Ben-Ari Z, Zemel R, Kazetsker A, Fraser G, Tur-Kaspa R
Liver Institute, Department of Medicine D, Felsenstein Medical Research Center, Petah Tiqva, Israel.
Am J Gastroenterol. 1999 Mar;94(3):663-7. doi: 10.1111/j.1572-0241.1999.00933.x.
Hepatitis B virus (HBV) precore mutant infection is associated with a more severe liver disease and a poorer response to interferon. We evaluated the efficacy and tolerance of lamivudine to induce complete and sustained suppression of viral replication in seven patients infected with HBV precore mutant (HBeAg-/HBeAb+/HBV DNA+) (in three patients mutation at codon 1896 was detected by direct sequencing).
Of the seven patients, five had decompensated HBV cirrhosis in a replicative phase and were liver transplant candidates (Group A) and two patients underwent orthotopic liver transplantation (OLT) for HBV liver cirrhosis and developed recurrent HBV infection in the grafted liver (Group B). Lamivudine 100 mg daily was administered orally for a period of 6-75 wk.
After 6-8 wk lamivudine therapy was well tolerated and successfully suppressed HBV replication to an undetectable serum level of HBV DNA by polymerase chain reaction in six patients. In Group A, two patients underwent successful OLT with no evidence of HBV reinfection 2-14 months later. Lamivudine was continued after OLT with no episodes of rejection. Three patients died before a suitable liver could be found (one remained serum HBV DNA+ after 6 wk of lamivudine therapy). In Group B, 9-14 months after lamivudine therapy both patients developed lamivudine resistance (increased liver enzymes, reappearance of serum HBsAg and HBV DNA [by hybridization]). In both patients liver histology had progressed and in both, mutation at codon 552 of the HBV polymerase gene was detected.
Lamivudine is well tolerated in patients with decompensated liver cirrhosis due to HBV precore mutant infection who are liver transplant candidates. In four patients (80%) potent suppression of viral replication was detected, allowing OLT to be performed. However, post-OLT, a resistant mutant developed under lamivudine therapy. Combination therapy with other antiviral agents should be evaluated to discourage the emergence of lamivudine-resistant mutants.
乙肝病毒（HBV）前核心区突变感染与更严重的肝脏疾病及对干扰素反应较差有关。我们评估了拉米夫定在7例感染HBV前核心区突变（HBeAg阴性/HBeAb阳性/HBV DNA阳性）患者（3例患者经直接测序检测到第1896位密码子突变）中诱导病毒复制完全且持续抑制的疗效和耐受性。
7例患者中，5例处于复制期的失代偿性HBV肝硬化患者，是肝移植候选者（A组），2例因HBV肝硬化接受原位肝移植（OLT），并在移植肝中发生复发性HBV感染（B组）。口服拉米夫定100mg/d，疗程6 - 75周。
拉米夫定治疗6 - 8周后耐受性良好，6例患者通过聚合酶链反应成功将HBV复制抑制至血清HBV DNA检测不到的水平。A组中，2例患者成功接受OLT，2 - 14个月后无HBV再感染证据。OLT后继续使用拉米夫定，无排斥反应发生。3例患者在找到合适肝脏前死亡（1例拉米夫定治疗6周后血清HBV DNA仍为阳性）。B组中，拉米夫定治疗9 - 14个月后2例患者均出现拉米夫定耐药（肝酶升高，血清HBsAg和HBV DNA重新出现[通过杂交检测]）。2例患者肝脏组织学均有进展，均检测到HBV聚合酶基因第552位密码子突变。
对于因HBV前核心区突变感染导致失代偿性肝硬化且为肝移植候选者的患者，拉米夫定耐受性良好。4例患者（80%）检测到病毒复制得到有效抑制，从而能够进行OLT。然而，OLT后，拉米夫定治疗期间出现了耐药突变体。应评估与其他抗病毒药物的联合治疗，以防止拉米夫定耐药突变体的出现。
