AASLD 2013:病毒反应核苷（酸）类肝硬化长期治疗防止失代偿

StephenW

TITLE: Viral response in long-term therapy with nucleos(t)ide analogues in chronic hepatitis B cirrhosis prevents decompensation
AUTHORS (FIRST NAME, LAST NAME): Ivana Carey1, Sarah Knighton1, Deepak Joshi1, Ashley Barnabas1, Suman Verma1, Phillip M. Harrison1, Abid Suddle1, Kosh Agarwal1
Institutional Author(s):
INSTITUTIONS (ALL): 1. Institute of Liver Studies, Kings College School of Medicine at King's College Hospital, London, United Kingdom.
ABSTRACT BODY: Long-term therapy with nucleos(t)ide analogues (NA) in chronic hepatitis B (CHB) reduces risk of liver disease progression, improves fibrosis and prevent liver disease related complications. Viral response (VR=HBV DNA<20IU/ml) in patients with liver cirrhosis prevents complication events. Only few studies have evaluated variable aspects of long-term NA therapy in CHB cirrhosis.
Aims: To investigate the role of viral response on the improvement of synthetic function tested by MELD and UKELD scores, parameters of portal hypertension [platelets (PLT) counts, size of spleen] and preventing cirrhosis complications in patients with CHB cirrhosis during long-term NA therapy
Patients: 190 monoinfected CHB cirrhotic patients (85%histological confirmation) (median age 45y, 78%males, 43%HBeAg+) were treated in single centre with entecavir 0.5mg/day (n=78) or tenofovir 245 mg/d (n=62) or lamivudine 100mg/d +adefovir 10mg/d (n=50) for at least 2 years (median duration 5 years) and based on VR response after 1 year on therapy were divided into 2 groups: complete responders (CR) (n=130) and partial responders (PR) (n=40). Patients achieving initial CR with viral breakthrough up to levels<100IU/ml (blips) were investigated separately (n=30).
Methods: HBV DNA [log10IU/ml], haematological and biochemical markers of liver synthetic function and HCC surveillance abdominal ultrasound including size of spleen [cm] were analysed at baseline and every 6 months during therapy and MELD & UKELD scores were calculated. 32 patients had varices present at baseline.
Results: Baseline median MELD & UKELD scores were 14 and 45 and were higher in PR than CR (14 vs 12,p=0.04; 45 vs 43,p=0.04). PLT counts and size of spleen were similar between PR and CR (145 vs 159,p=0.3 & 11.7 vs 10.9,p=0.2). Baseline HBV DNA was higher in PR than CR (7.33 vs 5.27,p<0.01). Yearly virological response had 77%, 84% 90%, 96% and 98% patients; 35% patients achieved HBeAg seroconversion and 5% had HBsAg loss after 5 years NA therapy. MELD & UKELD scores improved during therapy in all patients, year 5 median MELD and UKELD scores were 12 (12 vs. 13) and 42 (42 vs 43), but PLT counts improved only in CR (year 5: 194 vs. 154,p=0.03). 18 (9%) patients developed HCC and 14 (7%) had decompensation while on therapy. HCC occurred equally in CR and PR or blips patients, but decompensation was present only in patients with PR or blips.
Conclusions: Long-term antiviral therapy with NA in CHB patients with cirrhosis improved liver synthetic function in all patients. Viral response prevented decompensation and disease progression. HCC prevalence (2%patients/year) was similar viral responders and partial responders.

StephenW

：长期治疗的核苷（酸）类似物（ NA ）在慢性乙型肝炎（ CHB ）肝脏疾病进展，降低风险，提高纤维化，防止肝脏疾病相关的并发症。肝硬化患者的病毒响应（ VR = HBV DNA < 20IU/ml ）防止并发症发生的事件。只有极少数的研究已经评估变量方面的长期NA治疗慢性乙型肝炎肝硬化。
目的：探讨病毒反应的作用，改善合成功能测试和UKELD MELD分数，门脉高压症的参数[血小板计数（ PLT ） ，脾脏大小，和防止肝硬化并发症的慢性乙肝肝硬化患者在长期NA治疗
单中心共收治患者： 190 monoinfected的慢性乙型肝炎肝硬化患者（85％组织学确认） （年龄中位数45Y ， 78 ％为男性， 43 ％的HBeAg + ）与恩替卡韦或替诺福韦组（n = 78） 0.5mg/day 245毫克/天（ Ñ = 62）或拉米夫定100mg /天+阿德福韦10毫克/天组（n = 50 ）至少2年（中位数持续时间5年） ，治疗1年后，基于VR响应被分为2组：完全缓解（ CR ）组（n = 130）和部分反应（ PR ）组（n = 40 ） 。实现初始CR的患者病毒突破的水平< 100IU/ml （光点）进行了调查组（n = 30 ） 。
方法： HBV DNA [ log10IU/ml ]，肝脏合成功能和腹部超声监测HCC包括脾脏大小，血液学和生化标记[厘米]在基线和治疗期间每6个月进行了分析和MELD计算＆ UKELD分数。 32例静脉曲张出席基线。
结果：基线中位数MELD ＆ UKELD得分分别为14和45 ，均高于PR比CR （ 14比12 ， P = 0.04 ; 45比43， P = 0.04 ） 。血小板计数和脾脏大小， PR和CR （ 145比159 ，P = 0.3和11.7比10.9， P = 0.2 ）之间的相似。基线HBV DNA高PR比CR （7.33比5.27， P < 0.01 ） 。每年病毒学应答率有77％， 84 ％ ， 90 ％ ， 96 ％和98 ％的患者， 35 ％的患者实现HBeAg血清学转换， 5％ ， 5年后的HBsAg消失NA治疗。 MELD UKELD在所有患者在治疗过程中，今年的成绩提高5位数MELD和UKELD分数的分别为12 （12比13 ） ， 42 （ 42比43 ） ，但血小板计数改善只有在CR （ 5年： 194与154 ， P = 0.03 ） 。 18 （9％）患者发展为肝癌和14 （7％） ，而在治疗失代偿。同样在CR和PR或光点，患者肝癌发生，但失代偿期，目前只在患者与PR或光点。
结论： NA长期抗病毒治疗在慢性乙型肝炎患者，肝硬化患者改善肝合成功能在所有患者。病毒应答防止失代偿期和疾病进展。肝癌患病率（2 ％的患者/年）是相似的病毒反应和局部反应。