Since over half of the HBV-MN patients has been found to be PLA2R positive-a feature of idiopathic MN, descriptions of clinical features and prognosis of this entity are lacking. Our study showed the clinicopathological features and outcomes of 7 PLA2R positive HBV-MN patients with complete follow-up data in our center and compared them with PLA2R positive IMN patients.
There is currently no universally accepted diagnostic criteria for HBV-MN. The 2012 Kidney Disease Improving Global Outcomes (KDIGO) guidelines proposed that the diagnosis of HBV mediated glomerulonephritis includes detection of the virus in the blood and the exclusion of other causes of glomerular disease. While some studies used this criteria , most researches diagnosed the disease based on more stringent criteria established by a Chinese study which requires the presence of both serum and renal HBV antigens, consistent with the 2021 KDIGO guidelines . The 7 patient in our study were diagnosed according to such criteria. However, attributed to the importance of PLA2R in diagnosis and monitoring of IMN, concern about coincident occurrence of the two diseases was raised. In this study, we showed that though the 7 PLA2R positive HBV-MN patients shared similarities with regard to age, proteinuria severity and renal function with PLA2R positive IMN patients, they also presented some unique clinical features. These patients tended to be female dominant and had more severe hematuria, though there was no statistically significant difference which may be due to small sample size. In terms of pathology, kidney-biopsy specimens of HBV-MN patients showed more mesangial eletron-deposits, a hint of secondary MN. Importantly, we found that patients with PLA2R positive HBV-MN presented favorable outcome after antiviral treatment, showing more remission without immunosuppresants than IMN patients. All above indicated the presence of a secondary form of MN. Detectable PLA2R antigen or antibody in these patients may suggest the autoimmunity of PLA2R triggered by HBV infection.
HBV-MN usually progresses slowly; however, approximately 30% of adult patients was reported to progress to renal failure, and 10% of these patients required renal replacement therapy . The treatment of HBV-MN remains controversial. Antiviral therapy including interferon alpha (IFN-α) and nucleoside analogues was the first line treatment recommended by KDIGO guideline, which is effective in inducing long term remission in patients with HBV-MN [11,12,13,14]. However, owing to the poor prognosis, the necessity to use immunosuppressive therapy was raised in an attempt to achieve earlier relief of symptoms and improve prognosis. Prednisone was first used in 1991, showing no help but virus activation [15, 16]. To avoid the exacerbation of liver impairment, combination regimen of antiviral drugs and immunopressants was then introduced. It did improve the proteinuria in HBV-MN patients without altering HBV replication or damaging liver functions . However, only early remission rate were increased compared with antiviral therapy alone . To date, no evidence about the long-term effects of these regimen on renal functions has been published. In this study, patients were all treated with antiviral drugs with only one receiving immunosuppresants. All the patients receiving non-immunosuppressive therapy achieved remission with stable renal function during the follow-up. In contrast to the previous study on HBV-MN, this result indicated a favorable outcome of PLA2R positive HBV-MN. What’s more, this entity showed higher remission rate without immunosuppressive therapy than PLA2R positive IMN patients as the severity of nephrotic syndrome and renal function were similar in the two groups. It’s reasonable for HBV-MN patients to achieve remission of proteinuria after using antiviral drugs, since the deposition of HBeAg and anti-HBe immune complexes detected in the subepithelial region is suggested pivotal to disease pathogenesis . Still, more conservative treatment and longer observation period for HBV-MN patients in our center could partially attributed. Based on our findings, antiviral treatment should be recommended for PLA2R positive HBV-MN patients once the diagnosis established while immunosuppressive therapy would be unnecessary unless impaired renal function or lethal complications associated with severe nephrotic syndrome. Notably, there are one to three years’ antiviral treatment before the 6 patients in our study achieving spontaneous remission, which means a much longer observation period than in the treatment of IMN patients.
Nevertheless, this study was limited by its retrospectively observational analysis, small size and single-center experience. The 7 HBV-MN patients enrolled were with relatively mild involvement as less than half presented with severe nephrotic syndrome. In addition, the lack of PLA2R negative HBV-MN patients and the comparison between PLA2R positive and negative groups limited the investigation on the role of PLA2R in HBV-MN. Thus, a prospective, multi-center, randomized control trial including PLA2R negative HBV-MN patients is needed for further evaluation.
In conclusion, PLA2R positive HBV-MN usually presented with nephrotic syndrome, similar to IMN patients, but much more profound mesangial electronic deposits revealed by renal histopathology. In addition, PLA2R positive HBV-MN patients appears to have more favorable prognosis after antiviral therapy, which supports a secondary form of MN and effectiveness of antiviral therapy on this entity.