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      13-year nationwide cohort study of chronic kidney disease risk among treatment-naïve patients with chronic hepatitis B in Taiwan

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          Abstract

          Background

          Chronic hepatitis B virus (HBV) infection and chronic kidney disease (CKD) have high prevalences in Taiwan and worldwide. However, the association of untreated chronic hepatitis B virus (HBV) infection with chronic kidney disease (CKD) remains unclear.

          Methods

          This cohort study used claims data in the Taiwan National Health Insurance Research Database in 1996–2010, in which all diseases were classified by ICD-9-CM codes. We identified 17796 adults who had chronic HBV infection and did not take nucleos(t)ide analogues from 1998 to 2010 and also randomly selected 71184 matched controls without HBV in the same dataset. Cumulative incidences and adjusted hazard ratio (aHR) of incident CKD were evaluated through the end of 2010 after adjusting for competing mortality.

          Results

          The risk of CKD was significantly higher in the HBV cohort (13-year cumulative incidence, 6.2 %; 95 % confidence interval [CI], 5.4–7.1 %) than in the non-HBV cohort (2.7 %; 95 % CI, 2.5–3.0 %) ( p < 0.001), and the aHR was 2.58 (95 % CI, 1.95-3.42; p < 0.001). Multivariable stratified analysis further verified significant associations of CKD with HBV in men of any age (aHR, 2.98; 95 % CI, 2.32–3.83, p < 0.001 for men aged <50 years; aHR, 1.58; 95 % CI, 1.31–1.91, p < 0.001 for men aged ≧50 years) and women under the age of 50 (aHR, 2.99; 95 % CI, 2.04–4.42, p < 0.001), but no significant association in women aged 50 or over.

          Conclusion

          Untreated chronic HBV infection is associated with increased risk of CKD. Hence, high-risk HBV-infected subjects should have targeted monitoring for the development of CKD.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12882-015-0106-5) contains supplementary material, which is available to authorized users.

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          Most cited references35

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          Regression models in clinical studies: determining relationships between predictors and response.

          Multiple regression models are increasingly being applied to clinical studies. Such models are powerful analytic tools that yield valid statistical inferences and make reliable predictions if various assumptions are satisfied. Two types of assumptions made by regression models concern the distribution of the response variable and the nature or shape of the relationship between the predictors and the response. This paper addresses the latter assumption by applying a direct and flexible approach, cubic spline functions, to two widely used models: the logistic regression model for binary responses and the Cox proportional hazards regression model for survival time data.
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            Epidemiological features of CKD in Taiwan.

            The incidence of end-stage renal disease (ESRD) in Taiwan is the highest in the world. However, epidemiological features of earlier chronic kidney disease (CKD) have not been investigated. Since implementation of the National Health Insurance Program in 1995, more than 96% of the population in Taiwan has been enrolled. A nationally representative cohort of 200,000 individuals randomly sampled from the National Health Insurance enrollees was followed up from 1996 to 2003. Clinical conditions were defined by using diagnostic codes. The prevalence and incidence of clinically recognized CKD were assessed. We also identified risk factors associated with the development of CKD. The prevalence of clinically recognized CKD increased from 1.99% in 1996 to 9.83% in 2003. The overall incidence rate during 1997 to 2003 was 1.35/100 person-years. The multivariate model indicates that age is a key predictor of CKD, with an odds ratio of 13.95 for the group aged 75-plus years compared with the group younger than 20 years. Other factors associated with increased risk for the development of CKD include diabetes, hypertension, hyperlipidemia, and female sex. The prevalence and incidence of CKD in Taiwan are relatively high compared with other countries. Our finding provides a reasonable explanation for the subsequent epidemic of ESRD in Taiwan. Further study is needed to identify the entire burden of CKD and the effectiveness of risk-factor modification.
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              Association of nucleos(t)ide analogue therapy with reduced risk of hepatocellular carcinoma in patients with chronic hepatitis B: a nationwide cohort study.

              Treatment for hepatitis B virus infection reduces the risk of hepatocellular carcinoma (HCC). However, the long-term protective effects for subgroups of patients with chronic hepatitis B are unclear. We conducted a retrospective nationwide cohort study using data from Taiwan's National Health Insurance Research Database (from January 1, 1997, through December 31, 2010). Cumulative incidences were calculated and multivariable analyses were carried out after adjusting for competing mortality. Propensity scores were used to match 21,595 patients with chronic hepatitis B who received nucleoside analogue therapy for at least 90 days (treated cohort) with 21,595 untreated patients with chronic hepatitis B (controls), who received hepatoprotectants for at least 90 days. Data were collected from the treated cohort for a mean period of 3.46 years and from controls for 5.24 years. The treated cohort had a significantly lower 7-year incidence of HCC (7.32%; 95% confidence interval [CI], 6.77%-7.87%) than controls (22.7%; 95% CI, 22.1%-23.3%; P < .001). After adjusting for competing mortality and other confounders, nucleos(t)ide analogue treatment was associated with a reduced risk of HCC, with an adjusted hazard ratio of 0.37 (95% CI, 0.34-0.39; P < .001). Sensitivity analyses confirmed the association between nucleos(t)ide analogue treatment and reduced risk of HCC. Age, sex, cirrhosis, and diabetes mellitus modified this association. Based on a retrospective, nationwide study in Taiwan, nucleoside analogue therapy use is associated with reduced risk of HCC in patients with chronic hepatitis B virus infection. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                +886-5-2648000-5665 , chenyichun0320@yahoo.com.tw
                alineycc@gmail.com
                cyli99@mail.ncku.edu.tw
                df254246@tzuchi.com.tw
                Journal
                BMC Nephrol
                BMC Nephrol
                BMC Nephrology
                BioMed Central (London )
                1471-2369
                22 July 2015
                22 July 2015
                2015
                : 16
                : 110
                Affiliations
                [ ]Division of Nephrology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, No. 2, Minsheng Rd., Dalin Township, Chiayi, County 622 Taiwan
                [ ]School of Medicine, Tzu Chi University, Hualien, Taiwan
                [ ]Division of Hematology-Oncology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
                [ ]Department and Graduate Institute of Public Health, College of Medicine, National Cheng Hung University, Tainan, Taiwan
                [ ]Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan
                [ ]Department of Radiation Oncology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
                Article
                106
                10.1186/s12882-015-0106-5
                4508999
                26199000
                dae0ce80-1c51-4fba-960f-79dc72f86842
                © Chen et al. 2015

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 6 March 2015
                : 2 July 2015
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2015

                Nephrology
                hbv infection,chronic kidney disease,cohort study,taiwan national health insurance research database,competing mortality

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