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Hepatitis B virus and glomerulonephritis: Two silent killers

Hepatitis B virus (HBV) infection is one of the major public health threats in the world. Around 248 million subjects have a positive hepatitis B surface antigen (HBsAg) in sera, with a global seroprevalence rate of 3.61%. In Taiwan, despite the successful implementation of HBV vaccination and national viral hepatitis treatment program, the overall prevalence rate of chronic HBV infection is still as high as 13.7%. Hepatitis B now ranks 15th among the total causes of mortality in the world. Moreover, HBV infection contributes to around 30% of cirrhosis and 45% of hepatocellular carcinoma (HCC) deaths. However, substantial patients with chronic HBV infection are often underrecognized until the development of end-stage liver diseases due to a lack of symptoms in the early phase of this disease. Although HBV is a hepatotropic virus, several extrahepatic manifestations have been reported in around 10% to 20% of patients with chronic HBV infections, including renal diseases, vasculitis, peripheral neuropathy, and arthralgias. Among them, glomerulonephritis (GN) is the most common one, and it has been reported to be associated with HBV infection by Combes in 1971, soon after the discovery of HBV. One recent study from China demonstrated that, in elderly patients who received a renal biopsy, HBV-related GN is the second most common cause (16.02%) of nephrotic syndrome after idiopathic membranous nephropathy (50%). Various forms of GN have been reported to have a link to HBV infection, including membranous GN (MGN), membranoproliferative GN (MPGN), immunoglobulin (Ig) A nephropathy, mesangioproliferative GN, and focal segmental glomerulosclerosis (FSGS). Although it has not been fully elucidated, the immune complexes of viral antigen (including HBsAg, hepatitis B envelope [HBe] antigen, and hepatitis B core [HBc] antigen) and host antibody depositions in the renal tissues might play a crucial role in the pathogenesis of HBV-related GN. Like chronic HBV infection, HBV-related GN also has a wide spectrum of clinical manifestations, including chronic latent disease without overt symptoms, proteinuria, hematuria, and progressive kidney diseases. Generally, HBV-related GN has a relatively benign course in children. Nevertheless, around 30% of adult patients with HBV-related GN may progress to renal failure if not diagnosed and treated promptly. Moreover, it is very critical to diagnose HBV-related GN adequately because antiviral therapy is recommended for patients with HBVrelated renal disease and GN, while monotherapy with immunosuppressants, such as corticosteroids, may induce the reactivation of HBV, which may in turn lead to hepatitis flares, liver failure, and even cause the deteriorations of renal diseases. The diagnosis of HBV-related GN is established based on the presence of GN with the exclusion of other types of secondary nephritis and the presence of HBV antigen in kidney. Hence, a renal biopsy is required for the diagnosis of HBV-related GN. However, renal biopsy is an invasive procedure and is not feasible in some clinical settings. Moreover, although the incidence of HBV-related GN increases in patients with active HBV replication and positive HBeAg in sera, several studies demonstrated that HBV-related GN occurs in HBsAg serological-negative patients.11–13 Consequently, the prevalence of HBV-related GN might be underestimated because of the difficulty of diagnosis and lack of suspicion in the early phase of this disease by some clinical physicians. In Taiwan, the prevalence rates of chronic HBV infection and chronic kidney diseases are both high. Nevertheless, there are scarce data to investigate the epidemiology and risk factors for HBV-related GN in Taiwan till now. In this issue of the Advances in Digestive Medicine, Huang and his colleagues assessed the correlation between chronic HBV infection and the risk of GN in a large populationbased study in Taiwan. They demonstrated that, for patients with chronic HBV infection, they had a significantly higher risk of developing GN than the control group after adjusting for the potential confounding factors, such as age, gender, and comorbidities. Hence, a suggestion is made to screen for GN in patients with chronic HBV infection, especially for those with symptoms of nephrotic syndrome, such as proteinuria, hematuria, or impaired renal function. However, several issues should be addressed. First, the association between HBV infection and GN risk seemed to be more significant in patients who were younger than 50 years old in this study. The authors speculated that the active immune response in the HBV immune clearance Received: 25 October 2018 Accepted: 5 November 2018