Treating and Preventing Complications of Cirrhosis
ABSTRACT: Earlier diagnosis of cirrhosis and its complications and earlier interventions make more therapeutic options available.
CME OBJECTIVE: The reader will understand the major complications of cirrhosis and be aware of appropriate preventive and therapeutic options.
Brendan M. McGuire, MD, grants and research support Protective Life Inc. and Roche
Preventing and treating complications of cirrhosis early may provide better longitudinal care and more therapeutic opportunities for the 400,000 Americans who often have silent symptoms for years before diagnosis.
"Despite recent advances in cirrhosis treatment approaches, esophageal varices and hepatocellular carcinoma remain frequent, and potentially fatal, complications," UAB hepatologist Brendan M. McGuire, MD, says. "In fact, 1 of every 25 patients with hepatitis C and cirrhosis may develop hepatocellular carcinoma. Intervening as early as possible dramatically increases available treatment options."
Delaying Disease Progression
Finding strategies that help prevent or delay progression of cirrhosis is one of McGuire's goals as principal investigator of the UAB Interdisciplinary Cirrhosis Clinic, where patients have access to the latest diagnostic tools, treatments, and clinical trials. The clinic provides patient education extending from basic information about the liver and how it functions to treatments for potential complications and ways to prevent or delay disease progression. The clinic evaluates patients for hepatitis, hepatocellular carcinoma, variceal bleeding, spontaneous bacterial peritonitis, hepatopulmonary syndrome, hepatorenal syndrome, and liver transplantation. A planned Web site will soon allow patients access to detailed information about the clinic and its services.
"Early symptoms of cirrhosis include itching, fatigue, loss of appetite, anorexia, abdominal pain, nausea, and weakness. Patients may present with clinical features such as jaundice, variceal bleeding, ascites, edema, or hepatic encephalopathy," McGuire says. "Yet, by the time cirrhosis is diagnosed, patients are typically suffering from advanced forms of disease. As cirrhosis progresses, potential complications include hepatocellular carcinoma, hepatopulmonary syndrome, and hepatorenal syndrome."
Diagnosing Cirrhosis
Cirrhosis can be definitively diagnosed by liver biopsy, McGuire says. "However, biopsy may be contraindicated in patients with significant ascites or coagulopathy. Cirrhosis should be considered in the presence of splenomegaly or a history and physical exam revealing suspicious symptoms. A presumptive diagnosis can be made on the basis of computed tomography scan, ultrasound, or magnetic resonance imaging."
Cirrhosis usually progresses as a chronic, insidious process from long-term alcohol abuse, chronic viral infection such as hepatitis B or C, metabolic disorders such as hemochromatosis or Wilson disease, or autoimmune diseases, including autoimmune hepatitis, primary biliary cirrhosis, or primary sclerosing cholangitis. Outside the United States, cirrhosis is among the leading causes of death and is commonly caused by hepatitis B. Closer to home, one of the leading causes of cirrhosis today is hepatitis C, which has infected nearly 4 million Americans, according to the Centers for Disease Control and Prevention.
Complications of Cirrhosis
"As liver disease progresses, changes occur in the cirrhotic patient's hemodynamic circulatory state. These circulatory disturbances include portal hypertension and portosystemic shunting and increases in cardiac output, heart rate, and effective circulating blood volume, along with decreases in systemic vascular resistance and arterial blood pressure. These alterations contribute to many of the cardiac, pulmonary, and renal complications associated with cirrhosis," McGuire says.
One common complication cirrhotic patients develop is ascites. Treatment options include dietary salt restriction, diuretics such as furosemide or spironolactone, abdominal paracentesis, peritoneo-venous shunts, or transjugular intrahepatic portosystemic shunts. While McGuire generally advises a 2000 mg per day salt-restricted diet, he says limiting salt is extremely difficult, and patients must read nutritional labels carefully to measure sodium intake.
"Another complication of cirrhosis is hepatic encephalopathy, a reversible neuropsychiatric syndrome with metabolic abnormalities but no major neuropathic findings. The syndrome is treated with lactulose and/or antibiotics to purge the gut of ammonia and decrease colonic concentration of ammonia-producing bacteria," he says.
Esophageal varices will occur in up to 70% of cirrhotic patients with no prior upper gastrointestinal bleed (Hepatology. 1997;25:1346-1350 and Semin Liver Dis. 1999;19:475-505). The complication is fatal for nearly one third of cirrhotic patients who develop it, yet, variceal bleeding rates could drop from 70% to 40% if patients are medically managed with nonspecific b-blocker therapy (Gastroenterology. 2002;122[6]:1620-1630).
"All cirrhotic patients should be evaluated for varices with esophagogastroduodenoscopy. If no varices are seen or only small varices are present, the test should be repeated in 2 years. Patients with clinical signs of cirrhosis and those with significant varices should be treated with nonselective b-blockers, such as propranolol or nadolol, to prevent initial bleeding or rebleeding of ruptured varices. Nadolol is less lipophilic, is not metabolized by the liver, and does not cross the blood-brain barrier, so it is usually better tolerated than other nonselective b-blockers," McGuire says.
Mononitrates have also been used to decrease portal pressures but can cause more systemic vasodilation and are associated with increased mortality in cirrhotic patients aged 50 years and older.
In patients with cirrhosis, hepatorenal syndrome may occur as hyperdynamic circulatory changes progress. "Hepatorenal syndrome occurs in about one fifth of cirrhotic patients with tense ascites," McGuire says. "The renal arteries constrict, and the kidneys inappropriately retain fluid despite systemic fluid overload. Prognosis for people with hepatorenal syndrome is poor, and liver transplantation is the only proven treatment."
Cirrhotic patients also are at risk for hepatopulmonary syndrome, a triad of portal hypertension, intrapulmonary vasodilation, and hypoxemia. "Hepatopulmonary syndrome occurs in up to 20% of patients with cirrhosis. It is diagnosed by excluding major intrinsic cardiopulmonary disease and documenting intrapulmonary vasodilation with contrast echocardiography and/or perfusion lung scanning and hypoxemia by arterial blood gases. Liver transplantation reverses intrapulmonary vasodilation and hypoxemia," he says.
Hepatitis C-induced Cirrhosis
In 2004, the number of Americans who died with hepatitis C-induced cirrhosis exceeded the total number of liver transplants. "Many clinics have considered patients with hepatitis C-induced cirrhosis poor candidates for treatment with peginterferon and ribavirin," McGuire notes. "We would like to change the hepatitis C management paradigm by aggressively treating patients who will benefit most from therapy. The UAB Interdisciplinary Cirrhosis Clinic has a staff of seven hepatologists, strong clinical research programs, and partners with UAB's nationally recognized liver transplant program, making the clinic an ideal treatment environment for these patients," he says.
Liver Transplantation
"A healthy lifestyle and adherence to medical management may delay cirrhotic progression, but ultimately, many patients will face liver transplantation as their only option," McGuire says. UAB's Liver Transplant Program has performed more than 1000 liver transplants in its 16-year history, and the program's 90% 1-year survival rate is higher than the national average. In fact, a significant number of patients are celebrating 10 years or more of posttransplant survival.
Multidisciplinary Expertise
"Our clinic team includes gastroenterologists, hepatologists, transplantation surgeons, neuropsychologists, nutritionists, physical medicine and rehabilitation specialists, and support staff," McGuire says. "We provide a complete evaluation to screen for and treat potentially life-limiting cirrhotic complications, maximizing quality of life by improving physical and mental well-being."
For more information
Dr. Brendan McGuire
1.800.UAB.MIST
mist@uabmc.edu
Published in UAB Insight, Spring 2005