Adefovir dipivoxil therapy for lamivudine‐resistant hepatitis B in pre– and post–liver transplantation patients

• Published in: Hepatology (Baltimore, Md.) Vol. 38; no. 6; pp. 1419 - 1427
• Main Authors: Schiff, Eugene R., Lai, Ching‐Lung, Hadziyannis, Stefanos, Neuhaus, Peter, Terrault, Norah, Colombo, Massimo, Tillmann, Hans L., Samuel, Didier, Zeuzem, Stefan, Lilly, Leslie, Rendina, Maria, Villeneuve, Jean‐Pierre, Lama, Nicole, James, Craig, Wulfsohn, Michael S., Namini, Hamid, Westland, Christopher, Xiong, Shelly, Choy, Gavin S., Van Doren, Sally, Fry, John, Brosgart, Carol L.
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA W.B. Saunders 01-12-2003; Wiley
• Subjects: Adenine - adverse effects; Adenine - analogs & derivatives; Adenine - therapeutic use; Adolescent; Adult; Aged; Antiviral Agents - therapeutic use; Biological and medical sciences; Child; Drug Resistance, Viral; Female; Genotype; Hepatitis B virus - classification; Hepatitis B virus - genetics; Hepatitis B, Chronic - drug therapy; Hepatitis B, Chronic - virology; Human viral diseases; Humans; Infectious diseases; Kidney - drug effects; Lamivudine - therapeutic use; Liver Transplantation - adverse effects; Male; Medical sciences; Middle Aged; Organophosphonates; Viral diseases; Viral hepatitis; Acyclic nucleoside; RNA-directed DNA polymerase; Multicenter study; Hepatic disease; Viral hepatitis B; Reverse transcriptase inhibitor; Antiviral; Clinical trial; Pyrimidine nucleoside; Human; Purine nucleotide; Treatment resistance; Acyclic nucleotide; Enzyme; Transferases; Enzyme inhibitor; Lamivudine; Organic phosphonate; Biological activity; Infection; Nucleotidyltransferases; Adefovir; Chemotherapy; Dideoxynucleoside; Viral disease; Digestive diseases; Nucleosidic analog
• ISSN: 0270-9139; 1527-3350
• DOI: 10.1016/j.hep.2003.09.040

Three‐hundred and twenty‐four patients were enrolled in an open‐label, multicenter, international study in which pre‐ and post‐liver transplantation (LT) patients with recurrent chronic hepatitis B (CHB) and evidence of lamivudine‐resistant HBV were treated with adefovir dipivoxil 10 mg once daily. In the pre‐ and post‐LT cohorts, 128 and 196 patients were treated for a median duration of 18.7 and 56.1 weeks, respectively. In patients who received 48 weeks of treatment, 81% of the pre‐LT and 34% of the post‐LT cohort achieved undetectable serum hepatitis B virus (HBV) DNA (Roche Amplicor MonitorTM polymerase chain reaction [PCR] assay lower limit of quantification [LLQ] < 400 copies/mL) with a median change in serum HBV DNA from baseline of −4.1 log10 and −4.3 log10 copies/mL, respectively. Serum alanine aminotransferase (ALT), albumin, bilirubin, and prothrombin time normalized in 76%, 81%, 50%, and 83% of pre‐LT patients and 49%, 76%, 75%, and 20% of post‐LT patients. The Child‐Pugh‐Turcotte (CPT) score improved in over 90% of patients in both cohorts. Genotypic analysis of 122 HBV baseline samples revealed that 98% of these patients had lamivudine‐resistant mutant HBV. No adefovir resistance mutations were identified in patients after 48 weeks of therapy. One‐year survival was 84% for pre‐LT and 93% for post‐LT patients (Kaplan‐Meier analysis). Treatment‐related adverse effects associated with adefovir dipivoxil in this setting were primarily mild to moderate in severity. In conclusion, 48 weeks of adefovir dipivoxil resulted in significant improvements in virologic, biochemical, and clinical parameters in CHB patients pre‐ and post‐LT with lamivudine‐resistant HBV.