Prospective study on lamivudine-resistant hepatitis B in renal allograft recipients.
The natural history of lamivudine-resistant hepatitis B virus (HBV) infection in renal transplant recipients (RTx) is unclear, despite its increasing incidence. Twenty-nine HBsAg-positive RTx with rising HBV DNA received lamivudine therapy. The course of lamivudine-resistant HBV infection was studied prospectively. During 68.7 +/- 12.5 months of follow-up, 14 (48.3%) patients developed lamivudine resistance, at 10-35 months (mean 16.9 +/- 7.0). All showed mutant sequences at codons 552 and 528 of the YMDD motif, while 13 patients demonstrated wild-type sequence at codon 555. Lamivudine resistance was unrelated to patient demographics, HBeAg status/sero-conversion, or genotype. Following resistance, HBV DNA and alanine aminotransferase showed an initial increase followed by spontaneous gradual reduction. The subsequent peak HBV DNA was lower (1.26 +/- 1.09 x 10(9) vs. 6.26 +/- 12.23 x 10(9) copies/mL, p = 0.011), while that of alanine aminotransferase was higher (196 +/- 117 vs. 77 +/- 47 imicro/l, p = 0.005), compared with pretreatment levels. Post-resistance hepatitic flare occurred in 11 (78.6%) patients. This was transient in four (36.4%), but became chronic in six (54.5%) patients. Decompensation was noted in one patient during this flare, but all survived. We conclude that drug resistance is prevalent in lamivudine-treated RTx. Despite a lower ensuing peak viremia compared with baseline, hepatitic flare is common. While most patients have spontaneous resolution, a minority may develop potentially fatal decompensation during the preceding exacerbation.
Chan
Tak Mao
TM
Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong. dtmchan@hku.hk
Tse
Kai Chung
KC
Tang
Colin S O
CS
Lai
Kar Neng
KN
Ho
Stephen K N
SK
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000378:metabolism; D020816:Amino Acid Motifs; D003062:Codon; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000235:genetics; D024882:Drug Resistance, Viral; D005260:Female; D005500:Follow-Up Studies; D006505:Hepatitis / Q000821:virology; D006509:Hepatitis B / Q000209:etiology*; D006515:Hepatitis B virus / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D016030:Kidney Transplantation / Q000009:adverse effects*; D019259:Lamivudine / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D013997:Time Factors
D003062:Codon; D004279:DNA, Viral; D007166:Immunosuppressive Agents; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D000410:Alanine Transaminase