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| Journal of the New Zealand Medical Association,
25-February-2005, Vol 118 No 1210
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Elevation of serum liver enzymes after laparoscopic
cholecystectomy
George Sakorafas, George Anagnostopoulos, Vania Stafyla,
Theofilos Koletis, Nikolaos Kotsifopoulos, Stavros Tsiakos, George
Kassaras
Laparoscopic cholecystectomy (LC) has been widely accepted
as an alternative to laparotomy, and has become the standard treatment of benign
gallbladder diseases such as cholecystitis and gallbladder
stone.1 Despite its numerous advantages (i.e. a
shorter hospital stay, limited postoperative pain, quick recovery, fewer
complications), this procedure may impair hepatic function. It has been noticed
that following LC, the serum level of certain liver enzymes raises markedly in
patients who had preoperatively normal liver enzyme
values.2
We conducted a prospective clinical study to investigate the
effect of laparoscopic cholecystectomy on liver function in humans, comparing
changes in serum liver enzymes before and after laparoscopic and open
cholecystectomy.
Materials and methodsA total of 72 patients (38 men
and 34 women) with a mean age of 52 years (range, 31–88 years) were
admitted to the Department of Surgery, Hellenic Air Force and Veterans General
Hospital (in Athens, Greece) between May 2000 and January 2001 to undergo
laparoscopic cholecystectomy (LC group). Thirty-six patients (19 men and 17
women) with a mean age of 58.3 years (Range, 51–89 years) were admitted in
the same Department between May 2000 and July 2003 with symptomatic
cholelithiasis or gallbladder polyps, and underwent open cholecystectomy (OC
group). All patients selected for the study had normal serum transaminases
values prior to the procedures.
The laboratory tests were carried out at the same
laboratory using only one type of instrument. The normal range for the
haematological parameters was ALT, 11–26 U/L; ALT, 8–31 U/L; ALP,
46–150 U/L; GGT, 8–35 U/L, and total bilirubin 0.3–1.2 mg/dL.
The anaesthesiologic protocol was constant in all cases. Care was taken to
select drugs that interfered as little as possible with the enzymatic activity
of the liver.
The following patients were excluded from the
study:
The operations
were performed by the same medical staff. All patients received general
anaesthesia. During laparoscopic surgery, the intra-abdominal pressure was
maintained at 14 mmHg of
CO2.
Dissection of the gallbladder from the liver was performed with the use
of monopolar diathermy. To avoid hepatic enzyme alterations of iatrogenic
origin, intraoperative manipulation of the biliary tract (intraoperative
cholangiography) was avoided in all patients.
Postoperatively, all patients were given the same
intravenous glucose infusions and electrolytes plus antibiotics for 3–5
days (ceftazidime and metronidazole).
To assess liver function, serum values of alanine
aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase
(ALP), gamma glutamyl transferase (GGT), bilirubin, and INR were measured before
operations—and at 1,3,7, and 10 days postoperatively.
The mean and standard deviation of the collected data
were calculated. Student t-test was used for statistical evaluation. Results
were considered significant at p<0.05.
ResultsA statistically significant increase of ALT and AST was
noticed 24–72 hours after the operation in the LC group. The mean
preoperative ALT and AST values were 22.3±12.1 U/L and 21.6±13.4 U/L
in the LC group, and 18.4±11.5 U/L and 19.9±11.6 U/L in the OC group,
respectively (Table 1).
Twenty-four hours after the procedure, ALT and AST increased
statistically significantly in the LC group
(ALTLC24: 87.1±24.2 U/L, p<0.001;
ASTLC24: 82.8±19.1 U/L,
p<0.001)—whereas in the OC group, the serum value of ALT and AST was
above the upper normal limits in only in one patient 24 hours after the
procedure (ALTOC24: 23.8±10.9 U/L,
p>0.05; ASTOC24: 25.5±7.7 U/L,
p>0.05).
Seventy-two hours after the procedure, a further increase in
serum ALT and AST value was observed in 43 (59.7%) and 39 (54.1%) patients in
the LC group, respectively (ALTLC72:
99.3±19.5 U/L, p<0.001; ASTLC72H:
103.5±21.6 U/L, p<0.001)—whereas in the OC group, the mean value
of ALT and AST was within normal limits
(ALTOC72: 21.6±13.4 U/L, p>0.05;
ASTOC72: 20.9±10.4 U/L, p>0.05).
Seven days following the operations, the serum values of ALT
and AST in the LC group, although lower than on day 2, remained above normal
limits (ALTLC7D: 45.6±13.4 U/L,
p<0.05; ASTLC7D: 40.3±8.9 U/L,
p<0.05)—10 days after the procedure, liver enzyme values have returned
to normal values in the LC group.
We also measured the values of ALP, GGT, and bilirubin. No
statistically significant increase was noticed in any groups between the
preoperative and postoperative values of these enzymes.
Table 1. Preoperative and postoperative values of ALT
and AST liver-enzyme levels in laparoscopic-cholecystectomy and
open-cholecystectomy patients
ALT=alanine
aminotransferase; AST=aspartate aminotransferase; hr=hours; d=days;
preop=preoperative; postop=postoperative.
DiscussionIn our study, we observed transient
perioperative increases in ALT and AST in patients undergoing laparoscopic
cholecystectomy, but no such changes were observed in the open cholecystectomy
group. Ten days after the procedure, liver enzyme values had returned to normal
in all our patients. Several factors could be responsible for the transient
increase in aminotransferases values.
Despite the numerous clinical advantages, laparoscopy with
pneumoperitoneum leads to complex haemodynamic, metabolic, neurologic, and
humoral changes.3–6 The pneumoperitoneum
itself causes an increase in intra-abdominal pressure, which influences the
cardiorespiratory system, thus reducing the venous return to the right atrium
and (consequently) the cardiac flow.6–7
CO2
has high haematic solubility and can cause hypercapnia and respiratory
acidosis. Additionally, an intra-abdominal
pressure of 12–14 mmHg of
CO2 is
higher than the normal portal blood pressure of 7–10 mmHg, and is
therefore capable of reducing portal blood flow and of causing alterations of
the hepatic function.8–18
Giraudo et al19 showed that
a gasless technique causes smaller alterations in serological hepatic parameters
than pneumoperitoneum at 14 mmHg, while Morino et
al20 reported that postoperative increase of
liver enzymes was less when LC was performed with pneumoperitoneum at 10 mmHg.
On the other hand, free radical-induced lipid peroxidation associated with a
decrease in plasma antioxidant capacity, and altered hepatic function is
observed after deflation of the
pneumoperitoneum16.
It seems that free radicals are generated at the end of a
laparoscopic procedure, possibly as a result of an ischaemia-reperfusion
phenomenon induced by the inflation and deflation of the pneumoperitoneum. Free
radicals can damage tissues and organs, especially the Kupffer and the
endothelial cells of the hepatic sinusoids.16
Therefore, the elevated intra-abdominal pressure due to pneumoperitoneum may be
responsible for the increase of liver enzymes after LC.
Another possible factor is the effect of patient position on
blood flow. Sato et al8 monitored hepatic blood
flow during LC using transoesophageal echocardiography and concluded that the
combination of pneumoperitoneum and head-up positioning resulted in decreased
hepatic perfusion. Junghans et al21 also
reported that high intra-abdominal pressure combined with a head-up position
resulted in the greatest disturbance in hepatic perfusion.
Several studies support the hypothesis that alterations in
hepatic function after LC may be caused by the local effect of prolonged use of
diathermy to the liver surface and subsequent spread to the hepatic
parenchyma.22–25 However, changes in the
level of serum liver enzymes have been observed also after laparoscopic
colectomy where the focus is far from the liver.
The effect of surgical manipulation on the liver, and the
response to surgery-induced stress, may also lead to hepatocyte damage. Several
factors such as vasopressin and norepinephrine play a critical role in the
reduction of hepatic blood flow during LC.26
However, Giraudo et al19 studied laparoscopic
surgical interventions performed without any manipulation the hepatobiliary
structures. In this group of patients, the pneumoperitoneum of 14 mmHg provoked
a statistically significant increase in cytosolic enzymes even in the absence of
hepatobiliary manipulation.
The effect of general anaesthesia in liver function has been
discussed in some studies.27–30 It has
been proposed that anaesthesia induces changes in splachnic blood flow and
oxygen consumption. Yet, this theory does not explain why elevation of liver
enzymes does not occur after OC, since the same anaesthesia protocols are used.
A last possible mechanism of alterations of serum liver
enzymes after LC is the possible injury of the hepatic artery or any other
arterial branch. More than 20 alternative pathways have been described for the
hepatic artery. In 16% percent of people, it may run parallel to the cystic
duct, while in 30% it is located anteriorly to the hepatic duct. Therefore, this
vessel is frequently in the operative field and can easily be damaged. This,
however, should be followed by a massive increase in liver enzymes, and usually
has clinical implications difficult to predict in each patient.
Moreover, the fact that increase in liver enzyme values has
been reported to occur after laparoscopic colectomy, where the chance to injure
hepatic artery is minimal, suggests that arterial injury is not a possible
mechanism for the elevation of liver enzymes after LC.
In conclusion, we showed that transient elevation of ALT and
AST occurs after LC. CO2 pneumoperitoneum seems
to be the main reason for these changes, but other factors such as surgical
manipulation, diathermy, general anaesthesia, patient position, and arterial
injury may also contribute. These changes return to normal 7–10 days after
the procedure and they have no clinical consequences in patients with normal
hepatic function. However in patients with poor preoperative liver function,
prolonged laparoscopic procedures may not be the optimal choice for the
treatment of several abdominal diseases.
Author information:
George H Sakorafas, Consultant, Department of Surgery; George K Anagnostopoulos,
Resident, Department of Gastroenterology; Vania Stafyla, Resident, Department of
Surgery; Theofilos Koletis, Resident, Department of Surgery; Nikolaos
Kotsifopoulos, Consultant, Department of Surgery; Stavros Tsiakos, Resident,
Department of Gastroenterology; George Kassaras, Director, Department of
Surgery, Hellenic Air Force and Veterans General Hospital, Athens, Greece
Correspondence: Dr
George K Anagnostopoulos, Wolfson Digestive Diseases Centre, Queens Medical
Centre, Nottingham NG7 2UH, England. Fax +44 115 9422232; email george.anagnostopoulos@nottingham.ac.uk
References:
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