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      Impact of sustained virologic response on chronic kidney disease progression in hepatitis C

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          Abstract

          AIM

          To determine how sustained virological response at 12 wk (SVR12) with direct acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV) infection affects chronic kidney disease (CKD) progression.

          METHODS

          A retrospective analysis was performed in patients aged ≥ 18 years treated for HCV with DAAs at the VA Greater Los Angeles Healthcare System from 2014-2016. The treatment group was compared to patients with HCV from 2011-2013 who did not undergo HCV treatment, prior to the introduction of DAAs; the control group was matched to the study group in terms of age, gender, and ethnicity. Analysis of variance and co-variance was performed to compare means between SVR12 subgroups adjusting for co-variates.

          RESULTS

          Five hundred and twenty-three patients were evaluated. When comparing the rate of change in estimated glomerular filtration rate (eGFR) one-year after HCV treatment to one-year before treatment, patients who achieved SVR12 had a decline in GFR of 3.1 mL/min ± 0.75 mL/min per 1.73 m 2 compared to a decline in eGFR of 11.0 mL/min ± 2.81 mL/min per 1.73 m 2 in patients who did not achieve SVR12 ( P = 0.002). There were no significant clinical differences between patients who achieved SVR12 compared to those who did not in terms of cirrhosis, treatment course, treatment experience, CKD stage prior to treatment, diuretic use or other co-morbidities. The decline in eGFR in those with untreated HCV over 2 years was 2.8 mL/min ± 1.0 mL/min per 1.73 m 2, which was not significantly different from the eGFR decline noted in HCV-treated patients who achieved SVR12 ( P = 0.43).

          CONCLUSION

          Patients who achieve SVR12 have a lesser decline in renal function, but viral eradication in itself may not be associated improvement in renal disease progression.

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          Most cited references29

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          Chronic kidney disease and mortality risk: a systematic review.

          Current guidelines identify people with chronic kidney disease (CKD) as being at high risk for cardiovascular and all-cause mortality. Because as many as 19 million Americans may have CKD, a comprehensive summary of this risk would be potentially useful for planning public health policy. A systematic review of the association between non-dialysis-dependent CKD and the risk for all-cause and cardiovascular mortality was conducted. Patient- and study-related characteristics that influenced the magnitude of these associations also were investigated. MEDLINE and EMBASE databases were searched, and reference lists through December 2004 were consulted. Authors of 10 primary studies provided additional data. Cohort studies or cohort analyses of randomized, controlled trials that compared mortality between those with and without chronically reduced kidney function were included. Studies were excluded from review when participants were followed for < 1 yr or had ESRD. Two reviewers independently extracted data on study setting, quality, participant and renal function characteristics, and outcomes. Thirty-nine studies that followed a total of 1,371,990 participants were reviewed. The unadjusted relative risk for mortality in participants with reduced kidney function compared with those without ranged from 0.94 to 5.0 and was significantly more than 1.0 in 93% of cohorts. Among the 16 studies that provided suitable data, the absolute risk for death increased exponentially with decreasing renal function. Fourteen cohorts described the risk for mortality from reduced kidney function, after adjustment for other established risk factors. Although adjusted relative hazards were consistently lower than unadjusted relative risks (median reduction 17%), they remained significantly more than 1.0 in 71% of cohorts. This review supports current guidelines that identify individuals with CKD as being at high risk for cardiovascular mortality. Determining which interventions best offset this risk remains a health priority.
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            Chronic hepatitis C virus infection in the United States, National Health and Nutrition Examination Survey 2003 to 2010.

            Knowledge of the number of persons with chronic hepatitis C virus (HCV) infection in the United States is critical for public health and policy planning. To estimate the prevalence of chronic HCV infection between 2003 and 2010 and to identify factors associated with this condition. Nationally representative household survey. U.S. noninstitutionalized civilian population. 30,074 NHANES (National Health and Nutrition Examination Survey) participants between 2003 and 2010. Interviews to ascertain demographic characteristics and possible risks and exposures for HCV infection. Serum samples from participants aged 6 years or older were tested for antibody to HCV; if results were positive or indeterminate, the samples were tested for HCV RNA, which indicates current chronic infection. Based on 273 participants who tested positive for HCV RNA, the estimated prevalence of HCV infection was 1.0% (95% CI, 0.8% to 1.2%), corresponding to 2.7 million chronically infected persons (CI, 2.2 to 3.2 million persons) in the U.S. noninstitutionalized civilian population. Infected persons were more likely to be aged 40 to 59 years, male, and non-Hispanic black and to have less education and lower family income. Factors significantly associated with chronic HCV infection were illicit drug use (including injection drugs) and receipt of a blood transfusion before 1992; 49% of persons with HCV infection did not report either risk factor. Incarcerated and homeless persons were not surveyed. This analysis estimated that approximately 2.7 million U.S. residents in the population sampled by NHANES have chronic HCV infection, about 500,000 fewer than estimated in a similar analysis between 1999 and 2002. These data underscore the urgency of identifying the millions of persons who remain infected and linking them to appropriate care and treatment. None.
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              Hepatitis C virus infection and diabetes: direct involvement of the virus in the development of insulin resistance.

              Epidemiological studies have suggested a linkage between type 2 diabetes and chronic hepatitis C virus (HCV) infection. However, the presence of additional factors such as obesity, aging, or cirrhosis prevents the establishment of a definite relationship between these 2 conditions. A mouse model transgenic for the HCV core gene was used. In the glucose tolerance test, plasma glucose levels were higher at all time points including in the fasting state in the core gene transgenic mice than in control mice, although the difference was not statistically significant. In contrast, the transgenic mice exhibited a marked insulin resistance as revealed by the insulin tolerance test, as well as significantly higher basal serum insulin levels. Feeding with a high-fat diet led to the development of overt diabetes in the transgenic mice but not in control mice. A high level of tumor necrosis factor-alpha, which has been also observed in human chronic hepatitis C patients, was considered to be one of the bases of insulin resistance in the transgenic mice, which acts by disturbing tyrosine phosphorylation of insulin receptor substrate-1. Moreover, administration of an anti-tumor necrosis factor-alpha antibody restored insulin sensitivity. The ability of insulin to lower the plasma glucose level in the HCV transgenic mice was impaired, as observed in chronic hepatitis C patients. These results provide a direct experimental evidence for the contribution of HCV in the development of insulin resistance in human HCV infection, which finally leads to the development of type 2 diabetes.
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                Author and article information

                Contributors
                Journal
                World J Hepatol
                WJH
                World Journal of Hepatology
                Baishideng Publishing Group Inc
                1948-5182
                28 December 2017
                28 December 2017
                : 9
                : 36
                : 1352-1360
                Affiliations
                Division of Gastroenterology, Hepatology and Parenteral Nutrition, Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, United States
                the Vatche and Tamar Manoukian Division of Digestive Diseases, UCLA Los Angeles, Department of Medicine, University of California David Geffen School of Medicine, Los Angeles, CA 90095, United States
                Division of Gastroenterology, Hepatology and Parenteral Nutrition, Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, United States
                the Vatche and Tamar Manoukian Division of Digestive Diseases, UCLA Los Angeles, Department of Medicine, University of California David Geffen School of Medicine, Los Angeles, CA 90095, United States
                Division of Gastroenterology, Hepatology and Parenteral Nutrition, Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, United States
                Division of Gastroenterology, Hepatology and Parenteral Nutrition, Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, United States
                the Vatche and Tamar Manoukian Division of Digestive Diseases, UCLA Los Angeles, Department of Medicine, University of California David Geffen School of Medicine, Los Angeles, CA 90095, United States
                Division of Gastroenterology, Hepatology and Parenteral Nutrition, Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, United States. jbenhammou@ 123456mednet.ucla.edu
                the Vatche and Tamar Manoukian Division of Digestive Diseases, UCLA Los Angeles, Department of Medicine, University of California David Geffen School of Medicine, Los Angeles, CA 90095, United States
                Author notes

                Author contributions: Aby ES, Dong TS, Kawamoto J, Pisegna JR and Benhammou JN were involved in study concept and design; Aby ES and Dong TS were involved in data acquisition; Aby ES, Dong TS and Benhammou JN were involved in analysis and interpretation of data; Aby ES drafted the manuscript; Dong TS, Pisegna JR and Benhammou JN were involved in critical revision of the manuscript for important intellectual content; Dong TS performed the statistical analysis; Pisegna JR provided administrative, technical and material support as well as study supervision.

                Correspondence to: Jihane N Benhammou, MD, the Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, 11301 Wilshire Blvd., Los Angeles, CA 90073, United States. jbenhammou@ 123456mednet.ucla.edu

                Telephone: +1-310-2683131 Fax: +1-310-2684096

                Article
                jWJH.v9.i36.pg1352
                10.4254/wjh.v9.i36.1352
                5756725
                730ecd86-ce1d-4aa1-9da9-b55c9aacbf09
                ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.

                This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

                History
                : 6 October 2017
                : 17 November 2017
                : 5 December 2017
                Categories
                Retrospective Study

                hepatitis c,direct-acting antivirals,chronic kidney disease,end stage renal disease,sustained virological response

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