-Case Reports-

Seroconversion of Hepatitis B Envelope Antigen by Entecavir in a Child with Hepatitis B Virus-related Membranous Nephropathy

Toru Igarashi¹, Akira Shimizu², Tsutomu Igarashi³, Kazunari Hanaoka⁴, Kaoru Yoshizaki¹, Tomoko Shigemori¹, Shuji Shimizu⁵, Hirokazu Komeichi⁵ and Yasuhiko Itoh¹

¹Department of Pediatrics, Nippon Medical School
²Department of Pathology (Analytic Human Pathology), Nippon Medical School
³Department of Ophthalmology, Nippon Medical School
⁴Division of Kidney and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine
⁵Division of Cardiology, Hepatology, Geriatrics, and Integrated Medicine, Department of Internal Medicine, Graduate School of Medicine, Nippon Medical School

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.

J Nippon Med Sch 2013; 80: 387-395

Keywords
entecavir, hepatitis B, basement membrane, children

Correspondence to
Toru Igarashi, MD, Department of Pediatrics, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan
iga@nms.ac.jp

Received, August 29, 2012
Accepted, November 27, 2012