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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
It is recommended that Transfer
Factor to be used in autoimmune conditions.
Transfer Factor Plus is generally preferred for
conditions caused by infection. Transfer Factors
suppress over acting immune system
to ease autoimmune conditions.
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.
Non-alcoholic steato-hepatitis
Non-alcoholic steato-hepatitis (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 Non-alcoholic steato-hepatitis 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.
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