Hepatitis

Hepatitis

Hepatitis is a gastroenterological disease, featuring inflammation of the liver. The clinical signs and prognosis, as well as the therapy, depend on the cause.

Signs and Symptoms

Hepatitis is an inflammation of the liver characterized by malaise, joint aches, abdominal pain, vomiting 2-3 times per day for the first 5 days, defecation, loss of appetite, dark urine, fever, hepatomegaly (enlarged liver) and jaundice (icterus, yellowing of the eyes and skin). Some chronic forms of hepatitis show very few of these signs and are only present when the longstanding inflammation has led to the replacement of liver cells by connective tissue; this disease process is referred to as cirrhosis of the liver. Certain liver function tests can also indicate hepatitis.

Types of Hepatitis

Hepatitis A

Hepatitis B

Hepatitis C

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Hepatitis E

Hepatitis E produces symptoms similar to hepatitis A, although it can take a fulminant course in some patients, particularly pregnant women; it is more prevalent in the Indian subcontinent.

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Hepatitis G

Another type of hepatitis, hepatitis G, has been identified, and is probably spread by blood and sexual contact. There is, however, doubt about whether it causes hepatitis, or is just associated with hepatitis, as it does not appear to be primarily replicated in the liver.

Other viruses can cause infectious hepatitis:

Mumps virus
Rubella virus
Cytomegalovirus
Epstein-Barr virus
Other herpes viruses

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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 (dulled consciousness) 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 of cirrhosis in Western countries.

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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), rifampicin, and pyrazinamide (tuberculosis-specific antibiotics)
Phenytoin and valproic acid (antiepileptics)
Zidovudine (antiretroviral i.e. against AIDS)
Ketoconazole (antifungal)
Nifedipine (antihypertensive)
Ibuprofen and indometacin (NSAIDs)
Amitriptyline (antidepressant)
Amiodarone (antiarrhythmic)
Nitrofurantoin (antibiotic)
Hormonal contraceptives
Allopurinol
Azathioprine
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. Hormonal contraception 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.

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Other Toxins That Cause Hepatitis

Toxins and drugs can cause hepatitis:

Amatoxin-containing mushrooms, including the Death Cap (Amanita phalloides), the Destroying Angel (Amanita ocreata), and some species of Galerina. A portion of a single mushroom can be enough to be lethal (10 mg or less of α-amanitin).
Yellow phosphorus, an industrial toxin.
Paracetamol (acetaminophen in the United States) 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 chlorinated hydrocarbons, cause steatohepatitis (hepatitis with fatty liver).

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Metabolic Disorders

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.

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Obstructive

“Obstructive jaundice” is the term used to describe jaundice due to obstruction of the bile duct (by gallstones or external obstruction by cancer). If longstanding it leads to destruction and inflammation of liver tissue.

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Autoimmune

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 an incidence of 1-2 per 100,000 per year, and a prevalence of 15-20/100,000. 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 (classic form, responds well to low dose steroids).
Positive LKM-1 (typically female children and teenagers; disease can be severe).
All antibodies negative, positive antibodies against soluble liver antigen (SLA)(now designated SLP/LP). This group behaves like group 1.
No autoantibodies detected (~13%).

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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.

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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 hepatitis), which occurs in up to 80% of all clinically obese people. 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 radio logic imaging including ultrasound, computed tomography imaging, or magnetic resonance imaging. However, radio logic 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.

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Hepatitis Awareness

World Hepatitis Awareness Day is an annual event organized by several medial hepatitis advocacy groups to raise awareness of infectious hepatitis and demand action to curb the spread of the disease and treat people who are infected.