Is there an association of hepatitis B virus infection with minimal change disease of nephrotic syndrome? A clinical observational report

Abstract

The rate of hepatitis B virus (HBV) infection is high in the Chinese population, and the implications of HBV infection are widely recognized, and membranous nephropathy is the most common renal lesion to be associated with HBV infection. Minimal change disease (MCD) is one of the most important histopathological characteristics in patients with nephrotic syndrome. There is no any study to report that HBV infection is associated with the etiology of MCD. Herein, we report four MCD patients with HBV infection and speculate that there is an association of HBV infection with the pathological type of MCD. In this study, we also reported the treatment schedule for these four MCD patients, and found that the anti-virus alone and combination of anti-virus with immunosuppressive agent could obtain a benefit for MCD patients with HBV infection. However, a well-designed study should be performed to confirm this association.

• Glomerulonephritis
• HBV-DNA nephrotic syndrome
• Hepatitis B virus infection
• minimal change disease

Introduction

The rate of hepatitis B virus (HBV) infection is high in the Chinese population, and the implications of HBV infection are widely recognized, and membranous nephropathy is the most common renal lesion to be associated with HBV infection.1 Minimal change disease (MCD) of nephrotic syndrome is one of the most important histopathological characteristics in patients with nephrotic syndrome.2 Is there an association of HBV infection with the etiology of MCD? There was no study to answer this question. Herein, we reported four MCD patients with HBV infection and found that HBV infection was associated with the etiology of MCD. Furthermore, the treatment schedule for MCD patients with HBV infection was reported rarely. We also reported the treatment schedule for MCD patients with HBV infection in our clinic centre.

Patients’ characteristics

Four patients with MCD were diagnosed by the renal biopsy in the Sixth Affiliated Hospital, Sun Yat-Sen University. There were one male and three females, in the age group of 20–37 years. Other glomerular diseases of no-HBV infection were excluded from this study. The staining of HBV antibody also detected in the renal tissue and we found that the staining was negative. The characteristics are shown in the Table 1.

Table 1. The detailed characteristics of included cases.

Case (Sex/Age)	Proteinuria	Urine occult blood	Alb(g/L)	SCr (umol/L)	Pathological characteristics	HBV infection	Treatment schedule
Case 1 (Female/25-year-old)	Negative	2+	45.9	56	Light microscope: 11 glomeruli was observed. There was no segmental glomerular sclerosis and global sclerosis. Mesangial cells and matrix were slight hyperplasia. Immunofluorescence showed IgM was positive, and IgA, IgG, C3, C1q were negative. Diffuse electron microscopy observed foot process fusion and microvilli change.	HBsAb (+), HBeAb (+), HBcAb (+), HBV-DNA <5E+002 IU/ml	Monitor
Case 2 (Female/37-year-old)	4+	2+	21.6	90.8	Light microscope: 38 glomeruli was observed. One was ball glomerular sclerosis, and others were glomerular mesangial cells and matrix slight hyperplasia. Immunofluorescence showed IgM was positive, and IgA, IgG, C3, HBsAg, HBcAg were negative. Diffuse electron microscopy observed foot process fusion and microvilli changed.	HBV-DNA 1.89E+008 IU/ml	Lamivudine (After 56 days of treatment, the proteinuria, urine occult blood and Alb returned to normal)
Case 3 (Female/25-year-old)	±	2+	43.6	59	Light microscope: 32 glomeruli was observed. One was ball glomerular sclerosis, and others were glomerular mesangial cells and matrix slight hyperplasia. Immunofluorescence showed IgM (+)and C1q ±. It also indicated that IgA, IgG, C3, HBsAg, HBcAg were negative. Diffuse electron microscopy observed foot process fusion and microvilli changed.	HBsAg (+), HBcAb (+)	Telbivudine (After one month treatment, the proteinuria and urine occult blood were negative)
Case 4 (Male/20-year-old)	3+	±	22.5	69	Light microscope microscope detected a glomeruli. Immunofluorescence showed HBsAg, HBcAg were negative. Diffuse electron microscopy foot process fusion and microvilli changed, but not to the exclusion of FSGS	HBsAg (+), HBeAb (+), HBcAb (+), HBV-DNA <5E+002 IU/ml	Lamivudine, Methylprednisolone

Note: FSGS: focal segmental glomerulosclerosis.

Treatment schedule

In our clinical centre, those four MCD patients were with different schemes. The proteinuria of the Case 1 was negative and the HBV-DNA was normal, so we did not conduct the anti-virus treatment. Cases 2 and 3 were treated with anti-virus and the MCD disease was relieved (Table 1). Case 4 was the combination of anti-virus treatment with immunosuppressive agent (Methylprednisolone, MP), and the MCD was also relieved (Figure 1).

Figure 1. The treatment schedule and the treatment effectiveness evaluation of case 4.

Discussion

HBV-associated patterns of glomerulonephritis (GN) include membranous nephropathy, membrane proliferative glomerulonephritis, focal segmental glomerulosclerosis and immunoglobulin A nephropathy. Membranous nephropathy is the most common form of HBV-mediated GN, and the diagnosis of HBV-mediated GN requires detection of the virus in the blood and the exclusion of other causes of glomerular disease.3 In this report, we first showed that HBV infection was associated with the MCD. When the anti-virus treatment for HBV was conducted, the MCD disease was relieved (proteinuria was negative). Podocyte injury plays a pivotal role in the etiology of MCD. Zhang et al. reported that HBV infection was associated with podocyte damage and decreased number per glomerulus in patients with HBV-associated membranous nephropathy. We speculated that the HBV might induce the injury of podocyte and release the inflammatory factors to induce the onset of MCD. The HBV infection might be associated with the etiology of MCD. However, more studies in cell model and animal model should be conducted for its confirmation.

In adults, HBV-mediated GN is usually progressive.3 Patients with nephrotic syndrome have an even worse prognosis, with >50% progressing to ESRD in the short term.4 There is no randomized controlled trial on the treatment of HBV-mediated GN, and evidence-based treatment recommendations cannot be drew. In this report, we found that the anti-virus alone and combination of anti-virus with immunosuppressive agent were associated to MCD disease being relieved. However, we could not draw the conclusion as to which treatment schedule was better, due to the small sample size. This report shows that the comparison of anti-virus alone and combination of anti-virus with immunosuppressive agent for MCD patients with HBV infection is needed in the future.

In conclusion, HBV infection is associated with the etiology of MCD, and the anti-virus alone and combination of anti-virus with an immunosuppressive agent can be beneficial for MCD patients with HBV infection.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. This study was supported by the Nature Science Foundation of China (no. 81400719), and the sub-item of 985 Project Foundation of Sun Yat-Sen (The Hundred Talents Program Foundation; No. 88000-3311300).