a b s t r a c t

Introduction: We aimed to evaluate whether hepatic transaminase levels could predict the presence and severity of liver injury following abdominal trauma.

Methods: We performed a retrospective analysis of 75 surgically treated patients and 21 non-surgically treated patients with liver injury who were managed between 2004 and 2012. We retrieved demographic, laboratory, radiologic, and intraoperative data, as well as surgical procedures and the outcome from the patients’ medical records. We compared the findings between patients divided into 2 groups according to the severity of liver injury: group 1, including patients with Grade 1 or 2 liver injuries; and group 2, including patients with grade 3 to 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 patients (86.5%) and penetrating in 13 patients (13.5%). There were multiple traumas in 60 patients (62.5%). Overall, 43 patients (44.8%) had a total of 61 coexisting Intraabdominal injuries. The circulating aspartate aminotransferase, alanine aminotransferase, and Lactate dehydrogenase levels were significantly higher in group 2 than in group 1.

Conclusions: In patients with abdominal trauma, abnormal hepatic transaminase and LDH levels are associated with liver injury. Alanine aminotransferase <=76 U/L, aspartate aminotransferase b 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.

(C) 2014

Introduction

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 particularly vulnerable organ because of its size, and its fixed position in the right 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 are rarely clinically serious, with the patient generally requiring minimal resuscitation and observa- tion, without the need for surgery [2]. For hepatic injuries of Grade 3 or above, however, 20% to 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 Pediatric trauma patients have revealed a broad range in the threshold levels of Liver enzymes on admission, and patients with

? The authors have no commercial associations or sources of support that might pose a conflict of interest.

* Corresponding author at: Isci Bloklari mah. 1489. cad. Kardelen sitesi C/35 postal code: 06530, Balgat, Cankaya, Ankara. Tel.: +90 312 2840867; fax: +90 312 203 50 28.

E-mail address: [email protected] (I. Bilgic).

levels below these thresholds did not have clinically significant liver injury [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 determine the threshold levels of aspartate aminotransferase , alanine aminotransferase (ALT), and Lactate dehydrogenase on admission for predicting low-grade liver injury.

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 hemodynamic status or signs of Abdominal injury that required surgery. Three patients with stable hemodynam- ics on admission were initially treated conservatively, but these patients subsequently underwent laparotomy within 8 to 24 hours of admission because of deteriorations in their hemodynamic status. In 21 patients with stable hemodynamics and who had no Associated injuries requiring laparotomy, hepatic injury was diagnosed by computed tomography (CT). Two patients were excluded from the

http://dx.doi.org/10.1016/j.ajem.2014.03.052

0735-6757/(C) 2014

706 I. Bilgic et al. / American Journal of Emergency Medicine 32 (2014) 705–708

Table 1

Characteristics of patients according to the grade of liver injury

Group 1 (n = 76) Group 2 (n = 20)

Age (years), median (range) 32 (17-90) 35 (19-61) Gender, n (%)

Male 62 (81.5) 18 (90)

Female 14 (18.5) 2 (10)

Cause of injury, n (%)

Road traffic accident 52 (68.4) 15 (75)

Fall 8 (10.5) 3 (15)

Assault 5 (6.6) –

Stab wound 11 (14.5) 2 (10) Hemodynamic status on admission, n (%)

Stable 58 (76.3) 2 (10)

Unstable 18 (23.7) 18 (90) Outcome, n (%)

Alive 70 (92) 12 (60)

Dead 6 (8) 8 (40)

Surgical intervention, n (%)

Yes 56 (74) 19 (95)

No 20 (26) 1 (5)

Group 1, patients with grade 1 or 2 liver injuries; group 2, patients with grade 3-5 liver injury.

study because they had Chronic liver 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. Patients with gunshot wounds were also excluded. We did not include patients whose referral was delayed by N 6 h or who were referred from another center. We retrieved the following data from the patients’ medical records: demographic characteristics, AST, ALT, LDH, hemoglobin, and white blood cell count on admission; cause of injury; hemodynamic status on presentation; hepatic injury grade; and the presence of coexisting abdominal and extra-abdominal injuries. Coexisting extra-abdominal injuries were broadly divided into those affecting the cranium, chest (including rib fracture, hemothorax or pneumothorax, lung, and cardiac injury), musculo- skeletal system (including long bone 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 to 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). The Kolmogorov-Smirnov test was

used to evaluate the distribution of continuous variables. The ?² test or Fisher exact test was used to compare categorical data. For continuous variables showing a parametric distribution, Student t test was used to compare the mean values of 2 groups. For continuous variables showing a nonparametric distribution, the Kruskal-Wallis test or the Mann-Whitney U test was used to compare the median values among groups. Correlation analyses were performed using Pearson’s or Spearman’s methods. The odds ratio and 95% confidence intervals were calculated to estimate the relative risk between 2 groups with mortality as the outcome. Statistical significance was set at P b .05. The Clinical performances of AST, ALT, and LDH levels for predicting liver injury were estimated using receiver operating characteristic curves, which were used to calculate the likelihood ratios for cutoff values showing high sensitivity or high specificity for the outcome.

Results

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. There were 80 (83.3%) males and 16 (16.7%) females. Their age ranged from 17 to 90 years 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 character- istics 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 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 Grade 2 injury, and 1 (1%) patient had Grade 3 injury.

There were no differences in AST, ALT, LDH, hemoglobin, or WBC count on admission between patients with isolated liver injury and patients with liver injury and coexisting intraabdominal injury (Table 2). However, when patients were divided according 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

Table 2

Laboratory results in patients with coexisting intraabdominal injury or isolated liver injury

		Patients with liver injury and coexisting abdominal injury	Patients with isolated liver injury	P
AST	Mean +- SD	299.6 +- 416.9	258.8 +- 324.4	.49a
	Median (range)	92 (13-1733)	46.5 (11-1263)
	IQR	441	434.5
ALT, U/L	Mean +- SD	299.0 +- 457.7	234.1 +- 303.8	.46a
	Median (range)	76 (11-1551)	48.5 (8-1038)
	IQR	321.5	391.7
LDH, U/L	Mean +- SD	504.5 +- 583.7	486.7 +- 510.5	.67a
	Median (range)	229.0 (120-2577)	220.5 (106-2102)
	IQR	359	610
WBC count, cells/uL	Mean +- SD	14747 +- 7097	14356 +- 7456	.45a
	Median (range)	11650 (5600-33000)	10650 (5900-34200)
	IQR	9025	11375
Hemoglobin	Mean +- SD	13.3 +- 2.3	12.9 +- 2.1	.57b
	Median (range)	13.65 (7.6-18.30)	13.1 (9.4-16.6)
	IQR	3.38	3.92

SD, standard deviation; IQR, interquartile range; WBC, white blood cell.

^a Mann-Whitney U test.

^b Student t test.

I. Bilgic et al. / American Journal of Emergency Medicine 32 (2014) 705–708 707

Table 3

Laboratory results in patients with low- or high-grade liver injury

		Group 1	Group 2	P
AST	Mean +- SD	161.2 +- 228.8	692.1 +- 453.9	b.01a
	Median (range)	42.5 (11-970)	543 (140-1733)
	IQR	177	720
ALT	Mean +- SD	150.5 +- 237.3	652.8 +- 484.1	b.01a
	Median (range)	32 (8-1038)	410 (110-1551)
	IQR	156.75	578
LDH	Mean +- SD	343.5 +- 317.4	1034.67 +- 819.2	b.01a
	Median (range)	212.5 (106-1450)	1031 (120-2577)
	IQR	145	1561
WBC count, cells/uL	Mean +- SD	14088 +- 7104	16053 +- 7882	.42a
	Median (range)	10700 (5600-34200)	11800 (8500-33000)
	IQR	9200	12400
Hemoglobin	Mean +- SD	13.1 +- 2.1	13.0 +- 2.5	.86b
	Median (range)	13.5 (8.3-18.3)	13.7 (7.6-16.3)
	IQR	3.55	3.7

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.

^a Mann-Whitney U test.

^b Student t test.

differences in Hemoglobin levels or the WBC count between the 2 groups (Table 3). In addition, AST, ALT, and LDH levels on admission were correlated with the grade of liver injury (Table 4).

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 thresholds were determined to be b 76 U/L, <= 130 U/L, and <=410 U/L for Grade 1 or 2 liver injuries (Figure). The positive predictive value and negative predictive value for AST, ALT, and LDH are presented in Table 5.

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 Hemodynamically 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 requiring invasive monitoring. Patients can generally resume their regular activities within 4 to 6 weeks without sequelae. Higher-grade injuries routinely require observation in the intensive care unit, invasive monitoring, and serial blood sampling. In addition, 20% to 30% of these patients require adjunctive treatment, including Endoscopic retrograde cholangiopancreatography, angiog- raphy, or percutaneous drainage of bilomas [7].

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 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 in all healthcare institutions and a major limitation is that it requires highly

Table 4

Correlations between the grade of liver injury and AST, ALT, and LDH levels

Parameter r P

AST 0.498 b.001

ALT 0.548 b.001

LDH 0.408 b.001

r, correlation coefficient.

trained staff but, even in trained hands, may not be very good at grading liver injuries.

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 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]. Srivas- tava 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 Moham- med published a report of 63 adult blunt trauma patients with multiple 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 that the initial serum SGPT value neither excluded the presence of hepatic injury nor predicted the need for laparotomy, in our patients [12]. Also, Karam et al have demonstrated that it does not seem possible to determine cut- off values of LFTs under which liver injury 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 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 N 360 IU/L and a FAST with negative findings had a 88% chance of having any grade hepatic injury and a 44% chance of having a hepatic injury of grade III or greater, Patients with an AST level of b 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 have demonstrated that patients with ALT and AST N 2 times normal should be assumed to 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 N 57 U/L and AST N 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 b 76 U/L, <=130 U/L for Grade 1 or 2

708 I. Bilgic et al. / American Journal of Emergency Medicine 32 (2014) 705–708

Figure. ROC of (A) aspartate aminotransferase, (B) alanine aminotransferase and (C) lactate dehydrogenase. AUC, area under the ROC curve.

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.

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 ischemia or injury, for example. Because of its ubiquitous expression, the total serum LDH level is a highly 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 with mortality in multivariate analysis. High LDH levels may reflect the number of affected 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 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 children who had neither abdominal tenderness, femur fracture, nor low systolic blood pressure, and had a GCS [Glasgow Coma Scale] score of more than 13. Nine of these 10 patients had an AST N 200 U/L or ALT N 125 U/L [17]. For that reason, high AST, ALT levels 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.

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 biomarkers as a valuable tool in the work-up of patients with abdominal trauma, especially in remote centers in Developing countries with limited or no access to expensive, expert radiological facilities. Therefore, in centers with

limited resources, we advocate the 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 magnitude of the elevation could indicate the severity of liver injury.

References

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    Table 5

    Results of ROC curve analysis for predicting grade 1 or 2 liver injuries

    	Cutoff value (U/l)	Sensitivity (95% CI)	Specificity (95% CI)	PLR (95% CI)	NLR (95% CI)	PPV (95% CI)	NPV (95% CI)
    AST	b130	80.26 (69.5-88.5)	94.74 (74.0-99.9)	15.25 (2.3-103.1)	0.21 (0.1-0.3)	98.4 (91.3-100.0)	54.5 (36.1-72.2)
    ALT	<=76	77.63 (66.6-86.4)	100.00 (82.4-100.0)	–	0.22 (0.1-0.3)	100.0 (93.9-100.0)	52.8 (35.5-69.6)
    LDH	<=410	86.49 (76.5-93.3)	68.42 (43.4-87.4)	2.74 (1.4-5.3)	0.20 (0.1-0.4)	91.4 (82.3-96.8)	56.5 (34.5-76.8)

    CI, confidence interval; PLR, positive likelihood ratio; NLR, negative likelihood ratio; PPV, positive predictive value; NPV, negative predictive value.