wrongdoctors: Hepatitis Summary

In medicine (gastroenterology), hepatitis is any disease featuring inflammation of the liver. The clinical signs and prognosis, as well as the therapy, depend on the cause. Contents

Signs and Symptoms of Hepatitis

Hepatitis is characterised by abdominal pain, fever, hepatomegaly (enlarged liver) and jaundice (icterus). Some chronic forms of hepatitis show very few of these signs and only present when the longstanding inflammation has led to the replacement of liver cells by connective tissue; the result is cirrhosis.

Types of hepatitis

Viral Hepatitis

Most cases of acute hepatitis are due to viral infections:

Hepatitis A
Hepatitis B
Hepatitis C
Hepatitis D
Hepatitis E

Please see the respective articles for more detailed information

Alcoholic hepatitis

Ethanol, mostly in alcoholic beverages, is an important cause of hepatitis. Usually alcoholic hepatitis comes after a period of increased alcohol consumption. Alcoholic hepatitis is characterized by a variable constellation of symptoms, which may include feeling unwell, enlargement of the liver, development of fluid in the abdomen ascites, and modest elevation of liver blood tests. Alcoholic hepatitis can vary from mild with only liver test elevation to severe liver inflammation with development of jaundice, prolonged prothrombin time, and liver failure. Severe cases are characterized by either obtundation or the combination of elevated bilirubin levels and prolonged prothrombin time; the mortality rate in both categories is 50% within 30 days of onset.

Alcoholic hepatitis is distinct from cirrhosis caused by long term alcohol consumption. Alcoholic hepatitis can occur in patients with chronic alcoholic liver disease and alcoholic cirrhosis. Alcoholic hepatitis by itself does not lead to cirrhosis, but cirrhosis is more common in patients with long term alcohol consumption. Patients who drink alcohol to excess are also more often than others found to have hepatitis C. The combination of hepatitis C and alcohol consumption accelerates the development cirrhosis in Western countries.

Drug induced hepatitis

A large number of drugs can cause hepatitis. The anti-diabetic drug troglitazone was withdrawn in 2000 for causing hepatitis. Other drugs associated with hepatitis:

Halothane (a specific type of anesthetic gas)
Methyldopa (antihypertensive)
Isoniazid (INH) and rifampicin (tuberculosis-specific antibiotics)
Phenytoin and valproic acid (antiepileptics)
Zidovudine (antiretroviral i.e. against AIDS)
Ketoconazole (antifungal)
Nifedipine (antihypertensive)
Ibuprofen and indomethacin (NSAIDs)
Amitriptyline (antidepressant)
Amiodarone (antiarrhythmic)
Nitrofurantoin (antibiotic)
Oral contraceptives
Some herbs and nutritional supplements

The clinical course of drug-induced hepatitis is quite variable, depending on the drug and the patient's tendency to react to the drug. For example, halothane hepatitis can range from mild to fatal as can INH-induced hepatitis. Oral contraceptives can cause structural changes in the liver. Amiodarone hepatitis can be untreatable since the long half life of the drug (up to 60 days) means that there is no effective way to stop exposure to the drug. Statins can cause elevations of liver function blood tests normally without indicating an underlying hepatitis. Lastly, human variability is such that any drug can be a cause of hepatitis.

Other toxins that cause hepatitis

Toxins and drugs can cause hepatitis:

The Amanita (death-cap) mushroom (Amanita) contains amatoxins such as alpha-amanitin. A single mushroom can be enough to be lethal (10 mg of ?-amanitin).
Yellow phosphorus (a metal) is an industrial toxin.
Paracetamol (Acetaminophen in the USA) can cause hepatitis when taken in an overdose. The severity of liver damage can be limited by prompt administration of acetylcysteine.
Carbon tetrachloride ("tetra", a dry cleaning agent), chloroform and trichloroethylene, all chlorine-containing carbohydrates, cause steatohepatitis (hepatitis with fatty liver).

Metabolic disorders and Hepatitis

Some metabolic disorders cause different forms of hepatitis. Hemochromatosis (due to iron accumulation) and Wilson's disease (copper accumulation) can cause liver inflammation and necrosis.

See below for non-alcoholic steatohepatitis (NASH), effectively a consequence of metabolic syndrome.

Cholestatic Hepatitis

Longstanding obstruction of the bile duct (by gallstones or external obstruction by cancer) leads to destruction and inflammation of liver tissue.

Autoimmune Hepatitis

Anomalous presentation of human leukocyte antigen (HLA) class II on the surface of hepatocytes — possibly due to genetic predisposition or acute liver infection — causes a cell-mediated immune response against the body's own liver, resulting in autoimmune hepatitis. Autoimmune hepatitis has a prevalence of 1-2 per 1000. As with most other autoimmune diseases, it affects women much more often than men (8:1). Liver enzymes are elevated, as is bilirubin. Autoimmune Hepatitis can progress to cirrhosis. Treatment is with steroids and disease-modifying antirheumatic drugs (DMARDs).

The diagnosis of autoimmune Hepatitis is best achieved with a combination of clinical and laboratory findings. A number of specific antibodies found in the blood (antinuclear antibody (ANA), smooth muscle antibody (SMA), Liver/kidney microsomal antibody (LKM-1) and anti-mitochondrial antibody (AMA)) are of use, as is finding an increased Immunoglobulin G level. However, the diagnosis of autoimmune hepatitis always requires a liver biopsy. In complex cases a scoring system can be used to help determine if a patient has autoimmune hepatitis, which combines clinical and laboratory features of a given case. Four subtypes are recognised, but the clinical utility of distinguishing subtypes is limited.

Positive ANA and SMA, raised immunoglobulin G
Positive LKM-1 (typically children and teenagers; disease can be severe)
All antibodies negative, positive antibodies against soluble liver antigen (SLA)
No autoantibodies detected

Alpha 1-antitrypsin deficiency

In severe cases of alpha 1-antitrypsin deficiency (A1AD), the accumulated protein in the endoplasmic reticulum causes liver cell damage and inflammation.

Nonalcoholic steatohepatitis

Non-alcoholic steatohepatitis (NASH) is a type of hepatitis which resembles alcoholic hepatitis on liver biopsy (fat droplets, inflammatory cells, but usually no Mallory's hyalin) but occurs in patients who have no known history of alcohol abuse. NASH is more common in women and the most common cause is obesity or the metabolic syndrome. A related but less serious condition is called "fatty liver" (steatosis hepatis). A liver biopsy for fatty liver shows fat droplets throughout the liver, but no signs of inflammation or Mallory's hyalin.

The diagnosis depends on history, physical exam, blood tests, radiological imaging and sometimes a liver biopsy. The initial evaluation to identify the presence of fatty infiltration of the liver is radiologic imaging including ultrasound, computed tomographic imaging, or magnetic resonance imaging.

However, radiologic imaging cannot readily identify inflammation in the liver. Therefore, the differentiation between steatosis and NASH often requires a liver biopsy. It can also be difficult to distinguish NASH from Alcoholic Hepatitis when the patient has a history of alcohol consumption. Sometimes in such cases a trial of abstinence from alcohol along with follow up blood tests and a repeat liver biopsy are required. NASH is becoming recognized as the most important cause of liver disease second only to Hepatitis C in numbers of patients going on to cirrhosis.

wrongdoctors

Hepatitis Summary