Hepatic disorder in burn patients

Burns (1985)12,49-53

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Great Britain

49

Hepatic disorder in burn patients K. Miyoshi, Department

S. Tsukada, Y. Yasuda, S. Kawakami of Plastic and Reconstructive

and T. Sakurai

Surgery

Y. Matsuda and T. Ito Department

of Internal Medicine

H. Matsuno Department

of Pathology, Kanazawa Medical University, Ishikawa, Japan

Summary Changes in liver function were studied in 33 patients with burns. In 21 of these patients hepatic.disorder developed relatively early after the injury (early hepatic disorder), with a relapse of hepatic disorder occurring later in 8 patients (late hepatic disorder). Our study demonstrated that these hepatic dysfunctions may largely he attributable to post-transfusion acute hepatitis (non-A, non-B or B types).

INTRODUCTION As suggested by previous authors (Gilmore and Fozzard, 1960; Czaja et al., 1975; Ashur et al., 1979; Chlumsky et al., 1979; Konigova and Dolinayova, 1980), the burn itself (burn shock, hypovolaemia, etc.) may cause early hepatic disorder. As to late hepatic disorder, however, little work has been done (Chiarelli et al., 1983; Coursaget et al., 1983), yielding little information concerning the cause. The purpose of this study was to elucidate the cause of the late hepatic disorder we observed in 8 patients. PATIENTS AND METHODS Thirty-three patients (Table I) with burns admitted to the Department of Plastic and Reconstructive Surgery, Kanazawa Medical University Hospital, between June 1975 and December 1982, and undergoing long-term intensive study, comprise the subjects of this study. Changes over time in serum glutamate oxaloacetate transaminase (sGOT), serum glutamate pyruvate trans-

aminase (sGPT), alkaline phosphatase (ALP), thymal turbidity test (TIT), zinc sulphate turbidity test (ZTT), serum total bilirubin (T-Bit), and hepaplastin test were examined in terms of Burn Index and the nature and volume of transfusion fluids, including fresh frozen plasma (FFP). These 33 patients were compared with 9 nonburn control patients with post-transfusion acute hepatitis (non-A, non-B type) with respect to histopathological pattern and severity of hepatic disorder. Acute hepatitis was diagnosed based on liver biopsy and clinical symptoms. The leucocyte migration inhibition test was used to exclude cases of drug induced hepatitis. Hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (HBsAb) were detected using the reversed passive haemagglutination method, antihepatitis B core antibody (anti-HBc Ab), via the immune adherence haemagglutination method. and anti-hepatitis A antibody (anti-HA Ab), via the radio-immunoassay technique. Antibodies to other virus were detected by means of the complement fixation reaction. RESULTS The subjects were divided into three groups (Groups I, II and III) according to the pattern of changes in sGOT and sGPT, which in some cases showed a biphasic pattern (Table Ir). Late hepatic disorder in Group III patients was found in the convalescent stage or after recovery from the

50

Burns (1985)Vol.

Table 1. Clinical characteristics

lZ/No. 1

of burn patients (33 cases) Depth of burn (%)*

Case

Age W

Sex

Extent of burn (%I

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33

8 35 55 20 20 2 2 40 60 2 3 Month 39 56 15 17 20 55 37 31 43 3 71 37 14 30 27 57 23 27 20 48 48 65

M F M F F F L

30 20 20 50 60 45 60 15

0 0 0 20 60 45 570

F F M M M M M F F F F M F M M M M F M M F M

9 25 20 50 30 30 30 23 10 20 40 25 75 25 50 15 39 60 40 75 55 37 40 65 22

2 15 0 30 5 20 5 10 0 15 5 0 0 0 0 0 0 0 0 0 25 0 25 15 IO

* SDB, superficial

F

SDB

DDB

DB

B/t

Cause

30 20 20 30 0 0 15 3 7 10 20 20 20 0 5 8 0 5 25 0 75 15 10 10 0 45 20 35 25 27 15 40 10

0 0 0 0 0 0 0 0 0 0 0 0 5 IO 20 5 10 0 10 25 0 10 40 5 39 15 20 30 5 10 0 10 2

15 10 10 25 30 22.5 7.5 30 4.5 12.5 10 25 17.5 20 25 14 IO 10 25 25 37.5 17.5 45 10 39 37.5 30 47.5 30 23.5 20 37.5 12

Scald Flame Flame Scald Flame Scald Scald Flame Flame Scald Contact Scald Flame Flame Flame Flame Flame Flame Flame Contact Scald Flame Contact Scald Flame Flame Flame Flame Flame Contact Flame Flame Flame

dermal burn. DDB, deep dermal burn. DB, deep burn.

t BI, Burn lndex-

early hepatic disorder. Changes in enzyme levels in the late hepatic disorder were typical of acute hepatitis and similar to changes in sGOT and sGPT in the control group. As for the other laboratory data, T-Bil levels in the burn patients remained slightly elevated. T-Bil levels in Group III patients ranged from 1-l to 4.4mg/dl (mean 2.1) at the peak of the hepatic disorder and the major component of the bilirubin elevation was conjugated bilirubin. Clinical signs of sepsis, or hepatomegaly were not observed in any burn patient (Table IIt). Histopathological studies revealed that both Group III patients and controls showed a typical

picture of acute hepatitis with remarkable mobilization of Kupffer cells, scattered spotty necrosis, acidophile necrotic cells, and mild disorganization of the cytoarchitecture (Symmers et al., 1978) irrespective of the presence of burns (Figs. la and 6). The histopathological severity of these disorders were judged to be similar for patients of both groups. These findings were consistent with the clinical findings, that is, the hepaplastin tests in both groups were between 70 and 100 per cent at the peak of the hepatic disorder. Comparison of the Burn Index and the volumes of fluid transfused among Groups I, II and III (Tables IV and V) revealed that there were more

51

Miyoshi et al.: Hepatic disorder in burn patients

Table II. Classification Group

I (Cases l-11)

Group II (Cases 12-25)

Group Ill (Cases 26-33)

Table IV. Comparison the burn index

of burn cases (33 cases) Showing no changes in enzyme levels since burn incident Showing elevations in enzyme levels at early stage after the incident (day O-15, on day 6.6 on average) followed by normalization of those levels (day 8-30, on day 20 on average) Showing elevations in enzyme levels at early stage after the incident (day &12, on day 6.8 on average) followed by further elevations, or by normalization and then elevation again

patients with deep burns in Groups II and III and that a remarkably large amount of FFP was transfused into patients in Group III as compared to other groups (P
Possible causes of the late hepatic disorder in burn patients are: (1) sepsis, (2) malnutrition, hypoxaemia, (3) existing hepatic disorder, (4) drugs, (5) operation procedures, especially anaesthesia with halothane, (6) the burn itself, and (7) post-transfusion hepatitis. In our patients, Tab/e 111.Clinical characteristics

Burn index c-9 lo-19 2c-29 3c-39

Group 1 n=ll

Total bilirubin (0.2-l .2 mgldl) sGOT (9-41 U/I) sGPT (7-45 U/I) LDH (120-204 U/I ) ALP (33-105 U/I)

044f0.2 0.2- 1.1 24.7f8.6 9-40 22.95 10.6 3-45 176.6f27.4 123-200 83.5f19.8 44-105

Group .

.

. . .

. .

.

.

.

I

.

Group ii

. . . . .

. . .

. . .

. . .

.

.

40-49

Group Ill

. .

.

.

.

.

.

.

past histories, laboratory findings and clinical symptoms denied the possibilities of (l), (2), (5) could (3) and (4) (Table VI). Moreover, not be important, since patients in Groups I and II underwent the same anaesthetic treatments and operations without developing late hepatic disorder. Clinical symptoms and laboratory findings also did not support this possibility. As to (6) and (7), we thought (7), post-transfusion hepatitis, was the more possible cause, for the following reasons: (i) Only Group III patients developed the late hepatic disorder, although they were not different from Group II patients with respect to Burn Index; (ii) Some cases in Group III showed a transient normalization of laboratory findings prior to relapse despite no change in the status of the burn; (iii) The severity of the late hepatic disorder in Group III did not differ from that in the control group, either clinically or histopathologically. The patients in Group III did not show any hepatic tissue changes specific to burn; and (iv) A large volume of FFP was transfused to all patients in Group III.

of patients studied (mean&standard

Determinations (normal values)

of three groups according to

Group II n=14 0.7kO.5 0.2-2.8 59.3+48.2 IO-255 72.6k62.7 9-283 241.Ok87.4 112-587 132.2k69.6 37-382

deviation and range) Group 111 n=8 0.8IkO.6 0.2-4.4 155.1k176.5 8-885 191.8f242.3 g-1250 269.6k114.8 72-850 133.5+76.0 36-525

Control n=9 0.9kO.8 0.2-4.9 147.9f 195.7 5-895 181.1k218.6 7-912 264.3f 137.2 92-820 133.1+77.9 32-378

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Burns (1985) Vol. 12/No. 1

b Fig. 1. Histopathological findings: a, Burn patient (Group III Case 32) (haematoxylin and eosinX58); b, Non-burn control patient (haematoxylin and eosinx58). Table V. The number of patients transfused

Group I (Cases l-11) Group II (Cases 12-25) Group III (Cases 26-33) A, Preserved blood. 6, Packed red blood cells. C, Fresh frozen plasma (FFP).

and mean transfusion

units by 9roup

No. of patients transfused

Total

No. of transfusion

A

units (mh..d.l

6

C

9 11 8

6.2f 3.8 24.6+ 15.7 95.1+66.1

5.lf 3.7 10.8? 11.3 11.2rt13.4

0.5+ 1.1 3.22 3.7 7.6f 11.4

0.5+ 1.3 10.5k12.8 77.0f64.8

53

Miyoshi et al.: Hepatic disorder in burn patients

Tab/e VI. Results of leucocfle test (Group Ill)

Case

migration

Drug

inhibition

Migration index (%)*

26

PIPC (piperacillin) CET (cephalothin)

98 92

27

PIPC (piperacillin) SBPC (sulbenicillin) CET (cephalothin) CTM (cefotiam)

97 91 93 89

28

PIPC (piperacillin) CET (cephalothin) CTM (cefotiam)

29

TIPC (ticarcillin) CTM (cefotiam) CFS (cefsulodin)

90 98 91

30

PIPC (piperacillin) CTM (cefotiam)

94 92

31

PIPC (piperacillin) CTM (cefotiam)

105 94

32

PIPC (piperacillin) CFX (cefoxitin) CET (cephalothin)

99 93 92

33

PIPC (piperacillin) CET (cephalothin) CTM (cefotiam)

92 89 90

* Migration

102 95 91

index; normal range >70%.

Non-A, non-B acute hepatitis has been known to account for over 90 per cent of the cases of post-transfusion acute hepatitis (Feinstone et al., 1975; Aach and Kahan, 1980; Alter, 1980), easily changing to a chronic disease (Aach and Kahan, 1980), and to be fatal in some patients (Mathiesen et al., 1980). Studies of experimental infection with non-A, non-B acute hepatitis (Alter et al., 1978; Yoshizawa et al., 1981), and identification of virus-like particles in serum and liver homogenates (Shimizu et al., 1979; Yoshizawa et al., 1980) have been reported. These reports indicate that the improper use of FFP may increase the incidence of post-transfusion acute hepatitis, especially non-A, non-B type hepatitis. From the viewpoint of long-term prognosis, we should minimize the use of FFP for the treatment of burns.

REFERENCES Aach R. D. and Kahan R. A. (1980) Post-transfusion hepatitis: Current perspective. Ann. Infern. Med. 92, 539. Alter H. J. (1980) The dominant role of non-A, non-B in the pathogenesis of posttransfusion hepatitis. A clinical assessment. Clin. Gasfroenrerol. 9. (I), 155. Alter H. J., Purcell R. H., Holland P. V. et al. (1978) Transmissible agent in non-A, non-B hepatitis. Lanccl i, 459. Ashur H., Ben-Hur N., Kuperman 0. et al. (lY79) Liver dysfunction and immunological disturbances in the thermal burn injury. Burns 6. 160. Chiarelli A., Pornaro E.. Caliari L. et al. (1983) Hepatitis in burn patients. Chir. Plast. (Ital.). 15, 217. Chlumskj J., Chlumska A., Vrabec R. et al. (lY7Y) Liver changes after burn illness. Acfa Chir. Plasr. 21, (2). 120. Coursaget P., Levesque P., Baudet J.-P. et al. (1983) Incidence and chronicity of non-A, non-B hepatitis in burn patients. J. Burn Care Rehabil. 4 (3). 194. Czaja A. J., Rizzo T. A., Smith W. R. et al. (1975) Acute liver disease after cutaneous thermal injury. J. Trauma 1.5,887. Feinstone S. M., Kapikian A. Z., Purcell R. H. et al. (1975) Transfusion associated hepatitis not due to viral hepatitis type A or B. N. En@. J. Med. 292. 767. Gilmore J. P. and Fozzard H. A. (1960) Liver function following thermal injury. Am. J. Physiol. 199, 49 I. Kiinigovi R. and Dolinayovi 1. (1980) Biochemical changes in burn-affected liver. Acta Chir. Plasr. 22, (3), 171. Mathiesen L. R., Skinoj P., Nielsen J. 0. et al. (1YXO) Hepatitis type A. B and non-A, non-B in fulminant hepatitis. Gut 21, 72. Shimizu Y. K., Feinstone S. M. and Purcell R. H. (1979) Non-A, non-B hepatitis: Ultrastructural evidence for two agents in experimentally infected chimpanzees. Science 205, 197. Symmers W. S. and Weinbren K. (1978) Sysfemic Pathology, second edition. Edinburgh: Churchill Livingstone p. 1219. Yoshizawa H., Akahane Y., Itoh Y. et al. (lY80) Virus like particles in a plasma fraction (fibrinogen) and in the circulation of apparently healthy blood donors capable of inducing non-A/non-B hepatitis in humans and chimpanzees. Gastroenterology 79. 1512. Yoshizawa H., Itoh Y., Iwakiri S. et al. (1981) Demonstration of two different types of non-A, non-B hepatitis by reinjection and cross-challenge studies in chimpanzees. Gustroenferology 81, 107.

Paper accepted 5 July 1985

(hrrespondmw should he uddressed lo: K. Miyoshi MD, Department of Plastic and Reconstructive University. 1-I Daigaku, Uchinada, Ishikawa. Y2tHL?, Japan.

Surgery,

Kanazawa

Medlca]