Locasciulli 1997a

Methods	Prospective cohort study
Participants	N of patients original cohort: 125; N of patients described study group: 114; N of patients study group of interest: 114; N of patients with liver function tests: 114 Tumour: ALL, AML; Time period diagnosis/treatment: 1968‐1982; Age at diagnosis: mean 4 ± 2.6 yr; Age at follow‐up: nm; F/M%: 48/52; BMI: nm N of patients hepatitis virus infection: 28/114 (24.6%) anti‐HCV+, HCV‐RNA+ and 19/114 (16.7%) anti‐HCV+, HCV‐RNA‐ N of patients acute liver disease: 54/111 (48.7%) elevated ALT at end chemotherapy; liver biopsy in 36 patients at end chemotherapy: 5/36 (13.9%) nonspecific reactive hepatitis, 9/36 (25.0%) chronic lobular hepatitis, 15/36 (41.7%) chronic persistent hepatitis and 7/36 (19.4%) chronic active hepatitis Follow‐up duration: mean 17 ± 3.2 (13‐27) yr after end of treatment; Completion of follow‐up: 100%
Interventions	N of patients chemotherapy: 114/114 (100%); Chemotherapy type: nm; 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: nm
Outcomes	Method of detection of hepatic late adverse effects: ALT (measured yearly), liver biopsy (n=2 at follow‐up of 5 and 7 yr, respectively) Definition of hepatic late adverse effects: ALT > upper limit of normal (42 IU/L) N of patients hepatic late adverse effects at end of follow‐up: ALT: 33/114 (28.9%) of whom 4/114 (3.5%) had constantly abnormal values and 29/114 (25.4%) fluctuations from normal to abnormal values; liver biopsy: 1/2 (50.0%) chronic persistent hepatitis, 1/2 (50.0%) chronic lobular hepatitis Risk factors: Chronic HCV infection: 22/28 (78.6%) with chronic HCV infection elevated ALT versus 11/86 (12.8%) without chronic HCV infection elevated ALT (P=0.008) (Univariate)
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Representative study group	Low risk	Described study group consisted of more than 90% of the original cohort
Complete follow‐up assessment	Low risk	Outcome was assessed for more than 90% 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	High risk	Type of chemotherapy was not 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