USEFULNESS OF MELD SCORE IN PREDICTING IN - HOSPITAL MORTALITY IN PAT I ENTS WITH END STAGE LIVER DISEASE: AN OBSERVATIONAL STUDY

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J of Evolution of Med and Dent Sci/ eISSN- 2278-4802, pISSN- 2278-4748/ Vol. 4/ Issue 45/ June 04, 2015 Page 7734

USEFULNESS OF MELD SCORE IN PREDICTING IN-HOSPITAL MORTALITY

IN PATIENTS WITH END STAGE LIVER DISEASE: AN OBSERVATIONAL

STUDY

Keshava H. K1_{, Chikkalingaiah}2_{, Kamalesh T. N}3_{, Vinayaka G. P}4_{, Shashidhar B}5

HOW TO CITE THIS ARTICLE:

Keshava H. K, Chikkalingaiah, Kamalesh T. N, Vinayaka G. P, Shashidhar B. Usefulness of Meld Score in Predicting in-Hospital Mortality in Patients with End Stage Liver Disease: An Observational Study . Journal of Evolution of Medical and Dental Sciences 2015; Vol. 4, Issue 45, June 04; Page: 7734-7740,

DOI: 10.14260/jemds/2015/1126

ABSTRACT: BACKGROUND/AIMS: Model for End stage Liver Disease (MELD) score was previously used for predicting the outcome in patients undergoing elective Trans-jugular Intrahepatic Porto-systemic Shunts (TIPS) and in patients undergoing liver transplantation. Now-a-days MELD score has been shown to be of much use in predicting outcome in end stage liver disease. Although many studies have done on MELD score for prediction of 3 months and 6 months mortality in end stage liver disease, studies on MELD score for predicting in-hospital mortality is very sparse. AIMS AND OBJECTIVES: To study the usefulness of MELD score for predicting in-hospital mortality in patients with end stage liver disease. METHODS: It is an observational study involving 50 patients with end stage liver disease admitted to our hospital during the period of October 2012 to September 2014 who are fitting into the inclusion criteria. RESULTS: Out of 50 cirrhosis patients, 20 (40%) died within the hospital due to cirrhosis related complications. For analysis, study population was divided into discharge group and death group. Mean hospital stay was found to be 5.8 days in death group and 9.6 days in discharge group. Incidence of Hepatic encephalopathy and Hepatorenal syndrome was significantly higher (p value-0.038) in death group (70% and 30% resp.) compared to discharge group (40% and 23.3% resp.). The mean MELD score was higher in death group (28.5) compared to discharge group (22.03). Based on distribution of MELD score in the study population we calculated the best cut-off point using Youden index (Sensitivity+specicity–1) to predict in-hospital mortality. The best cut-off value came to be 22. At cut off value more than 22, MELD score had 80% sensitivity with good predictive power. CONCLUSION: Our study showed that MELD score is good predictor of in-hospital mortality in patients with end stage liver disease and best cut off value for MELD score is 22, above which the mortality rate is high.

KEYWORDS: MELD, End Stage Liver Disease, in-hospital mortality.

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Of late many studies have been conducted on MELD score in western countries and such studies are very sparse in India especially for predicting in-hospital mortality. There is a need for studies on these mortality predictors in end stage liver disease due to its high burden both on the health care system and the society. Hence this study was undertaken in our tertiary care hospital for the study of MELD score for predicting in-hospital mortality.

MATERIALS AND METHODS:

SOURCE OF DATA: The study was conducted on 50 patients of cirrhosis of liver admitted to KIMS. Hospital, Bangalore during the study period from October 2012 to September 2014.

TYPE OF STUDY: An observational study

METHOD OF COLLECTION OF DATA: Informed consent was obtained from all patients/care takers of the patients enrolled for the study. The data of the patients was collected in a well-designed pro-forma. All the patients with end stage liver disease were screened for exclusion criteria and those who met the inclusion criteria were enrolled for the study. The patients' demographics, presenting complaints, past medical history and detailed examination findings were recorded soon after admission.

The patients are selected based on clinical examinations, biochemical tests and ultrasound abdomen. Severity of cirrhosis of liver was assessed based on child-pugh-turcott score and patients were grouped into class A, B and C according to total score of 5-6, 7-9 and 10-15. MELD score was calculated at admission. The patients are followed until discharge or death in the hospital and were observed for any cirrhosis related complications.

MELD Score was calculated using the following Formula:

0.957×log (Creatinine in mg/dl)+0.378×log (Serum bilirubin in mg/dl)+1.12×log(INR)+0.643 The score is multiplied by 10 and rounded to the nearest whole number.

Inclusion Criteria: All patients more than 18 years of age with cirrhosis of liver (Diagnosed by clinical, biochemical and imaging study).

Exclusion Criteria:

 Patient on diuretic therapy.

 Patients on anti-coagulation therapy at admission.

STATISTICAL METHODS: The following methods of statistical analysis have been used in this study. Data was entered in Microsoft excel and analysed using SPSS (Statistical Package for Social Science, Ver.10.0.5) package,

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A non-parametric test (Distribution-free) used to compare two independent groups of sampled data. A receiver operating characteristic (ROC) curve analysis was used to assess the accuracy of MELD score for identifying risk factor (Death), or for identifying each factor separately. The optimal cutoff points were obtained from the point on the ROC curve which was closest to (0,1). This point was calculated as the minimum value of the square root of [(1-sensitivity) 2+(1-specificity)2]. In all the above test p value of less than 0.05 was accepted as indicating statistical significance.

RESULTS: This study was conducted in KIMS hospital Bangalore from September 2012 to august 2014. Total of 50 patients of end stage liver disease admitted to KIMS were studied. Out of 50 patients with end stage liver disease, 20 (40%) died in the hospital due to cirrhosis related complications (Table 01). For the purpose of analysis, we divided the study population into death group and discharge group and the parameters were compared between each group.

The average age was 44.7±12.040 years in discharge group and 54.1±9.910 years in death group.

The age span was 26–80 years in discharge group and 35 – 73 years in death group. There was male preponderance in both the study groups at a ratio of 4:1 in discharge group and 5.6:1 in death group. Gender difference with respect to in hospital mortality was not statistically significant.

Among the various clinical presentations, the incidence of jaundice (80% vs 62.1%), ascites (80% vs 70%), anemia (85% vs 76.7%) and hypotension (45% vs 13.3%) was higher in the death group. A statistically significant difference was noted with respect to hypotension with a p value of 0.012. The incidence of thrombocytopenia was found to be lower in death group (75%) compared to discharge group (83.3%). However there was no statistical difference with respect to thrombo-cytopenia.

The mean MELD score was found to be higher in death group (28.5) compared to discharge group (22.03) which was statistically very significant (Table 02).

Majority of the patients in the discharge group had MELD score between 10-19 (43.3%) and 30-39 (36.7%). In the death group majority of the patients had score of more than 20 (80%). So the MELD score was significantly higher in death group compared to discharge group (Table 03). The mean hospital stay was 5.8 days in death group compared to 9.6 days in discharge group. The best cut off value of MELD score was found to be 22 calculated using youden index. Using receiver operating curve, sensitivity and specificity of MELD score was calculated. MELD score had sensitivity of 80 % above the cut off value of 22.

OUT COME FREQUENCY %

DISCHARGE 30 60%

DEATH 20 40%

TOTAL 50 100

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Outcome

MELD

Total 2 value p value <9 10-19 20-29 30-39 >=40

Discharged

3 13 2 11 1 30

8.929 0.063 10.0% 43.3% 6.7% 36.7% 3.3% 100.0%

0Death

0 4 6 8 2 20

.0% 20.0% 30.0% 40.0% 10.0% 100.0%

Total

3 17 8 19 3 50

6.0% 34.0% 16.0% 38.0% 6.0% 100.0%

Table 2: distribution of MELD score

Outcome N Mean SD Median Min. Max. p

value

MELD

Discharged 30 22.03 10.759 19.00 7 44

0.002

Death 20 28.50 8.488 28.00 15 44

Total 50 24.62 10.32

9 25.00 7 44

Table 3: Comparison of MELD score between death and discharge group

DISCUSSION: In chronic liver diseases (CLD), accurate prognosis is essential, for prioritization of a patient for organ allocation for liver transplant (LT) and to predict mortality.1_{The Child-Turcott} score was introduced in 1964 which consisted of serum bilirubin (mg/dL), serum albumin (g/dL), ascites, encephalopathy, nutritional status.2_{Pugh (1973) modified this classification by excluding} nutritional status and adding prothrombin time (CTP).3_{CTP score is classified as: A(5-6), B(7-9),} C(10-15), by allotting 1-3 score for each of the five parameters; the higher the score (5-15), the greater the severity of CLD.3

CTP score following limitations: (i) it is partly subjective; (ii) prothrombin time measurement in laboratories is variable, depending on the sensitivity of the thromboplastin reagent used;4_(iii) serum bilirubin level more than 3 and prothrombin time more than 16 will not alter the CTP score;5

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Aetiology of liver was later excluded, as it did not significantly affect the MELD score. MELD is calculated from:

0.957×log (Creatinine in mg/dl)+0.378×log (erum bilirubin in mg/dl)+1.12×log (INR)+0.643 The score is multiplied by 10 and rounded to the nearest whole number.

If the MELD score is >25, 19-24, 11-18, ≤ 10, it is recalculated every 7 days, 1, 3, 12 months respectively. In patients of cirrhosis of liver, MELD score is more accurate than CTP score, (MELD score >40:71% mortality, <10:2%), in predicting mortality in next 3 months.6

If the patient is on haemodialysis, s.creatinine is automatically set to 4.0 (Candidates on dialysis is defined as having 2 or more dialysis treatment within prior 1 week). And if any s. creatinine is <1, the MELD assumes the score is equal to 1.7

The MELD scoring system provided continuous values by a logarithmic calculation of three laboratory-available parameters, serum bilirubin, international normalized ratio (INR) of prothrombin time, and creatinine level. A major breakthrough of the MELD system was the introduction of renal function into the prognostic model. Renal dysfunction is often seen in patients with liver cirrhosis and the development of hepatorenal syndrome is a consequence of deteriorated residual liver function in advanced cirrhotic patients.8_{Profound renal dysfunction usually indicates} an extremely poor prognosis in these patients.9

Therefore, incorporation of serum creatinine may further enhance its prognostic ability. After 2002, ample evidence subsequently confirmed the prognostic role of the MELD system in different clinical settings. If the patient is on haemodialysis, s. creatinine is automatically set to 4.0 (Candidates on dialysis is defined as having 2 or more dialysis treatment within prior 1 week). And if any s.creatinine is <1, the MELD assumes the score is equal to 1.7

The use of MELD score in patients with acute liver failure, whether related or not to paracetamol, seems highly questionable since neurological status, a crucial prognostic index in this context, is not taken into account. 3 month mortality prediction by MELD score;10

>40: 71.3% mortality 30-39: 52.6% mortality 20-29: 19.6% mortality 10-19: 6% mortality <9: 1.9% mortality

LIMITATIONS OF MELD SCORE11_:

1. In practice, creatinine and bilirubin can be altered by therapeutic interventions (Diuretics in particular), sepsis or hemolysis. The choice of INR rather than other markers of coagulation including prothrombin time and prothrombin index is a controversial issue. Not all centers have used INR as a marker of coagulation in cirrhotic patients.

2. Akin to Child–Pugh score, MELD score does not (or no longer) take into account particular causes of cirrhosis and aggravating factors.

3. The principal limitation of MELD score is the need for computation, limiting its usefulness at the bedside.

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5. Serum creatinine in most cirrhotics is usually relatively low because of low muscle mass and its blood levels fluctuates even in end stage liver disease.

In our study, out of 50 patients with end stage liver disease, 20 patients died within the hospital accounting for 40% in-hospital mortality. Mean hospital stay in our study was 9.6 days for survivor and 5.8 days for non-survivor group. Mean age of patients was 48.5±12.056 years and Male patients contributed to 82% of cases in our study. Most common presenting features in our study was abdominal distension (74%) followed by jaundice (69.4%), swelling of lower limbs (64%) and hypotension (26%). We assessed the severity of end stage liver disease at admission using Child-Turcott-Pugh score and grouped them into Child class A, B and C.

MELD score was calculated for each patient and the mean value for death and discharge group was calculated. We observed that mean MELD score was found to higher in death group which was statistical significant with a p value of 0.002. The best cut-off value came to be 22 similar to Cholangitas et al study.12_{This means MELD score of 22 or more is associated with significant} mortality.

CONCLUSION: Our study showed that MELD score is good predictor of in-hospital mortality in patients with end stage liver disease and best cut off value for MELD score is 22, above which the mortality rate is high.

ACKNOWLEDGEMENTS: We express our gratitude towards our patients for giving consent for their inclusion in the study.

REFERENCES:

1. Forman LM, Lucey MR. Predicting the prognosis of chronic liver disease: an evolution from Child to MELD. Hepatology 2001; 33: 473-5.

2. Child III CG, Turcotte JG. Surgery and portal hypertension. In: Child III CG, ed. The Liver and Portal Hypertension. Philadelphia: Saunders, 1964; pp.50.

3. Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 1973; 60: 646-9.

4. Robert A, Chazouillères O. Prothrombin time in liver failure: time, ratio, activity percentage, or international normalized ratio? Hepatology 1996; 24: 1392-4.

5. Kamath PS, Wiesner RH, Malinchoc M, et al. A model to predict survival in patients with end-stage liver disease. Hepatology 2001; 33: 464-70.

6. Wiesner RH, McDiarmid SV, Kamath PS, et al. MELD and PELD: application of survival models to liver allocation. Liver Transpl 2001; 7:567-80.

7. Kamath PS, Kim WR. Advanced Liver disease study group. The model for end-stage liver disease (MELD). Hepatology 2007; 45(3):797-805.

8. Eckardt KU. Renal failure in liver disease. Intensive Care Med 1999; 25: 5e14.

9. Schepke M, Appenrodt B, Heller J, Zielinski J, Sauerbruch T. Prognostic factors for patients with cirrhosis and kidney dysfunction in the era of MELD: results of a prospective study. Liver Int 2006; 26: 834e9.

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11.F. Durand, D. Valla. Assessment of the prognosis of cirrhosis: Child–Pugh versus MELD. Journal of Hepatology 42 (2005) S100–S107.

12.Sheila Sherlock, James Dooley; Hepatic Cirrhosis; in Diseases of Liver and Biliary System; Blackwell Science publishers; 11th ed.; 368-80.

AUTHORS:

1. Keshava H. K. 2. Chikkalingaiah 3. Kamalesh T. N. 4. Vinayaka G. P. 5. Shashidhar B.

PARTICULARS OF CONTRIBUTORS:

1. Associate Professor, Department of General Medicine, KIMS, Bengaluru. 2. Professor, Department of General

Medicine, KIMS, Bengaluru. 3. Post Graduate/Junior Resident,

Department of General Medicine, KIMS, Bengaluru.

FINANCIAL OR OTHER

COMPETING INTERESTS: None

4. Senior Resident, Department of General Medicine, KIMS, Bengaluru.

5. Post Graduate/Junior Resident, Department of General Medicine, KIMS, Bengaluru.

NAME ADDRESS EMAIL ID OF THE CORRESPONDING AUTHOR:

Dr. Kamalesh T. N,

Post Graduate/Junior Resident, Department of General Medicine, KIMS, Bengaluru.

E-mail: medkam88@gmail.com