Published in the September 2012 issue of Today’s Hospitalist
WHEN HOSPITALISTS ENCOUNTER PATIENTS WITH decompensated liver disease, they probably should worry less about hemorrhage and focus more on paracentesis. While they’re at it, hospitalists should also probably order albumin and prescribe antibiotics more frequently, and remember that beta-blockers can be helpful after variceal band ligation.
Those were the take-home messages at a session on managing decompensated liver disease at this spring’s Society of Hospital Medicine annual meeting. James R. Burton Jr., MD, a gastroenterologist, associate professor of medicine and medical director of liver transplantation at the University of Colorado Hospital, addressed a number of concerns that hospitalists have about treating patients with decompensated liver disease who need medical care while waiting for liver transplants.
Albumin for spontaneous bacterial peritonitis
About 12% of hospitalized patients will develop spontaneous bacterial peritonitis (SBP). Even when treated with antibiotics, the infection leads to renal failure in about one-third of those patients.
Dr. Burton reminded his audience that cirrhotic patients who develop renal failure have increased mortality. Part of the problem, he pointed out, is that many hospitalized patients with SBP do not exhibit classic symptoms of infection, such as abdominal pain or fever.
That’s why he’s adopted this maxim: “If you are sick enough to have cirrhosis and be in the hospital,” said Dr. Burton, “you are going to need a needle in your abdomen to rule out SBP.”
Albumin “the most abundant protein in blood plasma “has an important role to play in treating some of these patients. Recent studies have shown that cirrhotic patients not only have low albumin levels, but that their albumin may not work well to transport fatty acids, hormones and drugs.
A well-known study in the Aug. 5, 1999, issue of the New England of Journal of Medicine found that cirrhotic patients with SBP had fewer incidences of renal failure and death when albumin was added to cefotaxime treatment, compared to those treated with cefotaxime alone.
But a more recent study in the April 2007 issue of Gut found that those benefits help only high-risk patients. Based on that research, Dr. Burton said he now believes that albumin can be reserved for those patients with SBP whose serum bilirubin count is greater than 4 mg/dL and/ or whose BUN exceeds 30 mg/dL.
When giving albumin to liver patients, he prefers using 25% albumin because 5% solutions are high in sodium.
Cirrhotics with GI bleeds
Cirrhotic patients also run a higher risk of developing bacterial infections in the hospital if they have gastrointestinal bleeding. Dr. Burton said these patients are at particularly high risk for renal impairment “and infection can make bleeding worse.
As early as 1985, Dr. Burton said, clinicians knew that antibiotics could prevent infection in cirrhotics with GI hemorrhage. Studies have also found that antibiotics improve mortality.
Ceftriaxone appears to be the best antibiotic in these situations, Dr. Burton explained. He recommends writing automatically for ceftriaxone whenever you prescribe octreotide for cirrhotic patients with variceal bleeding. Patients should take the antibiotics for five to seven days in therapeutic “not prophylactic “doses.
Beta-blockers after variceal band ligation
Variceal bleeding is associated with high mortality rates. “If you do nothing,” Dr. Burton said, “patients are likely to re-bleed.”
That’s why many liver disease patients are referred for endoscopic variceal band ligation therapy. Studies show that treating patients with beta-blockers along with variceal band ligation helps more than just doing the procedure alone.
“Nonselective beta-blockers reduce portal hypertension, which reduces cardiac output and portal blood inflow,” Dr. Burton pointed out. “Beta-blockers have been shown to reduce the incidence of a first variceal bleed by 15% to 25%, and the effect is greater in medium to large varices.”
An important study published in the March 2005 issue of Hepatology showed that more patients were likely to be free of variceal rebleeding with a combination strategy of endoscopic variceal ligation plus nadolol. A meta-analysis in the July 15, 2008, Annals of Internal Medicine also found that combination therapy worked better than either endoscopic or drug therapy alone.
Dr. Burton suggested making sure that these patients aren’t having ongoing recurrent bleeding, then discontinuing octreotide, and finally switching to a nonselective beta-blocker such as 20 mg propranolol given twice a day or 20 mg nadolol given once a day. The goal then becomes titrating patients to a maximal tolerated dose as heart rate and blood pressure allow.
“Unfortunately, patients get started on these medications and are sent home, and they don’t come anywhere near reaching the goal,” Dr. Burton said. During the discharge process, he said, hospitalists should make sure not only that the proper beta-blockers have been started, but that patients have a follow-up appointment with their referring doctor the following week to check heart rates, blood pressures, symptoms and beta-blocker dose.
Another common concern is the safety of paracentesis, particularly when patients have an underlying coagulopathy. In the U.S., about 85% of cases of ascites will be due to cirrhosis. Of these, most (70%) will have abnormal prothrombin times.
But Dr. Burton reminded hospitalists that “coagulation tests don’t reflect the risks in cirrhotics, given the balance of procoagulants and anticoagulants.” Doctors shouldn’t interpret these tests to mean that paracentesis in these patients is risky.
“Serious complications with paracentesis are very unusual, with less than one in 1,000,” he said. During paracentesis, he does not regularly give patients fresh frozen plasma or platelets.
Managing hepatorenal syndrome
Many physicians find managing the care of patients with functional renal failure in the setting of advanced liver disease frustrating. Kidney failure, however, is potentially reversible if patients can get a liver transplant. “There are a number of studies,” said Dr. Burton, “of people who got kidney transplants at the time of liver transplantation and now have three functioning kidneys.”
About 8% of cirrhotic patients with ascites will develop hepatorenal syndrome each year, he explained. Type 2, characterized by moderate and steady functional renal failure, is the most common, and it is often seen in patients with refractory ascites. Type 1 is rapidly progressive renal failure, which is often brought on in a patient with type 2 hepatorenal syndrome by a precipitating event like SBP.
While the only treatment for type 1 is a liver transplant, type 2 can be treated. Sometimes, treatment consists of transjugular intrahepatic portosystemic shunts. More frequently, however, treatment is vasoconstrictor medications. The most frequently studied therapies are midodrine, octreotide and terlipressin, along with albumin.
Commonly used in Europe, terlipressen is not approved by the FDA. It appears to have the best results in improving renal function in patients with type 2 hepatorenal syndrome, according to several recently published studies.
Holding up FDA approval, said Dr. Burton, is the question of whether the drug improves patients’ survival rate when used with albumin. Terlipressen does, however, improve renal function better than a strategy of using midodrine plus octreotide and albumin, and Dr. Burton said he’s hoping for FDA approval.
“I think terlipressin may become an effective bridge to transplant for patients with hepatorenal syndrome,” he said.
Deborah Gesensway is a freelance writer who covers U.S. health care from Toronto.