Lee Yoon-Seon, Suh Dong Jin, Lim Young-Suk, Jung Suk Won, Kim Kang Mo, Lee Han Chu, Chung Young-Hwa, Lee Yung Sang, Yoo Wangdon, Kim Soo-Ok
Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
Hepatology. 2006 Jun;43(6):1385-91. doi: 10.1002/hep.21189.
Although adefovir dipivoxil (ADV) has a unique profile of delayed and infrequent resistance in treatment-naïve chronic hepatitis B patients, the association of ADV resistance with previous lamivudine (LAM) resistance is not well understood. We compared the emergence of the ADV-resistant mutations rtA181V/T and rtN236T between LAM-resistant patients and treatment-naïve patients at 48 weeks of ADV monotherapy. Fifty-seven LAM-resistant patients and 38 treatment-naïve patients were treated with 10 mg/d ADV for more than 48 weeks. Both baseline and 48-week blood samples were analyzed for ADV-resistant mutations via restriction fragment mass polymorphism analysis. Antiviral responses were evaluated according to changes in serum HBV DNA (measured via real-time polymerase chain reaction) and alanine aminotransferase (ALT) levels and loss of hepatitis B e antigen (HBeAg). After 48 weeks, 10 (18%) of the 57 LAM-resistant patients were found to have developed ADV-resistant mutations, whereas none of the 38 treatment-naïve patients developed such mutations (P < .01). Among LAM-resistant patients, the reduction in serum HBV DNA levels was significantly lower in patients with ADV-resistant mutations than in those without such mutations (-1.04 vs. -2.63 log10 copies/mL) (P = .01). However, the rates of serum ALT normalization (60% vs. 55%) and HBeAg loss (14% vs. 21%) were not significantly different between the 2 groups (P > .05). In conclusion, the emergence of the rtA181V/T and rtN236T mutations was more common in LAM-resistant patients than in treatment-naïve patients after 48 weeks of ADV therapy and was associated with reduced antiviral efficacy to drug treatment.
虽然阿德福韦酯（ADV）在初治慢性乙型肝炎患者中具有独特的延迟和罕见耐药特性，但ADV耐药与既往拉米夫定（LAM）耐药之间的关联尚不清楚。我们比较了LAM耐药患者和初治患者在接受ADV单药治疗48周时ADV耐药突变rtA181V/T和rtN236T的出现情况。57例LAM耐药患者和38例初治患者接受10mg/d的ADV治疗超过48周。通过限制性片段质量多态性分析对基线和48周时的血样进行ADV耐药突变分析。根据血清HBV DNA（通过实时聚合酶链反应测定）、丙氨酸氨基转移酶（ALT）水平的变化以及乙肝e抗原（HBeAg）的消失情况评估抗病毒反应。48周后，57例LAM耐药患者中有10例（18%）出现了ADV耐药突变，而38例初治患者中无一例出现此类突变（P<0.01）。在LAM耐药患者中，出现ADV耐药突变的患者血清HBV DNA水平的下降幅度显著低于未出现此类突变的患者（-1.04对-2.63 log10拷贝/mL）（P = 0.01）。然而，两组之间血清ALT正常化率（60%对55%）和HBeAg消失率（14%对21%）无显著差异（P>0.05）。总之，在ADV治疗48周后，rtA181V/T和rtN236T突变在LAM耐药患者中比在初治患者中更常见，并与药物治疗的抗病毒疗效降低有关。
