Successful use of lamivudine for severe acute hepatitis B virus infection in a cardiac transplant recipient.

Abstract

Acute hepatitis B virus (HBV*) infection in cardiac transplant recipients and other immunocompromised hosts has a high rate of chronicity. Lamivudine has previously been used in the treatment of chronic HBV infection and to prevent recurrence of this infection in patients undergoing orthotopic liver transplantation for decompensated cirrhosis secondary to chronic HBV infection. Its role in the treatment of acute HBV infection is unclear. We report a case of clinically severe acute hepatitis B infection, occurring in a cardiac recipient, that was successfully treated with lamivudine. Recent reports have established the efficacy of the nucleoside analogue lamivudine in treating chronic hepatitis B virus (HBV) infection and established the prophylactic role of lamivudine in preventing the recurrence of HBV infection after orthotopic liver transplantation (OLT) (1-4). However, lamivudine's role, if any, in the treatment of acute HBV infection is unclear because, in >95% of immunocompetent adults with acute HBV infection, the infection will spontaneously resolve with loss of hepatitis B surface antigen (HBsAg) and development of neutralizing hepatitis B surface antibody (HBsAb). Prior reports suggest that in organ transplant recipients, including orthotopic heart transplant (OHT) recipients, with acute HBV infection, the infection will not spontaneously resolve, and there may be an attendant increase in the risk of mortality (5, 6). Therefore, anti-viral therapy may be of use in the organ transplant recipient with acute HBV infection. Standard anti-viral therapy, such as alpha interferon, is generally ineffective in the immunocompromised patient and can be associated with an increased risk of graft rejection in the organ transplant recipient. Lamivudine, in contrast, seems to be well-tolerated in these patients, perhaps because its mechanism of action differs from that of other therapies. Lamivudine is a synthetic nucleoside analogue that works by causing premature termination of viral DNA chains during reverse transcription and has been well tolerated in liver transplant recipients (3, 4). CASE REPORT A 64-year-old man underwent OHT in 1987 for ischemic cardiomyopathy. Serological study results before and in the initial years after the transplant were negative for HBsAg and (HBcAb). Liver chemical analysis results were also normal (see Table 1). Nine years after his OHT, the patient sought medical attention for low grade fever, generalized fatigue, and a migratory arthritis during the preceding 2 months. Routine laboratory testing revealed biochemical evidence of hepatic dysfunction. Further studies revealed the presence of HBsAg, hepatitis B core antibody immunoglobulin M (HBcAb-IgM), and HBeAg in the absence of HBsAb, consistent with acute HBV infection. There was a history of recent acupuncture. No other potential sources of infection were identified.Table 1: Patient's biochemical, serologic, and virologic profile before and after acquiring acute HBV infection The patient's maintenance immunosuppression consisted of cyclosporin 75 mg p.o., b.i.d. and mycophenolate 250 mg, p.o., b.i.d. This regimen was not altered during the patient's subsequent course. Hepatitis B virus DNA (HBV DNA) levels, initially undetectable, became strongly positive. The patient's condition worsened with increasing fatigue, jaundice, early hepatic encephalopathy, and coagulopathy. Treatment with lamivudine 150 mg, p.o., q.d. was started 1 month after diagnosis after informed consent was obtained. No side effects or compromise of graft function were noted. Rapid clinical improvement coincided with clearance of HBV DNA and HBsAg after 4 weeks and 9.5 weeks of therapy, respectively. Absence of viral replication coincided with development of HBsAb. After 11 weeks of lamivudine, the patient was asymptomatic with normal liver chemical analysis results and lamivudine was discontinued. At the last follow-up, 19 months after diagnosis of acute HBV infection, the patient remains clinically well, without evidence of active HBV infection. DISCUSSION This is the first reported use of lamivudine for the treatment of acute HBV infection in a therapeutically immunosuppressed OHT recipient. An earlier report described some clinical improvement with protracted ganciclovir therapy in an OHT recipient having chronic HBV infection, but did not document clearance of HBV (7). Two retrospective case series of OHT patients with untreated acute HBV suggest that without therapy, HBV will not spontaneously resolve. In the first series (5), 10 of 10 patients with documented acute HBV after OHT remained positive for HBsAg, HBeAg, and HBV DNA during a median of 58 months of follow-up. In the second series (6), all 63 patients with serologically documented acute HBV after OHT remained HBsAg positive during up to 4 years of follow-up. Randomized, double-blind, dose-ranging studies have documented the efficacy of lamivudine in the treatment of chronic HBV infection (1, 2). In addition, small pilot studies suggest that lamivudine may be of benefit in preventing posttransplant recurrence of HBV infection in patients undergoing OLT for chronic HBV-associated liver disease (3, 4). In other reports, this potent nucleoside analogue has shown promising results in the management of renal transplant recipients with chronic HBV (8). Our experience, in conjunction with a recent report describing clearance of severe, acute HBV infection in a cadaveric renal transplant recipient (8), suggests that recognition of acute HBV in an organ transplant recipient should prompt consideration of lamivudine to abort development of severe HBV infection and/or progression to chronicity. Given the low rate of spontaneous HBV clearance among patients with acute HBV infection after OHT, we believe that lamivudine played a pivotal role in clearing our patient's post-OHT acute HBV infection. Furthermore, this patient's worrisome clinical course suggested that he was at risk of developing fulminant HBV infection, which has been observed in other transplant recipients with acute HBV (10); this outcome may have been prevented by the use of lamivudine. Future studies are warranted to better define the potential role of lamivudine in the treatment of immunocompromised patients with acute hepatitis B infection. Gareth Dulai Lisa Higa Jon Kobashigawa Paul Martin2 Division of Digestive Diseases; Division of Cardiology; Department of Medicine; UCLA School of Medicine; Los Angeles, California