Long-term lamivudine therapy reduces the risk of long-term complications of chronic hepatitis B infection even in patients without advanced disease.
BACKGROUND
Long-term effects of lamivudine treatment on chronic hepatitis B patients without advanced disease remain unknown. Our aim was to investigate the effects of long-term lamivudine treatment and lamivudine-resistant virus (YMDD) on the development of cirrhosis and hepatocellular carcinoma (HCC) in asymptomatic patients without advanced disease.


METHODS
One hundred and forty-two hepatitis B e antigen (HBeAg)-positive patients (median age: 33.9 years) on long-term lamivudine (median treatment duration: 89.9 months) and 124 HBeAg-positive controls (median age: 33.4 years) were prospectively followed up. Patients were monitored for the development of cirrhosis and HCC, liver biochemistry, hepatitis B virus (HBV) DNA levels, HBeAg seroconversion and hepatitis flares. YMDD mutations (YMDD-MT) were determined annually.


RESULTS
Lamivudine-treated patients had a significantly lower cumulative rate of development of cirrhosis and/or HCC compared with controls (P = 0.005). YMDD-MT occurred in 76.3% of patients after 8 years of lamivudine treatment. When compared with controls and patients with YMDD-MT, patients without YMDD-MT had the greatest reduction of HBV DNA and bilirubin levels, slowest decline of albumin level, highest rate of HBeAg seroconversion and lowest risk of hepatitis flare. Patients with YMDD-MT still had a lower risk for developing cirrhosis and/or HCC (P = 0.024) and a greater HBV DNA reduction (P = 0.001) in comparison with controls. Patients with YMDD-MT and controls had a similar chance of hepatitis flares and hepatic decompensation.


CONCLUSIONS
Long-term lamivudine treatment was associated with a reduced chance of developing cirrhosis and HCC in patients without advanced disease. Although YMDD-MT reduced the benefits from lamivudine therapy, the outcome of these patients was still better than untreated patients.
Yuen
Man-Fung
MF
Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.
Seto
Wai-Kay
WK
Chow
Danny Hoi-Fan
DH
Tsui
Kit
K
Wong
Danny Ka-Ho
DK
Ngai
Vincent Wing-Shun
VW
Wong
Benjamin Chun-Yu
BC
Fung
James
J
Yuen
John Chi-Hang
JC
Lai
Ching-Lung
CL
D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000209:etiology; D018450:Disease Progression; D024882:Drug Resistance, Viral; D005260:Female; D006515:Hepatitis B virus / Q000187:drug effects; D019694:Hepatitis B, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000209:etiology; D008113:Liver Neoplasms / Q000209:etiology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine