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Management of Gallstones and Acute Cholecystitis in Patients with Liver Cirrhosis: What Should We Consider When Performing Surgery?

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Management of Gallstones and Acute Cholecystitis in Patients with Liver Cirrhosis: What Should We Consider When Performing Surgery? Gut and Liver https://doi.org/10.5009/gnl20052 pISSN 1976-2283 eISSN 2005-1212 Review Article Management of Gallstones and Acute Cholecystitis in Patients with Liver Cirrhosis: What Should We Consider When Performing Surgery? Shang Yu Wang, Chun Nan Yeh, Yi Yin Jan, and Miin Fu Chen Department of General Surgery, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan Article Info Acute cholecystitis and several gallbladder stone-related conditions, such as impacted com- Received February 10, 2020 mon bile duct stones, cholangitis, and biliary pancreatitis, are common medical conditions in Revised June 19, 2020 daily practice. An early cholecystectomy or drainage procedure with delayed cholecystectomy Accepted July 27, 2020 is the current standard of treatment based on published clinical guidelines. Cirrhosis is not only Published online September 15, 2020 a condition of chronically impaired hepatic function but also has systemic effects in patients. In cirrhotic individuals, several predisposing factors, including changes in the bile acid composition, Corresponding Author increased nucleation of bile, and decreased motility of the gallbladder, contribute to the formation Chun Nan Yeh of biliary stones and the possibility of symptomatic cholelithiasis, which is an indication for surgi- ORCID https://orcid.org/0000-0003-1455-092X cal treatment. In addition to these predisposing factors for cholelithiasis, systemic effects and E-mail [email protected] local anatomic consequences related to cirrhosis lead to anesthesiologic risks and perioperative complications in cirrhotic patients. Therefore, the treatment of the aforementioned biliary condi- tions in cirrhotic patients has become a challenging issue. In this review, we focus on cholecys- tectomy for cirrhotic patients and summarize the surgical indications, risk stratification, surgical procedures, and surgical outcomes specific to cirrhotic patients with symptomatic cholelithiasis. (Gut Liver 2021;15:517-527) Key Words: Gallbladder stone; Cholelithiasis; Cirrhosis; Cholecystectomy; Laparoscopy INTRODUCTION stones in patients with cirrhosis, there are additional issues that should specifically be considered: (1) Should the surgi- Cirrhosis is one of the most complex human diseases cal indication be modified? (2) Do we have any strategy to and causes significant physiological changes, local ana- tackle the surgical difficulty that is increased in relation to tomical alterations, immune status modifications, and local conditions such as the presence of abundant collateral other associated risks, which influence the life expectancy vessels around the surgical field? (3) Similarly, how can we of patients. Cholelithiasis, a common medical condition, manage perioperative complications and improve surgical has been recognized to have a higher incidence in cirrhotic outcomes? In this review, we first summarize the patho- patients than in the general population.1 Currently, surgi- physiology of cholelithiasis in cirrhotic patients. Then, a cal treatments, laparoscopic cholecystectomy (LC) or open thorough review of several relevant surgical issues, includ- cholecystectomy (OC) via laparotomy are the standard ing surgical indications, surgical risks, surgical procedures, of care for symptomatic gallbladder stones (GB stones), and surgical outcomes, is presented. Finally, we propose a including cases with repeated episodes of pain, gallbladder suggested treatment flowchart for cirrhotic patients with polypoid lesions, choledocholithiasis with or without chol- symptomatic GB stones. angitis, acute cholecystitis, and biliary pancreatitis. With- out definite surgical treatment, the incidence of symptom relapse is high.2 Regarding surgical treatment for symptomatic GB Copyright © Gut and Liver. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. www.gutnliver.org Gut and Liver, Vol. 15, No. 4, July 2021 CHOLELITHIASIS IN CIRRHOTIC PATIENTS deterioration of hepatic function in cirrhotic patients changes the biochemical environment of bile and, combined with oth- Cholelithiasis is a common condition in the general er physiological changes, is the major causative factor, espe- population. The prevalence of cholelithiasis is approxi- cially for black stones (Fig. 1). In cirrhotic patients, the com- mately 10% to 20%, while symptomatic cholelithiasis oc- positions of secreted bile are changed, including decreased curs in approximately 20% of individuals with cholelithia- conjugated bilirubin, decreased phospholipid and bile acid sis.3 Cirrhotic patients, however, have been demonstrated production, and increased glycoprotein levels.3,6 The changes to have a higher prevalence of cholelithiasis.4,5 In addition, in bile composition enhance the nucleation of biliary stones. the cumulative incidence has also been proven to be corre- In addition, hemolysis is also an important contributor, and lated with the course of cirrhosis progression, and this phe- this coincides with the fact that black pigmented stones are nomenon reveals that a greater severity and a longer dura- the major type of stones found in cirrhotic patients. While tion of cirrhosis increase the risk of cholelithiasis.1,6 Sheen portal hypertension-related hypersplenism may increase the and Liaw5 reported a Taiwanese cohort of healthy persons destruction of erythrocytes (namely, hemolysis), a change in and chronic hepatitis B patients with or without cirrhosis the cholesterol-to-phospholipid ratio of the erythrocyte mem- (933 vs 500). According to their results, the prevalence of brane due to impaired hepatic function can alter the physiol- GB stones in cirrhotic patients was 4 to 5.5 times higher ogy, flexibility, and morphology of erythrocytes, increasing than that of healthy persons. In addition, the prevalence their destruction.9 Other factors, such as hypomotility of the of GB stones increased along with increasing duration and gallbladder and increased enterohepatic circulation of un- severity of chronic liver diseases, with good linear correla- conjugated bilirubin, have also been proposed. The change in tion. In cirrhotic patients, the formation of black pigment gallbladder motility has been confirmed by serial real-time stones surpassed that of cholesterol stones. Coelho et al.7 ultrasonography and dynamic studies of gallbladder motility, evaluated a series of patients undergoing liver transplanta- and the extent of gallbladder smooth-muscle dysfunction has tion. In Coelho’s cohort, the prevalence of cholelithiasis in also been proven to be correlated with the severity of cirrho- liver recipients was 24%, while that in the control group sis.10-12 Although the underlying mechanism is not well estab- was 9.5%. Among patients with cholelithiasis, 86.2% had lished, the observation of impaired motility of the gallbladder pigment stones. has been recognized to be a risk factor for cholelithiasis in Although the etiologies of cirrhosis, such as chronic viral cirrhotic patients based on currently published studies.10-12 hepatitis C and alcoholism, may increase lithogenesis,1,8 the Enterohepatic circulation occurs in the bowel segment of the Hypersplenism with Enterohepatic Etiology of cirrhosis Changes in bile GB hypomotility hemolysis cycling (HCV, alcoholism) composition with b-Glucuronidase Bilirubin conjugation supersaturation Hemolysis Nucleation * ~85% > ~15% Black stones Cholesterol stones Fig. 1. Pathogenesis of cholelithiasis formation in cirrhosis. In cirrhotic patients, pigmented black stones are more common than cholesterol stones. HCV, hepatitis C virus; GB, gallbladder. *The gallbladder-related effects contribute more significantly to cholesterol stone formation than black stone formation; †While hypersplenism related to portal hypertension causes the direct destruction of red blood cells, altered liver metabolism changes the components of their cell membranes. This effect facilitates hemolysis. 518 www.gutnliver.org Wang SY, et al: Cholecystectomy for Cirrhotic Patients distal ileum, and this physiologic process mainly facilitates bile complications was less than 2%. Although previous studies acid absorption.13 Over 90% to 95% of secreted bile acid will on the natural history of cirrhotic patients have revealed a be absorbed into the portal venous system and subsequently relatively high incidence of GB stones, the progression to resecreted into bile.14 While alcoholism is one of the major symptomatic conditions does not seem to be much differ- etiologies of cirrhosis, alcohol consumption can also impair ent from that in general populations.19,21 Therefore, obser- the absorption of bile acid, and this phenomenon further vational management is reasonable for cirrhotic patients increases the bile acid concentration in the gastrointestinal with asymptomatic GB stones. Currently, no evidence sup- tract.15,16 Intraluminal bile acid will increase the solubility of ports prophylactic cholecystectomy for asymptomatic GB unconjugated bilirubin, further boost the absorption of biliru- stones in cirrhotic patients.6 bin into the portal venous system, increase bilirubin secretion For cirrhotic patients with symptoms, the surgical in- from the liver, and then heighten the risk of cholelithiasis.16 In dications of cholecystectomy, especially in the era of LC, summary,
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