Azathioprine and 6-Mercaptopurine-induced Liver Injury: Clinical Features and Outcomes.
Azathioprine and 6-Mercaptopurine-induced Liver Injury: Clinical Features and Outcomes.
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DOI：
10.1097/mcg.0000000000000568
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发表时间：
2017-01
影响因子：
2.9
通讯作者：
DILIN Investigators
中科院分区：
文献类型：
--
作者：
Björnsson ES;Gu J;Kleiner DE;Chalasani N;Hayashi PH;Hoofnagle JH;DILIN Investigators
To define the clinical, biochemical and histologic features of liver injury from thiopurines. Azathioprine (Aza) and 6-mercaptopurine (6-MP) can cause liver injury but no large series exist. Clinical and laboratory data and 6-months outcomes were analyzed from patients with thiopurine hepatotoxicity from the Drug-Induced Liver Injury Network Prospective Study. 22 patients were identified, 12 due to Aza and 10 6-MP, with a median age of 55 years and the majority females (68%). Inflammatory bowel disease was the indication in 55%, and median thiopurine dose 150 (range 25–300) mg daily. The median latency to onset was 75 (range 3 to 2584) days. Injury first arose after a dose escalation in 59% of patients; the median latency after dose increase being 44 (range 3 to 254) days. At onset, the median alanine aminotransferase was 210 U/L, alkaline phosphatase 151 U/L and bilirubin 7.4 mg/dL (peak 13.4 mg/dL). There were no major differences between Aza and 6-MP cases, but anicteric cases typically had non-specific symptoms and a hepatocellular pattern of enzyme elevations, whereas icteric cases experienced a cholestatic hepatitis with modest enzyme elevations in a mixed pattern. One patient with pre-existing cirrhosis required liver transplantation, all others resolved clinically. One patient still had moderate alkaline phosphatase elevations 2 years after onset. Nearly three-quarters of patients with thiopurine-induced liver injury present with self-limited, cholestatic hepatitis, typically within 3 months of starting or a dose increase. The prognosis is favorable except in patients with pre-existing cirrhosis.
