Guido 1991

Methods	Cohort study
Participants	N of patients original cohort: nm; N of patients described study group: 54 with liver biopsy within 3 months after end chemotherapy; N of patients study group of interest: 54; N of patients with liver function tests: 19 with abnormal liver function 3 months after chemotherapy Tumour: ALL; Time period diagnosis/treatment: 1979‐1988; Age at diagnosis: mean 5.0, median 4.5 (1.5‐11.0) yra; Age at follow‐up: nm; F/M%: 49/51a; BMI: nm N of patients hepatitis virus infection: 6/19 (31.6%) anti‐HCV+, 4/19 (21.1%) HBsAntigen+ of whom 1/19 (5.3%) anti‐HDV+ co‐infection N of patients acute liver disease: 19/19 (100%) elevated ALT during chemotherapy; liver biopsy 3 months after end chemotherapy: 7/19 (36.8%) fibrosis, 8/19 (42.1%) acute hepatitis, 2/19 (10.5%) chronic persistent hepatitis, 1/19 (5.3%) chronic lobular hepatitis, 1/19 (5.3%) chronic active hepatitis and 0/19 (0.0%) cirrhosis Follow‐up duration: mean 3.2 (2‐7) yr after end of treatmenta; Completion of follow‐up: 35.2%
Interventions	N of patients chemotherapy: 19/19 (100%); Chemotherapy type: vincristine, prednisone, L‐asparaginase, doxorubicin, daunorubicin, methotrexate, 6‐mercaptopurine, cytosine arabinoside, 6‐thioguanine, cyclophosphamide, hydroxyurea, BCNU; Chemotherapy dose: nm N of patients radiotherapy involving the liver: nm; Radiotherapy field: nm; Radiotherapy dose: nm N of patients hepatectomy: nm N of patients BMT: nm N of patients blood transfusion: 19/19 (100%)
Outcomes	Method of detection of hepatic late adverse effects: ALT (measured 3‐6 monthly 1 yr after the end of treatment) Definition of hepatic late adverse effects: elevated ALT N of patients hepatic late adverse effects at end of follow‐up: 16/19 (84.2%) Risk factors: not evaluated
Notes	a Data of 72 patients with ALL with liver biopsy within 3 months after chemotherapy
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	High risk	Outcome was assessed for less 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	Low risk	Length of follow‐up was mentioned
Well defined outcome	High risk	Outcome definition was not objective and precise