Specific Therapies For ALF: Viral, Autoimmune and Wilson Disease

The aim of this review is to provide an updated overview of targeted treatments in ALF due to autoimmune hepatitis, viral infections, and Wilson's disease, emphasizing prognostic assessment and therapeutic decision-making. A structured literature search was performed in PubMed/MEDLINE and Embase for studies published between January 2000 and December 2025 using the terms "acute liver failure," "autoimmune hepatitis," "viral hepatitis," "herpes simplex virus," "Wilson's disease," and "therapeutic plasma exchange." Original articles, meta-analyses, and clinical guidelines in English were selected based on relevance to treatment strategies and outcomes. Acute severe autoimmune hepatitis carries high mortality. Corticosteroids remain first-line therapy, with response rates of 70%-80%. Early identification of non-responders using prognostic models (eg, SURFASA score or composite indices including bilirubin, INR, encephalopathy grade, and platelets) is essential to avoid delaying LT evaluation. Optimal steroid dosing remains debated, as moderate regimens may balance efficacy and infection risk. Viral hepatitis is a major global cause of ALF. In hepatitis B-related ALF or severe reactivation, early nucleos(t)ide analogue therapy improves transplant-free survival. Hepatitis A and E rarely progress to ALF but may cause severe disease in vulnerable individuals. Non-hepatotropic viruses-including HSV, CMV, EBV, VZV, and dengue-can lead to fulminant hepatitis; prompt empirical antivirals, particularly acyclovir for suspected HSV, are critical. Wilson's disease-related ALF is rapidly fatal without LT. Early recognition and validated prognostic indices support urgent transplant referral. Therapeutic plasma exchange may provide temporary stabilization and serve as a bridge to recovery or LT, although high-quality evidence is limited. Once grade 3-4 encephalopathy develops, aetiology-specific therapies often lose effectiveness, and emergency LT-accounting for 2%-8% of annual procedures-remains the only definitive treatment.