Park Chan Bog, Lim Hyun Jeung, Yun Byung Cheol, Lee Sang Uk, Han Byung Hoon
Department of Internal Medicine, Kosin University College of Medicine, Korea.
Korean J Hepatol. 2004 Jun;10(2):108-16.
BACKGROUND/AIMS: Viral breakthrough has been considered a major limitation of lamivudine in the treatment of hepatitis B virus related chronic liver disease. Its clinical meaning has not been thoroughly assessed.
64 patients who showed viral breakthrough during lamivudine treatment were retrospectively reviewed. We evaluated the rate of HBeAg seroconversion and hepatic decompensation after viral breakthrough.
After viral breakthrough, serum alanine transaminase (ALT) elevation more than 1.2 x upper limit of normal (ULN) was noticed in 40 patients (62.5%). Acute flare (serum ALT elevation > x 5 ULN, or serum bilirubin >3 mg/dL) occurred in 15 patients (23.4%). During the period of follow up (15.0 +/- 9.7 months; range, 0-31 months) since viral breakthrough, decreased serum HBV-DNA level to below the detection limit and serum ALT normalization was seen in 15 patients (23.4%). HBeAg seroconversion was noticed in 7 (13.7%) of a total of 51 HBeAg positive patients at base line; in 4 (15.4%) of 26 patients with non-hepatic failure (chronic hepatitis or Child-Pugh class A liver cirrhosis) at base line; and in 2 (40.0%) of 5 patients with non-hepatic failure at base line and acute flare after viral breakthrough. During this period, terminal hepatic decompensation (Child-Pugh class C) or death was noticed in 9 (90.0%) of 10 patients who had hepatic decompensation (Child-Pugh class B or C) at baseline and acute flare after viral breakthrough.
Acute flare after viral breakthrough seemed to continue during HBeAg seroconversion and rarely developed into terminal hepatic decompensation or death in patients with non-hepatic decompensation at baseline. Its incidence is not only high but lethal to most patients with hepatic decompensation at baseline.
背景/目的：病毒学突破一直被认为是拉米夫定治疗乙型肝炎病毒相关慢性肝病的主要局限性。其临床意义尚未得到充分评估。
对64例在拉米夫定治疗期间出现病毒学突破的患者进行回顾性分析。我们评估了病毒学突破后HBeAg血清学转换率和肝失代偿情况。
病毒学突破后，40例患者（62.5%）血清丙氨酸转氨酶（ALT）升高超过正常上限（ULN）的1.2倍。15例患者（23.4%）发生急性发作（血清ALT升高>5倍ULN，或血清胆红素>3mg/dL）。在病毒学突破后的随访期间（15.0±9.7个月；范围0 - 31个月），15例患者（23.4%）血清HBV - DNA水平降至检测限以下且血清ALT恢复正常。基线时51例HBeAg阳性患者中有7例（13.7%）出现HBeAg血清学转换；基线时26例非肝衰竭（慢性肝炎或Child - Pugh A级肝硬化）患者中有4例（15.4%）；基线时5例非肝衰竭且病毒学突破后发生急性发作的患者中有2例（40.0%）。在此期间，基线时存在肝失代偿（Child - Pugh B级或C级）且病毒学突破后发生急性发作的10例患者中有9例（90.0%）出现终末期肝失代偿（Child - Pugh C级）或死亡。
病毒学突破后的急性发作似乎在HBeAg血清学转换期间持续存在，对于基线时无肝失代偿的患者很少发展为终末期肝失代偿或死亡。其发生率不仅高，而且对大多数基线时存在肝失代偿的患者具有致死性。
