Rossetti 1991

Methods	Cohort study
Participants	N of patients original cohort: nm; N of patients described study group: 145; N of patients study group of interest: 145; N of patients with liver function tests: 96 Tumour: ALL; Time period diagnosis/treatment: 1967‐1983; Age at diagnosis: nm; Age at follow‐up: range 6‐26 yr; F/M%: 49/51; BMI: nm N of patients hepatitis virus infection: 60/96 (62.5%) HBsAntigen+ of whom 30/96 (31.3%) anti‐HDV+ co‐infection N of patients acute liver disease: 40/96 (41.7%) elevated ALT during chemotherapy; liver biopsy in 72 patients within 3 months after chemotherapy: 27/72 (37.5%) chronic active hepatitis or cirrhosis and 10/72 (13.9%) chronic persistent/lobular hepatitis Follow‐up duration: range 4‐20 yr from diagnosis, ≥2.0 yr after end of treatment; Completion of follow‐up: 66.2%
Interventions	N of patients chemotherapy: 96/96 (100%); Chemotherapy type: vincristine, L‐asparaginase, doxorubicin, daunorubicin, methotrexate (high‐dose) 6‐mercaptopurine, cytosine arabinoside, 6‐thioguanine, cyclophosphamide, hydroxyurea and 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: nm
Outcomes	Method of detection of hepatic late adverse effects: ALT (measured 3 monthly), albumin (frequency of testing nm) Definition of hepatic late adverse effects: ALT >2 times upper limit of normal (100 IU/L); Albumin nm N of patients hepatic late adverse effects at end of follow‐up: ALT:43/96 (44.8%); Albumin: 0/96 (0.0%) Risk factors: Chronic HBV‐HDV co‐infection and chronic HBV infection: 27/30 (90.0%) with chronic HBV‐HDV co‐infection elevated ALT versus 10/26 (38.5%) with chronic HBV infection elevated ALT versus 6/40 (15.0%) without chronic HBV infection elevated ALT (P<0.02) (Univariate)
Notes
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