Chronic hepatitis B reactivation and systemic glucocorticosteroid therapy.

SIR, We read with interest the article by Yang et al. in a recent issue of the Journal in which they retrospectively reviewed patients with pemphigus vulgaris and dermatomyositis treated with immunosuppressive therapies including systemic glucocorticosteroid (GC). In the article, the authors suggested that four of 98 patients had developed hepatitis because of GC-induced hepatitis B virus (HBV) reactivation. The observation is quite informative and is particularly important to those patients in HBV-endemic areas requiring long-term GC therapy. However, the findings should be interpreted cautiously before concluding that the use of GC has led to HBV reactivation directly in these patients. HBV reactivation is characterized by a temporal relationship between the rise in viral load of HBV, biochemical hepatitis and medication use. The occurrence of hepatitis during or immediately after cytotoxic chemotherapy is accompanied either by a 10-fold increase in HBV DNA levels or by an absolute increase that exceeds 9 log10 copies mL , in the absence of other systemic infections. Therefore, the baseline characteristics of HBV infection are essential to establish a definite diagnosis of HBV reactivation. The overt biochemical flares or hepatitis in the article may have alternative explanations. The diagnosis of HBV reactivation would not be definite without comparison with the baseline HBV DNA level, as the possibility of silent viraemia before treatment cannot be ruled out. Further, a single elevation of HBV DNA level alone does not guarantee an increment of the level. Besides, it is not uncommon for HBV carriers to develop spontaneous flares – the incidence may be up to 32% – and the use of GC in this setting could possibly be coincidental. Based on the observation of this case series, Yang et al. recommended concurrent use of antiviral agents in chronic HBV carriers receiving long-term immunosuppressive therapy. Current practices are mostly derived from the experience of cancer patients receiving chemotherapy. In a study of Chinese patients with lymphoma, 27% were found to be seropositive for hepatitis B surface antigen. Of these patients, 47% developed reactivation of HBV during chemotherapy and this resulted in 5% mortality. A study by Nakamura et al. of Japanese patients with lymphoma reported that only 3Æ3% of the patients had chronic HBV infection, but the incidence of severe hepatitis was found to be 53%, which was associated with a mortality rate of 24%. Thus, preventing HBV reactivation in HBV carriers with lamivudine has been advocated in patients with haematological malignancies treated with chemotherapy. However, little is known whether universal use of antiviral agents pre-emptively is indicated in noncancer patients under immunosuppressive or GC treatment because the antiviral agents are not panaceas. Prolonged use of lamivudine can decrease hepatitis flares. However, drug-resistant strains of HBV are an emerging problem (15% per year with lamivudine use). Therefore, identification of high-risk groups for HBV reactivation is important before starting immunosuppressive therapy. The risk factors identified in cancer patients receiving chemotherapy include male gender, young age, diagnosis of lymphoma or breast cancer, seropositive hepatitis B envelope antigen, high pretreatment HBV DNA level, use of GC and high cumulative dose of GC. In the article by Yang et al., the proportion of HBV-infected patients in the study group was lacking. We congratulate Yang et al. for this first report of possible HBV reactivation in dermatological patients on long-term GC. However, more studies are needed to draw a clear picture on this issue, such as the incidence, rate of severe complications and specific risk factors for HBV reactivation in this group of patients. At this moment, we cannot advocate the pre-emptive use of antiviral agents in these patients. For early detection of possible complications, we can screen the baseline HBV status and regularly monitor the liver function of these patients. When necessary, it is best for us to work in conjuction with gastroenterologists on this emerging problem.