毒理性
轻度的、短暂的、无症状的血清转氨酶水平升高在接受奥曲肽治疗的患者中小部分出现，并且在一些人中，这种升高是持久的，并且随着时间的推移可能会恶化，可能需要停药。此外，已经描述了几例急性、临床上明显的肝损伤，可归因于奥曲肽。发病通常在开始治疗后的1到6个月内，并且随着剂量较高，损伤可能更频繁。与奥曲肽治疗相关的肝损伤的大多数病例是无症状和非黄疸的，以血清ALT和AST显著升高为特征，血清碱性磷酸酶、GGT和胆红素正常或接近正常。然而，在某些情况下，尤其是在重新挑战时，会出现黄疸。尚无急性肝衰竭或消失胆管综合征与奥曲肽相关的实例，且损伤的特征是停止注射或输注后迅速改善。在接受持续高剂量奥曲肽输注的新生儿和婴儿中，已经报告了几例显著转氨酶升高并在停止后迅速改善的实例。
奥曲肽会导致胆囊收缩力抑制和胆汁分泌减少，长期治疗与胆结石形成的高发生率相关。在前瞻性研究中，接受维持奥曲肽治疗的肢端肥大症患者中，有25%至65%的患者通过超声检查发现胆结石，并且一部分患者发展为有症状的胆石症，需要住院和胆囊切除术。即使在胆囊切除术后，胆总管和肝内胆管中也可能形成胆固醇结石，导致症状、败血症发作和需要部分肝切除。乌索罗丁治疗似乎不能预防奥曲肽治疗期间的胆结石形成，尽管可能有帮助。奥曲肽还与急性胰腺炎有关，这可能是由于其抑制胃肠激素释放的作用，尽管其他病例可能是由于胆结石通过和胰腺导管阻塞引起的。
可能性评分：C（临床上明显肝损伤的可能原因）。
Mild, transient, asymptomatic elevations in serum aminotransferase levels occur in a small proportion of patients receiving octreotide, and in some individuals the elevations are persistent and worsen over time and may require drug discontinuation. In addition, several instances of acute, clinically apparent liver injury attributable to octreotide have been described. The onset is generally within 1 to 6 months of starting therapy and injury may be more frequent with higher doses. Most cases of liver injury associated with octreotide therapy have been asymptomatic and anicteric, and marked by prominent elevations in serum ALT and AST with normal or near normal serum alkaline phosphatase, GGT and bilirubin. In some instances, however, jaundice has arisen, particularly with rechallenge. There have been no instances of acute liver failure or vanishing bile duct syndrome associated with octreotide, and a characteristic feature of the injury is the rapidity of improvement upon stopping the injections or infusions. Several instances of marked aminotransferase elevations with rapid improvements on stopping have been reported in newborns and infants with congenital hyperinsulinemia who were treated with continuous infusions of high doses of octreotide.
Octreotide causes inhibition of gall bladder contractility and decrease in bile secretion, and long term therapy is associated with a high rate of cholesterol gallstone formation. In prospective studies, between 25% and 65% of patients with acromegaly treated with maintenance octreotide developed gallstones detected by ultrasonography and a proportion developed symptomatic cholelithiasis requiring hospitalization and cholecystectomy. Even after cholecystectomy, cholesterol stones may form in the common bile duct and intrahepatic ducts causing symptoms, episodes of sepsis and need for partial hepatic resection. Therapy with ursodiol does not appear to prevent gallstone formation during octreotide therapy, although it may help. Octreotide has also been associated with acute pancreatitis, which may be due to its inhibitory effect on gastrointestinal hormone release, although other cases may be secondary to passage of gall bladder stones and pancreatic duct obstruction.
Likelihood score: C (probable cause of clinically apparent liver injury).
来源:LiverTox
