Matsuzaki 2001

Methods	Prospective cohort study
Participants	N of patients original cohort: nm; N of patients described study group: 132; N of patients study group of interest: 132; N of patients with liver function tests: 105 Tumour: ALL; Time period diagnosis/treatment: 1984‐1990; Age at diagnosis: nm; Age at follow‐up: nm; F/M%: 42/58a; BMI: nm (one patient with obesity) N of patients hepatitis virus infection: 9/105 (8.6%) HCV infection (not specified) N of patients acute liver disease: nm Follow‐up duration: nm; Completion of follow‐up: 79.5%
Interventions	N of patients chemotherapy: 105/105 (100%); Chemotherapy type: vincristine, prednisolone, L‐asparaginase, daunorubicin, cytosine arabinoside, methotrexate, 6‐mercaptopurine, enocitabine, doxorubicin, dexamethasone and cyclophosphamidea; Chemotherapy dose: induction consisted of 4 times 2 mg/m2 vincristine, 4 weeks 60 mg/m2 prednisolone, 7 times 10,000 U/m2 L‐asparaginase, 2 times 25 mg/m2 daunorubicin and 4 times 500 mg/m2 cytosine arabinoside. Consolidation consisted of 300 + 400 mg/m2 or 2 times 500 mg/m2 methotrexate, 14 days 120 mg/m2 6‐mercaptopurine and 8 times 150 mg/m2 enocitabine. Reinduction consisted of 4 times 2 mg/m2 vincristine, 2 to 4 weeks 8 mg/m2 dexamethasone, 4 times 1 g/m2 high‐dose cytosine arabinoside and 1 time 10,000 U/m2 L‐asparaginase. Maintenance consisted of 4 days 120 mg/m2 6‐mercaptopurine, 600 mg/m2 intravenous cyclophosphamide, 4 days 70 mg/m2 cyclophosphamide by mouth, 45 mg/m2 daunorubicin, 200 mg/m2 cytosine arabinoside, 4 days 10 mg/m2 methotrexate and 2 mg/m2 vincristinea N of patients radiotherapy involving the liver: 0 (0.0%); Radiotherapy field: not applicable; Radiotherapy dose: not applicable N of patients hepatectomy: nm N of patients BMT: 0 (0.0%) N of patients blood transfusion: nm
Outcomes	Method of detection of hepatic late adverse effects: transaminase (frequency of testing nm) Definition of hepatic late adverse effects: transaminase <100 IU/L N of patients hepatic late adverse effects at end of follow‐up: 19/105 (18.1%) Risk factors: not evaluated
Notes	a Data of 187 patients with ALL
Risk of bias
Bias	Authors' judgement	Support for judgement
Representative study group	Unclear risk	Unclear if described study group consisted of more than 90% of the original cohort or if it was a random sample with respect to cancer treatment
Complete follow‐up assessment	Low risk	Outcome was assessed for more than 60% of the study group of interest
Blinded outcome assessor	Unclear risk	Unclear if outcome assessors were blinded to the investigated determinant
Well defined study group	Low risk	Type of chemotherapy and number of patients with hepatitis virus infection were mentioned
Well defined follow‐up	High risk	Length of follow‐up was not mentioned
Well defined outcome	High risk	Outcome definition was not objective and precise