Please select the eligibility criteria that correspond to the clinical trial below.
Title: N/A
Brief Summary: It is widely believed that people who abuse alcohol can sustain a liver injury after taking doses of acetaminophen just above the recommended maximum dose. This study is designed to look at the interaction between acetaminophen, liver injury and alcohol abuse. Subjects will undergo baseline tests to ensure that they do not have liver damage at the time of enrollment. Each subject will be randomly assigned to receive either a therapeutic dose of acetaminophen or a placebo three times a day for four days. Subjects will have blood work drawn on a daily basis to monitor the status of the liver. These tests will include conventional markers of liver injury in addition to a novel biomarker of liver function, a-GST. Previous work in the investigators' group has shown that a-GST is a more sensitive indicator of liver injury following acetaminophen overdose (Sivilotti 1999, Sivilotti 2002 x 2). However, it has never been used to study the alcoholic population. The investigators believe that a-GST may detect a subclinical acetaminophen-induced liver injury that has previously gone unrecognized in the alcoholic population.


Options:
A: Inclusion Criteria:

* Any patient admitted to hospital within 36 hours of a single acute paracetamol overdose; AND
* Requires treatment with acetylcysteine.

These patients will include:

* Patients with no risk factors and timed paracetamol concentrations above the 200-line on the UK paracetamol overdose treatment nomogram.
* Patients with at least 1 risk factor and timed paracetamol concentrations above the 100-line on the UK paracetamol overdose treatment nomogram
* Patients presenting \>8 hours, and at risk of liver damage based on history of dose ingested (BNF) that need immediate treatment

Risk factors are defined as follows:

* Nutritional deficiency, malnourished and/or debilitating disease: acute or chronic starvation, eating disorders, cachexia, malabsorption syndromes, AIDS, cystic fibrosis, hepatitis C, chronic alcoholism.
* Enzyme induction: use of drugs with this property (carbamazepine, rifampicin, barbiturates, phenytoin, rifabutin, efavirenz, nevirapine, St John's Wort; regular consumption of ethanol above advised amounts.

Exclusion Criteria:

Patients:

* \< 16 years old
* Detained under the Mental Health Act
* With known permanent cognitive impairment
* With a life-threatening illness
* Who are known to be pregnant
* Who have previously participated in the study
* Unreliable history of paracetamol overdose
* Vomiting and requiring treatment antiemetic prior to randomisation
* Presenting after 36 hours of a single acute paracetamol overdose
* Presenting after taking a staggered paracetamol overdose (defined as when the overdose of paracetamol is taken over a period of more than 2 hours)
* Who take anticoagulants (e.g. warfarin) therapeutically or have taken an overdose of anticoagulants
* Who, in the opinion of the responsible clinician/nurse, are unlikely to complete the full course of acetylcysteine e.g. expressing wish to self-discharge
* Who in the opinion of the responsible clinician/nurse are unable to complete the initial questionnaire either themselves or with nurse assistance.
* Who have a history of hypersensitivity to 5HT3 antagonists
* Non-English speaking patients. (Trial information material will only be produced in English in view of the known and stable demographic of the Edinburgh and Newcastle self harm population)
B: Inclusion Criteria:

* Patients with severe or sub-severe hepatitis, with an indication or a contraindication to liver transplantation

Exclusion Criteria:

* Sepsis severe not controlled
* Haemorrhage activates not controlled
* Clinical Obviousness of disseminated intravascular coagulation
* Severe Pathology cardiopulmonary (NYHA \> or = 2)
* Pregnancy, breast feeding
* Average blood Pressure \< 40 mmHg more than 10 minutes in spite of a support by the inotrope
* Nonhepatic coma of origin
* Cholestases extra-hepatitic
* Antecedents of heavy surgery in the 4 previous weeks or surgical problems unsolved
* Absolute counter-indication with hepatic transplantation (extra Neoplasia hepatic evolutionary, irreversible cerebral Attack, irreversible multi-visceral Failure, visceral tares contra-indicating the transplantation)
* Positive serology HIV
* Hepatic Demonstrations of the malignant hemopathies
* Participation in another therapeutic test in the 4 previous weeks
C: ALF Inclusion Criteria:

* Written Informed consent from patient's next of kin
* Altered mentation of any degree (encephalopathy)
* Evidence of moderately severe coagulopathy (INR ≥ 1.5)
* A presumed acute illness onset of less than 26 weeks
* The NIH guidelines on the inclusion of women and minorities as subjects in clinical research will be observed

ALF Exclusion Criteria:

* Cirrhosis patients
* Alcohol induced liver failure
* Known pre-existing chronic liver disease

ALI Inclusion Criteria:

Acetaminophen (APAP) etiology: acute illness \< 2 wks

* INR ≥ 2.0, ALT ≥ 10X ULN Non-acetaminophen etiology: acute illness \< 26 wks
* INR≥ 2.0, ALT≥ 10X ULN, TBili ≥ 3 mg/dl

ALI Exclusion Criteria:

• Altered mentation of any degree (encephalopathy)
D: Inclusion Criteria:

* Individuals who self-report consuming at least 6 drinks per day, daily, for at least 6 weeks and who are currently enrolled at the Detoxification Center, Hotel Dieu Hospital.
* Last alcohol consumption occurring between 12 and 72 hours prior to screening for study.

Exclusion Criteria:

* Individuals with a self-reported or previously documented history of hepatitis A, B, C or HIV.
* Individuals who have ingested any acetaminophen regardless of dose in the previous 48 hours.
* Individuals who have ingested \> 4 grams of acetaminophen/day in any of the previous 7 days.
* Individuals \< 18 years of age.
* Individuals with abnormal liver function at baseline (defined as AST or ALT \> 120 IU/L, International Normalized Ratio \[INR\] \> 1.5, and a-GST \> 7.5 7 :g/L).
* Individuals who have an allergy or sensitivity to acetaminophen.

Answer: D