核苷（酸）类似物治疗乙型肝炎病毒相关肝硬化的长期结局。
Long-term outcomes of hepatitis B virus-related cirrhosis treated with nucleos(t)ide analogs.
机构信息
Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
出版信息
J Formos Med Assoc. 2017 Jul;116(7):512-521. doi: 10.1016/j.jfma.2016.08.006. Epub 2016 Oct 5.
BACKGROUND/PURPOSE: This study aimed to evaluate the outcomes of chronic hepatitis B patients with cirrhosis who received long-term nucleos(t)ide analog therapy.
METHODS
A total of 546 consecutive cirrhotic patients treated with entecavir (n = 359), telbivudine (n = 104), or tenofovir (n = 83) for chronic hepatitis B were enrolled. The incidence of hepatocellular carcinoma (HCC) and overall survival were evaluated.
RESULTS
During a median follow-up of 39 months, 56 (10.3%) patients developed HCC and 14 (2.6%) patients died. These outcomes were not associated with different antiviral use. Cox proportional hazard analysis showed that old age (≥60 years) [hazard ratio (HR), 1.74; p = 0.046], statin use (HR, 2.42; p = 0.017), low platelet count (<100,000/μL; HR, 2.00; p = 0.039), and variceal bleeding history (HR, 5.12; p < 0.001) were independent factors for HCC development. With regard to survival, Child-Pugh B/C (HR, 3.78; p = 0.039) and low platelet count (<10/μL; HR, 7.82; p = 0.049) were independent factors. The estimated glomerular filtration rate significantly increased in patients receiving telbivudine (p = 0.047), but decreased in those receiving tenofovir (p < 0.001) at Year 2. Tenofovir use (HR, 1.98; p = 0.005) was one of the independent factors associated with the progression of chronic kidney disease stage.
CONCLUSION
Long-term nucleos(t)ide analog therapy does not guarantee against the HCC development and mortality in chronic hepatitis B-related cirrhotic patients. Careful HCC surveillance is necessary in patients with old age, statin use, low platelet count, and variceal bleeding history.
背景/目的：本研究旨在评估接受长期核苷（酸）类似物治疗的慢性乙型肝炎肝硬化患者的结局。
方法
共纳入 546 例接受恩替卡韦（n=359）、替比夫定（n=104）或替诺福韦（n=83）治疗的慢性乙型肝炎肝硬化患者。评估肝细胞癌（HCC）的发生率和总生存率。
结果
在中位随访 39 个月期间，56 例（10.3%）患者发生 HCC，14 例（2.6%）患者死亡。这些结果与不同的抗病毒治疗无关。Cox 比例风险分析表明，高龄（≥60 岁）[风险比（HR），1.74；p=0.046]、他汀类药物使用（HR，2.42；p=0.017）、血小板计数低（<100,000/μL；HR，2.00；p=0.039）和静脉曲张出血史（HR，5.12；p<0.001）是 HCC 发生的独立因素。至于生存情况，Child-Pugh B/C（HR，3.78；p=0.039）和血小板计数低（<10/μL；HR，7.82；p=0.049）是独立因素。接受替比夫定治疗的患者估计肾小球滤过率（eGFR）显著升高（p=0.047），而接受替诺福韦治疗的患者 eGFR 显著降低（p<0.001）。接受替诺福韦治疗（HR，1.98；p=0.005）是与慢性肾脏病分期进展相关的独立因素之一。
结论
长期核苷（酸）类似物治疗并不能保证慢性乙型肝炎相关肝硬化患者不会发生 HCC 和死亡。对于高龄、他汀类药物使用、血小板计数低和静脉曲张出血史的患者，需要仔细进行 HCC 监测。
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