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.
Signs and symptoms
Hepatitis is characterized by
(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
Most cases of acute hepatitis are due to viral infections:
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 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), 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, or touching wounds on
infected persons. Needle-exchange programs 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 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.
Hepatitis B infections result in 500,000 to
1,200,000 deaths per year worldwide due to the complications of
chronic hepatitis, cirrhosis, and
Hepatitis B is endemic in a number of (mainly South-East Asian) countries,
making cirrhosis and
hepatocellular carcinoma big killers.
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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
However, patients with hepatitis C are prone to severe hepatitis if
they contract either hepatitis A or B. Therefore all
patients should be immunized against Hepatitis A and
Hepatitis B if
they are not already immune.
Hepatitis D and E
Two other hepatitis viruses are known,
hepatitis D and E. The
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 been identified.
Other viruses can cause infectious hepatitis:
- Mumps virus
- Rubella virus
- Epstein-Barr virus
- Other herpes viruses
Ethanol, mostly in alcoholic beverages, is an important cause of
hepatitis. Usually alcoholic hepatitis comes on 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, together
with hepatitis C.
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 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).
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.
Longstanding obstruction of the bile duct (by gallstones or external
obstruction by cancer) leads to destruction and inflammation of liver
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
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
Four subtypes are recognized, 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
- All antibodies negative, positive antibodies against soluble liver
- No autoantibodies detected
Alpha 1-antitrypsin deficiency
In severe cases of alpha 1-antitrypsin deficiency (A1AD), the
accumulated protein causes in the endoplasmic reticulum causes liver
cell damage and inflammation.
Non-alcoholic steatohepatitis (NASH) is a type of hepatitis which
looks like alcoholic hepatitis on liver biopsy (fat droplets,
inflammatory cells, and Mallory's hyalin) but is in a patient who does
not have alcoholic liver disease as the cause. The most common cause
of this condition is obesity or the metabolic Syndrome X.
NASH is becoming recognized as the most important cause of liver
disease second only to Hepatitis C in numbers of patients going on to
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
The condition called "fatty liver" (steatosis hepatis) is related but
less serious. Liver biopsy in fatty liver does not show inflammation
or Mallory's hyaline, but fat droplets are seen throughout the liver.