Treatment of hepatitis B virus-associated membranous nephropathy with adenine arabinoside and thymic extract

Abstract

Previously we found that corticosteroid treatment in the hepatitis B virus (HBV)-associated membranous nephropathy (HBVMN) was not associated with a favorable outcome. To distinguish the differences of the HBV DNA in macrophage, T and B cells among HBVMN patients with or without corticosteroid treatment, serial studies at different time points were investigated. HBV DNA appeared as an "episomal" molecule as with 3.2 kb in macrophage, T and B cells. This molecule disappeared after 12 months among HBVMN patients without corticosteroid treatment. HBV DNA, by contrast, appeared as episomal form even three years later in T cells, with frequent proteinuria among HBVMN patients with corticosteroid treatment. This finding indicates that the use of corticosteroids leads to a potential risk of enhancing HBV viral replication in T cells. We studied 24 HBVMN patients who had previously received corticosteroid treatment and had persistent proteinuria, who were administered combination therapy with adenine arabinoside for two weeks and thymic extract (Thymostimulin) for six months to decrease urine protein loss and obtain seroconversion. These 24 patients had heavy (22 of 24, 91.6%) or mild (2 of 24, 8.4%) proteinuria prior to adenine arabinoside and thymostimulin treatment. All 24 patients demonstrated HBV DNA in mononuclear cells and simultaneously exhibited sera positive with HBsAg and HBeAg. In contrast, after treatment only one case (4.2%) had heavy and two cases (8.4%) mild proteinuria; HBV DNA was demonstrated in macrophage (4 of 24, 16.7%), T cells (9 of 24, 37.5%), and B cells (6 of 24, 25%) as well as serum (24 of 24, 100%) prior to treatment. The decreases to 16.7%, 37.5%, 25% and 41.6% in the macrophage, T cell, B cell, and serum respectively, were statistically significant (P < 0.01) in each instance. In addition, six cases with complete remission of proteinuria changed their hepatitis B markers. Four cases (16.7%) changed from HBe (+)/anti-HBe (-) to HBe (-)/anti-HBe (-). These results suggest that combination therapy of adenine arabinoside and Thymostimulin in HBVMN patients is more effective in the improvement of proteinuria than corticosteroid treatment.