroshima Japan
| | | | - Takuji Torimura
- Department of General Internal Medicine 2 General Medical Center, Kawasaki Medical School Okayama Japan
| | - Atsushi Nakajima
- Division of Gastroenterology, Department of Medicine Kurume University School of Medicine Kurume Japan
| | - Katsutoshi Tokushige
- Department of Gastroenterology and Hepatology Yokohama City University Graduate School of Medicine Yokohama Japan
| | - Kazuaki Chayama
- Department of Internal Medicine and Gastroenterology Tokyo Women's Medical University Tokyo Japan
| | - Yuichiro Eguchi
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences Hiroshima University Hiroshima Japan
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Hsu CS, Liu WL, Li Q, Lowey B, Hertz L, Chao YC, Liang TJ, Chen DS, Kao JH. Hepatitis C virus genotypes 1-3 infections regulate lipogenic signaling and suppress cholesterol biosynthesis in hepatocytes. J Formos Med Assoc 2020; 119:1382-1395. [PMID: 32284164 PMCID: PMC11492201 DOI: 10.1016/j.jfma.2020.03.018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Revised: 03/18/2020] [Accepted: 03/23/2020] [Indexed: 01/14/2023] Open
Abstract
BACKGROUND Patients with different hepatitis C virus (HCV) genotype infections are associated with varying metabolic disorders. Although alteration of lipid metabolism has been confirmed as a virus-induced metabolic derangement in chronic hepatitis C patients, the impact of various HCV genotypes on hepatic cholesterol metabolism remains elusive. In this study, we thus investigated the HCV genotype-specific lipogenic and cholesterol metabolism profiles in an in vitro cell culture system. METHODS We first conducted HCV cell culture system (HCVcc) assays by infecting Huh7.5.1 cells with multiple infection-competent HCV strains, including the genotype 2a JFH1 and JFH1-based intergenotypic recombinants 1b and 3a. We then examined the expression levels of various lipid and cholesterol-related genes. RESULTS The data showed that infection with individual HCV genotypes exerted unique gene expression regulatory effects on lipoproteins and cholesterol metabolism genes. Of note, all HCV strains suppressed cholesterol biosynthesis in hepatocytes through downregulating the expression of HMG-CoA reductase (HMGCR) and farnesyl-diphosphate farnesyltransferase 1 (FDFT1) - two essential enzymes for cholesterol biosynthesis. These HCV-mediated inhibitory effects could be reversed by treatment with sofosbuvir, a pangenotypic NS5B inhibitor. In addition, overexpression of HCV genotype 1b, 2a or 3a core protein significantly suppressed HMGCR mRNA transcription and translation, thus diminished cellular cholesterol biosynthesis. Nonetheless, the core protein had no effect on FDFT1 expression. CONCLUSION Although HCV infection regulates host lipid metabolism in a genotype-specific manner, its inhibition on hepatocellular cholesterogenic gene expression and total cholesterol biosynthesis is a common effect among HCV genotype 1b, 2a and 3a.
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Affiliation(s)
- Ching-Sheng Hsu
- Liver Diseases Research Center, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan; School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien, Taiwan; Division of Gastroenterology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan
| | - Wei-Liang Liu
- National Mosquito-Borne Diseases Control Research Center, National Health Research Institutes, Miaoli, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Qisheng Li
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA
| | - Brianna Lowey
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA
| | - Laura Hertz
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA
| | - You-Chen Chao
- Division of Gastroenterology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan
| | - T Jake Liang
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA
| | - Ding-Shinn Chen
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan; Genomics Research Center, Academia Sinica, Nankang, 11549, Taiwan
| | - Jia-Horng Kao
- National Mosquito-Borne Diseases Control Research Center, National Health Research Institutes, Miaoli, Taiwan; Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Research, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan.
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Russo FP, Zanetto A, Gambato M, Bortoluzzi I, Al Zoairy R, Franceschet E, De Marchi F, Marzi L, Lynch EN, Floreani A, Farinati F, Schaefer B, Burra P, Zoller H, Mega A. Hepatitis C virus eradication with direct-acting antiviral improves insulin resistance. J Viral Hepat 2020; 27:188-194. [PMID: 31596996 DOI: 10.1111/jvh.13215] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Revised: 08/20/2019] [Accepted: 09/01/2019] [Indexed: 12/15/2022]
Abstract
Sustained virological response (SVR) after interferon-based therapy is associated with improvement of insulin resistance (IR) in HCV-infected patients. Few data are available in the direct-acting antivirals (DAAs) era, especially in cirrhotic patients. We prospectively evaluated the long-term effect of DAAs on IR. Patients treated with DAAs between May 2015 and December 2016 in 3 tertiary care centres were recruited. Patients with diabetes were excluded. Biochemical and virological data were collected at baseline, 12/24/48 weeks (W) after the end of therapy (EOT). Presence of IR was defined by a 'homeostasis model assessment index for IR' [HOMA-IR])> 2.5. Liver fibroscan was performed at baseline, at 24/48W after EOT. Hundred and thirty-eight patients were enrolled (mean age 58 years, M/F 85/53, GT1 61%, 68.8% cirrhotic). Sixty-eight patients (94/138) had IR. Patients with IR had significantly higher stiffness than patients without it (23 ± 12 vs 15 ± 8; P < .0001). SVR12 was achieved in 135 (98%) patients, and 124 (90%) patients reached the 48W post-EOT. At this time point, the percentage of patients with IR significantly decreased to 49% (P = 0,01). HOMA-IR was significantly lower than baseline (1.8 vs 3; P < .001), and this was related to a significant reduction of insulin level (11.7 ± 6.3 vs 16.4 ± 8.3). High BMI was associated with a significantly lower probability of achieving a non-IR status at 24W (P = .05) and 48W (P = .03).In conclusion, SVR following DAAs led to a significant reduction of IR, even in patients with cirrhosis. Nevertheless, IR can persist after the achievement of SVR, especially in patients with high BMI.
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Affiliation(s)
- Francesco Paolo Russo
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Alberto Zanetto
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Martina Gambato
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | | | - Ramona Al Zoairy
- Department of Medicine I, Department of Gastroenterology, Hepatology and Endocrinology, Medical University of Innsbruck, Innsbruck, Austria
| | - Enrica Franceschet
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | | | - Luca Marzi
- Division of Gastroenterology, Bolzano Regional Hospital, Bolzano, Italy
| | - Erica Nicola Lynch
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Annarosa Floreani
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Fabio Farinati
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Benedikt Schaefer
- Department of Medicine I, Department of Gastroenterology, Hepatology and Endocrinology, Medical University of Innsbruck, Innsbruck, Austria
| | - Patrizia Burra
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Heinz Zoller
- Department of Medicine I, Department of Gastroenterology, Hepatology and Endocrinology, Medical University of Innsbruck, Innsbruck, Austria
| | - Andrea Mega
- Division of Gastroenterology, Bolzano Regional Hospital, Bolzano, Italy
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Muñoz Díaz HA, Lúquez Mindiola AJ, Gómez Aldana AJ. Fisiopatología de la hepatitis C y diabetes mellitus. Hacia la cura de dos epidemias en el siglo XXI. REVISTA COLOMBIANA DE GASTROENTEROLOGÍA 2019; 34:277-287. [DOI: 10.22516/25007440.322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/01/2024]
Abstract
La infección crónica por virus de la hepatitis C (VHC) y la diabetes mellitus (DM) son dos problemas de salud pública que impactan los sistemas de salud, con una alta carga económica global. La infección por VHC produce manifestaciones hepáticas tales como hepatitis, cirrosis y carcinoma hepatocelular; asimismo, se ha involucrado en la patogénesis de manifestaciones extrahepáticas, entre las cuales se ha asociado con alteraciones metabólicas como la DM. Estudios longitudinales y transversales han reportado mayor incidencia y prevalencia de DM en pacientes con infección crónica por VHC. La DM acelera la progresión histológica y clínica en pacientes con infección crónica por VHC y las complicaciones cardiovasculares. Recientemente se ha avanzado en el tratamiento y la introducción de nuevos medicamentos como los antivirales de acción directa, que mejoran el control glucémico en estos pacientes.
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Todorovska B, Joksimovic N, Caloska-Ivanova V, Dimitrova-Genadieva M, Trajkovska M, Curakova E, Kiprijanovska S, Zafirova-Ivanovska B, Serafimoski V. Factors That Influence the Virological Response in Patients with Chronic Hepatitis C Treated with Pegylated Interferon and Ribavirin. ACTA ACUST UNITED AC 2019; 38:25-33. [PMID: 28593897 DOI: 10.1515/prilozi-2017-0003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
INTRODUCTION The success of the antiviral treatment in patients with chronic hepatitis C depends on the factors related to the virus and the host. The aim of the study is the analysis of the antiviral therapy which is a combination of pegylated interferon and ribavirin, considering various factors that will identify the predictors of the sustained virological response. MATERIAL AND METHODS This retrospective study included 226 patients, divided in two groups. Patients with sustained virological response and patients without sustained virological response were compared in terms of the following factors: genotype, viral load, gender, age, inflammatory and fibrotic changes in the liver, metabolic abnormalities, obesity and fatty liver. RESULTS The rate of the sustained virological response is 83.6%, more frequently in patients with genotype 3, with evidenced statistical significance (90.54%). The factors that significantly contribute to sustained virological response are related to the age (p = 0.0001), genotype (p = 0.002), mode of transmission (p = 0.005), inflammatory changes in the liver (p = 0.028), body mass index (p = 0.022) and insulin resistance (p = 0.039). The high rate of sustained virological response is related to the younger age of the patients which indirectly means short Hepatitis C Virus infection duration, absence of advanced liver disease and lack of significant co-morbid conditions. Single confirmed independent predictors of sustained virological response are the age (OR 0.928, p = 0.0001) and genotype (OR 3.134, p = 0.005). CONCLUSIONS Factors that are related to the virological response are the age, genotype, mode of transmission, inflammatory changes in the liver, body mass index and insulin resistance, but still, independent predictors of sustained virologic response are the age and the genotype.
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Affiliation(s)
- Beti Todorovska
- University Clinic of Gastroenterohepatology, Faculty of Medicine, University "Ss. Cyril and Methodius", Skopje
| | - Nenad Joksimovic
- University Clinic of Gastroenterohepatology, Faculty of Medicine, University "Ss. Cyril and Methodius", Skopje
| | - Viktorija Caloska-Ivanova
- University Clinic of Gastroenterohepatology, Faculty of Medicine, University "Ss. Cyril and Methodius", Skopje
| | | | - Meri Trajkovska
- University Clinic of Gastroenterohepatology, Faculty of Medicine, University "Ss. Cyril and Methodius", Skopje
| | - Elena Curakova
- University Clinic of Gastroenterohepatology, Faculty of Medicine, University "Ss. Cyril and Methodius", Skopje
| | - Sanja Kiprijanovska
- Research Center for Genetic Engineering and Biotechnology "Georgi D. Efremov", Macedonian Academy of Sciences and Arts, Skopje
| | - Beti Zafirova-Ivanovska
- Institute of Epidemiology and Biostatistics, Faculty of Medicine, University "Ss. Cyril and Methodius", Skopje
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Li Y, Wang X, Yu G, Sun H, Lv J, Chi X, Wu R, Gao X, Niu J. The association of hepatitis c virus infection status with serum glucose levels. BMC Gastroenterol 2019; 19:86. [PMID: 31195990 PMCID: PMC6567554 DOI: 10.1186/s12876-019-1003-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2017] [Accepted: 05/29/2019] [Indexed: 12/15/2022] Open
Abstract
Background Hepatitis C virus (HCV) infection is commonly associated with a disturbance of glucose metabolism. However, there have been conflicting reports on whether the clearance of the HCV may be followed by changes of serum blood glucose and insulin resistance. The aim of the present study was to evaluate the impact of HCV and antiviral treatment on serum glucose levels and other glucose metabolism parameters. Methods A retrospective analysis of 306 HCV-infected patients was performed. Fasting serum blood glucose (FBG) levels in these patients were compared with that of 325 healthy individuals. Serum parameters of glucose metabolism were measured in 183 patients with chronic hepatitis C at baseline, at the end of interferon α-2b plus ribavirin treatment, and at 24 weeks post-treatment. Results Patients with HCV infection had significantly higher FBG level than healthy controls (5.57 ± 0.74 vs. 5.11 ± 0.83 mmol/l, P < 0.001). After antiviral treatment, we found a significant reduction in FBG levels regardless of the outcome of treatment. However, after stopping treatment the serum FBG levels were significantly elevated in the sustained virological response (SVR) and non-responder groups, and maintained high level until week 24 post-treatment. In both groups, the levels of serum FBG after 24 weeks post-treatment were still lower than pre-treatment levels. In sustained responders, fasting insulin (P = 0.007), C-peptide (P < 0.001) and HOMA-IR (P < 0.001) significantly decreased, and the insulin sensitivity index (ISI) increased (P < 0.001) at the end of the treatment comparing with pre-treatment levels, while no significant difference was observed in non-responder group. HOMA-β values were increased in both groups at the end of treatment (both P < 0.001). Conclusion The total serum FBG level in HCV infected patients was higher than that in healthy controls. Clearance of HCV was associated with reduced glucose and improved insulin resistance.
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Affiliation(s)
- Yinping Li
- Department of Hepatology, the First hospital of Jilin University, No.71 Xinmin Str, Changchun, 130021, China.,Department of Gastroenterology, Shouguang City People's Hospital, Shouguang, 262700, China
| | - Xiaomei Wang
- Department of Hepatology, the First hospital of Jilin University, No.71 Xinmin Str, Changchun, 130021, China.,Key Laboratory of Zoonosis Research, Ministry Education, Changchun, 130021, China
| | - Ge Yu
- Department of Hepatology, the First hospital of Jilin University, No.71 Xinmin Str, Changchun, 130021, China
| | - Haibo Sun
- Department of Hepatology, the First hospital of Jilin University, No.71 Xinmin Str, Changchun, 130021, China
| | - Juan Lv
- Department of Hepatology, the First hospital of Jilin University, No.71 Xinmin Str, Changchun, 130021, China
| | - Xiumei Chi
- Department of Hepatology, the First hospital of Jilin University, No.71 Xinmin Str, Changchun, 130021, China.,Key Laboratory of Zoonosis Research, Ministry Education, Changchun, 130021, China
| | - Ruihong Wu
- Department of Hepatology, the First hospital of Jilin University, No.71 Xinmin Str, Changchun, 130021, China.,Key Laboratory of Zoonosis Research, Ministry Education, Changchun, 130021, China
| | - Xiuzhu Gao
- Department of Hepatology, the First hospital of Jilin University, No.71 Xinmin Str, Changchun, 130021, China.,Key Laboratory of Zoonosis Research, Ministry Education, Changchun, 130021, China
| | - Junqi Niu
- Department of Hepatology, the First hospital of Jilin University, No.71 Xinmin Str, Changchun, 130021, China. .,Key Laboratory of Zoonosis Research, Ministry Education, Changchun, 130021, China.
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Gastaldi G, Gomes D, Schneiter P, Montet X, Tappy L, Clément S, Negro F. Treatment with direct-acting antivirals improves peripheral insulin sensitivity in non-diabetic, lean chronic hepatitis C patients. PLoS One 2019; 14:e0217751. [PMID: 31170218 PMCID: PMC6553748 DOI: 10.1371/journal.pone.0217751] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Accepted: 05/08/2019] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND AND AIMS Hepatitis C virus (HCV) infection is associated with insulin resistance, which may lead to type 2 diabetes and its complications. Although HCV infects mainly hepatocytes, it may impair insulin sensitivity at the level of uninfected extrahepatic tissues (muscles and adipose tissue). The aim of this study was to assess whether an interferon-free, antiviral therapy may improve HCV-associated hepatic vs. peripheral insulin sensitivity. METHODS In a single-arm exploratory trial, 17 non-diabetic, lean chronic hepatitis C patients without significant fibrosis were enrolled, and 12 completed the study. Patients were treated with a combination of sofosbuvir/ledipasvir and ribavirin for 12 weeks, and were submitted to a 2-step euglycemic hyperinsulinemic clamp with tracers, together with indirect calorimetry measurement, to measure insulin sensitivity before and after 6 weeks of antivirals. A panel of 27 metabolically active cytokines was analyzed at baseline and after therapy-induced viral suppression. RESULTS Clamp analysis performed in 12 patients who achieved complete viral suppression after 6 weeks of therapy showed a significant improvement of the peripheral insulin sensitivity (13.1% [4.6-36.7], p = 0.003), whereas no difference was observed neither in the endogenous glucose production, in lipolysis suppression nor in substrate oxidation. A distinct subset of hepatokines, potentially involved in liver-to-periphery crosstalk, was modified by the antiviral therapy. CONCLUSION Pharmacological inhibition of HCV improves peripheral (but not hepatic) insulin sensitivity in non-diabetic, lean individuals with chronic hepatitis C without significant fibrosis.
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Affiliation(s)
- Giacomo Gastaldi
- Division of Endocrinology, diabetology, hypertension and nutrition, Geneva University Hospitals, Geneva, Switzerland
| | - Diana Gomes
- Department of Pathology and immunology, University of Geneva, Geneva, Switzerland
| | - Philippe Schneiter
- Department of Physiology, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
| | - Xavier Montet
- Division of Radiology, Geneva University Hospitals, Geneva, Switzerland
| | - Luc Tappy
- Department of Physiology, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
| | - Sophie Clément
- Division of Clinical Pathology, Geneva University Hospitals, Geneva, Switzerland
| | - Francesco Negro
- Division of Clinical Pathology, Geneva University Hospitals, Geneva, Switzerland
- Division of Gastroenterology and hepatology, Geneva University Hospitals, Geneva, Switzerland
- * E-mail:
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Diabetes Mellitus and Risk of Hepatic Fibrosis/Cirrhosis. BIOMED RESEARCH INTERNATIONAL 2019; 2019:5308308. [PMID: 31080822 PMCID: PMC6475555 DOI: 10.1155/2019/5308308] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/25/2018] [Accepted: 03/27/2019] [Indexed: 02/06/2023]
Abstract
Development of cirrhosis is two- to threefold greater in patients with diabetes mellitus (DM), and in this setting, the prevalence of cirrhosis is surging worldwide. The present review served to examine clinical ties between DM and liver fibrosis and hepatic cirrhosis and explore related biologic mechanisms. Pathways contributing to various etiologies of cirrhosis in conjunction with DM were key investigative targets.
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31
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Lim TR, Hazlehurst JM, Oprescu AI, Armstrong MJ, Abdullah SF, Davies NP, Flintham R, Balfe P, Mutimer DJ, McKeating JA, Tomlinson JW. Hepatitis C virus infection is associated with hepatic and adipose tissue insulin resistance that improves after viral cure. Clin Endocrinol (Oxf) 2019; 90:440-448. [PMID: 30586166 PMCID: PMC6446809 DOI: 10.1111/cen.13924] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2018] [Revised: 12/10/2018] [Accepted: 12/20/2018] [Indexed: 12/17/2022]
Abstract
BACKGROUND Chronic hepatitis C (CHC) is associated with systemic insulin resistance, yet there are limited data on the tissue-specific contribution in vivo to this adverse metabolic phenotype, and the effect of HCV cure. METHODS We examined tissue-specific insulin sensitivity in a cohort study involving 13 patients with CHC compared to 12 BMI-matched healthy control subjects. All subjects underwent a two-step clamp incorporating the use of stable isotopes to measure carbohydrate and lipid flux (hepatic and global insulin sensitivity) with concomitant subcutaneous adipose tissue microdialysis and biopsy (subcutaneous adipose tissue insulin sensitivity). Investigations were repeated in seven patients with CHC following antiviral therapy with a documented sustained virological response. RESULTS Adipose tissue was more insulin resistant in patients with CHC compared to healthy controls, as evidence by elevated glycerol production rate and impaired insulin-mediated suppression of both circulating nonesterified fatty acids (NEFA) and adipose interstitial fluid glycerol release during the hyperinsulinaemic euglycaemic clamp. Hepatic and muscle insulin sensitivity were similar between patients with CHC and controls. Following viral eradication, hepatic insulin sensitivity improved as demonstrated by a reduction in endogenous glucose production rate. In addition, circulating NEFA decreased with sustained virological response (SVR) and insulin was more effective at suppressing adipose tissue interstitial glycerol release with a parallel increase in the expression of insulin signalling cascade genes in adipose tissue consistent with enhanced adipose tissue insulin sensitivity. CONCLUSION Chronic hepatitis C patients have profound subcutaneous adipose tissue insulin resistance in comparison with BMI-matched controls. For the first time, we have demonstrated that viral eradication improves global, hepatic and adipose tissue insulin sensitivity.
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Affiliation(s)
- Teegan R. Lim
- NIHR Liver Biomedical Research UnitUniversity of BirminghamBirminghamUK
- CRUK Clinical Trials UnitUniversity of BirminghamBirminghamUK
| | | | - Andrei I. Oprescu
- NIHR Liver Biomedical Research UnitUniversity of BirminghamBirminghamUK
| | - Matthew J. Armstrong
- NIHR Liver Biomedical Research UnitUniversity of BirminghamBirminghamUK
- CRUK Clinical Trials UnitUniversity of BirminghamBirminghamUK
| | - Sewa F. Abdullah
- School of Sport, Exercise & Rehabilitation SciencesUniversity of BirminghamBirminghamUK
| | | | | | - Peter Balfe
- NIHR Liver Biomedical Research UnitUniversity of BirminghamBirminghamUK
| | - David J. Mutimer
- NIHR Liver Biomedical Research UnitUniversity of BirminghamBirminghamUK
- CRUK Clinical Trials UnitUniversity of BirminghamBirminghamUK
| | | | - Jeremy W. Tomlinson
- Oxford Centre for Diabetes, Endocrinology & MetabolismUniversity of OxfordOxfordUK
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Carnovale C, Pozzi M, Dassano A, D'Addio F, Gentili M, Magni C, Clementi E, Radice S, Fiorina P. The impact of a successful treatment of hepatitis C virus on glyco-metabolic control in diabetic patients: a systematic review and meta-analysis. Acta Diabetol 2019; 56:341-354. [PMID: 30478781 DOI: 10.1007/s00592-018-1257-1] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2018] [Accepted: 11/06/2018] [Indexed: 01/06/2023]
Abstract
AIMS The effect of HCV eradication following the use of direct-acting antiviral drugs (DAAs) on the glyco-metabolic control is unknown. Through a meta-analysis of available clinical studies, we investigated whether eradication of HCV infection with interferon-free DAAs is associated with improved glyco-metabolic control in diabetic patients. METHODS We searched the PubMed, MEDLINE and Embase, up to 08th June 2018, for all studies evaluating whether eradication of HCV infection with DAAs is associated with changes in glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) levels from baseline in human subjects, without restrictions for study type and language. Data were independently extracted by two researchers using pre-specified forms. Random effects meta-analyses were conducted on HbA1c and FPG levels before/after HCV eradication. RESULTS We found a significant mean reduction in HbA1c levels of - 0.45% (95% CI - 0.60 to - 0.30%; P < 0.001) and in FPG levels of - 22.03 mg/dL (95% CI - 41.61 to - 2.44 mg/dL; P = 0.03), with high heterogeneity between studies (χ2 = 20.4, P < 0.001, I2 = 80% and χ2 = 35.8, P = 0.001, I2 = 94%, respectively). The number of available manuscripts did not allow conducting a meta-regression to elucidate the role of sustained virological response and other confounders in determining the effect of direct-acting antiviral agents on HbA1c reduction. CONCLUSIONS We found a significant improvement in glyco-metabolic control after HCV eradication (in terms of glycated haemoglobin and fasting plasma glucose levels reduction) following direct-acting antiviral treatment in patients with established diabetes, including a consequent positive impact on anti-diabetic therapies.
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Affiliation(s)
- Carla Carnovale
- Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences L. Sacco, "Luigi Sacco" University Hospital, Università di Milano, Via GB Grassi 74, 20157, Milan, Italy
| | - Marco Pozzi
- Scientific Institute IRCCS Eugenio Medea, 23842, Bosisio Parini, Lecco, Italy
| | - Alice Dassano
- International Center for T1D, Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, Università di Milano, 20157, Milan, Italy
| | - Francesca D'Addio
- International Center for T1D, Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, Università di Milano, 20157, Milan, Italy
| | - Marta Gentili
- Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences L. Sacco, "Luigi Sacco" University Hospital, Università di Milano, Via GB Grassi 74, 20157, Milan, Italy
| | - Carlo Magni
- 1st Division of Infectious Diseases, ASST Fatebenefratelli-Sacco, 20157, Milan, Italy
| | - Emilio Clementi
- Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences L. Sacco, "Luigi Sacco" University Hospital, Università di Milano, Via GB Grassi 74, 20157, Milan, Italy
- Scientific Institute IRCCS Eugenio Medea, 23842, Bosisio Parini, Lecco, Italy
| | - Sonia Radice
- Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences L. Sacco, "Luigi Sacco" University Hospital, Università di Milano, Via GB Grassi 74, 20157, Milan, Italy
| | - Paolo Fiorina
- International Center for T1D, Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, Università di Milano, 20157, Milan, Italy
- Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
- Division of Endocrinology, ASST Fatebenefratelli-Sacco, 20157, Milan, Italy
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Andrade VGD, Yamashiro FDS, Oliveira CV, Moreira A, Winckler FC, Silva GF. INSULIN RESISTANCE REDUCTION AFTER SUSTAINED VIROLOGICAL RESPONSE WITH DIRECT ACTING ANTIVIRAL:NOT EVERY POPULATION IMPROVES. ARQUIVOS DE GASTROENTEROLOGIA 2019; 55:274-278. [PMID: 30540091 DOI: 10.1590/s0004-2803.201800000-69] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Accepted: 08/15/2018] [Indexed: 12/18/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is a serious public health problem, that affects approximately 170 million people worldwide. Chronic HCV infection is associated with hepatic insulin resistance and an increased risk of diabetes HCV-infected patients has been well documented. OBJECTIVE To assess the homeostasis model assessment of insulin resistance (HOMA-IR) index in patients treated with direct acting antiviral (DAAs) medication in the sustained virological response (SVR), categorized by the presence or absence of cirrhosis. METHODS A prospective study was conducted. Data were collected at the beginning of treatment (t-base) and in the twelfth week after the completion of treatment (t-SVR12). The inclusion criteria were presence of: HCV infection (RNA-HCV positive), age ≥18 years, completion of DAAs' therapy, and presence of diabetes with use of oral hypoglycemic agents. All samples were collected during the study period. The exclusion criteria were: presence of HBV/HIV co-infection, hepatocellular carcinoma at baseline, diabetic patients taking insulin and transplanted patients (liver/kidney). Fibrosis was assessed by hepatic elastography or biopsy (METAVIR). Cirrhosis was determined by clinical results or imaging. HOMA-IR was calculated as fasting insulin (μU/mL) × fasting glucose (mmol/L)/22.5) The patients were divided into two groups: the general study population (all patients, including the diabetic patients) and the special population (patients with normal values of HOMA-IR, which is >2.5, and without diabetes). The delta HOMA-IR value was calculated as: HOMA-IR at t-base - HOMA-IR at t-SVR12. For the descriptive statistical analysis, the paired t-test and generalized linear model assuming the log binding function were performed. A P value of < 0.05 was considered significant. RESULTS We included 150 patients, and 75 were cirrhotic. The mean age was 55.3±9.97 and body mass index was 27.4±5.18. Twenty-two (14.67%) were diabetic patients using oral hypoglycemic agents, and 17 (11%) were cirrhotic. In the general study population, the mean glucose and HOMA-IR values increased at t-SVR12, but insulin decreased. Delta HOMA-IR was negative at t-SVR12, but there was no significant difference. Excluding diabetic patients and those with normal HOMA-IR values (<2.5), mean glucose, insulin and HOMA-IR decreased at t-SVR12. Delta HOMA-IR decreased significantly at t-SVR12 (P: 0.02). CONCLUSION In the general population, glucose and HOMA-IR values increased at t-SVR12, but insulin decreased. In the special population, glucose, insulin, HOMA-IR and Delta HOMA-IR decreased at t-SVR12.
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Affiliation(s)
- Vanessa Gutierrez de Andrade
- Universidade Estadual Paulista (UNESP), Faculdade de Medicina, Departamento de Clínica Médica, Botucatu, SP, Brasil
| | - Fábio da Silva Yamashiro
- Universidade Estadual Paulista (UNESP), Faculdade de Medicina, Departamento de Clínica Médica, Botucatu, SP, Brasil
| | - Cássio Vieira Oliveira
- Universidade Estadual Paulista (UNESP), Faculdade de Medicina, Departamento de Clínica Médica, Botucatu, SP, Brasil
| | - Alecsandro Moreira
- Universidade Estadual Paulista (UNESP), Faculdade de Medicina, Departamento de Clínica Médica, Botucatu, SP, Brasil
| | - Fernanda Cristina Winckler
- Universidade Estadual Paulista (UNESP), Faculdade de Medicina, Departamento de Clínica Médica, Botucatu, SP, Brasil
| | - Giovanni Faria Silva
- Universidade Estadual Paulista (UNESP), Faculdade de Medicina, Departamento de Clínica Médica, Botucatu, SP, Brasil
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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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Drazilova S, Janicko M, Skladany L, Kristian P, Oltman M, Szantova M, Krkoska D, Mazuchova E, Piesecka L, Vahalova V, Rac M, Schreter I, Virag L, Koller T, Liptakova A, Ondrasova M, Jarcuska P. Glucose Metabolism Changes in Patients with Chronic Hepatitis C Treated with Direct Acting Antivirals. Can J Gastroenterol Hepatol 2018; 2018:6095097. [PMID: 30402450 PMCID: PMC6192081 DOI: 10.1155/2018/6095097] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2018] [Revised: 08/19/2018] [Accepted: 09/18/2018] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND AND AIMS Chronic hepatitis C is a systemic disease and type 2 diabetes mellitus (T2DM) belongs to more common extrahepatic. The aim of this study was to (i) explore the prevalence of impaired fasting glucose (IFG) and T2DM in patients with chronic hepatitis C, (ii) explore the effect of direct acting antivirals (DAA) treatment on the glycemia, and (iii) explore the factors that modulate the effect of DAA treatment on glycemia in patients with chronic hepatitis C. METHODS We performed a longitudinal retrospective observational study focused on the patients undergoing DAA treatment of chronic hepatitis C. Data about glycemia, history of diabetes, hepatitis C virus, treatment, and liver status, including elastography, were obtained at baseline (before treatment start), at the end of treatment and 12 weeks after the end of treatment. Patients were treated with various regimens of direct acting antivirals. RESULTS We included 370 patients; 45.9% had F4 fibrosis. At baseline, the prevalence of T2DM increased with the degree of fibrosis (F0-F2 14.4%, F3 21.3%, and F4 31.8%, p=0.004). Fasting glycemia also increased with the degree of fibrosis (F0-F2 5.75±0.18 F3 5.84±0.17, and F4 6.69±0.2 mmol/L, p=0.001). We saw significant decrease of glycemia after treatment in all patients, but patients without T2DM or IFG from 6.21±0.12 to 6.08±0.15 mmol/L (p=0.002). The decrease was also visible in treatment experienced patients and patients with Child-Pugh A cirrhosis. CONCLUSION We confirmed that the prevalence of either T2DM or IFG increases in chronic hepatitis C patients with the degree of fibrosis. The predictive factors for T2DM were, besides F4, fibrosis also higher age and BMI. Significant decrease of fasting glycemia after the DAA treatment was observed in the whole cohort and in subgroups of patients with T2DM, IFG, cirrhotic, and treatment experienced patients.
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Affiliation(s)
- Sylvia Drazilova
- Department of Internal Medicine, Hospital Poprad, Banícka 803/28, Poprad, 05801, Slovakia
| | - Martin Janicko
- 1st Department of Internal Medicine, PJ Safarik University, Faculty of Medicine and L Pasteur University Hospital, Trieda SNP 1, Kosice, 04001, Slovakia
| | - Lubomir Skladany
- 2nd Department of Internal Medicine, FD Roosevelt University Hospital, Ludvíka Svobodu 1, Banska Bystrica, 97517, Slovakia
| | - Pavol Kristian
- Department of Infectious Diseases and Travel Medicine, PJ Safarik Unversity, Faculty of Medicine and L Pasteur University Hospital, Rastislavova 43, Kosice, 04001, Slovakia
| | - Marian Oltman
- Center for Gastroenterology and Hepatology Thalion, Tomášikova 50/C, Bratislava, 83104, Slovakia
| | - Maria Szantova
- 3rd Department of Internal Medicine, Commenius University, Faculty of Medicine and University Hospital, Limbová 5, Bratislava, 83305, Slovakia
| | - Dusan Krkoska
- Department of Infectious Diseases and Travel Medicine, Commenius University, Jesenius Faculty of Medicine and University Hospital, Štefanovičova 689/3, Martin, 03601, Slovakia
| | - Eva Mazuchova
- Department of Infectious Diseases and Travel Medicine, Commenius University, Jesenius Faculty of Medicine and University Hospital, Štefanovičova 689/3, Martin, 03601, Slovakia
| | - Lubica Piesecka
- Department of Infectious Diseases, Teaching Hospital Nitra, Špitálska 6, Nitra, 95001, Slovakia
| | - Veronika Vahalova
- Department of Infectious Diseases, Teaching Hospital Nitra, Špitálska 6, Nitra, 95001, Slovakia
| | - Marek Rac
- Department of Internal Medicine, Teaching Hospital Nitra, Špitálska 6, Nitra, 95001, Slovakia
| | - Ivan Schreter
- Department of Infectious Diseases and Travel Medicine, PJ Safarik Unversity, Faculty of Medicine and L Pasteur University Hospital, Rastislavova 43, Kosice, 04001, Slovakia
| | - Ladislav Virag
- Department of Infectious Diseases and Travel Medicine, PJ Safarik Unversity, Faculty of Medicine and L Pasteur University Hospital, Rastislavova 43, Kosice, 04001, Slovakia
| | - Tomas Koller
- 5th Department of Internal Medicine, Commenius University, Faculty of Medicine and University Hospital, Ružinovská 6, Bratislava, 82606, Slovakia
| | - Adriana Liptakova
- Department of Microbiology, Commenius University, Faculty of Medicine and University Hospital, Špitálska 13, Bratislava, 81372, Slovakia
| | - Miriam Ondrasova
- Saint Elisabeth University of Health and Social Sciences, Palackého 1, Bratislava, 81000, Slovakia
| | - Peter Jarcuska
- 1st Department of Internal Medicine, PJ Safarik University, Faculty of Medicine and L Pasteur University Hospital, Trieda SNP 1, Kosice, 04001, Slovakia
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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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Drazilova S, Gazda J, Janicko M, Jarcuska P. Chronic Hepatitis C Association with Diabetes Mellitus and Cardiovascular Risk in the Era of DAA Therapy. Can J Gastroenterol Hepatol 2018; 2018:6150861. [PMID: 30186821 PMCID: PMC6110000 DOI: 10.1155/2018/6150861] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2018] [Accepted: 07/31/2018] [Indexed: 12/15/2022] Open
Abstract
Patients with chronic hepatitis C have both higher prevalence of diabetes mellitus type 2 (T2DM) and increased cardiovascular risk compared to never infected people. Sustained viral response (SVR) achievement led to decreasing incidence and prevalence of T2DM during the interferon era of HCV treatment. Currently, direct-acting antiviral drugs (DAA) are the gold standard for treating HCV infection, while yielding SVR in nearly all patients. In chronic HCV patients with T2DM (prediabetes most likely too), DAA therapy is associated with both better fasting glucose and glycated hemoglobin (HbA1C) controls; thus reducing pharmacotherapy in a certain part of patients is possible. Papers mentioned in the review confirmed DAA role in both total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) increase. This alteration was accompanied by an increase in high-density lipoprotein cholesterol (HDL-C) and a decrease in triglycerides (TG) verified by most of the studies. However, the clinical significance of lipoprotein alterations caused by DAA therapy has not been explained yet. Moreover, DAA treatment of chronic hepatitis C improves hypertension control and atherosclerotic plaques. It is very likely that DAA therapeutic regimens will decrease both T2DM prevalence and cardiovascular risk in chronic hepatitis C patients; further research, however, is needed.
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Affiliation(s)
- Sylvia Drazilova
- Department of Internal Medicine, Hospital Poprad, Poprad, Slovakia
| | - Jakub Gazda
- 1st Department of Internal Medicine, PJ Safarik University, Faculty of Medicine and L Pasteur University Hospital, Kosice, Slovakia
| | - Martin Janicko
- 1st Department of Internal Medicine, PJ Safarik University, Faculty of Medicine and L Pasteur University Hospital, Kosice, Slovakia
| | - Peter Jarcuska
- 1st Department of Internal Medicine, PJ Safarik University, Faculty of Medicine and L Pasteur University Hospital, Kosice, Slovakia
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Salomone F, Catania M, Montineri A, Bertino G, Godos J, Rizzo L, Magrì G, Li Volti G. Hepatitis C virus eradication by direct antiviral agents improves glucose tolerance and reduces post-load insulin resistance in nondiabetic patients with genotype 1. Liver Int 2018; 38:1206-1211. [PMID: 29265719 DOI: 10.1111/liv.13669] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2017] [Accepted: 12/11/2017] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIMS Genotype 1 chronic hepatitis C is associated with an impairment of glucose homoeostasis, especially in the advanced stages of the disease. Glucose tolerance is an independent predictor of liver-related mortality in patients with cirrhosis because of chronic hepatitis C. However, no study has demonstrated so far weather hepatitis C virus clearance affects glucose tolerance. METHODS To this aim, we performed a prospective study assessing the effects of direct antiviral agents treatment in nondiabetic cirrhotic patients with genotypes 1a/1b and impaired glucose tolerance based on a 75-g oral glucose tolerance test. Impaired glucose tolerance was diagnosed by a 2-hour plasma glucose between 140 and 199 mg/dL. Insulin resistance was estimated by the oral glucose insulin sensitivity index, an oral glucose tolerance test-derived measure. RESULTS After meeting the inclusion criteria, the study population included 32 outpatients (26/6 genotypes 1b/1a; age 62 ± 7.4 years; 18 males) with compensated Child-A cirrhosis. All patients achieved a sustained virological response following direct antiviral agents treatment. After viral eradication, we did not observe change in fasting plasma glucose (103.5 ± 7.1 vs 102.8 ± 7.2 mg/dL, P = .15) but 2-hour plasma glucose was reduced (165.2 ± 22.7 vs 138.5 ± 21.3 mg/dL, P < .001). Hepatitis C virus eradication led also to a significant reduction in HbA1c (6.1 ± 0.2% vs 5.7 ± 0.3%, P < .001) and post-load insulin resistance as assessed by the oral glucose insulin sensitivity index (6.92 ± 1.56 vs 9.52 ± 1.39 mg/kg/min, P < .001). These effects were observed despite no change in body mass index from baseline to follow-up (25.6 ± 4.3 vs 25.8 ± 4.4, P > .5). CONCLUSIONS Our results indicate that hepatitis C virus eradication may early improve glucose tolerance in patients with hepatitis C virus-related cirrhosis.
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Affiliation(s)
- Federico Salomone
- Division of Gastroenterology, Ospedale di Acireale, Azienda Sanitaria Provinciale di Catania, Catania, Italy
| | - Maurizio Catania
- Division of Laboratory Medicine, Ospedale di Acireale, Azienda Sanitaria Provinciale di Catania, Catania, Italy
| | - Arturo Montineri
- Division of Infectious Diseases, Ospedale "Ferrarotto", Catania, Italy
| | - Gaetano Bertino
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| | - Justyna Godos
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | | | - Giovanni Magrì
- Division of Gastroenterology, Ospedale di Acireale, Azienda Sanitaria Provinciale di Catania, Catania, Italy
| | - Giovanni Li Volti
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
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Castedal M, Skoglund C, Axelson C, Bennet W. Steroid-free immunosuppression with low-dose tacrolimus is safe and significantly reduces the incidence of new-onset diabetes mellitus following liver transplantation. Scand J Gastroenterol 2018; 53:741-747. [PMID: 29688072 DOI: 10.1080/00365521.2018.1463390] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES Corticosteroids (CS) are traditionally used as part of the basal immunosuppression (IS) following liver transplantation (LT) but are known to be associated with an increased risk of new-onset diabetes mellitus (NODM), cardiovascular morbidity and mortality. The aim of this study was to retrospectively compare the incidence of transient as well as persistent NODM, rejection rate and patient- and graft survival between patients receiving steroid-based and steroid-free maintenance IS. MATERIALS AND METHODS A total of 238 patients liver transplanted (2008-2011) with deceased donor livers were divided into two groups, one group that received steroid-based IS (tacrolimus (TAC), corticosteroids (CS), ± mycophenolate mofetil (MMF); n = 155) (2008-2011) and another group of non-autoimmune recipients that received steroid-free IS (TAC, MMF; n = 83) according to our new maintenance IS-protocol starting January 2010. The primary and secondary end-points were patient- and graft survival, rejection rates and the incidence of NODM. The median follow-up times were 1248 days and 681 days, respectively. RESULTS The one-year patient- and graft survival in the steroid-based and steroid-free group was 92.7% and 93.3% (ns) and 87.6% and 84.9% (ns), respectively. The incidence of biopsy proven acute rejection (BPAR) was 27.7% in both groups (ns) during follow-up. The overall incidence of persistent NODM in the two groups were 16.8% and 2.9%, respectively (p < .01). CONCLUSIONS The results show that steroid-free low-dose tacrolimus-based IS following LT is safe and decreases the incidence of NODM significantly.
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Affiliation(s)
- M Castedal
- a The Transplant Institute , Sahlgrenska University Hospital, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden
| | - C Skoglund
- a The Transplant Institute , Sahlgrenska University Hospital, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden
| | - C Axelson
- a The Transplant Institute , Sahlgrenska University Hospital, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden
| | - W Bennet
- a The Transplant Institute , Sahlgrenska University Hospital, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden
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Noor-E-Alam SM. Management of Hepatocellular Carcinoma: Bangladesh Perspective. Euroasian J Hepatogastroenterol 2018; 8:52-53. [PMID: 29963462 PMCID: PMC6024033 DOI: 10.5005/jp-journals-10018-1258] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2018] [Accepted: 02/10/2018] [Indexed: 12/02/2022] Open
Abstract
Bangladesh is one of the countries facing huge burden of hepatocellular carcinoma (HCC). Hepatocellular carcinoma is the third commonest cancer in the country and it is just behind to cancer of the lung and cancer of the stomach. Hepatitis B virus (HBV) is responsible for 66% of HCC in Bangladesh. Presumptive prevalence of HBV and hepatitis C virus (HCV) may be as high as 5.4 and 0.84%, respectively, in Bangladesh, and liver diseases occupied 8 to 12% of admission in medicine wards of Public Medical College. In this mini review, I would like to highlight the impact of HBV and HCV in the development of HCC and the management of HCC from a Bangladesh perspective. How to cite this article: Noor-E-Alam SM. Management of Hepatocellular Carcinoma: Bangladesh Perspective. Euroasian J Hepato-Gastroenterol 2018;8(1):52-53.
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Affiliation(s)
- Sheikh M Noor-E-Alam
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
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41
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Nath P, P Singh S. Nonalcoholic Fatty Liver Disease: Time to Take the Bull by the Horns. Euroasian J Hepatogastroenterol 2018; 8:47-51. [PMID: 29963461 PMCID: PMC6024035 DOI: 10.5005/jp-journals-10018-1257] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2018] [Accepted: 01/25/2018] [Indexed: 12/12/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world affecting almost one-fourth of the population. It may progress to nonalcoholic steatohepatitis (NASH), cirrhosis, end-stage liver disease, and liver cancer in the long run. Besides, it may make the natural history in other chronic liver diseases worse too. Furthermore, patients of NAFLD more often suffer from metabolic syndrome, ischemic heart disease, and extrahepatic malignancies than others, leading to a lower overall survival than the general population. Obesity and sedentary lifestyle are among the most important risk factors for NAFLD apart from increasing age, male sex, and certain genetic factors. Due to the rising incidence, possible adverse consequences, and the futile available treatment options, prevention is the key to tackle this health menace. Spreading awareness, adopting a healthy lifestyle with appropriate dietary modifications, regular physical activity are the cornerstones for challenging this unfolding monster. How to cite this article: Nath P, Singh SP. Nonalcoholic Fatty Liver Disease: Time to Take the Bull by the Horns. Euroasian J Hepato-Gastroenterol 2018;8(1):47-51.
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Affiliation(s)
- Preetam Nath
- Department of Gastroenterology, Kalinga Institute of Medical Sciences, Kalinga Institute of Industrial Technology, Bhubaneswar, Odisha India
| | - Shivaram P Singh
- Department of Gastroenterology, Srirama Chandra Bhanja Medical College & Hospital, Cuttack, Odisha, India
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Raihan R, Azzeri A, H Shabaruddin F, Mohamed R. Hepatocellular Carcinoma in Malaysia and Its Changing Trend. Euroasian J Hepatogastroenterol 2018; 8:54-56. [PMID: 29963463 PMCID: PMC6024046 DOI: 10.5005/jp-journals-10018-1259] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2018] [Accepted: 02/10/2018] [Indexed: 01/18/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of death globally. In Malaysia liver cancer is the eighth most common cause of cancer for both gender and fifth most common cause of cancer for males. Liver cancer is a cause of premature death in Malaysia: The trend from 1990 to 2010 was observed upward. Since 1990, the annual years of life lost (YLLs) from liver cancer have increased by 31.5%. Older persons are at higher risk and there is male predominance observed. Curative surgical resection, liver transplantation, and supportive symptomatic care, including percutaneous ethanol injection and radiofrequency ablation (RFA), and noncurative transarterial chemoembolization (TACE) are among available treatment facilities. Yet the survival rate is very poor as majority of patients present at very advanced stage. Hepatitis B virus (HBV) remained the leading cause of HCC in Malaysia. Several studies showed cryptogenic causes, which are mainly nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) among the predominant causes of HCC in Malaysia than hepatitis C virus (HCV), alcohol, or any other reason. This mainly correlates with the increasing incidence of diabetes and obesity in Malaysia. How to cite this article: Raihan R, Azzeri A, Shabaruddin FH, Mohamed R. Hepatocellular Carcinoma in Malaysia and Its Changing Trend. Euroasian J Hepato-Gastroenterol 2018;8(1):54-56.
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Affiliation(s)
- Ruksana Raihan
- Department of Microbiology, Faculty of Medicine, AIMST University, Kedah, Malaysia
| | - Amirah Azzeri
- Department of Social and Preventive Medicine Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Fatiha H Shabaruddin
- Department of Pharmacy, Faculty of Medicine, University of Malaya Kuala Lumpur, Malaysia
| | - Rosmawati Mohamed
- Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
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Hu CC, Weng CH, Chang LC, Lin CL, Chen YT, Hu CF, Hua MC, Chen LW, Chien RN. Simple score to predict risk of hepatocellular carcinoma in chronic hepatitis C patients with advanced fibrosis after pegylated interferon and ribavirin therapy. Ther Clin Risk Manag 2018; 14:783-791. [PMID: 29750037 PMCID: PMC5933468 DOI: 10.2147/tcrm.s158424] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Purpose Eradication of chronic hepatitis C virus (HCV) after interferon-based therapy and its association with the reduction of risk of hepatocellular carcinoma (HCC) in HCV-infected patients with advanced fibrosis is controversial. The study is aimed to develop a simple scoring model for HCC prediction among advanced fibrotic chronic hepatitis C (CHC) patients after pegylated interferon (pegIFN) and ribavirin (RBV) therapy. Patients and methods We enrolled 271 biopsy-proven CHC patients with advanced fibrosis between 2003 and 2016, and divided them into non-HCC (n=211) and HCC (n=60) groups. The median observation duration was 6.0 years (range: 0.9–12.6 years). Results The HCC prevalence after pegIFN and RBV therapy in CHC patients with sustained virologic response (SVR) and without SVR was 14.7% and 32.2%, respectively. Multivariate Cox regression showed age ≥59.5 years old at initiation of therapy (HR: 2.542, 95% CI: 1.390–4.650, P=0.002), pretreatment total bilirubin ≥1.1 mg/dL (HR: 2.630, 95% CI: 1.420–4.871, P=0.002), pretreatment platelet counts <146.5 × 103/μL (HR: 2.751, 95% CI: 1.373–5.511, P=0.004), no achievement of SVR (HR: 2.331, 95% CI: 1.277–4.253, P=0.006), and no diabetes at treatment initiation (HR: 3.085, 95% CI: 1.283–7.418, P=0.012) were significant predictors of HCC development. The scoring model consisted of the five categorical predictors and had an optimal cutoff point of 2.5. The area under receiver operating characteristic (AUROC) of the scoring model was 0.774±0.035 (P<0.001). The sensitivity and specificity of the cutoff value to detect HCC were 81.3% and 57.5%. The 5-year and 10-year cumulative incidence of HCC was 4.9% and 10.0% in patients with simple score ≤2; and 25.9% and 44.6% in patients with simple score ≥3 (P<0.001). Conclusion The simple clinical-guided score has high discriminatory power for HCC prediction in advanced fibrotic CHC patients after pegIFN and RBV therapy.
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Affiliation(s)
- Ching-Chih Hu
- Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Keelung, Taiwan.,College of Medicine, Chang Gung University, Linkou, Taiwan
| | - Cheng-Hao Weng
- College of Medicine, Chang Gung University, Linkou, Taiwan.,Department of Nephrology and Poison Center, Chang Gung Memorial Hospital, Linkou, Taiwan
| | - Liang-Che Chang
- Department of Pathology, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Chih-Lang Lin
- Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Keelung, Taiwan.,College of Medicine, Chang Gung University, Linkou, Taiwan
| | - Yen-Ting Chen
- Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Ching-Fang Hu
- Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Man-Chin Hua
- College of Medicine, Chang Gung University, Linkou, Taiwan.,Department of Pediatrics, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Li-Wei Chen
- Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Rong-Nan Chien
- College of Medicine, Chang Gung University, Linkou, Taiwan.,Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Linkou, Taiwan
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Abstract
BACKGROUND Hepatitis C (HCV) is more prevalent in African Americans than in any other racial group in the United States. However, African Americans are more likely to be deemed ineligible for HCV treatment than non-African Americans. There has been limited research into the origins of racial disparities in HCV treatment eligibility. AIM The purpose of this study was to compare medical and non-medical characteristics commonly assessed in clinical practice that could potentially contribute to HCV treatment ineligibility disparities between African American and non-African American patients. MATERIAL AND METHODS Patients with confirmed HCV RNA considering treatment (n = 309) were recruited from university-affiliated and VA liver and infectious disease clinics. RESULTS African Americans and non-African Americans did not differ in prevalence of lifetime and current psychiatric disorders and risky behaviors, and HCV knowledge. HCV clinical characteristics were similar between both groups in terms of HCV exposure history, number of months aware of HCV diagnosis, stage of fibrosis, and HCV virologic levels. African Americans did have higher proportions of diabetes, renal disease, and bleeding ulcer. CONCLUSIONS No clinical evidence was found to indicate that African Americans should be more often deemed ineligible for HCV treatment than other racial groups. Diabetes and renal disease do not fully explain the HCV treatment ineligibility racial disparity, because HCV patients with these conditions are priority patients for HCV treatment because of their greater risk for cirrhosis, steatosis, and hepatocellular carcinoma. The findings suggest that an underlying contributor to the HCV treatment eligibility disparity disfavoring African Americans could be racial discrimination.
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Affiliation(s)
- Omar Sims
- Department of Social Work, College of Arts and Sciences. † Department of Health Behavior, School of Public Health. The University of Alabama at Birmingham, Birmingham, AL, USA
| | - David Pollio
- Department of Social Work, College of Arts and Sciences. † Department of Health Behavior, School of Public Health. The University of Alabama at Birmingham, Birmingham, AL, USA
| | - Barry Hong
- Department of Psychiatry, School of Medicine, Washington University, St. Louis, MO, USA
| | - Carol North
- Department of Psychiatry, School of Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA
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Singhal A, Agrawal A, Ling J. Regulation of insulin resistance and type II diabetes by hepatitis C virus infection: A driver function of circulating miRNAs. J Cell Mol Med 2018; 22:2071-2085. [PMID: 29411512 PMCID: PMC5867149 DOI: 10.1111/jcmm.13553] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2017] [Accepted: 01/04/2018] [Indexed: 12/15/2022] Open
Abstract
Hepatitis C virus (HCV) infection is a serious worldwide healthcare issue. Its association with various liver diseases including hepatocellular carcinoma (HCC) is well studied. However, the study on the relationship between HCV infection and the development of insulin resistance and diabetes is very limited. Current research has already elucidated some underlying mechanisms, especially on the regulation of metabolism and insulin signalling by viral proteins. More studies have emerged recently on the correlation between HCV infection‐derived miRNAs and diabetes and insulin resistance. However, no studies have been carried out to directly address if these miRNAs, especially circulating miRNAs, have causal effects on the development of insulin resistance and diabetes. Here, we proposed a new perspective that circulating miRNAs can perform regulatory functions to modulate gene expression in peripheral tissues leading to insulin resistance and diabetes, rather than just a passive factor associated with these pathological processes. The detailed rationales were elaborated through comprehensive literature review and bioinformatic analyses. miR‐122 was identified to be one of the most potential circulating miRNAs to cause insulin resistance. This result along with the idea about the driver function of circulating miRNAs will promote further investigations that eventually lead to the development of novel strategies to treat HCV infection‐associated extrahepatic comorbidities.
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Affiliation(s)
- Adit Singhal
- Geisinger Commonwealth School of Medicine, Scranton, PA, USA
| | | | - Jun Ling
- Geisinger Commonwealth School of Medicine, Scranton, PA, USA
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del Campo JA, García-Valdecasas M, Gil-Gómez A, Rojas Á, Gallego P, Ampuero J, Gallego-Durán R, Pastor H, Grande L, Padillo FJ, Muntané J, Romero-Gómez M. Simvastatin and metformin inhibit cell growth in hepatitis C virus infected cells via mTOR increasing PTEN and autophagy. PLoS One 2018; 13:e0191805. [PMID: 29385181 PMCID: PMC5791999 DOI: 10.1371/journal.pone.0191805] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Accepted: 01/11/2018] [Indexed: 01/24/2023] Open
Abstract
Hepatitis C virus (HCV) infection has been related to increased risk of development of hepatocellular carcinoma (HCC) while metformin (M) and statins treatment seemed to protect against HCC development. In this work, we aim to identify the mechanisms by which metformin and simvastatin (S) could protect from liver cancer. Huh7.5 cells were infected with HCV particles and treated with M+S. Human primary hepatocytes were treated with M+S. Treatment with both drugs inhibited Huh7.5 cell growth and HCV infection. In non-infected cells S increased translational controlled tumor protein (TCTP) and phosphatase and tensin homolog (PTEN) proteins while M inhibited mammalian target of rapamycin (mTOR) and TCTP. Simvastatin and metformin co-administered down-regulated mTOR and TCTP, while PTEN was increased. In cells infected by HCV, mTOR, TCTP, p62 and light chain 3B II (LC3BII) were increased and PTEN was decreased. S+M treatment increased PTEN, p62 and LC3BII in Huh7.5 cells. In human primary hepatocytes, metformin treatment inhibited mTOR and PTEN, but up-regulated p62, LC3BII and Caspase 3. In conclusion, simvastatin and metformin inhibited cell growth and HCV infection in vitro. In human hepatocytes, metformin increased cell-death markers. These findings suggest that M+S treatment could be useful in therapeutic prevention of HCV-related hepatocellular carcinoma.
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Affiliation(s)
- José A. del Campo
- Department of Digestive Diseases and CIBERehd, Valme University Hospital, Servicio Andaluz de Salud, Seville, Spain
- * E-mail:
| | - Marta García-Valdecasas
- Department of Digestive Disease, Biomedicine Institute of Seville & CIBERehd, Rocío University Hospital, Seville, Spain
| | - Antonio Gil-Gómez
- Department of Digestive Disease, Biomedicine Institute of Seville & CIBERehd, Rocío University Hospital, Seville, Spain
| | - Ángela Rojas
- Department of Digestive Disease, Biomedicine Institute of Seville & CIBERehd, Rocío University Hospital, Seville, Spain
| | - Paloma Gallego
- Department of Digestive Diseases and CIBERehd, Valme University Hospital, Servicio Andaluz de Salud, Seville, Spain
| | - Javier Ampuero
- Department of Digestive Disease, Biomedicine Institute of Seville & CIBERehd, Rocío University Hospital, Seville, Spain
| | - Rocío Gallego-Durán
- Department of Digestive Disease, Biomedicine Institute of Seville & CIBERehd, Rocío University Hospital, Seville, Spain
| | - Helena Pastor
- Department of Digestive Disease, Biomedicine Institute of Seville & CIBERehd, Rocío University Hospital, Seville, Spain
| | - Lourdes Grande
- Department of Digestive Diseases and CIBERehd, Valme University Hospital, Servicio Andaluz de Salud, Seville, Spain
| | - Francisco J. Padillo
- Department of General Surgery, Rocío University Hospital, CSIC and University of Seville, Seville, Spain
| | - Jordi Muntané
- Department of General Surgery, Rocío University Hospital, CSIC and University of Seville, Seville, Spain
| | - Manuel Romero-Gómez
- Department of Digestive Disease, Biomedicine Institute of Seville & CIBERehd, Rocío University Hospital, Seville, Spain
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Fabrizi F, Messa P, Martin P, Takkouche B. Hepatitis C Virus Infection and Post-Transplant Diabetes Mellitus among Renal Transplant Patients: A Meta-Analysis. Int J Artif Organs 2018; 31:675-82. [DOI: 10.1177/039139880803100801] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Objective To examine the association between HCV infection and the occurrence of post-transplant diabetes mellitus (PTDM) among renal transplant patients. Design Meta-analysis of observational studies. Data Sources We retrieved studies published in any language by systematically searching Medline, and Embase and by manually examining the references of the original articles, reviews, and monographs retrieved. Review Methods We included cohort and case-control studies reporting relative risk estimates and 95% confidence intervals (CIs) for PTDM occurrence with HCV after renal transplantation. Thirteen studies providing information on a total of 30,099 unique patients were included in our meta-analysis. Results Study-specific relative risks were weighted by the inverse of their variance to obtain fixed- and random-effects pooled estimates. The pooled relative risk (RR) for PTDM after RT was 2.73 with a 95% confidence interval (CI) of 1.94; 3.83 (10 studies). In a stratified analysis including only large studies (2 studies), the pooled RR was 1.36 (95% CI, 1.21; 1.54). Egger's regression test showed some evidence of publication bias (p=0.0001), but our sensitivity analysis showed that this issue did not meaningfully change the results. Conclusions Our study shows a marked increase of the risk of post-transplant diabetes mellitus in anti-hepatitis C virus-positive renal transplant recipients. The excess risk of death in hepatitis C virus-positive renal transplant recipients may be at least partially attributed to post-transplant diabetes mellitus with its attendant complications.
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Affiliation(s)
- F. Fabrizi
- Division of Nephrology and Dialysis, Maggiore Hospital, IRCCS, Milan - Italy
| | - P. Messa
- Division of Nephrology and Dialysis, Maggiore Hospital, IRCCS, Milan - Italy
| | - P. Martin
- Division of Liver Diseases, Mount Sinai School of Medicine, New York City, NY - USA
| | - B. Takkouche
- Department of Preventive Medicine, University School of Medicine, Santiago de Compostela - Spain
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48
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Villar LM, Caldas GC, Scalioni LDP, Miguel JC, da Silva EF, Marques VA, Villela-Nogueira CA, Lewis-Ximenez LL, Lampe E. High prevalence of insulin resistance among Brazilian chronic hepatitis C patients. ARCHIVES OF ENDOCRINOLOGY AND METABOLISM 2017; 61:628-632. [PMID: 29412389 PMCID: PMC10522051 DOI: 10.1590/2359-3997000000315] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/31/2016] [Accepted: 07/31/2017] [Indexed: 11/22/2022]
Abstract
OBJECTIVE This study aims to estimate the prevalence of insulin resistance (IR) among chronic hepatitis C (CHC) patients and their related laboratory and demographic data. SUBJECTS AND METHODS In this study, non-diabetic CHC patients referred to Viral Hepatitis Ambulatories from Rio de Janeiro (Brazil) donated blood samples. Insulin was measured using a chemiluminescence immunoassay. IR was determined by HOMA-IR, where HOMA-IR > 2 was defined as IR. RESULTS A total of 214 CHC patients were recruited (123 females aged 53.6 years ± 10.9 years). IR was present in 133 patients (62.1%) and was associated in bivariate analysis to higher mean values of age (p = 0.040), triglycerides (p = 0.032), glucose (p = 0.000), insulin (p = 0.000), waist circumference (p = 0.001), and body mass index (p = 0.007); however, none of these variables were significant in the multivariate analysis. CONCLUSIONS The high prevalence of IR was observed among CHC patients, and there was no difference in clinical or laboratory parameters when both groups were compared in the multivariate analysis. This high IR prevalence could lead to a high risk for development of cardiovascular disease and metabolic disorders.
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Affiliation(s)
- Livia Melo Villar
- Instituto Oswaldo CruzLaboratório de Hepatite ViralRio de JaneiroRJBrasilLaboratório de Hepatite Viral, Instituto Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brasil
| | - Gabriela Cardoso Caldas
- Instituto Oswaldo CruzLaboratório de Hepatite ViralRio de JaneiroRJBrasilLaboratório de Hepatite Viral, Instituto Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brasil
| | - Leticia de Paula Scalioni
- Instituto Oswaldo CruzLaboratório de Hepatite ViralRio de JaneiroRJBrasilLaboratório de Hepatite Viral, Instituto Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brasil
| | - Juliana Custódio Miguel
- Instituto Oswaldo CruzLaboratório de Hepatite ViralRio de JaneiroRJBrasilLaboratório de Hepatite Viral, Instituto Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brasil
| | - Elisangela Ferreira da Silva
- Instituto Oswaldo CruzLaboratório de Hepatite ViralRio de JaneiroRJBrasilLaboratório de Hepatite Viral, Instituto Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brasil
| | - Vanessa Alves Marques
- Instituto Oswaldo CruzLaboratório de Hepatite ViralRio de JaneiroRJBrasilLaboratório de Hepatite Viral, Instituto Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brasil
| | - Cristiane Alves Villela-Nogueira
- Universidade Federal do Rio de JaneiroHospital Universitário Clementino Fraga Filho (HUCFF)Departamento de Clínica MédicaRio de JaneiroRJBrasilUnidade de Hepatologia, Departamento de Clínica Médica, Hospital Universitário Clementino Fraga Filho (HUCFF), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brasil
| | - Lia Laura Lewis-Ximenez
- Instituto Oswaldo CruzLaboratório de Hepatite ViralRio de JaneiroRJBrasilLaboratório de Hepatite Viral, Instituto Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brasil
| | - Elisabeth Lampe
- Instituto Oswaldo CruzLaboratório de Hepatite ViralRio de JaneiroRJBrasilLaboratório de Hepatite Viral, Instituto Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brasil
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49
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Ciancio A, Bosio R, Bo S, Pellegrini M, Sacco M, Vogliotti E, Fassio G, Bianco Mauthe Degerfeld AGF, Gallo M, Giordanino C, Terzi di Bergamo L, Ribaldone D, Bugianesi E, Smedile A, Rizzetto M, Saracco GM. Significant improvement of glycemic control in diabetic patients with HCV infection responding to direct-acting antiviral agents. J Med Virol 2017; 90:320-327. [DOI: 10.1002/jmv.24954] [Citation(s) in RCA: 75] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2017] [Accepted: 09/19/2017] [Indexed: 02/06/2023]
Affiliation(s)
- Alessia Ciancio
- Gastroenterology Unit; Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Roberta Bosio
- Gastroenterology Unit; San Luigi Hospital; University of Turin; Torino Italy
| | - Simona Bo
- Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Marianna Pellegrini
- Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Marco Sacco
- Gastroenterology Unit; Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Edoardo Vogliotti
- Gastroenterology Unit; Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Giulia Fassio
- Gastroenterology Unit; San Luigi Hospital; University of Turin; Torino Italy
| | | | - Monica Gallo
- Gastroenterology Unit; San Luigi Hospital; University of Turin; Torino Italy
| | - Chiara Giordanino
- Gastroenterology Unit; San Luigi Hospital; University of Turin; Torino Italy
| | - Lodovico Terzi di Bergamo
- Gastroenterology Unit; Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Davide Ribaldone
- Gastroenterology Unit; Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Elisabetta Bugianesi
- Gastroenterology Unit; Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Antonina Smedile
- Gastroenterology Unit; Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Mario Rizzetto
- Gastroenterology Unit; Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Giorgio Maria Saracco
- Gastroenterology Unit; Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
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50
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Ocaña-Mondragón A, Mata-Marín JA, Uriarte-López M, Bekker-Méndez C, Alcalá-Martínez E, Ribas-Aparicio RM, Uribe-Noguéz LA, Rodríguez-Galindo DM, Martínez-Rodríguez MDLL. Effect of branched-chain amino acid supplementation on insulin resistance and quality of life in chronic hepatitis C patients. Biomed Rep 2017; 8:85-90. [PMID: 29399341 DOI: 10.3892/br.2017.1012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2017] [Accepted: 10/19/2017] [Indexed: 12/23/2022] Open
Abstract
The incidence rate of insulin resistance (IR) in patients with chronic hepatitis C (CHC) is high. Recently, branched-chain amino acids (BCAA) have been shown to attenuate IR in CHC patients; however, their effect on patient quality of life remains unclear. Therefore, the aim of the current prospective study was to determine the effects of BCAA supplement on IR and health-related quality of life (HR-QoL) in patients with CHC. In the study, 20 non-diabetic patients with CHC, who were non-responders to peginterferon-α and ribavirin, were recruited. Patients took a BCAA supplement once a day (30 g, after a minimum 10-h overnight fast) for 3 months. Serum levels of glucose, insulin, albumin, triglycerides and cholesterol were measured at 0 and 3 months. Additionally, IR was measured using the Homeostasis Model Assessment-IR, HR-QoL was assessed using the 36-item Short Form Health Survey and viral load was measured by reverse transcription polymerase chain reaction using Taqman probes. The Wilcoxon signed-rank test was used to determine statistical significance. The results indicated that 70% of the subjects were positive for IR, which decreased to 50% by the end of the study; furthermore, 85% of the subjects demonstrated some level of improvement. Overall, the BCAA treatment significantly decreased IR (P=0.006) and augmented serum albumin concentration (P=0.008) compared with basal values. Additionally, by the end of the treatment, viral load and triglycerides levels had decreased, though these results were not significant (P=0.084 and P=0.080, respectively). BCAA treatment also improved HR-QoL regarding role limitations due to physical health problems (P=0.017), role limitations due to emotional problems (P=0.026) and social function (P=0.008). In conclusion, BCAA supplementation reduced IR and improved HR-QoL in patients with CHC. These findings support the application of IR therapy as a possible therapeutic strategy for hepatitis C infection.
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Affiliation(s)
- Alicia Ocaña-Mondragón
- Unidad de Investigación Biomédica en Infectología e Inmunología, Hospital de Infectología, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social, Mexico City 02990, Mexico
| | - José Antonio Mata-Marín
- Unidad Médica de Alta Especialidad, Hospital de Infectología, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social, Mexico City 02990, Mexico
| | - Mario Uriarte-López
- Departamento de Investigación y Desarrollo, AYDSA Aminas y Derivados S.A. de C.V., Mexico City 06400, Mexico
| | - Carolina Bekker-Méndez
- Unidad de Investigación Biomédica en Infectología e Inmunología, Hospital de Infectología, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social, Mexico City 02990, Mexico
| | - Enrique Alcalá-Martínez
- Unidad Médica de Alta Especialidad, Hospital de Infectología, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social, Mexico City 02990, Mexico
| | - Rosa María Ribas-Aparicio
- Departamento de Microbiología, Programa en Biomedicina y Biotecnología Molecular, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City 11340, Mexico
| | - Luis Antonio Uribe-Noguéz
- Unidad de Investigación Biomédica en Infectología e Inmunología, Hospital de Infectología, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social, Mexico City 02990, Mexico.,Departamento de Microbiología, Programa en Biomedicina y Biotecnología Molecular, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City 11340, Mexico
| | - Dulce María Rodríguez-Galindo
- Departamento de Psicología Clínica, Unidad Médica de Alta Especialidad, Hospital de Especialidades, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social, Mexico City 02990, Mexico
| | - María de La Luz Martínez-Rodríguez
- Unidad de Investigación Biomédica en Infectología e Inmunología, Hospital de Infectología, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social, Mexico City 02990, Mexico
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