Liver Enzymes Over 1000: 9 Causes Explained In-depth.
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Several diseases and conditions can lead to massive elevation of the liver enzymes (ALT and AST) to over 1000 U/L. Today, we will explain (in-depth) each of the
The possible causes of liver enzymes over 1000 include:
- Acute hepatitis A.
- Other causes of ACUTE viral hepatitis such as HBV, HCV, HDV, and HEV.
- Acetaminophen toxicity, other medications, and herbal toxins.
- Wilson’s disease.
- Autoimmune hepatitis.
- Acute Budd-Chiari Syndrome.
- Acute biliary obstruction.
- Liver ischemia (shocked liver and hepatic artery ligation.
The table below shows the most commonly used reference ranges (specific for age and sex):
|Gender||Age range (years)||ALT levels (U/L)|
|18 or more||<33|
|18 or more.||<45|
1 . Acute Hepatitis A.
Hepatitis A is a common cause of acute onset jaundice and elevated liver enzymes over 1000.
Quick Facts about Hepatitis A virus infection (reference):
- Common: Hepatitis A virus (HAV) infection is one of the commonest causes of acute hepatitis in children and adults (with liver enzymes often over 1000).
- Transmission: The hepatitis A virus (HAV) is transmitted through the digestive system (through contact with an infected person or eating contaminated foods or drinks).
- Long incubation period: The time between getting the infection and the appearance of symptoms ranges from 15-50 days (an average of 28 days). This makes it challenging to define the source of infection.
- Self-limiting: the virus causes self-limiting acute illnesses which rarely turn chronic.
- Liver failure due to hepatitis A is rare, occurring in less than 1% of the cases.
- Life-long immunity: following an attack of acute hepatitis A, life-long immunity develops against subsequent infection.
- HAV vaccine: HAV vaccine has been developed and is available in different world regions. It also provides a life-long immunity against the virus.
Symptoms of acute hepatitis A:
- The symptoms appear at an average of 28 days after infection (range from 15 to 50 days.
- 30% of adults with HAV infection develop NO symptoms (reference).
The digestive symptoms stage(for a few days):
- Acute onset nausea, vomiting, anorexia (lost appetite).
- Abdominal pain.
- Fever and body aches.
The jaundice stage (about a week after digestive symptoms):
- Dark urine.
- Pale stools.
- Jaundice (yellowish skin and eye whites) (in up to 70% of the cases; not in all cases).
- The early signs and symptoms (nausea, vomiting, abdominal pain, fever) often disappear.
- Jaundice typically peaks within two weeks.
- Right upper quadrant pain (liver pain).
- Non-liver symptoms include skin rash, joint pain (in 10-15%), and others.
Your doctor diagnoses acute hepatitis A based on the clinical scenario explained above together with investigations:
- Liver enzymes (ALT and AST are often over 1000).
- Bilirubin levels are often above 10 mg/dL.
- Hepatitis A antibodies detection in the blood (serum HAV IgM).
Treatment and recovery:
Acute hepatitis A infection is often a self-limiting disease. Although the liver enzymes are severely elevated (over 1000 and sometimes reaches 3000 or 4000), spontaneous recovery occurs 99% of the time.
Approximately 85% of patients will recover (jaundice disappears, and liver enzymes return to normal) within two to three months.
The remaining 15% may take up to 6 months to fully recover. Complications such as relapse and liver failure are rare.
Treatment options are limited and mainly supportive (no drug kills the virus). It includes:
- No specific treatment, your body’s immune system will get rid of the virus on its own.
- Avoid medications that may harm the liver, such as nonsteroidal anti-inflammatory drugs.
- Bland food, avoid fatty and fried foods as they may induce nausea and vomiting.
- Stay hydrated.
- Manage nausea: Snaking throughout the day. Ask your doctor about an OTC anti-nausea or anti-vomiting medications if the symptoms are severe.
2. Other causes of acute viral hepatitis (B, C, D, E).
Hepatitis A virus is the most common viral cause of acute hepatitis. Other viral infections mainly cause chronic from mildly elevated liver enzymes) or are rare.
Acute hepatitis with other viruses (such as Hepatitis B, C, D, or E) is much lower and occurs sporadically. You may get infected with hepatitis B or C viruses without passing into the acute stage.
The picture of acute hepatitis is essentially the same. The difference is that other viruses cause minor digestive symptoms (nausea, vomiting, abdominal pain) than HAV.
The table below illustrates the features of acute hepatitis due to viruses other than HAV:
|Acute hepatitis B||– Up to 70 of people with acute hepatitis B have NO symptoms.|
– Symptoms of acute hepatitis appear one to four months after getting infected.
– Early constitutional symptoms (fatigue, anorexia, nausea, jaundice, land liver pain).
– the symptoms and jaundice often disappear after one to three months.
– during the acute attack, The liver enzymes are often over 1000 or 2000. and ALT is often higher than AST.
– The acute attack often turns into chronic HBV infection or latent infection.
– Acute liver failure following acute hepatitis B occurs in only 0.5 to 1.0%.
|Acute hepatitis C.||– Acute hepatitis C accounts for 15% of symptomatic cases of acute hepatitis in the USA (reference).|
– However, The majority of cases of acute hepatitis C pass unnoticed.
– Symptomatic patients have jaundice, dark urine, pale stools, and fatigue, typically developing 1-26 weeks after infection.
– Fulminant liver failure is very rare with acute HCV infection.
– Liver enzymes may become over 1000, but they are highly variable.
|Hepatitis D infections||– It is a (defective) virus that often causes acute hepatitis with the help of the hepatitis B virus.|
– It often infects high-risk groups (such as IV abusers and patients receiving multiple blood transfusions).
– Around 10% of people with HBV infection may also have HDV simultaneously (reference).
– HDV may cause severe acute hepatitis (enzymes over 1000) in patients with HBV infection.
Hepatitis E infection
|– HEV is transmitted by contaminated foods or drinks (similar to HAV).|
– It often causes acute hepatitis similar to HAV (with liver enzymes Over 1000).
– it can cause acute liver failure in pregnant women.
|Others||– Other groups of viruses collectively called (non-hepatotropic viruses) may also cause acute hepatitis.|
– They include Cytomegalovirus (CMV), Ebstein-Barr virus (EBV), and Herpes viruses.
– They often have multisystem symptoms.
– The rise in liver enzymes is mainly mild to moderate. Rarely, They can cause elevated liver enzymes over 1000.
3. Acetaminophen (paracetamol) toxicity.
Acetaminophen or paracetamol (Tylinol®) is the most widely used analgesic and fever medication in the united states and worldwide.
The drug is considered safe; However, at high doses, it can cause severe acute hepatitis with elevated liver enzymes over 1000.
Paracetamol is the most common cause of acute liver failure in the united states accounting for 505 of all reported cases (reference).
The maximum recommended dose of paracetamol is 4000 mg (8 tablets of paracetamol 500 mg per day). The maximum recommended daily dose in children is 80 mg per K (reference).
Acetaminophen Toxic dose (reference):
- A single dose of 250 mg/kg (about 17,000 mg single dose). It is about 34 tablets of paracetamol 500mg as a single dose.
- A total dose of 12,000 mg over 24 hours.
- Toxicity is unlikely for doses less than 10,000 mg in adults.
So, the safety margin is high with paracetamol, and there is no need to panic as long as you use the recommended doses. But unfortunately, these doses are often intentionally taken to induce self-harm.
- History of taking a very large dose (multiple tablets or entire stips of the drug) in a single dose or a very short period.
- Stage I (0.5 to 24 hours): Nausea, vomiting, sweating, pallor, dizziness, and malaise. Some may be asymptomatic. Liver enzymes are often normal during this stage.
- Stage II (24 to 72 hours): Stage one symptoms often resolve, liver pain develops. Liver enzymes start to elevate, and liver functions deteriorate.
- Stage III (72 to 96 hours): Symptoms of liver failure (jaundice, confusion, dark stool, elevated liver enzymes over 1000 and may exceed 10,000. Acute renal failure and death may occur.
- Stage IV (4 days to two weeks): Patients who survive will enter the recovery stage with gradual improvement of symptoms and a decline in liver enzymes.
4. Other medications or toxins.
More than 1000 medications, herbal supplements, and toxins can cause injury to the liver. However, not all of them cause a significant elevation of liver enzymes to over 1000.
The complete list of a searchable database of drugs that cause liver injury is here.
Call your doctor if you recently ingested a medication or suspected toxin.
Common examples include:
- Acetaminophen (paracetamol): Explained above.
- Nonsteroidal anti-inflammatory drugs such as Aspirin and ibuprofen.
- Man-made medicines such as testosterone.
- Some antibiotics such as sulfa medicines.
- Oral contraceptive pills.
- Stations (medications that lower cholesterol).
- Anti-epileptic medications.
- Herbal medicines such as ephedra, Germander, and others.
Other (less common causes):
5. Autoimmune hepatitis.
Your immune system can attack the liver, causing inflammation (autoimmune hepatitis.
The inflammation can be acute or chronic, and it may end in liver cirrhosis.
The acute type of autoimmune hepatitis can present with typical symptoms of acute hepatitis (jaundice, pale stools, dark urine, liver pain, etc.).
The liver enzymes in the acute form of autoimmune hepatitis are often about 10 to 20 times the upper limit of normal, and they may become over 1000 in severe causes (reference).
The disease can come at any age and in all ethnic groups. However, it is more common in women than in men.
Learn more about autoimmune hepatitis.
6. Wilson’s disease.
Wilson’s disease is a genetic disorder of copper metabolism. In Wilson’s disease, your liver is unable to excrete copper properly. As a result, copper accumulates and causes liver damage.
Wilson’s disease is a rare disease affecting one in every 30,000 liver births.
It affects the liver and accumulates in other body organs, causing problems such as the brain, the kidneys, and the cornea.
It typically presents with neurological, psychiatric, and liver symptoms.
Acute hepatitis due to Wilson’s disease commonly affects children and young adults with a typical picture of acute hepatitis (liver enzymes over 1000) and may end in acute liver failure.
Learn more about Wilson’s disease.
7. Budd-Chiari syndrome (Acute form).
Budd-Chiari syndrome occurs when the liver becomes unable to get rid of venous blood (venous outflow obstruction). It is often due to a block or inflammation of the hepatic vein.
It is more common in women. The acute form develops over weeks.
Acute Budd-Chiari syndrome often manifests with abdominal swelling (ascites and liver pain (right upper quadrant). The condition may be severe to the degree of acute liver failure.
Liver enzymes are often around 100 to 200 U/L, but they may exceed 1000 U/L (reference).
Learn more about acute Budd-Chiari Syndorme.
8. Acute bile duct obstruction.
Acute bile outflow obstruction from the liver is commonly due to an impacted stone in the common bile duct. Also, some cases of pancreatic head cancer can cause such conditions.
Acute obstruction of the bile outflow from the liver causes infection and inflammation of the bile ducts (cholangitis).
Severe cholangitis can present with highly elevated liver enzymes. However, They rarely exceed 1000 U/L.
9. Ischemic hepatitis (shocked liver)
Conditions that cause sudden loss of blood supply to the liver cause transient but significant liver injury.
The most common cause is transient severe hypotension (for example, during bleeding or operations) or ligation of the main hepatic artery during an abdominal operation.
The condition is characterized by a severe rise in liver enzymes (similar to acute viral hepatitis and acetaminophen toxicity)y.
- Hypovolemic shock during bleeding or severe vomiting and diarrhea.
- Hypotension during operations (from bleeding or anesthesia).
- Septic shock with severe infections.
- Hepatic artery thrombosis.
- Hepatic artery ligation.
- During liver transplantation operations.
Ischemic Hepatitis should be considered in patients with liver enzymes over 1000 with a recent history of hypotension and shock.
The condition often improves rapidly, and liver enzymes decline after restoring liver perfusion with blood. However, more extended periods of liver ischemia can result in liver infarction (death) and failure.
Learn more about ischemic hepatitis.