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 characterised by fatigue, malaise, joint aches, abdominal pain, vomiting 2-3 times per day for the first 5 days, loss of appetite, dark urine, 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. Certain liver function tests can also indicate hepatitis.

Viral
Most cases of acute hepatitis are due to viral infections:
 * Hepatitis A
 * Hepatitis B
 * Hepatitis C
 * D-agent (requires presence of the hepatitis B virus)
 * Hepatitis E
 * Hepatitis F (discredited)
 * Hepatitis G
 * In addition to the hepatitis viruses, some other viruses can cause hepatitis, including cytomegalovirus, Epstein-Barr virus, yellow fever, etc.
 * Please see the respective articles for more detailed information.
 * ''See also infectious canine hepatitis.

Hepatitis A
Hepatitis A or infectious jaundice is an enterovirus transmitted by the orofecal route, transmitted to humans through methods such as contaminated food. It causes an acute form of hepatitis and does not have a chronic stage. The patient's immune system makes antibodies against hepatitis A that confer immunity against future infection. People with hepatitis A are advised to rest, stay hydrated and avoid alcohol. A vaccine is available that will prevent infection from hepatitis A for life. It can be spread through personal contact, consumption of raw sea food or drinking contaminated water. Hepatitis A is primarily spread in third world countries, and can also be more often found in southern Europe than in northern and western Europe. Hepatitis A is transmitted fecal-orally, generally by ingesting contaminated water or food. Strict personal hygiene and the avoidance of raw and unpeeled foods can help prevent an infection. Infected persons already begin excreting the hepatitis A virus with their stool two weeks after the appearance of the first symptoms. The time between the infection and the start of the illness can run from 15 to 45 days.

Hepatitis B
Hepatitis B causes both acute and chronic hepatitis in some patients who are unable to eliminate the virus. Identified methods of transmission include blood (blood transfusion, now rare), tattoos (both amateur and professionally done), horizontally (sexually or through contact with blood or bodily fluids), or vertically (from mother to her unborn child). However, in about half of cases the source of infection cannot be determined. Blood contact can occur by sharing syringes in intravenous drug use, shaving accessories such as razor blades, or touching wounds on infected persons. Needle-exchange programmes have been created in many countries as a form of prevention. In the United States, 95% of patients clear their infection and develop antibodies against hepatitis B virus. 5% of patients do not clear the infection and develop chronic infection; only these people are at risk of long term complications of hepatitis B.

Patients with chronic hepatitis B have antibodies against hepatitis B, but these antibodies are not enough to clear the infection that establishes itself in the DNA of the affected liver cells. The continued production of virus combined with antibodies is a likely cause of immune complex disease seen in these patients. A vaccine is available that will prevent infection from hepatitis B for life. Hepatitis B infections result in 500,000 to 1,200,000 deaths per year worldwide due to the complications of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Hepatitis B is endemic in a number of (mainly South-East Asian) countries, making cirrhosis and hepatocellular carcinoma big killers. There are three, FDA-approved treatment options available for persons with a chronic hepatitis B infection: alpha-interferon, adefovir and lamivudine. In about 45% of persons on treatment achieve a sustained response.

Hepatitis C
Hepatitis C (originally "non-A non-B hepatitis") can be transmitted through contact with blood (including through sexual contact). It may lead to a chronic form of hepatitis, culminating in cirrhosis. It can remain asymptomatic for 10-20 years. No vaccine is available for hepatitis C. Patients with hepatitis C are prone to severe hepatitis if they contract either hepatitis A or B, so all hepatitis C patients should be immunized against hepatitis A and hepatitis B if they are not already immune. However, hepatitis C itself is a very lethal virus and can cause cirrhosis of the liver. The virus, if detected early on can be treated by a combination of interferon and the antiviral drug ribavirin. There are variations in the response to this treatment regimen based on the genotype of the infecting virus.

Hepatitis D
Hepatitis D is a virus like substance that has been called the delta agent. It is the closest thing to a viroid that infects a human being. Some scientist class it as a viroid. It cannot proliferate without the presence of hepatitis B virus, because its genome lacks certain essential genes.

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.

Hepatitis G
Another kind of hepatitis, hepatitis G, has been identified.

Other viruses can cause infectious hepatitis:
 * Mumps virus
 * Rubella virus
 * Cytomegalovirus
 * Epstein-Barr virus
 * Other herpes viruses

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.

Roughly one in four people that consume more than three drinks per day during a period of ten to fifteen years will experience some level of alcoholic hepatitis.

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.

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)
 * Oral 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. 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:
 * 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 &alpha;-amanitin).
 * Yellow phosphorus is 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).

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.

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.

Autoimmune
Anomalous presentation of human leukocyte antigen (HLA) class II on the surface of hepatocytes&mdash;possibly due to genetic predisposition or acute liver infection&mdash;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.
 * 1) Positive ANA and SMA, raised immunoglobulin G
 * 2) Positive LKM-1 (typically children and teenagers; disease can be severe)
 * 3) All antibodies negative, positive antibodies against soluble liver antigen (SLA)
 * 4) 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), 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 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.