BACKGROUND/AIMS: Anti-viral therapy using hepatitis B immune globulin and lamivudine could not prevent HBV recurrence after liver transplantation (LT) completely. Adefovir dipivoxil is a acyclic nucleotide phosphate analogue and known to have potent anti-HBV effect. In this study, we analyzed the therapeutic effect of adefovir for recurrent or de novo HBV infection after LT. METHODS: From December 2002 to October 2004, adefovir was administered in 12 post-LT patients of HBV infection (11 recurrent and 1 de novo infection). In these patients, lamivudine and other combined therapies were used before the introduction of adefovir. Thereafter, adefovir combined with lamivudine was administered to all patients. RESULTS: The duration of adefovir administration was 5.5-18 (median, 15.5) months. The median values of serum AST and ALT levels were significantly reduced from 86+/-80 IU/L and 140+/-103 IU/L, respectively before the adefovir administration to 42+/-19 IU/L and 38+/-33 IU/L after 2 months of administration. This trend of improved liver function persisted throughout the follow-up period. HBeAg seroconversion was achieved in 4 of 10 patients (40%) and HBsAg seroconversion was observed in 1 of 10 patients (10%). HBV DNA levels have decreased to undetectable levels by hybridization assay in 6 of 7 patients within the first 2 months of therapy. Nephrotoxicity and hypophosphatemia were not found in all of these patients. CONCLUSIONS: Based on this preliminary result, adefovir dipivoxil seems to be an effective and safe antiviral agent leading to viral inhibition and clinical improvement in post-LT patients with recurrent or de novo HBV infection.
Adenine/administration & dosage/*analogs & derivatives ; Adult ; Antiviral Agents/*administration & dosage ; Drug Therapy, Combination ; English Abstract ; Female ; Hepatitis B, Chronic/*drug therapy ; Humans ; Lamivudine/administration & dosage ; *Liver Transplantation ; Male ; Middle Aged ; Phosphonic Acids/*administration & dosage ; Recurrence ; Reverse Transcriptase Inhibitors/administration & dosage

BACKGROUNDS/AIMS: Continuation of lamivudine therapy is controversial for patients with chronic hepatitis B when viral breakthrough occurs. Moreover, the effect of continuous lamivudine therapy is unknown in patients with acute exacerbation after viral breakthrough. We assessed clinical course of acute exacerbation after viral breakthrough in patients who continued and discontinued lamivudine therapy. METHODS: Medical records of 109 patients with viral breakthrough during lamivudine therapy were reviewed. Of 40 patients with acute exacerbation (ALT level > 5 x ULN), adefovir dipivoxil was unavailable in 38 patients. These 38 patients (mean age 42.6 years; male/female, 34/6) were divided into continuation (n=21) and discontinuation (n=17) groups. Clinical courses of the 2 groups were compared. RESULTS: During follow-up period (mean, 27 months; range, 6-60 months), ALT levels decreased to < 2 x ULN in 11 patients (52%) of continuation group and 9 patients (53%) of discontinuation group, varied from 2 x to 5 x ULN in 9 (43%) and 5 (29%), respectively, and increased to > 5 x ULN in 1 (5%) and 3 (18%), respectively, with no statistical significance (P=.417). CONCLUSIONS: When acute exacerbation of ALT levels occurs after viral breakthrough during lamivudine administration in patients with compensated chronic hepatitis B, continuation of lamivudine may have no advantage over discontinuation.
Phosphonic Acids/therapeutic use ; Middle Aged ; Male ; Lamivudine/*administration & dosage ; Humans ; Hepatitis B, Chronic/drug therapy/enzymology/*virology ; Hepatitis B virus/*isolation & purification ; Female ; Antiviral Agents/*administration & dosage ; Alanine Transaminase/blood ; Aged ; Adult ; Adenine/analogs & derivatives/therapeutic use ; Acute Disease

The purpose of this prospective study was to evaluate the efficacy and safety of adefovir dipivoxil with or without ongoing lamivudine in decompensated lamivudine-resistant chronic hepatitis B patients. Forty-six hepatitis B e antigen (HBeAg)-positive patients with decompensated liver function and lamivudine-resistant hepatitis B virus (HBV) were assigned to adefovir dipivoxil monotherapy (n=18) or combination therapy with ongoing lamivudine (n=28) according to their own preference. After 24 weeks of treatment, 83% of monotherapy and 86% of combination therapy showed serum HBV DNA below detection limit (<0.5 pg/mL). Alanine aminotransferase (ALT) normalized in 78% and 82% respectively. Median Child-Pugh-Turcotte (CPT) score or Model for End-Stage Liver Disease (MELD) score reduced significantly by 3 or 5 point in monotherapy and 2 or 2 point in combination therapy respectively. There were no significant differences in rate of undetectable serum HBV DNA, median change of ALT and median reduction of CPT or MELD scores between the two groups. In conclusion, both adefovir dipivoxil monotherapy and combination therapy with ongoing lamivudine result in comparable virologic, biochemical, and clinical improvements in HBeAg-positive patients with decompensated liver function and lamivudine-resistant HBV. Combination with lamivudine showed no additional benefit over monotherapy during 24 weeks of treatment in these patients.
Adenine/administration and dosage/*analogs and derivatives ; Adolescent ; Adult ; Anti-HIV Agents/administration and dosage ; Antiviral Agents/administration and dosage ; Drug Combinations ; Drug Resistance, Viral/drug effects ; Female ; Hepatitis B/*complications/*drug therapy ; Humans ; Lamivudine/*administration and dosage ; Liver Cirrhosis/*etiology/*prevention and control ; Male ; Middle Aged ; Phosphonic Acids/*administration and dosage ; Research Support, Non-U.S. Gov't ; Treatment Outcome

BACKGROUND/AIMS: The therapeutic strategies of applying adefovir for treating lamivudine resistant HBV mutants are controversial. Thus, we observed the clinical outcomes after discontinuation of lamivudine to establish the timing to initiate adefovir therapy. METHODS: Fifty chronic hepatitis B (CHB) patients with lamivudine resistant HBV mutants who had received lamivudine for more than 12 months were included in the study. We investigated the clinical outcomes at 6 months after the end of treatment (EOT). We compared the serial clinical outcomes among respective groups based on serum ALT at the EOT and the clinical characteristics of patients with or without acute exacerbation (AE) and the HBeAg loss. We also investigated the predictive parameters of AE and HBeAg loss. RESULTS: Fifteen patients (30%) had experienced AE at 6 months after the EOT. Four patients received antiviral agents because of their hepatic decompensation. Patients with AE had higher serum ALT values and lower HBV DNA titers at EOT compared with those patients without AE. Serum ALT at the EOT was the predictive parameter of AE. Eight patients (21.6%) had newly developed HBeAg loss at 6 months after EOT. The total bilirubin at EOT was the predictive parameter of HBeAg loss. CONCLUSIONS: CHB patients with lamivudine resistant HBV mutants had favorable clinical outcomes at 6 months after EOT. Therefore, we can consider observing the clinical courses after discontinuation of lamivudine and it is not always required to overlap the adefovir for treating lamivudine resistant HBV mutants except for the treatment of patients with a high risk of developing decompensation.
Adenine/administration & dosage/analogs & derivatives ; Adult ; Antiviral Agents/*administration & dosage ; *Drug Resistance, Viral ; English Abstract ; Female ; Hepatitis B e Antigens/blood ; Hepatitis B virus/drug effects ; Hepatitis B, Chronic/*drug therapy/virology ; Humans ; Lamivudine/*administration & dosage ; Male ; Middle Aged ; Phosphonic Acids/administration & dosage ; Reverse Transcriptase Inhibitors/*therapeutic use ; Treatment Outcome

Adefovir dipivoxyl (ADV) effectively suppresses hepatitis B virus (HBV) replication but exhibits nephrotoxicity with severe hypophosphatemia when administered at a high dosage. This is the first report of severe hypophosphatemic osteomalacia induced by ADV at 10 mg/day. A 42-year-old man with HBV-related chronic liver disease presented with generalized bone pain, especially in the left ankle. He had been taking ADV for more than 1.5 years following a clinical breakthrough due to lamivudine-resistant HBV. Aggravating severe hypophosphatemia and elevated serum alkaline phosphatase levels with high bone fraction had been noted after 6 months of ADV therapy. Bone densitometry, simple bone X-rays, and a whole-body bone scan demonstrated osteoporosis and multiple areas with hot uptake, especially in the left ankle. All the image findings and symptoms improved after correcting the hypophosphatemia.
Absorptiometry, Photon ; Adenine/administration & dosage/adverse effects/*analogs & derivatives ; Adult ; Antiviral Agents/administration & dosage/*adverse effects ; Bone Density ; DNA, Viral/analysis ; Drug Resistance, Viral ; Hepatitis B virus/drug effects ; Hepatitis B, Chronic/complications/*drug therapy/virology ; Humans ; Hypophosphatemia/*chemically induced ; Lamivudine/therapeutic use ; Liver Cirrhosis/*virology ; Male ; Phosphonic Acids/administration & dosage/*adverse effects ; Tomography, X-Ray Computed