Acute liver failure (ALF) is a serious condition in which the liver suddenly stops working, often leading to life-threatening complications. While N-Acetylcysteine (NAC) is widely used to treat ALF caused by acetaminophen overdose, its benefits in ALF due to other causes, such as viral infections or drug reactions, remain uncertain.

This study is a randomized controlled trial designed to investigate whether NAC can improve survival rates and reduce hospital stays in patients with non-acetaminophen-induced ALF. Participants will be randomly assigned to receive either NAC along with standard supportive care or standard supportive care alone. The study will measure survival rates, hospital stay duration, and improvement in liver function tests.

By exploring NAC's potential benefits beyond acetaminophen-related cases, this research aims to provide evidence-based guidance on how to better manage patients with ALF from other causes.

This study was conducted with the necessary ethical considerations. Ethical approval was obtained from the ethical review board of the institution. Informed consent was obtained from each participant or their legal guardians before enrollment in the study. Participants were selected based on predefined selection criteria. Comprehensive baseline data were gathered from all participants, including demographic information (age, gender), detailed medical history (duration of symptoms, known etiologies), and past medical conditions (comorbidities, chronic viral hepatitis, tuberculosis).

Baseline investigations included a comprehensive set of laboratory tests: bilirubin, albumin, International Normalized Ratio (INR), Aspartate Aminotransferase, Alanine Aminotransferase, complete blood count, renal function tests, electrolytes, blood glucose, and viral serology (Hepatitis B Surface Antigen, Hepatitis B Core Immunoglobulin M, Hepatitis A Virus Immunoglobulin M, Hepatitis C Virus Antibody), along with additional tests as indicated by clinical suspicion (e.g., autoimmune markers, Wilson profile, iron profile, Herpes Simplex Virus / Cytomegalovirus / Epstein-Barr Virus serology). All patients were admitted to the Intensive Care Unit. Participants were randomly assigned to either the NAC treatment group or the control group using the lottery method.

NAC Group: NAC was administered at a dose of 140 mg/kg orally or via a nasogastric tube every 4 hours for the first 16 hours, followed by the same dose at intervals of 6-8 hours. It was continued for 3 days.

Control Group: Participants received the standard supportive care protocol for ALF.

Throughout the study, participants received standard supportive care treatment, which remained consistent in both groups. This care included measures to prevent hypoglycemia, the administration of broad-spectrum prophylactic antimicrobials, proton pump inhibitors for stress-related ulcers, and maintenance of fluid and electrolyte balance. In cases of advanced hepatic encephalopathy, anti-encephalopathy measures were provided. Fresh frozen plasma was administered to patients experiencing spontaneous bleeding. Blood and urine cultures were obtained in cases where sepsis was suspected, and treatment was administered based on sensitivity. Patients were followed for up to 28 days to assess outcomes. Data were collected using a data collection proforma.

Inclusion Criteria:

• Patients with either gender (male or female) aged 18-60 years.
• Diagnosed with non-acetaminophen-induced acute hepatic failure (NAI-AHF) as per operational definition.
• Cases where the etiology is attributed to factors other than acetaminophen overdose, including viral hepatitis (HAV, HBV, HEV), drug-induced liver injury (excluding acetaminophen), or idiopathic causes.
• Patients who have not received N-acetylcysteine (NAC) treatment for the current episode of acute hepatic failure before enrollment.

Exclusion Criteria:

• Patients with a history of chronic liver disease or cirrhosis.
• Patients with previous history of severe cardiac, renal, neurological, or infectious diseases that could confound treatment outcomes.
• Patients who have undergone a liver transplant or potential candidate of liver transplant.
• Known allergy or contraindication to N-acetylcysteine.
• Pregnant women.