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      Glucose Metabolism Changes in Patients with Chronic Hepatitis C Treated with Direct Acting Antivirals

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          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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          Most cited references31

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          Non-invasive evaluation of liver fibrosis using transient elastography.

          Transient elastography (TE, FibroScan) is a novel non-invasive method that has been proposed for the assessment of hepatic fibrosis in patients with chronic liver diseases, by measuring liver stiffness. TE is a rapid and user-friendly technique that can be easily performed at the bedside or in the outpatient clinic with immediate results and good reproducibility. Limitations include failure in around 5% of cases, mainly in obese patients. So far, TE has been mostly validated in chronic hepatitis C, with diagnostic performance equivalent to that of serum markers for the diagnosis of significant fibrosis. Combining TE with serum markers increases diagnostic accuracy and as a result, liver biopsy could be avoided for initial assessment in most patients with chronic hepatitis C. This strategy warrants further evaluation in other aetiological types of chronic liver diseases. TE appears to be an excellent tool for early detection of cirrhosis and may have prognostic value in this setting. As TE has excellent patient acceptance it could be useful for monitoring fibrosis progression and regression in the individual case, but more data are awaited for this application. Guidelines are needed for the use of TE in clinical practice.
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            Insulin resistance impairs sustained response rate to peginterferon plus ribavirin in chronic hepatitis C patients.

            We evaluated the effect of insulin resistance and viral factors on sustained virological response in patients with chronic hepatitis C treated with peginterferon plus ribavirin. Patients (n=159; 94 men; age, 41.7 +/- 11.1 years) with chronic hepatitis C (genotype 1, n=113; non-1 genotype, n=46) received treatment with interferon plus ribavirin. Serum levels of leptin and insulin were measured, and the insulin resistance index (HOMA-IR: homeostasis model of assessment) and body mass index were calculated. A sustained virological response was associated with lower age, insulin resistance index, body mass index, and gamma-glutamyltranspeptidase and serum leptin levels. There was no association with viral load, sex, type of interferon, or cholesterol levels. A sustained virological response was achieved in 43.4% (46/113) of genotype 1 and 89% (32/36) of genotype 2 and 3 (P=.0001) patients. Necroinflammatory activity and steatosis were not associated with the sustained virological response rate. Multivariate regression analysis indicated that the independent variables related to sustained virological response were genotype (odds ratio, 3.57; 95% confidence interval, 1.49-8.3; P=.001), insulin resistance index (odds ratio, 1.82; 95% confidence interval, 1.08-3.06; P=.012), and fibrosis (odds ratio, 1.36; 95% confidence interval, 1.01-1.84; P=.029). A sustained virological response in patients with genotype 1 and insulin resistance (HOMA-IR > 2) occurred in 23 of 70 (32.8%; 95% confidence interval, 21.9%-43.9%) patients, vs. 26 of 43 (60.5%; 95% confidence interval, 45.9%-75.1%) genotype 1 patients without insulin resistance (P=.007; odds ratio, 3.12, 95% confidence interval, 1.42-6.89). Insulin resistance, fibrosis, and genotype are independent predictors of the response to antiviral therapy in chronic hepatitis C patients treated with peginterferon plus ribavirin.
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              Diabetes in Europe: an update.

              Diabetes is among the leading causes of death in the IDF Europe Region (EUR), continues to increase in prevalence with diabetic macro- and microvascular complications resulting in increased disability and enormous healthcare costs. In 2013, the number of people with diabetes is estimated to be 56 million in EUR with an overall estimated prevalence of 8.5%. However, estimates of diabetes prevalence in 2013 vary widely in the 56 diverse countries in EUR from 2.4% in Moldova to 14.9% in Turkey. Trends in diabetes prevalence also vary between countries with stable prevalence since 2002 for many countries but a doubling of diabetes prevalence in Turkey. For 2035, a further increase of nearly 10 million people with diabetes is projected for the EUR. Prevalence of type 1 has also increased over the past 20 years in EUR and there was estimated to be 129,350 cases in children aged 0-14 years in 2013. Registries provide valid information on incidence of type 1 diabetes with more complete data available for children than for adults. There are large differences in distribution of risk factors for diabetes at the population level in EUR. Modifiable risk factors such as obesity, physical inactivity, smoking behaviour (including secondhand smoking), environmental pollutants, psychosocial factors and socioeconomic deprivation could be tackled to reduce the incidence of type 2 diabetes in Europe. In addition, diabetes management is a major challenge to health services in the European countries. Improved networking practices of health professionals and other stakeholders in combination with empowerment of people with diabetes and continuous quality monitoring need to be further developed in Europe. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Can J Gastroenterol Hepatol
                Can J Gastroenterol Hepatol
                CJGH
                Canadian Journal of Gastroenterology & Hepatology
                Hindawi
                2291-2789
                2291-2797
                2018
                3 October 2018
                : 2018
                : 6095097
                Affiliations
                1Department of Internal Medicine, Hospital Poprad, Banícka 803/28, Poprad, 05801, Slovakia
                21st Department of Internal Medicine, PJ Safarik University, Faculty of Medicine and L Pasteur University Hospital, Trieda SNP 1, Kosice, 04001, Slovakia
                32nd Department of Internal Medicine, FD Roosevelt University Hospital, Ludvíka Svobodu 1, Banska Bystrica, 97517, Slovakia
                4Department of Infectious Diseases and Travel Medicine, PJ Safarik Unversity, Faculty of Medicine and L Pasteur University Hospital, Rastislavova 43, Kosice, 04001, Slovakia
                5Center for Gastroenterology and Hepatology Thalion, Tomášikova 50/C, Bratislava, 83104, Slovakia
                63rd Department of Internal Medicine, Commenius University, Faculty of Medicine and University Hospital, Limbová 5, Bratislava, 83305, Slovakia
                7Department of Infectious Diseases and Travel Medicine, Commenius University, Jesenius Faculty of Medicine and University Hospital, Štefanovičova 689/3, Martin, 03601, Slovakia
                8Department of Infectious Diseases, Teaching Hospital Nitra, Špitálska 6, Nitra, 95001, Slovakia
                9Department of Internal Medicine, Teaching Hospital Nitra, Špitálska 6, Nitra, 95001, Slovakia
                105th Department of Internal Medicine, Commenius University, Faculty of Medicine and University Hospital, Ružinovská 6, Bratislava, 82606, Slovakia
                11Department of Microbiology, Commenius University, Faculty of Medicine and University Hospital, Špitálska 13, Bratislava, 81372, Slovakia
                12Saint Elisabeth University of Health and Social Sciences, Palackého 1, Bratislava, 81000, Slovakia
                Author notes

                Academic Editor: Emmanuel Tsochatzis

                Author information
                http://orcid.org/0000-0002-3329-3968
                http://orcid.org/0000-0002-4143-1355
                http://orcid.org/0000-0001-7418-0073
                http://orcid.org/0000-0001-6169-9984
                Article
                10.1155/2018/6095097
                6192081
                30402450
                3d6eeb1b-770e-4f22-821f-094b3a71402c
                Copyright © 2018 Sylvia Drazilova et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 25 May 2018
                : 19 August 2018
                : 18 September 2018
                Funding
                Funded by: AbbVie
                Categories
                Research Article

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