Primary Biliary Cirrhosis (cont.)
John M. Vierling, MD, FACP
John M. Vierling, MD, FACP
John M. Vierling M.D. is Professor of Medicine and Surgery at the Baylor College of Medicine in Houston, Texas, where he also serves as Director of Baylor Liver Health and Chief of Hepatology. In addition, he is the Director of Advanced Liver Therapies, a center devoted to clinical research in hepatobiliary diseases at St. Luke's Episcopal Hospital. Dr. Vierling is board certified in internal medicine and gastroenterology and a Fellow of the American College of Physicians.
Leslie J. Schoenfield, MD, PhD
Leslie J. Schoenfield, MD, PhD
Dr. Schoenfield served as associate professor of medicine and consultant in gastroenterology on the faculty of the Mayo Clinic for seven years. He became a professor of medicine in residence at UCLA from 1972 to 1999 (now emeritus). He was the director of gastroenterology at Cedars-Sinai Medical Center in Los Angeles for 25 years, where he received the chief resident's teaching award, the president's award, and the pioneer of medicine award.
In this Article
What are the manifestations of the complications of cirrhosis in PBC?
The manifestations of the following complications of cirrhosis will be discussed:
Edema and ascites
As cirrhosis of the liver develops, signals are sent to the kidneys to retain salt and water. This excess fluid first accumulates in the tissue beneath the skin of the ankles and legs (due to the pressure of gravity). This accumulation of fluid is called edema or pitting edema. Pitting edema refers to the observation that pressing a fingertip against a swollen ankle or leg causes an indentation that persists for some time after release of the pressure. Actually, any type of sufficient pressure, such as from the elastic part of socks, can produce pitting edema. The swelling often is worse at the end of the day and may lessen overnight. As more salt and water are retained and liver function decreases, fluid may also accumulate in the abdomen. This accumulation of fluid (called ascites) causes swelling of the abdomen.
Bleeding from varices
In cirrhosis, the scar tissue (fibrosis) and the regenerating nodules of hepatocytes block (obstruct) blood flow in the portal vein in virtually all patients. The portal vein carries blood from the intestines, spleen, and other abdominal organs to the liver on the way back to the heart and lungs. The build-up of pressure caused by the blockage in the portal vein is called portal hypertension. When pressure in the portal vein becomes high enough, it causes blood to flow through alternative vessels (paths of lesser resistance.) Often, these vessels include veins in the lining of the lower part of the esophagus and the upper part of the stomach.
When these veins distend (dilate) because of the increased blood flow and pressure, they are referred to as esophageal or gastric varices, depending on where they are located. So, portal hypertension and varices develop in PBC after cirrhosis is established. Only a minority of patients with PBC develops portal hypertension and varices before cirrhosis occurs. The higher the portal pressure, the larger are the varices (distended veins).
Accordingly, patients with large varices are at risk for the varices to burst and bleed into the gut. It is recommended, therefore, that patients with PBC have an upper endoscopy done at the time of diagnosis and approximately every three years thereafter to detect and then, if necessary, treat the varices. An upper endoscopy is a direct look with a tubular instrument (an upper endoscope) into the esophagus and stomach.
The protein in our diet is converted by bacteria normally present in the gut into substances that can alter the function of the brain. When these substances (ammonia, for example) accumulate in the body, they become toxic. Ordinarily, these potentially toxic compounds are carried in the portal vein to the normal liver where they are detoxified.
When cirrhosis and portal hypertension are present, part of the blood flow in the portal vein, as already described, bypasses the liver by flowing through alternative blood vessels. Some of the toxic compounds take this bypass route and, thereby escape detoxification by the liver. The rest of the toxic compounds travel with the rest of the portal blood flow to the liver. However, a damaged liver may be functioning so poorly that it cannot detoxify the toxic compounds present in the portal blood. In this situation, the toxic compounds can go right through the liver and escape detoxification.
Thus, in these two ways, in variable proportions - going around (bypassing) the liver and going right through the liver -- the toxic compounds accumulate in the blood. When the accumulated toxic compounds in the blood stream impair the function of the brain, the condition is called hepatic encephalopathy. Sleeping during the day rather than at night (reversal of the normal sleep pattern) is among the earliest symptoms of hepatic encephalopathy. Other symptoms include irritability, inability to concentrate or perform calculations, loss of memory, confusion, or depressed levels of consciousness. Ultimately, severe hepatic encephalopathy causes coma.
The spleen normally acts as a filter removing older red blood cells, white blood cells, and platelets (small particles that help stop bleeding from a cut surface) from the blood. As the portal pressure rises, it increasingly blocks blood flow from the spleen to the liver. The resulting backward pressure in the blood vessels coming from the spleen causes the organ to enlarge (splenomegaly). Sometimes, the spleen is stretched so large that it causes abdominal pain.
As the spleen enlarges, it filters out more and more of the blood elements. Hypersplenism is the term used to describe splenomegaly associated with a low red blood cell count (anemia), low white blood cell count (leucopenia), and/or low platelet count (thrombocytopenia). The anemia can cause weakness, the leucopenia contributes to susceptibility to infections, and the thrombocytopenia can impair the clotting of blood.
Patients with advanced liver disease and portal hypertension can sometimes develop the hepatorenal syndrome. This syndrome is a serious problem with the functioning of the kidneys without actual physical damage to the kidneys themselves. The hepatorenal syndrome is defined by progressive failure of the kidneys to clear substances from the blood and produce adequate volumes of urine even though some other kidney functions, such as retention of salt, are maintained. If liver function improves or a healthy liver is transplanted into a patient with hepatorenal syndrome, the kidneys often begin to work normally. This restoration of kidney function indicates that liver failure is associated with an inability of the liver to either produce or detoxify substances that affect kidney function.
Rarely, some patients with advanced cirrhosis can develop the hepatopulmonary syndrome. These patients can experience difficulty with breathing because certain hormones released in advanced cirrhosis cause abnormal functioning of the lungs. The basic lung problem in the hepatopulmonary syndrome is that the blood flowing through the small vessels in the lungs does not come in sufficient contact with the alveoli (air pockets) of the lungs. Therefore, the blood cannot pick up enough oxygen from the air that is breathed and the patient experiences difficulty breathing.
Liver cancer (hepatocellular carcinoma)
Patients with PBC that develop cirrhosis have an increased risk of developing a primary cancer of the liver cells (hepatocytes) called liver cancer (hepatocellular carcinoma). Primary refers to the fact that the tumor originates in the liver. A secondary tumor originates elsewhere in the body and can spread (metastasize) to the liver.
Cirrhosis due to any cause increases the risk of liver cancer. Therefore, the development of a primary liver cancer in an individual with PBC is not unexpected. However, the risk of hepatocellular carcinoma in PBC appears to be lower than the risk in cirrhosis caused by some other liver diseases, such as chronic viral hepatitis. A 2003 report indicated that hepatocellular carcinoma might be more common in men than women with PBC. Indeed, this one series of 273 patients with advanced PBC found hepatocellular carcinoma in 20% of the men compared to only 4.1% of the women. The way hepatocellular cancer develops in PBC, however, is not understood.
The most common symptoms and signs of primary liver cancer are abdominal pain and swelling, an enlarged liver, weight loss, and fever. In addition, these liver tumors can produce and release a number of substances, including ones that cause an increase in red blood cells (erythrocytosis), low blood sugar (hypoglycemia), and high blood calcium (hypercalcemia).
The most useful diagnostic tests for hepatocellular carcinoma are a blood test called an alpha-fetoprotein and an imaging study of the liver (either a CT Scan or an MRI with intravenous dye/contrast). The best screening tests for early detection of hepatocellular carcinoma in patients with cirrhosis are serial alpha-fetoprotein levels and ultrasound examinations of the liver every 6 to 12 months. It is important to note that about 40% of hepatocellular cancers do not produce elevated levels of alpha-fetoprotein.
Medically Reviewed by a Doctor on 1/9/2014
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