Risk Assessment of Laparoscopic Cholecystectomy in Liver Cirrhotic Patients with Clinically Significant Portal Hypertension: A Retrospective Cohort Study

Abstract

Objective:

This study was aimed to evaluate the correlation between clinically significant portal hypertension (CSPH) and postoperative complications and risk predictors of postoperative complications.

Methods:

The retrospective study was conducted to identify the effect. The cirrhotic patients were divided into two groups, those with or without CSPH. The intraoperative and postoperative conditions were evaluated. Multivariate logistic regression analysis was performed to identify potential risk predictors for postoperative complications in cirrhotic patients with CSPH.

Results:

The cirrhotic patients with CSPH who underwent laparoscopic cholecystectomy (LC) had postoperative hospitalization than the patients without CSPH. However, the incidence of postoperative complications between two groups showed no significant difference. The results of multivariate analysis showed that male, gallbladder wall >3 mm, size of stones ≥1 cm, scores of Model for end-stage liver disease (MELD) ≥10, and operation time >60 minutes were the potential risk predictors for postoperative complications.

Conclusions:

CSPH did not increase the incidence of postoperative complications in cirrhotic patients who underwent LC, but increased conversion rate and prolonged postoperative hospitalization. Furthermore, our study showed that gender, sizes of gallbladder wall and stones, scores of MELD, and operation time were the important postoperative risk predictors for cirrhotic patients with CSPH.

Introduction

Cirrhosis is a high risk factor for the incidence of cholecystolithiasis. Previous research has shown that the incidence of cholecystolithiasis in cirrhotic patients is double that of noncirrhotic patients.¹ Laparoscopic cholecystectomy (LC) is currently considered the gold standard treatment for patients with symptomatic cholecystolithiasis. Compared with traditional open cholecystectomy, LC has the following advantages: lower postoperative complications, faster recovery, less trauma, shorter hospital stays, and earlier return to work.² Historically, cirrhosis was considered to be a relative contraindication of LC because of its potential risk of bleeding and postoperative liver failure.³

However, some studies have confirmed that the LC can be safely performed in cirrhotic patients with appropriate patient selection.^4,5 Although the number of liver cirrhotic patients who could undergo LC is increasing, there are few studies that explore the correlation between clinically significant portal hypertension (CSPH) and postoperative complications. We performed a single-center retrospective study to estimate the correlation between CSPH and postoperative complications after LC in cirrhotic patients and risk predictors of postoperative complications.

Patients and Methods

Patients selection

The medical records of liver cirrhotic patients and noncirrhotic counterparts undergoing LC in Second Affiliated Hospital of Chongqing Medical University from January 2013 to August 2018 were retrospectively analyzed. All patients underwent complete clinical examinations and laboratory examinations (with emphasis on chronic liver disease and gallstones). The research process conformed to the STROCSS criteria.⁶ This study was registered with the ChiCTR registry, number ChiCTR1800018812.

Inclusion criteria were as follows: (1) clear diagnosis of liver cirrhosis before the operation,⁷ diagnosed according to laboratory examination or liver biopsy and (2) patients who had symptomatic cholecystolithiasis with biliary colic or acute cholecystitis who were able to undergo laparoscopic surgery. The cholecystolithiasis was diagnosed by imaging examination such as ultrasonography (US), computed tomography (CT) scan, or magnetic resonance imaging (MRI).

Exclusion criteria were as follows: (1) patients with severe heart, brain, or lung insufficiency before surgery; (2) patients with acute pancreatitis, acute cholangitis, or other hepatobiliary diseases; (3) patients with a history of abdominal surgery; and (4) patients who were unsuitable for laparoscopic surgery.

Selected cirrhotic patients were divided into two groups, those with or without CSPH. The indirect diagnosis of CSPH was based on Austrian consensus guidelines.⁸ If the cirrhotic patient had gastroesophageal varices by gastroscopy, the history of variceal hemorrhage, ascites (without significant cardiac, malignant, peritoneal, or renal comorbidities), or large portosystemic collaterals on imaging examination, the clinically significant PH was clearly diagnosed. Baseline characteristics were comparable between two groups.

Laparoscopy procedures

All patients underwent a standard four-port laparoscopic procedure under general anesthesia. The umbilical trocar was inserted by open Hasson technique to avoid injury of abdominal wall collaterals. The carbon dioxide pneumoperitoneum was established at a pressure of 12 mmHg. Inserting 10 mm Trocar as laparoscopic observation hole was to observe the degree of liver cirrhosis, gallbladder size, position, severity of inflammation, and adhesion with the surrounding tissue. The specific location of the rest of the operation holes were decided according to the severity of liver cirrhosis and gallbladder. The cystohepatic triangle was dissected first during the operation. Dissociating the anterior and posterior cystohepatic triangle with the electrocoagulation hook, the cystic duct and cystic artery were distinguished clearly. Clipping and cutting off the cystic artery was with the absorbable clamp and the electrocoagulation hook. Meanwhile, the proximal and distal cystic duct were clipped and cut. Antegrade or retrograde cholecystectomy was chosen according to the severity of adhesions surrounding the gallbladder caused by gallbladder inflammation. After completing hemostasis of gallbladder bed, an abdominal drainage tube was placed in epiploic foramen according to the situation in the operation.

Outcomes

Postoperative complications included postoperative bleeding, wound infection, ascites, liver failure, biliary injury, reoperation, and mortality. Postoperative complications were sorted according to the Clavien–Dindo scaling.⁹ Predefined secondary outcomes included postoperative hospitalization time.

Statistical analysis

Continuous data were described with mean ± standard deviation (M ± SD). Dichotomous data were described with frequency (percentage). The difference between each group was tested with t-test, chi-square test, or rank-sum test.¹⁰ Risk predictors of postoperative situations were explored using the multivariate logistic regression. SPSS Statistics 17.0 was used for statistical analysis. A two-sided value of P < .05 was regarded as statistical significance.

Results

A total of 188 cirrhotic patients who underwent LC procedure between January 1, 2013 and August 31, 2018 in the hospital were included. These patients were divided into two groups according to CSPH: 62 patients with CSPH and 126 patients without CSPH. Baseline characteristics between two groups were collected (Table 1).

Table 1.

Baseline Characteristics Between Two Groups

	Without PH (n = 126)	With PH (n = 62)	P
Age, years	54.3 ± 11.7	48.8 ± 7.9	<.010^*
Gender			.046^*
Female	42 (33.3%)	12 (19.4%)
Male	84 (66.7%)	50 (80.6%)
Body mass index	23.4 ± 3.6	24.7 ± 3.5	.070
ASA classification			.856
ASA I	20 (15.9%)	10 (16.1%)
ASA II	92 (73.0%)	44 (71.0%)
ASA III	14 (11.1%)	8 (12.9%)
Chronic cholecystitis	62 (49.2%)	40 (64.5%)	.048^*
Wall thickness			.419
≤3 mm	44 (34.9%)	18 (29.0%)
>3 mm	82 (65.1%)	44 (71.0%)
Size of stones (cm)	1.2 ± 0.7	1.3 ± 0.9	.480
Stone position			.343
Neck	40 (31.7%)	24 (38.7%)
Other positions	86 (68.3%)	38 (61.3%)
Cirrhosis etiology			.228
Viral hepatitis	78 (61.9%)	52 (83.9%)
Alcoholic hepatitis	28 (22.2%)	6 (9.7%)
Autoimmune hepatitis	20 (15.9%)	4 (6.4%)
Splenomegaly	30 (23.8%)	54 (87.1%)	<.010^*
Child–Pugh classification			<.010^*
A	118 (93.6%)	36 (58.1%)
B	6 (4.8%)	22 (35.5%)
C	2 (1.6%)	4 (6.4%)
Preoperative MELD score	9.7 ± 1.7	11.0 ± 2.8	<.010^*
MELD score stratifying			<.010^*
1–4	4 (3.2%)	2 (3.2%)
5–9	66 (52.4%)	18 (29.0%)
10–14	56 (44.4%)	32 (51.6%)
15–19	0	10 (16.1%)
Preoperative ALT level	42.3 ± 33.6	40.6 ± 23.9	.727
Preoperative ALB level	42.0 ± 4.0	39.3 ± 5.4	<.010^*
Preoperative TB level	17.9 ± 12.2	32.3 ± 29.9	<.010^*

The difference was statistically significant.

ASA, American Society of Anesthesiologists; MELD, model for end-stage liver disease; ALT, alanine aminotransferase; ALB, albumin; TB, total bilirubin.

The mean operative time of the cirrhotic patients without CSPH was 69.2 ± 21.3 minutes and the mean blood loss was 56.5 ± 41.9 mL. There were 2 patients (incidence rate of 1.6%) without CSPH who needed to switch to laparotomy because of severe abdominal adhesions. However, the mean operative time of the cirrhotic patients with CSPH was 110.5 ± 62.5 minutes and the mean blood loss was 233.9 ± 189.0 mL. There were 14 patients (incidence rate of 22.6%) with CSPH who needed to switch to laparotomy because of severe abdominal adhesions (8 patients) or hemorrhage (6 patients). The differences of these results were statistically significant (Table 2).

Table 2.

Univariate Analysis of Intraoperation and Postoperative Conditions

	Without PH (n = 126)	With PH (n = 62)	P
Intraoperation
Operative time (min)	69.2 ± 21.3	110.5 ± 62.5	<.010^*
Blood loss (mL)	56.5 ± 41.9	233.9 ± 189.0	<.010^*
Conversion	2 (1.6%)	14 (22.6%)	<.010^*
Postoperation
Complications	36 (28.6%)	24 (38.7%)	.161
Clavien–Dindo grade⁺			.094
I	30 (83.3%)	16 (66.7%)
II	6 (16.7%)	4 (16.7%)
III	/	2 (8.3%)
IV	/	2 (8.3%)
Hospitalization (days)	4.2 ± 2.1	6.0 ± 5.1	<.010^*

Clavien–Dindo grade I: wound infection, hepatic function lesion; grade II: postoperative bleeding; grade III: bile leakage; grade IV: hemorrhagic shock.

The difference was statistically significant.

PH, portal hypertension.

/, there was no patient.

Postoperative outcomes

None in the two groups died. A total of 36 cirrhotic patients without CSPH (incidence rate of 28.6%) experienced postoperative complications: 30 cases were classified as Clavien–Dindo Grade I (20 cases with wound infection and 10 cases with hepatic function lesion) and 6 cases were classified as Clavien–Dindo Grade II (postoperative bleeding). Meanwhile, a total of 24 cirrhotic patients with CSPH (incidence rate of 38.7%) experienced postoperative complications: 16 cases were classified as Clavien–Dindo Grade I (12 cases with wound infection and 4 cases with hepatic function lesion), 4 cases were classified as Clavien–Dindo Grade II (postoperative bleeding), 2 cases were classified as Clavien–Dindo Grade III (bile leakage), and 2 cases were classified as Clavien–Dindo Grade IV (hemorrhagic shock). The mean postoperative hospitalization of cirrhotic patients without CSPH was 4.2 ± 2.1 days, but the mean postoperative hospitalization of cirrhotic patients with CSPH was 6.0 ± 5.1 days. The differences of these results were statistically significant (Table 2).

Multivariate analysis

The multivariate logistic regression analysis identified that the following variables significantly correlated with postoperative complications: male (odds ratio [OR] = 31.632; 95% confidence interval [CI]: 5.219–191.715; P < .010), gallbladder wall ≤3 mm (OR = 0.168; 95% CI: 0.048–0.586; P < .010), size of stones ≥1 cm (OR = 5.722; 95% CI: 1.659–19.732; P < .010), score of MELD ≥10 (OR = 8.275; 95% CI: 2.019–33.916; P < .010), and operation time >60 minutes (P = .013). The longer the operation time the higher the incidence of postoperative complications (Table 3).

Table 3.

Multivariate Logistic Analysis of Potential Risk Factors for Postoperative Complications

Variable	B	SE	P	OR	95% CI
Variable	B	SE	P	OR	Low	Up
Age ≥60	1.134	0.681	.096	3.109	0.819	11.803
Male	3.454	0.919	<.010^*	31.632	5.219	191.715
Chronic cholecystitis	−0.649	0.503	.197	0.522	0.195	1.400
Gallbladder wall ≤3 mm	−1.785	0.638	<.010^*	0.168	0.048	0.586
Size of stones ≥1 cm	1.744	0.632	<.010^*	5.722	1.659	19.732
Stones in neck of gallbladder	0.549	0.557	.324	1.732	0.581	5.162
Splenomegaly	−1.046	0.656	.111	0.351	0.097	1.271
Child–Pugh classification	/	/	.611	/	/	/
A	Reference	Reference	Reference	Reference	Reference	Reference
B	0.907	1.045	.385	2.478	0.320	19.201
C	−0.101	1.802	.955	0.904	0.026	30.888
MELD scores ≥10	2.113	0.720	<.010^*	8.275	2.019	33.916
Operation time	/	/	.013^*	/	/	/
≤60 min	Reference	Reference	Reference	Reference	Reference	Reference
60<T ≤ 120 min	1.505	0.660	.023^*	4.505	1.235	16.436
>120 min	5.590	2.165	<.010^*	267.764	3.846	18641.762
Blood loss	/	/	.178	/	/	/
≤50 mL	Reference	Reference	Reference	Reference	Reference	Reference
50<T ≤ 100 mL	−0.849	0.638	.183	0.428	0.122	1.494
>100 mL	−2.316	1.628	.155	0.099	0.004	2.398
Conversion	1.114	1.462	0.446	3.047	0.174	53.461

The difference was statistically significant.

/, there was no statistic because it served as a reference standard.

OR, odds ratio; CI, confidence interval; MELD, model for end-stage liver disease; ALT, alanine aminotransferase; ALB, albumin; TB, total bilirubin.

Discussion

Liver cirrhosis is a high risk factor for cholecystolithiasis. Thirty percent of cirrhotic patients suffer from cholecystolithiasis. However, the incidence of cholecystolithiasis in noncirrhotic patients is only 13%.¹¹ Laparoscopic surgical treatment is the best choice for cirrhotic patients with symptomatic cholecystolithiasis, which was a great challenge to cirrhotic patients. The mortality of liver cirrhosis undergoing LC is higher than that of noncirrhotic patients, particularly in patients with portal hypertension.¹² Bile infection caused by accidental gallbladder rupture and massive intraoperative blood loss are considered to be the main causes of postoperative morbidity and mortality in cirrhotic patients.¹³ Cirrhosis has been considered as a relative contraindication for LC in the past. A meta-analysis indicated that cirrhotic patients have longer operating time, higher conversion to open surgery, risk of severe bleeding, and postoperative morbidity than noncirrhotic patients.¹⁴ However, on further study, it was found that it is not an absolute contraindication. Advanced laparoscopic procedure is safe for patients with mild degree cirrhosis, although there was a technical challenge because of portal hypertension and varices.^15,16 It indicates that effective and radical treatment can be achieved for cirrhotic patients with symptomatic cholecystolithiasis. But how to evaluate the risk predictors of postoperative complications for cirrhotic patients undergoing LC is still a problem to be solved. The correlation research indicated that LC can be safe and of low risk in cirrhotic patients with appropriate selection. Child–Pugh classification system or model for end-stage liver disease (MELD) score may be a good predictor of clinical outcomes in these patients.^17,18 Moreover, some studies showed that cirrhotic patients with portal hypertension can cause systemic multiple organ dysfunction, which involves the heart, lungs, kidneys, the immune systems, and other organ systems.^19,20 Therefore, we suspected that portal hypertension was also one of the risk factors. There were some meta-analyses and trials indicating that cirrhotic patients have longer operating time, higher conversion to open surgery, risk of severe bleeding, and postoperative morbidity than noncirrhotic patients, but the potential influences of portal hypertension on cirrhotic patients was still unclear. And the risk predictors of postoperative complications in cirrhotic patients also were unknown. This study was performed to estimate the correlation between CSPH and postoperative complications after LC in cirrhotic patients. Meanwhile, the multivariate logistic regression was performed to identify the risk predictors of postoperative complications.

In this retrospective study, the included cirrhotic patients were grouped as with CSPH or without CSPH. Because patients with CSPH often suffered from severe cirrhosis, surgery for these patients should be more cautious. Because of venous circuitous dilation and poor coagulation function, patients with CSPH were more prone to intraoperative bleeding. Then, the operation time was prolonged and the conversion rate to laparotomy was increased. However, the incidence of postoperative complications was not significantly different. Although the Clavien–Dindo grades of two groups were not significantly different, the postoperative complications of patients with CSPH were more serious. In the group of patients with CSPH, bile leakage and hemorrhagic shock occurred. This may be more worthy of attention.

The results indicated that patients with CSPH needed longer hospitalization time after operation. This may increase the patients' body and financial burden. Because of the limitations of retrospective study, the criteria for postoperative treatment cannot be fully unified. It may lead to inaccurate clinical economics evaluation. Thus the high-quality prospective randomized controlled trials will be needed to explore its clinical economic value.

The multivariate analysis showed that gender, sizes of gallbladder wall and stones, scores of MELD, and operation time were important predictors of postoperative complications for cirrhotic patients with CSPH. Male patients were more likely to suffer from postoperative complications than female patients. The result showed that there were some hormones in the body related to the difference. The patients with gallbladder wall >3 mm, stones >1 cm, MELD scores >10, or operation time >60 minutes were more likely to suffer from postoperative complications. Because MELD was usually higher in patients with CSPH, we hypothesized that there may be a stronger correlation between complications and CSPH with high MELD scores than just portal hypertension. The high-quality trials will be needed to explore this correlation. Therefore, positive measures should be taken to prevent postoperative complications for these patients.

This study had several limitations. This research just was a single-center retrospective study. The evidence strength of the results was limited. It also should be noted that the sample size of this study was small, which may lead to some biases in the results. Moreover, portal vein pressure was not measured directly. A few patients with portal vein broadened may be no CSPH. Considering limitations of research methods and sample capacity, the conclusion still needs further verification.

Conclusion

CSPH did not increase the incidence of postoperative complications in cirrhotic patients who underwent LC, but increased conversion rate and prolonged postoperative hospitalization time. Furthermore, our study showed that gender, sizes of gallbladder wall and stones, scores of MELD and operation time were the important postoperative risk predictors for cirrhotic patients with CSPH.

Declaration

Ethics approval and consent to participate

Because of the retrospective nature of the study, informed consent was waived. The study was approved by the Ethics Committee of the Second Hospital Affiliated of Chongqing Medical University.

Data Availability

The data set analyzed in this study cannot be opened to public because patients' privacy must be protected. However, data are available from the author upon reasonable request.

Footnotes

Acknowledgments

The authors appreciate Dr. Li Pei-zhi and Pro. Yang Kang for reviewing an early draft of this article and giving valuable comments, Mr. Gong Jun-fei for collecting and analyzing the data, and Miss. Tang Wen-hao for polishing to improve the literary readability of the language.

Disclosure Statement

The authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article.

References

Silva

, Wong

. Gallstones in chronic liver disease. J Gastrointest Surg, 2005; 9:739–746.

Al Talhi

, Shirah

, Altowairqi

, et al. Laparoscopic cholecystectomy for cholelithiasis in children with sickle cell disease. Clin J Gastroenterol, 2017; 10:320–326.

Gallstones and laparoscopic cholecystectomy. NIH Consens Statement, 1992; 10:1–28.

Ralph

, Quillin

III

, Justin

, et al. Laparoscopic cholecystectomy in the cirrhotic patient: Predictors of outcome. Surgery, 2013; 153:634–640.

McGillicuddy

, Villar

, Rohan

, et al. Is cirrhosis a contraindication to laparoscopic cholecystectomy?. Am Surg, 2015; 81:52–55.

Agha

, Borrelli

, Vella-Baldacchino

, Thavayogan

, and Orgill

; for the STROCSS Group. The STROCSS Statement: Strengthening the Reporting of Cohort Studies in Surgery. Int J Surg, 2017; 46:198–202.

Gross

. Liver cirrhosis and the most common complications: Diagnosis and treatment. MMW Fortschr Med, 2015; 157: 75–79.

Reiberger

, Puspok

, Schoder

, et al. Austrian consensus guidelines on the management and treatment of portal hypertension (Billroth III). Wien Klin Wochenschr, 2017; 129:135–158.

Daniel

, Nicolas

, Pierre-Alain

. Classification of surgical complications: A new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg, 2004; 240:205–213.

10.

Zhang

. Univariate description and bivariate statistical inference: The first step delving into data. Ann Transl Med, 2016; 4:91.

11.

Cucinotta

, Lazzara

, Melita

. Laparoscopic cholecystectomy in cirrhotic patients. Surg Endosc, 2003; 17:1958–1960.

12.

Delis

, Bakoyiannis

, Madariaga

, et al. Laparoscopic cholecystectomy in cirrhotic patients: The value of MELD score and Child-Pugh classification in predicting outcome. Surg Endosc, 2010; 24:407–412.

13.

Csikesz

, Nguyen

, Tseng

, et al. Nationwide volume and mortality after elective surgery in cirrhotic patients. J Am Coll Surg, 2009; 208:96–103.

14.

Clark

, Wills

, Hunt

. Cirrhosis and laparoscopic cholecystectomy. Surg Laparosc Endosc Percutan Tech, 2001; 11:165–169.

15.

Puggioni

, Wong

. A meta-analysis of laparoscopic cholecystectomy in patients with cirrhosis. J Am Coll Surg, 2003; 197:921–926.

16.

Cobb

, Heniford

, Burns

, et al. Cirrhosis is not a contraindication to laparoscopic surgery. Surg Endosc, 2005; 19:418–423.

17.

Machado

. Laparoscopic cholecystectomy in cirrhotics. JSLS, 2012; 16:392–400.

18.

Quillin

, Burns

, Pineda

, et al. Laparoscopic cholecystectomy in the cirrhotic patient: Predictors of outcome. Surgery, 2013; 153:634–640.

19.

Cheng

, Zhao

, Chen

, et al. Comparison of the ability of the PDD-ICG clearance test, CTP, MELD, and MELD-Na to predict short-term and medium-term mortality in patients with decompensated hepatitis B cirrhosis. Eur J Gastroenterol Hepatol, 2016; 28:444–448.

20.

Møller

, Henriksen

, Bendtsen

. Extrahepatic complications to cirrhosis and portal hypertension: Haemodynamic and homeostatic aspects. World J Gastroenterol, 2014; 20:15499–15517.