Original Article

Prognostic Value of the Monoethylglycinexylidide Test in

Alcoholic Cirrhosis
Satish B. Bhise, Remeth J. Dias*, Kailas K. Mali*

Government College of
Pharmacy, Vidyanagar,
Karad, Satara - 415 124,
(MS), *Satara College of
ABSTRACT
Background: The existing conventional liver function tests (LFTs) are indirect, inferior and have limited
prognostic value. Therefore, the monoethylglycinexylidide (MEGX) test, which provides a direct measure of

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Pharmacy, Plot No. 1539, the actual functional state of the liver, is proposed as a real-time liver function test. The objective of this study
Behind Spicer India Ltd., was to assess the prognostic value of the MEGX test in cirrhosis by comparing it with Child-Turcotte-Pugh

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New Add MIDC, Degaon, (CTP), the Mayo end stage liver disease (MELD) and discriminant function (DF) scores. Materials and Methods:
Satara - 415 004, (MS), India

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The study was carried out in Satara, India during the period of January 2005 to June 2006 and included 79
Address: adult alcoholic cirrhotic patients. The serum specimen from each patient was analyzed using conventional

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Mr. Remeth J. Dias LFTs and the MEGX test. The prognostic scores-CTP, MELD and DF scores were calculated and statistical
analyses was performed. Results: Based on receiver operating characteristic (ROC) curves, the MELD score and

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Principal, Satara College of
Pharmacy, Plot No. 1539, MEGX60 showed excellent sensitivity and specificity. The comparison of area under ROC curves showed that
MELD and MEGX60 had superior prognostic accuracy when compared to other scores. Kaplan-Meier survival

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Behind Spicer India Ltd.,
New Add MIDC, Degaon, curves for corresponding cutoff values clearly differentiated between patients with different survival times.
Satara - 415 004, (MS) India. Conclusion: The MEGX test has shown more sensitivity, specificity and accuracy than CTP and DF scores in
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E-mail: determining cases with the possibility of three- and six-month survival. Thus, it can be concluded that MEGX test
alongwith MELD, is an effective prognostic tool in the hands of clinicians for predicting short-term survival.
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rjdias75@rediffmail.com
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Key Words: Monoethylglycinexylidide, alcoholic cirrhosis

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Received 22.02.2007, Accepted 06.05.2007

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The Saudi Journal of Gastroenterology 2007 13(3):118-23

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Cirrhosis is the twelfth leading cause of death by disease, MELD prognostic scoring system has substituted the CTP
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killing about 26,000 people each year. [1] The accurate score in the process of patient allocation to liver transplant
prognosis of patients with cirrhosis is important so as to plan waiting lists in the USA since 2002.[15] The Mayo end stage
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their management as well as the choice of therapy.[2] The liver disease (MELD) score has been demonstrated to be
prognosis in patients with cirrhosis depends on the etiology, accurate to estimate short-, intermediate- and long-term
progress of the disease and associated complications. Several mortality across a broad spectrum of liver disease.[16-17] The
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investigators have suggested various prognostic models to discriminant function (DF) formula proposed by Maddrey et
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accurately predict the prognosis of cirrhotic patients.
The Child-Turcotte-Pugh (CTP) score has been widely
used as a clinically reliable method for classification of
cirrhosis.[3] However, the subjectivity of clinical parameters
and limited discriminating ability are some drawbacks of the
CTP score.[4] Therefore, several prognostic models and liver
function tests (LFTs)were developed in order to find a LFT
with a superior predictive power for survival of patients with
advanced cirrhosis.[5-7] Quantitative LFTs like indocyanine
green, galactose elimination capacity and aminopyrine breath
tests have been studied for their prognostic utility.[8-9]
The monoethylglycinexylidide (MEGX) test is a quantitative
LFT, which gives the functional capability of the liver at given
point of time and shows good correlation with medium- and
short-term survival prognosis of cirrhotic patients.[10-14] The
118 The Saudi Journal of
Volume 13, Number 3 Gastroenterology
Jumada AlThany 1428
July 2007
al. is a widely used prognostic index in the clinic in alcoholic
hepatitic and cirrhotic patients. A DF score of ≥ 32 correlates
with ≥ 50% mortality risk in one month.[18]
There are a few conflicting international studies questioning
the use of MEGX test. In this light, the utility of the MEGX
test for prognosis of cirrhosis needs to be tested in the Indian
hospital setting. Hence, the aim of this study was to assess
the prognostic value of MEGX test in cirrhosis by comparing
MEGX concentrations with CTP, MELD and DF scores.
MATERIALS AND METHODS
Patient population
The study was conducted in Civil Hospital, Satara (India)
during January 2005 to June 2006 and included 79 adult,
male, alcoholic cirrhotic patients with a median age of 42 (23-
 Prognostic value of MEGX test

65) years. Informed consent was obtained from all patients
before participation in the study. The protocol for the study
was approved by the Institutional Ethics Committee.
The diagnosis of cirrhosis was done on the basis of clinical
and biochemical parameters and was confirmed by either
ultrasonographic findings or by liver biopsy, wherever it was
feasible. Survival at 90 and 180 days following admission was
determined by follow-up of all the patients.
Laboratory analysis and MEGX testing
Statistical analysis
Statistical analysis was done by using GraphPad Prism 4
and DTREG software. Statistical analysis was performed
on all 79 patients, evaluating three- and six-month survival
cases. Comparisons between groups were performed using
ANOVA and confirmed by the Mann-Whitney U test.
Results are expressed as median (range). Receivers operating
characteristic (ROC) curves were used to determine the
cutoff values of MEGX, CTP, MELD and DF, with the best
sensitivity and specificity in discriminating between survival
and nonsurvival cases.

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Before the injection of lidocaine, the serum specimen from
each patient was analyzed for alanine aminotransferase (ALT), The prognostic utility of all these scores was assessed by

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aspartate aminotransferase (AST), alkaline phosphatase determining the area under the curve of a ROC curve
(AP), total bilirubin (TB), albumin (ALB) and prothrombin

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(AUROC). Univariate survival curves were estimated
time (PT) by using an ASCA automatic analyzer. using the Kaplan-Meier method. The survival analysis was

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performed by means of logistic regression to determine the

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MEGX testing was performed on all patients after an variables independently associated with three month- and
overnight fast. The patients were given a dose of 1 mg/kg six-month mortality. For all analyses, a P value < 0.05 was

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of 20 g/L lidocaine hydrochloride (Xylocaine) injection considered statistically significant.
intravenously, slowly over a period of 2 min. After the
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lidocaine injection, all patients remained supine for two RESULTS
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hours, were asked to report any subjective adverse effects
and their vital signs were closely monitored. The blood The clinical and biochemical characteristics of the patients
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samples were taken at 0, 15, 30 and 60 min after the lidocaine along with CTP, MELD, DF scores and MEGX values are
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administration. given in Table 1 while the data categorized according to

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three- and six-month survival are given in Table 2. CTP,

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Blood was centrifuged and serum samples were stored at -

20oC until assayed. MEGX concentrations were determined Table 1: Demographic data of the patients included in
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by high performance liquid chromatography (HPLC) the study

method with ultraviolet detection as described by Chen et
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Characteristics Median (range)

al.[19] The calibration graph was linear over the range 4-250
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Clinical parameters
ng/ml with intra- and interassay relative standard deviations Encephalopathy (yes/no) 7/72
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of 8 and 9% respectively. The limit of detection (LOD) for Ascites (yes/no) 26/53
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the method was 3 ng/ml while limit of quantification (LOQ) Biochemical tests
was 4 ng/ml. Albumin (g/dl) 3.42 (1.92-4.51)
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Bilirubin (mg/dl) 2.45 (0.32-12.7)

Prothrombin time (sec) 19 (13-36)
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Derivation of prognostic scores INR 1.47 (0.91-2.8)

The CTP score was calculated as described elsewhere.[3] The Creatinine (mg/dl) 0.97 (0.43-5.82)
patients were divided as per CTP classification: 30 = Child MEGX15 (ng/ml) 24.53 (5.26-67.6)
class A, 27 = Child class B and 22 = Child class C. MEGX30 (ng/ml) 33.04 (5.43-89.97)
MEGX60 (ng/ml) 38.4 (8.6-96.54)
The MELD score was calculated according to the following Prognostic scores
Child-Turcotte-Pugh 7 (5-15)
formula proposed by the Mayo Clinic group: MELD score
Mayo end stage liver disease 7.22 (-4-34.56)
= 3.8 x loge (bilirubin, mg/dl) +11.2 x loge (INR) +9.6 x Discriminant function 26.91 (-4.1-105.1)
loge (creatinine, mg/dl) + 6.4 (etiology). Reasons for admission
Ascites / encephalopathy / variceal 26 / 7 / 29 / 11 / 6
The DF score was calculated by using following formula: bleeding / jaundice / anemia
DF = 4.6 x (patient’s PT - control PT) + total bilirubin Reasons for death
(mg/dl). Hepatic failure / hepatorenal syndrome / 2/7/3/1
cardiorespiratory failure /
hepatocellular carcinoma
All the scores were calculated based on laboratory values
MEGX - monoethylglycinexylidide
obtained within 24 hours of admission.

The Saudi Journal of 119

Gastroenterology Volume 13, Number 3
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Bhise, et al.

Table 2: Characteristics of patients categorized according to three and six months’ survivals
Characteristics Three months’ mortality Six months’ mortality
Survivals Nonsurvivals Survivals Nonsurvivals
Encephalopathy (Yes / No) 5 / 67 2/5 4 / 62 3 / 10
Ascites (Yes / No) 21 / 51 5/2 19 / 47 7/6
Bilirubin (mg/dl) 2.4 (0.32-5.2) 3.6* (1.4-12.7) 2.24 (0.32-4.9) 3.6** (1.5-12.7)
Albumin (g/dl) 3.5 (1.9-4.5) 2.9** (2.1-3.4) 3.5 (1.9-4.5) 2.9** (1.9-3.9)
Prothrombin time (sec) 19 (13-36) 25* (17-33) 18 (13-35) 24** (14-36)
Child-Turcotte-Pugh score 7 (5-14) 11** (8-15) 7 (5-14) 11** (5-15)
Creatinine (mg/dl) 0.94 (0.43-5.8) 1.8** (1.4-4.5) 0.9 (0.43-2.76) 2.1*** (0.53-5.8)
INR 1.44 (0.9-2.8) 1.94* (1.3-2.6) 1.4 (0.91-2.7) 1.9** (1.1-2.8)

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Mayo end stage liver disease score 6.2 (-4-33.6) 18** (12.7-34.6) 4.5 (-4-24.3) 16.7*** (10.7-35)
DF score 25.5 (-4.1-105) 56.3* (15.2-100) 20.8 (-4.1-100) 50.9** (2.7-105)
MEGX15 (ng/ml) 25.4 (5.3-67.6) 9.4* (8.1-21.6) 26.1 (5.3-67.6) 9.2** (6.7-29.3)

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MEGX30 (ng/ml) 35.5 (5.4-90) 15.2** (6.3-24.9) 37.1 (5.4-90) 15.2*** (5.9-31.1)

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MEGX60 (ng/ml) 40.7 (9.1-96.5) 21.6** (8.6-27.4) 42.32 (9.2-96.5) 21.5*** (8.6-37.5)
Survival vs nonsurvivals: *P < 0.05, **P < 0.01, ***P < 0.001, ¶P > 0.05. The results are given as median (range); P < 0.05 is considered statistically signiÞcant.

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INR - International normalized ratio for prothrombin time, MEGX - Monoethylglycinexylidide.

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MELD, DF scores and MEGX values at each sampling time with three- and six-months’ mortality, logistic regression
were significantly different both at three and six months
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between survival and nonsurvival cases. MELD and DF scores and on MEGX60 concentration. This
analysis showed that MEGX60 and bilirubin were significantly
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The cutoff values with the best sensitivity and specificity associated with three months’ mortality while MEGX60,
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in predicting three-month and six-month survival were ascites and creatinine were significantly associated with six
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calculated using ROC curves for CTP scores, MELD scores, months’ mortality.
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DF scores and MEGX serum levels as given in Table 3.

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AUROC was calculated for evaluating the accuracy of each DISCUSSION

model. MELD score and MEGX60 showed the best sensitivity
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and specificity in predicting three- and six-month survival. Improvement of the course and outcome of the patient’s
disease is a primary objective of clinicians. Thus, assessment
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After AUROC analysis, MELD and MEGX60 scores showed of the patient’s prognosis is an important part of the
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excellent prognostic accuracy as compared to other scores. evaluation, which will have a significant influence on the
Figures 1 and 2 show the comparison of AUROC for three choice of therapy.[4] The issue of an accurate prognosis
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and six months respectively. Kaplan-Meier survival curves for in cirrhosis has become increasingly important with the
corresponding cutoff values are given in Figures 3 and 4. It advent of liver transplantation. Over a period of decades,
can be seen that CTP, MELD, DF and MEGX60 cutoff values a large number of prognostic models have been developed
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identified by means of ROC curves clearly differentiated for cirrhosis in general and for various specific chronic liver
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between patients with different survival times. diseases in particular.[20-21]

Furthermore, to identify parameters independently associated The CTP score was defined empirically in 1964 and has

Table 3: Prognostic utility of Child-Turcotte-Pugh, Mayo end stage liver disease, discriminant function scores and
monoethylglycinexylidide concentrations at 15, 30, and 60 min
Models Three-month survivals Six-month survivals
Cutoff Sensitivity (%) Specificity (%) AUROC Cutoff Sensitivity (%) Specificity (%) AUROC
Child-Turcotte-Pugh 8.5 85 73 0.8343 8.5 69 75 0.77
MELD 14 86 80 0.873 12 92 80 0.885
DF 39 85 69 0.787 39 69 71 0.773
MEGX15 (ng/ml) 15 85 72 0.817 17 85 75 0.813
MEGX30 (ng/ml) 19 85 75 0.831 25 85 72 0.842
MEGX60 (ng /ml) 26 85 77 0.853 28 85 77 0.855
MELD - Mayo end stage liver disease, MEGX - Monoethylglycinexylidide, AUROC - Area under receiver operating characteristic curve

120 The Saudi Journal of

Volume 13, Number 3 Gastroenterology
Jumada AlThany 1428
July 2007
 Prognostic value of MEGX test

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Figure 1: ROC curves for three-month survival cases Figure 4: Kaplan-Meier curves for six-month survival cases

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been widely used as a prognostic tool.[3] It is based on serum

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bilirubin, serum albumin, prothrombin time, ascites and
exephalopathy.[4] This model has weaknesses such as the
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inclusion of subjective clinical variables like ascites and
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encephalopathy and the use of cutoff points for quantitative

variables like bilirubin, albumin and prothrombin time.
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Although these limitations reduce its prognostic ability this

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model is widely used.

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The MELD score first published in 2000,[15] has sound

statistical and clinical validity, relying on a few important
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objective variables and being generalizable to a heterogeneous

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group of patients. The MELD score has replaced the CTP

score for patient allocation to liver transplant waiting lists
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due to its objective criteria and continuous scale.[22] DF

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score has been used as a predictor of mortality in alcoholic

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Figure 2: ROC curves for six-month survival cases cirrhotic patients.[18]

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The MEGX test, which is based on the conversion of

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lidocaine to the major metabolite MEGX through sequential

oxidation by hepatic cytochrome P450 enzymes, has been
proposed to assess liver function.[11] The MEGX test has
found widespread application in hepatology and critical care
medicine. The advantages of the MEGX test are that it gives
an idea about the residual function of the liver and its rapid
turn-around time. Its disadvantages are that it is an invasive
test requiring frequent blood sampling and sophisticated
instrumentation and that it shows wide variability and
overlapping of the results among subjects.

The MEGX test has shown good correlation with medium-

Figure 3: Kaplan-Meier curves for three-month survival cases
and short-term survival prognosis of cirrhotic patients. It
has been shown that one-year survival in adults with MEGX
production < 10 ng/ml was only 50% compared with 90%
when MEGX was ≥ 10 ng /ml.[23] However, there are a few
conflicting studies questioning the validity of the MEGX

The Saudi Journal of 121

Gastroenterology Volume 13, Number 3
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Bhise, et al.

test.[24,25] The predictive ability of the MEGX test has not
been evaluated in India. Furthermore, the utility of the CTP
and MELD scores has also not been studied in the Indian
hospital setting.
Hence, the aim of this study was to evaluate the predictive
ability of the MEGX test in alcoholic cirrhotic patients by
comparing it with CTP, MELD and DF scores. The MEGX
test could discriminate well between deceased (nonsurvival
cases) and surviving patients in both three and six months
at all sampling times. MEGX60 (60 minute concentrations of
CONCLUSION
The MEGX test, a dynamic liver function test, has an
excellent prognostic ability in predicting short-term mortality
in alcoholic cirrhosis. This is because it is the most significant
parameter found to be associated with both three and six
months’ mortality. However, due to the invasiveness and
cost involved in MEGX testing, MELD becomes the first-
choice prognostic model. However, the MEGX test can be
used along with the MELD system to help the clinicians in
effective prognosis of alcoholic cirrhotic patients.

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MEGX) was found to be more discriminative than MEGX15
and MEGX30. MEGX60 values were found to be higher than ACKNOWLEDGEMENTS

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corresponding 15 min and 30 min concentrations. Also, the

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percent coefficient of variation was found to decrease as the T h e a u t h o r s w i s h t o t h a n k D r. Ya d a v, D r. G h e v a r i ,
sampling time increased from 15 to 60 min.

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Dr. Kulkarni, the nursing staff of Civil Hospital and Dr. Khadtare

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of Disha Labs, Satara for their assistance in performance of this
So, it was evident that the results were more stabilized and study.
hence, the efficiency of the test was maximal at 60 min.

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et al. Adaptation of the mayo primary biliary cirrhosis natural history
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