| Background and ObjectiveApproximately one third of the world’s population show serological evidence of past or present infection with Hepatitis B virus(HBV), and 350-400 million people are carriers of chronic Hepatitis B virus surface antigen(HBs Ag); Asian countries have high Hepatitis B virus prevalence, making Hepatitis B virus be one of the most common human pathogens.China was identified as an area with a high prevalence of Hepatitis B virus in 2006.Hepatitis B virus infection has been shown to induce several extra-hepatic lesions.Kidney is an most commonly involved organ, the manifestation is Hepatitis B virus-associated glomerulonephritis(HBV-GN), and the most common pathological pattern is membranous nephropathy(MN). In children, HBV-associated membranous nephropathy has a favorable prognosis with a high spontaneous remission rate,in adult paients of HBV-associated membranous nephropathy, however, approximately 30% progress to the end-stage renal disease,but the treatment of HBV-associated membranous nephropathy remains a heavily-debated issue.Although the treatment of HBV-associated membranous nephropathy remains a heavily-debated issue, antiviral treatment with nucleos(t)ide analogues is generally accepted.We conducted a randomly controlled, prospective trial, evaluating the curative effect of tacrolimus, corticosteroids and entecavir in treat of adult patients with biopsy-proven hepatitis B virus-associated membrane nephropathy(HBV-MN).MethodsA total of 38 patients with biopsy-confirmed HBV-MN were randomized divided into two group,the tacrolimus group(n=19) and the control group(n=19). All drugs were administered orally in all patients of the two groups.Patients in tacrolimus group received combination therapy of tacrolimus(0.05 mg/kg/d), corticosteroids(prednisone acetate, 0.5 mg/k/d) and entecavir(0.5 mg/d), whereas patients in control group received entecavir mono-therapy(0.5 mg/d).The whole blood truogh concentrations of tacrolimus was controlled at 3-5 ng/ml for the first 1 month of treatment. If patient’s proteinuria was not relieved after 2-month tacrolimus treatment, the dose of tacrolimus was increased till the whole blood trough concentration reaching 5-8 ng/ml. When patient’s proteinuria was less than 0.5 g/24 h, which maintained two months tacrolimus was tapered by 25% per month till stopping the tacrolimus treatment, and the reduction in the dose of corticosteroids was performed in the same way. urine protein, renal function, blood glucose,blood lipid level,the whole blood trough,glomemlar filtration rate(GFR),Hepatitis Be Antigen(HBe Ag) hepatitis B e antibody(HBe Ab),hepatitis B virus-deoxyribonucleic acid(HBV-DNA),concentration of tacrolimus were checked regularly. The primary end point was used to assess patient’s outcomes,which include the percentage of patients reaching complete remission(CR) or partial remission(PR),The secondary end points was used to estimate whether withdrew from the study.ResultsThere were no significant differences in baseline clinical and laboratory parameters between the two groups.After 6 and 12 months,The probability of remission in the treatment group was 88.89% and 94.44%, but only 38.89% and 58.82% in the control group, respectively.The reduction of proteinuria was significantly greater in the tacrolimus group than in the control group at all time points, at 6 months the P value was 0.001, at 12 months P=0.022,at 18 months P=0.025 and 24 months P=0.030. The changes in HBsAg, anti-HBeAb and HBV-MN by the end of the treatment showed no difference between the two groups(P>0.05).In the tacrolimus group, the HBsAg-negative rate increased from zero to 27.78%(P=0.047), the HBV-DNA negative rate increased from zero to 66.67%(P=0.000). In the control group, the HBs Ag-negative rate increased from zero to 29.41%(P=0.039), and the HBV-DNA negative rate increased from zero to 64.71%(P=0.000). Notably, two patients in the control group and one patient in the treatment group reached the secondary end point.The tacrolimus blood concentration fluctuated at 1.8-10.2 ng/ml in the first month of the treatment; however, the average concentration was stable and remained between 3 and 8 ng/ml later on. In patients who achieved CR, the mean blood trough level of tacrolimus was 4.01ng/ml. One patient in the tacrolimus-treated group showed a relapse during the taper period. The side effects observed in both the control and the tacrolimus groups were mild and transient and controllable, there was no statistical difference between the two groups.ConclusionWe conclude that the combination therapy of tacrolimus, corticosteroids and entecavir is a useful therapeutic option for patients with HBV-MN. Our treatment protocol have the advantages of controlling HBV-DNA replication, reducing proteinuria and kidney damage, and improving the outcome of HBV-MN patients. |
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