744
U N I T 8
Gastrointestinal and Hepatobiliary Function
The low pH favors the conversion of ammonia to
ammonium ions, which are not absorbed by the blood.
The acid pH also inhibits the intestinal degradation
of amino acids, proteins, and blood. A nonabsorbable
antibiotic, such as neomycin, or rifaximin may also be
given to eradicate bacteria from the bowel and thus pre-
vent this cause of ammonia production.
38
Treatment.
The treatment of liver failure is directed
toward symptom management; preventing infections;
providing sufficient calories and protein to rebuild and
maintain protein stores; and correcting fluid and elec-
trolyte imbalances. In many cases, liver transplantation
remains the only effective treatment. Currently, 1-year
survival rates approach 90%, and a 5-year survival rate
of 70% to 80% is achieved at many transplantation
centers in the United States.
39
Unfortunately, the short-
age of donor organs severely limits the number of trans-
plantations that are done, and many persons die each
year while waiting for a transplant. Innovative meth-
ods developed to deal with the shortage include split
liver transplantation, in which a cadaver liver is split
and transplanted into two recipients, and living donor
transplantation, in which a segment or lobe from a liv-
ing donor is transplanted.
39
Cancer of the Liver
Malignant tumors of the liver can be primary or meta-
static. Although primary tumors of the liver are rela-
tively rare in developed countries of the world, the liver
shares with the lung the distinction of being the most
common site of metastatic tumors.
Primary Liver Cancers
There are two major types of primary liver cancer: hepa-
tocellular carcinoma, which arises from the liver cells,
and cholangiocarcinoma, which is a primary cancer of
bile duct cells.
3,4
Hepatocellular Carcinoma.
Hepatocellular carci-
noma, the most common form of liver cancer, is the fifth
most common cancer and third leading cause of cancer-
related mortality worldwide.
40
In Europe, Australia, and
the United States, the incidence is approximately 3 cases
per 100,000. There has been an increased incidence,
however, in developed countries as a consequence of
chronic HCV infection.
40
Among the factors identified as etiologic agents in
liver cancer are chronic hepatitis B and C, chronic alco-
holism, nonalcoholic fatty liver disease, and long-term
exposure to environmental agents such as aflatoxin.
3,41
Aflatoxins, produced by food spoilage molds in certain
areas endemic for hepatocellular carcinoma, are partic-
ularly potent carcinogenic agents.
3
They are activated
by hepatocytes and their products incorporated into
the host DNA with the potential for developing cancer-producing mutations.
The manifestations of hepatocellular cancer often
are insidious in onset and masked by those related to
cirrhosis or chronic hepatitis. The initial symptoms
include weakness, anorexia, weight loss, fatigue, bloat-
ing, a sensation of abdominal fullness, and a dull, ach-
ing abdominal pain.
40,41
Ascites, which often obscures
weight loss, is common. Jaundice, if present, usually is
mild. There may be a rapid increase in liver size and
worsening of ascites in persons with preexisting cirrho-
sis. Various paraneoplastic syndromes (e.g., disturbances
due to ectopic hormone or growth factor production by
the tumor (see Chapter 7) have been associated with
hepatocellular cancer, including erythrocytosis (eryth-
ropoietin), hypoglycemia (insulin-like growth factor),
and hypercalcemia (parathyroid-related protein). Serum
α
-fetoprotein, which is present during fetal life but
barely detectable in the serum after the age of 2 years,
is present in 50% of persons with hepatocellular carci-
noma.
3
However, the test lacks specificity and is not very
useful as a surveillance or diagnostic tool. Diagnostic
methods include ultrasonography, CT scans, and MRI.
Liver biopsy may be used to confirm the diagnosis.
Hepatocellular carcinoma is often far advanced at
the time of diagnosis. The treatment of choice is hepatic
resection if conditions permit. Depending on size and
placement of the tumor, other available treatments
include liver transplantation, tumor-directed radio-
frequency ablation, chemoembolization, and radio-
embolization.
41,42
Image-guided ablation is now the
conventional treatment for early-stage hepatocellular
cancer. Ablation induces tumor necrosis by injection of
chemicals (ethanol, acetic acid) or temperature modifica-
tion (radiofrequency, microwave, laser, or cryoablation)
into the tumor area. Sorefenib, a chemotherrapeutic
agent that is taken orally, has recently been approved
for the treatment of hepatocellular carcinoma.
41,42
Cholangiocarcinoma.
Cholangiocarcinoma is a
malignancy of the biliary tree, arising from bile ducts
within and outside the liver. It accounts for 7.6% of
cancer deaths worldwide and 3% of cancer deaths in
the United States.
3
The etiology, clinical features, and
prognosis vary considerably with the part of the bili-
ary tree that is the site of origin. Cholangiocarcinoma is
not associated with the same risk factors as hepatocel-
lular carcinoma. Instead, most of the risk factors revolve
around long-standing inflammation and injury of the
bile duct epithelium. Cholangiocarcinoma often pres-
ents with pain, weight loss, anorexia, and abdominal
swelling or awareness of a mass in the right hypochon-
drium. Tumors affecting the central or distal bile ducts
may present with jaundice.
MetastaticTumors
Metastatic tumors of the liver are much more com-
mon than primary tumors.
3,4
Common sources include
colorectal, breast, lung, and urogenital cancer. In addi-
tion, tumors of neuroendocrine origin spread to the
liver. It often is difficult to distinguish primary from
metastatic tumors with the use of CT scans, MRI, or
ultrasonography. Usually the diagnosis is confirmed by
biopsy.
