entecavir and Glomerulonephritis--Membranous

The activation of complement system is associated with the development of hepatitis B virus-associated membranous nephropathy (HBV-MN) and heparin could inhibit the activation of complement system.. This was a three-center trial. Seventy-nine patients with HBV-MN participated in the study. The follow-up of the study consisted of two periods: Stage 1 (S1) and Stage 2 (S2). All patients received 0.5mg entecavir plus 150-300mg/day of irbesartan but sulodexide was prescribed during S1. They were randomized into 4 groups according to sulodexide dose: blank (Group 1), 250 lipasemic unit (lsu)/day for 1year (Group 2), 500 lsu/day for 1year (Group 3) and 1000 lsu/day for 6months followed by 250 lsu/day for 6months (Group 4). Major clinical outcomes were valid remission (VR): (1) urine albumin/creatinine ratio (UACR) <150mg/mmol and >50% decline of baseline; (2) albumin >35g/L; (3) glomerular filtration rate (GFR) >90ml/(min*1.73m(2)).. (1) Groups 3 and 4 had significantly lower UACR and higher albumin than did Groups 1 and 2 at major visits; (2) Groups 3 and 4 achieved more VR compared with Group 1 (42.1% and 60.0% vs. 9.1%, p both<0.05); (3) in Groups 3 and 4, instead of Groups 1 and 2, more C3 deposition in the kidney was observed in those achieving VR; (4) plasma C3a, C5a and C5b-9 decreased significantly in Groups 3 and 4 during S1.. (1) The prescription of both sulodexide and entecavir could improve the prognosis of patients with HBV-MN but their mechanisms might be different; (2) the renoprotection of sulodexide in HBV-MN might probably relate to the inhibition of complement system.

Topics: Adult; Anticoagulants; Antihypertensive Agents; Antiviral Agents; Biphenyl Compounds; Complement System Proteins; Drug Therapy, Combination; Female; Glomerulonephritis, Membranous; Glycosaminoglycans; Guanine; Hepatitis B; Hepatitis B virus; Humans; Irbesartan; Male; Middle Aged; Pilot Projects; Tetrazoles; Treatment Outcome

hepatitis B virus-associated membranous nephropathy (HBV-MN) is the most common pathological type of hepatitis B virus-associated glomerulonephritis. This study evaluated the efficacy of entecavir antiviral therapy for HBV-MN patients due to the intolerable side effects of interferon-alpha and high incidence rate of drug-resistance in lamivudine therapy.. thirty-two patients with HBV-MN were identified by biopsy and treated with entecavir for 52 weeks. These patients were followed up to evaluate outcomes of entecavir-treatment. Descriptive statistics were used to summarize patient demographics and treatment outcomes.. entecavir treatment reduced 24-h urinary protein excretion. The total probability of partial proteinuria and complete remission at 24 and 52 weeks was 53.1 and 78.1 %, respectively. A decrease of circulating HBV-DNA was observed in all patients with active HBV replication. The significant decrease of 24-h urinary protein began at 12 weeks, as early as the decrease of serum HBV-DNA level. The serum HBV DNA titers at baseline and after 52 weeks of treatment were 4.3 ± 2.8 log10 and 2.3 ± 1.7 log10, respectively. Meanwhile, eGFR increased from 100.3 ± 20.5 ml/min/1.73 m2 at baseline to 107.7 ± 15.9 ml/min/1.73 m2 after 52 weeks of treatment. The serum alanine aminotransferase level (ALT) gradually decreased to normal during entecavir antiviral treatment.. entecavir treatment in HBV-MN patients was carefully described. Complete remission and HBV replication suppression were induced by entecavir treatment in HBV-MN patients. Patients with high serum creatinine (Scr), ALT and low eGFR levels benefit more from entecavir treatment. Entecavir therapy is well tolerated by patients and no adverse reactions were observed.

Topics: Antiviral Agents; Glomerulonephritis, Membranous; Guanine; Hepatitis B virus; Hepatitis B, Chronic; Humans; Lamivudine; Treatment Outcome

We report the case of a 7-year-old unimmunized boy who presented with generalized anasarca for the first time, along with nephrotic-range proteinuria, hypoalbuminemia, microscopic hematuria and hypertension. Special investigations revealed ELISA test to be positive for hepatitis B surface antigen (HBsAg) and hepatitis B envelope antigen (HBeAg); hepatitis B viral DNA load (HBV DNA) level (real-time polymerase chain reaction) was 54 360 903 IU/ml. For hepatitis B virus (HBV)-related glomerulopathy, he was started on enalapril and lasilactone, and percutaneous renal biopsy was performed, which revealed membranous nephropathy (MN). A diagnosis of MN secondary to HBV infection contracted via horizontal transmission was made. The patient was started on peginterferon alfa-2b (50 μg/week) for 24 weeks. He failed to attain remission and seroconversion after interferon (IFN) therapy. Then, oral therapy with entecavir was started, and he attained remission as well as seroconversion after 3 months of therapy. He maintained his seroconversion status at his 6-month and the recent 12-month (quantitative HBV DNA level was 373 IU/ml) follow-up visit. Entecavir seems a promising drug for HBV-related glomerulopathy, especially in IFN-resistant cases.

Topics: Antiviral Agents; Biopsy; Child; DNA, Viral; Enalapril; Enzyme-Linked Immunosorbent Assay; Glomerulonephritis, Membranous; Guanine; Hepatitis B; Hepatitis B e Antigens; Hepatitis B Surface Antigens; Hepatitis B virus; Humans; Kidney; Male; Pyrrolizidine Alkaloids; Real-Time Polymerase Chain Reaction; Remission Induction; Treatment Outcome

We have reported a case of occult hepatitis B virus infection (OBI) associated membranous nephropathy (MN) with complete remission under an ongoing 3.5-year entecavir monotherapy. A 59-year-old man with a 3-year history of liver cirrhosis was introduced to our department because of oliguria, proteinuria and microscopic haematuria. He, with negative serum HBV surface antigen, was not detected HBV DNA in his serum. Renal biopsy was performed and was compatible with a diagnosis of hepatitis B virus-related membranous nephropathy (HBV-MN). The patient was prescribed diuretics and intravenous albumin, and his ascites and oedema remitted gradually. At the same time, entecavir 0.5 mg per day was started. Entecavir treatment was continuing for 3.5 years and finally resulted in complete remission of proteinuria. This suggests that entecavir monotherapy may induce and maintain complete remission of MN associated with OBI.

Topics: Antiviral Agents; Glomerulonephritis, Membranous; Guanine; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Kidney; Male; Middle Aged; Treatment Outcome

Topics: Antiviral Agents; Drug Therapy, Combination; Glomerulonephritis, Membranous; Guanine; Hepatitis B; Hepatitis B virus; Humans; Immunosuppressive Agents; Male; Middle Aged; Time Factors; Treatment Outcome

Membranous nephropathy (MN) is caused by subepithelial deposition of immune complexes in the glomerular basement membrane, with secondary MN arising in association with infection. In secondary MN caused by hepatitis B virus (HBV), seroconversion has been known to occur after the onset of MN, particularly in children. In patients with high serum concentrations of HBV DNA, treatment with interferon-α2b or a nucleoside analog has been reported to induce seroconversion and suppress HBV-DNA levels. We treated a 7-year-old boy who presented with proteinuria and liver dysfunction. He had a history of HBV infection since shortly after birth, as his mother was HBV-positive, and he was neither vaccinated nor treated with immunoglobulin at birth. Chronic hepatitis related to HBV was diagnosed following percutaneous needle biopsy of the liver. Percutaneous renal biopsy revealed HBV-related glomerulonephritis with diffuse global subepithelial and focal segmental mesangial and subendothelial deposits. Therefore, HBV-associated MN was diagnosed. Treatment with the nucleoside analog lamivudine was started to reduce serum HBV-DNA levels, but lamivudine was discontinued and treatment with entecavir was started at a dosage of 0.5 mg/day after 6 weeks because of possible adverse effects. Tests for HB envelope antibody were positive in week 16 of treatment, and proteinuria had resolved by week 22. Elevated levels of aspartate aminotransferase and alanine aminotransferase were seen with both treatments but were probably attributable to the developing immune response to HBV. In the present case, HBV levels needed to be reduced to: 1) lower elevated serum HBV-DNA titers, which put the patient at high risk of hepatocellular carcinoma; and 2) remove the immune complexes causing MN. Use of nucleoside analogs to suppress the HBV load may facilitate early remission of MN, and entecavir therapy did not cause any serious adverse reactions in this case. Given the advent of lamivudine-resistant HBV, entecavir appears promising for patients with elevated serum levels of HBV DNA.

Topics: Antiviral Agents; Biomarkers; Biopsy, Needle; Child; DNA, Viral; Glomerulonephritis, Membranous; Guanine; Hepatitis B e Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Kidney; Liver; Male; Time Factors; Treatment Outcome; Viral Load

We reported a case of Hepatitis B virus-related membranous nephropathy (HBV-MN) with improvement under an ongoing 4.5-year of entecavir monotherapy. A 37 years old man with a 5 years' history of chronic hepatitis B (CHB) who was taken to our department because of proteinuria and microscopic haematuria. A renal biopsy led to a diagnosis of HBV-MN with mesangioproliferative. Interferon-alpha 2b (IFN-α2b) was stopped after 24 weeks due to the increasement of HBV-DNA and sustained HBeAg positive. Therefore, we started using 0.5mg entecavir per day. After 2 months' treatment, HBV-DNA was not detected in the blood, and the ALT and AST decreased to normal degree. After 3 years of entecavir therapy, virological tests revealed HBeAg seroconversion. With no further intervention during the next one and a half years, there was improvement of proteinuria gradually. This suggested that entecavir monotherapy may induce and maintain complete remission of membranous nephropathy associated with hepatitis B.

Topics: Adult; Antiviral Agents; Glomerulonephritis, Membranous; Guanine; Hepatitis B, Chronic; Humans; Male; Remission Induction

Interferon is used to treat chronic viral hepatitis because of low drug resistance and a high remission rate. However, its propensity to induce and modify autoimmunity has been reported. We used pegylated interferon α-2a to treat a patient with chronic viral hepatitis B. After 5 months of this therapy, the patient developed membranous nephropathy. Complete remission of his nephrotic syndrome was achieved after 1 year of cyclosporine and corticosteroid therapy. During this same period, his chronic viral hepatitis B was controlled by entecavir. To our knowledge, this is the first case in which membranous nephropathy developed during pegylated interferon α-2a therapy for chronic hepatitis B. The autoimmune modulation induced by interferon is the most likely mechanism for this complication.

Topics: Adrenal Cortex Hormones; Adult; Antiviral Agents; Biopsy; Cyclosporine; Drug Substitution; Glomerulonephritis, Membranous; Guanine; Hepatitis B, Chronic; Humans; Immunohistochemistry; Immunosuppressive Agents; Interferon-alpha; Kidney; Male; Nephrotic Syndrome; Polyethylene Glycols; Recombinant Proteins; Treatment Outcome

Chronic hepatitis B infection is a common cause of secondary membranous nephropathy (MN) in endemic areas. Lamivudine treatment improves renal outcome in patients with hepatitis B virus-associated MN (HBV-MN), but prolonged use leads to the emergence of lamivudine-resistant variants. We describe our experience treating lamivudine-resistant and other strains of HBV-MN with new antiviral drugs.. Of the 89 patients biopsied and diagnosed with MN from 1996 to 2011, 10 positive for hepatitis B surface antigen were recruited for this study. We investigated the clinical courses, therapeutic responses, and prognoses of patients with HBV-MN.. The incidence of HBV-MN among the original 89 patients was 11.2%. Of these patients, four were treated with supportive care and six with antiviral drugs. One of the four patients treated with supportive care had a spontaneous remission. Four of the six patients treated with antiviral drugs were given lamivudine, and the other two were given entecavir. Two of the four patients treated with lamivudine achieved complete remission with seroconversion (i.e., development of anti-hepatitis B e antigen antibodies), whereas the other two had lamivudine-resistant strains, which were detected at 22 and 23 months after lamivudine treatment, respectively. We added adefovir to the treatment regimen for one of these patients, and for the other patient we substituted clevudine for lamivudine. Both of these patients experienced complete remission, as did the two patients initially treated with entecavir, neither of whom showed resistance to the drug.. New nucleoside analogues, such as entecavir, adefovir, and clevudine, can be effective for treatment of HBV-MN, including lamivudine-resistant strains.

Topics: Adenine; Adult; Antiviral Agents; Arabinofuranosyluracil; Drug Resistance, Viral; Female; Glomerulonephritis, Membranous; Guanine; Hepatitis B, Chronic; Humans; Lamivudine; Male; Middle Aged; Organophosphonates; Young Adult

Topics: Antiviral Agents; Biomarkers; Biopsy; Creatinine; DNA, Viral; Female; Glomerulonephritis, Membranous; Guanine; Hepatitis B; Hepatitis B Antibodies; Hepatitis B e Antigens; Hepatitis B virus; Humans; Middle Aged; Proteinuria; Time Factors; Treatment Outcome; Viral Load