Russo Mark W, Galanko Joseph A, Shrestha Roshan, Fried Michael W, Watkins Paul
Division of Gastroenterology and Hepatology, Department of Medicine and Center for Gastrointestinal Biology and Diseases, University of North Carolina, Chapel Hill, NC 27599-7080, USA.
Liver Transpl. 2004 Aug;10(8):1018-23. doi: 10.1002/lt.20204.
Studies of acute liver failure from drugs have included cases mostly attributed to acetaminophen (APAP) but have reported limited data on other drugs. We used the United Network for Organ Sharing (UNOS) liver transplant database from 1990 to 2002 to identify recipients and estimate a U.S. population-based rate of liver transplantation due to acute liver failure from drugs. Patients were identified if their diagnosis was acute hepatic necrosis from an implicated drug at the time of transplant. Liver transplantation for drug hepatotoxicity accounted for 15% of liver transplants for acute liver failure over the study period. In our cohort (n = 270), 206 (76%) recipients were female. APAP alone, or in combination with another drug, accounted for 133 (49%) cases. In the non-acetaminophen (non-APAP) group (n = 137), the most frequently implicated drugs were: isoniazid, n = 24 (17.5%); propylthiouracil, n = 13 (9.5%); and phenytoin and valproate in 10 (7.3%) cases each. One-year patient and graft survival for the entire cohort was 77 and 71%, respectively. Among Caucasians (n = 206) and African-Americans (n = 48), APAP only was implicated in 110 (53%) patients and 12 (25%) patients, respectively, and non-APAP drugs were implicated in 96 (47%) patients and 36 (75%) patients, respectively (P =.0004). Among African-Americans in the non-APAP group, 28 (78%) were women. In conclusion four drugs were implicated in 42% of patients undergoing liver transplantation for acute liver failure due to drugs other than APAP. The increased frequency of African-American women undergoing liver transplantation for non-APAP drug induced liver injury warrants further study.
药物所致急性肝衰竭的研究大多涵盖了主要归因于对乙酰氨基酚(APAP)的病例,但关于其他药物的数据报道有限。我们利用1990年至2002年器官共享联合网络(UNOS)的肝移植数据库来确定受者,并估算美国基于人群的因药物所致急性肝衰竭进行肝移植的发生率。若患者在移植时的诊断为某种相关药物所致的急性肝坏死,则将其识别出来。在研究期间,因药物肝毒性进行的肝移植占急性肝衰竭肝移植的15%。在我们的队列(n = 270)中,206名(76%)受者为女性。仅APAP或与另一种药物联用导致的病例有133例(49%)。在非对乙酰氨基酚(非APAP)组(n = 137)中,最常涉及的药物为:异烟肼,n = 24例(17.5%);丙硫氧嘧啶,n = 13例(9.5%);苯妥英和丙戊酸各10例(7.3%)。整个队列的1年患者生存率和移植物生存率分别为77%和71%。在白种人(n = 206)和非裔美国人(n = 48)中,仅APAP导致肝损伤的患者分别为110例(53%)和12例(25%),非APAP药物导致肝损伤的患者分别为96例(47%)和36例(75%)(P = 0.0004)。在非APAP组的非裔美国人中,28例(78%)为女性。总之,对于因APAP以外的药物所致急性肝衰竭而接受肝移植的患者,42%的病例涉及4种药物。非裔美国女性因非APAP药物性肝损伤接受肝移植的频率增加,这值得进一步研究。