Yang Ju Dong, Larson Joseph J, Watt Kymberly D, Allen Alina M, Wiesner Russell H, Gores Gregory J, Roberts Lewis R, Heimbach Julie A, Leise Michael D
Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota.
Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, Minnesota.
Clin Gastroenterol Hepatol. 2017 May;15(5):767-775.e3. doi: 10.1016/j.cgh.2016.11.034. Epub 2016 Dec 21.
BACKGROUND & AIMS: Management strategies for patients with hepatitis C virus (HCV) infection and hepatocellular carcinoma (HCC) have changed, along with liver allocation policies based on model for end-stage liver disease score. We investigated etiologic-specific trends in liver transplantation in the United States during different time periods.
We performed a retrospective study, using the United Network for Organ Sharing/Organ Procurement and Transplantation Network registry data, to identify all adult patients registered for liver transplantation in the United States from January 1, 2004, through December 31, 2015. For subjects listed with multiple diagnoses, HCC was considered the primary listing diagnosis. To determine whether availability of direct-acting antiviral agents, which began in 2011, affected pretransplant (death or drop-out) and post-transplant outcomes for patients with HCV infection, we compared data from the time periods of 2004 to 2010 and 2011 to 2014. We used competing-risk analysis to compare differences in end points between these periods. Differences between periods in pretransplantation and post-transplantation outcomes were estimated using Kaplan-Maier analysis and compared using the log-rank test. Associations between year of listing and pre-liver transplant outcome, and year of liver transplant and survival after transplant, were examined using the log-rank test. Proportional hazard regression was used to evaluate the reliability of the time period effect with potential confounders.
Among 109,018 registrants, 18.5% were registered for liver transplantation because of HCC. In 2015, HCC was the leading diagnosis among registrants (23.9% of registrations) and recipients (27.2% of recipients). Between 2004 and 2015, the ratio of registrants with vs without HCC increased 5.6-fold for patients with HCV infection, 1.9-fold for patients with hepatitis B virus (HBV) infection, 2.7-fold for patients with alcohol abuse, and 10.2-fold for patients with nonalcoholic steatohepatitis. After adjusting for covariates, we associated the period of 2011 to 2014 with a decreased probability that HCC registrants would undergo liver transplantation (hazard ratio [HR], 0.62; P < .0001). The period of 2011 to 2014 also was associated with a decreased probability of drop-out owing to deterioration or death from HCV-induced (HR, 0.90; P = .0003), HBV-induced (HR, 0.71; P = .002), or alcohol-induced (HR, 0.90; P = .01) liver disease, and an increased probability of delisting as a result of clinical improvement in patients with HCV infection (HR, 3.4; P < .0001), HBV infection (HR, 2.3; P = .004), or alcohol abuse (HR, 2.2; P < .0001). The period of 2011 to 2014 was associated with a decreased risk of graft loss or death, with the largest effect seen in HCV-infected recipients (HR, 0.76; P < .0001).
HCC was the leading indication for liver transplantation in the United States in 2015. Despite this, the probability of liver transplantation decreased the most in registrants with HCC. Pretransplantation and post-transplantation outcomes have improved, particularly in patients with HCV infection.
丙型肝炎病毒(HCV)感染合并肝细胞癌(HCC)患者的管理策略以及基于终末期肝病模型评分的肝脏分配政策均已发生变化。我们调查了美国不同时间段内肝移植的病因特异性趋势。
我们进行了一项回顾性研究,利用器官共享联合网络/器官获取与移植网络登记数据,确定2004年1月1日至2015年12月31日期间在美国登记进行肝移植的所有成年患者。对于列出多种诊断的受试者,HCC被视为主要登记诊断。为了确定2011年开始使用的直接抗病毒药物的可用性是否影响HCV感染患者的移植前(死亡或退出)和移植后结局,我们比较了2004年至2010年和2011年至2014年这两个时间段的数据。我们使用竞争风险分析来比较这些时间段之间终点的差异。使用Kaplan - Meier分析估计移植前和移植后结局在不同时间段之间的差异,并使用对数秩检验进行比较。使用对数秩检验检查登记年份与肝移植前结局之间以及肝移植年份与移植后生存之间的关联。使用比例风险回归来评估时间段效应与潜在混杂因素的可靠性。
在109,018名登记者中,18.5%因HCC登记进行肝移植。2015年,HCC是登记者(占登记的23.9%)和受者(占受者的27.2%)中的主要诊断。2004年至2015年期间,HCV感染患者中伴有与不伴有HCC的登记者比例增加了5.6倍,乙型肝炎病毒(HBV)感染患者增加了1.9倍,酒精滥用患者增加了2.7倍,非酒精性脂肪性肝炎患者增加了10.2倍。在对协变量进行调整后,我们发现2011年至2014年期间HCC登记者进行肝移植的概率降低(风险比[HR],0.62;P <.0001)。2011年至2014年期间因HCV诱导(HR,0.90;P =.0003)、HBV诱导(HR,0.71;P =.002)或酒精诱导(HR,0.90;P =.01)的肝病恶化或死亡而退出的概率也降低,并且由于HCV感染(HR,3.4;P <.0001)、HBV感染(HR,2.3;P =.004)或酒精滥用(HR,2.2;P <.0001)患者临床改善而被除名的概率增加。2011年至2014年期间移植物丢失或死亡的风险降低,在HCV感染的受者中影响最大(HR,0.76;P <.0001)。
2015年HCC是美国肝移植的主要指征。尽管如此,HCC登记者中肝移植的概率下降幅度最大。移植前和移植后结局均有所改善,尤其是HCV感染患者。