sign in sign up
<<
Home , Cholecystitis, Cholestasis, Gallbladder disease

J Clin Pathol 1994;47:457-460 457 changes associated with

J M Geraghty, R D Goldin J Clin Pathol: first published as 10.1136/jcp.47.5.457 on 1 May 1994. Downloaded from

Abstract Previous studies correlating the presence of Aims-To investigate the histopathologi- gall stones with changes in liver histology have cal changes in the of patients given conflicting results.49 In particular, the undergoing and to relate reported incidences of portal tract fibrosis dif- these changes to the underlying biliary fered considerably, and its association with tract pathology. the localisation of gall stones has been poorly Methods-Liver changes in 67 patients defined. More importantly, the histological undergoing cholecystectomy were inves- changes have not been described in detail. tigated. Sixty three had gall stones, one The aim of this study, therefore, was to cholesterolosis only, and there were three determine the prevalence and extent of liver cases of acute acalculous cholecystitis. disease, and to assess the value ofperoperative Results-Only 34% of the patients had liver biopsy specimens in patients undergoing completely normal liver biopsy speci- cholecystectomy for gall stones and cholecys- mens. The most clinically important titis. Clinical assessment, pathology was found in 11 of the 14 and biliary microbiology were correlated with patients with choledocholithiasis: three liver and gall bladder histology and the distrib- of these had cholangitis and eight had ution of gall stones in the biliary tree. features of large duct obstruction (four also had chronic and portal-portal linking fibrosis). Non-spe- Methods cific reactive was the most com- Peroperative protocol liver biopsy specimens mon abnormality in the remaining 53 distal to the gall bladder bed were obtained patients with cholecystitis alone, and was from 67 consecutive patients undergoing found in 18. A further four patients had cholecystectomy at St Mary's Hospital, chronic cholestasis without fibrosis and London, between January 1984 and March early primary biliary was a 1989. The series included 41 women, mean coincidental finding in another. Clinical age 47.6 years (range 18 to 83 years), and 26 http://jcp.bmj.com/ symptoms were poorly correlated with men, mean age 57.6 years (range 32 to 75 gall bladder and liver pathology apart years), a distribution similar to that expected from an association between for the British population.' 01' and choledocholithiasis. Liver function Forty patients presented with acute symp- tests of obstructive pattern were noted in toms and underwent emergency cholecystec- 23 of 58 patients, most of whom had tomy. Twenty one of these had had a history choledocholithiasis or non-specific reac- of gall stone related disease of between four on September 25, 2021 by guest. Protected copyright. tive hepatitis. Bile cultures were positive weeks' and 10 years' duration. Elective in 10 of 42 patients, predominantly in surgery was carried out in the remaining 27 cases of cholangitis and acute chole- patients, who had histories of gall stone cystitis. related disease of between eight weeks and 15 Conclusions-Cholangitis and extensive years. None of the patients was alcoholic, had fibrosis associated with large , or was known to be taking obstruction are common findings in drugs associated with liver damage. The patients with choledocholithiasis. The results of preoperative liver function tests may progress to secondary (serum , aspartate amino transferase, biliary cirrhosis if the obstruction is not and ), taken within three relieved, emphasising the need for early days before surgery, were available in 53 surgery. A peroperative liver biopsy may patients. be useful to exclude cirrhosis in these The distribution of gall stones within the patients, but is unlikely to be informative biliary tree was determined by a combination in those with cholecystitis alone. of radiological and ultrasound findings before Department of surgery and those at surgery including per- , St ( Clin Pathol 1994;47:457-460) operative cholangiography and exploration of Mary's Hospital the . Peroperative bile Medical School, Norfolk Place, London swabs from the gall bladder and common bile W2 IPG Liver damage in patients with gall stones is duct were cultured aerobically and anaerobi- J M Geraghty thought to be the result of chronic extra- cally by standard methods, and results were R D Goldin hepatic large bile duct obstruction with or available for 42 patients. Correspondence to: 2 Dr R D Goldin without repeated episodes of cholangitis" The liver biopsy specimens (stained with Accepted for publication and may ultimately progress to secondary haematoxylin and eosin, reticulin, and orcein 25 November 1993 biliary cirrhosis.' stains) and blocks from the gall bladders 458 Geraghty, Goldin

T;able 1 Gall bladder histology in 67patients undergoing CORRELATION BETWEEN LIVER AND cholecystectomy, with percentages ofthe total in GALL BLADDER HISTOLOGY parentheses Normal liver histology and reactive hepatitis Normal 2(3 0) were common in all categories of gall bladder Acute cholecystitis 8(11 9) J Clin Pathol: first published as 10.1136/jcp.47.5.457 on 1 May 1994. Downloaded from Acute-on-chronic 22(32-8) disease. Large droplet fatty change and acute cholecystitis or chronic large duct obstruction were seen Chronic cholecystitis 34(50 7) Cholesterolosis only 1(1.5) mainly in cases of acute-on-chronic or chronic cholecystitis. All those patients with cholangitis or reactive hepatitis with acute inflammatory cells in portal tracts had either acute or acute- (fundus, neck, and body) were assessed on-chronic cholecystitis. independently by both authors and designated histological categories according to standard CLINICAL SYMPTOMS texts.'12 Discrepancies were settled by con- The most common symptoms were abdomi- sensus. nal pain with or without jaundice. There was no correlation between the timing of the pain and gall bladder or liver histology. Results Thirteen (19%) patients presented with GALL BLADDER HISTOLOGY AND DISTRIBUTION acute and jaundice, with the OF GAIL STONES following liver histology: acute cholangitis (n = Histological changes in the gall bladder are 3); acute large duct obstruction (n = 4); acute documented in table 1. Cholelithiasis was pre- large duct obstruction with chronic cholestasis sent in 63 patients, 14 of whom also had (n = 2); non-specific reactive hepatitis (n = choledocholithiasis. Three had acute acalcu- 1); and cholestasis only (n = 3). None had lous cholecystitis and another only choles- normal liver histology. All three patients with terolosis. The distribution of stones and the cholangitis had swinging in addition to gall bladder histology were similar in men and abdominal pain and jaundice. women (results not shown). Forty two patients had no history of jaun- dice, including two with the changes of acute LIVER HISTOLOGY (TABLE 2) large duct obstruction with chronic cholesta- Although minor differences were seen in the sis, both of whom had histories of abdominal frequency of histological changes between pain of more than two years. men and women, these were not significant All four patients with only chronic cholesta- (results not shown). Liver histology was nor- sis had histories of recurrent abdominal pain, mal in 23 (34%) patients. The commonest of at least three months' duration, but none abnormalities were non-specific reactive had had jaundice before. hepatitis and large droplet fatty change. Of In general, there was poor correlation the 18 patients (27%) with reactive hepatitis between symptoms and gall bladder pathol- http://jcp.bmj.com/ seven also had acute inflammatory cells in ogy. portal tracts not involving the bile ducts. More clinically important pathology in the CHOLEDOCHOLITHIASIS form of cholestasis, cholangitis, or large duct The results of liver histology for the 14 obstruction was present in 18 patients. patients with choledocholithiasis are given in Extensive fibrosis with portal-portal linking table 3. was confined to the four patients with acute on September 25, 2021 by guest. Protected copyright. large duct obstruction who also showed fea- LIVER FUNCTION TESTS tures of chronic cholestasis, including the Abnormal preoperative liver function tests are accumulation of copper associated protein in correlated with liver histology in table 4. periportal ."3 None of the patients Twenty eight of the 53 (53%) patients in had secondary biliary cirrhosis. The liver whom results were available had abnormal biopsy specimen from one woman displayed liver function tests. The most sensitive indica- the features of primary biliary cirrhosis (stage tor of clinically important liver pathology was a 2), subsequently confirmed by a positive test raised serum alkaline phosphatase value, pre- for serum mitochondrial antibodies. sent in 23 (43%) patients. None of the A frequent observation was the presence of patients with acalculous cholecystitis had a focal necroses and collections of neutrophils raised alkaline phosphatase activity. in the sinusoids, which are generally accepted to be the result of surgery and anaesthesia.' BILJARY MICROBIOLOGY Of the 42 patients in whom the results of peroperative bile swab microbiology were Table 2 Liver histology in 67patients undergoing cholecystectomy with percentages ofthe total Table 3 Liver histology in 14 patients with Normal 23(34-3) choledocholithiasis Large droplet fatty change only 7(10-4) Non-specific reactive hepatitis 18(26-8) Liver histology No. of cases Acute cholestasis only 3(4-5) Chronic cholestasis only 4(6 0) Normal 3 Acute cholangitis 3(4 5) Acute cholangitis 3 Acute large duct obstruction 4(6 0) Acute large duct obstruction 4 Acute large duct obstruction 3(6-0) Acute large duct obstruction 4 with chronic cholestasis with chronic cholestasis Primary biliary cirrhosis 1(1-5) Total 14 Liver changes associated with cholecystitis 459

Table 4 Abnormal liverfunction tests in patients undergoing cholecystectomy the obstruction is relieved,'4 which emphasises Raised Raised alkaline Total the importance of early surgery. bilirubin RaisedAST phospatase (total No of Others have reported minor degrees of (>1 7mmolll) (>40 U/l) (>130 U/l) patients tested) fibrosis or the prominence of acute inflamma- J Clin Pathol: first published as 10.1136/jcp.47.5.457 on 1 May 1994. Downloaded from Nonnal 1 1 1 3(18) tory cells in portal tracts in patients with Large droplet fatty 0 0 0 0(1) change only cholecystitis or choledocholithiasis, but the Non-specific reactive 5 6 7 9(16) presence or absence of the changes of large hepatitis Acute cholestasis 3 2 2 3(3) duct obstruction, cholangitis, and cholestasis only were not emphasised in these studies.5 8 9 Chronic cholestasis 0 0 2 2(3) only The presence of acute and chronic Acute 3 3 3 3(3) cholestasis alone in two and four cholangitis patients, Acute large duct 4 3 4 4(4) respectively, with cholelithiasis, is most likely obstruction related to previous choledocholithiasis with Acute large duct 2 3 3 3(4) obstruction with expulsion of the stone before surgery. This is chronic cholestasis supported by the obstructive pattern of liver Primarybiliary 0 1 1 1(1) cirrhosis function tests present in four of these cases. Total 18 19 23 28(53) None of these patients had extensive fibrosis. Non-specific reactive hepatitis was a fre- quent finding in this study and was confined to patients with acute or chronic cholecystitis. None had choledocholithiasis, but nine had available, 10 (24%) had positive cultures of abnormal liver function tests, most of obstruc- one or more organisms, including six of the tive pattern. Reactive hepatitis might, there- 14 with choledocholithiasis (results were fore, be the result of a recent episode of unavailable in two of these). Infected bile was common bile duct obstruction in some seen mainly in acute or acute-on-chronic patients. Chronic in portal cholecystitis. Only two of these patients had tracts, with or without large droplet fatty chronic cholecystitis with no acute inflamma- change, has been reported by others with sim- tory component. ilar frequency.458 Reactive hepatitis has been Liver histology in these patients was as fol- described in patients with a variety of condi- lows: acute cholangitis (n = 3); reactive tions, including febrile illnesses, hepatic hepatitis (n = 3, two with an acute inflamma- space-occupying lesions, venous outflow tory component); acute large duct obstruction obstruction and intestinal infections.' As a with chronic cholestasis (n = 1); acute common disease, cholecystitis should be cholestasis only (n = 1); and normal (n = 2). regarded as an important additional cause. Bacterial isolates comprised Some patients with reactive hepatitis also had

(six patients), faecalis (three acute inflammatory cells in portal tracts and http://jcp.bmj.com/ patients), Bacteroides fragilis (one patient), this correlated with acute inflammation in the Pseudomonas aeruginosa (one patient), and gall bladder. perfringens (one patient). The finding of a single case of primary bil- All categories of gall bladder and liver his- iary cirrhosis among these patients should be tology, apart from cholangitis, were repre- regarded as coincidental. There is no known sented among the 32 patients with sterile bile association between the two diseases.

cultures. Clinical symptoms were ofpoor discrimina- on September 25, 2021 by guest. Protected copyright. tive value in predicting the underlying pathol- ogy, in accordance with the findings of Discussion others.9 The duration of abdominal pain This study has shown that a high proportion could not be correlated with either liver or gall (66%) of patients with gall stones and chole- bladder pathology. Jaundice was often present cystitis had abnormal liver histology. The in patients with cholangitis or large duct most common findings were non-specific obstruction, but the association was not reactive hepatitis and large droplet fatty invariable. A previous history of jaundice was change. More clinically important liver not correlated with extensive liver pathology. pathology, in the form of large duct obstruc- Conversely, six of the eight patients with tion or cholangitis, was associated with chole- chronic cholestasis had never been jaundiced, docholithiasis, which is similar to the findings similar to the findings in the early stages of of others.267 primary biliary cirrhosis. 15 Extensive fibrosis with portal-portal linking Abnormal liver function tests were most was present in four of the patients with large common in patients with choledocholithiasis. duct obstruction. This was shown to be the An obstructive pattern with raised alkaline result of chronic by the demon- phosphatase values was the most frequent stration of chronic cholestasis in each case. abnormality, which was similar to the findings This observation is important because the of others.'6 fibrosis could ultimately progress to irre- The noted high incidence of positive bile versible secondary biliary cirrhosis.236 The cultures in patients with choledocholithiasis, mean interval between the onset of partial bil- cholangitis, and acute cholecystitis and the iary obstruction by gall stones and the confir- spectrum of bacterial isolates was as expected mation of cirrhosis has been estimated at 4-6 from other series.8 17-20 years.' Considerable resolution may still be This study has shown that cholangitis and possible at the stage of portal-portal linking if extensive fibrosis associated with large bile 460 Geraghty, Goldin

duct obstruction are common in patients with 8 Flinn WR, Olson DF, Oyasu R, Beal JM. Biliary bacteria and hepatic histopathologic changes in disease. choledocholithiasis. The liver disease may Ann Surg 1977;185:593-7. progress to secondary biliary cirrhosis if the 9 Triger DR, Maclver AG, Gamlen TR, Wilken BJ. Liver abnormalities and : a prospective combined obstruction is not relieved, emphasising the clinical, histological and surgical study. Br Surg J Clin Pathol: first published as 10.1136/jcp.47.5.457 on 1 May 1994. Downloaded from need for early surgery. A peroperative liver 1976;63:272-7. 10 Bateson MC. disease and cholecystectomy biopsy may be useful to exclude cirrhosis in rate are independently variable. Lancet 1984;il:621-4. these patients, but is unlikely to be informa- 11 Bateson MC. Gallbladder surgery in Scotland. Lancet 1988;ii: 1250. tive in those with cholecystitis alone. 12 Weedon D. Diseases of the gallbladder. In: MacSween RNM, Anthony PP, Scheuer PJ, eds. Pathology of the liver. 2nd edn. Edinburgh: Churchill Livingstone, 1987:454-77. 1 Scheuer PJ. Liver biopsy interpretation. 4th ed. London: 13 Guarascio P, Yentis F, Cevikbas U, Portnann B, Williams Bailliere Tindall, 1988. R. Value of copper-associated protein in diagnostic 2 Desmet VJ. Cholestasis: extrahepatic obstruction and sec- assessment of liver biopsy. Clin Pathol 1983;36: 18-23. ondary biliary cirrhosis. In: MacSween RNM, Anthony 14 Yeong ML, Nicholson GI, Lee SP. Regression of biliary PP, Scheuer PJ, eds. Pathology of the liver. 2nd ed. cirrhosis after choledochal cyst drainage. Edinburgh: Churchill livingstone, 1987:364-423. 1982;82:332-5. 3 Scobie BA, Summerskill WHJ. Hepatic cirrhosis sec- 15 Portmann B, MacSween RNM. Diseases of the intrahep- ondary to obstruction of the biliary system. Am Jf Dig Dis atic bile ducts. In: MacSween RNM, Anthony PP, 1965;10:135-46. Scheuer PJ, eds. Pathology of the liver. 2nd edn. 4 Mateer JG, Hartmann FW, Blatz JJ, Fallis LD, McGraw Edinburgh: Churchill Livingstone, 1987:424-53. AB, Steele HH. Combined liver biopsy and liver func- 16 Lindenauer SM, Child CG. Disturbances of liver function tion study in 132 cases of cholelithiasis and 31 cases of in disease. Surg Gynecol Obstet 1966;123: peptic ulcer (operated cases). Gastroenterology 1948;11: 1205-11. 284-302. 17 Salk RP, Greenburg AG, Farris JM, Perkin GW. Spectrum 5 Savory PB, Shively JA, Talbert PC, Caylor HD. Biliary of cholangitis. Am Jf Surg 1975;130: 143-50. system inflammation and cholecystitis. Am Surg 1955; 18 Haw CS, Gunn AA. The significance of infection in biliary 90:562-7. disease. Roy Coil Surg Edin 1973;18:209-12. 6 Edlund YA, Zettergren LSW. Microstructure of the liver 19 Pitt HA, Postier RG, Cameron JL. Consequences of pre- in biliary tract disease. Acta Chir Scand 1957;113: operative cholangitis and its treatment on the outcome 201-10. of operation for choledocholithiasis. Surgery 1983;94: 7 Poulsen H, Christoffersen P. Histological changes in liver 447-52. biopsies from patients with surgical bile duct disorders. 20 England DM, Rosenblatt JE. Anaerobes in human biliary Acta Pathol Microbiol Scand 1970;78:571-9. tracts. _J Clin Microbiol 1977;6:494-8. http://jcp.bmj.com/ on September 25, 2021 by guest. Protected copyright.