Kwang Hyub Han, M.D., Jin Suk Kim, M.D., Hyo Young Chung1,
Sang Hoon Ahn, M.D., Yong Han Paik, M.D., Kwan Sik Lee, M.D.,
Chae Yoon Chon, M.D. and Young Myoung Moon, M.D.
Background/Aims : We studied to evaluate the virological and biochemical responses to lamivudine and to detect YMDD mutants in patients who received long-term lamivudine therapy. Methods : We conducted a one-year trial of lamivudine in 45 Korean patients with chronic liver disease due to hepatitis B virus. The patients were treated with a single oral average dose of 100 mg of lamivudine every day for 12 months. Results : The suppression of serum HBV DNA was sustained in 77.8% of the patients and the normalization of serum ALT in 80%. The proportions of patients with HBeAg seroconversion were 25%. YMDD mutants were detected in 4 of 8 patients who showed sustained HBV DNA and serum ALT response (n=31) and in 3 of 8 patients who showed HBV DNA or serum ALT breakthrough (n=9). The response to lamivudine therapy in HBeAg-negative patients was excellent. Conclusion : Lamivudine therapy resulted in a significant virological and biochemical improvements and were well tolerated. But, YMDD mutants were detected during lamivudine therapy. (Korean J Hepatol 1999;5:97-104)
Background / Aims : It has been reported in patients with chronic hepatitis B, that the response rate of lamivudine therapy increases in proportion to the duration of the therapty. What was not well known was the durability of the therapeutic response after the cessation of lamivudine therapy in patients with chronic hepatitis B. Patients and Methods : We retrospectively analyzes 73 patients with chronic hepatitis B who were treated with lamivudine 100 mg orally once daily and followed up for more than 12 months between April 1997 and March 1999. Sixty-three patients were initially hepatitis B e antigen (HBeAg) positive and Hepatitis B virus (HBV) DNA positive(group Ⅰ). Ten patients were HBeAg negative and HBV DNA positive (group Ⅱ). Results : The response rates of group Ⅰ and group Ⅱwere 68.3% and 70.0% at 12 months, respectively(p=NS). In group I, cumulative HBeAg seroconversion rates art 1 year, 2years, and 3 years were 30.2%, 38.8%, and 42.4%, respectively. The cumulative durability of response was higher in group I than in group II (64.6% vs 33.3% at 1 year ; 35.4% vs 22.2% at 22.2% at 2 years p=.079); lamivudine therapy for more than 6 months after HBeAg seroconversion than for less than 6 months (90.0% vs 40.0% at 1 year ; 90.0% vs 20.0% at 2 years ; p=.013). Conclusions : The long-term response to lamivudine therapy showed no difference between HBeAg - negative/HBV DNA-positive and HBeAg - positive patients. The HBeAg serocinversion rate increased in proportion to the duration of lamivudine therapy. The durability of response. (Korean J Hepatol 200 1;7 :423 - 431)
Background/Aims Lamivudine is a potent inhibitor of hepatitis B virus replication, but an increased
incidence of YMDD mutation may be associated with its long term use. Thus, the decision to initiate therapy
should be based on variables that are predictive of lamivudine-induced HBeAg loss. The objective of this
analysis was to determine patient-dependent or laboratory variables that predict HBeAg loss. Methods: We
retrospectively analyzed 99 HBeAg-positive patients with chronic hepatitis B who were treated with
lamivudine and followed up for more than 52 weeks. All patients had a liver biopsy before starting
lamivudine therapy. HBeAg loss and HBeAg seroconversion after 52 weeks of treatment were defined as
endpoints. Results: The overall rates of HBeAg loss and HBeAg seroconversion were 41.4% (41/99) and
37.4% (37/99), respectively. The rates of HBeAg loss increased as pretreatment ALT levels increased
(P=0.013) and were highest among patients with pretreatment ALT levels greater than 5 times the upper
limit of normal, occurring in 56.8% of those patients. The rate of HBeAg loss was higher in patients with
more active histologic disease on pretreatment liver biopsy (Grade 1&2 vs. Grade 3&4, 28.3% vs 56.5%,
P=0.004). Similar results were seen with HBeAg seroconversion, though seroconversion occurred less
frequently than HBeAg loss. Multivariate analysis showed that elevated baseline ALT levels (P<0.05) and
histologic activity (P<0.05) were the best independent predictors of HBeAg loss and seroconversion in
response to lamivudine. Conclusions: Pretreatment ALT levels and histologic activity were the most
important predictors for response to lamivudine.(Korean J Hepatol 2002;10:31-41)