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      Successful entecavir plus prednisolone treatment for hepatitis B virus-associated membranoproliferative glomerulonephritis : A case report

      case-report
      , MD, PhD a , b , , MD, PhD a , b , , , MD a , , MD a , , MD a , , MD a , , MD a , c , , MD a , , MD, PhD a , , MD, PhD a , , MD, PhD a , , MD d , , MD d , , MD d , , MD, PhD e , , MD, PhD e , , MD, PhD a , a , , MD, PhD d , , MD, PhD f , , MD, PhD a
      Medicine
      Wolters Kluwer Health
      entecavir, glomerular hypertrophy, hepatitis B surface antigen, hepatitis B virus, membranoproliferative glomerulonephritis, steroids

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          Abstract

          Rationale:

          Adult-onset hepatitis B virus-associated membranoproliferative glomerulonephritis (HBV-MPGN) is generally refractory, and an effective treatment for this condition has not been established. The indications for steroids in HBV-MPGN are an important clinical concern.

          Patient concerns:

          A 28-year-old woman with a chronic hepatitis B virus infection developed nephrotic syndrome in her second month of pregnancy, with urinary protein levels of 3 to 10 g/d that continued into her postpartum period. She was a carrier of HBV with HBeAg seroconversion. As her renal impairment could have been a result of pregnancy, we observed her for 10 months postpartum without any intervention. However, spontaneous remission after childbirth was not achieved and urine protein levels were sustained at 1 to 3 g/d. About 10 months after delivery, elevated serum liver enzyme levels were observed.

          Diagnosis:

          Biopsies showed MPGN, with deposition of hepatitis B antigen in the glomeruli, and chronic B-type hepatitis with a severity grade of A1F0. She was diagnosed with HBV-MPGN.

          Interventions:

          The patient was started on entecavir 0.5 mg/d in March 2008. Within 1 month, serum HBV DNA became undetectable; within 3 months, her alanine aminotransferase levels normalized. However, urinary protein excretion did not decrease to <2 g/d. On a second renal biopsy, performed 7 months after entecavir treatment, proliferative lesions of the glomeruli were observed; therefore, prednisolone was started at an initial dose of 30 mg/d.

          Outcomes:

          Her proteinuria improved immediately and prednisolone was tapered over 10 months. A third renal biopsy showed a remarkable resolution of HBV-MPGN, with a significant decrease in mesangial proliferation and immune complex deposition. HBV reactivation was not observed during the prednisolone treatment.

          Lessons:

          Additional prednisolone therapy in combination with antiviral therapy should be considered for refractory HBV-MPGN, with sufficient care taken regarding HBV reactivation.

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          Most cited references21

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          Hepatitis B cure: From discovery to regulatory approval

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            Association of C4d deposition with clinical outcomes in IgA nephropathy.

            Several studies have suggested that activation of the complement system is a contributing pathogenic mechanism in IgA nephropathy (IgAN). C4d staining is an inexpensive and easy-to-perform method for the analysis of renal biopsies. This study aimed to assess the clinical and prognostic implications of C4d staining in IgAN.
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              Hepatitis B Virus-Associated Nephropathy

              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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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                January 2019
                11 January 2019
                : 98
                : 2
                : e14014
                Affiliations
                [a ]Department of Medicine Kidney Center
                [b ]Clinical Research Division for Polycystic Kidney Disease, Department of Medicine, Kidney Center
                [c ]Department of Surgical Pathology, Tokyo Women's Medical University, Tokyo
                [d ]Department of Nephrology & Hypertension, Kameda Medical Center, Chiba
                [e ]Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa
                [f ]Department of Anatomy, Showa University, Tokyo, Japan.
                Author notes
                []Correspondence: Toshio Mochizuki, Department of Medicine, Kidney center, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan (e-mail: mtoshi@ 123456twmu.ac.jp ).
                Article
                MD-D-18-06566 14014
                10.1097/MD.0000000000014014
                6336600
                30633192
                7d957ef8-e541-4698-ae0e-538ff44f5909
                Copyright © 2019 the Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0

                History
                : 14 September 2018
                : 7 December 2018
                : 13 December 2018
                Categories
                3600
                Research Article
                Clinical Case Report
                Custom metadata
                TRUE

                entecavir,glomerular hypertrophy,hepatitis b surface antigen,hepatitis b virus,membranoproliferative glomerulonephritis,steroids

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