Other than the liver which of the following organs is most commonly affected by ethanol injury

• Confirmed history of alcohol use

• Liver function tests and complete blood count (CBC)

Alcohol is suspected as the cause of liver disease in any patient who chronically consumes excess alcohol, particularly > 80 g/day. When the patient's alcohol consumption is in doubt, history should be confirmed by family members. Patients can be screened for alcohol use disorder using the CAGE questionnaire (need to Cut down, Annoyed by criticism, Guilty about drinking, and need for a morning Eye-opener). There is no specific test for alcohol-related liver disease, but if the diagnosis is suspected, liver tests (PT; serum bilirubin, aminotransferase, and albumin levels) and CBC are done to detect signs of liver injury and anemia.

• Serum bilirubin, which represents secretory function

• Prothrombin time or international normalized ratio, which reflects synthetic ability

If abnormalities suggest alcohol-related liver disease, screening tests for other treatable forms of liver disease, especially viral hepatitis, should be done.

Not all experts agree on the indications for liver biopsy. Proposed indications include the following:

• Unclear clinical diagnosis (eg, equivocal clinical and laboratory findings, unexplained persistent elevations of aminotransferase levels)

• Clinical suspicion of > 1 cause of liver disease (eg, alcohol plus viral hepatitis)

• Desire for a precise prediction of prognosis

Acetaminophen is one of the most commonly used oral analgesics and antipyretics. [1] It has an excellent safety profile when administered in proper therapeutic doses, but hepatotoxicity can occur after overdose or when misused in at-risk populations. In the United States, acetaminophen toxicity has replaced viral hepatitis as the most common cause of acute liver failure. [2]

Acetaminophen metabolism occurs primarily in the liver and is illustrated in the image below.

Most patients who overdose on acetaminophen will initially be asymptomatic, as clinical symptoms of end-organ toxicity do not manifest until 24-48 hours after an acute ingestion. Therefore, to identify a patient who may be at risk of hepatoxicity, the clinician should determine the time(s) of ingestion, the quantity, and the formulation of acetaminophen ingested.

Minimum toxic doses of acetaminophen for a single ingestion, posing significant risk of severe hepatotoxicity, are as follows:

• Adults: 7.5-10 g

• Children: 150 mg/kg; 200 mg/kg in healthy children aged 1-6 years

The clinical course of acetaminophen toxicity generally is divided into four phases. Physical findings may vary, depending on the degree of hepatotoxicity.

Phase 1

• 0.5-24 hours after ingestion

• Patients may be asymptomatic or report anorexia, nausea or vomiting, and malaise

• Physical examination may reveal pallor, diaphoresis, malaise, and fatigue

Phase 2

• 18-72 h after ingestion

• Patients develop right upper quadrant abdominal pain, anorexia, nausea, and vomiting

• Right upper quadrant tenderness may be present

• Tachycardia and hypotension may indicate volume losses

• Some patients may report decreased urinary output (oliguria)

Phase 3: Hepatic phase

• 72-96 h after ingestion

• Patients have continued nausea and vomiting, abdominal pain, and a tender hepatic edge

• Hepatic necrosis and dysfunction may manifest as jaundice, coagulopathy, hypoglycemia, and hepatic encephalopathy

• Acute kidney injury develops in some critically ill patients

• Death from multiorgan failure may occur

Phase 4: Recovery phase

• 4 d to 3 wk after ingestion

• Patients who survive critical illness in phase 3 have complete resolution of symptoms and complete resolution of organ failure

See Presentation for more detail.

The serum acetaminophen concentration is the basis for diagnosis and treatment. A diagnostic serum concentration is helpful, even in the absence of clinical symptoms, because clinical symtpoms are delayed. The Rumack-Matthew nomogram interprets the acetaminophen concentration (in micrograms per mL), in relation to time (in hours) after ingestion, and is predictive of possible hepatotoxicity after single, acute ingestions of acetaminophen.

Recommended serum studies are follows:

• Liver function tests (alanine aminotransferase [ALT], aspartate aminotransferase [AST]), bilirubin [total and fractionated], alkaline phosphatase)

• Prothrombin time (PT) with international normalized ratio (INR)

• Glucose

• Kidney function studies (electrolytes, BUN, creatinine)

• Lipase and amylase (in patients with abdominal pain)

• Human chorionic gonadotropin (hCG) (in females of childbearing age)

• Salicylate level (in patients with concern of co-ingestants)

• Arterial blood gas and ammonia (in clinically compromised patients)

Additional recommended studies are as follows:

• Urinalysis (to check for hematuria and proteinuria)

• ECG (to detect additional clues for co-ingestants)

In patients with mental status changes, strongly consider serum ammonia levels and CT scanning of the brain. Laboratory findings in the phases of acetaminophen hepatotoxicity are as follows:

• Phase 1: Approximately 12 hours after an acute ingestion, liver function studies show a subclinical rise in serum transaminase concentrations (ALT, AST)

• Phase 2: Elevated serum ALT and AST, PT, and bilirubin concentration; renal function abnormalities may also be present and indicate nephrotoxicity

• Phase 3: Severe hepatotoxicity is evident on serum studies; hepatic centrilobular necrosis is diagnosed on liver biopsy

Rumack-Matthew nomogram

• Used to interpret plasma acetaminophen values to assess hepatotoxicity risk after a single, acute ingestion

• Nomogram tracking begins 4 hours after ingestion (time when acetaminophen absorption is likely to be complete) and ends 24 hours after ingestion

• About 60% of patients with values above the "probable" line develop hepatotoxicity

See Workup for more detail.

Gastrointestinal decontamination agents can be used in the emergency setting during the immediate postingestion time frame. Administer activated charcoal (AC) if the patient is alert and presents, ideally, within 1 hour post ingestion. This time frame can be extended if the patient has ingested an acetaminophen-based sustained-release medication or if the ingestion includes agents that are known to slow gastric emptying. Patients with acetaminophen concentrations below the “possible" line for hepatotoxicity on the Rumack-Matthew nomogram may be discharged home after they are medically cleared.

Admit patients with acetaminophen concentration above the "possible" line on the Rumack-Matthew nomogram for treatment with N -acetylcysteine (NAC). NAC is nearly 100% hepatoprotective when it is given within 8 hours after an acute acetaminophen ingestion, but can be beneficial in patients who present more than 24 hours after ingestion. NAC is approved for both oral and IV administration.

The FDA-approved regimen for oral administration of NAC (Mucomyst) is as follows:

• Loading dose of 140 mg/kg

• 17 doses of 70 mg/kg given every 4 hours

• Total treatment duration of 72 hours

The IV formulation of NAC (Acetadote) is commonly used in many institutions for the treatment of acetaminophen ingestion. Use of the IV formulation of NAC is preferred in the following situations:

• Altered mental status

• GI bleeding and/or obstruction

• A history of caustic ingestion

• Potential toxicity in a pregnant woman

• Inability to tolerate oral NAC because of emesis refractory to proper use of antiemetics

Surgical evaluation for possible liver transplantation is indicated for patients who have severe hepatotoxicity and potential to progress to hepatic failure. Criteria for liver transplantation include the following:

• Metabolic acidosis, persistent after fluid resuscitation

• Kidney failure

• Coagulopathy

• Encephalopathy

See Treatment and Medication for more detail.

See also the following:

For patient education information, see Tylenol Poisoning.