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Alshoaibi IA, Al-Gamli A, Abdullah M, Abdo B, Alzanen KH, Alhakamy M, Al-Namer M, Ahmed F, Tamesh M, Mahdi W, Abdo Z, Mohammed M. Effectiveness of Ledipasvir-Sofosbuvir 12 Weeks After Hepatitis C Virus Genotype 1 Infection and the Factors Associated With Sustained Virologic Response: A Retrospective Study. Cureus 2024; 16:e68249. [PMID: 39350869 PMCID: PMC11439843 DOI: 10.7759/cureus.68249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/30/2024] [Indexed: 10/04/2024] Open
Abstract
BACKGROUND The combination of ledipasvir and sofosbuvir (LDV/SOF) has been licensed to treat genotype 1 hepatitis C virus infection (HCV) with a 12-week regimen. However, there is scant data from Yemen regarding this combination regimen. Here, we investigate sustained virologic responses (SVR) 12 weeks after HCV treatment with LDV/SOF regimens and the factors that contribute to SVR failure. MATERIAL AND METHOD A retrospective cross-sectional study was conducted at Althora General Hospital in Ibb, Yemen, from June 1, 2019, to October 31, 2022, on 53 cases with HCV genotype 1 infection who received combined therapy of LDV/SOF and completed treatment for 12 weeks. The clinical characteristics and treatment follow-up were obtained from patient medical records. Factors associated with SVR failure were investigated in univariate analysis with odds ratio (OR) and 95% confidence interval (CI). RESULT The mean age was 50 ± 15.3 years, and most cases were female (n=36, 67.9%). Comorbidities were diabetes, hypertension, and fatty liver, which were represented in 12 (22.6%), nine (17.0%), and eight (15.1%) cases, respectively. A total of 13 (24.5%) patients had compensated liver cirrhosis, while the remaining 40 patients (75.5%) were non-cirrhotic healthy individuals. The baseline viral load (HCV RNA) was more than 800000 IU/mL in 21 patients (39.6%). Early virological response (ERV) was achieved in 51 patients (96.2%). After treatment, 46 of the patients (86.8%) achieved SVR at Week 12, while failure occurred in two patients (3.8%) and relapse occurred in five patients (9.4%). Blood liver enzymes, including alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase, returned to normal, with statistically significant improvements in non-cirrhotic healthy persons than compensated liver cirrhosis individuals (p= 0.006, 0.006, and 0.010; respectively). Factors associated with SVR failure were older age (OR:1.13; 95% CI: 1.03-1.30, p=0.009), presence of liver cirrhosis (OR: 5.48; 95% CI: 1.04-28.98, p=0.031), having diabetes (OR: 6.33; 95% CI: 1.19-37.93, p= 0.019), baseline higher viral load (OR: 2.27; 95% CI: 0.45-12.73, p<0.001), and not achieving EVR (OR:7.63; 95% CI: 3.77- 17.78, p= 0.009). CONCLUSION In this study, we found that LDV/SOF regimens are effective against HCV genotype one infection, allowing for the expansion of 12-week treatment for suitable patients in clinical settings. Additionally, older age, liver cirrhosis, diabetes, higher pretreatment viral load, and non-completion of EVR were associated with SVR failure. However, due to the small number of HCV genotype 1 infected individuals in this study, more corporate data is required to get a clear conclusion.
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Affiliation(s)
| | | | | | - Basheer Abdo
- Internal Medicine, School of Medicine, Ibb University, Ibb, YEM
| | | | | | - Mamoon Al-Namer
- Internal Medicine, School of Medicine, Ibb University, Ibb, YEM
| | - Faisal Ahmed
- Urology, School of Medicine, Ibb University, Ibb, YEM
| | - Munther Tamesh
- Pharmacy, University of Science and Technology, Ibb, YEM
| | - Wadhah Mahdi
- Pharmacy, University of Science and Technology, Ibb, YEM
| | - Zeyad Abdo
- Pharmacy, University of Science and Technology, Ibb, YEM
| | - Marwa Mohammed
- General Practice, School of Medicine, Ibb University, Ibb, YEM
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Reiberger T, Lens S, Cabibbo G, Nahon P, Zignego AL, Deterding K, Elsharkawy AM, Forns X. EASL position paper on clinical follow-up after HCV cure. J Hepatol 2024; 81:326-344. [PMID: 38845253 DOI: 10.1016/j.jhep.2024.04.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Accepted: 04/05/2024] [Indexed: 07/26/2024]
Abstract
Following the advent of direct-acting antivirals (DAAs), hepatitis C virus (HCV) infection can be cured in almost all infected patients. This has led to a number of clinical questions regarding the optimal management of the millions of patients cured of HCV. This position statement provides specific guidance on the appropriate follow-up after a sustained virological response in patients without advanced fibrosis, those with compensated advanced chronic liver disease, and those with decompensated cirrhosis. Guidance on hepatocellular carcinoma risk assessment and the management of extrahepatic manifestations of HCV is also provided. Finally, guidance is provided on the monitoring and treatment of reinfection in at-risk patients. The recommendations are based on the best available evidence and are intended to help healthcare professionals involved in the management of patients after treatment for HCV.
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Affiliation(s)
- Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria. CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
| | - Sabela Lens
- Liver Unit, Hospital Clinic Barcelona. IDIBAPS. Liver and Digestive Diseases Networking Biomedical Research Centre (CIBERehd). University of Barcelona. Spain
| | - Giuseppe Cabibbo
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties PROMISE, University of Palermo, Italy
| | - Pierre Nahon
- AP-HP, Hôpitaux Universitaires Paris Seine Saint-Denis, Liver Unit, Bobigny; Université Sorbonne Paris Nord, F-93000 Bobigny; Inserm, UMR-1138 "Functional Genomics of Solid Tumors", Centre de Recherche des Cordeliers, Université de Paris, France
| | - Anna Linda Zignego
- Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy
| | - Katja Deterding
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School. Germany
| | - Ahmed M Elsharkawy
- Liver Unit, Queen Elizabeth Hospital Birmingham. NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham, United Kingdom
| | - Xavier Forns
- Liver Unit, Hospital Clinic Barcelona. IDIBAPS. Liver and Digestive Diseases Networking Biomedical Research Centre (CIBERehd). University of Barcelona. Spain.
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An N, Zhang Y, Sha Z, Xu Z, Liu X. T2DM may exert a protective effect against digestive system tumors in East Asian populations: a Mendelian randomization analysis. Front Oncol 2024; 14:1327154. [PMID: 38947888 PMCID: PMC11211363 DOI: 10.3389/fonc.2024.1327154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Accepted: 05/29/2024] [Indexed: 07/02/2024] Open
Abstract
Introduction Type 2 diabetes mellitus (T2DM) was associated with digestive system tumors. We analyzed publicly available data from GWAS studies using Mendelian randomization methods to clarify its causal relationship and mechanisms. Five common digestive system tumors and four diabetes-related phenotypes were included. Methods Inverse variance weighted method was the main analytical method. Meta-analysis was used to summarize results of multiple data sources. Horizontal pleiotropy was tested using Egger-intercept method and validated by MRPRESSO method. Heterogeneity and sensitivity analysis were conducted by Cochran's Q test and leave-one-out method, respectively. Results T2DM is associated with a reduced risk of esophageal (OR: 0.77, 95% CI: 0.71 to 0.83, P< 0.001), gastric (OR: 0.87, 95% CI: 0.84 to 0.90, P< 0.001) and colorectal cancer (OR: 0.88, 95% CI: 0.85 to 0.91, P< 0.001) and hepatocellular carcinoma (OR: 0.92, 95% CI: 0.86 to 0.97, P = 0.005) and an increased risk of pancreatic cancer (OR: 1.92, 95% CI: 1.47 to 2.50, P< 0.001) in East Asian population. T2DM causes decreased fasting insulin levels (OR = 0.966, 95% CI: 0.95 to 0.98, P< 0.001) and increased glycated hemoglobin levels (OR=1.41, 95% CI: 1.39 to 1.44, P<0.001). Elevated fasting insulin levels increase the risk of esophageal cancer (OR = 10.35, 95% CI: 1.10 to 97.25, P = 0.041), while increased glycated hemoglobin levels increase pancreatic cancer risk (OR=2.33, 95% CI: 1.37 to 3.97, P=0.002) but decrease gastric cancer risk (OR=0.801, 95% CI: 0.65 to 0.99, P=0.044). Conclusion T2DM is associated with a reduced risk of esophageal, gastric and colorectal cancer and hepatocellular carcinoma in East Asian populations. The causal relationships between T2DM with esophageal and gastric cancer are partially mediated by decreased fasting insulin and increased glycated hemoglobin levels, respectively. T2DM indirectly increases the risk of pancreatic cancer by increasing glycated hemoglobin levels.
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Affiliation(s)
- Ni An
- Department of Anesthesiology, The Eighth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yu Zhang
- No.91126 Military Hospital of Chinese PLA, Dalian, China
| | - Zhilin Sha
- Department I of Biliary Tract Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
| | - Zhen Xu
- Department of Anesthesiology, The Eighth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Xiuzhen Liu
- Department of Anesthesiology, The Eighth Medical Center of Chinese PLA General Hospital, Beijing, China
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Ateya RM, Afifi SA, Abd Al Monem N, Al-Karamany AS, Bessar AA, Rageh F, Ahmed SS, Ghareeb D. Impact of IL-28B gene polymorphism on chronic hepatitis-C patients progression with diabetes and non-diabetes. EGYPTIAN JOURNAL OF MEDICAL HUMAN GENETICS 2022. [DOI: 10.1186/s43042-022-00239-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Chronic hepatitis C (CHC) is a silent viral infection; however, elevated mortality and morbidity rates are noted in Egypt due to its adverse effects. The augmented incidence of diabetes in patients with viral C infection may be owing to glucose intolerance, high BMI, senility, and inherited factors.
Purpose of the study
Little information is available about the connection between interleukin-28B (IL-28B) genotype in disease progression among CHC patients with diabetes. Thus, we aimed to assess the association between IL-28B genotype (rs12979860) in CHC with type 2 diabetes mellitus (T2DM) versus those without diabetes in disease progression among Egyptian patients.
Results
CC genotype was significantly lower in diabetics than in non-diabetics (13.7% vs. 36.3%). While (CT/TT) were significantly higher in diabetics than in non-diabetics (CT 58.8% vs. 43.7%), (TT 27.5% vs. 20%) (p = 0.03) and likewise alleles (p = 0.04). Multivariate logistic regression analysis was significant with viral load p < 0.001, alanine aminotransferase (ALT) p < 0.001, genotype CC versus TT p = 0.04 & T2DM p = 0.03.
Conclusion
CC genotype might be used as a protective factor and TT genotype as a risk factor in disease progression among CHC patients with T2DM. Additionally, viral load, ALT & T2DM might interplay as predictors of disease severity. Detecting the genetic factors can be helpful in predicting and preventing the complications of diabetes associated with the hepatitis C virus (HCV).
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HCV Genotype Has No Influence on the Incidence of Diabetes-EpiTer Multicentre Study. J Clin Med 2022; 11:jcm11020379. [PMID: 35054072 PMCID: PMC8780546 DOI: 10.3390/jcm11020379] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 12/30/2021] [Accepted: 01/05/2022] [Indexed: 12/17/2022] Open
Abstract
HCV infection is one of the main reasons for liver cirrhosis and hepatocellular carcinoma. In recent years, one finds more and more extrahepatic manifestations of HCV infection, including its possible influence on the development of diabetes. In the presented work, one finds the frequency analysis of the incidence of diabetes among 2898 HCV infected patients treated in Poland, and the assessment of their relevance to the HCV genotype and the progression of fibrosis. The results indicate that the hepatitis C infection seems to be a risk factor for diabetes in persons with more advanced liver fibrosis, for older people, and for the male gender. Thus, one found no differences regarding the frequency of its incidence depending on HCV genotype, including genotype 3.
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Pabjan P, Brzdęk M, Chrapek M, Dziedzic K, Dobrowolska K, Paluch K, Garbat A, Błoniarczyk P, Reczko K, Stępień P, Zarębska-Michaluk D. Are There Still Difficult-to-Treat Patients with Chronic Hepatitis C in the Era of Direct-Acting Antivirals? Viruses 2022; 14:96. [PMID: 35062302 PMCID: PMC8779728 DOI: 10.3390/v14010096] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2021] [Revised: 12/29/2021] [Accepted: 01/04/2022] [Indexed: 12/17/2022] Open
Abstract
Difficult-to-treat populations with chronic hepatitis C (CHC), in the era of interferon treatment, included patients with liver cirrhosis, kidney impairment, treatment-experienced individuals, and those coinfected with the human immunodeficiency virus. The current study aimed to determine whether, in the era of direct-acting antivirals (DAA), there are still patients that are difficult-to-treat. The study included all consecutive patients chronically infected with hepatitis C virus (HCV) who started interferon-free therapy between July 2015 and December 2020 in the Department of Infectious Diseases in Kielce. The analyzed real-world population consisted of 963 patients, and most of them were infected with genotype 1 (87.6%) with the predominance of subtype 1b and were treatment-naïve (78.8%). Liver cirrhosis was determined in 207 individuals (21.5%), of whom 82.6% were compensated. The overall sustained virologic response, after exclusion of non-virologic failures, was achieved in 98.4%. The univariable analysis demonstrated the significantly lower response rates in males, patients with liver cirrhosis, decompensation of hepatic function at baseline, documented esophageal varices, concomitant diabetes, body mass index ≥25, and previous ineffective antiviral treatment. Despite an overall very high effectiveness, some unfavorable factors, including male gender, genotype 3 infection, liver cirrhosis, and treatment experience, significantly reduce the chances for a virologic response were identified.
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Affiliation(s)
- Paweł Pabjan
- Department of Infectious Diseases, Voivodship Hospital, Jan Kochanowski University, 25-317 Kielce, Poland; (P.P.); (K.P.); (A.G.); (P.B.); (K.R.); (P.S.)
| | - Michał Brzdęk
- Collegium Medicum, Jan Kochanowski University, 25-369 Kielce, Poland; (M.B.); (K.D.); (K.D.)
| | - Magdalena Chrapek
- Faculty of Natural Sciences, Jan Kochanowski University, 25-369 Kielce, Poland;
| | - Kacper Dziedzic
- Collegium Medicum, Jan Kochanowski University, 25-369 Kielce, Poland; (M.B.); (K.D.); (K.D.)
| | - Krystyna Dobrowolska
- Collegium Medicum, Jan Kochanowski University, 25-369 Kielce, Poland; (M.B.); (K.D.); (K.D.)
| | - Katarzyna Paluch
- Department of Infectious Diseases, Voivodship Hospital, Jan Kochanowski University, 25-317 Kielce, Poland; (P.P.); (K.P.); (A.G.); (P.B.); (K.R.); (P.S.)
| | - Anna Garbat
- Department of Infectious Diseases, Voivodship Hospital, Jan Kochanowski University, 25-317 Kielce, Poland; (P.P.); (K.P.); (A.G.); (P.B.); (K.R.); (P.S.)
| | - Piotr Błoniarczyk
- Department of Infectious Diseases, Voivodship Hospital, Jan Kochanowski University, 25-317 Kielce, Poland; (P.P.); (K.P.); (A.G.); (P.B.); (K.R.); (P.S.)
| | - Katarzyna Reczko
- Department of Infectious Diseases, Voivodship Hospital, Jan Kochanowski University, 25-317 Kielce, Poland; (P.P.); (K.P.); (A.G.); (P.B.); (K.R.); (P.S.)
| | - Piotr Stępień
- Department of Infectious Diseases, Voivodship Hospital, Jan Kochanowski University, 25-317 Kielce, Poland; (P.P.); (K.P.); (A.G.); (P.B.); (K.R.); (P.S.)
| | - Dorota Zarębska-Michaluk
- Department of Infectious Diseases, Voivodship Hospital, Jan Kochanowski University, 25-317 Kielce, Poland; (P.P.); (K.P.); (A.G.); (P.B.); (K.R.); (P.S.)
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Hagag RY, Selim AF, Darrag OM, Zied H, Aboelnasr MS. Does Hepatitis C Virus Treatment by Directly Acting Antivirals Obligate Shifting Patients with Type 2 Diabetes from Oral Hypoglycemic Drugs to Insulin Therapy? Diabetes Metab Syndr Obes 2022; 15:1261-1268. [PMID: 35502409 PMCID: PMC9056022 DOI: 10.2147/dmso.s354023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2021] [Accepted: 04/06/2022] [Indexed: 12/15/2022] Open
Abstract
PURPOSE The aim of the present work was to investigate whether hepatitis C virus treatment by directly acting antivirals obligate shifting patients with type 2 diabetes from oral hypoglycemic drugs to insulin therapy. METHODS This was a prospective study including 92 treatment-naïve patients with chronic hepatitis C virus infection and type 2 diabetes who were eligible for treatment with directly acting antivirals (sofosbuvir + daclatasvir ± ribavirin). Patients in the study were divided into two groups; group 1 included 22 patients on insulin therapy and group 2 included 70 patients on oral antidiabetic medications. Patients were advised to keep on their anti-diabetic treatment. RESULTS All our patients achieved sustained virologic response with significantly lower HbA1c 12 weeks after the end of therapy (p. values 0.001 for group 1 and group 2). There was no statistically significant difference in HbA1c level post-treatment between both groups (p. value 0.352). CONCLUSION Achievement of sustained virologic response using interferon free, directly acting antivirals-based regimen was associated with significantly lower HbA1c 12 weeks after the end of therapy. The type of treatment used for type 2 diabetes (oral drugs or insulin) did not affect improved glycemic control observed after achieving sustained virologic response.
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Affiliation(s)
- Rasha Youssef Hagag
- Department of internal medicine, Faculty of medicine, Tanta University, Tanta, Egypt
| | - Ahmed Fawzy Selim
- Department of internal medicine, Faculty of medicine, Tanta University, Tanta, Egypt
| | - Omneya Mohamed Darrag
- Department of internal medicine, Faculty of medicine, Tanta University, Tanta, Egypt
| | - Hassan Zied
- Kafr-Elsheikh Liver Institute, Kafr-Elsheikh, Egypt
| | - Mohamed Sabry Aboelnasr
- Department of internal medicine, Faculty of medicine, Tanta University, Tanta, Egypt
- Correspondence: Mohamed Sabry Aboelnasr, Elgeish Street, Aboelelasorour Building, Floor 6, Kafrelzayat, Gharbia Governorate, 31611, Egypt, Tel +20 1066276267, Email ;
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Cárdaba-García ME, Abad-Lecha E, Calleja-Hernández MÁ. Effectiveness of direct-acting antiviral drugs against hepatitis C virus: predictive factors of response to the treatment. Libyan J Med 2021; 16:1949797. [PMID: 34308801 PMCID: PMC8317931 DOI: 10.1080/19932820.2021.1949797] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Accepted: 06/27/2021] [Indexed: 11/08/2022] Open
Abstract
Background/Aims. Despite the high efficacy and safety of direct-acting antivirals against hepatitis C virus shown in clinical trials, treatment failures continue to occur. Our aim was to establish the effectiveness of these drugs in routine clinical practice, as well as to determine factors that could influence the response to the treatment.Matherials/methods. Single-center, observational, retrospective study. Clinical, virological and pharmacotherapeutic variables were registered at baseline. Adverse drug reactions that occurred were recorded until week 24 of follow-up. Achievement of sustained virologic response was also recorded. Univariate and multivariate analysis were done to determine factors of response.Results. A total of 333 treatment regimens corresponding to 330 different patients were evaluated. Sustained virologic response rate was 94.6% [95%CI: 91.6-96.6%]. 67.9% of the patients experienced adverse drugs reactions (92.2% were grade 1). The univariate analysis identified a higher baseline of platelets, albumin and total cholesterol as predictive factors of sustained virologic response (p < 0.05). Presence of diabetes and complications related to liver disease (splenomegaly, portal hypertension, portal hypertensive gastropathy), body mass index ≥30, greater liver fibrosis, receiving simeprevir and higher baseline levels of glucose, aspartate-aminotransferase, alanine-aminotransferase and alkaline-phosphatase, have been identified as predictive factors of non-response (p < 0.05). The multivariate analysis detected the following independent factors of non-response: body mass index ≥30 and presence of complications related to liver disease.Conclusion. The effectiveness and safety of direct-acting antivirals against hepatitis C virus have been maintained in routine clinical practice. Further research on predictive factors of response is required in order to develop more reliable and reproducible predictive models.
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Affiliation(s)
- María E. Cárdaba-García
- Faculty of Pharmacy, University of Granada, Campus Universitario de Cartuja, Granada, Spain
- Hospital Pharmacy, Hospital Clínico Universitario de Valladolid, Valladolid, Spain
| | | | - Miguel Á. Calleja-Hernández
- Faculty of Pharmacy, University of Granada, Campus Universitario de Cartuja, Granada, Spain
- Hospital Pharmacy, Virgen Macarena University Hospital, Sevilla, Spain
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Recipient IL28B genotype CT is a predictor of new onset diabetes mellitus in liver transplant patients with chronic hepatitis C. Int J Diabetes Dev Ctries 2021. [DOI: 10.1007/s13410-021-01015-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
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Cacciola I, Russo G, Filomia R, Pitrone C, Caccamo G, Giandalia A, Alibrandi A, Stella Franzè M, Porcari S, Maimone S, Saitta C, Squadrito G, Raimondo G. Over time evaluation of glycaemic control in direct-acting antiviral-treated hepatitis C virus/diabetic individuals with chronic hepatitis or with cirrhosis. Liver Int 2021; 41:2059-2067. [PMID: 33894103 PMCID: PMC8506140 DOI: 10.1111/liv.14905] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Revised: 04/07/2021] [Accepted: 04/15/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND Data concerning the impact of hepatitis C virus (HCV) cure on type 2 diabetes mellitus (T2DM) are controversial. The aim of the study was to evaluate the effects of anti-HCV direct-acting antiviral (DAA) treatments on long-term glucose control in HCV/T2DM patients with chronic hepatitis C (CHC) or with cirrhosis. METHODS One hundred and eighty-two consecutive HCV/T2DM patients who achieved a viral clearance by DAA treatment were enrolled. Seventy or 182 of them had CHC, and 112 had cirrhosis. Clinical, biochemical and instrumental parameters were recorded at baseline and at 48, 96 and 120 weeks (48w, 96w and 120w, respectively) after stopping DAA therapy. RESULTS At baseline, the overall study population had a mean of glycated haemoglobin (HbA1c) value of 7.2% (ranging from 5 to 11.2), without any significant differences between CHC and cirrhosis [7.1 and 7.2, respectively]. Evaluation over time of HbA1c variations showed a significant improvement of glucose control at all post-treatment time points compared with baseline in CHC patients (P = .001). In cirrhotic patients, a significant decrease of HbA1c levels was only found when comparing HbA1c values between baseline and 48w time-point (P = .001), whereas this improvement disappeared at both 98w and 120w (P = .8 and P = .3, respectively). Multivariate logistic regression analysis showed that patients with chronic hepatitis have a 2.5 (CI 1.066-5.945) times greater chance of achieving an improvement of glycaemic values than patients with liver cirrhosis (P = .035). CONCLUSION DAA-based HCV cure induces a significant and persistent amelioration of glycaemic control in HCV/diabetic patients with chronic hepatitis, whereas cirrhotic HCV/diabetic subjects have only a transient benefit from the virus elimination.
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Affiliation(s)
- Irene Cacciola
- Department of Clinical and Experimental MedicineUniversity of MessinaMessinaItaly,Division of Medicine and HepatologyDepartment of Internal MedicineUniversity Hospital of MessinaMessinaItaly
| | - Giuseppina Russo
- Department of Clinical and Experimental MedicineUniversity of MessinaMessinaItaly,Division of Medicine and DiabetologyDepartment of Internal MedicineUniversity Hospital of MessinaMessinaItaly
| | - Roberto Filomia
- Division of Medicine and HepatologyDepartment of Internal MedicineUniversity Hospital of MessinaMessinaItaly
| | - Concetta Pitrone
- Department of Clinical and Experimental MedicineUniversity of MessinaMessinaItaly,Division of Medicine and HepatologyDepartment of Internal MedicineUniversity Hospital of MessinaMessinaItaly
| | - Gaia Caccamo
- Division of Medicine and HepatologyDepartment of Internal MedicineUniversity Hospital of MessinaMessinaItaly
| | - Annalisa Giandalia
- Department of Clinical and Experimental MedicineUniversity of MessinaMessinaItaly,Division of Medicine and DiabetologyDepartment of Internal MedicineUniversity Hospital of MessinaMessinaItaly
| | - Angela Alibrandi
- Department of Economics Unit of Statistical and Mathematical Science of MessinaUniversity of MessinaMessinaItaly
| | - Maria Stella Franzè
- Department of Clinical and Experimental MedicineUniversity of MessinaMessinaItaly,Division of Medicine and HepatologyDepartment of Internal MedicineUniversity Hospital of MessinaMessinaItaly
| | - Serena Porcari
- Department of Clinical and Experimental MedicineUniversity of MessinaMessinaItaly,Division of Medicine and HepatologyDepartment of Internal MedicineUniversity Hospital of MessinaMessinaItaly
| | - Sergio Maimone
- Division of Medicine and HepatologyDepartment of Internal MedicineUniversity Hospital of MessinaMessinaItaly
| | - Carlo Saitta
- Division of Medicine and HepatologyDepartment of Internal MedicineUniversity Hospital of MessinaMessinaItaly
| | - Giovanni Squadrito
- Department of Clinical and Experimental MedicineUniversity of MessinaMessinaItaly,Division of Internal MedicineDepartment of Internal MedicineUniversity Hospital of MessinaMessinaItaly
| | - Giovanni Raimondo
- Department of Clinical and Experimental MedicineUniversity of MessinaMessinaItaly,Division of Medicine and HepatologyDepartment of Internal MedicineUniversity Hospital of MessinaMessinaItaly
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Yunihastuti E, Hariyanto R, Sulaiman AS, Harimurti K. Hepatitis C continuum of care: Experience of integrative hepatitis C treatment within a human immunodeficiency virus clinic in Indonesia. PLoS One 2021; 16:e0256164. [PMID: 34383853 PMCID: PMC8360535 DOI: 10.1371/journal.pone.0256164] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 08/01/2021] [Indexed: 12/24/2022] Open
Abstract
INTRODUCTION Direct-acting antiviral drugs (DAAs) have changed the paradigm of hepatitis C therapy for both HCV/HIV co-infected and HCV mono-infected patients. We aimed to describe the HCV continuum of care of HIV-infected patients treated in an HIV clinic after a free DAA program in Indonesia and identify factors correlated with sofosbuvir-daclatasvir (SOF-DCV) treatment failure. METHODS We did a retrospective cohort study of adult HIV/HCV co-infected patients under routine HIV-care from November 2019 to April 2020 in the HIV integrated clinic of Cipto Mangunkusumo Hospital, Jakarta, Indonesia. We evaluated some factors correlated with sofosbuvir-daclatasvir treatment failure: gender, diabetes mellitus, previous IFN failure, cirrhosis, concomitant ribavirin use, high baseline HCV-RNA, and low CD4 cell count. RESULTS AND DISCUSSION Overall, 640 anti-HCV positive patients were included in the study. Most of them were male (88.3%) and former intravenous drug users (76.6%) with a mean age of 40.95 (SD 4.60) years old. Numbers and percentages for the stages of the HCV continuum of care were as follows: HCV-RNA tested (411; 64.2%), pre-therapeutic evaluation done (271; 42.3%), HCV treatment initiated (210; 32.8%), HCV treatment completed (207; 32.2%), but only 178 of these patients had follow-up HCV-RNA tests to allow SVR assessment; and finally SVR12 achieved (178; 27.8%). For the 184 who completed SOF-DCV treatment, SVR12 was achieved by 95.7%. In multivariate analysis, diabetes mellitus remained a significant factor correlated with SOF-DCV treatment failure (adjusted RR 17.0, 95%CI: 3.28-88.23, p = 0.001). CONCLUSIONS This study found that in the HCV continuum of care for HIV/HCV co-infected patients, gaps still exist at all stages. As the most commonly used DAA combination, sofosbuvir daclatasvir treatment proved to be effective and well-tolerated in HIV/HCV co-infected patients. Diabetes mellitus was significant factor correlated with not achieving SVR12 in this population.
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Affiliation(s)
- Evy Yunihastuti
- Department Internal Medicine, Faculty of Medicine Universitas Indonesia/Cipto Mangunkusumo Hospital, Jakarta, Indonesia
- HIV Integrated Clinic, Cipto Mangunkusumo Hospital, Jakarta, Indonesia
| | - Rahmat Hariyanto
- Department Internal Medicine, Faculty of Medicine Universitas Indonesia/Cipto Mangunkusumo Hospital, Jakarta, Indonesia
| | - Andri Sanityoso Sulaiman
- Department Internal Medicine, Faculty of Medicine Universitas Indonesia/Cipto Mangunkusumo Hospital, Jakarta, Indonesia
| | - Kuntjoro Harimurti
- Department Internal Medicine, Faculty of Medicine Universitas Indonesia/Cipto Mangunkusumo Hospital, Jakarta, Indonesia
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12
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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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Broker M, Frager SZ, Patel NS, Lebovics E, Frishman WH. The Inflammatory Relationship Between Hepatitis C Virus With Coronary and Carotid Atherosclerosis. Cardiol Rev 2021; 29:178-183. [PMID: 32618587 DOI: 10.1097/crd.0000000000000314] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
Hepatitis C virus (HCV), a global health concern, has been linked to various hepatic and extrahepatic deleterious manifestations. Several observational studies have either supported the increased likelihood of coronary and carotid atherosclerosis after infection with HCV or refuted it. To date, there has been no clear consensus to support either train of thought, as randomized, controlled clinical trials have not been completed. In this review, we first discuss articles that support the notion that HCV infection leads to increased plaque formation due to systemic inflammation and then focus on articles that refute this idea. From the literature, we do know that both inflammatory and lipid processes play a role in plaque formation, and thus both components are important in the successful treatment of atherosclerosis. Based on our review of the literature, we do believe that HCV-infected individuals are at an increased risk for more severe coronary artery disease than their healthy counterparts. Although there is no irrefutable evidence that links HCV infection with plaque formation and/or rupture, cardioprotective measures should be taken to reduce poor health outcomes, especially in those individuals who are already at risk of coronary disease.
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Affiliation(s)
- Michael Broker
- From the Department of Medicine, New York Medical College/Westchester Medical Center, Valhalla, NY
| | - Shalom Z Frager
- Department of Medicine, Division of Gastroenterology and Hepatology, New York Medical College/Westchester Medical Center, Valhalla, NY
| | - Nayan S Patel
- Department of Medicine, University of Rochester/Strong Memorial Hospital, Rochester, NY
| | - Edward Lebovics
- Department of Medicine, Division of Gastroenterology and Hepatology, New York Medical College/Westchester Medical Center, Valhalla, NY
| | - William H Frishman
- From the Department of Medicine, New York Medical College/Westchester Medical Center, Valhalla, NY
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14
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Lapumnuaypol K, Pisarcik D, Putthapiban P, Sukhumthammarat W, Wijarnpreecha K, Thongprayoon C, Ungprasert P. Direct-acting antiviral agents decrease haemoglobin A1c level in patients with diabetes infected with hepatitis C virus: A systematic review & meta-analysis. Indian J Med Res 2021; 152:562-567. [PMID: 34145095 PMCID: PMC8224154 DOI: 10.4103/ijmr.ijmr_1088_18] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/09/2022] Open
Abstract
Background & objectives: Several epidemiologic studies have demonstrated that type 2 diabetes mellitus (T2DM) is more prevalent in patients infected with hepatitis C virus (HCV), and the eradication of HCV has been shown to decrease the risk of T2DM. This meta-analysis was undertaken to see if treatment with direct-acting antiviral (DAA) agents would improve glycaemic control among HCV-infected patients with T2DM . Methods: A systematic review was conducted using MEDLINE and EMBASE databases since inception to February 2018. Eligible studies must be cohort studies that recruited HCV-infected patients with T2DM and received DAA therapy. The studies must report the change of haemoglobin A1c (HbA1c) level (before vs. after DAA therapy). Patients who achieved sustained virologic response (SVR) were included in the meta-analysis. The mean HbA1c level and standard deviation of participants were extracted from each study to calculate the mean difference (MD). Pooled MD was then calculated using the random effects model. Results: Four cohort studies with 2648 patients were included. Among HCV-infected T2DM patients who achieved SVR with DAA agents, the mean HbA1c level after treatment was significantly lower than the mean HbA1c level before treatment, with the pooled MD of −0.50 per cent (95% confidence interval, −0.66 to −0.34, I2 = 77%). The main limitation of this study was the lack of comparison groups. Therefore, it could not be concluded that the observed decreased HbA1c level was a direct result of DAA therapy. Interpretation & conclusions: Treatment with DAA agents was found to be associated with a significant reduction of post-treatment HbA1c level compared with pre-treatment HbA1c level among T2DM patients who achieved SVR.
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Affiliation(s)
| | - David Pisarcik
- Department of Internal Medicine, Philadelphia College of Osteopathic Medicine, PA, USA
| | | | | | - Karn Wijarnpreecha
- Department of Gastroenterology, Mayo Clinic Hospital, Gastroenterology - Jacksonville, FL, USA
| | - Charat Thongprayoon
- Department of Nephrology, Mayo Clinic, Nephrology & Hypertension Rochester, MN, USA
| | - Patompong Ungprasert
- Department of Research & Development, Division of Clinical Epidemiology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
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15
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Compagnoni S, Bruno EM, Madonia G, Cannizzaro M, Madonia S. Direct antiviral agents in hepatitis C virus related liver disease: Don't count the chickens before they're hatched. World J Gastroenterol 2021; 27:2771-2783. [PMID: 34135553 PMCID: PMC8173378 DOI: 10.3748/wjg.v27.i21.2771] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 03/26/2021] [Accepted: 04/28/2021] [Indexed: 02/06/2023] Open
Abstract
Since molecules with direct-acting antiviral (DAA) became available, the landscape of the treatment of hepatitis C virus (HCV) infection has completely changed. The new drugs are extremely effective in eradicating infection, and treatment is very well tolerated with a duration of 8-12 wk. This review aims to report the outstanding clinical benefits of DAA and to highlight their critical disadvantages, identifying some clinically relevant hot topics. First, do the rates of virological response remain as high when patients with more advanced cirrhosis are considered? Large studies have shown slightly lower but still satisfactory rates of response in these patients. Nevertheless, modified schedules with an extended treatment duration and use of ribavirin may be necessary. Second, does the treatment of HCV infection affect the risk of occurrence and recurrence of liver cancer? Incidence is reduced after viral eradication but remains high enough to warrant periodic surveillance for an early diagnosis. In contrast, the risk of recurrence seems to be unaffected by viral clearance; however, DAA treatment improves survival because of the reduced risk of progression of liver disease. Third, can HCV treatment also have favorable effects on major comorbidities? HCV eradication is associated with a reduced incidence of diabetes, an improvement in glycemic control and a decreased risk of cardiovascular events; nevertheless, a risk of hypoglycemia during DAA treatment has been reported. Finally, is it safe to treat patients with HCV/ hepatitis B virus (HBV) coinfection? In this setting, HCV is usually the main driver of viral activity, while HBV replication is suppressed. Because various studies have described HBV reactivation after HCV clearance, a baseline evaluation for HBV coinfection and a specific follow-up is mandatory.
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Affiliation(s)
- Stella Compagnoni
- Department of Internal Medicine, V. Cervello Hospital, University of Palermo, Palermo 90146, Italy
| | - Erica Maria Bruno
- Department of Internal Medicine, V. Cervello Hospital, University of Palermo, Palermo 90146, Italy
| | - Giorgio Madonia
- Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo 90127, Italy
| | - Marco Cannizzaro
- Department of Emergency Medicine, A. Ajello Hospital, Trapani 91026, Italy
| | - Salvatore Madonia
- Department of Internal Medicine, V. Cervello Hospital, Palermo 90146, Italy
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16
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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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17
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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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Butt AA, Yan P, Aslam S, Shaikh OS, Abou-Samra AB. Hepatitis C Virus (HCV) Treatment With Directly Acting Agents Reduces the Risk of Incident Diabetes: Results From Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES). Clin Infect Dis 2021; 70:1153-1160. [PMID: 30977808 DOI: 10.1093/cid/ciz304] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Accepted: 04/09/2019] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND The effects of interferon-based therapies for hepatitis C virus (HCV) upon the risk of diabetes are controversial. The effects of newer, directly acting antiviral agents (DAA) upon this risk are unknown. We sought to determine the effects of HCV treatment upon the risk and incidence of diabetes. METHODS Using the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) database for persons with chronic HCV infection (n = 242 680), we identified those treated with a pegylated interferon and ribavirin regimen (PEG/RBV, n = 4764) or a DAA-containing regimen (n = 21 279), after excluding those with diabetes at baseline, those with a human immunodeficiency virus or hepatitis B virus coinfection, and those treated with both PEG/RBV and DAA regimens. Age-, race-, sex-, and propensity score-matched controls (1:1) were also identified. RESULTS Diabetes incidence rates per 1000 person-years were 20.6 (95% confidence interval [CI] 19.6-21.6) among untreated persons, 19.8 (95% CI 18.3-21.4) among those treated with PEG/RBV, and 9.89 (95% CI 8.7-11.1) among DAA-treated persons (P < .001). Among the treated, rates were 13.3 (95% CI 12.2-14.5) for those with a sustained virologic response (SVR) and 19.2 (95% CI 17.4-21.1) for those without an SVR (P < .0001). A larger reduction was observed in persons with more advanced fibrosis/cirrhosis (absolute difference 2.9 for fibrosis severity score [FIB-4] < 1.25; 5.7 for FIB-4 1.26-3.25; 9.8 for FIB-4 >3.25). DAA treatment (hazard ratio [HR] 0.53, 95% CI .46-.63) and SVR (HR 0.81, 95% CI .70-.93) were associated with a significantly reduced risk of diabetes. DAA-treated persons had longer diabetes-free survival rates, compared to untreated and PEG/RBV-treated persons. There was no significant difference in diabetes-free survival rates between untreated and PEG/RBV-treated persons. The results were similar in inverse probability of treatment and censoring weight models. CONCLUSIONS DAA therapy significantly reduces the incidence and risk of subsequent diabetes. Treatment benefits are more pronounced in persons with more advanced liver fibrosis.
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Affiliation(s)
- Adeel A Butt
- Veterans Health Administration Pittsburgh Healthcare System, Pennsylvania.,Weill Cornell Medical College, New York, New York.,Hamad Medical Corporation, Doha, Qatar
| | - Peng Yan
- Veterans Health Administration Pittsburgh Healthcare System, Pennsylvania
| | - Samia Aslam
- Veterans Health Administration Pittsburgh Healthcare System, Pennsylvania
| | - Obaid S Shaikh
- Veterans Health Administration Pittsburgh Healthcare System, Pennsylvania
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19
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Cheng CH, Chu CY, Chen HL, Lin IT, Wu CH, Lee YK, Bair MJ. Virus Elimination by Direct-Acting Antiviral Agents Impacts Glucose Homeostasis in Chronic Hepatitis C Patients. Front Endocrinol (Lausanne) 2021; 12:799382. [PMID: 35095765 PMCID: PMC8792856 DOI: 10.3389/fendo.2021.799382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Accepted: 12/20/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND AND AIMS Chronic hepatitis C virus (HCV) infection is associated with dysregulation of glucose homeostasis, including insulin resistance (IR) and type 2 diabetes. However, independent risk factors associated with IR in chronic HCV-infected patients have not been detailly elucidated. Previous data regarding the impact of HCV elimination by direct-acting antiviral agents (DAAs) on glucose homeostasis is insufficient and controversial. This study aimed to analyze the independent factors associated with IR and to evaluate the changes in glucose homeostasis in chronic HCV-infected patients treated with DAAs therapies. METHODS We screened 704 patients with chronic HCV infection who underwent treatment with interferon-free DAAs. Patients' baseline characteristics, biochemical and virological data were collected. The outcome measurements were their IR and β-cell function assessed by the homeostasis model assessment (HOMA) method at baseline and 12-weeks post-treatment. RESULTS High IR (HOMA-IR ≥ 2.5) was observed in 35.1% of the patients. Multivariable logistic regression analysis revealed that body mass index (BMI) >25 kg/m2, treatment experience, elevated baseline levels of alanine aminotransferase (ALT) and triglyceride, as well as Fibrosis-4 score >3.25 were independently associated with high IR. In patients who achieved sustained virological response (SVR), no significant change in mean HOMA-IR was observed from baseline to 12-weeks post-treatment (2.74 ± 2.78 to 2.54 ± 2.20, p = 0.128). We observed a significant improvement in β-cell secretion stress from 121.0 ± 110.1 to 107.6 ± 93.0 (p = 0.015). Subgroup analysis revealed that SVR was associated with a significant reduction in mean HOMA-IR in patients with baseline HOMA-IR ≥ 2.5 (5.31 ± 3.39 to 3.68 ± 2.57, p < 0.001), HCV genotype 1 (3.05 ± 3.11 to 2.62 ± 2.05, p = 0.027), and treatment experience (4.00 ± 3.37 to 3.01 ± 2.49, p = 0.039). CONCLUSIONS There were several independent factors associated with IR in patients with chronic HCV infection, including obesity, treatment experience, high serum ALT and triglyceride levels, as well as advanced hepatic fibrosis. After viral elimination by DAAs, we observed a significant reduction in mean HOMA-IR in patients with baseline high IR, HCV genotype 1, and treatment experience.
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Affiliation(s)
- Chun-Han Cheng
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan
- Department of Medicine, Mackay Medical College, New Taipei, Taiwan
| | - Chia-Ying Chu
- Department of Pathology, Taitung Mackay Memorial Hospital, Taitung, Taiwan
| | - Huan-Lin Chen
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan
- Department of Medicine, Mackay Medical College, New Taipei, Taiwan
| | - I-Tsung Lin
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan
- Department of Medicine, Mackay Medical College, New Taipei, Taiwan
| | - Chia-Hsien Wu
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan
- Department of Medicine, Mackay Medical College, New Taipei, Taiwan
| | - Yuan-Kai Lee
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan
- Department of Medicine, Mackay Medical College, New Taipei, Taiwan
| | - Ming-Jong Bair
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan
- Department of Medicine, Mackay Medical College, New Taipei, Taiwan
- *Correspondence: Ming-Jong Bair,
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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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Adinolfi LE, Petta S, Fracanzani AL, Nevola R, Coppola C, Narciso V, Rinaldi L, Calvaruso V, Pafundi PC, Lombardi R, Staiano L, Di Marco V, Solano A, Marrone A, Saturnino M, Rini F, Guerrera B, Troina G, Giordano M, Craxì A, Sasso FC. Reduced incidence of type 2 diabetes in patients with chronic hepatitis C virus infection cleared by direct-acting antiviral therapy: A prospective study. Diabetes Obes Metab 2020; 22:2408-2416. [PMID: 32761721 DOI: 10.1111/dom.14168] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 07/30/2020] [Accepted: 08/03/2020] [Indexed: 12/12/2022]
Abstract
AIM To assess the effect of hepatitis C virus (HCV) eradication on type 2 diabetes mellitus (T2DM). incidence. METHODS A prospective multicentre case-control study was performed, which included 2426 patients with HCV, 42% of whom had liver fibrosis stage F0-F2 and 58% of whom had liver fibrosis stage F3-F4. The study population consisted of a control group including 1099 untreated patients and 1327 cases treated with direct-acting antivirals (DAAs). T2DM incidence was assessed during a median (interquartile range) follow-up period of 30 (28-42) months. Risk factors for T2DM were assessed using a Cox regression model (relative risk [RR], hazard ratio [HR], Kaplan-Meier analysis). Insulin sensitivity was evaluated by homeostatic model assessment (HOMA) and changes by repeated-measures ANOVA. Factors independently associated with T2DM were assessed by multivariate analysis. RESULTS The absolute incidence of T2DM for controls and cases was 28 and 7/1000 person-years, respectively (P = 0.001). In cases compared to controls, HCV clearance reduced the RR and HR of T2DM by 81% and 75% to 93%, respectively (P = 0.001). It was calculated that, for every 15 patients who obtained HCV clearance, one case of T2DM was saved. HCV clearance was associated with significant reductions in HOMA-insulin resistance and HOMA-β-cell function and an increase in HOMA-insulin sensitivity, as assessed in 384 patients before and after HCV clearance. At multivariate analysis, HCV clearance emerged as independently associated with a reduced T2DM risk. CONCLUSION The results showed that HCV clearance by DAA treatment reduces T2DM incidence probably by restoring the HCV-induced alteration of glucose homeostasis mechanisms.
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Affiliation(s)
- Luigi E Adinolfi
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Salvatore Petta
- Division of Gastroenterology and Hepatology, PROMISE, University of Palermo, Palermo, Italy
| | - Anna L Fracanzani
- Department of Pathophysiology and Transplantation, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
| | - Riccardo Nevola
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Carmine Coppola
- Unit of Internal Medicine and Hepatolology, Gragnano Hospital, ASL Napoli 3 Sud, Naples, Italy
| | - Vincenzo Narciso
- Unit of Hepatology, Pellegrini Hospital, ASL Napoli 1 Centro, Naples, Italy
| | - Luca Rinaldi
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Vincenza Calvaruso
- Division of Gastroenterology and Hepatology, PROMISE, University of Palermo, Palermo, Italy
| | - Pia Clara Pafundi
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Rosa Lombardi
- Department of Pathophysiology and Transplantation, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
| | - Laura Staiano
- Unit of Internal Medicine and Hepatolology, Gragnano Hospital, ASL Napoli 3 Sud, Naples, Italy
| | - Vito Di Marco
- Division of Gastroenterology and Hepatology, PROMISE, University of Palermo, Palermo, Italy
| | - Antonio Solano
- Unit of Hepatology, Pellegrini Hospital, ASL Napoli 1 Centro, Naples, Italy
| | - Aldo Marrone
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Mariarosaria Saturnino
- Unit of Internal Medicine and Hepatolology, Gragnano Hospital, ASL Napoli 3 Sud, Naples, Italy
| | - Francesca Rini
- Division of Gastroenterology and Hepatology, PROMISE, University of Palermo, Palermo, Italy
| | - Barbara Guerrera
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Graziano Troina
- Division of Gastroenterology and Hepatology, PROMISE, University of Palermo, Palermo, Italy
| | - Mauro Giordano
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Antonio Craxì
- Division of Gastroenterology and Hepatology, PROMISE, University of Palermo, Palermo, Italy
| | - Ferdinando C Sasso
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
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22
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Tsai MC, Kao KL, Huang HC, Chen W, Fang CK, Sung FC, Wu SI, Stewart R. Incidence of Type 2 Diabetes in Patients With Chronic Hepatitis C Receiving Interferon-Based Therapy. Diabetes Care 2020; 43:e63-e64. [PMID: 32209648 PMCID: PMC7245353 DOI: 10.2337/dc19-1704] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2019] [Accepted: 02/17/2020] [Indexed: 02/03/2023]
Affiliation(s)
- Ming-Chieh Tsai
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Mackay Memorial Hospital, Tamshui Branch, New Taipei City, Taiwan
| | - Kai-Liang Kao
- Department of Pediatrics, Far Eastern Memory Hospital, New Taipei City, Taiwan
| | - Hui-Chun Huang
- Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan.,Mackay Medicine, Nursing and Management College, Taipei, Taiwan
| | - Weishan Chen
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan
| | - Chun-Kai Fang
- Section of Psychiatry, Mackay Memorial Hospital, Taipei, Taiwan
| | - Fung-Chang Sung
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan.,Department of Health Services Administration, China Medical University College of Public Health, Taichung, Taiwan
| | - Shu-I Wu
- Section of Psychiatry, Mackay Memorial Hospital, Taipei, Taiwan .,Department of Medicine, Mackay Medical College, Taipei, Taiwan
| | - Robert Stewart
- Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, U.K.,South London and Maudsley NHS Foundation Trust, London, U.K
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23
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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] [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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24
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Sevastianos VA, Voulgaris TA, Dourakis SP. Hepatitis C, systemic inflammation and oxidative stress: correlations with metabolic diseases. Expert Rev Gastroenterol Hepatol 2020; 14:27-37. [PMID: 31868062 DOI: 10.1080/17474124.2020.1708191] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Introduction: Hepatitis C chronic infection has long been correlated with numerous systemic diseases, such as diabetes mellitus and hepatic steatosis. Recent studies have also revealed an association with atherosclerosis.Areas covered: An analysis is presented on the mechanisms through which the hepatitis C viral infection can lead to a systemic increase in pro-inflammatory markers, especially tumor necrosis factor-a and interleukin-6. The immunological imbalance created may, through different mechanisms, act on the metabolic pathways that contribute to the development of insulin resistance, the accumulation of lipids in the liver, and even the formation of atherosclerotic plaques. Moreover, an additional contributing factor to the above-mentioned metabolic derangements is the unopposed oxidative stress observed in chronic hepatitis C viral infection. The virus itself contributes to the formation of oxidative stress, through alterations in the trace metal homeostasis and its effect on pro-inflammatory cytokines, such as tumor necrosis factor-a.Expert opinion: The scope of this review is to emphasize the importance of the metabolic manifestations of hepatitis C viral infection and to elucidate the pathophysiological mechanisms behind their emergence.
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Affiliation(s)
- Vassilios A Sevastianos
- Department of Internal Medicine and Liver Outpatient Clinic, "Evangelismos" General Hospital, Athens, Greece
| | - Theodoros A Voulgaris
- Department of Internal Medicine and Liver Outpatient Clinic, "Evangelismos" General Hospital, Athens, Greece
| | - Spyros P Dourakis
- Department of Internal Μedicine, Medical School, National and Kapodistrian University of Athens, General Hospital of Athens Ippokrateio, Athens, Greece
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25
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Sustained Improvement in Type 2 Diabetes Mellitus is Common After Treatment of Hepatitis C Virus With Direct-acting Antiviral Therapy. J Clin Gastroenterol 2019; 53:616-620. [PMID: 30614943 DOI: 10.1097/mcg.0000000000001168] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
GOALS To determine whether diabetic patients with hepatitis C virus (HCV) treated with direct-acting antiviral agents have improved diabetes, accounting for change in both hemoglobin A1c (HbA1c) and diabetes medications, and whether any improvement was sustained. BACKGROUND HCV infection is associated with an increased risk of diabetes, with improvement in glycemic control after eradication. There remains uncertainty about the durability and magnitude of this effect. STUDY HbA1c and diabetes medications were recorded at 6-month intervals for 1.5 years pretreatment and posttreatment for 122 patients. Subjects were classified as having improved diabetes if there was a decrease in HbA1c≥0.5% with no increase in diabetes medications or a decrease in diabetes medications with a stable HbA1c. RESULTS HbA1c at the nearest time point before treatment was 8.4%±1.9%, compared with 7.8%±1.7% after treatment, a mean difference of 0.6% [95% CI (0.2, 0.9), P<0.01]. A linear mixed effects model incorporating each subject's repeated measurements over time also demonstrated a reduction after treatment of 0.5% [95% CI, (0.3, 0.8), P<0.001]. Accounting for both HbA1c and diabetes medications, 42 of 122 (34%) had an improvement in diabetes after HCV treatment, and 20 of 28 (71%) of these subjects sustained improvement at 1.5 years follow-up. Prescription of insulin was associated with improved diabetes. CONCLUSIONS Treatment of HCV with direct-acting antiviral agents was associated with improved diabetes in a significant portion of patients with an average reduction in HbA1c of clinically significant magnitude. Among responders, this effect was sustained over 1.5 years of follow-up.
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26
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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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27
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Todorovska B, Caloska-Ivanova V, Dimitrova-Genadieva M, Trajkovska M, Popova-Jovanovska R, Grivceva-Stardelova K, Licoska-Josifovic F, Andreevski V, Curakova-Ristovska E, Joksimovic N. Atorvastatin in Combination with Pegylated Interferon and Ribavirin Provided High Rate of Sustained Virological Response in Patients with Genotype 3 Hepatitis C Virus. Open Access Maced J Med Sci 2019; 7:1641-1648. [PMID: 31210815 PMCID: PMC6560281 DOI: 10.3889/oamjms.2019.459] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Revised: 05/19/2019] [Accepted: 05/20/2019] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND: Chronic hepatitis C virus infection represents a more frequent cause of liver cirrhosis and hepatocellular carcinoma. Statins, inhibit HCV replication in vitro, enhance the antiviral effect of the already known antiviral drugs and reduce their resistance. AIM: To determine the impact of additional therapy (treatment with Atorvastatin 20 mg) to the standard antiviral therapy (pegylated interferon alpha-peg-IFN α and ribavirin) on achieving sustained virological response (SVR). MATERIAL AND METHODS: In the study which is comparative, open-label, prospective-retrospective, 70 patients diagnosed with chronic hepatitis C virus infection who met criteria for treatment with standard antiviral therapy combined with anti-lipemic therapy (Atorvastatin 20 mg) were included. Patients in the study were divided into two groups: one group of 35 patients receiving combination therapy (Atorvastatin + peg-IFN α + Ribavirin) and another group of 35 patients received only standard antiviral therapy. Those parameters were followed in all patients: genotyping, quantification of the virus, histological assessment of liver inflammation and fibrosis degree (before starting treatment), the presence of steatosis, laboratory analysis: hematology, liver, lipid and carbohydrate status, insulin blood level (the calculation of HOMA-IR) and body mass index (BMI) calculation. The overall treatment of the patients depends from the virus genotype, thus, patients with genotype 1 and 4 received 48 weeks standard antiviral therapy, but patients with genotypes 2 and 3 received 24 weeks of antiviral therapy. SVR was considered an undetectable level of HCV RNA levels 24 weeks after completion of antiviral therapy. The results were statistically analysed, and all results for p < 0.05 were considered statistically significant. RESULTS: Combination therapy leads to a slightly higher percentage of SVR (85.71%) in patients with chronic hepatitis C versus standard therapy (74.29%), but in a group of patients with genotype 3 this rate of SVR amounting to 95.83%. Combination therapy leads to significant improvement of lipid and glucose status after treatment, and in terms of side effects, there was no appearance of serious adverse events that would be a reason for discontinuation of the therapy. CONCLUSION: Combination therapy Atorvastatin + pegylated interferon alpha + Ribavirin leads to high rate of SVR of 95.83% in patients with chronic hepatitis C, genotype 3. Statins can be used safely in patients with chronic hepatitis C.
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Affiliation(s)
- Beti Todorovska
- University Clinic of Gastroenterohepatology, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje, Republic of Macedonia
| | - Viktorija Caloska-Ivanova
- University Clinic of Gastroenterohepatology, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje, Republic of Macedonia
| | - Magdalena Dimitrova-Genadieva
- University Clinic of Gastroenterohepatology, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje, Republic of Macedonia
| | - Meri Trajkovska
- University Clinic of Gastroenterohepatology, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje, Republic of Macedonia
| | - Rozalinda Popova-Jovanovska
- University Clinic of Gastroenterohepatology, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje, Republic of Macedonia
| | - Kalina Grivceva-Stardelova
- University Clinic of Gastroenterohepatology, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje, Republic of Macedonia
| | - Fana Licoska-Josifovic
- University Clinic of Gastroenterohepatology, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje, Republic of Macedonia
| | - Vladimir Andreevski
- University Clinic of Gastroenterohepatology, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje, Republic of Macedonia
| | - Elena Curakova-Ristovska
- University Clinic of Gastroenterohepatology, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje, Republic of Macedonia
| | - Nenad Joksimovic
- University Clinic of Gastroenterohepatology, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje, Republic of Macedonia
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28
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Liang J, Lv C, Chen M, Xu M, Zhao C, Yang Y, Wang J, Zhu D, Gao J, Rong R, Zhu T, Yu M. Effects of preoperative hepatitis B virus infection, hepatitis C virus infection, and coinfection on the development of new-onset diabetes after kidney transplantation. J Diabetes 2019; 11:370-378. [PMID: 30203544 DOI: 10.1111/1753-0407.12853] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2018] [Revised: 09/03/2018] [Accepted: 09/05/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The effects of preoperative hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, and HBV plus HCV coinfection on the development of new-onset diabetes after transplantation (NODAT) remain unexplored in kidney transplant recipients (KTRs). This study examined the association between preoperative viral status (i.e., HBV, HCV, and HBC + HCV infection) and incident NODAT in a large population of Chinese KTRs. METHODS This population-based retrospective cohort study enrolled 557 subjects who underwent kidney transplantation between 1993 and 2014 at Zhongshan Hospital. Pre-, peri-, and postoperative data were extracted and analyzed. Viral status was defined by serological results for hepatitis B surface antigen and anti-HCV antibody. The cumulative incidence of NODAT was compared across four groups of KTRs with different viral status. Multivariate Cox regression models were used to estimate the effects of HBV, HCV, and HBC + HCV infection on incident NODAT after adjusting for important confounders. RESULTS Patients seropositive for HCV (both HCV monoinfection and HBC + HCV coinfection) had a significantly higher cumulative incidence of NODAT than KTRs who were not infected with HCV (P < 0.05 for both). However, only HCV infection alone was found to be a risk factor for NODAT, increasing the NODAT risk 3.03-fold (95% confidence interval 1.77-5.18; P < 0.001). There was no independent correlation between HBV infection (alone or combined with HCV) and incident NODAT in KTRs. CONCLUSIONS Preoperative HCV infection significantly increased the risk of NODAT in Chinese KTRs, whereas HBV infection and HBC + HCV coinfection were not correlated with NODAT development.
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Affiliation(s)
- Jing Liang
- Departments of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Chaoyang Lv
- Departments of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
- Department of Geriatric Endocrinology, Zhengzhou Seventh People's Hospital, Zhengzhou, China
| | - Minling Chen
- Departments of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
- Departments of Endocrinology and Metabolism, People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine (The People's Hospital of Fujian Province), Fuzhou, China
| | - Ming Xu
- Department of Urology, Zhongshan Hospital, Fudan University, Shanghai Key Laboratory of Organ Transplantation, Shanghai, China
| | - Chenhe Zhao
- Departments of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yinqiu Yang
- Departments of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jina Wang
- Department of Urology, Zhongshan Hospital, Fudan University, Shanghai Key Laboratory of Organ Transplantation, Shanghai, China
| | - Dong Zhu
- Department of Urology, Zhongshan Hospital, Fudan University, Shanghai Key Laboratory of Organ Transplantation, Shanghai, China
| | - Jian Gao
- Center of Clinical Epidemiology and Evidence-based Medicine, Fudan University, Shanghai, China
| | - Ruiming Rong
- Department of Urology, Zhongshan Hospital, Fudan University, Shanghai Key Laboratory of Organ Transplantation, Shanghai, China
- Department of Transfusion, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Tongyu Zhu
- Department of Urology, Zhongshan Hospital, Fudan University, Shanghai Key Laboratory of Organ Transplantation, Shanghai, China
| | - Mingxiang Yu
- Departments of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
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29
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Gualerzi A, Bellan M, Smirne C, Tran Minh M, Rigamonti C, Burlone ME, Bonometti R, Bianco S, Re A, Favretto S, Bellomo G, Minisini R, Carnevale Schianca GP, Pirisi M. Improvement of insulin sensitivity in diabetic and non diabetic patients with chronic hepatitis C treated with direct antiviral agents. PLoS One 2018; 13:e0209216. [PMID: 30571711 PMCID: PMC6301649 DOI: 10.1371/journal.pone.0209216] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2018] [Accepted: 11/30/2018] [Indexed: 12/17/2022] Open
Abstract
Background The increased incidence of type 2 diabetes mellitus among hepatitis C virus (HCV) infected patients is likely due to viral-induced insulin resistance (IR). Indeed, control of diabetes in these patients benefits of successful antiviral treatment; whether the same applies to subtler alterations of glucose metabolism is unknown. We aimed to fill this gap. Methods The study population included 82 HCV-RNA positive patients (48 males, median age 66 years, 73 with advanced fibrosis, 41 HCV-1b), attending the liver clinic of an academic hospital to receive direct antivirals. None was previously known to be diabetic. All underwent a standard oral glucose tolerance test (OGTT) before antiviral treatment and right after its conclusion. Results At baseline, the majority of patients had evidence of abnormal glucose metabolism (N. = 45, 55%; impaired fasting glucose 10%, impaired glucose tolerance16%, both the above 12%, 17% diabetes), while only 37 (45%) were normally glucose tolerant (NGT). At the end of treatment, HCV-RNA quantification was below the detection threshold (HCV-RNA <12 UI/ml), for all patients enrolled. A significant decrease in glucose and insulin plasma concentrations was observed, leading to a significant reduction in Homeostasis Model Assessment (HOMA)-IR (from 3.42 [2.66–5.38] to 2.80 [1.78–3.95];p<0.001) and a corresponding increase in insulin sensitivity (ISI Belfiore from 0.49 [0.26–0.75] to 0.64 [0.42–0.91];p<0.001), despite a significant reduction in insulin secretion (EFP Stumvoll from 1363 [959–1730] to 1264 [976–1588];p = 0.027). Importantly, HOMA-IR reduction occurred also in the subgroup of NGT patients (p = 0.017). The number of NGT patients increased to 53, 65% (p = 0.013) paralleled by a reduced number of those satisfying criteria for prediabetic conditions (31 (38%) vs. 17 (21%); p = 0.025). Conclusions Glucose metabolism parameters of HCV infected patients improve early after antiviral treatment, with benefits that are not limited to diabetics. These findings confirm how deep and widespread is the impairment of insulin pathways exerted by HCV infection.
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Affiliation(s)
- Alessandro Gualerzi
- Department of Translational Medicine, Università del Piemonte Orientale UPO, Novara, Italy
- Division of Internal Medicine, “AOU Maggiore della Carità”, Novara, Italy
| | - Mattia Bellan
- Department of Translational Medicine, Università del Piemonte Orientale UPO, Novara, Italy
- Division of Internal Medicine, “Sant’Andrea Hospital”, Vercelli, Italy
- IRCAD, Interdisciplinary Research Center of Autoimmune Diseases, Novara, Italy
- * E-mail:
| | - Carlo Smirne
- Department of Translational Medicine, Università del Piemonte Orientale UPO, Novara, Italy
- Division of Internal Medicine, “AOU Maggiore della Carità”, Novara, Italy
| | - Margherita Tran Minh
- Department of Translational Medicine, Università del Piemonte Orientale UPO, Novara, Italy
- Division of Internal Medicine, “AOU Maggiore della Carità”, Novara, Italy
| | - Cristina Rigamonti
- Department of Translational Medicine, Università del Piemonte Orientale UPO, Novara, Italy
- Division of Internal Medicine, “AOU Maggiore della Carità”, Novara, Italy
| | - Michela Emma Burlone
- Department of Translational Medicine, Università del Piemonte Orientale UPO, Novara, Italy
- Division of Internal Medicine, “AOU Maggiore della Carità”, Novara, Italy
| | - Ramona Bonometti
- Department of Translational Medicine, Università del Piemonte Orientale UPO, Novara, Italy
- Division of Internal Medicine, “AOU Maggiore della Carità”, Novara, Italy
| | - Sara Bianco
- Department of Translational Medicine, Università del Piemonte Orientale UPO, Novara, Italy
- Division of Internal Medicine, “AOU Maggiore della Carità”, Novara, Italy
| | - Azzurra Re
- Department of Translational Medicine, Università del Piemonte Orientale UPO, Novara, Italy
- Division of Internal Medicine, “AOU Maggiore della Carità”, Novara, Italy
| | - Serena Favretto
- Department of Translational Medicine, Università del Piemonte Orientale UPO, Novara, Italy
- Division of Internal Medicine, “AOU Maggiore della Carità”, Novara, Italy
| | - Giorgio Bellomo
- Department of Health Sciences, Università del Piemonte Orientale UPO, Novara, Italy
| | - Rosalba Minisini
- Department of Translational Medicine, Università del Piemonte Orientale UPO, Novara, Italy
| | | | - Mario Pirisi
- Department of Translational Medicine, Università del Piemonte Orientale UPO, Novara, Italy
- Division of Internal Medicine, “AOU Maggiore della Carità”, Novara, Italy
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Lo Re V. Extrahepatic Complications of Hepatitis C Virus Infection in HIV and the Impact of Successful Antiviral Treatment. Clin Infect Dis 2018; 64:498-500. [PMID: 28172488 DOI: 10.1093/cid/ciw814] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2016] [Accepted: 12/06/2016] [Indexed: 12/14/2022] Open
Affiliation(s)
- Vincent Lo Re
- Division of Infectious Diseases, Department of Medicine, Penn Center for AIDS Research, Penn Center for Viral Hepatitis,Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics, Center for Pharmacoepidemiology Research and Training, Perelman School of Medicine, University of Pennsylvania, Philadelphia
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31
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Hamed AE, Elsahar M, Elwan NM, El-Nakeep S, Naguib M, Soliman HH, Ahmed Aboubakr A, AbdelMaqsod A, Sedrak H, Assaad SN, Elwakil R, Esmat G, Salh S, Mostafa T, Mogawer S, Sadek SE, Saber MM, Ezelarab H, Mahmoud AA, Sultan S, El Kassas M, Kamal E, ElSayed NM, Moussa S. Managing diabetes and liver disease association. Arab J Gastroenterol 2018; 19:166-179. [PMID: 30420265 DOI: 10.1016/j.ajg.2018.08.003] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Accepted: 08/26/2018] [Indexed: 02/05/2023]
Abstract
There is strong association between liver diseases and diabetes (DM) which is higher than expected by a chance association of two very common disorders. It can be classified into three categories: Liver disease related to diabetes, hepatogenous diabetes (HD), and liver disease occurring coincidentally with DM. The criteria for the diagnosis of diabetes associating liver disease are the same for primary diabetes. Two hours post glucose load is a better screening test for HD. HbA1c may not be suitable for diagnosis or monitoring of diabetes associating advanced liver disease. Apart from the increased cardiovascular risk in patients with type 2 DM (T2 DM) and NAFLD, the cardiovascular and retinopathy risk is low in HD. Patients with metabolic derangement should be screened for NAFLD which in turn may predict T2 DM development. Similarly, patients with established T2 DM should also be screened for NAFLD which further contributes to diabetes worsening. Diabetes is a significant risk factor for progression of the chronic liver disease. It is associated with poor patient survival. Treatment of diabetes associating liver disease appears beneficial. Metformin, if tolerated and not contraindicated, is recommended as a first-line therapy for patients with diabetes and chronic liver disease (CLD). If the hepatic disease is severe, insulin secretagogues should be avoided because of the increased risk of hypoglycaemia. Pioglitazone may be useful in patients with fatty liver disease. DPP-4 inhibitors showed effectiveness and safety for the treatment of T2 DM in CLD patients up to those with child B stage. GLP-1 receptor agonists and SGLT-2 inhibitors exhibit positive effects on weight and are associated with minimal risk of hypoglycaemia. Insulin must be used with caution, as hypoglycaemia may be a problem. Insulin analogues are preferred in the context of hypoglycaemia Statins can be used to treat dyslipidaemia in NAFLD, also the use of angiotensin II receptor antagonist for hypertension is safe and beneficial Given the clear association between diabetes mellitus and hepatocellular carcinoma, the strict control of glycaemia with insulin sensitizers can be essential in its prevention. The addition of DM to the currently used scores (Child-Pugh and MELD scores) may enhance the sensitivity and the specificity for prediction of morbidity and mortality rates in cirrhotic patients. In the new era of directly acting antiviral agents (DAAs) for HCV treatment, it is recommended to follow up lipid profile and blood sugar levels following SVR in order to adjust doses of medications used in diabetic (SVR is associated with reduction in insulin requirements) and dyslipidaemic patients (rebound increase in the lipid profile after clearing the virus may increase risk of cardiovascular disease (CVD)). The issues of post liver transplant diabetes and relation between DM and chronic HBV are highlighted. This narrative review and Consensus-based practice guidance (under revision and criticism) are based on a formal review and analysis of the recently published world literature on the topic (Medline search up to September 2017); and the experience of the authors and independent reviewers.
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Affiliation(s)
- Abd Elkhalek Hamed
- The Egyptian Association for the Study of Liver and Gastrointestinal Disease (EASLGD), Egypt; Department of Internal Medicine, Hepatology, and Diabetes, Egyptian Military Medical Academy, Egypt.
| | - Medhat Elsahar
- The Egyptian Association for the Study of Liver and Gastrointestinal Disease (EASLGD), Egypt; Police Medical Academy, Egypt
| | | | | | | | | | - Ashraf Ahmed Aboubakr
- Department of Internal Medicine, Hepatology, and Diabetes, Egyptian Military Medical Academy, Egypt
| | | | | | | | - Reda Elwakil
- The Egyptian Association for the Study of Liver and Gastrointestinal Disease (EASLGD), Egypt; Ain Shams University, Egypt
| | - Gamal Esmat
- The Egyptian Association for the Study of Liver and Gastrointestinal Disease (EASLGD), Egypt; Kasr Al Aini, Egypt
| | - Samira Salh
- Department of Pharmacy, Cairo University, Egypt
| | | | | | - Sameh Emil Sadek
- Department of Internal Medicine, Hepatology, and Diabetes, Egyptian Military Medical Academy, Egypt
| | - Maha M Saber
- Department of Clinical Nutrition National Research Centre, Egypt
| | - Hanan Ezelarab
- Department of Clinical Nutrition National Research Centre, Egypt
| | - Asem Ashraf Mahmoud
- Department of Internal Medicine, Hepatology, and Diabetes, Egyptian Military Medical Academy, Egypt
| | | | | | - Ehab Kamal
- Medical Department, National Research Centre, Egypt
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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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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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Wigneswaran J, Van Wyck D, Pegues D, Gholam P, Nissenson AR. Hepatitis C virus infection in patients with end-stage renal disease. Hemodial Int 2018; 22:297-307. [DOI: 10.1111/hdi.12672] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2018] [Revised: 03/27/2018] [Indexed: 12/22/2022]
Affiliation(s)
| | | | - David Pegues
- Hospital of the University of Pennsylvania; Philadelphia Pennsylvania USA
| | - Pierre Gholam
- Liver Center of Excellence; University Hospitals of Cleveland; Cleveland Ohio USA
| | - Allen R. Nissenson
- DaVita, Inc.; Denver Colorado USA
- David Geffen School of Medicine; University of California; Los Angeles California USA
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Li J, Zhang T, Gordon SC, Rupp LB, Trudeau S, Holmberg SD, Moorman AC, Spradling PR, Teshale EH, Boscarino JA, Schmidt MA, Daida YG, Lu M. Impact of sustained virologic response on risk of type 2 diabetes among hepatitis C patients in the United States. J Viral Hepat 2018; 25:952-958. [PMID: 29478263 PMCID: PMC6205163 DOI: 10.1111/jvh.12887] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2017] [Accepted: 01/16/2018] [Indexed: 12/27/2022]
Abstract
Data regarding the impact of hepatitis C (HCV) therapy on incidence of type 2 diabetes mellitus are limited. We used the data from the longitudinal Chronic Hepatitis Cohort Study-drawn from four large US health systems-to investigate how response to HCV treatment impacts the risk of subsequent diabetes. Among HCV patients without a history of type 2 diabetes mellitus or hepatitis B, we investigated the incidence of type 2 diabetes from 12 weeks post-HCV treatment through December 2015. Cox proportional hazards models were used to test the effect of treatment status (sustained virologic response [SVR] or treatment failure) and baseline risk factors on the development of diabetes, considering any possible risk factor-by-SVR interactions, and death as a competing risk. Among 5127 patients with an average follow-up of 3.7 years, diabetes incidence was significantly lower among patients who achieved SVR (231/3748; 6.2%) than among patients with treatment failure (299/1379; 21.7%; adjusted hazard ratio [aHR] = 0.79; 95% CI: 0.65-0.96). Risk of diabetes was higher among African American and Asian American patients than White patients (aHR = 1.82 and 1.75, respectively; P < .05), and among Hispanic patients than non-Hispanics (aHR = 1.86). Patients with BMI ≥ 30 and 25-30 (demonstrated higher risk of diabetes aHR = 3.62 and 1.72, respectively; P < .05) than those with BMI < 25; patients with cirrhosis at baseline had higher risk than those without cirrhosis (aHR = 1.47). Among a large US cohort of patients treated for HCV, patients who achieved SVR demonstrated a substantially lower risk for the development of type 2 diabetes mellitus than patients with treatment failure.
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Affiliation(s)
- J. Li
- Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA
| | - T. Zhang
- Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA
| | - S. C. Gordon
- Division of Gastroenterology and Hepatology, Henry Ford Health System, Detroit, MI, USA
| | - L. B. Rupp
- Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, MI, USA
| | - S. Trudeau
- Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA
| | - S. D. Holmberg
- Division of Viral Hepatitis, National Center for HIV, Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - A. C. Moorman
- Division of Viral Hepatitis, National Center for HIV, Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - P. R. Spradling
- Division of Viral Hepatitis, National Center for HIV, Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - E. H. Teshale
- Division of Viral Hepatitis, National Center for HIV, Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - J. A. Boscarino
- Department of Epidemiology and Health Services Research, Geisinger Clinic, Danville, PA, USA
| | - M. A. Schmidt
- Center for Health Research, Kaiser Permanente–Northwest, Portland, OR, USAs
| | - Y. G. Daida
- Center for Health Research, Kaiser Permanente–Hawaii, Honolulu, HI, USA
| | - M. Lu
- Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA
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Petta S, Adinolfi LE, Fracanzani AL, Rini F, Caldarella R, Calvaruso V, Cammà C, Ciaccio M, Di Marco V, Grimaudo S, Licata A, Marrone A, Nevola R, Pipitone RM, Pinto A, Rinaldi L, Torres D, Tuttolomondo A, Valenti L, Fargion S, Craxì A. Hepatitis C virus eradication by direct-acting antiviral agents improves carotid atherosclerosis in patients with severe liver fibrosis. J Hepatol 2018; 69:18-24. [PMID: 29505844 DOI: 10.1016/j.jhep.2018.02.015] [Citation(s) in RCA: 92] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Revised: 02/14/2018] [Accepted: 02/19/2018] [Indexed: 12/22/2022]
Abstract
BACKGROUND AND AIMS Recent studies suggest an association between hepatitis C virus (HCV) infection and cardiovascular damage, including carotid atherosclerosis, with a possible effect of HCV clearance on cardiovascular outcomes. We aimed to examine whether HCV eradication by direct-acting antiviral agents (DAA) improves carotid atherosclerosis in HCV-infected patients with advanced fibrosis/compensated cirrhosis. MATERIALS AND METHODS One hundred eighty-two consecutive patients with HCV and advanced fibrosis or compensated cirrhosis were evaluated. All patients underwent DAA-based antiviral therapy according to AISF/EASL guidelines. Intima-media thickness (IMT), carotid thickening (IMT ≥1 mm) and carotid plaques, defined as focal thickening of ≥1.5 mm at the level of the common carotid, were evaluated by ultrasonography (US) at baseline and 9-12 months after the end of therapy. Fifty-six percent of patients were male, mean age 63.1 ± 10.4 years, and 65.9% had compensated cirrhosis. One in five had diabetes, 14.3% were obese, 41.8% had arterial hypertension and 35.2% were smokers. At baseline, mean IMT was 0.94 ± 0.29 mm, 42.8% had IMT ≥1 mm, and 42.8% had carotid plaques. RESULTS All patients achieved a 12-week sustained virological response. IMT significantly decreased from baseline to follow-up (0.94 ± 0.29 mm vs. 0.81 ± 0.27, p <0.001). Consistently, a significant reduction in the prevalence of patients with carotid thickening from baseline to follow-up was observed (42.8% vs. 17%, p <0.001), while no changes were reported for carotid plaques (42.8% vs. 47.8%, p = 0.34). These results were confirmed in subgroups of patients stratified for cardiovascular risk factors and liver disease severity. CONCLUSION HCV eradication by DAA improves carotid atherosclerosis in patients with severe fibrosis with or without additional metabolic risk factors. The impact of this improvement in the atherosclerotic burden in terms of reduction of major cardiovascular outcomes is worth investigating in the long term. LAY SUMMARY Hepatitis C virus eradication by direct-acting antiviral agents improves carotid atherosclerosis in patients with advanced fibrosis/compensated cirrhosis. The improvement in intima-media thickness and carotid thickening was confirmed after stratification for severity of liver disease and cardiovascular risk factors. Hepatitis C virus eradication by direct-acting antiviral agents also lead to improvement in glucose homeostasis and increased cholesterol levels.
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Affiliation(s)
- Salvatore Petta
- Sezione di Gastroenterologia e Epatologia, Di.Bi.M.I.S, Università di Palermo, Italy.
| | - Luigi Elio Adinolfi
- Department of Medical, Surgical, Neurological, Geriatric, and Metabolic Sciences, University of Campania "Luigi Vanvitelli", 80100 Naples, Italy
| | - Anna Ludovica Fracanzani
- Department of Pathophysiology and Transplantation, Ca' Granda IRCCS Foundation, Policlinico Hospital, University of Milan, Italy
| | - Francesca Rini
- Sezione di Gastroenterologia e Epatologia, Di.Bi.M.I.S, Università di Palermo, Italy
| | - Rosalia Caldarella
- Department of Biopathology and Medical Biotechnologies, University of Palermo, Palermo, Italy
| | - Vincenza Calvaruso
- Sezione di Gastroenterologia e Epatologia, Di.Bi.M.I.S, Università di Palermo, Italy
| | - Calogero Cammà
- Sezione di Gastroenterologia e Epatologia, Di.Bi.M.I.S, Università di Palermo, Italy
| | - Marcello Ciaccio
- Department of Biopathology and Medical Biotechnologies, University of Palermo, Palermo, Italy
| | - Vito Di Marco
- Sezione di Gastroenterologia e Epatologia, Di.Bi.M.I.S, Università di Palermo, Italy
| | - Stefania Grimaudo
- Sezione di Gastroenterologia e Epatologia, Di.Bi.M.I.S, Università di Palermo, Italy
| | - Anna Licata
- Sezione di Gastroenterologia e Epatologia, Di.Bi.M.I.S, Università di Palermo, Italy
| | - Aldo Marrone
- Department of Medical, Surgical, Neurological, Geriatric, and Metabolic Sciences, University of Campania "Luigi Vanvitelli", 80100 Naples, Italy
| | - Riccardo Nevola
- Department of Medical, Surgical, Neurological, Geriatric, and Metabolic Sciences, University of Campania "Luigi Vanvitelli", 80100 Naples, Italy
| | | | - Antonio Pinto
- Sezione di Medicina Interna con Stroke Care, Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S), Università di Palermo, Italy
| | - Luca Rinaldi
- Department of Medical, Surgical, Neurological, Geriatric, and Metabolic Sciences, University of Campania "Luigi Vanvitelli", 80100 Naples, Italy
| | - Daniele Torres
- Sezione di Medicina Interna con Stroke Care, Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S), Università di Palermo, Italy
| | - Antonino Tuttolomondo
- Sezione di Medicina Interna con Stroke Care, Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S), Università di Palermo, Italy
| | - Luca Valenti
- Department of Pathophysiology and Transplantation, Ca' Granda IRCCS Foundation, Policlinico Hospital, University of Milan, Italy
| | - Silvia Fargion
- Department of Pathophysiology and Transplantation, Ca' Granda IRCCS Foundation, Policlinico Hospital, University of Milan, Italy
| | - Antonio Craxì
- Sezione di Gastroenterologia e Epatologia, Di.Bi.M.I.S, Università di Palermo, Italy
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Adinolfi LE, Nevola R, Guerrera B, D'Alterio G, Marrone A, Giordano M, Rinaldi L. Hepatitis C virus clearance by direct-acting antiviral treatments and impact on insulin resistance in chronic hepatitis C patients. J Gastroenterol Hepatol 2018; 33:1379-1382. [PMID: 29228501 DOI: 10.1111/jgh.14067] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2017] [Accepted: 12/04/2017] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND AIM Chronic hepatitis C virus (HCV), particularly genotype 1, is associated with insulin resistance (IR) and diabetes. This study evaluated the impact of HCV clearance by all-oral direct-acting antiviral treatments on IR and glycemic control. METHODS Included in this prospective case-control study were 133 consecutive HCV-genotype 1 patients with advance liver fibrosis (F3-F4) without type 2 diabetes. Sixty eight were treated with direct-acting antiviral and 65 were untreated. Liver fibrosis was assessed by transient elastography. Pre-treatment, end-treatment, and 3 months post-treatment withdrawal IR homeostasis was assessed by homeostatic model assessment (HOMA)-IR, HOMA-S, and HOMA-B. RESULTS At baseline, treated, and untreated patients showed similar liver fibrosis levels, HOMA-IR was 4.90 ± 4.62 and 4.64 ± 5.62, respectively. HOMA-IR correlated with HCV RNA levels. At the end of treatment, all patients cleared HCV RNA, regardless of liver fibrosis and body mass index, and a reduction in HOMA-IR at 2.42 ± 1.85 was showed (P < 0.001); in addition, increased insulin sensitivity, decreased insulin secretion, reduction of serum glucose, and insulin levels were observed. Data were confirmed 3 months after treatment withdrawal in the 65 patients who cleared HCV. No variation occurred in untreated patients. Overall, 76.5% of sustained virologic response patients showed IR improvements, of which 41.2% normalized IR. Improvement of IR was strictly associated with HCV clearance; however, patients with the highest levels of fibrosis remain associated with some degree of IR. CONCLUSIONS The data underline a role of HCV in development of IR and that viral eradication reverses IR and improves glycemic control and this could prevent IR-related clinical manifestations and complications.
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Affiliation(s)
- Luigi E Adinolfi
- Internal Medicine, Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Riccardo Nevola
- Clinical Hospital of Marcianise, ASL Caserta, Caserta, Italy
| | | | - Giovanni D'Alterio
- Internal Medicine, Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Aldo Marrone
- Internal Medicine, Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Mauro Giordano
- Clinical Hospital of Marcianise, ASL Caserta, Caserta, Italy
| | - Luca Rinaldi
- Internal Medicine, Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
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38
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Yen YH, Lin MT, Kuo FY, Chang KC, Tsai MC, Tseng PL, Wu CK, Lin JT, Hu TH, Lu SN, Wang JH, Hung CH, Chen CH. The association between steatosis and diabetes with hepatocellular carcinoma in non-genotype 3 chronic hepatitis C patients. Liver Int 2018; 38:1064-1073. [PMID: 29164767 DOI: 10.1111/liv.13633] [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: 07/07/2017] [Accepted: 11/13/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Diabetes mellitus (DM) has been found to be strongly associated with an increased risk of hepatocellular carcinoma (HCC) among chronic hepatitis C (CHC) patients. Several studies have also found an association between metabolic steatosis and the risk of HCC in CHC patients, whether this latter association has been accounted for by the known relationship between DM and HCC is still unknown. METHODS A cohort consisting of 976 non-genotype 3 patients histologically proven to have CHC and treated with interferon and ribavirin was studied. Cumulative incidence and HCC risk were analysed using the Kaplan-Meier method and Cox proportional hazard analysis. RESULTS Hepatocellular carcinoma developed in 140 subjects over a median follow-up period of 97.3 months, while 699 patients achieved sustained virological response (SVR). According to multivariate analyses, age ≥ 60 years, advanced fibrosis and genotype 1 were identified as independent factors significantly associated with HCC development in SVR patients. Furthermore, using the absence of steatosis and absence of DM as references, the presence of steatosis without DM (HR = 2.09, 95% CI = 1.12-3.9, P = .021), the presence of DM without steatosis (HR = 2.78, 95% CI = 1.3-5.92, P = .008) and the combined presence of steatosis and DM (HR = 3.25, 95% CI = 1.44-7.33, P = .004) were identified as independent factors significantly associated with HCC development in the SVR patients. In contrast, steatosis alone, DM alone and the combined presence of steatosis and DM were not associated with HCC development in non-SVR patients. CONCLUSIONS Steatosis and DM may be associated with HCC development in non-genotype 3 CHC patients with SVR.
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Affiliation(s)
- Yi-Hao Yen
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Ming-Tsung Lin
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Fang-Ying Kuo
- Department of Pathology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Kuo-Chin Chang
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Ming-Chao Tsai
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Po-Lin Tseng
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Cheng-Kun Wu
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Jung-Ting Lin
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Tsung-Hui Hu
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Sheng-Nan Lu
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Jing-Houng Wang
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chien-Hung Chen
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan
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39
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Adinolfi LE, Jacobson I, Bondin M, Cacoub P. Expert opinion on managing chronic HCV infection in patients with type 2 diabetes mellitus. Antivir Ther 2018; 23:11-21. [PMID: 30451154 DOI: 10.3851/imp3255] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/27/2018] [Indexed: 02/07/2023]
Abstract
Type 2 diabetes mellitus (T2DM) has been identified as an extrahepatic manifestation of chronic HCV infection. Conversely, in the context of chronic HCV infection, T2DM can accelerate the course of HCV-induced liver disease leading to increased risk of fibrosis, cirrhosis and hepatocellular carcinoma. The presence of T2DM negatively impacts the efficacy of interferon-based antiviral therapy, but real-world data with high-efficacy direct-acting antiviral therapies suggest high viral clearance rates in T2DM patients. In HCV-infected individuals, viral eradication is associated with a reduced risk of de novo T2DM in non-diabetic patients and beneficial metabolic changes in patients with T2DM, highlighting the importance of antiviral treatment and physician awareness of this association.
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MESH Headings
- Antiviral Agents/therapeutic use
- Blood Glucose/drug effects
- Carcinoma, Hepatocellular/drug therapy
- Carcinoma, Hepatocellular/etiology
- Carcinoma, Hepatocellular/pathology
- Carcinoma, Hepatocellular/virology
- Diabetes Mellitus, Type 2/complications
- Diabetes Mellitus, Type 2/drug therapy
- Diabetes Mellitus, Type 2/prevention & control
- Diabetes Mellitus, Type 2/virology
- Disease Management
- Drug Combinations
- Glycated Hemoglobin/antagonists & inhibitors
- Glycated Hemoglobin/metabolism
- Hepatitis C, Chronic/complications
- Hepatitis C, Chronic/drug therapy
- Hepatitis C, Chronic/pathology
- Hepatitis C, Chronic/virology
- Humans
- Insulin Resistance
- Liver/drug effects
- Liver/metabolism
- Liver/pathology
- Liver/virology
- Liver Cirrhosis/drug therapy
- Liver Cirrhosis/etiology
- Liver Cirrhosis/pathology
- Liver Cirrhosis/virology
- Liver Neoplasms/drug therapy
- Liver Neoplasms/etiology
- Liver Neoplasms/pathology
- Liver Neoplasms/virology
- Risk Factors
- Treatment Outcome
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Affiliation(s)
- Luigi Elio Adinolfi
- Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, Università degli Studi della Campania 'Luigi Vanvitelli', Naples, Italy
| | | | | | - Patrice Cacoub
- Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France
- INSERM, UMR_S 959, Paris, France
- CNRS, FRE3632, Paris, France
- AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
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40
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Abdel Alem S, Elsharkawy A, Fouad R, Adel E, Abdellatif Z, Musa S, Nagy A, Hussein MS, Yosry A, Esmat G. Improvement of glycemic state among responders to Sofosbuvir-based treatment regimens: Single center experience. J Med Virol 2017; 89:2181-2187. [PMID: 28688190 DOI: 10.1002/jmv.24897] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2017] [Accepted: 07/01/2017] [Indexed: 12/11/2022]
Abstract
Chronic HCV infection has emerged as a complex multifaceted disease with manifestations extending beyond the liver. HCV plays a direct role in glucose metabolism leading to both insulin resistance and type 2 diabetes. To evaluate the changes in the glycemic state following Sofosbuvir-based treatment regimens in diabetic HCV patients. Four hundred chronic hepatitis C patients who underwent Sofosbuvir-based treatment regimens were retrospectively screened. Sixty-five diabetic HCV patients only enrolled in our analysis. Baseline demographic and laboratory data were recorded. Pretreatment Transient elastography was performed. At 24-week post EOT (SVR24), Fasting Plasma glucose, and Hemoglobin A1c were re-evaluated and compared with baseline. All enrolled diabetic patients were responders. They showed statistically significant decline in Fasting Plasma glucose and Hemoglobin A1c values at SVR24. Whatever the degree of hepatic fibrosis, the level of Fasting Plasma glucose and Hemoglobin A1c decreased at SVR24 in comparison to baseline level. Fifty-one patients showed improvement in their Hemoglobin A1c values at SVR24 and this improvement was more likely to occur among patients with low Body mass index. The reduction in Fasting Plasma glucose >20 mg/dL (>1.1 mmol/L) and Hemoglobin A1c ≥0.5% was not associated with age, gender or hepatic fibrosis stage. Sofosbuvir-based regimens are a highly efficient antiviral therapy for diabetic chronic HCV patients resulted in improvement in Fasting Plasma glucose and Hemoglobin A1c.
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Affiliation(s)
- Shereen Abdel Alem
- Endemic Medicine and Hepatology Department, Faculty of medicine, Cairo University, Cairo, Egypt.,Kasr Al-Ainy viral hepatitis Centre, Cairo University, Cairo, Egypt
| | - Aisha Elsharkawy
- Endemic Medicine and Hepatology Department, Faculty of medicine, Cairo University, Cairo, Egypt.,Kasr Al-Ainy viral hepatitis Centre, Cairo University, Cairo, Egypt
| | - Rabab Fouad
- Endemic Medicine and Hepatology Department, Faculty of medicine, Cairo University, Cairo, Egypt.,Kasr Al-Ainy viral hepatitis Centre, Cairo University, Cairo, Egypt
| | - Eman Adel
- Kasr Al-Ainy viral hepatitis Centre, Cairo University, Cairo, Egypt
| | - Zeinab Abdellatif
- Endemic Medicine and Hepatology Department, Faculty of medicine, Cairo University, Cairo, Egypt.,Kasr Al-Ainy viral hepatitis Centre, Cairo University, Cairo, Egypt
| | - Sherief Musa
- Endemic Medicine and Hepatology Department, Faculty of medicine, Cairo University, Cairo, Egypt
| | - Ahmed Nagy
- Kasr Al-Ainy viral hepatitis Centre, Cairo University, Cairo, Egypt
| | | | - Ayman Yosry
- Endemic Medicine and Hepatology Department, Faculty of medicine, Cairo University, Cairo, Egypt
| | - Gamal Esmat
- Endemic Medicine and Hepatology Department, Faculty of medicine, Cairo University, Cairo, Egypt.,Kasr Al-Ainy viral hepatitis Centre, Cairo University, Cairo, Egypt
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41
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Abstract
Chronic infection with hepatitis C virus (HCV) is a multifaceted disease characterized by many extrahepatic manifestations (EHMs) that affect outcome and quality of life. HCV eradication by antiviral treatment has been proved beneficial in preventing the development of EHMs and is also able to improve many HCV-related severe disorders and neurocognitive outcomes and quality of life. Until recently, antiviral therapy of EHMs was limited to the presence of interferon-based treatment, and was contraindicated in many patients because of hematologic toxicity or risk of exacerbating immune-mediated disorders. The availability of interferon-free regimens solves this issue allowing for enhanced safety and efficacy to provide universal treatment of HCV-related EHMs.
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42
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Mihai C, Mihai B, Trifan A, Stanciu C, Gheorghe L, Diculescu M, Curescu M, Brisc C, Goldis A, Bataga S, Sandulescu L, Rogoveanu I, Seicean A, Cijevschi Prelipcean C. Metabolic Syndrome and Genotype 1 Virus C Compensated Liver Cirrhosis in the Era of Directly Acting Antiviral Therapy. HEPATITIS MONTHLY 2017; 17. [DOI: 10.5812/hepatmon.58022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
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43
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Lerat H, Imache MR, Polyte J, Gaudin A, Mercey M, Donati F, Baudesson C, Higgs MR, Picard A, Magnan C, Foufelle F, Pawlotsky JM. Hepatitis C virus induces a prediabetic state by directly impairing hepatic glucose metabolism in mice. J Biol Chem 2017; 292:12860-12873. [PMID: 28559285 DOI: 10.1074/jbc.m117.785030] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2017] [Revised: 05/18/2017] [Indexed: 12/15/2022] Open
Abstract
Virus-related type 2 diabetes is commonly observed in individuals infected with the hepatitis C virus (HCV); however, the underlying molecular mechanisms remain unknown. Our aim was to unravel these mechanisms using FL-N/35 transgenic mice expressing the full HCV ORF. We observed that these mice displayed glucose intolerance and insulin resistance. We also found that Glut-2 membrane expression was reduced in FL-N/35 mice and that hepatocyte glucose uptake was perturbed, partly accounting for the HCV-induced glucose intolerance in these mice. Early steps of the hepatic insulin signaling pathway, from IRS2 to PDK1 phosphorylation, were constitutively impaired in FL-N/35 primary hepatocytes via deregulation of TNFα/SOCS3. Higher hepatic glucose production was observed in the HCV mice, despite higher fasting insulinemia, concomitant with decreased expression of hepatic gluconeogenic genes. Akt kinase activity was higher in HCV mice than in WT mice, but Akt-dependent phosphorylation of the forkhead transcription factor FoxO1 at serine 256, which triggers its nuclear exclusion, was lower in HCV mouse livers. These findings indicate an uncoupling of the canonical Akt/FoxO1 pathway in HCV protein-expressing hepatocytes. Thus, the expression of HCV proteins in the liver is sufficient to induce insulin resistance by impairing insulin signaling and glucose uptake. In conclusion, we observed a complete set of events leading to a prediabetic state in HCV-transgenic mice, providing a valuable mechanistic explanation for HCV-induced diabetes in humans.
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Affiliation(s)
- Hervé Lerat
- INSERM, U955, Team "Pathophysiology and Therapy of Chronic Viral Hepatitis and Related Cancers", 94010 Créteil, France; Université Paris-Est Créteil Val de Marne, 94010 Créteil, France.
| | - Mohamed Rabah Imache
- INSERM, U955, Team "Pathophysiology and Therapy of Chronic Viral Hepatitis and Related Cancers", 94010 Créteil, France
| | - Jacqueline Polyte
- INSERM, U955, Team "Pathophysiology and Therapy of Chronic Viral Hepatitis and Related Cancers", 94010 Créteil, France
| | - Aurore Gaudin
- INSERM, U955, Team "Pathophysiology and Therapy of Chronic Viral Hepatitis and Related Cancers", 94010 Créteil, France
| | - Marion Mercey
- INSERM, U955, Team "Pathophysiology and Therapy of Chronic Viral Hepatitis and Related Cancers", 94010 Créteil, France
| | - Flora Donati
- INSERM, U955, Team "Pathophysiology and Therapy of Chronic Viral Hepatitis and Related Cancers", 94010 Créteil, France
| | - Camille Baudesson
- INSERM, U955, Team "Pathophysiology and Therapy of Chronic Viral Hepatitis and Related Cancers", 94010 Créteil, France
| | - Martin R Higgs
- INSERM, U955, Team "Pathophysiology and Therapy of Chronic Viral Hepatitis and Related Cancers", 94010 Créteil, France
| | - Alexandre Picard
- Unité de Biologie Fonctionnelle et Adaptative, Sorbonne Paris Cité, CNRS UMR 8251, Université Paris Diderot, 75013 Paris, France
| | - Christophe Magnan
- Unité de Biologie Fonctionnelle et Adaptative, Sorbonne Paris Cité, CNRS UMR 8251, Université Paris Diderot, 75013 Paris, France
| | - Fabienne Foufelle
- INSERM, UMRS 1138, Centre de Recherche des Cordeliers, 75006 Paris, France
| | - Jean-Michel Pawlotsky
- INSERM, U955, Team "Pathophysiology and Therapy of Chronic Viral Hepatitis and Related Cancers", 94010 Créteil, France; Université Paris-Est Créteil Val de Marne, 94010 Créteil, France; National Reference Center for Viral Hepatitis B, C and Delta, Department of Virology, Hôpital Henri Mondor, AP-HP, 94010 Créteil, France
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44
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Desbois AC, Cacoub P. Diabetes mellitus, insulin resistance and hepatitis C virus infection: A contemporary review. World J Gastroenterol 2017; 23:1697-1711. [PMID: 28321170 PMCID: PMC5340821 DOI: 10.3748/wjg.v23.i9.1697] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2016] [Revised: 11/10/2016] [Accepted: 02/08/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To summarise the literature data on hepatitis C virus (HCV)-infected patients concerning the prevalence of glucose abnormalities and associated risk.
METHODS We conducted a PubMed search and selected all studies found with the key words "HCV" or "hepatitis C virus" and "diabetes" or "insulin resistance". We included only comparative studies written in English or in French, published from January 2000 to April 2015. We collected the literature data on HCV-infected patients concerning the prevalence of glucose abnormalities [diabetes mellitus (DM) and insulin resistance (IR)] and associated risk [i.e., severe liver fibrosis, response to antivirals, and the occurrence of hepatocellular carcinoma (HCC)].
RESULTS HCV infection is significantly associated with DM/IR compared with healthy volunteers and patients with hepatitis B virus infection. Glucose abnormalities were associated with advanced liver fibrosis, lack of sustained virologic response to interferon alfa-based treatment and with a higher risk of HCC development. As new antiviral therapies may offer a cure for HCV infection, such data should be taken into account, from a therapeutic and preventive point of view, for liver and non-liver consequences of HCV disease. The efficacy of antidiabetic treatment in improving the response to antiviral treatment and in decreasing the risk of HCC has been reported by some studies but not by others. Thus, the effects of glucose abnormalities correction in reducing liver events need further studies.
CONCLUSION Glucose abnormalities are strongly associated with HCV infection and show a negative impact on the main liver related outcomes.
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45
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Gastaldi G, Goossens N, Clément S, Negro F. Current level of evidence on causal association between hepatitis C virus and type 2 diabetes: A review. J Adv Res 2017; 8:149-159. [PMID: 28149650 PMCID: PMC5272937 DOI: 10.1016/j.jare.2016.11.003] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2016] [Revised: 11/16/2016] [Accepted: 11/23/2016] [Indexed: 12/15/2022] Open
Abstract
The association between hepatitis C virus (HCV) infection and type 2 diabetes (T2D) has been known for over 20 years. Cross-sectional and longitudinal studies have shown a higher prevalence and incidence, respectively, of T2D in patients with chronic HCV infection. HCV induces glucose metabolism alterations mostly interfering with the insulin signaling chain in hepatocytes, although extrahepatic mechanisms seem to contribute. Both IR and T2D accelerate the histological and clinical progression of chronic hepatitis C as well as the risk of extra-hepatic complications such as nephropathy, acute coronary events and ischemic stroke. Before the availability of direct-acting antivirals (DAAs), the therapeutic choice was limited to interferon (IFN)-based therapy, which reduced the incidence of the extra-hepatic manifestations but was burdened with several contraindications and poor tolerability. A better understanding of HCV-associated glucose metabolism derangements and their reversibility is expected with the use of DAAs.
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Affiliation(s)
- Giacomo Gastaldi
- Divisions of Endocrinology, Diabetology, Hypertension and Nutrition, Geneva University Hospitals, Rue Gabrielle Perret-Gentil, 1211 Genève 14, Switzerland
| | - Nicolas Goossens
- Gastroenterology and Hepatology, Geneva University Hospitals, Rue Gabrielle Perret-Gentil, 1211 Genève 14, Switzerland
| | - Sophie Clément
- Clinical Pathology, Geneva University Hospitals, Rue Gabrielle Perret-Gentil, 1211 Genève 14, Switzerland
| | - Francesco Negro
- Gastroenterology and Hepatology, Geneva University Hospitals, Rue Gabrielle Perret-Gentil, 1211 Genève 14, Switzerland
- Clinical Pathology, Geneva University Hospitals, Rue Gabrielle Perret-Gentil, 1211 Genève 14, Switzerland
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46
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Shiffman ML, Gunn NT. Impact of hepatitis C virus therapy on metabolism and public health. Liver Int 2017; 37 Suppl 1:13-18. [PMID: 28052632 DOI: 10.1111/liv.13282] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2016] [Accepted: 10/20/2016] [Indexed: 12/22/2022]
Abstract
Chronic hepatitis C virus (HCV) is associated with insulin resistance (IR) and leads to type 2 diabetes mellitus (T2DM) and hepatic steatosis in many patients. These metabolic complications of HCV have been shown to accelerate the progression of fibrosis to cirrhosis and increase the risk of hepatocellular carcinoma. The metabolic syndrome is a common disorder that also includes IR, T2DM and hepatic steatosis. Approximately 20%-30% of patients with chronic HCV also have co-existent metabolic syndrome. The cause of steatosis in patients with the features of both the metabolic syndrome and chronic HCV is sometime difficult to determine. Patients with metabolic syndrome and chronic HCV are also at risk of developing renal, cardiovascular and cerebrovascular disease. Recent data suggest that HCV is an independent risk factor for renal, coronary and cerebral vascular disease, and may increase mortality associated with these disorders. The treatment of HCV can now result in a sustained virological response and cure nearly all patients with chronic HCV. The eradication of HCV reduces the risk of developing IR and T2DM, improves IR and 2TDM, reduces the risk of developing chronic kidney disease, end-stage renal disease, acute cardiac syndrome and stroke in patients with 2TDM. Thus, treatment of chronic HCV can provide a significant public health benefit, but only if all patients with chronic HCV are identified and universally treated.
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Affiliation(s)
- Mitchell L Shiffman
- Liver Institute of Virginia, Bon Secours Health System, Richmond and Newport News, VA, USA
| | - Nadege T Gunn
- Liver Institute of Virginia, Bon Secours Health System, Richmond and Newport News, VA, USA
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47
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Stine JG, Wynter JA, Niccum B, Kelly V, Caldwell SH, Shah NL, Marquez V. Effect of Treatment with Direct Acting Antiviral on Glycemic Control in Patients with Diabetes Mellitus and Chronic Hepatitis C. Ann Hepatol 2017; 16:215-220. [PMID: 31153414 PMCID: PMC6600819 DOI: 10.5604/16652681.1231581] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2016] [Accepted: 07/17/2017] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND AIM The effect of the new direct acting antiviral drugs (DAAs) for chronic hepatitis C (HCV) on glycemic control is unknown. MATERIALS AND METHODS We conducted a retrospective cohort study of patients who were treated for chronic HCV with direct-acting antiviral medications at a single academic institution between May 2013 and April 2016. Univariate analysis was performed comparing subjects pre- and post-treatment. RESULTS One hundred seventy-five consecutive adult patients were treated for chronic HCV and met enrollment criteria. The majority (80.8%) were genotype 1 and overall cohort sustained virologic response at week 12 (SVR12) was 97.8%. Thirty-one (18.5%) had diabetes mellitus (DM); twenty-six had pre- and post-treatment HbA1c values. Of these, 76.9% were male and 61.5% had cirrhosis. Ninety-six percent were prescribed sofosbuvir-based therapy and all but one (96.8%) achieved SVR12. Three patients were started on treatment despite meeting the definition for poorly controlled DM (HbA1c > 9 mg/dL). There was no significant difference when comparing pre-treatment (7.36 mg/dL, 95% CI 6.55-8.16) to post-treatment HbA1c (7.11 mg/dL, 95% CI 6.34-7.88, p = 0.268). Thirty-one percent of subjects required dose escalation or the initiation of insulin based therapy during treatment. DISCUSSION Although chronic HCV is associated with exacerbation of insulin resistance, our results showed HbA1c to be unaffected by eradication of chronic HCV with DAA in diabetic patients with and without cirrhosis. Paradoxically, almost 1/3 of patients required escalation of anti-diabetic therapy during treatment. Long-term studies are warranted to understand the relationship between HCV viral eradication and insulin metabolism.
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Affiliation(s)
- Jonathan G. Stine
- Division of Gastroenterology & Hepatology, University of Virginia, Charlottesville, Virginia, United States
| | - Javelle A. Wynter
- Department of Medicine, University of Virginia, Charlottesville, Virginia, United States
| | - Blake Niccum
- School of Medicine, University of Virginia, Charlottesville, Virginia, United States
| | - Virginia Kelly
- Division of Gastroenterology & Hepatology, University of Virginia, Charlottesville, Virginia, United States
| | - Stephen H. Caldwell
- Division of Gastroenterology & Hepatology, University of Virginia, Charlottesville, Virginia, United States
| | - Neeral L. Shah
- Division of Gastroenterology & Hepatology, University of Virginia, Charlottesville, Virginia, United States
| | - Vladimir Marquez
- Division of Gastroenterology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada
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48
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Zhao Y, Xing H. A Different Perspective for Management of Diabetes Mellitus: Controlling Viral Liver Diseases. J Diabetes Res 2017; 2017:5625371. [PMID: 28352640 PMCID: PMC5352886 DOI: 10.1155/2017/5625371] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2016] [Revised: 01/21/2017] [Accepted: 01/30/2017] [Indexed: 02/07/2023] Open
Abstract
Knowing how to prevent and treat diabetes mellitus (DM) earlier is essential to improving outcomes. Through participating in synthesis and catabolism of glycogen, the liver helps to regulate glucose homeostasis. Viral related liver diseases are associated with glycometabolism disorders, which means effective management of viral liver diseases may be a therapeutic strategy for DM. The present article reviews the correlation between DM and liver diseases to give an update of the management of DM rooted by viral liver diseases.
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Affiliation(s)
- Yingying Zhao
- Department of Hepatology, Division 3, Beijing Ditan Hospital, Capital Medical University and Teaching Hospital of Peking University, 8 Jingshundong Street, Beijing 100015, China
| | - Huichun Xing
- Department of Hepatology, Division 3, Beijing Ditan Hospital, Capital Medical University and Teaching Hospital of Peking University, 8 Jingshundong Street, Beijing 100015, China
- *Huichun Xing:
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Morales AL, Junga Z, Singla MB, Sjogren M, Torres D. Hepatitis C eradication with sofosbuvir leads to significant metabolic changes. World J Hepatol 2016; 8:1557-1563. [PMID: 28050236 PMCID: PMC5165269 DOI: 10.4254/wjh.v8.i35.1557] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2016] [Revised: 09/20/2016] [Accepted: 10/24/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To assess the effect of sofosbuvir (SOF) based regimens on glycemic and lipid control.
METHODS This is a retrospective analysis of hepatitis C virus (HCV)-infected patients treated and cured with a SOF regimen [SOF/ribavirin/interferon, SOF/simeprevir, or SOF/ledipasvir (LDV) ± ribavirin] from January 2014 to March 2015. Patients with hemoglobin A1C (HbA1C) and lipid panels within six months before and six months after therapy were identified and included in our study. Due to the known hemolytic effect of ribavirin, HbA1C was obtained a minimum of three months post-treatment for the patients treated with a ribavirin regimen. Medical history, demographics, HCV genotype, pre-therapy RNA, and liver biopsies were included in our analysis. The patients who started a new medication or had an adjustment of baseline medical management for hyperlipidemia or diabetes mellitus (DM) were excluded from our analysis.
RESULTS Two hundred and thirty-four patients were reviewed, of which 60 patients met inclusion criteria. Sixty-three point three percent were male, 26.7% were Caucasian, 41.7% were African American and 91.7% were infected with hepatitis C genotype 1. Mean age was 60.6 ± 6.7 years. Thirty-nine patients had HbA1C checked before and after treatment, of which 22 had the diagnosis of DM type 2. HbA1C significantly decreased with treatment of HCV (pretreatment 6.66% ± 0.95% vs post-treatment 6.14% ± 0.65%, P < 0.005). Those treated with SOF/LDV had a lower HbA1C response than those treated with other regimens (0.26% ± 0.53% vs 0.71% ± 0.83%, P = 0.070). Fifty-two patients had pre- and post-treatment lipid panels; there was a significant increase in low-density lipoprotein (LDL) and total cholesterol (TC) after treatment (LDL: 99.5 ± 28.9 mg/dL vs 128.3 ± 34.9 mg/dL, P < 0.001; TC: 171.6 ± 32.5 mg/dL vs 199.7 ± 40.0 mg/dL, P < 0.001). Pre-treatment body-mass index (BMI) did not differ from post-treatment BMI (P = 0.684).
CONCLUSION Eradication of HCV with a SOF regimen resulted in a significant drop in HbA1C and an increase in LDL and TC post therapy.
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Nuño Solinís R, Arratibel Ugarte P, Rojo A, Sanchez Gonzalez Y. Value of Treating All Stages of Chronic Hepatitis C: A Comprehensive Review of Clinical and Economic Evidence. Infect Dis Ther 2016; 5:491-508. [PMID: 27783223 PMCID: PMC5125137 DOI: 10.1007/s40121-016-0134-x] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2016] [Indexed: 02/06/2023] Open
Abstract
INTRODUCTION The goal of chronic hepatitis C (CHC) treatment is to achieve a sustained virologic response (SVR). The new generation of direct-acting antivirals (DAAs) offers 90-100% SVR rates. However, access to these treatments is generally limited to patients with advanced liver disease. The aim of this review is to provide an overview of the clinical and economic benefits of achieving SVR and to better understand the full value of CHC treatment in all stages of liver disease. METHODS A comprehensive literature review was performed using the PubMed, Embase, and Cochrane library databases to identify articles examining the clinical, economic, and quality of life benefits associated with SVR. Articles were limited to those published in English language from January 2006 through January 2016. Inclusion criteria were (1) patients with CHC, (2) retrospective and prospective studies, (3) reporting of mortality, liver morbidity, extrahepatic manifestations (EHMs), and economic outcomes and, (4) availability of an abstract or full-text publication. RESULTS Overall this review identified 354 studies involving more than 500,000 CHC patients worldwide. Evidence from 38 studies (n = 73,861) shows a significant mortality benefit of achieving SVR in patients with all stages of fibrosis. Long-term studies with follow-up of 5-12 years suggest that, particularly among non-cirrhotic patients, there is a significant decrease in mortality in SVR versus non-SVR groups. Ninety-nine studies conducted in 235,891 CHC patients in all stages of fibrosis show that SVR reduces liver-related mortality, incidence of hepatocellular carcinoma (HCC), and decompensation. A total of 233 studies show that chronic HCV infection is associated with several serious EHMs, some of which can have high mortality. Evidence from four modeling studies shows that delaying treatment to CHC patient populations could significantly increase mortality, morbidity, and medical costs. CONCLUSIONS There is a robust body of evidence demonstrating diverse sources of value from achieving SVR in all stages of liver disease. While access to treatment is generally limited to late-stage patients, less restrictive treatment strategies that target HCV eradication have the potential to abate the burdens of mortality, liver morbidity and extrahepatic manifestations, and the associated healthcare costs.
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Affiliation(s)
- Roberto Nuño Solinís
- Deusto Business School Health, University of Deusto, Bilbao, Basque Country, Spain
| | | | - Ander Rojo
- Deusto Business School Health, University of Deusto, Bilbao, Basque Country, Spain
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