Journal of the New Zealand Medical Association, 25-February-2005, Vol 118 No 1210
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 methods
A 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.
A 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.
In 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 firstname.lastname@example.org
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