Changes in serum albumin during treatment of chronic hepatitis B with lamivudine: effects of response and emergence of drug resistance.
OBJECTIVE
In chronic hepatitis B patients treated with lamivudine, the incidence of drug resistance increases with the duration of therapy. The effect of drug resistance on hepatic synthetic function is not well defined. The aim of the present study was to assess the effect of lamivudine therapy on hepatic synthetic function in patients with moderately severe chronic hepatitis B and, particularly, to determine the effect of drug resistance.


METHODS
Hepatic synthetic function was assessed using serial measurements of serum albumin in 38 patients (26 with cirrhosis) in an open-label treatment program.


RESULTS
An initial antiviral response (hepatitis B virus [HBV] DNA undetectable by hybridization assay) occurred in all patients, and nine of 22 (41%) hepatitis B e antigen-positive cases underwent hepatitis B e antigen seroconversion. Among 29 patients with undetectable serum HBV DNA at the end of observation, the mean serum albumin concentration rose from 39.9 +/- 0.7 to 43.2 +/- 0.6 g/L, corresponding to a yearly increase of 1.85 g/L (p < 0.001). This was largely attributable to an increase among cirrhotic patients. Nine patients (24%) developed resistance to lamivudine, all after 12 months of treatment. Among them, the mean serum albumin concentration had increased from 39.6 +/- 1.2 to 42.9 +/- 0.8 g/L before resistance emerged, but then decreased to 39.3 +/- 1.7 g/L (p = 0.01) at the time of reappearance of HBV DNA.


CONCLUSIONS
Suppression of viral replication by lamivudine improves hepatic synthetic function in chronic hepatitis B patients, but emergence of drug resistance is associated with a rapid decline in serum albumin, at least to pretreatment levels.
Hui
Jason M
JM
Storr Liver Unit, Westmead Millennium Institute, University of Sydney at Westmead Hospital, New South Wales, Australia.
George
Jacob
J
Liddle
Christopher
C
Lin
Rita
R
Samarasinghe
Dev
D
Crewe
Evelyn
E
Farrell
Geoffrey C
GC
D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000502:physiology*; D005260:Female; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology* / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D012709:Serum Albumin / Q000032:analysis* / Q000187:drug effects*; D013997:Time Factors; D016896:Treatment Outcome
D000998:Antiviral Agents; D012709:Serum Albumin; D019259:Lamivudine