Locasciulli 1983

Methods	Retrospective and prospective cohort study
Participants	N of patients original cohort: nm; N of patients described study group: 70 with abnormal liver function during chemotherapy; N of patients study group of interest: 70; N of patients with liver function tests: 56 Tumour: ALL, ANLL; Time period diagnosis/treatment: 1972‐1981; Age at diagnosis: mean 8 (4‐19) yra; Age at follow‐up: nm; F/M%: 43/57b; BMI: nm N of patients hepatitis virus infection: 30/56 (53.6%) HBV markers (i.e. antigens or antibodies for HBV) N of patients acute liver disease: 56/56 (100%) elevated ALT/AST during chemotherapy; liver biopsy in 38 patients at end chemotherapy: 5/38 (13.1%) chronic lobular hepatitis, 17/38 (44.7%) chronic persistent hepatitis and 9/38 (23.6%) chronic active hepatitis Follow‐up duration: mean 2.0 (0.5‐7.0) yr after end of treatment; Completion of follow‐up: 80.0%
Interventions	N of patients chemotherapy: 56/56 (100%); Chemotherapy type: vincristine, prednisone, 6‐mercaptopurine, methotrexate, vinblastine, L‐asparaginase, daunorubicin, cytosine arabinoside, doxorubicin, cyclophosphamide, 6‐thioguanine; 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: 53/56 (94.6%)
Outcomes	Method of detection of hepatic late adverse effects: ALT, AST (measured 3‐6 monthly) Definition of hepatic late adverse effects: ALT/AST >3 times upper limit of normal (60 IU/L) for ≥6 months N of patients hepatic late adverse effects at end of follow‐up: ≥6 months: 22/56 (39.3%), <6 months: 10/56 (17.9%) Risk factors: Cleared or persistent chronic HBV infection: 17/22 (77.3%) with persistently high transaminases HBV markers versus 3/24 (12.5%) with normal transaminases HBV markers (P<0.001); histological diagnosis of chronic hepatitis: 19/27 (70.4%) with histological diagnosis of chronic hepatitis persistently elevated transaminases versus 1/4 (25.0%) with minimal changes persistently elevated transaminases (P<0.005) (Univariate)
Notes	a Data of 103 patients with ALL/ANLL b Data of 70 patients in the original cohort
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
Adjustment important confounders	High risk	Important prognostic factors or follow‐up were not taken into account
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	Low risk	Outcome definition was objective and precise
Well defined risk estimation	Low risk	Chi2 was calculated