Background: End stage liver disease (ESLD) and cirrhosis are characterized by symptom burden, decreased quality of life, hospitalizations, unpredictable exacerbations, and limited disease-directed therapies other than liver transplantation (1).  It is a common cause of morbidity (15^th) and death (11^th) in the United States (2,3). This Fast Fact assimilates the evidence to help clinicians more accurately prognosticate in patients with ESLD and cirrhosis. 

Compensated vs decompensated ESLD: Patients with compensated chronic liver failure (meaning liver failure without evidence of current or prior ascites, variceal bleeding, encephalopathy, or jaundice) have a median survival of 12 years (4).  Patients with decompensated cirrhosis or ESLD, have a far poorer median survival of about 2 years without transplantation (5).

The Child’s-Turcotte-Pugh (CTP) Score: It stratifies patients into three severity classes using two subjective and three objective parameters.  Although the CTP was originally created to guide patient selection for portal decompression surgery, it now guides probabilistic prognosis estimates, transplant candidacy, and organ allocation (6-8). Patients who score 5-6 total points are “Class A”; 7-9 total points are “Class B”; and 10-15 points “Class C.” The CTP is limited in its ability to differentiate disease severity and predict a specific mortality estimate. However, available evidence suggests that the 1-year median survival for Class A is nearly 100%, Class B is 80%, Class C is 45% (7,8); 5-year median survival for Class A is ~64%, Class B is 60-75%, Class C is 34-50% (9,10).Many experienced hepatologists have opined that the CTP does not accurately identify Class C patients with a high 90-day mortality. The MELD score was in part created to help clinicians identify patients at risk of dying <90 days more accurately.

	Numerical Value
Variable	1	2	3
Ascites	None	Slight	Moderate/Severe
Encephalopathy	None	Grade 1-2	Grade 3-4
Bilirubin (mg/dL)	< 2.0	2.0-3.0	>3.0
Albumin (mg/L)	> 3.5	2.8-3.5	<2.8
Increase in seconds from normal prothrombin time	1-3	4-6	>6.0

The Model for End-stage Liver Disease (MELD) Score (11-12): It was developed in 2000 and then updated in 2008 to reflect the addition of serum sodium levels (MELD-Na).  It is validated in patients 12 years and older as an independent predictor of survival in patients with cirrhosis (alcoholic and non-alcoholic), acute liver failure, and acute hepatitis.  It is also used by the United Network of Organ Sharing (UNOS) for prioritizing allocation of liver transplantation. It relies on laboratory values alone (serum creatinine, total bilirubin, Na, INR). An additional benefit over CTP is that it can predict prognosis on the order of months with more precision, making it helpful for determining hospice eligibility in the US. The formula to calculate MELD score is complex. Online calculators are available (13).

MELD Score	Predicted 6- month survival	Predicted 12-month survival	Predicted 24-month survival
0-9	98%	93%	90%
10-19	92%	86%	80%
20-29	78%	71%	66%
30-39	40%	37%	33%

Other variables: Many factors which are not accounted for by CTP and MELD-Na greatly affect prognosis in patients with ESLD including age, persistent alcohol use, unmanaged hepatitis B/C, and medical comorbidities such as peripheral vascular disease and heart failure. Therefore, clinician judgement, the rate of decompensation, the likelihood of transplantation and the presence of one or more of the following complications may have more prognostic value than the CTP or MELD score alone.

• Hepatorenal syndrome (HRS) –caused by renal arterial underfilling.  Patients with type-1 HRS (rapid and severe renal failure) have a median survival of 2 weeks with few patients surviving more than 10 weeks even with renal replacement therapy (14,15).  Median survival with type-2 HRS (chronic, less severe with serum creatinine usually 1.5-2 mg/dL) is 3-6 months (14,15).  If the patient survives to transplant, renal function can improve quickly and significantly (16).
• Ascites— presence of excessive peritoneal fluid from portal hypertension resulting in activation of renin angiotensin aldosterone system—suggests a mortality of 50% at 2 years (17).
• Variceal hemorrhage—enlarged veins secondary to portal hypertension that are at risk for rupture and bleeding. There is a 20% of death within 6-weeks following of each bleeding episode (18).
• Hypotension isa well-recognized and dangerous complication of ESLD stemming from portal hypertension.  It is associated with an increased 6-month mortality risk in cirrhosis.
• Hepatocellular carcinoma (HCC) –Chronic inflammation during the progression towards cirrhosis is a risk factor for HCC. Median survival of HCC without treatment is 8 months (19). Patients with Class B or Class C cirrhosis are rarely eligible for disease-directed HCC therapy (19).

References

1. D’Amico, et al. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J Hepatology. 2006; 44:217–231.
2. Cheemerla S & Balakrishana M. Global epidemiology of chronic liver disease. Clinical Liver Disease 2021;17(5):365-370.
3. National Vital Statistics System- Mortality Data (2020)
4. Zipprich A, Garcia-Tsao G, Rogowaksi S, Fleig WE, Seufferiein T, Dollinger MM. Prognostic indicators of survival in patients with compensated and decompensated cirrhosis. Liver Int 2012,32(9):1407-14.
5. Fleming KM, Aithal GP, Card TR, West J. All-cause mortality in people with cirrhosis compared with the general population: a population-based cohort study. Liver Int 2012,32:79-84
6. Diehl A. Alcoholic and nonalcoholic steatohepatitis. In: Goldman L, Ausiello D, eds. Cecil Textbook of Medicine. 22nd ed. Philadelphia, PA: Saunders; 2004:935–6.  
7. Child CG, Turcotte JG. Surgery and portal hypertension. Major Probl Clin Surg. 1964;1:1-85.
8. Cholongitas E, Burroughs AK. The evolution in the prioritization for liver transplantation. Ann Gastroenterol. 2012;25(1):6-13.
9. Angermayr B, Cejna M, et al. Child-Pugh versus MELD score in predicting survival in patients undergoing transjugular intrahepatic portosystemic shunt. Gut. 2003, 52(6):879-885.
10. Khwaja K, Pomfret EA. Chapter 5 – Organ Allocation: The U.S. Model. Editor(s): Busuttil RW, Klintmalm GBG. Transplantation of the Liver (Third Edition), W.B. Saunders, 2015, Pages 64-71

11. Cholongitas, et al. Systematic review: the model for end-stage liver disease – should it replace Child-Pugh’s classification for assessing prognosis in cirrhosis? Alimentary Pharmacol Therapeutics. 2005; 22:1079-1089.
12. Said, et al. Model for end stage liver disease score predicts mortality across a broad spectrum of liver disease.  J Hepatology. 2004; 40:897-903.
13. Last accessed November 1, 2022.  Available at: http://reference.medscape.com/calculator/meld-score-end-stage-liver-disease 
14. Cardenas, et al.  Hepatorenal Syndrome: A dreaded complication of end-stage liver disease.  Am J Gastroenterol. 2005; 100:460-467.
15. Fabrizi F, Aghemo A, Messa P. Hepatorenal syndrome and novel advances in its management. Kidney Blood Pressure Research. 2012;37:588-601.
16. Cassinello C, Moreno E, et al. Effects of orthotopic liver transplantation on vasoactive systems and renal function in patients with advanced liver cirrhosis. Dig Dis Sci 2003; 48:179-186.
17. Moore KP & Aithal GP. Guidelines on the management of ascites in cirrhosis. Gut. 2006;55(6):vi1-vi12.
18. Cremers I & Ribeiro S. Management of variceal and nonvariceal upper gastrointestinal bleeding in patients with cirrhosis. Therapeutic Advances in Gastroenterology. 2014;7(5):206-216.
19. Llovet Jm, Kelley RK, Villaneuva A, Singal AG, Pikarsky E, Roayaie S, Lencioni R, Koike K, Zucman-Rossi J, Finn RS. Hepatocellular carcinoma. Nature Reviews Disease Primers 2021;7(6)

Version History:  Originally published September 2007.  Updated versions published in May 2009 and July 2015. Then a much more significant update occurred in November 2022 by Dr. Angela Chang.

Fast Facts and Concepts are edited by Sean Marks MD (Medical College of Wisconsin) and associate editor Drew A Rosielle MD (University of Minnesota Medical School), with the generous support of a volunteer peer-review editorial board, and are made available online by the Palliative Care Network of Wisconsin (PCNOW); the authors of each individual Fast Fact are solely responsible for that Fast Fact’s content. The full set of Fast Facts are available at Palliative Care Network of Wisconsin with contact information, and how to reference Fast Facts.

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