Department of Gastroenterology, University of California, San Francisco, San Francisco, California.
Massachusetts General Hospital Institute for Technology Assessment, Boston, Massachusetts; Institute for Clinical and Economic Review, Boston, Massachusetts.
Gastroenterology. 2019 Aug;157(2):472-480.e5. doi: 10.1053/j.gastro.2019.04.012. Epub 2019 Apr 15.
BACKGROUND & AIMS: Early liver transplantation (without requiring a minimum period of sobriety) for severe alcohol-associated hepatitis (AH) is controversial: many centers delay eligibility until a specific period of sobriety (such as 6 months) has been achieved. To inform ongoing debate and policy, we modeled long-term outcomes of early vs delayed liver transplantation for patients with AH.
We developed a mathematical model to simulate early vs delayed liver transplantation for patients with severe AH and different amounts of alcohol use after transplantation: abstinence, slip (alcohol use followed by sobriety), or sustained use. Mortality of patients before transplantation was determined by joint-effect model (based on Model for End-Stage Liver Disease [MELD] and Lille scores). We estimated life expectancies of patients receiving early vs delayed transplantation (6-month wait before placement on the waitlist) and life years lost attributable to alcohol use after receiving the liver transplant.
Patients offered early liver transplantation were estimated to have an average life expectancy of 6.55 life years, compared with an average life expectancy of 1.46 life years for patients offered delayed liver transplantation (4.49-fold increase). The net increase in life expectancy from offering early transplantation was highest for patients with Lille scores of 0.50-0.82 and MELD scores of 32 or more. Patients who were offered early transplantation and had no alcohol use afterward were predicted to survive 10.85 years compared with 3.62 years for patients with sustained alcohol use after transplantation (7.23 life years lost). Compared with delayed transplantation, early liver transplantation increased survival times in all simulated scenarios and combinations of Lille and MELD scores.
In a modeling study of assumed carefully selected patients with AH, early vs delayed liver transplantation (6 months of abstinence from alcohol before transplantation) increased survival times of patients, regardless of estimated risk of sustained alcohol use after transplantation. These findings support early liver transplantation for patients with severe AH. The net increase in life expectancy was maintained in all simulated extreme scenarios but should be confirmed in prospective studies. Sustained alcohol use after transplantation significantly reduced but did not eliminate the benefits of early transplantation. Strategies are needed to prevent and treat posttransplantation use of alcohol.
对于严重酒精性肝炎（AH），早期肝移植（无需达到最低戒酒期）存在争议：许多中心会延迟患者的资格，直到其达到特定的戒酒期（如 6 个月）。为了参与正在进行的辩论和制定相关政策，我们建立了一个数学模型，以模拟早期和延迟肝移植对 AH 患者的长期影响。
我们开发了一个数学模型，以模拟严重 AH 患者的早期和延迟肝移植，以及移植后不同的饮酒量：戒酒、复饮（饮酒后戒酒）或持续饮酒。移植前患者的死亡率由联合效应模型（基于终末期肝病模型[MELD]和 Lille 评分）确定。我们估计了接受早期和延迟肝移植（等待名单前等待 6 个月）的患者的预期寿命，以及因接受肝移植后饮酒而导致的预期寿命损失。
与等待延迟肝移植的患者相比（等待名单前等待 6 个月），接受早期肝移植的患者估计平均预期寿命为 6.55 年，而接受延迟肝移植的患者平均预期寿命为 1.46 年（增加了 4.49 倍）。对于 Lille 评分为 0.50-0.82 和 MELD 评分为 32 或更高的患者，提供早期肝移植的净预期寿命增加幅度最大。接受早期肝移植且之后不饮酒的患者预计可存活 10.85 年，而接受移植后持续饮酒的患者预计可存活 3.62 年（损失 7.23 年预期寿命）。与延迟肝移植相比，早期肝移植增加了所有模拟场景和 Lille 和 MELD 评分组合中的生存时间。
在一项针对假设的精心挑选的 AH 患者的建模研究中，与延迟肝移植（移植前 6 个月戒酒）相比，早期肝移植（移植前 6 个月戒酒）增加了患者的生存时间，无论患者在移植后持续饮酒的风险如何。这些发现支持对严重 AH 患者进行早期肝移植。但在所有模拟的极端情况下，净预期寿命的增加仍保持不变，需要在前瞻性研究中加以证实。移植后持续饮酒显著降低但并未消除早期移植的益处。需要制定策略来预防和治疗移植后饮酒。
