Chronic hepatitis B virus infection and risk of chronic kidney disease: a population-based prospective cohort study of 0.5 million Chinese adults

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Abstract

Background

Existing evidence remains inconclusive as to the association between chronic hepatitis B virus (HBV) infection and the risk of chronic kidney disease (CKD). We prospectively examined the association between chronic HBV infection and CKD risk, and the joint associations of HBV infection with established risk factors of several lifestyle factors and prevalent diseases on CKD risk.

Methods

Participants from the China Kadoorie Biobank were enrolled during 2004–2008 and followed up until 31 December 2015. After excluding participants with previously diagnosed CKD, cancer, heart disease, and stroke at baseline, the present study included 469,459 participants. Hepatitis B surface antigen (HBsAg) was qualitatively tested at baseline. Incident CKD cases were identified mainly through the health insurance system and disease and death registries.

Results

During a median follow-up of 9.1 years (4.2 million person-years), we documented 4555 incident cases of CKD. Cox regression yielded multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Compared with HBsAg-negative participants, the multivariable-adjusted HR (95% CI) for CKD was 1.37 (1.18, 1.60) for HBsAg-positive participants. The association was stronger in men (HR = 1.77; 95% CI: 1.43, 2.20) than in women (HR = 1.10; 95% CI: 0.88, 1.36). HBsAg-positive participants, with or without hepatitis or cirrhosis, whether or not under treatment, all showed increased risk of developing CKD. We observed positive additive interactions of HBsAg positivity with smoking, physical inactivity, or diabetes on CKD risk. Compared with HBsAg-negative participants who were nonsmokers, more physically active, or did not have diabetes at baseline, the greatest CKD risk for HBsAg-positive participants was for those who were smokers (HR = 1.85; 95% CI: 1.44, 2.38), physically inactive (HR = 1.91; 95% CI: 1.52, 2.40), or diabetic (HR = 6.11; 95% CI: 4.47, 8.36).

Conclusions

In countries with a high endemicity of HBV infection, kidney damage associated with chronic HBV infection should be a non-negligible concern. Our findings also highlight the importance of health advice on quitting smoking, increasing physical activity, improving glucose control, and early screening for CKD in people with chronic HBV infection.

Electronic supplementary material

The online version of this article (10.1186/s12916-018-1084-9) contains supplementary material, which is available to authorized users.

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Most cited references 16

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Chronic kidney disease.

Paul Drawz, Mahboob Rahman (2015)

This issue provides a clinical overview of chronic kidney disease, focusing on prevention, diagnosis, treatment, and patient information. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including ACP Smart Medicine and MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic from these primary sources in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of science writers and physician writers. Editorial consultants from ACP Smart Medicine and MKSAP provide expert review of the content. Readers who are interested in these primary resources for more detail can consult http://smartmedicine.acponline.org, http://mksap.acponline.org, and other resources referenced in each issue of In the Clinic.

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Hepatitis B Virus-Associated Nephropathy

Rajendra Bhimma, Hoosen Mohamed Coovadia (2004)

A direct causal association between hepatitis B virus (HBV) infection and the development of nephropathy remains controversial. Epidemiological studies have shown that chronic carriage of HBV in some individuals (particularly children) leads to the development of nephrotic syndrome with a strong male predominance, the commonest histological type being membranous nephropathy (MN). Spontaneous clearance of HBV antigens (particularly the HBeAg) leads to abrogation of proteinuria. The isolation of immune complexes in the kidney suggests that the pathogenesis of the disease may have an immune-complex basis. Recent studies showing expression of HBV viral antigens in kidney tissue suggest direct viral-induced pathological alterations and chronic immunologic injury. Biosocial studies have detected no correlation between HBV carriage and proteinuria using both quantitative and qualitative urinary protein analysis. Genetic studies of HLA class I and II genes showed a predisposition to MN but no similar correlation in those with milder degrees of proteinuria. These findings suggest that milder proteinuria is unrelated to HBV carriage or genetic factors but the development of nephropathy, particularly MN, in patients with chronic HBV carriage (HBsAg and/or HBV DNA positive) is based on an interaction of virus and host factors. Although the natural history of the disease tends to remission with preservation of renal function, there is considerable morbidity and a small but significant mortality. Use of naturally occurring cytokines (such as interferon-α2b) and other candidate therapies accelerates clearance of the virus and proteinuria. The most effective tool in reducing the incidence of the disease is the use of HBV vaccines.

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Hepatic steatosis in hepatitis B virus infected patients: meta-analysis of risk factors and comparison with hepatitis C infected patients.

André Oliveira, Michael H. Cortez, Flávia Machado (2011)

Although hepatic steatosis (HS) has an association with hepatitis C virus (HCV) infection, an association with hepatitis B virus (HBV) is controversial. We performed a meta-analysis to evaluate HS prevalence and risk factors, in HBV infection. Standard guidelines for performance of meta-analyses were followed. Studies with HS assessed by histology were included. Pooled odd ratios (OR) and standardized mean differences (SMD) were obtained with the random-effects model and DerSimonian-Laid method. Seventeen out of 21 studies were included, comprising 4100 HBV infected patients. Overall HS prevalence was 29.6%. Eight studies also included 945 HCV infected patients, showing decreased risk of HS in HBV versus HCV patients (OR 0.55, 95%CI [0.45-0.67], P < 0.001). In HBV, HS positively associated with male gender (OR 1.74, 95%CI [1.28-2.38], P < 0.001), body mass index (SMD 2.17, 95%CI [1.23, 3.11], P < 0.001), obesity (OR 6.59, 95%CI [3.51-12.257], P = 0.003), diabetes (OR 2.62, 95%CI [1.37-4.00], P = 0.004), glycemia (SMD 0.84, 95%CI [0.00, 1.67], P = 0.049), triglycerides (SMD 1.18, 95%CI [0.48, 1.89], P = 0.001), cholesterol (SMD 0.88, 95%CI [0.31, 1.45], P = 0.003), moderate alcohol consumption (OR 1.54, 95%CI [1.10-2.15], P = 0.011) and negatively with HBV DNA (SMD -74.12, 95%CI [-82.93, -65.31], P < 0.001). HS had no association with aminotransferases, HBeAg, genotype or hepatic histology, necroinflammation or fibrosis. HS in HBV seems to be as frequent as in the general population, and lower than in HCV infected patients, relating to metabolic factors but not with hepatic histology severity. A puzzling strong negative association between viral load and HS, may even suggest a protective effect of the virus on HS. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

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Author and article information

Contributors

Jun Lv: 86-10-82801528 , lvjun@bjmu.edu.cn

Journal

Journal ID (nlm-ta): BMC Med

Journal ID (iso-abbrev): BMC Med

Title: BMC Medicine

Publisher: BioMed Central (London )

ISSN (Electronic): 1741-7015

Publication date (Electronic): 18 June 2018

Publication date PMC-release: 18 June 2018

Publication date Collection: 2018

Volume: 16

Electronic Location Identifier: 93

Affiliations

[1 ]ISNI 0000 0001 2256 9319, GRID grid.11135.37, Department of Epidemiology and Biostatistics, School of Public Health, , Peking University Health Science Center, ; 38 Xueyuan Road, Beijing, 100191 China

[2 ]ISNI 0000 0001 0662 3178, GRID grid.12527.33, Chinese Academy of Medical Sciences, ; Beijing, China

[3 ]ISNI 0000 0004 1936 8948, GRID grid.4991.5, Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, , University of Oxford, ; Oxford, UK

[4 ]Hunan Center for Disease Control & Prevention, Changsha, Hunan China

[5 ]Liuzhou Traditional Chinese Medical Hospital, Liuzhou, Guangxi China

[6 ]Liuzhou Center for Disease Control & Prevention, Liuzhou, Guangxi China

[7 ]ISNI 0000 0004 4914 5614, GRID grid.464207.3, China National Center for Food Safety Risk Assessment, ; Beijing, China

[8 ]ISNI 0000 0001 2256 9319, GRID grid.11135.37, Peking University Institute of Environmental Medicine, ; Beijing, China

Article

Publisher ID: 1084

DOI: 10.1186/s12916-018-1084-9

PMC ID: 6004660

PubMed ID: 29909773

SO-VID: 0d29f074-e86c-4870-92db-2a09d2c03562

License:

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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

Date received : 29 November 2017

Date accepted : 23 May 2018

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;

Award ID: 81390540

Award ID: 81390544

Award ID: 81390541

Award Recipient : Jun Lv Liming Li

Funded by: National Key Research and Development Program of China

Award ID: 2016YFC0900500

Award ID: 2016YFC0900501

Award ID: 2016YFC0900504

Award Recipient : Canqing Yu Yu Guo

Funded by: Kadoorie Charitable Foundation

Funded by: FundRef http://dx.doi.org/10.13039/100004440, Wellcome Trust;

Award ID: 202922/Z/16/Z

Award ID: 088158/Z/09/Z

Award ID: 104085/Z/14/Z

Funded by: Chinese Ministry of Science and Technology

Award ID: 2011BAI09B01

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ScienceOpen disciplines: Medicine

Keywords: chronic hepatitis b virus infection,chronic kidney disease,prospective cohort study

Data availability:

ScienceOpen disciplines: Medicine

Keywords: chronic hepatitis b virus infection, chronic kidney disease, prospective cohort study

Chronic hepatitis B virus infection and risk of chronic kidney disease: a population-based prospective cohort study of 0.5 million Chinese adults

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Abstract

Background

Methods

Results

Conclusions

Electronic supplementary material

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Most cited references 16

Chronic kidney disease.

Hepatitis B Virus-Associated Nephropathy

Hepatic steatosis in hepatitis B virus infected patients: meta-analysis of risk factors and comparison with hepatitis C infected patients.

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