736
U N I T 8
Gastrointestinal and Hepatobiliary Function
The differential diagnosis includes measures to
exclude other causes of liver disease, including hepatitis
B and C. A characteristic laboratory finding is that of a
marked elevation in serum gamma globulins. A biopsy
is used to confirm the diagnosis. Corticosteroid and
immunosuppressant drugs are the treatment of choice.
Although some persons remain in remission after drug
treatment is withdrawn, most require long-term mainte-
nance treatment. Liver transplantation may be required
for persons who are refractory to or intolerant of immu-
nosuppressive therapy and in whom end-stage liver dis-
ease develops.
Acute Fulminant Hepatitis
Acute fulminant hepatitis or hepatic failure is hepatic
insufficiency that progresses from onset of hepatitis
symptoms to hepatic encephalopathy within 2 to 3
weeks in persons who do not have chronic liver disease.
3
Viral hepatitis is responsible for about 10% of cases
of fulminant hepatitis, with about 8% of those being
caused by HBV and the rest by HAV.
3,21
Acetaminophen
(Tylenol) toxicity (to be discussed) is the most common
cause, accounting for at least 46% of cases in the United
States.
21
Other causes include idiosyncratic drug reac-
tions (now the second most common cause), poisonous
mushrooms, fatty liver of pregnancy, and other disor-
ders of fatty acid oxidation.
Acute fulminant liver failure often presents with gas-
trointestinal symptoms, signs of the systemic inflam-
matory response (see Chapter 20), and hemorrhagic
phenomenon. Jaundice may be absent or minimal early,
but laboratory tests show severe hepatocellular damage.
The blood ammonia level is typically elevated and corre-
lates with the development of encephalopathy and cere-
bral edema. Survival of more than a week may permit
replication of residual hepatocytes.
The treatment for acute liver failure is directed
toward correcting the underlying liver abnormality and
providing supportive care. Liver transplantation is the
only option for persons who do not succumb to second-
ary infections or other organ failure. The mortality rate
of fulminant hepatitis is about 85% without transplant
and about 35% with transplant.
3
Intrahepatic Biliary Disorders
Intrahepatic biliary diseases disrupt the flow of bile
through the liver, causing cholestasis and biliary cirrho-
sis. Among the causes of intrahepatic biliary disease are
primary biliary cirrhosis and secondary biliary cirrhosis.
Primary Biliary Cirrhosis
Primary biliary cirrhosis is a chronic disease of the liver
characterized by the autoimmune destruction of the
medium-sized intrahepatic bile ducts with cholestasis and
eventual development of cirrhosis and liver failure.
3,22
Cirrhosis develops only after many years; thus, the name
primary biliary cirrhosis
is somewhat misleading for per-
sons diagnosed early in the precirrhotic stage.
3
The disease is seen most commonly in women 40 to
60 years of age. Both the incidence and prevalence are
increasing, and geographic clustering of the disease has
been reported, suggesting genetic and environmental
factors are important in its pathogenesis. Family mem-
bers of persons with the disease have increased risk of
developing the disease. The disease may be associated
with other autoimmune disorders such as Sjögren syn-
drome (sicca complex of dry eyes and mouth), autoim-
mune thyroid disease, rheumatoid arthritis, Raynaud
phenomenon, and celiac disease.
The disorder is characterized by an extremely insidi-
ous onset, and persons may be symptom-free for many
years. Morphologically, there is progressive scarring and
destruction of liver tissue. The liver becomes enlarged
and takes on a green hue because of the accumulated
bile. The earliest symptoms are unexplained pruritus
(itching), weight loss, and fatigue, followed by dark
urine and pale stools. Vitamin D malabsorption–related
osteoporosis occurs in up to one third of persons with
the disorder.
22
Jaundice is a late manifestation of the dis-
order, as are other signs of liver failure. Serum alkaline
phosphatase (ALP) levels are elevated in persons with
primary biliary cirrhosis.
Treatment for primary biliary cirrhosis is ursodeoxy-
cholic acid (ursodiol), a drug that increases bile flow
and decreases the toxicity of bile contents, and has been
shown to decrease the rate of clinical deterioration.
Cholestyramine, a bile acid–binding drug, or rifampi-
cin can be beneficial for treatment of pruritus. Liver
transplantation, however, remains the only treatment
for advanced disease. Primary biliary cirrhosis does not
recur after liver transplantation if appropriate immuno-
suppression is used.
Secondary Biliary Cirrhosis
Secondary biliary cirrhosis results from prolonged
obstruction of the extrabiliary tree.
3
The most common
cause is cholelithiasis (gallstones). Other causes of sec-
ondary biliary cirrhosis are malignant neoplasms of the
biliary tree or head of the pancreas and strictures of the
common duct caused by previous surgical procedures.
Extrahepatic biliary cirrhosis may benefit from surgical
procedures designed to relieve the obstruction.
Drug- and Alcohol-Induced Liver
Disease
By virtue of its many enzyme systems that are involved in
biochemical processes, the liver has an important role in
the metabolism of many drugs and chemical substances.
The liver is particularly important in the metabolism of
lipid-soluble substances that cannot be directly excreted
by the kidney.
Drug Metabolism
There are two major types of reactions involved in
the hepatic detoxification and metabolism of drugs
and other chemicals: phase 1 and phase 2 reactions.
23
