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.

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

Please see the respective articles for more detailed information

Hepatitis A is an enterovirus transmitted by the orofecal route, 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. A vaccine is available that will prevent infection from hepatitis A.

Hepatitis B causes both acute and chronic hepatitis in some patients who are unable to eliminate the virus. Identified methods of trasmission include blood (blood transfusion, now rare), tatoos (both amateur and professionally done), sexually 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 (as on the hit TV show Survivor), 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. However, 5% of patients do not clear the infection and develop chronic infection. Only these people are at risk of long term complications of Hepatits 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. Hepatitis B is endemic in a number of (mainly South-East Asian) countries, making cirrhosis and hepatocellular carcinoma big killers. Hepatitis B infections result in 500,000 to 1,200,000 deaths per year due to the complications of chronic hepatitis, cirrhosis, and hepatocellular cancer. A vaccine is available that will prevent infection from hepatitis B.

Hepatitis C (originally "non-A non-B hepatitis") is probably not transmitted sexually but only by blood contact. It leads to a chronic form of hepatitis, culminating in cirrhosis. It can remain asymptomatic for 10-20 years. No vaccine is available for hepatitis C. However, patients with hepatitis C are prone to severe hepatitis if they contract either hepatitis A or B. Therefore all hepatitis C patients should be immunized against Hepatitis A and Hepatitis B if they are not already immune.

Two other hepatitisviruses are known, hepatitis D and E. The D agent, an RNA passenger virus, cannot proliferate without the presence of hepatitis B virus, because its genome lacks certain essential genes. Hepatitis E produces a picture quite 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.

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

Other viruses can cause infectious hepatitis:

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

Toxins and drugs can cause hepatitis:

• Ethanol, mostly in alcoholic beverages, is an important cause of hepatitis. Although in alcoholics it is generally quite mild—taking a chronic course—it can exacerbate after a drinking spree. It is one of main causes of cirrhosis in Western countries, together with hepatitis C.
• The Amanita (death-cap) mushroom (Amanita) contains the poison alpha-amantin. A single mushroom can be enough to be lethal (10 mg).
• 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).

A large number of drugs can cause hepatitis, including the very commonly used statins. The anti-diabetic drug troglitazone was withdrawn in 2000 for causing hepatitis. Other drugs associated with hepatitis[1]:

• Halothane (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)
• Nitrofurantoin (antibiotic)
• Oral contraceptives
• Some herbs and nutritional supplements

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.

Non-alcoholic steatohepatitis is closely related to insulin resistance and its related diseases (syndrome X).

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

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.

The diagnosis is confirmed by testing for antibodies: antinuclear antibody (ANA), smooth muscle antibody (SMA), Liver/kidney microsomal antibody (LKM-1) and anti-mitochondrial antibody (AMA). There is often an increased immunoglobulin level.

Four types are recognised:

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

Treatment is with steroids and disease-modifying antirheumatic drugs (DMARDs). Chronic inflammation can progress to cirrhosis.

In severe cases of alpha 1-antitrypsin deficiency (A1AD), the acculumated protein causes in the endoplasmic reticulum causes liver cell damage and inflammation. This is technically not an autoimmune disease.

Non-alcoholic Steato Hepatitis (NASH) is a type of hepatits which looks like alcoholic hepatitis on liver biopsy but is in a patient who does not have alcoholic liver disease as the cause. Liver biopsies in such patients have the appearance of alcoholic liver disease, with fat droplets, inflammatory cells, and Mallory's hyalin. The most common cause of this condition is obesity or the Metabolic syndrome. NASH is becoming recognized as the most important cause of liver disease second only to Hepatitis C in numbers os patients going on to cirrhosis. Diagnosis depends on history, blood tests, and a liver biopsy. It can be difficult to distinguish NASH from Alcoholic Hepatitis when the patient has a history of alcohol consumption. Some times in such cases a trial off alcohol, follow up blood tests, and a repeat liver biopsy are needed.

The condition called fatty liver is related but less serious. Liver biopsy in fatty liver does not show inflammation or Mallory's hyalin, but fat droplets are seen throughout the liver.

• The Center for Disease Control's Viral Hepatitis website