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Late Effects of the Digestive System

    Table 5. Digestive Tract Late Effects continued...

    Nodular regenerative hyperplasia is a rare condition characterized by the development of multiple monoacinar regenerative hepatic nodules and mild fibrosis. The pathogenesis is not well established, but may represent a nonspecific tissue adaptation to heterogeneous hepatic blood flow.[57] Nodular regenerative hyperplasia has rarely been observed in survivors of childhood cancer treated with chemotherapy, with or without liver radiation therapy.[58,59] Biopsy may be necessary to distinguish nodular regenerative hyperplasia from a subsequent malignancy.

    In a cohort who recently completed intensified therapy for acute lymphoblastic leukemia, histologic evidence of fatty infiltration was noted in 93% and siderosis in up to 70% of patients.[60] Fibrosis developed in 11% and was associated with higher serum low-density lipoprotein (LDL) cholesterol. Fatty liver with insulin resistance has also been reported to develop more frequently in long-term childhood cancer survivors treated with cranial radiation before allogeneic stem cell transplantation who were not overweight or obese.[61] Prospective studies are needed to define whether acute posttherapy fatty liver change contributes to the development of steatohepatitis or the metabolic syndrome in this population. Likewise, information about the long-term outcomes of transfusion-related iron overload is lacking, especially among survivor cohorts who did not undergo hematopoietic cell transplantation.

    Survivors with liver dysfunction should be counseled regarding risk-reduction methods to prevent hepatic injury. Standard recommendations include maintenance of a healthy body weight, abstinence from alcohol use, and immunization against hepatitis A and B viruses. In patients with chronic hepatitis, precautions to reduce viral transmission to household and sexual contacts should also be reviewed.

    Table 6. Hepatobiliary Late Effects

    Predisposing TherapyHepatic EffectsHealth Screening/Interventions
    ALT = alanine aminotransferase; AST = aspartate aminotransferase; HSCT = hematopoietic stem cell transplantation.
    Methotrexate; mercaptopurine/thioguanine; HSCTHepatic dysfunctionLab: ALT, AST, bilirubin levels
    Ferritin in those treated with HSCT
    Mercaptopurine/thioguanine; HSCTVeno-occlusive disease/sinusoidal obstructive syndromeExam: scleral icterus, jaundice, ascites, hepatomegaly, splenomegaly
    Lab: ALT, AST, bilirubin, platelet levels
    Ferritin in those treated with HSCT
    Radiation impacting liver/biliary tract; HSCTHepatic fibrosis/cirrhosisExam: jaundice, spider angiomas, palmar erythema, xanthomata hepatomegaly, splenomegaly
    Lab: ALT, AST, bilirubin levels
    Ferritin in those treated with HSCT
    Prothrombin time for evaluation of hepatic synthetic function in patients with abnormal liver screening tests
    Screen for viral hepatitis in patients with persistently abnormal liver function or any patient transfused prior to 1993
    Gastroenterology/hepatology consultation in patients with persistent liver dysfunction
    Hepatitis A and B immunizations in patients lacking immunity
    Consider phlebotomy and chelation therapy for iron overload
    Radiation impacting liver/biliary tractCholelithiasisHistory: colicky abdominal pain related to fatty food intake, excessive flatulence
    Exam: right upper quadrant or epigastric tenderness (acute episode)
    Consider gallbladder ultrasound in patients with chronic abdominal pain
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