Core promoter mutant HBV non-responding to adefovir after viral breakthrough on lamivudine: rapid virologic response to tenofovir plus lamivudine in a cirrhotic patient.
BACKGROUND
In chronic hepatitis B patients undergoing therapy with LAM or ADV, viral breakthrough is possible due to the emergence of drug resistance. LAM resistant HBV strains are susceptible to ADV, while ADV resistant mutants remain sensitive to LAM.


METHODS
A male patient with HBV-related cirrhosis developed viral breakthrough (HBV DNA>1.8 x 106 IU/ml) after 4 1/2 years of treatment with LAM, and therapy was switched to ADV (10 mg/d). After three months, HBV remained highly replicative without any changes of ALT values, and ADV dose was increased (20 mg/d). Because of unchanged VL sequence analysis was performed three months later, which showed the mutation (rtS219A) and the concomitant mutation (sS210R) and 2 mutations in core promoter region (A1762T), (G1764A). During the sixth month of ADV monotherapy the patient developed liver failure. After administration of TDF plus LAM, HBV DNA became undetectable within 39 days. At day 41, the patient underwent OLT. TDF plus LAM were well tolerated, and the patient maintained undetectable HBV DNA levels, and in addition to HBIG a sustained HBsAg negative status over twenty-eight months post OLT.


CONCLUSIONS
TDF plus LAM is a safe drug combination in case of viral breakthrough during LAM treatment and subsequent primary non-response to ADV. High VL persisting for >or= 6 months of continuous antiviral treatment may indicate drug resistance. Especially in cirrhotic patients with LAM resistance, "add on" of a nucleotide analogue is the right therapeutic strategy even before viral breakthrough gets apparent.
Katsounas
A
A
Medical Department gastroenterology and hepatology, University of Duisburg-Essen, Germany.
Jochum
C
C
Canbay
A
A
Schlaak
J
J
Gerlich
W H
WH
Gerken
G
G
D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000601:surgery / Q000821:virology*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage* / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000821:virology; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009154:Mutation; D063065:Organophosphonates / Q000008:administration & dosage* / Q000627:therapeutic use*; D011401:Promoter Regions, Genetic; D000068698:Tenofovir
D004279:DNA, Viral; D063065:Organophosphonates; D019259:Lamivudine; C053001:adefovir; D000068698:Tenofovir; D000225:Adenine