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All patients presented with acute elevations in transaminases , ). Immungolulins and autoantibodies were normal. One patient developed acute synthetic dysfunction with no encephalopathy (Bilirubin 64, INR 1.5). 79% received steriods (mean dose:1.3 mg/kg); 34% MMF. Steroid refractory ALI was treated with anti-thymocyte globulin (ATG) in 4 patients.Pathological findings (n=6 liver biopsies) revealed lobular hepatitis and myelo-lymphoid cell infiltrate/aggregates (CD3+, CD8+,CD68+). Patients with severe, refractory (grade 4) ALI had signifcant reductions in circulating lymphocytes/monocytes. 63% (n=35) had a temporal association between recent infection and ALI. 15% (n=8) had colitis prior to onset of ALI. Anti-TNF-a administration for colitis was not associated with more severe ALI. 21% (n=11) developed bacterial infections. Fungal sepsis (aspergillus) occurred in all ATG (n=4) treated patients.Overall 14 patients died with 93% (n=13) due to disease progression and 7% (n=1) due to immunotherapy related neuropathy. All deaths due to progressive disease were in patients with grade 3-4 ALI. Acturial median survival was significantly lower in grade 3-4 (14.5 months) vs grade 1-2 (25 months) liver injury. Conclusion Our data report on the largest cohort of CPI induced ALI identifying disease evolution, markers of disease severity and strong correlation with increased morbidity and mortality. Further research is required to delineate triggers and pathogenesis of CPI induced ALI in order to develop calibrated therapies to ameliorate liver injury.