Porth's Essentials of Pathophysiology, 4e

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Gastrointestinal and Hepatobiliary Function

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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.

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