May 2, 2012

Lab Values Predict Acute-on-Chronic Liver Failure Mortality

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From Medscape Medical News

Daniel M. Keller, PhD

May 2, 2012 (Barcelona, Spain) — High international normalized ratio (INR), serum creatinine, and serum bilirubin levels independently predict mortality in patients with acute-on-chronic liver failure (ACLF).

Although the causes of underlying liver disease and acute liver insults differ in Asia and Western countries, the mortality rates are similar, Hitendra Garg, MD, DM, assistant professor at the Institute of Liver and Biliary Sciences and member of the Department of Gastroenterology at the G.B. Pant Hospital in New Delhi, India, reported here at the International Liver Congress 2012.

ACLF, a condition with high mortality, results from an acute hepatic insult in a patient with diagnosed or undiagnosed chronic liver disease. It manifests as jaundice and coagulopathy followed by ascites and/or encephalopathy. Little is known about the natural history of ACLF and the predictors of survival.

Dr. Garg explained that chronic liver disease in the West is mainly of alcoholic (65%) and viral (17%) origin; in the East, the main causes are hepatitis B virus (HBV) infection (37%) and alcohol (34%).

For this prospective study involving 8 Asian and South Asian countries, the investigators enrolled 340 patients from October 2009 to October 2011 with an acute hepatic insult, bilirubin of at least 5 mg/dL, and INR greater than 1.5, complicated within 4 weeks by ascites and/or encephalopathy in patients with chronic liver disease. Patients were excluded if they had hepatocellular carcinoma, portal vein thrombosis, cardiovascular comorbidities, or sepsis.

Mean patient age was 42 ± 13 years, and there were 3 times as many men as women. They were evaluated and given standard medical treatment.

As expected, the most common causes of chronic liver disease were alcohol and HBV. The most common causes of acute liver insult were alcoholic hepatitis, hepatitis E virus infection, and reactivation of chronic HBV. Dr. Garg said that most of the patients with HBV were given the antiviral drug tenofovir.

At 3-month follow-up, 53% (176 of 340) of the cohort had died. At 1 month, the mortality was 40%. For the 126 evaluated patients who died, the cause was multiorgan failure in 75%, progressive liver failure in 10%, and upper gastrointestinal bleeding in 6%.

In a multivariate analysis, 3 baseline parameters emerged as significant predictors of mortality within 3 months: hepatic encephalopathy (odds ratio [OR], 2.5; 95% confidence interval [CI], 0.28 to 0.73; P = .001), serum bilirubin greater than 21.7 mg/dL (OR, 1.8; 95% CI, 1.02 to 1.10; P = .006), and INR greater than 2.2 (OR, 1.6; 95% CI, 1.1 to 1.7; P = .001).

There was no difference in mortality between patients with HBV reactivation, those with alcoholic hepatitis, and those with other causes, Dr. Garg said.

Session moderator Rajendar Reddy, MD, professor of medicine, director of hepatology, and medical director of liver transplantation at the University of Pennsylvania in Philadelphia, told Medscape Medical News that the definitions of ACLF are different in the East and the West; there is a lot of alcoholic hepatitis, reactivation of HBV, and superinfection with hepatitis A or E in the East.

"In the United States...we see acute infections that cause liver failure in a patient who has stable underlying liver disease, so fundamentally, there's a difference in the definitions," he said. Although Dr. Reddy struggles with whether these findings are clinically useful in the West, he said that ACLF in both regions is associated with increased morbidity and mortality, and that all the patients go on to multiorgan failure.

Dr. Reddy thinks the predictors of mortality should be valid regardless of the causes of ACLF, "although there's one other major difference.... In areas where liver transplantation is available, we potentially could rescue quite a few of those patients, so the mortality rate may not be similar." Dr. Reddy explained.

He called ACLF "an ominous phenomenon," and said strategies are needed to prevent it, including ways to prevent infections.

Dr. Reddy has disclosed no relevant financial relationships.

The International Liver Congress 2012: Abstract 69. Presented April 20, 2012.

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