Predictive value of liver transaminases levels in abdominal trauma Ismail Bilgic, Sibel Gelecek, Ali Emre Akgun, M. Mahir Ozmen PII: DOI: Reference:
S0735-6757(14)00240-X doi: 10.1016/j.ajem.2014.03.052 YAJEM 54230
To appear in:
American Journal of Emergency Medicine
Received date: Revised date: Accepted date:
16 January 2014 30 March 2014 31 March 2014
Please cite this article as: Bilgic Ismail, Gelecek Sibel, Akgun Ali Emre, Mahir Ozmen M, Predictive value of liver transaminases levels in abdominal trauma, American Journal of Emergency Medicine (2014), doi: 10.1016/j.ajem.2014.03.052
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT “PREDICTIVE VALUE OF LIVER TRANSAMINASES LEVELS IN ABDOMINAL TRAUMA”
T
Short running head: “Liver transaminases in abdominal trauma”
RI P
Ismail Bilgica, Sibel Geleceka, Ali Emre Akguna, M. Mahir Ozmena,b
Department of Surgery, Ankara Numune Teaching and Research Hospital, Ankara-Turkey
b
Department of Surgery, Hacettepe University, Medical School, Ankara-Turkey
Corresponding Author: Name: Ismail BILGIC
MA NU
SC
a
Address: İşçi Blokları mah. 1489. cad. Kardelen sitesi C/35 postal code: 06530, Balgat,
Phone: +90 (0312) 2840867
PT
Faks: +90 (0312) 203 50 28
ED
Çankaya, ANKARA
E-Mail: [email protected]
AC
of interest.
CE
The authors have no commercial associations or sources of support that might pose a conflict
Keywords: abdomen; liver; liver enzymes; trauma
Abstract Introduction: We aimed to evaluate whether hepatic transaminase levels could predict the presence and severity of liver injury following abdominal trauma.
ACCEPTED MANUSCRIPT Methods: We performed a retrospective analysis of 75 surgically treated patients and 21 nonsurgically treated patients with liver injury who were managed between 2004 and 2012. We
T
retrieved demographic, laboratory, radiologic, and intraoperative data, as well as surgical
RI P
procedures and the outcome from the patients’ medical records. We compared the findings between patients divided into two groups according to the severity of liver injury: Group 1,
SC
including patients with Grade 1 or 2 liver injuries; and Group 2, including patients with Grade
MA NU
3–5 liver injury.
Results: There were 87 (90.6%) males and 9 (9.4%) females. The mean age was 34 years (range 17–90 years). The overall mortality rate was 14.6% (n = 14). The injury was blunt in 83 (86.5%) patients and penetrating in 13 (13.5%) patients. There were multiple traumas in 60
ED
(62.5%) patients. Overall, 43 (44.8%) patients had a total of 61 coexisting intraabdominal injuries. The circulating aspartate aminotransferase, alanine aminotransferase, and lactate
PT
dehydrogenase (LDH) levels were significantly higher in Group 2 than in Group 1.
CE
Conclusions: In patients with abdominal trauma, abnormal hepatic transaminase and LDH levels are associated with liver injury. Alanine aminotransferase ≤ 76 U/l, aspartate
AC
aminotransferase < 130 U/l, and LDH ≤ 410 U/l are predictive of low-grade liver injury, and patients with serum liver levels below these levels can be managed conservatively.
1. Introduction
ACCEPTED MANUSCRIPT The liver is the most frequently injured organ following abdominal trauma [1], and liver injury significantly increases the risk of morbidity and mortality. The liver is a
T
particularly vulnerable organ because of its size, and its fixed position in the right
RI P
hypochondrium. In recent years, nonsurgical treatment of hepatic injury has entered clinical practice and has helped to avoid unnecessary laparotomy. Hepatic injuries of Grade 2 or lower
SC
are rarely clinically serious, with the patient generally requiring minimal resuscitation and observation, without the need for surgery [2]. For hepatic injuries of Grade 3 or above,
MA NU
however, 20%–30% of patients require adjunctive treatments together with invasive monitoring [2]. Serum hepatic enzyme levels are routinely measured as part of the initial laboratory evaluation of trauma patients. However, small-scale studies of paediatric trauma patients have revealed a broad range in the threshold levels of liver enzymes on admission,
ED
and patients with levels below these thresholds did not have clinically significant liver injury
PT
[3,4]. So far, very few articles have described the potential value of serum hepatic enzymes for the diagnosis of liver injury in adults. Therefore, the purpose of this study was to
CE
determine the threshold levels of aspartate aminotransferase (AST), alanine aminotransferase
AC
(ALT), and lactate dehydrogenase (LDH) on admission for predicting low-grade liver injury.
2. Materials and methods
This retrospective clinical study was performed at the Emergency Service Department of Ankara Numune Teaching and Research Hospital between August 2004 and January 2012. We reviewed 101 consecutive patients, of which 96 were included in this study. In 75 patients, liver trauma was confirmed by exploratory surgery. These patients had an unstable haemodynamic status or signs of abdominal injury that required surgery. Three patients with
ACCEPTED MANUSCRIPT stable haemodynamics on admission were initially treated conservatively, but these patients subsequently underwent laparotomy within 8–24 h of admission because of deteriorations in
T
their haemodynamic status. In 21 patients with stable haemodynamics and who had no
RI P
associated injuries requiring laparotomy, hepatic injury was diagnosed by computed tomography (CT). Two patients were excluded from the study because they had chronic liver
SC
disease caused by viral hepatitis. Three patients who were in cardiopulmonary arrest on admission and underwent surgery soon after resuscitation were not included the study.
MA NU
Patients with gunshot wounds were also excluded. We did not include patients whose referral was delayed by > 6 h or who were referred from another centre. We retrieved the following data from the patients’ medical records: demographic characteristics, AST, ALT, LDH, haemoglobin, and white blood cell (WBC) count on admission; cause of injury;
ED
haemodynamic status on presentation; hepatic injury grade; and the presence of coexisting
PT
abdominal and extra-abdominal injuries. Coexisting extra-abdominal injuries were broadly divided into those affecting the cranium, chest (including rib fracture, haemothorax or
CE
pneumothorax, lung, and cardiac injury), musculoskeletal system (including long bone
AC
fractures), and retroperitoneum (including pelvic fracture and great vessel injury). Using surgical records, liver injury was graded according to the Organ Injury Scale of the American Association for the Surgery of Trauma [5]. We divided the patients according to liver injury grade into two groups: Group 1 included patients with Grade 1 or 2 liver injuries, while Group 2 included patients with Grade 3–5 liver injury. We compared the characteristics of patients with coexisting intraabdominal and extra-abdominal injury. Data were analyzed using PASW software version 18.0 for Windows (SPSS, Chicago, IL, USA). The Kolmogorov–Smirnov test was used to evaluate the distribution of continuous variables. The χ2 test or Fisher’s exact test was used to compare categorical data. For continuous variables showing a parametric distribution, Student’s t test was used to compare
ACCEPTED MANUSCRIPT the mean values of two groups. For continuous variables showing a nonparametric distribution, the Kruskal–Wallis test or the Mann–Whitney U test was used to compare the
T
median values among groups. Correlation analyses were performed using Pearson’s or
RI P
Spearman’s methods. The odds ratio and 95% confidence intervals were calculated to estimate the relative risk between two groups with mortality as the outcome. Statistical
SC
significance was set at P < 0.05. The clinical performances of AST, ALT, and LDH levels for predicting liver injury were estimated using receiver operating characteristic (ROC) curves,
high specificity for the outcome.
ED
3. Results
MA NU
which were used to calculate the likelihood ratios for cutoff values showing high sensitivity or
PT
Between August 2004 and January 2012, 96 patients with liver injury were admitted to the Emergency Service Department of Ankara Numune Teaching and Research Hospital.
CE
There were 80 (83.3%) males and 16 (16.7%) females. Their age ranged from 17 to 90 years
AC
with a mean age of 34 years. The overall mortality rate was 14.6% (n = 14). Other demographic characteristics are listed in Table 1. The cause of injury was blunt trauma in 83 (86.5%) patients and penetrating injury in 13 (13.5%) patients. According to the characteristics of intraabdominal injury, 32 (33.3%) patients had isolated liver injury while the other 43 (44.8%) patients had 61 coexisting intraabdominal injuries. Liver injury was caused by multiple traumas in 60 (62.5%) patients. Musculoskeletal system injuries were the most common types of coexisting injury. In terms of intraoperative findings defined according to the Organ Injury Scale of the American Association for the Surgery of Trauma, 23 (24%) patients had Grade 1 injury, 32 (34%) patients had Grade 2 injury, 12 (12.5%) patients had Grade 3 injury, 5 (4%) patients
ACCEPTED MANUSCRIPT had Grade 4 injury, and 2 (2%) patients had Grade 5 injury. According to CT findings in the non-surgically treated group, 10 (10%) patients had Grade 1 injury, 11 (11.5%) patients had
T
Grade 2 injury, and 1 (1%) patient had Grade 3 injury.
RI P
There were no differences in AST, ALT, LDH, haemoglobin, or WBC count on admission between patients with isolated liver injury and patients with liver injury and
SC
coexisting intraabdominal injury (Table 2). However, when patients were divided according
MA NU
to the grade of liver injury, we found that AST, ALT, and LDH levels were significantly higher in Group 2 than in Group 1, but there were no differences in haemoglobin levels or the WBC count between the two groups (Table 3). In addition, AST, ALT, and LDH levels on admission were correlated with the grade of liver injury (Table 4).
ED
ROC curve analysis demonstrated that laboratory tests were a good discriminator for detecting serious liver injury. Using the ROC curves, the optimum ALT, AST, and LDH
PT
thresholds were determined to be < 76 U/l, ≤ 130 U/l, and ≤ 410 U/l for Grade 1 or 2 liver
CE
injuries (Figure 1). The positive predictive value and negative predictive value for AST, ALT,
AC
and LDH are presented in Table 5.
4. Discussion
Although splenic injury is common following blunt abdominal trauma, the liver is the most frequently injured intraabdominal organ [6]. Complex liver injuries are a challenging problem for clinicians and are associated with a mortality rate of up to 50%. However, Grade 1 and 2 liver injuries can usually be managed non-surgically with conservative methods. Indeed, conservative treatments are becoming a standard of care for haemodynamically stable patients with liver injury [2]. Patients with Grade 1 or 2 hepatic injuries can usually be resuscitated and carefully setting with serial examinations and daily blood sampling without
ACCEPTED MANUSCRIPT requiring invasive monitoring. Patients can generally resume their regular activities within 4– 6 weeks without sequelae. Higher-grade injuries routinely require observation in the intensive
T
care unit, invasive monitoring, and serial blood sampling. In addition, 20%–30% of these
RI P
patients require adjunctive treatment, including endoscopic retrograde
cholangiopancreatography, angiography, or percutaneous drainage of bilomas [7].
SC
Tan et al. reported that abdominal CT scanning has become the imaging mode of choice in trauma patients, but it can only be performed if available and in hemodynamically
MA NU
stable patients [8]. Furthermore, CT is costly, requires radiation exposure, and removes patients from direct clinical care. Because a significant number of health institutions worldwide do not have direct access to CT, the initial assessment and focused assessment with sonography in trauma (FAST) are vital aspects of care. However, FAST is not available
ED
in all healthcare institutions and a major limitation is that it requires highly trained staff, but
PT
even in trained hands may not be very good at grading liver injuries..
CE
Serum AST and ALT levels are often elevated in patients with blunt traumatic liver injury. In previous animal models and human studies, the levels of these enzymes increased
AC
within a few hours after blunt liver trauma, and the magnitude of the increase was correlated with the severity of liver injury [9], as was observed in the present study. In the few studies performed to date in pediatrics and adult patients, elevated transaminase (ALT and AST) levels were associated with the presence of hepatic injury after abdominal trauma [2–4,10]. Srivastava et al. reported that the median ALT level in patients who survived blunt liver injury or those who died because of a factor unrelated to liver trauma was significantly lower to that in patients who died because of blunt trauma liver injury [11]. Sahdev et al. reported that elevated AST and ALT levels were sensitive markers for abdominal involvement in patients with blunt trauma [10]. In another study to determine the utility of laboratory testing, Al-Mulhim and Mohammed published a report of 63 adult blunt trauma patients with multiple
ACCEPTED MANUSCRIPT injuries. All 63 patients had liver injuries proven by CT scan. There were no differences according to ALT levels between operative and nonoperative group. They have concluded
T
that the initial serum SGPT value neither excluded the presence of hepatic injury nor
RI P
predicted the need for laparotomy, in our patients [12]. Also, Karam et al. have demonstated that it does not seem possible to determine cut-off values of LFTs under which liver injury
SC
can be excluded [13]. However Lee et al. have shown a cut off level for liver laceration in patient who had abdominal trauma. In their study they have found that elevations of serum
MA NU
AST greater than 100 IU/L, ALT greater than 80 IU/L, and WBC count greater than 10 000/mm3 with a sensitivity and specificity of 90.0% and 92.3%, respectively, in the 42 liver laceration victims [14]. Also Stassen et al. have shown that patients with an admission AST level > 360 IU/L and a FAST with negative findings had a 88% chance of having any grade
ED
hepatic injury and a 44% chance of having a hepatic injury of grade III or greater, Patients
PT
with an AST level of < 360 IU/L and a FAST with negative findings only had a 14% chance of having a liver injury and no chance of having an injury of grade III or greater [2]. Tan et al.
CE
have demonstrated that patients with ALT and AST>2 times normal should be assumed to
AC
possess major hepatic trauma and managed accordingly, Patients with normal ALT, AST and LDH are unlikely to have major liver injuries [8]. Tian et al have suggested that in patients with blunt abdominal trauma, abnormal transaminase levels are associated with liver injury. Patients with ALT >57 U/l and AST >113 U/l are strongly associated with liver injury and require further imaging studies and close management [15]. In the present study, the optimum ALT, AST thresholds were determined to be < 76 U/l, ≤ 130 U/l for Grade 1 or 2 liver injuries. The differences between AST and ALT levels in the literature may be related to nature of studies whether retrospective or prospective. We have also found that AST and ALT levels on admission were correlated with mortality.
ACCEPTED MANUSCRIPT LDH is a cytoplasmic enzyme that is expressed in almost all major organ systems. It is released into the peripheral blood following cell death caused by ischaemia or injury, for
T
example. Because of its ubiquitous expression, the total serum LDH level is a highly
RI P
sensitive, but nonspecific test. In the present study, the LDH level on admission was correlated with mortality and the severity of liver injury. It was also independently associated
SC
with mortality in multivariate analysis. High LDH levels may reflect the number of affected
MA NU
organs and the severity of injury.
Hodgsons et al. reported that elevated AST and ALT levels had different clinical implications [16]. They reported that undiagnosed hepatic rupture accounted for 37% of deaths in an emergency department and that, even if the initial ultrasound is negative for free
ED
fluid or liver lesions, clinically suspected injuries should prompt further diagnostic evaluation during autopsy. Also Holmes and coworkers demonstrated CT-scan proven liver injuries in 10
PT
children who had neither abdominal tenderness, femur fracture, nor low systolic blood
CE
pressure, and had a GCS [Glasgow Coma Scale] score of more than 13. Nine of these 10 patients had an AST >200 U/L or ALT >125 U/L [17]. For that reason, high AST, ALT levels
AC
on admission may be warning for clinician even if absent of clinical findings. A combination of AST, ALT, and LDH levels may be a useful factor for predicting the presence of liver injury. However, prospective controlled studies with large numbers of patients are needed to determine their optimal cutoff values for predicting mortality. Our study has a number of limitations. It was retrospective in design and had small sample size. Another limitation is that muscle injury can cause significant rise in liver function tests that may confound the results in patients with significant musculoskeletal injuries.
ACCEPTED MANUSCRIPT In conclusion, the advantages of circulating biomarkers, including the ease of measurement, low cost, and quick turnaround time of results should encourage the use of
T
biomarkers as a valuable tool in the work-up of patients with abdominal trauma, especially in
RI P
remote centres in developing countries with limited or no access to expensive, expert radiological facilities. Therefore, in centres with limited resources, we advocate the
SC
measurement of serum ALT, AST, and LDH as part of the initial assessment of patients after abdominal trauma. Elevated ALT, AST, or LDH levels could indicate hepatic injuries, and the
MA NU
magnitude of the elevation could indicate the severity of liver injury.
1.
ED
References
Slotta JE, Justinger C, Kollmar O et al.: Liver injury following blunt abdominal
Stassen NA, Lukan JK, Carrillo EH et al.: Examination of the role of abdominal
CE
2.
PT
trauma: a new mechanism-driven classification. Surg Today 2014; 44(2):241-6.
computed tomography in the evaluation of victims of trauma with increased aspartate
AC
aminotransferase in the era of focused abdominal sonography for trauma. Surgery 2002; 132:642–646. 3.
Karaduman D, Sarioglu-Buke A, Kilic I et al.: The role of elevated liver transaminase
levels in children with blunt abdominal trauma. Injury 2003; 34:249–252. 4.
Miller K, Kou D, Sivit C et al.: Pediatric hepatic trauma: does clinical course support
intensive care unit stay? J Pediatr Surg 1998; 33:1459–1462. 5.
Moore EE, Cogbill TH, Jurkovich GJ et al.: Organ injury scaling: spleen and liver
(1994 revision). J Trauma 1995; 38:323–324.
ACCEPTED MANUSCRIPT 6.
Parks RW, Chrysos E, Diamond T: Management of liver trauma. Br J Surg 1999;
86:1121–1135. Carrillo EH, Spain DA, Wohltmann CD et al.: Interventional techniques are useful
T
7.
Tan KK, Bang SL, Vijayan A et al.: Hepatic enzymes have a role in the diagnosis of
SC
8.
RI P
adjuncts in nonoperative management of hepatic injuries. J Trauma 1999; 46:619–622.
hepatic injury after blunt abdominal trauma. Injury 2009; 40:978–983. Ritchie AH, Williscroft DM: Elevated liver enzymes as a predictor of liver injury in
MA NU
9.
stable blunt abdominal trauma patients: case report and systematic review of the literature. Can J Rural Med 2006; 11:283–287.
Sahdev P, Garramone Jr R, Schwartz RJ et al.: Evaluation of liver function tests in
ED
10.
11.
PT
screening for intraabdominal injuries. Ann Emerg Med 1991; 20:838–841. Srivastava AR, Kumar S, Agarwal GG et al.: Blunt abdominal injury: serum ALT-A
Al-Mulhim A, Mohammad H: Non-operative management of blunt hepatic injury in
AC
12.
CE
marker of liver injury and a guide to assessment of its severity. Injury 2007; 38:1069–1074.
multiply injured adult patients. Surgeon 2003; 1(2):81-5. 13.
Karam O, La Scala G, Le Coultre C et al.: Liver function tests in children with blunt
abdominal traumas. Eur J Pediatr Surg 2007; 17(5):313-6. 14.
Lee WC, Kuo LC, Cheng YC et al.: Combination of white blood cell count with liver
enzymes in the diagnosis of blunt liver laceration. Am J Emerg Med 2010; 28(9):1024-9. 15.
Tian Z, Liu H, Su X et al.: Role of elevated liver transaminase levels in the diagnosis
of liver injury after blunt abdominal trauma. Exp Ther Med 2012; 4(2):255-260.
ACCEPTED MANUSCRIPT 16.
Hodgsons NF, Stewart TC, Girotti MJ: Autopsies and death certification in deaths due
to blunt trauma: what are we missing? Can J Surg 2000; 43:130–136. Holmes J, Sokolove P, Brant W et al.: Identification of children with intra-abdominal
SC
RI P
injuires after blunt trauma. Ann Emerg Med 2002; 39:500-8.
T
17.
Figure-1 Receiver operating characteristic (ROC) of (A) aspartate aminotransferase, (B)
MA NU
alanine aminotransferase and (C) lactate dehydrogenase. AUC: Area under the ROC curve Table-1 Characteristics of patients according to the grade of liver injury Table-2 Laboratory results in patients with coexisting intraabdominal injury or isolated liver
ED
injury
PT
Table-3 Laboratory results in patients with low- or high-grade liver injury
CE
Table-4 Correlations between the grade of liver injury and AST, ALT, and LDH levels
AC
Table-5 Results of ROC curve analysis for predicting Grade 1 or 2 liver injuries
AC
CE
PT
ED
MA NU
SC
RI P
T
ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT Table-1
(n = 76)
(n = 20)
32 (17–90)
T
Group 2
35 (19–61)
RI P
Age (years), median (range)
Group 1
Gender, n (%)
62 (81.5)
Female
14 (18.5)
SC
Male
MA NU
Cause of injury, n (%) Road traffic accident
18 (90) 2 (10)
52 (68.4)
15 (75)
8 (10.5)
3 (15)
5 (6.6)
–
11 (14.5)
2 (10)
58 (76.3)
2 (10)
18 (23.7)
18 (90)
70 (92)
12 (60)
6 (8)
8 (40)
Yes
56 (74)
19 (95)
No
20 (26)
1 (5)
Fall
ED
Assault Stab wound
PT
Haemodynamic status on admission, n (%)
Unstable
Alive Dead
AC
Outcome, n (%)
CE
StableStabile
Surgical intervention, n (%)
Group 1, patients with Grade 1 or 2 liver injuries; Group 2, patients with Grade 3–5 liver injury.
ACCEPTED MANUSCRIPT
RI P
T
Table-2
Patients with
and coexisting abdominal
isolated liver injury
injury 299.6 ± 416.9
Median (range)
92 (13–1733)
46.5 (11–1263)
IQR
441
434.5
Mean ± SD
299.0 ± 457.7
234.1 ± 303.8
Median (range)
76 (11–1551)
48.5 (8–1038)
IQR
321.5
391.7
Mean ± SD
504.5 ± 583.7
486.7 ± 510.5
Median (range)
229.0 (120–2577)
220.5 (106–2102)
IQR
359
610
WBC count,
Mean ± SD
14747 ± 7097
14356 ± 7456
cells/µl
Median (range)
11650 (5600–33000)
10650 (5900–34200)
IQR
9025
11375
13.3 ± 2.3
12.9 ± 2.1
Median (range)
13.65 (7.6–18.30)
13.1 (9.4–16.6)
IQR
3.38
3.92
AC
LDH, U/l
CE
PT
ALT, U/l
Haemoglobin Mean ± SD
a
Mann-Whitney U test.
b
Student’s t test.
MA NU
Mean ± SD
ED
AST
SC
Patients with liver injury
258.8 ± 324.4
SD, standard deviation; IQR, interquartile range; WBC, white blood cell.
P
0.49a
0.46a
0.67a
0.45a
0.57b
ACCEPTED MANUSCRIPT Table-3
LDH
Mean ± SD
161.2 ± 228.8
692.1 ± 453.9
< 0.01a
Median (range)
42.5 (11–970)
543 (140–1733)
IQR
177
Mean ± SD
150.5 ± 237.3
Median (range)
32 (8–1038)
IQR
156.75
Mean ± SD
343.5 ± 317.4
1034.67 ± 819.2
Median (range)
212.5 (106–1450)
1031 (120–2577)
IQR
145
1561
Mean ± SD
cells/µl
Median (range)
RI P 720
14088 ± 7104
410 (110–1551) 578
16053 ± 7882
13.1 ± 2.1
13.0 ± 2.5
Median (range)
13.5 (8.3–18.3)
13.7 (7.6–16.3)
3.55
3.7
CE
Mean ± SD
a
Mann-Whitney U test.
b
Student’s t test.
< 0.01a
0.42a
10700 (5600–34200) 11800 (8500–33000) 12400
IQR
< 0.01a
SC
652.8 ± 484.1
9200
AC
Haemoglobin
PT
WBC count,
IQR
T
P
MA NU
ALT
Group 2
ED
AST
Group 1
0.86b
Group 1, patients with Grade 1 or 2 liver injury; Group 2, patients with Grade 3–5 liver injury; SD, standard deviation; IQR, interquartile range; WBC, white blood cell.
ACCEPTED MANUSCRIPT
r
P
AST
0.498
< 0.001
ALT
0.548
< 0.001
LDH
0.408
< 0.001
RI P
Parameter
T
Table-4
MA NU
SC
r, correlation coefficient; AST, aspartate aminotransferase; ALT, alanine aminotransferase; LDH, lactate dehydrogenase.
Table 5
NLR
PPV
NPV
value (U/l)
(95% CI)
(95% CI)
(95% CI)
(95% CI)
(95% CI)
(95% CI)
< 130
80.26
94.74
15.25
0.21
98.4
54.5
(69.5–88.5)
(74.0–99.9)
(2.3–103.1)
(0.1–0.3)
(91.3–100.0)
(36.1–72.2)
77.63
100.00
-
0.22
100.0
52.8
(0.1–0.3)
(93.9–100.0)
(35.5–69.6)
≤ 76
≤ 410
ED
PLR
(66.6–86.4)
(82.4–100.0)
86.49
68.42
2.74
0.20
91.4
56.5
(76.5–93.3)
(43.4–87.4)
(1.4–5.3)
(0.1–0.4)
(82.3–96.8)
(34.5–76.8)
AC
LDH
Specificity
PT
ALT
Sensitivity
CE
AST
Cutoff
ROC, receiver-operating characteristic; CI, confidence interval; PLR, positive likelihood ratio; NLR, negative likelihood ratio; PPV, positive predictive value; NPV, negative predictive value; AST, aspartate aminotransferase; ALT, alanine aminotransferase; LDH, lactate dehydrogenase
S0735-6757(14)00240-X doi: 10.1016/j.ajem.2014.03.052 YAJEM 54230
To appear in:
American Journal of Emergency Medicine
Received date: Revised date: Accepted date:
16 January 2014 30 March 2014 31 March 2014
Please cite this article as: Bilgic Ismail, Gelecek Sibel, Akgun Ali Emre, Mahir Ozmen M, Predictive value of liver transaminases levels in abdominal trauma, American Journal of Emergency Medicine (2014), doi: 10.1016/j.ajem.2014.03.052
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT “PREDICTIVE VALUE OF LIVER TRANSAMINASES LEVELS IN ABDOMINAL TRAUMA”
T
Short running head: “Liver transaminases in abdominal trauma”
RI P
Ismail Bilgica, Sibel Geleceka, Ali Emre Akguna, M. Mahir Ozmena,b
Department of Surgery, Ankara Numune Teaching and Research Hospital, Ankara-Turkey
b
Department of Surgery, Hacettepe University, Medical School, Ankara-Turkey
Corresponding Author: Name: Ismail BILGIC
MA NU
SC
a
Address: İşçi Blokları mah. 1489. cad. Kardelen sitesi C/35 postal code: 06530, Balgat,
Phone: +90 (0312) 2840867
PT
Faks: +90 (0312) 203 50 28
ED
Çankaya, ANKARA
E-Mail: [email protected]
AC
of interest.
CE
The authors have no commercial associations or sources of support that might pose a conflict
Keywords: abdomen; liver; liver enzymes; trauma
Abstract Introduction: We aimed to evaluate whether hepatic transaminase levels could predict the presence and severity of liver injury following abdominal trauma.
ACCEPTED MANUSCRIPT Methods: We performed a retrospective analysis of 75 surgically treated patients and 21 nonsurgically treated patients with liver injury who were managed between 2004 and 2012. We
T
retrieved demographic, laboratory, radiologic, and intraoperative data, as well as surgical
RI P
procedures and the outcome from the patients’ medical records. We compared the findings between patients divided into two groups according to the severity of liver injury: Group 1,
SC
including patients with Grade 1 or 2 liver injuries; and Group 2, including patients with Grade
MA NU
3–5 liver injury.
Results: There were 87 (90.6%) males and 9 (9.4%) females. The mean age was 34 years (range 17–90 years). The overall mortality rate was 14.6% (n = 14). The injury was blunt in 83 (86.5%) patients and penetrating in 13 (13.5%) patients. There were multiple traumas in 60
ED
(62.5%) patients. Overall, 43 (44.8%) patients had a total of 61 coexisting intraabdominal injuries. The circulating aspartate aminotransferase, alanine aminotransferase, and lactate
PT
dehydrogenase (LDH) levels were significantly higher in Group 2 than in Group 1.
CE
Conclusions: In patients with abdominal trauma, abnormal hepatic transaminase and LDH levels are associated with liver injury. Alanine aminotransferase ≤ 76 U/l, aspartate
AC
aminotransferase < 130 U/l, and LDH ≤ 410 U/l are predictive of low-grade liver injury, and patients with serum liver levels below these levels can be managed conservatively.
1. Introduction
ACCEPTED MANUSCRIPT The liver is the most frequently injured organ following abdominal trauma [1], and liver injury significantly increases the risk of morbidity and mortality. The liver is a
T
particularly vulnerable organ because of its size, and its fixed position in the right
RI P
hypochondrium. In recent years, nonsurgical treatment of hepatic injury has entered clinical practice and has helped to avoid unnecessary laparotomy. Hepatic injuries of Grade 2 or lower
SC
are rarely clinically serious, with the patient generally requiring minimal resuscitation and observation, without the need for surgery [2]. For hepatic injuries of Grade 3 or above,
MA NU
however, 20%–30% of patients require adjunctive treatments together with invasive monitoring [2]. Serum hepatic enzyme levels are routinely measured as part of the initial laboratory evaluation of trauma patients. However, small-scale studies of paediatric trauma patients have revealed a broad range in the threshold levels of liver enzymes on admission,
ED
and patients with levels below these thresholds did not have clinically significant liver injury
PT
[3,4]. So far, very few articles have described the potential value of serum hepatic enzymes for the diagnosis of liver injury in adults. Therefore, the purpose of this study was to
CE
determine the threshold levels of aspartate aminotransferase (AST), alanine aminotransferase
AC
(ALT), and lactate dehydrogenase (LDH) on admission for predicting low-grade liver injury.
2. Materials and methods
This retrospective clinical study was performed at the Emergency Service Department of Ankara Numune Teaching and Research Hospital between August 2004 and January 2012. We reviewed 101 consecutive patients, of which 96 were included in this study. In 75 patients, liver trauma was confirmed by exploratory surgery. These patients had an unstable haemodynamic status or signs of abdominal injury that required surgery. Three patients with
ACCEPTED MANUSCRIPT stable haemodynamics on admission were initially treated conservatively, but these patients subsequently underwent laparotomy within 8–24 h of admission because of deteriorations in
T
their haemodynamic status. In 21 patients with stable haemodynamics and who had no
RI P
associated injuries requiring laparotomy, hepatic injury was diagnosed by computed tomography (CT). Two patients were excluded from the study because they had chronic liver
SC
disease caused by viral hepatitis. Three patients who were in cardiopulmonary arrest on admission and underwent surgery soon after resuscitation were not included the study.
MA NU
Patients with gunshot wounds were also excluded. We did not include patients whose referral was delayed by > 6 h or who were referred from another centre. We retrieved the following data from the patients’ medical records: demographic characteristics, AST, ALT, LDH, haemoglobin, and white blood cell (WBC) count on admission; cause of injury;
ED
haemodynamic status on presentation; hepatic injury grade; and the presence of coexisting
PT
abdominal and extra-abdominal injuries. Coexisting extra-abdominal injuries were broadly divided into those affecting the cranium, chest (including rib fracture, haemothorax or
CE
pneumothorax, lung, and cardiac injury), musculoskeletal system (including long bone
AC
fractures), and retroperitoneum (including pelvic fracture and great vessel injury). Using surgical records, liver injury was graded according to the Organ Injury Scale of the American Association for the Surgery of Trauma [5]. We divided the patients according to liver injury grade into two groups: Group 1 included patients with Grade 1 or 2 liver injuries, while Group 2 included patients with Grade 3–5 liver injury. We compared the characteristics of patients with coexisting intraabdominal and extra-abdominal injury. Data were analyzed using PASW software version 18.0 for Windows (SPSS, Chicago, IL, USA). The Kolmogorov–Smirnov test was used to evaluate the distribution of continuous variables. The χ2 test or Fisher’s exact test was used to compare categorical data. For continuous variables showing a parametric distribution, Student’s t test was used to compare
ACCEPTED MANUSCRIPT the mean values of two groups. For continuous variables showing a nonparametric distribution, the Kruskal–Wallis test or the Mann–Whitney U test was used to compare the
T
median values among groups. Correlation analyses were performed using Pearson’s or
RI P
Spearman’s methods. The odds ratio and 95% confidence intervals were calculated to estimate the relative risk between two groups with mortality as the outcome. Statistical
SC
significance was set at P < 0.05. The clinical performances of AST, ALT, and LDH levels for predicting liver injury were estimated using receiver operating characteristic (ROC) curves,
high specificity for the outcome.
ED
3. Results
MA NU
which were used to calculate the likelihood ratios for cutoff values showing high sensitivity or
PT
Between August 2004 and January 2012, 96 patients with liver injury were admitted to the Emergency Service Department of Ankara Numune Teaching and Research Hospital.
CE
There were 80 (83.3%) males and 16 (16.7%) females. Their age ranged from 17 to 90 years
AC
with a mean age of 34 years. The overall mortality rate was 14.6% (n = 14). Other demographic characteristics are listed in Table 1. The cause of injury was blunt trauma in 83 (86.5%) patients and penetrating injury in 13 (13.5%) patients. According to the characteristics of intraabdominal injury, 32 (33.3%) patients had isolated liver injury while the other 43 (44.8%) patients had 61 coexisting intraabdominal injuries. Liver injury was caused by multiple traumas in 60 (62.5%) patients. Musculoskeletal system injuries were the most common types of coexisting injury. In terms of intraoperative findings defined according to the Organ Injury Scale of the American Association for the Surgery of Trauma, 23 (24%) patients had Grade 1 injury, 32 (34%) patients had Grade 2 injury, 12 (12.5%) patients had Grade 3 injury, 5 (4%) patients
ACCEPTED MANUSCRIPT had Grade 4 injury, and 2 (2%) patients had Grade 5 injury. According to CT findings in the non-surgically treated group, 10 (10%) patients had Grade 1 injury, 11 (11.5%) patients had
T
Grade 2 injury, and 1 (1%) patient had Grade 3 injury.
RI P
There were no differences in AST, ALT, LDH, haemoglobin, or WBC count on admission between patients with isolated liver injury and patients with liver injury and
SC
coexisting intraabdominal injury (Table 2). However, when patients were divided according
MA NU
to the grade of liver injury, we found that AST, ALT, and LDH levels were significantly higher in Group 2 than in Group 1, but there were no differences in haemoglobin levels or the WBC count between the two groups (Table 3). In addition, AST, ALT, and LDH levels on admission were correlated with the grade of liver injury (Table 4).
ED
ROC curve analysis demonstrated that laboratory tests were a good discriminator for detecting serious liver injury. Using the ROC curves, the optimum ALT, AST, and LDH
PT
thresholds were determined to be < 76 U/l, ≤ 130 U/l, and ≤ 410 U/l for Grade 1 or 2 liver
CE
injuries (Figure 1). The positive predictive value and negative predictive value for AST, ALT,
AC
and LDH are presented in Table 5.
4. Discussion
Although splenic injury is common following blunt abdominal trauma, the liver is the most frequently injured intraabdominal organ [6]. Complex liver injuries are a challenging problem for clinicians and are associated with a mortality rate of up to 50%. However, Grade 1 and 2 liver injuries can usually be managed non-surgically with conservative methods. Indeed, conservative treatments are becoming a standard of care for haemodynamically stable patients with liver injury [2]. Patients with Grade 1 or 2 hepatic injuries can usually be resuscitated and carefully setting with serial examinations and daily blood sampling without
ACCEPTED MANUSCRIPT requiring invasive monitoring. Patients can generally resume their regular activities within 4– 6 weeks without sequelae. Higher-grade injuries routinely require observation in the intensive
T
care unit, invasive monitoring, and serial blood sampling. In addition, 20%–30% of these
RI P
patients require adjunctive treatment, including endoscopic retrograde
cholangiopancreatography, angiography, or percutaneous drainage of bilomas [7].
SC
Tan et al. reported that abdominal CT scanning has become the imaging mode of choice in trauma patients, but it can only be performed if available and in hemodynamically
MA NU
stable patients [8]. Furthermore, CT is costly, requires radiation exposure, and removes patients from direct clinical care. Because a significant number of health institutions worldwide do not have direct access to CT, the initial assessment and focused assessment with sonography in trauma (FAST) are vital aspects of care. However, FAST is not available
ED
in all healthcare institutions and a major limitation is that it requires highly trained staff, but
PT
even in trained hands may not be very good at grading liver injuries..
CE
Serum AST and ALT levels are often elevated in patients with blunt traumatic liver injury. In previous animal models and human studies, the levels of these enzymes increased
AC
within a few hours after blunt liver trauma, and the magnitude of the increase was correlated with the severity of liver injury [9], as was observed in the present study. In the few studies performed to date in pediatrics and adult patients, elevated transaminase (ALT and AST) levels were associated with the presence of hepatic injury after abdominal trauma [2–4,10]. Srivastava et al. reported that the median ALT level in patients who survived blunt liver injury or those who died because of a factor unrelated to liver trauma was significantly lower to that in patients who died because of blunt trauma liver injury [11]. Sahdev et al. reported that elevated AST and ALT levels were sensitive markers for abdominal involvement in patients with blunt trauma [10]. In another study to determine the utility of laboratory testing, Al-Mulhim and Mohammed published a report of 63 adult blunt trauma patients with multiple
ACCEPTED MANUSCRIPT injuries. All 63 patients had liver injuries proven by CT scan. There were no differences according to ALT levels between operative and nonoperative group. They have concluded
T
that the initial serum SGPT value neither excluded the presence of hepatic injury nor
RI P
predicted the need for laparotomy, in our patients [12]. Also, Karam et al. have demonstated that it does not seem possible to determine cut-off values of LFTs under which liver injury
SC
can be excluded [13]. However Lee et al. have shown a cut off level for liver laceration in patient who had abdominal trauma. In their study they have found that elevations of serum
MA NU
AST greater than 100 IU/L, ALT greater than 80 IU/L, and WBC count greater than 10 000/mm3 with a sensitivity and specificity of 90.0% and 92.3%, respectively, in the 42 liver laceration victims [14]. Also Stassen et al. have shown that patients with an admission AST level > 360 IU/L and a FAST with negative findings had a 88% chance of having any grade
ED
hepatic injury and a 44% chance of having a hepatic injury of grade III or greater, Patients
PT
with an AST level of < 360 IU/L and a FAST with negative findings only had a 14% chance of having a liver injury and no chance of having an injury of grade III or greater [2]. Tan et al.
CE
have demonstrated that patients with ALT and AST>2 times normal should be assumed to
AC
possess major hepatic trauma and managed accordingly, Patients with normal ALT, AST and LDH are unlikely to have major liver injuries [8]. Tian et al have suggested that in patients with blunt abdominal trauma, abnormal transaminase levels are associated with liver injury. Patients with ALT >57 U/l and AST >113 U/l are strongly associated with liver injury and require further imaging studies and close management [15]. In the present study, the optimum ALT, AST thresholds were determined to be < 76 U/l, ≤ 130 U/l for Grade 1 or 2 liver injuries. The differences between AST and ALT levels in the literature may be related to nature of studies whether retrospective or prospective. We have also found that AST and ALT levels on admission were correlated with mortality.
ACCEPTED MANUSCRIPT LDH is a cytoplasmic enzyme that is expressed in almost all major organ systems. It is released into the peripheral blood following cell death caused by ischaemia or injury, for
T
example. Because of its ubiquitous expression, the total serum LDH level is a highly
RI P
sensitive, but nonspecific test. In the present study, the LDH level on admission was correlated with mortality and the severity of liver injury. It was also independently associated
SC
with mortality in multivariate analysis. High LDH levels may reflect the number of affected
MA NU
organs and the severity of injury.
Hodgsons et al. reported that elevated AST and ALT levels had different clinical implications [16]. They reported that undiagnosed hepatic rupture accounted for 37% of deaths in an emergency department and that, even if the initial ultrasound is negative for free
ED
fluid or liver lesions, clinically suspected injuries should prompt further diagnostic evaluation during autopsy. Also Holmes and coworkers demonstrated CT-scan proven liver injuries in 10
PT
children who had neither abdominal tenderness, femur fracture, nor low systolic blood
CE
pressure, and had a GCS [Glasgow Coma Scale] score of more than 13. Nine of these 10 patients had an AST >200 U/L or ALT >125 U/L [17]. For that reason, high AST, ALT levels
AC
on admission may be warning for clinician even if absent of clinical findings. A combination of AST, ALT, and LDH levels may be a useful factor for predicting the presence of liver injury. However, prospective controlled studies with large numbers of patients are needed to determine their optimal cutoff values for predicting mortality. Our study has a number of limitations. It was retrospective in design and had small sample size. Another limitation is that muscle injury can cause significant rise in liver function tests that may confound the results in patients with significant musculoskeletal injuries.
ACCEPTED MANUSCRIPT In conclusion, the advantages of circulating biomarkers, including the ease of measurement, low cost, and quick turnaround time of results should encourage the use of
T
biomarkers as a valuable tool in the work-up of patients with abdominal trauma, especially in
RI P
remote centres in developing countries with limited or no access to expensive, expert radiological facilities. Therefore, in centres with limited resources, we advocate the
SC
measurement of serum ALT, AST, and LDH as part of the initial assessment of patients after abdominal trauma. Elevated ALT, AST, or LDH levels could indicate hepatic injuries, and the
MA NU
magnitude of the elevation could indicate the severity of liver injury.
1.
ED
References
Slotta JE, Justinger C, Kollmar O et al.: Liver injury following blunt abdominal
Stassen NA, Lukan JK, Carrillo EH et al.: Examination of the role of abdominal
CE
2.
PT
trauma: a new mechanism-driven classification. Surg Today 2014; 44(2):241-6.
computed tomography in the evaluation of victims of trauma with increased aspartate
AC
aminotransferase in the era of focused abdominal sonography for trauma. Surgery 2002; 132:642–646. 3.
Karaduman D, Sarioglu-Buke A, Kilic I et al.: The role of elevated liver transaminase
levels in children with blunt abdominal trauma. Injury 2003; 34:249–252. 4.
Miller K, Kou D, Sivit C et al.: Pediatric hepatic trauma: does clinical course support
intensive care unit stay? J Pediatr Surg 1998; 33:1459–1462. 5.
Moore EE, Cogbill TH, Jurkovich GJ et al.: Organ injury scaling: spleen and liver
(1994 revision). J Trauma 1995; 38:323–324.
ACCEPTED MANUSCRIPT 6.
Parks RW, Chrysos E, Diamond T: Management of liver trauma. Br J Surg 1999;
86:1121–1135. Carrillo EH, Spain DA, Wohltmann CD et al.: Interventional techniques are useful
T
7.
Tan KK, Bang SL, Vijayan A et al.: Hepatic enzymes have a role in the diagnosis of
SC
8.
RI P
adjuncts in nonoperative management of hepatic injuries. J Trauma 1999; 46:619–622.
hepatic injury after blunt abdominal trauma. Injury 2009; 40:978–983. Ritchie AH, Williscroft DM: Elevated liver enzymes as a predictor of liver injury in
MA NU
9.
stable blunt abdominal trauma patients: case report and systematic review of the literature. Can J Rural Med 2006; 11:283–287.
Sahdev P, Garramone Jr R, Schwartz RJ et al.: Evaluation of liver function tests in
ED
10.
11.
PT
screening for intraabdominal injuries. Ann Emerg Med 1991; 20:838–841. Srivastava AR, Kumar S, Agarwal GG et al.: Blunt abdominal injury: serum ALT-A
Al-Mulhim A, Mohammad H: Non-operative management of blunt hepatic injury in
AC
12.
CE
marker of liver injury and a guide to assessment of its severity. Injury 2007; 38:1069–1074.
multiply injured adult patients. Surgeon 2003; 1(2):81-5. 13.
Karam O, La Scala G, Le Coultre C et al.: Liver function tests in children with blunt
abdominal traumas. Eur J Pediatr Surg 2007; 17(5):313-6. 14.
Lee WC, Kuo LC, Cheng YC et al.: Combination of white blood cell count with liver
enzymes in the diagnosis of blunt liver laceration. Am J Emerg Med 2010; 28(9):1024-9. 15.
Tian Z, Liu H, Su X et al.: Role of elevated liver transaminase levels in the diagnosis
of liver injury after blunt abdominal trauma. Exp Ther Med 2012; 4(2):255-260.
ACCEPTED MANUSCRIPT 16.
Hodgsons NF, Stewart TC, Girotti MJ: Autopsies and death certification in deaths due
to blunt trauma: what are we missing? Can J Surg 2000; 43:130–136. Holmes J, Sokolove P, Brant W et al.: Identification of children with intra-abdominal
SC
RI P
injuires after blunt trauma. Ann Emerg Med 2002; 39:500-8.
T
17.
Figure-1 Receiver operating characteristic (ROC) of (A) aspartate aminotransferase, (B)
MA NU
alanine aminotransferase and (C) lactate dehydrogenase. AUC: Area under the ROC curve Table-1 Characteristics of patients according to the grade of liver injury Table-2 Laboratory results in patients with coexisting intraabdominal injury or isolated liver
ED
injury
PT
Table-3 Laboratory results in patients with low- or high-grade liver injury
CE
Table-4 Correlations between the grade of liver injury and AST, ALT, and LDH levels
AC
Table-5 Results of ROC curve analysis for predicting Grade 1 or 2 liver injuries
AC
CE
PT
ED
MA NU
SC
RI P
T
ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT Table-1
(n = 76)
(n = 20)
32 (17–90)
T
Group 2
35 (19–61)
RI P
Age (years), median (range)
Group 1
Gender, n (%)
62 (81.5)
Female
14 (18.5)
SC
Male
MA NU
Cause of injury, n (%) Road traffic accident
18 (90) 2 (10)
52 (68.4)
15 (75)
8 (10.5)
3 (15)
5 (6.6)
–
11 (14.5)
2 (10)
58 (76.3)
2 (10)
18 (23.7)
18 (90)
70 (92)
12 (60)
6 (8)
8 (40)
Yes
56 (74)
19 (95)
No
20 (26)
1 (5)
Fall
ED
Assault Stab wound
PT
Haemodynamic status on admission, n (%)
Unstable
Alive Dead
AC
Outcome, n (%)
CE
StableStabile
Surgical intervention, n (%)
Group 1, patients with Grade 1 or 2 liver injuries; Group 2, patients with Grade 3–5 liver injury.
ACCEPTED MANUSCRIPT
RI P
T
Table-2
Patients with
and coexisting abdominal
isolated liver injury
injury 299.6 ± 416.9
Median (range)
92 (13–1733)
46.5 (11–1263)
IQR
441
434.5
Mean ± SD
299.0 ± 457.7
234.1 ± 303.8
Median (range)
76 (11–1551)
48.5 (8–1038)
IQR
321.5
391.7
Mean ± SD
504.5 ± 583.7
486.7 ± 510.5
Median (range)
229.0 (120–2577)
220.5 (106–2102)
IQR
359
610
WBC count,
Mean ± SD
14747 ± 7097
14356 ± 7456
cells/µl
Median (range)
11650 (5600–33000)
10650 (5900–34200)
IQR
9025
11375
13.3 ± 2.3
12.9 ± 2.1
Median (range)
13.65 (7.6–18.30)
13.1 (9.4–16.6)
IQR
3.38
3.92
AC
LDH, U/l
CE
PT
ALT, U/l
Haemoglobin Mean ± SD
a
Mann-Whitney U test.
b
Student’s t test.
MA NU
Mean ± SD
ED
AST
SC
Patients with liver injury
258.8 ± 324.4
SD, standard deviation; IQR, interquartile range; WBC, white blood cell.
P
0.49a
0.46a
0.67a
0.45a
0.57b
ACCEPTED MANUSCRIPT Table-3
LDH
Mean ± SD
161.2 ± 228.8
692.1 ± 453.9
< 0.01a
Median (range)
42.5 (11–970)
543 (140–1733)
IQR
177
Mean ± SD
150.5 ± 237.3
Median (range)
32 (8–1038)
IQR
156.75
Mean ± SD
343.5 ± 317.4
1034.67 ± 819.2
Median (range)
212.5 (106–1450)
1031 (120–2577)
IQR
145
1561
Mean ± SD
cells/µl
Median (range)
RI P 720
14088 ± 7104
410 (110–1551) 578
16053 ± 7882
13.1 ± 2.1
13.0 ± 2.5
Median (range)
13.5 (8.3–18.3)
13.7 (7.6–16.3)
3.55
3.7
CE
Mean ± SD
a
Mann-Whitney U test.
b
Student’s t test.
< 0.01a
0.42a
10700 (5600–34200) 11800 (8500–33000) 12400
IQR
< 0.01a
SC
652.8 ± 484.1
9200
AC
Haemoglobin
PT
WBC count,
IQR
T
P
MA NU
ALT
Group 2
ED
AST
Group 1
0.86b
Group 1, patients with Grade 1 or 2 liver injury; Group 2, patients with Grade 3–5 liver injury; SD, standard deviation; IQR, interquartile range; WBC, white blood cell.
ACCEPTED MANUSCRIPT
r
P
AST
0.498
< 0.001
ALT
0.548
< 0.001
LDH
0.408
< 0.001
RI P
Parameter
T
Table-4
MA NU
SC
r, correlation coefficient; AST, aspartate aminotransferase; ALT, alanine aminotransferase; LDH, lactate dehydrogenase.
Table 5
NLR
PPV
NPV
value (U/l)
(95% CI)
(95% CI)
(95% CI)
(95% CI)
(95% CI)
(95% CI)
< 130
80.26
94.74
15.25
0.21
98.4
54.5
(69.5–88.5)
(74.0–99.9)
(2.3–103.1)
(0.1–0.3)
(91.3–100.0)
(36.1–72.2)
77.63
100.00
-
0.22
100.0
52.8
(0.1–0.3)
(93.9–100.0)
(35.5–69.6)
≤ 76
≤ 410
ED
PLR
(66.6–86.4)
(82.4–100.0)
86.49
68.42
2.74
0.20
91.4
56.5
(76.5–93.3)
(43.4–87.4)
(1.4–5.3)
(0.1–0.4)
(82.3–96.8)
(34.5–76.8)
AC
LDH
Specificity
PT
ALT
Sensitivity
CE
AST
Cutoff
ROC, receiver-operating characteristic; CI, confidence interval; PLR, positive likelihood ratio; NLR, negative likelihood ratio; PPV, positive predictive value; NPV, negative predictive value; AST, aspartate aminotransferase; ALT, alanine aminotransferase; LDH, lactate dehydrogenase
