MELD SCORE CORRELATION WITH LABORATORY FINDINGS AND COMPLICATIONS OF HEPATITIS C CAUSED LIVER CIRRHOSIS Текст научной статьи по специальности «Клиническая медицина»

КОРРЕЛЯЦИЯ ШКАЛЫ MELD С КЛИНИКО-ЛАБОРАТОРНЫМИ ПРОЯВЛЕНИЯМИ И ОСЛОЖНЕНИЯМИ ЦИРРОЗА ПЕЧЕНИ, АССОЦИИРОВАННОГО С HCV ИНФЕКЦИЕЙ

Мясникова М.1, Рудака И.1, Зелтиня И.1-2, Лайвацума С.1-2, Деровс А.1-2

1 Рижский Университет им. П. Страдыня, Рига, Латвия

2 Рижская Восточная клиническая университетская больница, Рига, Латвия

MELD SCORE CORRELATION WITH LABORATORY FINDINGS AND COMPLICATIONS OF HEPATITIS C CAUSED LIVER CIRRHOSIS

Mjasnikova M.1, Rudaka I.1, Zeltina I.1 2, Laivacuma S.1 2, Derovs A.1 2

1 Riga Stradins University, Riga, Latvia

2 Riga East clinical university hospital, Riga, Latvia

Мясникова М. Медицинский факультет Рижского Университета им. П. Страдыня Рудака И. Медицинский факультет Рижского Университета им. П. Страдыня

Зелтиня И. Старший гепатолог клиники Гастроэнтерологии, гепатологии и клинического питания Рижской Восточной клинической университетской больницы. Рижский Университет им. П. Страдыня, Кафедра Инфектологии и Дерматологии; д.м.н., ассоциированный профессор

Лаивацума С. Инфектолог Рижской Восточной клинической университетской больницы. Рижский Университет им. П. Страдыня, Кафедра Инфектологии и Дерматологии; ассистент

Деровс А., Заведующий клиникой Гастроэнтерологии, гепатологии и клинического питания Рижской Восточной клинической университетской больницы. Рижский Университет им. П. Страдыня, Кафедра Внутренних болезней; д.м.н., доцент Mjasnikova M. Riga Stradins University Faculty of Medicine Rudaka I. Riga Stradins University Faculty of Medicine

Zeltina I. Riga Stradins University, Department of Infectology and Dermatology; Gastroenterology, hepatology and nutrition clinic at Riga East clinical university hospital; MD, PhD, associate professor

Laivacuma S. Infectologist at Riga East clinical university hospital. Riga Stradins university, Department of Infectology and Dermatology; MD, assistant

Derovs A. Head of Gastroenterology, hepatology and nutrition clinic at Riga East clinical university hospital. Riga Stradins University, Department of Internal Diseases; MD, PhD, assistant professor

Резюме

Введение. Шкала MELD (от англ. Model for End Stage Liver Disease) используется для оценки тяжести хронических заболеваний печени. Шкала основывается на объективных показателях и прогнозирует уровень смертности у различных групп пациентов [1, 2]. Цель исследования. Анализ потенциальной связи между показателем шкалы MELD и лабораторными показателями и осложнениями вызванными циррозом печени у больных хроническим гепатитом С. Материалы и методы. Ретроспективное кросс-секционное исследование было проведено основываясь на данных историй болезни пациентов Рижской Восточной Клинической Университетской больницы в период с 2010 по 2014 год. Были созданы оригинальный протокол и база данных с последующим статистическим анализом, используя программу IBM SPSS Statistics ver 20.0. Результаты. В исследование был включен 221 пациент с циррозом печени, вызванным хроническим гепатитом С, из них 128 (58%) мужчин и 93 (42%) женщины. Средний возраст пациентов 52.7 ± 13.4 года. Статистически значимая корреляция была выявлена между уровнем лейкоцитов (r = 0.4, p < 0.001), альбумином (r = -0.4, p < 0.001), мочевиной (r = 0.4, p < 0.001), C-реактивным белком (r = 0.4, p < 0.001) и показателями шкалы MELD. Более высокий уровень лейкоцитов, мочевины, C реактивного белка и более низкий уровень альбумина связан с более высокой степенью MELD. Во время госпитализации у 208 (94%) пациентов были осложнения вызванные циррозом. Статистически значимая корреляция была отмечена между уровнем MELD и такими осложнениями, как варикозное расширение вен пищевода (r = 0.2, p < 0.05) и кровотечение из них (r = 0.2, p < 0.05). Из этого следует, что у пациентов с варикозным расширением вен пищевода или кровотечением показатель MELD выше. Заключение. Более высокое значение MELD наблюдается у пациентов с более высоким уровнем лейкоцитов и мочевины, более низким уровнем альбумина, а так же у пациентов с варикозным расширением вен пищевода и кровотечением из них.

Ключевые слова: хронический гепатит С, цирроз печени, MELD.

Экспериментальная и клиническая гастроэнтерология 2016; 131 (7): 13-17

Деровс Алексей

Derovs Aleksejs

aleksejs.derovs@

gastroenterologs.lv

Summary

Introduction. Model for End-Stage Liver Disease (MELD) is a scoring system used to estimate the severity of chronic liver disease. Score is based on objective variables and predicts survival among different populations of patients. Study Aim. The aim of the study was to retrospectively analyze potential connection between MELD score and laboratory findings and complications of hepatitis C caused liver cirrhosis. Materials and Methods. A retrospective cross-sectional study based on data from Riga East Clinical University Hospital from the time period of 2010 to 2014 was performed. Original protocol and database were developed with consequential data statistical analysis using IBM SPSS Statistics ver.20.0. Results. In total 221 cirrhosis cases were enrolled in the study. 128 (58%) cases were male and 93 (42%) female. Mean age was 52.7 ± 13.4 years. Statistically significant correlation was found between leukocytes (r = 0.4, p < 0.001), blood urea (r = 0.4, p < 0.001), serum albumin (r = -0.4, p < 0.001), C-reactive protein (r = 0.4, p < 0.001) and MELD score. Higher leukocytes, higher urea, C-reactive protein and lower serum albumin rates give higher MELD score. At the time of hospitalization 208 (94%) of the patients had different complications of liver cirrhosis. Correlation between MELD score varied significantly with esophageal varices (r = 0.2, p < 0.05) and esophageal vein bleeding (r = 0.2, p < 0.05). Results show, if patient is present with esophageal varices and esophageal vein bleeding, MELD score is higher. Conclusion. Patients with higher leukocytes, blood urea nitrogen and lower serum albumin level are presenting higher MELD score. In patients who presented with esophageal varices and esophageal vein bleeding, higher MELD score was observed.

Keywords: chronic hepatitis C, cirrhosis, MELD.

Eksperimental'naya i Klinicheskaya Gastroenterologiya 2016; 131 (7): 13-17

Introduction

Prognosis is an important component of baseline assessment of chronic hepatitis C infection caused liver cirrhosis [1]. For an ideal prognostic score, it is essential to be objective, validated across the world, accurate, easy to calculate and able to guide treatment process. Most of these criteria are combined in MELD score, being used worldwide for different liver diseases [2].

MELD score, based on serum creatinine, serum bilirubin, INR for protrombin time and etiology of the liver disease, was developed to predict three-month survival in patients following transjugular intrahepatic portosystemic shunt (TIPS) procedure. As etiology of liver disease did not show an impact on mortality,

it was removed from model. Furthermore, MELD score is found to be a reliable predictor to assess short-term survival in patients with advanced chronic liver disease in general [2, 3].

The MELD score is modern alternative to other prognostic models, for example, Child-Turcotte-Pugh score, in patients with end-stage liver disease, because of using only objective parameters.

In a variety of different clinical cases, MELD score has shown to be valid to prognosticate the lifespan with advanced liver diseases. The validity ofthe MELD score has been shown in a variety of clinical scenarios to prognosticate survival in patients with advanced liver disease [4].

Aim of the study

The goal of the research was to analyze and look for findings and complications of patients with chronic correlations between MELD score and laboratory hepatitis C caused liver cirrhosis.

Materials and methods

Study design. A retrospective cross-sectional study was performed.

Patients: Documented cases of liver cirrhosis due to chronic hepatitis C (HCV) for the time period of 2011-2014 were found in medical archive of Riga East clinical university hospital (a 6 clinic, 2270-bed medical center) and enrolled into the study. Patients' clinical features (signs and symptoms) and laboratory findings (foul blood count, biochemical markers, hepatitis serological analyses etc.) were analyzed. Model for End-Stage Liver Disease (MELD) score was calculated, using United Network for Organ Sharing approved formula: MELD = 9.57 x ln (creatinine mg/dL) + 3.78 x ln (bilirubin mg/dL) + 11.2 x ln (INR) + 6.43. Values

less than 1 were set to 1 in order to avoid negative scores. Since January 2016 new modified MELD score is used (including serum sodium level in the formula). However during our study, we have used the old above mentioned score calculation.

Quality assessment. The research was carried out in accordance with the Helsinki Declaration

Statistical analysis. IBM SPSS Statistics ver. 20.0 was used for all statistical analyses. Correlations were analysed by Pearson's r and Point Biserial rpb coefficients. Kruskal-Wallis and Mann-Whitney U tests were performed for groups' comparison. P-values less than 0.05 were considered statistically significant.

Results

In total 221 patients cases were enrolled into the study. Out of these 128 (58%) cases were male and 93 (42%) female. Patients' age varied between 25 and 85 years (mean 52.7 ± 13.4) (Table 1). Among all patients, 7 were co-infected with hepatitis B virus (HBV) and in 85 cases cirrhosis was due to both HCV and alcohol consumption.

Table 1 shows baseline demographic and clinical profile. MELD score was possible to calculate in 167 cases, which varied between 7 and 44 with mean of 16.6 ± 7.3.

There was no statistically significant impact of gender on MELD score (p = 0.99). As well as MELD score did not show a statistically significant difference between groups of different causes of cirrhosis (p = 0.324).

Table 2 shows results of correlation analysis between MELD score and clinical characteristics. Statistically significant correlation was found between leukocytes (r = 0.4, p < 0.001), CRP (r = 0.4, p < 0.001), blood urea (r = 0.4, p < 0.001), serum albumin (r = -0.4, p < 0.001) and MELD score, which means that higher leukocytes, CRP, blood urea and lower serum albumin rates give higher

Gender, n (%)

Male 128 (57.9)

Female 93 (42.1)

Mean age, years (SD) 52.7 (13.4)

Etiology of cirrhosis, n (%)

Chronic HCV infection 135 (61.1)

Chronic HCV + alcohol consumption 79 (35.7)

Chronic HCV + chronic HBV infection 1 (0.5)

Chronic HCV + HBV + alcohol consumption 6 (2.7)

Mean MELD score (SD) 16.6 (7.7)

Male (SD) 16.9 (8.4)

Female (SD) 16.2 (6.5)

Cirrhosis caused complications, n (%) 208 (94.1)

Portal hypertension, n (%) 197 (94.7)

Ascites, n (%) 135 (60.1)

Esophageal varices, n (%) 128 (61.5)

Esophageal variceal bleeding, n (%) 70 (33.7)

Portal vein thrombosis, n (%) 9 (4.3)

Hepatorenal syndrome, n (%) 21 (10.1)

Spontaneous bacterial peritonitis, n (%) 5 (2.4)

Hepatic encephalopathy, n (%) 45 (21.6)

Hepatocellular carcinoma, n (%) 24 (11.5)

Table 1

Baseline characteristics of patients

SD — standartdeviation, HCV — hepatitis C virus

Exitus letalis, n (%)

49 (22.2)

Variable Mean ± SD Correlation coefficient p-value

Hemoglobin, g/dL 10.1 (3.1) 0.5 0.519

Platelet x109/L 143.6 (111.1) -0.039 0.617

Leukocytes x109/L 8.27 (5.8) 0.433 < 0.001

CRP, mg/L 20.9 (35) 0.404 < 0.001

ALAT, U/L 74 (157.3) 0.058 0.463

ASAT, U/L 170.2 (438.8) 0.116 0.163

Glucose, mmol/L 11.6 (60.7) -0.102 0.195

Lipase, U/L 114.7 (239.8) 0.037 0.715

Serum albumin, g/L 27 (6.6) -0.389 < 0.001

Blood urea, mmol/L 9.2 (16.3) 0.441 < 0.001

Alkaline phosphatase, U/L 145.9 (168.2) 0.262 0.079

YGT, U/L 179.5 (248.5) 0.182 0.227

Table 2

Correlation of MELD score and laboratory findings in patients of HCV caused cirrhosis

Correlations are analysed by Pearson's r coefficient. SD — Standartdeviation, CRP — C-reactive protein, ALAT — Alanine aminotransferase, ASAT — Aspartate aminotransferase, yGT — Gamma glytamiltransferase

Graph 1 (left)

Correlation of MELD score and esophageal vein varicosis in patients with HCV caused liver cirrhosis

Graph 2 (right)

Correlation of MELD score and esophageal vein bleeding in patients with HCV caused liver cirrhosis

Yes No

Esophageal vein varicosis

Yes No

Esophageal vein bleeding

MELD score. Blood urea was significantly higher in patients with hepatorenal syndrome (17.6 mmol/L vs. 8.2 mmol/L, p < 0.001) and esophageal variceal bleeding (13.4 mmol/L vs. 7 mmol/L, p < 0.05).

At the time of hospitalization 208 (94%) of the patients had different complications of liver

cirrhosis. Correlation between MELD score varied significantly with esophageal varices (r = 0.2, p < 0.05) and esophageal vein bleeding (r = 0.2, p < 0.05). (Figure 1 and 2) Results show, if patient is present with esophageal varices and esophageal vein bleeding, MELD score is higher.

Discussion

By analyzing the correlation between MELD score and laboratory findings in patients with HCV related cirrhosis, we found that score was significantly associated with increased levels of CRP, urea and with reduced level of serum albumin.

In previous studies CRP is found to be a relevant predictor of short-term mortality in cirrhotic patients [5, 6]. CRP is a sensitive marker of inflammation and tissue damage, produced in hepatocytes [7] and CRP levels show positive correlation with MELD score, so we assume it can be used as a mortality predictor both as independent marker, or in combination with MELD score.

Serum albumin is found to be significantly associated with MELD score — patients with higher MELD presented with lower serum albumin. In previously published studies albumin showed positive impact on MELD predictive possibilities. Modification of MELD by adding serum albumin value is associated with significant improvement in prognostic performance [8, 9].

Urea is one of end products of nitrogenous metabolism and is predominantly synthesized in the liver [10]. Diminished urea synthesis and high clearance due to increased intravascular volume are the causes of reduced blood urea concentration in cirrhotic patients [11, 12]. This study shows that high

level of blood urea is associated with worse prognosis. Furthermore, blood urea showed a significant positive correlation with cirrhosis decompensation features, such as esophageal variceal bleeding and hepatorenal syndrome.

Recent studies show that impaired lipid profile is also associated with worse prognosis and may improve predictive value of scoring systems [13-16]. This aspect was not evaluated in this study, so a further research must be done including other clinical features of cirrhotic patients.

Statistically significant difference was found between MELD score and two complications of chronic hepatitis C caused cirrrhosis: eosphageal vein varicosis and esophageal vein bleeding.

The estimated prevalence of esophageal varices in cirrhosis patients is about 50%. Esophageal variceal bleeding represents a predominant cause for morbidity and mortality in this group [17]. Previous studies show, that MELD score is a reliable predictor of outcome after variceal hemorrhage. Patients with more than 18 points are at increased risk of rebleeding within first 5 days and overall mortality at 6 weeks. [2]. The positive correlation between MELD score and variceal bleeding, which was found during our study, confirms this association and indicates worse prognosis in patients presenting with this complication.

References

1. Kim HJ, Lee HW. Important predictor of mortality in 2. Signal AK, Kamath PS. Model for End-stage

patients with end-stage liver disease // Clin Mol Liver Disease // J Clin Exp Hepatol. — 2012. —

Hepatol. — 2013. — 19(2), 105-115. 3(1), 50-60.

3. Kamath PS, Wiesner RH, Malinchoc M et al. A model to predict survival in patients with end-stage liver disease // Hepatology. — 2001. — 33(2), 464-70.

4. Lau T, Ahmad J. Clinical application of the Model for End-Stage Liver Disease (MELD) in hepatic medicine // Hepat Med. — 2013. — 5, 1-10.

5. Cervoni JP, Thevenot T, Weil D et al. C-reactive protein predicts short-term mortality in patients with cirrhosis // J Hepatol. — 2012 — 56(6), 1299-304.

6. Di Martino V, Coutris C, Cervoni JP et al. Prognostic value of C-reactive protein levels in patients with cirrhosis // Liver Transpl. — 2015 — 21(6), 753 -60.

7. Pepys MB, Hirschfield GM. C-reactive protein: a critical update // J Clin Invest. — 2003 — 111(12), 1805-812.

8. Myers RP, Shaheen AA, Faris P et al. Revision of MELD to include serum albumin improves prediction of mortality on the liver transplant waiting list // PLoS One. — 2013 — 8(1), e51926.

9. Myers RP, Tandon P, Ney M et al. Validation of the five-variable Model for End-stage Liver Disease (5vMELD) for prediction of mortality on the liver transplant waiting list // Liver Int. — 2014 — 34(8), 1176-83.

10. Hosten AO BUN and Creatinine // Walker HK, Hall WD, Hurst JW (ed.) Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. — Boston: Butterworth, 1990.

11. Decaux G, Dumont I, Naeije N et al. High uric acid and urea clearance in cirrhosis secondary to increased "effective vascular volume" // Am J Med. — 1982 — 73(3), 328-34.

12. Decaux G, Prospert F, Namias B et al. Raised urea clearance in cirrhotic patients with high uric acid clearance is related to low salt excretion // Gut. — 1992 — 33(8), 1105-108.

13. Bassani L, Fernandes SA, Raimundo FV et al. Lipid Profile of Cirrhotic patients and its association with parognostic scores: a cross-sectional study // Arg Gastroenterol. — 2015 — 52(3), 210-15.

14. Boemeke L, Bassani L, Marroni CA, Gottschall CB Lipid profile in cirrhotic patients and its relation to clinical outcome // Arg Bras Cir Dig. — 2015 — 28(2), 132-35.

15. Abbasi A, Bhutto AR, Butt N et al. Serum cholesterol: could it be a sixth parameter of Child-Pugh scoring system in cirrhotics due to viral hepatitis? // J Coll Physicians Surg Pak. — 2012 — 22(8), 484-87.

16. Ghadir MR, Riahin AA, Havaspour A et al. The relationship between lipid profile and severity of liver damage in cirrhotic patients // Hepat Mon. — 2010 — 10(4), 285-88.

17. Xiao-Dan Xu, Jian-Jun Dai, Jian-Qing Qian et al. New index to predict esophageal variceal bleeding in cirrhotic patients//World J Gastroenterol. — 2014 — 20(22), 6989-994.