Clinical course of non-alcoholic fatty liver disease and the implications for clinical trial design.
Clinical course of non-alcoholic fatty liver disease and the implications for clinical trial design.
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DOI：
10.1016/j.jhep.2022.07.004
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发表时间：
2022-11
影响因子：
25.7
通讯作者：
Kamath, Patrick S.
中科院分区：
文献类型：
--
作者：
Allen, Alina M.;Therneau, Terry M.;Ahmed, Omar T.;Gidener, Tolga;Mara, Kristin C.;Larson, Joseph J.;Canning, Rachel E.;Benson, Joanne T.;Kamath, Patrick S.
在人群中，NAFLD进展至肝脏结局的预测风险和时间轴尚未得到很好的描述。我们的目的是在长期随访的当代人群中检查进展为肝硬化、肝功能失代偿和死亡的风险和时间，以便为肝硬化临床试验中的有效性终点和样本计算提供信息。这是一项回顾性研究，对医疗记录链接系统中前瞻性收集的数据进行回顾性研究，包括1996-2016年明尼苏达州奥姆斯特德县通过临床，生化和放射学标准诊断为NAFLD的所有成年人，并随访至2019年。肝脏相关结果和死亡通过个人病历审查确定和验证。使用多状态模型评估从NAFLD进展到肝硬化、失代偿和死亡的时间和风险。共有5123名NAFLD患者（中位年龄52岁，53%为女性）接受了中位6.4年（范围1-23年）的随访。进展风险如下：从NAFLD到肝硬化：15年内为3%;代偿性肝硬化到首次失代偿：4年内为33%（8%/年）;首次失代偿到2年或以上：2年内为47%。白蛋白、胆红素、非出血性食管静脉曲张和糖尿病是失代偿的独立预测因子。在575例死亡中，6%与肝脏有关。代偿性肝硬化的治疗性试验需要至少2，886例受试者的最低入组标准，随访2年以上，以检测肝脏终点至少15%的相对降低。在这个基于人群的队列中，纵向随访23年，NAFLD进展缓慢，肝脏相关结局仅影响一小部分人。临床试验中肝脏相关终点的减少需要大样本量和长期随访。对于代偿性NASH肝硬化患者，在这种状态下花费的时间和进展为失代偿的风险在人群中并不清楚。我们研究了一个大型人群队列的临床过程，随访时间超过23年。我们发现患有代偿性肝硬化的成年人平均在这种状态下度过4年，并且每年有10%的风险进展为肝硬化或死亡。患有肝硬化和一个失代偿的成年人的风险高出三倍。这些结果反映了药物临床试验中安慰剂组的风险，对于估计足够的样本量至关重要。
The predicted risk and timeline to progression to liver outcomes in NAFLD are not well-characterized in the population. We aimed to examine the risk and time to progression to cirrhosis, hepatic decompensation and death in a contemporary population with long follow-up, in order to inform effectiveness endpoints and sample calculations in clinical trials of cirrhosis. This is a retrospective study of prospectively collected data in a medical record linkage system including all adults diagnosed with NAFLD between 1996-2016 by clinical, biochemical and radiological criteria in Olmsted County, Minnesota and followed until 2019. Liver-related outcomes and death were ascertained and validated by individual medical record review. Time and risk of progression from NAFLD to cirrhosis to decompensation and death were assessed using multistate modeling. A total of 5123 NAFLD individuals (median age 52 years, 53% women) were followed for a median of 6.4 (range 1-23) years. The risk of progression was as follows: from NAFLD to cirrhosis: 3% in 15 years; compensated cirrhosis to first decompensation: 33% in 4 years (8%/year); first decompensation to two or more: 47% in 2 years. Albumin, bilirubin, non-bleeding esophageal varices and diabetes were independent predictors of decompensation. Among the 575 deaths, 6% were liver-related. Therapeutic trials in compensated cirrhosis would require minimum enrollment criteria of 2,886 subjects followed over 2 years to detect at least 15% relative decrease in liver endpoints. In this population-based cohort with 23 years of longitudinal follow-up, NAFLD was slowly progressive, with liver-related outcomes affecting only a small proportion of people. Reduction in liver related endpoints in clinical trials require large sample sizes and long follow-up. For patients with compensated NASH cirrhosis, the time spent in this state and the risk of progression to decompensation are not well-known in the population. We examined the clinical course of a large population-based cohort over 23 years of follow-up. We identified that adults with compensated cirrhosis spend a mean time of 4 years in this state and have a 10% per year risk of progression to cirrhosis or death. The risk is three-fold higher in adults with cirrhosis and one decompensation. These results are reflective of placebo arm risks in drug clinical trials and are essential in the estimation of adequate sample sizes.
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DOI：
10.1056/nejmoa2029349
发表时间：
2021-10-21
期刊：
The New England journal of medicine
影响因子：
--
作者：
Sanyal AJ;Van Natta ML;Clark J;Neuschwander-Tetri BA;Diehl A;Dasarathy S;Loomba R;Chalasani N;Kowdley K;Hameed B;Wilson LA;Yates KP;Belt P;Lazo M;Kleiner DE;Behling C;Tonascia J;NASH Clinical Research Network (CRN)
通讯作者：
NASH Clinical Research Network (CRN)
影响因子：
13.5
作者：
Siddiqui, Mohammad Shadab;Harrison, Stephen A.;Sanyal, Arun J.
通讯作者：
Sanyal, Arun J.
影响因子：
24.5
作者：
Simon TG;Roelstraete B;Khalili H;Hagström H;Ludvigsson JF
通讯作者：
Ludvigsson JF
DOI：
10.1016/j.cgh.2014.09.046
发表时间：
2015-03
期刊：
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
影响因子：
--
作者：
Singh S;Venkatesh SK;Wang Z;Miller FH;Motosugi U;Low RN;Hassanein T;Asbach P;Godfrey EM;Yin M;Chen J;Keaveny AP;Bridges M;Bohte A;Murad MH;Lomas DJ;Talwalkar JA;Ehman RL
通讯作者：
Ehman RL
影响因子：
12.6
作者：
Guha, Indra Neil;Harris, Rebecca;Johnson, Philip J.
通讯作者：
Johnson, Philip J.