An open-label study of lamivudine for chronic hepatitis B in six patients with chronic renal failure before and after kidney transplantation

OBJECTIVE: The course of hepatitis B virus (HBV) infection after kidney tra nsplantation is aggressive, with a high mortality rate from liver disease m ainly in patients who were serum hepatitis B e antigen (HBeAg) or WBV DNA-p ositive before transplantation. Lamivudine has been shown to be a potent in hibitor of HBV replication. The aim of the study was to examine the efficac y and safety of lamivudine therapy in patients with chronic renal failure a nd chronic HBV infection. METHODS: The study population consisted of six potential candidates for kid ney or combined kidney and liver transplantation aged 25-49 yr (four patien ts had already undergone a kidney transplantation and developed chronic rej ection). All were serum HBeAg and/or HBV DNA-positive and had been maintain ed on hemodialysis for 3 months to 3 yr. The duration of HBV infection was 7 months to 14 yr. Serum alanine aminotransferase (ALT) levels ranged from 72 to 610 U/L (median, 158 U/L). Liver histological evaluation showed mild to moderate chronic hepatitis (n = 4) or liver cirrhosis (n = 2). None of t he patients was infected with hepatitis C or D viruses. In four patients, t reatment consisted of 10 mg of oral lamivudine per day. In the other two pa tients, a virological and biochemical response could be achieved only when the dose was increased to 40 mg/day. RESULTS: Lamivudine treatment was associated with 1) normalization of serum ALT levels and rapid disappearance of serum HBV DNA (by hybridization) (fi ve patients, one of whom died from sepsis); 2) seroconversion: disappearanc e of HBeAg (three patients) and HBsAg (two patients); 3) minor side effects : abdominal pain and nausea tone patient); 4) clinically asymptomatic lamiv udine resistance 8 months after treatment tone patient); and 5) successful combined kidney and liver transplantation with no evidence of recurrent HBV infection at 6-8 months postoperatively (two patients with cirrhosis). CONCLUSIONS: Lamivudine therapy is effective as an HBV replication inhibito r in patients with chronic renal failure and HBV infection. Prospective stu dies of lamivudine pharmacokinetics and dosing in renal failure are needed to be able to treat patients appropriately. Although our study is small and further follow-up is needed, our data suggest that lamivudine therapy may enable selected patients with chronic hepatitis B to undergo kidney or comb ined kidney and liver transplantation in patients with established cirrhosi s. (C) 2000 by Am. Cell. of Gastroenterology.