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1
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Kanduri SR, Peleg Y, Wadhwani S. Liver Disease-Associated Glomerulopathies. ADVANCES IN KIDNEY DISEASE AND HEALTH 2024; 31:147-156. [PMID: 38649219 DOI: 10.1053/j.akdh.2023.11.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Revised: 10/11/2023] [Accepted: 11/22/2023] [Indexed: 04/25/2024]
Abstract
Hepatitis B virus (HBV) and hepatitis C virus (HCV) infect a significant number of individuals globally and their extra-hepatic manifestations, including glomerular disease, are well established. Additionally, liver disease-associated IgA nephropathy is the leading cause of secondary IgA nephropathy with disease course varying from asymptomatic urinary abnormalities to progressive kidney injury. Herein we provide an updated review on the epidemiology, pathogenesis, clinical manifestations, and treatment of HBV- and HCV-related glomerulonephritis as well as IgA nephropathy in patients with liver disease. The most common HBV-related glomerulonephritis is membranous nephropathy, although membranoproliferative glomerulonephritis and podocytopathies have been described. The best described HCV-related glomerulonephritis is cryoglobulinemic glomerulonephritis occurring in about 30% of patients with mixed cryoglobulinemic vasculitis. The mainstay of treatment for HBV-GN and HCV-GN is antiviral therapy, with significant improvement in outcomes since the emergence of the direct-acting antivirals. However, cases with severe pathology and/or a more aggressive disease trajectory can be offered a course of immunosuppression, commonly anti-CD20 therapy, particularly in the case of cryoglobulinemic glomerulonephritis.
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Affiliation(s)
- Swetha R Kanduri
- Department of Nephrology, Ochsner Health System, New Orleans, LA; Ochsner Clinical School, The University of Queensland, New Orleans, LA.
| | - Yonatan Peleg
- Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Shikha Wadhwani
- Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, IL
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Sharma P, Sawtell R, Wang Q, Sise ME. Management of Hepatitis C Virus and Hepatitis B Virus Infection in the Setting of Kidney Disease. ADVANCES IN KIDNEY DISEASE AND HEALTH 2023; 30:343-355. [PMID: 37657881 PMCID: PMC10479952 DOI: 10.1053/j.akdh.2023.04.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 04/04/2023] [Accepted: 04/19/2023] [Indexed: 09/03/2023]
Abstract
Treatment of chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infection poses unique challenges in patients with kidney disease. Direct-acting antivirals have been a major breakthrough in eradicating HCV infection, and several pangenotypic regimens are available for patients with chronic kidney disease or end-stage kidney disease requiring dialysis with high cure rates and no need for dose adjustment. Direct-acting antiviral therapy alone can treat HCV-associated cryoglobulinemic glomerulonephritis; concurrent antiviral and immunosuppressive therapy is needed for cases of severe, organ-threatening manifestations of cryoglobulinemia. Immunosuppression may be needed for HBV-associated kidney disease (polyarteritis nodosa or membranous nephropathy) when there is evidence of severe immune-mediated injury while weighing the risk of potential viral activation. Most HBV antiviral agents need to be dose-adjusted in patients with chronic kidney disease or end-stage kidney disease requiring dialysis, and drug-drug interactions need to be carefully evaluated in patients with kidney transplants. Considerations for accepting HCV- and HBV-infected donors for kidney transplantation are discussed.
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Affiliation(s)
- Purva Sharma
- Department of Medicine, Division of Nephrology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell; Glomerular Disease Center at Northwell Health, Hempstead, NY
| | - Rani Sawtell
- Department of Medicine, Division of Nephrology, Massachusetts General Hospital, Boston, MA
| | - Qiyu Wang
- Department of Medicine, Division of Nephrology, Massachusetts General Hospital, Boston, MA
| | - Meghan E Sise
- Department of Medicine, Division of Nephrology, Massachusetts General Hospital, Boston, MA.
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Chen R, Wang J, Xie Q, Zheng J, Liu S, Xue J, Hao C. Favorable outcome in PLA2R positive HBV-associated membranous nephropathy. BMC Nephrol 2022; 23:246. [PMID: 35818032 PMCID: PMC9275132 DOI: 10.1186/s12882-022-02871-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 06/30/2022] [Indexed: 11/10/2022] Open
Abstract
Introduction Over half of the patients with hepatitis B virus associated membranous nephropathy (HBV-MN) were found to be phospholipase A2 receptor (PLA2R) positive. Whether MN is really secondary to hepatitis B or just coincidence of hepatitis and PLA2R positive idiopathic MN (IMN) remains controversial. Methods We retrospectively studied seven PLA2R positive HBV-MN patients with complete data in Huashan Hospital from 2009 to 2016 and compared them with PLA2R positive idiopathic MN patients. Results Proteinuria and renal function of these 7 HBV-MN patients were similar to that of IMN patients. However, 5 of them were female and half showed hypocomplementemia, while in IMN group only 32.4% were female and 20% had hypocomplementemia, and the level of hematuria was 94.5/μL in HBV-MN patients and 64.9 /μL in IMN patients, though there was no statistically significant difference. Renal biopsies revealed significantly increased mesangial eletron-deposits in HBV-MN patients. All 7 patients received antiviral therapy, and one patient received immunosuppresants due to severe nephrotic syndrome with acute myocardial infarction and elevated serum creatinine. Compared with IMN group, the prevalence of remission without immunosuppressive therapy of HBV-MN patients was higher (85.7% vs. 43.7%), while the percentage of patients receiving immunosuppresants was lower (14.3% vs. 47.9%) (P=0.048). Conclusion Compared with IMN patients, PLA2R positive HBV-MN patients had a more favorable prognosis after antiviral therapy, indicating a secondary form of MN. For these patients, antiviral treatment is recommended and long observation time should be provided before use of immunosuppressive treatment.
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Affiliation(s)
- Ruiying Chen
- Division of Nephrology, Huashan Hospital, Fudan University, No.12, Middle Wulumuqi Road, Shanghai, 200040, China
| | - Jia Wang
- Division of Nephrology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Qionghong Xie
- Division of Nephrology, Huashan Hospital, Fudan University, No.12, Middle Wulumuqi Road, Shanghai, 200040, China.
| | - Jianming Zheng
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Shaojun Liu
- Division of Nephrology, Huashan Hospital, Fudan University, No.12, Middle Wulumuqi Road, Shanghai, 200040, China
| | - Jun Xue
- Division of Nephrology, Huashan Hospital, Fudan University, No.12, Middle Wulumuqi Road, Shanghai, 200040, China
| | - Chuanming Hao
- Division of Nephrology, Huashan Hospital, Fudan University, No.12, Middle Wulumuqi Road, Shanghai, 200040, China
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Rovin BH, Adler SG, Barratt J, Bridoux F, Burdge KA, Chan TM, Cook HT, Fervenza FC, Gibson KL, Glassock RJ, Jayne DR, Jha V, Liew A, Liu ZH, Mejía-Vilet JM, Nester CM, Radhakrishnan J, Rave EM, Reich HN, Ronco P, Sanders JSF, Sethi S, Suzuki Y, Tang SC, Tesar V, Vivarelli M, Wetzels JF, Floege J. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int 2021; 100:S1-S276. [PMID: 34556256 DOI: 10.1016/j.kint.2021.05.021] [Citation(s) in RCA: 1020] [Impact Index Per Article: 255.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Accepted: 05/25/2021] [Indexed: 12/13/2022]
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Fu B, Ji Y, Hu S, Ren T, Bhuva MS, Li G, Yang H. Efficacy and safety of anti-viral therapy for Hepatitis B virus-associated glomerulonephritis: A meta-analysis. PLoS One 2020; 15:e0227532. [PMID: 31940324 PMCID: PMC6961902 DOI: 10.1371/journal.pone.0227532] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2019] [Accepted: 12/21/2019] [Indexed: 12/14/2022] Open
Abstract
Objectives To assess the potency of anti-viral treatment for hepatitis B virus-associated glomerulonephritis (HBV-GN). Method: We searched for controlled clinical trials on anti-viral therapy for HBV-GN in MEDLINE, Embase, the Cochrane Library, and PubMed from inception to March 11th 2019. Seven trials, including 182 patients met the criteria for evaluating. The primary outcome measures were proteinuria and changes in the estimated glomerular filtration rate, and the secondary outcome measure was hepatitis B e-antigen clearance. A fixed or random effect model was established to analyze the data. Subgroup analyses were performed to explore the effects of clinical trial type, anti-viral drug type, age, and follow-up duration. Results The total remission rate of proteinuria (OR = 10.48, 95% CI: 4.60−23.89, I2 = 0%), complete remission rate of proteinuria (OR = 11.64, 95% CI: 5.17−26.21, I2 = 23%) and clearance rate of Hepatitis Be Antigen (HBeAg) were significantly higher in the anti-viral treatment group than in the control group (OR = 27.08, 95% CI: 3.71−197.88, I2 = 63%). However, antiviral therapy was not as effective regarding the eGFR (MD = 5.74, 95% CI: -4.24−15.73). In the subgroup analysis, age and drug type had significant impacts on proteinuria remission, and study type and follow-up duration only slightly affected the heterogeneity. Conclusion Antiviral therapy induced remission of proteinuria and increased HBeAg clearance but failed to improve the eGFR. Pediatric patients were more sensitive to antiviral therapy than adults. IFNs seem more effective but are accompanied by more adverse reactions than NAs.
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Affiliation(s)
- Baohui Fu
- Department of Nephrology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yue Ji
- Department of Nephrology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Shouci Hu
- The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Zhejiang, China
| | - Tong Ren
- Department of Nephrology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Maheshkumar Satishkumar Bhuva
- International Department, Tongji University School of Medicine Affiliated Shanghai Pulmonary Hospital, Shanghai, China
| | - Ge Li
- Public Health Science and Engineering College, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- * E-mail: (HY); (GL)
| | - Hongtao Yang
- Department of Nephrology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
- * E-mail: (HY); (GL)
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Fabrizi F, Cerutti R, Ridruejo E. Hepatitis B virus infection as a risk factor for chronic kidney disease. Expert Rev Clin Pharmacol 2019; 12:867-874. [PMID: 31456441 DOI: 10.1080/17512433.2019.1657828] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Introduction: Hepatitis B virus is an important cause of liver disease and has numerous extra-hepatic manifestations. HBV leads to important morbidity and mortality in the general population and recent evidence suggests a role of HBV in the incidence and progression of chronic kidney disease. Areas covered: The mechanisms underlying the link between HBV and CKD remain unclear. Nucleos(t)ide analogues for the antiviral treatment of HBV are currently available; these drugs are provided with high efficacy even in patients with CKD. Expert opinion: A recent meta-analysis of clinical studies showed that HBV results in a greater risk of CKD in the general population. According to an updated review (studies were identified from PubMed, EMBASE, and the Cochrane database), we retrieved six clinical studies (n = 1,034,773 unique patients), adjusted RR, 1.41 (95% CI, 1.09; 1.82, P < 0.001). The significant heterogeneity observed precluded more definitive conclusions. Various mechanisms have been cited to explain the greater risk of CKD among HBsAg positive carriers. Novel evidence shows that untreated HBV and therapy with nucleos(t)ide analogues are associated with increased and decreased risk of end-stage renal disease in CKD population, respectively. We recommend that patients with HBV are assessed for kidney function and urinary changes at baseline and over the follow-up.
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Affiliation(s)
- Fabrizio Fabrizi
- Division of Nephrology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico , Milano , Italy
| | - Roberta Cerutti
- Division of Nephrology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico , Milano , Italy
| | - Ezequiel Ridruejo
- Hepatology Section, Department of Medicine, Centro de Educacion Medica e Investigaciones Clinicas Norberto Quirno ''CEMIC'' , Ciudad Autonoma de Buenos Aires , Argentina.,Hepatology and Liver Transplant Unit, Hospital Universitario Austral , Pilar , Argentina.,Latin American Liver Research, Educational and Awareness Network (LALREAN) , Pilar , Argentina
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Carrion AF, Martin P. Prevention and Management of HBV Infection in Patients with Chronic Kidney Disease Requiring Renal Transplantation. CURRENT HEPATOLOGY REPORTS 2018; 17:485-491. [DOI: 10.1007/s11901-018-0438-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2025]
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Huang CW, Lin CH, Chuang YW, Yang SS, Lee TY, Yeh HZ, Chang CS, Lu IT. Association of hepatitis B virus infection and glomerulonephritis in a HBV-endemic area: A population-based study. ADVANCES IN DIGESTIVE MEDICINE 2018. [DOI: 10.1002/aid2.13092] [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: 11/12/2022]
Affiliation(s)
- Chiao-Wei Huang
- Division of Gastroenterology & Hepatology, Department of Internal Medicine; Taichung Veterans General Hospital; Taichung Taiwan
| | - Cheng-Heng Lin
- Department of Medical Research; Taichung Veterans General Hospital; Taichung Taiwan
| | - Ya-Wen Chuang
- Division of Nephrology, Department of Internal Medicine; Taichung Veterans General Hospital; Taichung Taiwan
| | - Sheng-Shun Yang
- Division of Gastroenterology & Hepatology, Department of Internal Medicine; Taichung Veterans General Hospital; Taichung Taiwan
- Faculty of Medicine, College of Medicine; National Yang-Ming University; Taipei Taiwan
| | - Teng-Yu Lee
- Division of Gastroenterology & Hepatology, Department of Internal Medicine; Taichung Veterans General Hospital; Taichung Taiwan
- School of Medicine; Chung Shan Medical University; Taichung Taiwan
| | - Hong-Zen Yeh
- Division of Gastroenterology & Hepatology, Department of Internal Medicine; Taichung Veterans General Hospital; Taichung Taiwan
- Faculty of Medicine, College of Medicine; National Yang-Ming University; Taipei Taiwan
| | - Chi-Sen Chang
- Division of Gastroenterology & Hepatology, Department of Internal Medicine; Taichung Veterans General Hospital; Taichung Taiwan
- School of Medicine; Chung Shan Medical University; Taichung Taiwan
| | - I-Ta Lu
- Division of Gastroenterology & Hepatology, Department of Internal Medicine; Taichung Veterans General Hospital; Taichung Taiwan
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Yan Z, Qiao B, Zhang H, Wang Y, Gou W. Effectiveness of telbivudine antiviral treatment in patients with hepatitis B virus-associated glomerulonephritis: A 104-week pilot study. Medicine (Baltimore) 2018; 97:e11716. [PMID: 30075577 PMCID: PMC6081091 DOI: 10.1097/md.0000000000011716] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
The aim of this study was to evaluate clinical efficacy of telbivudine in treatment of hepatitis B virus-associated glomerulonephritis (HBV-GN).A total of 43 HBV-GN patients combined with chronic hepatitis B were treated with telbivudine for 104 weeks. Serum levels of HBV DNA viral load, HBeAg, HBeAb, alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum creatinine (Cr), and 24-hour urinary protein were evaluated after telbivudine treatment of 12, 24, 52, 76, and 104 weeks. Estimated glomerular filtration rate (eGFR) was calculated at baseline, 24 weeks, 52 weeks, and 104 weeks of treatment, respectively. Complete remission (CR) was defined as urinary protein <0.3 g/day, with normal ALT, AST, Cr, and eGFR. Criteria for partial remission include: 24-hour urinary protein excretion decreased by >50% compared with baseline level, and ALT and AST decreased >50%.Proteinuria level gradually decreased in patients with HBV-GN after telbivudine treatment. The percentages of PR + CR were 90.7% and 95.3%, respectively, at 52 and 104 weeks. Compared to baseline, eGFR were significantly increased from 69.2 ± 23.1 mL/min/1.73 m to 116.2 ± 26.3 mL/min/1.73 m at 104 weeks of treatment. Multivariate analysis indicated that baseline HBV DNA viral load (odds ratio [OR] = 1.19, 95% confidence interval [CI] 1.11-2.19, P = .02) and baseline urinary protein (OR = 1.08, 95% CI 1.04-2.44, P = .03) were independent risk factors associated with CR after telbivudine treatment among patients with HBV-GN.Our study demonstrates that telbivudine can be used to treat HBV-GN and effectively improve eGFR in these patients.
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Affiliation(s)
- Zhaoping Yan
- Lab of Glycobiololgy, School of Medicine and Pharmacy, Ocean University of China
| | | | | | - Yanling Wang
- Department of Dermatology, No. 6 People's Hospital of Qingdao, Qingdao, Shandong, China
| | - Wei Gou
- The sixth Department of Hepatology
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Chen YC, Li CY, Tsai SJ, Chen YC. Nationwide cohort study suggests that nucleos(t)ide analogue therapy decreases dialysis risk in Taiwanese chronic kidney disease patients acquiring hepatitis B virus infection. World J Gastroenterol 2018; 24:917-928. [PMID: 29491685 PMCID: PMC5829155 DOI: 10.3748/wjg.v24.i8.917] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2017] [Revised: 12/10/2017] [Accepted: 12/20/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the risk of end-stage renal disease (ESRD) in hepatitis B virus (HBV)-infected patients with chronic kidney disease (CKD) with and without nucleos(t)ide analogue (NA) therapy.
METHODS This nationwide cohort study included 103444 Taiwanese CKD adults without hepatitis C virus infection from the Taiwan Longitudinal Health Insurance Database 2005 between 1997 and 2012. We identified 2916 CKD patients who acquired HBV infection and did not receive NAs (untreated cohort), and they were propensity-matched 1:4 with 11664 uninfected counterparts. We also identified 442 CKD patients who acquired HBV infection and received NAs (treated cohort), and they were propensity-matched 1:3 with 1326 untreated counterparts. The association between HBV infection, NA use, and ESRD was analyzed using competing risk analysis.
RESULTS Multivariable Cox regression analysis showed a 1.67-fold higher risk (P < 0.0001) of ESRD in the untreated cohort (16-year cumulative incidence, 10.1%) than in the matched uninfected cohort (16-year cumulative incidence, 6.6%), which was independent of cirrhosis or diabetes. The treated cohort (16-year cumulative incidence, 2.2%) had an 87% lower ESRD risk (P < 0.0001) compared with the matched untreated cohort (16-year cumulative incidence, 11.9%). The number needed to treat for one fewer ESRD after NA use at 12 years was 12. Multivariable stratified analyses verified these associations in all subgroups.
CONCLUSION This study suggests that untreated HBV infection and NA therapy are associated with increased and decreased risk of ESRD, respectively, in CKD patients. Identification of HBV status and targeted monitoring for ESRD development are important in CKD patients living in HBV-endemic areas.
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Affiliation(s)
- Yi-Chun Chen
- Division of Nephrology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi County 622, Taiwan
- School of Medicine, Tzu Chi University, Hualien 970, Taiwan
| | - Chung-Yi Li
- Department and Graduate Institute of Public Health, College of Medicine, National Cheng Hung University, Tainan 701, Taiwan
- Department of Public Health, College of Public Health, China Medical University, Taichung 404, Taiwan
| | - Shiang-Jiun Tsai
- Department of Medical Research, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi County 622, Taiwan
| | - Yen-Chun Chen
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi County 622, Taiwan
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Peng T, Xie T, Liu L, Zhen J, Yang X. Analysis of clinical features and pathology of serum HBsAg positive glomerulonephritis. J Med Virol 2017; 90:612-615. [PMID: 28975633 DOI: 10.1002/jmv.24959] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2017] [Accepted: 09/12/2017] [Indexed: 01/16/2023]
Abstract
To analyze the relationship between the factors related to the occurrence of HBV-GN and serum HBsAg-positive glomerulonephritis. A total of 56 patients were enrolled in the present study. All enrolled cases were divided into two groups according to whether HBsAg and/or HBcAg was present in renal kidney tissue: patients with Hepatitis B virus-associated nephritis (HBV-GN group, 30 cases) and patients with hepatitis B virus-combined nephritis (HBV-CG group, 26 cases). We sought to analyze the differences in clinical features and pathological characteristics in both groups. The rate of HBeAg positivity in the HBV-GN group was considerably increased in the HBV-CG group (P < 0.05), and the number of patients with HBsAg+HBeAg+HBcAb+ in the HBV-GN group was considerably increased in the HBV-CG group (21 cases vs 10 cases) (P < 0.05). Moreover, the number of MCD patients diagnosed by renal biopsy in the HBV-GN group was reduced compared with the HBV-CG group (1 case vs 7 cases) (P < 0.05). HBV infection and high-virus proliferation status were closely related with HBV-GN.
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Affiliation(s)
- Tao Peng
- Department of Nephrology, Shandong University Qilu Hospital, Jinan, Shandong, P.R. China
| | - Tingting Xie
- Department of Nephrology, Liaocheng People's Hospital, Liaocheng, Shandong, P.R. China
| | - Lei Liu
- Department of Nephrology, Shandong University Qilu Hospital, Jinan, Shandong, P.R. China
| | - Junhui Zhen
- Department of Pathology, Shandong University Qilu Hospital, Jinan, Shandong, P.R. China
| | - Xiangdong Yang
- Department of Nephrology, Shandong University Qilu Hospital, Jinan, Shandong, P.R. China
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Abstract
The diagnosis and treatment of infection with hepatitis B and C has undergone a paradigm shift in the past decade. Although children with these infections are usually asymptomatic with normal liver function, their evaluation and management can often involve complex issues and require specialized expertise. Here the authors review the common clinical scenarios which might be encountered by a general pediatrician, explain the various tests available for diagnosis, and provide practical guidelines for managing these children.
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Affiliation(s)
- Rohan Malik
- Department of Pediatric Gastroenterology, Hepatology and Clinical Nutrition, Royal Children's Hospital, 50 Flemington Road, Parkville, 3052, Victoria, Melbourne, Australia
| | - Winita Hardikar
- Department of Pediatric Gastroenterology, Hepatology and Clinical Nutrition, Royal Children's Hospital, 50 Flemington Road, Parkville, 3052, Victoria, Melbourne, Australia.
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13
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A Meta-Analysis of Antiviral Therapy for Hepatitis B Virus-Associated Membranous Nephropathy. PLoS One 2016; 11:e0160437. [PMID: 27598699 PMCID: PMC5012684 DOI: 10.1371/journal.pone.0160437] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2016] [Accepted: 07/19/2016] [Indexed: 12/20/2022] Open
Abstract
Hepatitis B virus-associated membranous nephropathy (HBV-MN) is the most common renal extra-hepatic manifestation in patients with chronic HBV infection. In September 2015, we searched the MEDLINE, EMBASE, and CENTRAL databases, and the reference lists of retrieved articles, to identify relevant studies. Descriptions of antiviral drugs used to treat HBV-MN were included in our review. Two authors independently screened all relevant articles, extracted data, and assessed the risk of bias. Nine hundred and fifty-four papers have been considered after electronic and manual searching, only five relevant studies were identified. Complete remission (OR = 26.87, 95% CI: 8.06 to 89.52), total remission (OR = 10.31, 95% CI: 3.59 to 29.63) of proteinuria and HBeAg clearance (OR = 20.91, 95% CI: 6.90 to 63.39) increased significantly after antiviral therapy. No significant differences were seen between interferon and nucleoside analog treatments. Our study found that antiviral therapy was an effective treatment in HBV-MN patients; interferon and nucleoside analogs were equally effective at causing proteinuria remission and HBeAg clearance.
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14
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Hepatitis B virus-related glomerulonephritis: not a predominant cause of proteinuria in korean patients with chronic hepatitis B. Gastroenterol Res Pract 2015; 2015:126532. [PMID: 25788940 PMCID: PMC4348579 DOI: 10.1155/2015/126532] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2014] [Revised: 01/28/2015] [Accepted: 01/29/2015] [Indexed: 11/17/2022] Open
Abstract
Background/Aims. Hepatitis B virus (HBV) can form immune complexes which may result in various types of glomerulonephritis (GN). However, proteinuria can occur because of other kidney diseases besides HBV-related GN (HBV-GN). The aim of this study is to elucidate the causes of proteinuria and report on the clinical outcomes of HBV-GN. Methods. We reviewed the medical records of patients positive for serum hepatitis B surface antigen who underwent renal biopsies due to proteinuria at a tertiary medical center in Korea. Results. A total of 55 patients were included. HBV-GN was diagnosed in 20 (36.4%) of the patients by confirming the presence of immune complexes (12 of 13 membranoproliferative glomerulonephritis, 7 of 8 membranous glomerulonephritis, and 1 of 13 immunoglobulin A nephropathy). Twenty-one patients had other types of GN. A total of 13 (65%) HBV-GN patients were treated with antiviral agents for a median of 11 months. However, the degrees of proteinuria were not significantly reduced in the antiviral intervention group when compared to the control group. Conclusions. Proteinuria can be caused by various glomerular diseases and HBV-GN accounts for one-third of total GN cases. Well-designed prospective study is needed to assess whether antiviral therapy against HBV infection may improve the prognosis of HBV-GN.
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Liu T, Yang S, Yue Z, Kuang Y, Guan W, Sun L. Clinical and pathological characteristics of 5 children with HBV surface antigen (HBsAg)-negative hepatitis B virus-associated glomerulonephritis. J Clin Virol 2015; 66:1-5. [PMID: 25866326 DOI: 10.1016/j.jcv.2015.02.012] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2014] [Revised: 02/11/2015] [Accepted: 02/19/2015] [Indexed: 11/28/2022]
Abstract
BACKGROUND Hepatitis B virus-associated glomerulonephritis (HBV-GN) mainly occurs in children. Patients with HBV-GN are frequently positive for serum HBV surface antigen (HBsAg), but they are rarely negative. OBJECTIVE To explore the clinical and pathological characteristics of patients with HBV-GN who are serum HBsAg negative. STUDY DESIGN Five children with HBV-GN who are negative for HBsAg were included in this study. Their clinical and pathological characteristics were collected and analyzed. RESULTS All 5 children presented with different levels of proteinuria and microscopic hematuria. Renal biopsies showed membranous nephropathy accompanied by HBsAg and/or HBcAg deposits in glomeruli in all of the children. Steroids and/or other immunosuppressants were administered in all cases without antiviral therapy during the early stages of treatment. Two children achieved complete remission but relapsed after the drugs were tapered down. The other 3 children were initially non-responsive but achieved remission after lamivudine was added. CONCLUSIONS Treatment of HBsAg-negative HBV-GN patients with immunosuppressants alone could not achieve satisfactory effects. Antiviral treatment is effective and may be necessary in this type of patient.
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Affiliation(s)
- Ting Liu
- Children's Kidney Disease Center, Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Shicong Yang
- Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhihui Yue
- Children's Kidney Disease Center, Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yu Kuang
- Department of Clinical Laboratory, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Weiming Guan
- Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Liangzhong Sun
- Children's Kidney Disease Center, Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
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Treatment of hepatitis B in patients with chronic kidney disease. Kidney Int 2013; 84:880-5. [PMID: 23783238 DOI: 10.1038/ki.2013.249] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2013] [Revised: 04/17/2013] [Accepted: 04/25/2013] [Indexed: 02/07/2023]
Abstract
Although the prevalence of chronic hepatitis B virus (HBV) infection in patients with chronic kidney disease remains low in developed countries, clinicians should be aware of the rationale for treatment in this setting. This patient population presents particular features and various complicating conditions requiring special treatment strategies. Interferon, the standard treatment for HBV infection, has been poorly tolerated by patients with chronic kidney disease, has presented relatively low efficacy, and has posed renal transplant recipients under the risk of acute rejection. The advent of effective nucleos(t)ide analogs (NAs) has offered the opportunity to minimize the consequences of HBV infection in HBV-positive patients with chronic kidney disease. Combination with immunosuppressive agents might be considered in cases of rapid renal function deterioration and/or severe proteinuria. Among the newer NAs, entecavir may be preferred, because of its high potency, high genetic barrier to resistance, and favorable renal safety profile. However, entecavir presented low efficacy in case of lamivudine or telbivudine resistance, and thus tenofovir may be a better option in that setting. All HBsAg-positive candidates should be treated with NAs before renal transplantation in order to maintain undetectable HBV DNA, reduce liver fibrosis, and prevent hepatic decompensation after renal transplantation. This review summarizes updated issues related to treatment of chronic HBV infection in all categories of population with chronic kidney disease (those exhibiting HBV-associated glomerular disease, those treated with hemodialysis, as well as renal transplant candidates, donors, and recipients).
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Comparison of prednisolone and lamivudine combined therapy with prednisolone monotherapy on carriers of hepatitis B virus with IgA nephropathy: a prospective cohort study. Int Urol Nephrol 2013; 46:49-56. [PMID: 23756850 DOI: 10.1007/s11255-013-0480-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2012] [Accepted: 05/27/2013] [Indexed: 10/26/2022]
Abstract
OBJECTIVE Chronic hepatitis B virus (HBV) carrier status has a critical impact on clinical management of patients with IgA nephropathy (IgAN) who are treated with corticosteroids, because corticosteroids may enhance HBV replication. This study compared corticosteroids and antivirals combined therapy with corticosteroids monotherapy on patients of IgAN who were also HBV carriers. METHODS This was a prospective, open-label cohort study on Chinese adults of HBV inactive carriers with concurrent IgAN (proteinuria ≥ 3.5 g/day). The patients were self-assigned to combined therapy group (prednisolone + lamivudine) or monotherapy group (prednisolone). Prednisolone 1 mg/kg/day for 2 months, tapered gradually, duration 12 months. Lamivudine (100 mg/day) was administrated 2 weeks before starting prednisolone and maintained 6 months after prednisolone withdrawal. All patients were followed up for 18 months. Outcome measures were rates of complete remission of proteinuria (<0.5 g/day), persistent massive proteinuria (≥ 3.5 g/day), HBV reactivation (detectable serum HBV-DNA or HBeAg), and significant alanine aminotransferase (ALT) elevation (>120 μ/L). RESULTS Except 3 patients were lost to follow-up, 46 patients (29 of combined therapy group, 17 of monotherapy group) were included in the analysis. There were no differences in baseline characteristics of clinical and histopathological features between two groups (p > 0.05). At the end of follow-up, 19/29 (65.52 %) in combined therapy group and 9/17 (52.94 %) in monotherapy group achieved complete remission of proteinuria (p = 0.399), while 0/29 (0 %) and 2/17 (11.76 %) remained persistent massive proteinuria (p = 0.059). HBV reactivation and significant ALT elevation was 3/17 (17.65 %) of patients in monotherapy group, more than 0/29 (0 %) of combined therapy group (p = 0.019). Three HBV recurrent patients using prednisolone monotherapy were all male and young, with relatively short term of HBV infection history, HBV reactivation and severe liver impairment developed after 3 months of corticosteroids treatment, and daily proteinuria increased remarkably after prednisolone withdrawal. CONCLUSIONS This study successfully treated with combined lamivudine and prednisolone in inactive HBV carriers with IgAN. We believe the combination of prednisolone and lamivudine was more efficacious than prednisolone alone in providing long-term viral suppression and liver enzyme normalization in inactive HBV carrier with IgAN.
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Mou S, Li J, Yu Z, Wang Q, Ni Z. Keto acid-supplemented low-protein diet for treatment of adult patients with hepatitis B virus infection and chronic glomerulonephritis. J Int Med Res 2013; 41:129-37. [PMID: 23569138 DOI: 10.1177/0300060512474758] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
Objectives An open-label, randomized, controlled, single-centre clinical trial to evaluate the effects of low-protein intake, with or without keto acid supplementation, on nutritional status and proteinuria, in patients with hepatitis B virus (HBV) and early stage chronic glomerulonephritis. Methods Patients with chronic glomerulonephritis and HBV infection were randomized to receive a low-protein diet (0.6–0.8 g/kg ideal body weight [IBW] per day) either without (LP group) or with (sLP group) keto acid supplementation (0.1 g/kg IBW per day), for 12 months. Nutritional, clinical and safety parameters were recorded. Results The study included 17 patients (LP group n = 9; sLP group n = 8). Proteinuria and microalbuminuria were significantly lower in the sLP group at 6 and 12 months compared with baseline, and at 12 months compared with the LP group. There were no significant differences in serum creatinine level or estimated glomerular filtration rate. Nutritional parameters (serum albumin and prealbumin) were significantly improved at 12 months, compared with baseline, in the sLP group. Conclusions Restriction of dietary protein intake to 0.6–0.8 g/kg IBW per day appears to have an acceptable safety profile. Supplementation with keto acids is associated with decreased urine protein excretion.
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Affiliation(s)
- Shan Mou
- Renal Division, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jialin Li
- Renal Division, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zanzhe Yu
- Renal Division, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qin Wang
- Renal Division, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhaohui Ni
- Renal Division, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Shah HH, Patel C, Jhaveri KD. Complete Remission of Hepatitis B Virus-Associated Nephrotic Syndrome from IgA Nephropathy Following Peginterferon Therapy. Ren Fail 2012. [DOI: 10.3109/0886022x.2012.745785] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
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Ladapo TA, Onifade EU, Lesi AE, Lesi OA. Successful treatment of hepatitis B virus associated nephrotic syndrome with oral Lamivudine in a Nigerian child: a case report. J Trop Pediatr 2012; 58:157-8. [PMID: 21624925 DOI: 10.1093/tropej/fmr046] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Hepatitis B virus is a well described cause of nephrotic syndrome (NS) worldwide, the typical lesion being membranous glomerulonephropathy. HBV associated NS has been successfully treated with intravenous alpha interferon (IFN), an anti-viral agent. In recent times there have been reports of treatment with lamivudine, an orally administered nucleoside analogue inhibitor of HBV DNA polymerase in Caucasian children. Data is however limited and it's actual efficacy and safety in children is yet to be determined. We present the case of an 8-year-old Nigerian boy with NS and active hepatitis B virus infection. He went into remission 3 months after commencing oral lamivudine which he had for a year with no significant side effects observed. He remains in remission 3 years later. This, to our knowledge is the first report in literature of successful treatment in an African child.
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Affiliation(s)
- Taiwo A Ladapo
- Department of Pediatrics, Lagos University Teaching Hospital, Lagos, Nigeria.
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Zheng XY, Wei RB, Tang L, Li P, Zheng XD. Meta-analysis of combined therapy for adult hepatitis B virus-associated glomerulonephritis. World J Gastroenterol 2012; 18:821-32. [PMID: 22371643 PMCID: PMC3286146 DOI: 10.3748/wjg.v18.i8.821] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2011] [Revised: 09/13/2011] [Accepted: 10/28/2011] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the efficacy and safety of combined antiviral and immunosuppressant therapy in adult hepatitis B virus-associated glomerulonephritis (HBV-GN) patients.
METHODS: A computerized literature search was carried out in the PubMed database, Embase, the Cochrane Library, Chinese BioMedical Literature on disc, Chinese Medical Current Contents, Chinese National Knowledge Infrastructure, Wanfang and VIP (Chinese Technological Journal of Database) to collect articles between June 1980 and December 2010 on therapy with immunosuppressants, e.g., glucorticosteroids, mycophenolate mofetil and leflunomide, combined with antivirals, e.g., interferon, lamivudine, entecavir and adefovir dipivoxil, in adult HBV-GN patients. The primary outcomes were remission of proteinuria, clearance of HBV e-antigen, and elevation of serum albumin. The secondary outcomes were blood levels of alanine aminotransferase, serum creatinine, and HBV-DNA titer. Meta-analysis was performed using Review Manager 5.1. Fixed or random effect models were employed to combine the results after a heterogeneity test. The effects of the combined therapy were analyzed for different doses of glucorticosteroid and different types of HBV-GN.
RESULTS: Twelve clinical trials with 317 patients were included. A significantly higher incidence of HBV-GN was found in male patients (relative risk = 2.40, 95% CI: 1.98-2.93). Combined therapy reduced the proteinuria significantly with a mean difference of 4.19 (95% CI: 3.86-4.53) and increased the serum albumin concentration significantly with a mean difference of -11.95 (95% CI: -12.97-10.93) without significant alterations of liver function (mean difference: 4.62, 95% CI: -2.55-11.79) and renal function (mean difference: 10.29, 95% CI: 0.14-20.45). No significant activation of HBV-DNA replication occurred (mean difference: 0.12, 95% CI: -0.37-0.62). There was no significant difference between the high dose glucorticosteroid group and the low dose glucorticosteroid group in terms of proteinuria remission (P = 0.76) and between different pathological types of HBV-GN [membranous glomerulonephritis (MN) vs mesangial proliferative glomerulonephritis, P = 0.68; MN vs membranoproliferative glomerulonephritis, P = 0.27].
CONCLUSION: Combined antiviral and immunosuppressant therapy can improve the proteinuria in HBV-GN patients without altering HBV replication or damaging liver and renal functions.
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Nasri H, Mubarak M. Sudden deterioration of renal function in a patient with nephrotic syndrome and a very high hepatitis B viral DNA load. J Renal Inj Prev 2012; 1:39-41. [PMID: 25340103 PMCID: PMC4205971 DOI: 10.12861/jrip.2012.14] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2011] [Accepted: 11/14/2011] [Indexed: 11/22/2022] Open
Affiliation(s)
- Hamid Nasri
- Department of Nephrology, Division of Nephropathology, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Muhammed Mubarak
- Department of Histopathology, Sindh Institute of Urology and Transplantation (SIUT), Karachi, Pakistan
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Xiong QF, Yang YF. Antiviral therapy in patients with hepatitis B virus-associated glomerulonephritis. Shijie Huaren Xiaohua Zazhi 2011; 19:1620-1623. [DOI: 10.11569/wcjd.v19.i15.1620] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus-associated glomerulonephritis (HBV-GN) is a common clinical condition. Up to now, the optimal therapy is undefined although several approaches have been made. This paper reviews the efficacy and safety of antiviral therapy (including interferon and lamivudine) in the treatment of HBV-GN. Interferon-α is efficacious in remission of proteinuria, clearance of HBeAg and delay of renal function deterioration. Remission of proteinuria is often accompanied by clearance of HBV replication markers. Corticosteroid treatment could not improve renal outcome in patients with HBV-GN.
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Xu G, Huang T. Hepatitis B virus-associated glomerular nephritis in East Asia: progress and challenges. Eur J Intern Med 2011; 22:161-6. [PMID: 21402246 DOI: 10.1016/j.ejim.2010.11.005] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2010] [Revised: 10/18/2010] [Accepted: 11/16/2010] [Indexed: 12/30/2022]
Abstract
BACKGROUND Hepatitis B virus-associated glomerular nephritis (HBV-GN) is the most common secondary glomerulonephritis in East Asia. Part of the patients developed to renal insufficiency within 10 years, which cause a great burden for patients' family and society. METHODS We reviewed basic and clinical research work in China, Japan, Korea, and Mongolia, eastern part of Asia. Comparisons between data from East Asia and those from other regions were made. RESULTS The genetic variations conferring susceptibility to HBV-GN and disease progression as well as the pathogenic role in HBV-GN progression were investigated. Clinical features of HBV-GN in East Asia were different from that of other regions in the world. Clinical trials showed that treatment with anti-viral agents was effective to promote the disease remission. CONCLUSION HBV-GN remains a great challenge to East Asian nephrologists. In-depth basic studies and multi-centered clinical trials are needed in the future.
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Affiliation(s)
- Gaosi Xu
- Department of Nephrology, Second Affiliated Hospital, Nanchang University, China.
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Yang DK, Sun YF, Liang HJ, Shen BS, Qiao HC. Treatment of hepatitis B virus-associated glomerulonephritis with compound glycyrrhizin and lamivudine: an analysis of 40 cases. Shijie Huaren Xiaohua Zazhi 2010; 18:1380-1383. [DOI: 10.11569/wcjd.v18.i13.1380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To observe the efficacy of compound glycyrrhizin in combination with lamivudine in the treatment of hepatitis B virus-associated glomerulonephritis (HBV-GN).
METHODS: Eighty HBV-GN patients were randomly and equally divided into two groups: control group and treatment group. The treatment group was treated with compound glycyrrhizin in combination with lamivudine, while the control group was treated with lamivudine alone. The treatment lasted one year. During treatment, the use of other immuosuppressive agents or cytotoxic agents was forbidden. The levels of urinary protein and serum albumin, liver and kidney function and adverse reactions were monitored.
RESULTS: In months 3, 6 and 12, the 24-h urinary protein (4.31 g ± 2.18 g vs 5.89 g ± 3.01 g, 2.34 g ± 1.57 g vs 4.25 g ± 2.27 g, and 1.59 g ± 0.64 g vs 3.43 g ± 2.12 g, all P < 0.05) and serum albumin (28.26 g/L ± 2.15 g/L vs 23.65 g/L ± 6.13 g/L, 30.54 g/L ± 2.58 g/L vs 27.36 ± 2.23 g/L, and 35.46 g/L ± 2.12 g/L vs 31.35 g/L ± 3.35 g/L, all P < 0.05) differed significantly between the treatment group and the control group.
CONCLUSION: Compound glycyrrhizin in combination with lamivudine has better efficacy and less adverse effects than lamivudine alone in the treatment of HBV-GN. Some HBV-GN patients may develop HBV resistance to lamivudine with the prolongation of treatment duration. Once lamivudine resistance is noted, adefovir should be given promptly.
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