Use of the BreathID to Assess Hepatic Metabolic Reserve and to Predict Hepatic Decompensation in Patients With Cirrhosis in Need of Liver Transplantation

BACKGROUND:

1. Mortality in patients with chronic liver disease and cirrhosis:

Chronic liver disease is the 9th most common cause of death in the United States. Unfortunately, mortality secondary to chronic liver disease, cirrhosis and its complications is expected to increase in the future. This is primarily due to the maturation of the Hepatitis C Virus (HCV) epidemic, a rising rate of hepatocellular carcinoma (HCC)and an increasing prevalence of non-alcoholic steatohepatitis (NASH).

Mortality in patients with chronic liver disease is typically confined to patients with cirrhosis; and the mortality risk in these patients has long been assessed by the Child-Pugh-Turcotte (CTP) score. More recently, the Model of End-Stage Liver Disease (MELD) has been shown to more accurately predict 30 day survival in patients with cirrhosis. The MELD score is now utilized by the United Network for Organ Sharing (UNOS) to prioritize patients awaiting liver transplantation.

In general, declining liver function and an increase in the CTP and/or MELD scores are precipitated by the complications of cirrhosis; gastrointestinal bleeding from portal hypertension (variceal and non-variceal), ascites, spontaneous bacterial peritonitis (SBP), hepatic encephalopathy (NE), hepato-renal syndrome (types 1 and 2) and HCC. Patients are considered to have stable cirrhosis when they have intact hepatic function and no prior complications of cirrhosis. Such patients have a CTP score of less than 7; reflective of Childs class A cirrhosis. Approximately 3-5% of patients with stable Child class A cirrhosis will develop worsening in hepatic function and/or complications of cirrhosis and decompensate on a yearly basis. In many patients the development of these complications, the deterioration in global liver function and the rise in MELD is a slow gradual process which allows sufficient time for successful transplantation. In contrast, approximately one-third of patients with cirrhosis develop rapid hepatic decompensation a precipitous rise in MELD and die from complications of cirrhosis before they can either be considered for or receive a liver transplant. This observation explains why pre-transplant mortality for patients on the UNOS waiting list is actually greatest in patients with low MELD, not high MELD scores. It is currently believed that such patients have marginal hepatic metabolic capacity or hepatic reserve which both places them at risk for developing complications of cirrhosis and for rapid deterioration when complications occur. 2. Identifying patients with marginal hepatic reserve at risk for complications and decompensation: