Effectiveness and long-term outcome of lamivudine therapy for acute hepatitis B
Introduction
Hepatitis B virus is a causative agent of acute liver failure. Hepatitis B virus infection is usually self-limiting, but it sometimes progresses to fulminant hepatitis. Despite intensive medical care, the survival rates of patients with acute liver failure treated with non-transplant therapy alone are poor, and the only effective treatment is orthotopic liver transplantation (OLT) [1].
Lamivudine shows promise as a treatment for HBV as it rapidly suppresses the elevation of serum HBV DNA in patients with chronic hepatitis B (CHB) and it is tolerated well [2], [3]. Clinically significant improvements in liver histology and biochemical parameters have been seen in a wide range of CHB patients treated with lamivudine [4]. In contrast, only a few studies have demonstrated the ability of this drug to treat severe acute hepatitis B (AHB) [5], [6]. To our knowledge, the outcome of long-term lamivudine treatment in AHB patients is unknown. The precise mechanisms of liver injury induced by AHB viral infection and factors contributing to progression to fulminant hepatitis remain unknown. However, acute liver failure could be prevented by inhibiting viral replication; this is the rationale for our decision to use lamivudine to treat severe AHB in the present three patients. The clinical course of all three patients treated with lamivudine was self-limited and accompanied by the disappearance of HBV DNA from the sera and normalization of the alanine aminotransferase (ALT) level. HBsAb was undetectable in two of the three patients over a 1-year follow-up period, and none of the patients exhibited reactivation. We describe the three patients in detail.
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Patients
Lamivudine therapy was administered to three male patients (age range, 27–31 years) between August 1999 and April 2000 at our hospital. The source of hepatitis B infection was unknown in one patient and prostitutes for the other two. We had no prior experience of using lamivudine at our hospital to treat acute self-limited hepatitis B. However, we treated these three patients with lamivudine because of a prolonged course of hepatic injury (Table 1). Levels of HBV DNA were measured by
Clinical outcome
The lamivudine therapy for patient 1 was discontinued because of seroconversion from HBsAg to HBsAb. Patients 2 and 3 continued to receive lamivudine for 11 and 13 months, respectively. The dose of lamivudine given to patient 2 was diminished to 75 mg per day, 7 months after the start of therapy. The clinical courses are shown in Fig. 1. Liver biopsies during the acute phase revealed virally induced acute hepatitis in all three patients (Fig. 2). Liver function tests rapidly recovered, and HBV
Discussion
Lamivudine has been approved as a safe and effective treatment for CHB. Besides treatment for CHB, lamivudine has also been used to treat patients with AHB infection, including those with severe acute hepatitis and fulminant hepatitis [5], [6]. The three patients described in the present report also responded very well, since ALT rapidly normalized and HBV-DNA disappeared. No side effects were evident during long-term administration. Lamivudine is more effective for treating patients with CHB
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