Karlas T, Hartmann J, Weimann A, Maier M, Bartels M, Jonas S, Mössner J, Berg T, Tillmann H L, Wiegand J
Department of Medicine, Dermatology and Neurology, Division of Gastroenterology and Rheumatology, University of Leipzig, Leipzig, Germany.
Transpl Infect Dis. 2011 Jun;13(3):299-302. doi: 10.1111/j.1399-3062.2010.00591.x. Epub 2010 Dec 16.
Combination therapy with antivirals plus hepatitis B immunoglobulin (HBIg) has become the standard treatment for prevention of post-liver transplant hepatitis B virus (HBV) recurrence. However, HBIg therapy is inconvenient and expensive. Alternative therapeutic approaches with modern nucleos(t)ide analogues are limited so far. The present case report describes prevention of HBV recurrence with entecavir and tenofovir. A 48-year-old male patient with hepatitis B-induced decompensated liver cirrhosis initially improved on lamivudine (LAM) until LAM resistance (rtL180M and rtM204V) emerged followed by renewed decompensation. Therefore, tenofovir was added to LAM leading to undetectable HBV DNA (<200 copies/mL). Six months later, low-level viremia (479 copies/mL) was detected. Treatment was escalated to tenofovir plus entecavir. HBV DNA became negative again, and the patient underwent orthotopic liver transplantation. HBIg was administered during transplantation (10,000 IU) and on the second and third postoperative days (total dose 26,000 IU). Subsequently, the anti-hepatitis B surface (HBs) titer rose to 1477 IU/L at day 4 post transplantation. Although HBIg should have been continued, the patient remained on combination therapy with tenofovir plus entecavir only. The anti-HBs titer decreased and became negative 4 months later. However, under continued combination therapy with oral antivirals, HBV DNA and hepatitis B surface antigen remained negative during the entire follow-up of 21 months after liver transplantation. Combination therapy with entecavir plus tenofovir may prevent post-liver transplant hepatitis B recurrence even without HBIg maintenance therapy. This case illustrates that combination oral antiviral therapy might substitute for HBIg as indefinite prophylactic regimen due to profound antiviral efficacy and low risk of viral resistance. Efficacy and safety must be further investigated in randomized controlled trials.
抗病毒药物联合乙型肝炎免疫球蛋白（HBIg）治疗已成为预防肝移植后乙型肝炎病毒（HBV）复发的标准治疗方法。然而，HBIg治疗不方便且昂贵。迄今为止，使用现代核苷（酸）类似物的替代治疗方法有限。本病例报告描述了使用恩替卡韦和替诺福韦预防HBV复发的情况。一名48岁男性患者，因乙型肝炎导致失代偿性肝硬化，最初使用拉米夫定（LAM）治疗时病情有所改善，直至出现拉米夫定耐药（rtL180M和rtM204V），随后病情再次失代偿。因此，在拉米夫定基础上加用替诺福韦，使HBV DNA检测不到（<200拷贝/毫升）。6个月后，检测到低水平病毒血症（479拷贝/毫升）。治疗升级为替诺福韦加恩替卡韦。HBV DNA再次转阴，患者接受了原位肝移植。移植期间给予HBIg（10,000 IU），术后第二天和第三天也给予HBIg（总剂量26,000 IU）。随后，移植后第4天抗乙型肝炎表面（HBs）抗体滴度升至1477 IU/L。尽管应继续使用HBIg，但患者仅继续接受替诺福韦加恩替卡韦联合治疗。4个月后抗-HBs抗体滴度下降并转阴。然而，在继续口服抗病毒药物联合治疗的情况下，肝移植后21个月的整个随访期间，HBV DNA和乙型肝炎表面抗原均保持阴性。恩替卡韦加替诺福韦联合治疗即使不进行HBIg维持治疗也可能预防肝移植后乙型肝炎复发。本病例表明，由于具有强大的抗病毒疗效和较低的病毒耐药风险，联合口服抗病毒治疗可能替代HBIg作为长期预防方案。其疗效和安全性必须在随机对照试验中进一步研究。
