The use of MELD scores in critically ill cirrhotic patients

The Model for End-Stage Liver Disease (MELD) was originally created to predict survival following transjugular intrahepatic portosystemic shunt and was subsequently found to accurately predict mortality in patients with end-stage liver disease. It has been used in the United States for liver allocation since 2002, and implementation of the MELD score resulted in a reduction in total number of deaths on the waitlist and a reduction in waiting time. Critically ill cirrhotic patients have an in-hospital mortality greater than 50%. Although the MELD score was also found to be an accurate predictor of in-ICU mortality and in-hospital mortality after ICU admission in critically ill cirrhotic patients, the Sequential Organ Failure Assessment (SOFA) score appears to perform better in many studies. The Chronic Liver Failure Consortium Acute-onChronic Liver Failure (CLIF-C ACLF) score was later developed by using specific cut-points for each organ failure score system in CLIF patients to predict mortality in patients with ACLF. Neither the MELD nor SOFA score independently predicts post-liver transplantation mortality in cirrhotic patients with extrahepatic organ failure and should not be use as a delisting criterion for these patients. More data are needed to determine the accuracy of the CLIF-C ACLF score in predicting post-liver transplantation outcomes. Prospective evaluation of critically ill cirrhotic patients is needed to optimize liver organ allocation. Key words-Cirrhosis, MELD score, SOFA score


INTRODUCTION
The Model for End-Stage Liver Disease (MELD) is a numerical scale, ranging from 6 to 40, that was originally created to predict survival following transjugular intrahepatic portosystemic shunt (TIPS) for refractory variceal bleeding or refractory ascites. 1 The score is calculated by a formula using serum bilirubin, serum creatinine, and the International Normalized Ratio (INR).It was later adopted by the United Network for Organ Sharing (UNOS) to determine priority for liver organ allocation in the United States in February 2002. 2 The MELD score predicts liver transplantation (LT) waitlist mortality with estimated three-month mortality of 4%, 27%, 76%, 83%, and 100% for MELD scores of <10, 10-19, 20-29, 30-39, and ≥ 40, respectively. 3 Implementation of the MELD score for organ allocation resulted in a reduction in total number of deaths on the waitlist and a reduction in waiting time. 4In January 2016, the MELD-Na score was implemented for LT allocation, as hyponatremia also strongly predicts mortality in these patients. 5- 7Apart from prioritizing the urgency for LT, the MELD score accurately predicts outcomes in cirrhotic patients with infection [8][9][10] , variceal bleeding 11,12 , trauma 13 , and surgery other than LT, including liver resection. 14,15 t is also used as one of the liver-specific prognosis scores for critically ill cirrhotic patients in the intensive care unit (ICU).

Prognostic scoring systems for critically ill cirrhotic patients in ICU
Liver cirrhosis is the 12 th leading cause of death in the United States. 16The prevalence of liver cirrhosis is increasing and is estimated to be present in approximately 630,000 adults in the United States. 17Cirrhotic patients are at an increased risk for developing decompensation related to cirrhosis and portal hypertension, including variceal bleeding, ascites, hepatic encephalopathy, hepato-renal syndrome, spontaneous bacterial peritonitis, and sepsis.Patients with cirrhosis admitted to the ICU have a substantially high mortality rate of 50% to 100%. 18Liver-specific prognosis scores [Child-Turcotte-Pugh (CTP) and MELD] and ICU-specific prognosis scores [Simplified Acute Physiology Score (SAPS) II, Acute Physiology and Chronic Health Evaluation (APACHE), and Sequential Organ Failure Assessment (SOFA)] have been proposed to assess disease severity and outcomes in these patients.

MELD score as a prognostic predictor for cirrhotic patients in ICU
The MELD score is calculated by the formula 3. Unfortunately, other than renal dysfunction, the MELD score does not directly account for other complications of portal hypertension, such as ascites, variceal bleeding, hepatic encephalopathy, hepatopulmonary syndrome, portopulmonary hypertension, and cirrhotic cardiomyopathy.Thus patients with significant decompensation from complications of portal hypertension may have low MELD scores that do not accurately reflect the severity of their liver disease and are at a disadvantage with our current method of organ allocation using the MELD score.A system of exception points has been implemented for those patients with complications of portal hypertension that are not captured by the MELD score, such as hepatopulmonary syndrome and portopulmonary hypertension, to increase their waitlist priority.The MELD score can also be influenced by acute illnesses that alter bilirubin, creatinine, or INR values (Table 1).
The main cause of death in cirrhotic patients in the ICU is multisystem organ failure. 26everal studies have shown that besides hepatic failure, cardiovascular system dysfunction 27,28 , renal failure 21,29 , elevated lactate [30][31][32] , and ascites 32 were independent factors for mortality.Unlike the MELD score which focuses only on hepatic and renal function, ICU-specific prognosis scores also consider other organ system dysfunction (Table 2).

Comparing MELD score and ICU-specific scores (SAPS II, APACHE II, SOFA)
Many studies have compared MELD scores with ICU-specific prognosis scores in predicting in-ICU mortality and in-hospital mortality for cirrhotic patients after ICU admission.Most studies have shown that SOFA scores correlate with mortality better than MELD scores [31][32][33][34][35][36][37][38] , APACHE II scores 31,32,34,[38][39][40][41] , and SAPS II scores. 37Das et al reported the presence of five non-hematologic organ failures in the SOFA score at the admission to the ICU was associated with 100% in-hospital mortality. 33oreover, the accuracy of SOFA scores was improved when reassessed at 48 to 72 hours after the admission to the ICU. 18,38 owever, Boone et al reported that both SOFA scores and MELD scores did not perform well in predicting 28-day mortality in the surgical ICU patients. 42ach of the six different organ failures in the SOFA score has a different weight in cirrhotic patients. 43Hematologic failure in SOFA score defined by platelet count < 50 k/μL has no impact on the prognosis in cirrhotic patients 33 New cut-off values for SOFA scores dedicated to cirrhotic patients were proposed resulting in a development of new scoring systems: the Chronic Liver Failure-SOFA (CLIF-SOFA) score and the Chronic Liver Failure Consortium Acute-on-Chronic Liver Failure (CLIF-C ACLF) score.
The CLIF-C ACLF score was specifically developed using data from patients with the diagnosis of ACLF, which was defined as an acute deterioration in liver function in an individual with pre-existing chronic liver disease and hepatic and extrahepatic organ failures. 44Validation of the score was confirmed with external single center prospective cohort study of ACLF patients admitted to the ICU. 37Jalan et al reported that CLIF-C ACLF score correlates with mortality better than the MELD score, MELD-Na score, CTP score, and CLIF-SOFA score in patients with ACLF. 44Sequential use of the score also improves the predictive performance and should be considered as a good prognostic predictor for cirrhotic patients. 44vidence for the MELD score, SOFA score, and CLIF-C ACLF score predicting post-LT outcome is lacking.A systematic review by Cholongitas et al found that the MELD score does not predict post-LT mortality. 45A recent study by Karvellas et al reported that the SOFA score was not associated with an increased risk of 90-day post-LT mortality. 46Optimal organ allocation in cirrhotic patients with extrahepatic organ failure should be prospectively evaluated.

CONCLUSION
The MELD score predicts liver transplantation waitlist mortality and has been used in the United States for liver allocation since 2002.Prior studies have compared the MELD score with ICU-specific prognosis scores in predicting in-ICU mortality and in-hospital mortality of cirrhotic patients after ICU admission.
Although the MELD score was found to be an accurate predictor of mortality in critically ill cirrhotic patients, the CLIF-C ACLF score correlates with mortality better than the MELD score, MELD-Na score, CTP score, and CLIF-SOFA score in patients with ACLF.Thus we recommend the CLIF-C ACLF score as a prognostic predictor for patients with acute-onchronic liver failure.

Table 2 Components of ICU-specific prognosis scores Organ system ICU-specific prognosis scores
SAPS-Simplified Acute Physiology Score; APACHE-Acute Physiology and Chronic Health Evaluation;SOFA-Sequential Organ Failure AssessmentThe Southwest Respiratory and Critical Care Chronicles 2016;4(16)