In people with liver disease, predicting whether the liver will eventually fail is not always easy. Once acute liver failure is imminent, doctors must then quickly decide whether or not the patient is a candidate for a liver transplant or not.

In fact, experts describe acute liver failure as "one of the most intriguing and challenging conditions in the entire field of internal medicine."¹

Helping Physicians Make Prognoses
Now, a new study points to a possible biological indicator in the body that could help doctors determine which of their patients face a poor prognosis, and thus, need a liver transplant.² Doctors in Australia say higher levels of blood lactate is the marker that may indicate such a grim prognosis for these patients.

According to the study authors, up to 7% of all liver transplants are performed because of fulminant, or acute, liver failure. But because complications can arise during surgery and also due to the fact that some patients with this condition can recover before a transplant is performed, it is highly important that doctors make rather expeditious decisions about whether or not the patient should have such a transplant.

Current Prognostic Methods
There are various methods already in place that doctors can use to establish a patient's prognosis, such as the King's College Hospital criteria, which is the most widely used. These criteria help establish a person's prognosis in the context of liver disease by measurements of certain blood substances in the body. However, while these criteria can be helpful in indicating the need for a transplant, they do not predict which patients might survive without one. Among other things, the criteria establishes thresholds in terms of levels of certain blood chemicals, the amount of time it takes for blood to clot, and the progression of a patient's encephalopathy, a degenerative brain disease associated with liver failure.³

New Indicators Emerging?
For their study, researchers in the department of Gastroenterology and Hepatology at the Sir Charles Gairdner Hospital in Nedlands, Australia examined the potential effectiveness of two markers that could play a role in predicting acute liver failure prognosis: blood levels of phosphate or lactate. It has been suggested that abnormally high levels of these substances in the bloodstream may indicate that patients with fulminant liver failure may not recover without a transplant. So, the researchers led by Dr. Gerry MacQuillan in the department of Medicine set out to determine which of these two substances may be of more prognostic value.

The study involved information on 83 patients with fulminant liver failure admitted to the Liver Unit at Queen Elizabeth Hospital in Birmingham, England over a 3-year period. Patients were divided into groups comprised of those who survived with medical treatment, those who underwent a liver transplant, and those who died. Patients were also grouped based on whether or not they had overdosed on paracetamol (Tylenol), a common cause of acute liver failure.

Of all 83 patients, 58 percent survived with standard medical treatment, about one-fourth underwent liver transplant procedures, and the remaining 19 percent had died. Of those who had overdosed on paracetamol, a much higher recovery rate was found: 73 percent of the patients survived with medical treatment, compared to 26 percent of those who had not overdosed.

Phosphate Levels Had Little Value
MacQuillan and his team found that blood levels of phosphate were significantly higher in those patients who died or who underwent a transplant. But there was not a significant difference in phosphate levels between the patients who had died and those who were treated without having a transplant.

However, the researchers found that levels of lactate in the blood were significantly higher during a 12-hour period following hospital admission in acute liver failure patients who eventually died or underwent a transplant, and this difference was also seen between those who died and those who survived with other medical treatment besides a transplant. In those who died, lactate levels were consistently higher, the research team found. These differences in lactate levels were seen regardless of whether or not a patient had overdosed on paracetamol.

As a result, MacQuillan's group concluded that significantly higher levels of lactate in the blood can predict a poorer prognosis for those with fulminant liver failure as compared to levels of phosphate. "Our data has showed that serial blood lactate measurements were higher in non-survivors, with increasing significance in relation to time," the study team wrote. "This raises the importance of close monitoring of serial arterial blood lactate levels."

Other Experts: Measuring Lactate May be Useful
In an editorial connected to this study,⁴ Obaid Shakil, MD, of the division of Gastroenterology, Hepatology, and Nutrition at the University of Pittsburgh School of Medicine wrote that in determining whether patients with fulminant liver failure need a transplant or not, decisions must be made rather quickly, relative to other liver diseases. Additionally, the current criteria used to help doctors determine a patient's prognosis are inadequate, Shakil wrote.

Any delay in such decisions about treatment could result in life-threatening complications like worsening cerebral edema and multiorgan failure, he explained.
 
However, the apparent value of measuring blood levels of lactate may be valuable to doctors who otherwise have little to go on. "If validated by well-powered prospective studies, blood lactate level may serve as an additional criteria to the well-tested King's College Hospital criteria," he wrote.

However, Shakil was quick to caution that doctors should not rely solely on these tests, but instead, should incorporate them into a comprehensive plan of action that includes other available information about a particular patient's case.

"Even the best-developed prognostic model has its limitations," Shakil explained. "Despite belonging to a well-defined disease state such as 'fulminant [liver] failure', there is considerable variation among individual patients, particularly when a large number of variables are assessed."

1. Schiodt FV, Lee WM. Fulminant liver disease. Clin Liver Dis 2003 May;7(2):331-49, vi.
2. MacQuillan GC, Seyam MS, Nightingale P, Neuberger JM, Murphy N. Blood lactate but not serum phosphate levels can predict patient outcome in fulminant hepatic failure. Liver Transpl 2005 Sep;11(9):1073-9.
3. Marrero J, Martinez FJ, Hyzy R. Advances in critical care hepatology. Am J Respir Crit Care Med 2003 Dec 15;168(12):1421-6.
4. Shakil AO. Predicting the outcome of fulminant hepatic failure. Liver Transpl 2005 Sep;11(9):1028-30.

John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.