Adefovir dipivoxil for wait-listed and post–liver transplantation patients with lamivudine-resistant hepatitis B: Final long-term results

Abstract

Wait-listed (n ϭ 226) or post-liver transplantation (n ϭ 241) chronic hepatitis B (CHB) patients with lamivudine-resistant hepatitis B virus (HBV) were treated with adefovir dipivoxil for a median of 39 and 99 weeks, respectively. Among wait-listed patients, serum HBV DNA levels became undetectable (Ͻ1,000 copies/mL) in 59% and 65% at weeks 48 and 96, respectively. After 48 weeks, alanine aminotransferase (ALT), albumin, bilirubin, and prothrombin time normalized in 77%, 76%, 60%, and 84% of wait-listed patients, respectively. Among posttransplantation patients, serum HBV DNA levels became undetectable in 40% and 65% at weeks 48 and 96, respectively. After 48 weeks, ALT, albumin, bilirubin, and prothrombin time normalized in 51%, 81%, 76%, and 56% of posttransplantation patients, respectively. Among wait-listed patients who underwent on-study liver transplantation, protection from graft reinfection over a median of 35 weeks was similar among patients who did (n ϭ 34) or did not (n ϭ 23) receive hepatitis B immunoglobulin (HBIg). Hepatitis B surface antigen was detected on the first measurement only in 6% and 9% of patients who did or did not receive HBIg, respectively. Serum HBV DNA was detected on consecutive visits in 6% and 0% of patients who did or did not receive HBIg, respectively. Treatment-related adverse events led to discontinuation of adefovir dipivoxil in 4% of patients. Cumulative probabilities of resistance were 0%, 2%, and 2% at weeks 48, 96, and 144, respectively. In conclusion, adefovir dipivoxil is effective and safe in wait-listed or posttransplantation CHB patients with lamivudine-resistant HBV and prevents graft reinfection with or without HBIg. Liver Transpl 13:349-360, 2007.

Tenofovir disoproxil fumarate (TDF), emtricitabine/TDF, and entecavir in patients with decompensated chronic hepatitis B liver disease

“…21,22 Six deaths, two in each randomized treatment group, were all considered unrelated to study drug and reflective of endstage liver disease (except one case of septic shock due to V. vulnificus). All occurred within 6 months of entry, which is consistent with mortality patterns for other studies of ADV, 19 lamivudine, 16 and ETV 21 in decompensated CHB patients. Since the initiation of the present study, lactic acidosis has been reported in decompensated CHB patients treated with ETV.…”

“…14 Present treatment guidelines advocate oral antivirals in decompensated CHB patients. [3][4][5] Studies with lamivudine [15][16][17] and ADV 18,19 have demonstrated improved clinical outcomes (decreased mortality and improved liver function) in decompensated CHB patients. Notably, lamivudine resistance mutations emerging during lamivudine treatment can negate therapeutic benefit, resulting in increased Child-Turcotte-Pugh (CTP) scores.…”

“…Notably, lamivudine resistance mutations emerging during lamivudine treatment can negate therapeutic benefit, resulting in increased Child-Turcotte-Pugh (CTP) scores. 17 In an open-label compassionate use trial, ADV benefited pre-and posttransplant patients with lamivudine-resistant CHB including decompensated cirrhotics, 18,19 in terms of HBV DNA suppression and CTP score improvement. Consistent with outcomes in lamivudine-treated patients, the majority of deaths in the trial occurred during the first 6 months, particularly in patients extremely ill at entry.…”

Hepatitis B virus treatment: Which patients require immediate treatment

“…In one study involving 226 wait-listed patients, clinical improvement led to delisting in 20% of cases. 7 Entecavir and tenofovir are currently preferred for the treatment of decompensated cirrhosis because of greater antiviral potency and a high genetic barrier to resistance. In a multinational study, 191 patients with decompensated cirrhosis (mean CTP score 8.8, Model for End-Stage Liver Disease [MELD] score 17.1) were treated with entecavir or adefovir for up to 96 weeks.…”

Recent data on treatment of chronic hepatitis B with nucleos(t)ide analogues

“…The cumulative probabilities of resistance were 0, 2, and 2% at weeks 48, 96, and 144, respectively. There were 4% of patients who discontinued adefovir for treatmentrelated adverse events [79].…”