Rapid HBV DNA decrease (week 12) is an important prognostic factor for first-line treatment with adefovir dipivoxil for chronic hepatitis B.
BACKGROUND
The aim of the study was to estimate the effect of viral factors (HBV genotype, viral load and kinetics) to treatment response in chronic hepatitis B (CHB) and first-line therapy with adefovir dipivoxil (ADV).


METHODS
Sixty-six patients (60% males, 65% HBeAg negative) were treated with 10 mg ADV QD. Quantitative HBV DNA and ALT levels were determined at weeks 4, 12, 24, 48, 72 and 96. Nonresponse or viral resistance to ADV was assessed in patients with either persistent elevated HBV DNA levels (week 24) or with an increase in HBV DNA of at least 1 log after initial decline.


RESULTS
Most patients were infected with genotype D (66.7%; genotype A: 27.3%; genotype E: 6%); 86.4% achieved a virological (VR) and 54.5% a biochemical response (BR) in week 48, more often in patients with genotype A (P < 0.01). In week 96, BR increased to 60.5%, whereas a negative HBV DNA was observed in 83.3%. In 3% an ADV-induced viral resistance was detected. As an important predictive parameter for VR, a rapid decline of viral load at week 12 was observed. Of the patients with a negative PCR or drop of viral load of at least 3 log, 96% were still HBV DNA negative at the end of week 96; 77% of patients with a partial response achieved a VR. In contrast, no patient with nonresponse (week 12) reached a negative PCR at week 96 (P < 0.0001).


CONCLUSIONS
These results underline the importance of early viral kinetics to assess treatment response in CHB. In ADV nonresponders (week 12), an advanced antiviral therapy or switch to another nucleoside analogue should be considered.
Hass
Holger G
HG
Department of Internal Medicine and Oncology, Paracelsus Hospital, Scheidegg, Germany. Dr.Holger.Hass@pk-mx.de
Bock
Thomas
T
Nehls
Oliver
O
Kaiser
Stephan
S
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood*; D024882:Drug Resistance, Viral / Q000187:drug effects; D005260:Female; D005838:Genotype; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*; D011379:Prognosis; D012189:Retrospective Studies; D019562:Viral Load
D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D000410:Alanine Transaminase; D000225:Adenine; C106812:adefovir dipivoxil