Department of Clinical Medicine, Gastroenterology Unit, St. Orsola-Malpighi Hospital, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy.
Dig Dis Sci. 2012 Feb;57(2):561-7. doi: 10.1007/s10620-011-1873-x. Epub 2011 Sep 1.
Before tenofovir approval for chronic hepatitis B therapy, the clinical management of patients with suboptimal response or virological breakthrough during combination treatment with lamivudine and adefovir dipivoxil was a difficult clinical challenge.
In order to improve virologic response and reduce the risk of decompensation, we evaluate the efficacy of a high dose of lamivudine on chronic HBV patients who have previously presented an unsatisfactory response during treatment with lamivudine 100mg/day and adefovir 10mg/day.
Six patients with HBV-related liver cirrhosis were prospectively enrolled. All were HBeAg-negative and presented a suboptimal response or virological breakthrough after "adefovir add-on" because of development of clinical breakthrough during Lamivudine treatment. Lamivudine dose was increased to 200 or 300 mg, depending on viral load. After 12 months of follow-up, virological and biochemical response were evaluated.
After 12 months of high-dose lamivudine, all patients (6/6, 100%) achieved a significant decrease of serum HBV DNA (mean reduction 2,62 ± 1,15 Log10 UI/ml, P = 0.03) and normalized ALT. In three patients (3/6, 50%), HBV DNA became undetectable within 6 months. No patient developed liver decompensation and no significant changes occurred in serum creatinine, serum and urinary electrolytes. No adverse events were registered.
In our experience, rescue strategy with high-dose lamivudine inhibited viral replication leading to undetectability of serum HBVDNA. This rescue treatment presented a good safety profile, without adverse events during the study period. Customized increase of nucleos(t)ide analogues dose in difficult-to-treat patients may be a proficient approach in challenging clinical setting.
替诺福韦获得批准用于慢性乙型肝炎治疗之前，对于拉米夫定和阿德福韦酯联合治疗中出现应答不佳或病毒学突破的患者，临床管理是一个具有挑战性的难题。
为了提高病毒学应答率并降低失代偿风险，我们评估了高剂量拉米夫定对先前接受每日 100mg 拉米夫定和每日 10mg 阿德福韦酯治疗但应答不佳或病毒学突破的慢性乙型肝炎病毒（HBV）患者的疗效。
前瞻性纳入 6 例 HBV 相关肝硬化患者。所有患者 HBeAg 阴性，在拉米夫定治疗过程中出现临床突破后因阿德福韦酯“加用”而出现应答不佳或病毒学突破。根据病毒载量，将拉米夫定剂量增加至 200 或 300mg。在 12 个月的随访后，评估病毒学和生化学应答。
高剂量拉米夫定治疗 12 个月后，所有患者（6/6，100%）均实现血清 HBV DNA 显著下降（平均降低 2.62±1.15log10IU/ml，P=0.03）和 ALT 正常化。在 3 例患者（3/6，50%）中，HBV DNA 在 6 个月内转为不可检测。无患者发生肝功能失代偿，血清肌酐、血清和尿电解质无显著变化。未发生不良事件。
根据我们的经验，高剂量拉米夫定挽救治疗抑制病毒复制，导致血清 HBVDNA 不可检测。这种挽救治疗具有良好的安全性，在研究期间未发生不良事件。在具有挑战性的临床环境中，对难治疗患者定制增加核苷（酸）类似物剂量可能是一种有效的方法。
