Role of N-Acetylcysteine in Non-Acetaminophen-Induced Acute Liver Failure

Role of N-Acetylcysteine in Non-Acetaminophen-Induced Acute Liver Failure: a Randomized Controlled Trial

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Acute Liver Failure; Drug-Induced Liver Injury
• Intervention / Treatment: Drug: N-Acetylcysteine (NAC) Treatment; Other: Standard supportive care

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Pakistan
  • Punjab
    • Lahore, Punjab, Pakistan, 54000
      • Lahore General Hospital, Lahore

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NAC Group; Participants in this group received N-Acetylcysteine (NAC) along with standard supportive care for acute liver failure. NAC was administered orally or via a nasogastric tube.	Drug: N-Acetylcysteine (NAC) Treatment; Participants in this group received N-Acetylcysteine (NAC) 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 for a total of 3 days, alongside standard supportive care for acute liver failure.
Placebo Comparator: Control Group; Participants in this group received only standard supportive care, without N-Acetylcysteine (NAC).	Other: Standard supportive care; Participants in this group received only standard supportive care for acute liver failure, without N-Acetylcysteine (NAC). Standard supportive care included measures to prevent hypoglycemia, administration of broad-spectrum antimicrobials, proton pump inhibitors, fluid and electrolyte balance maintenance, and supportive treatment for hepatic encephalopathy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival Rate	It is defined as the proportion of patients with non-acetaminophen-induced acute liver injury who remain alive at 28th day after enrollment.	28 days post-enrollment
Mortality Rate	Proportion of patients who die within 28 days after enrollment in the study.	28 days post-enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of Hospital Stay	The total number of days each participant hospitalized from admission to discharge or death.	Through study completion, an average of 28 days

Collaborators and Investigators

• Sponsor: Lahore General Hospital
• Investigators: Principal Investigator: Muhammad Irfan Jamil, Lahore General Hospital, Lahore

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2025
• Primary Completion (Estimated): July 15, 2025
• Study Completion (Estimated): July 15, 2025

Study Registration Dates

• First Submitted: February 27, 2025
• First Submitted That Met QC Criteria: March 6, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 6, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Non-Acetaminophen-Induced Liver Injury; N-Acetylcysteine (NAC); Drug-Induced Hepatotoxicity
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Chemically-Induced Disorders; Drug-Related Side Effects and Adverse Reactions; Poisoning; Liver Failure; Hepatic Insufficiency; Liver Failure, Acute; Chemical and Drug Induced Liver Injury; Anti-Infective Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antiviral Agents; Antioxidants; Protective Agents; Expectorants; Respiratory System Agents; Free Radical Scavengers; Antidotes; Acetylcysteine; N-monoacetylcystine
• Other Study ID Numbers: LahoreGeneralH3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No