Objectives: Cytokines as prognostic markers in acute liver failure (ALF) have not been evaluated in the Indian subcontinent with hepatitis E as the commonest aetiological agent. We investigated the clinical significance of proinflammatory/apoptotic cytokines soluble Fas ligand (sFasL) and tumour necrosis factor (TNF)-α in ALF of specific aetiology. Methods: A total of 82 cases, 37 ALF and 45 acute hepatitis (AH), and 60 healthy controls were recruited. Serum levels of sFasL and TNF-α were determined at admission and death/recovery. Results: Mean sFasL and TNF-α serum levels at admission were significantly higher ( p < 0.001) in patients with ALF than AH, but no marked difference was observed between ALF-E (expired, n = 23) and ALF-S (survivors, n = 14), although the former had comparatively higher levels. ALF-E had higher than baseline TNF-α and sFasL concentrations at death, while in the ALF-S group the samples obtained from the patients as soon as they came out of encephalopathy, showed either lower or similar TNF-α and sFasL levels as found at admission. Conclusion: The high levels of sFasL and TNF-α are associated with ALF. Following the trend of these cytokines can be useful in predicting death and timely referral to a transplant centre. [ABSTRACT FROM AUTHOR]