Biliary Disease Differential Diagnoses
- Author: Annie T Chemmanur, MD; Chief Editor: BS Anand, MD more...
Diagnostic ConsiderationsImportant considerationsSpecial concerns
Choose the procedure that is appropriate for the patient. Know the limitations of the procedure. The presence of dense adhesions, advanced liver disease, unexpected cancer, or a severely inflamed gallbladder or encountering troublesome bleeding should prompt assessment of the need to convert to an open procedure.
The persistence, recurrence, or development of pain following removal of the gallbladder is referred to as the postcholecystectomy syndrome. It occurs in 10-15% of the 600,000 cholecystectomies performed annually in the United States.
A retained common duct stone can be identified in 0.3-18% of cases. A history of recurrent biliary-type pain associated with nausea, vomiting, fever, and chills is suggestive of a retained common duct stone, and sonographic evidence of ductal dilation is supportive of this diagnosis. An intraoperative cholangiogram is very useful to exclude a retained common duct stone.
Biliary leaks or fistula occur in 0.1-0.4% of all gallbladder operations. Leakage from the cystic duct stump is most common, but it may (1) emanate from accessory ducts along the gallbladder fossa, (2) be the result from an injury to a major extrahepatic duct, or (3) follow T-tube removal after open cholecystectomy and common bile duct exploration. In the past, these were associated with a mortality rate of about 30%.
Benign biliary strictures occur with a frequency of 0.1-0.8% of all gallbladder operations. This usually is the result of an operative injury to the bile duct. The first type results from a surgical misadventure such as inadvertent duct ligation or placing clips on the bile duct. Only 10% of patients present with pain and jaundice in the first week, and another 60% present within 3 months of the surgery. The second type results either from ischemic injury or from crush injury from clamps. Many months or years may pass before mild cholestasis or symptoms develop when biliary sludge or stones form proximal to a stricture.
Cystic duct remnants are a rare and controversial cause of postcholecystectomy pain. The long cystic duct stump promotes bile stasis within which microlithiasis or stones may form. The passage of this material through the papilla is believed to cause intermittent biliary-type pain. In extremely rare instances, a neuroma or granuloma of the cystic duct stump can cause pain.
Sphincter of Oddi dysfunction
Sphincter of Oddi dysfunction is an uncommon, probably overdiagnosed, cause of biliary-type pain. The 2 subtypes are papillary stenosis and sphincter of Oddi dyskinesia. The former is a mechanical problem, and the latter is a functional problem.
Papillary stenosis is a mechanical problem involving an inflammatory stenosis of the duodenal papilla of Vater. It may be caused by choledocholithiasis, ascariasis, sclerosing cholangitis, pancreatitis, iatrogenic instrumentation of the duodenal papilla, peptic duodenitis, and Crohn disease involving the duodenum and cholesterolosis of the papilla. It is diagnosed manometrically when the sphincter of Oddi manometry reveals a basal sphincter pressure greater than 40 mm Hg that does not decrease in response to CCK or amyl nitrate. It also may be diagnosed surgically via the inability to pass a #3 Bakes dilator through the sphincter or during ERCP via an inability to advance a 5F cannula retrograde over a wire placed into the bile duct.
Endoscopic sphincterotomy alleviates biliary-type pain in most, but not all, patients with papillary stenosis.
The term sphincter of Oddi dysfunction has been used to describe a clinical syndrome of biliary or pancreatic obstruction related to mechanical or functional abnormalities of the sphincter of Oddi.
Sphincter of Oddi dysfunction is diagnosed by a sphincter manometry revealing a basal pressure greater than 40 mm Hg that is responsive to CCK or amyl nitrate. Other supportive features may include phasic wave contractions with a peak amplitude greater than 220 mm Hg, contraction duration greater than 8 seconds, and frequency of greater than 10 per minute. An increased percentage of retrograde contractions have also been cited. Abnormal sphincter motility is uncommon, identified in 1% of 454 patients following cholecystectomy; 14% of those were diagnosed with a postcholecystectomy syndrome.
Several biliary tract abnormalities are associated with HIV infection, but the CD4+ lymphocytes are usually below 100 cells per microliter before these problems develop. These include acalculous cholecystitis, papillary stenosis, and a sclerosing cholangitis–like picture. The causes include opportunistic infections, such as infection with cytomegalovirus, Cryptosporidium species, Enterocytozoon bieneusi, and Mycobacterium species, or neoplasms, such as Kaposi sarcoma and non-Hodgkin lymphoma. Liver-associated enzymes usually show a cholestatic picture, without significant hyperbilirubinemia, unless a neoplasm obstructs the bile duct. Medical therapy to date has been ineffective in treating opportunistic infections.
UDCA has been used in the treatment of primary sclerosing cholangitis, a disorder with similar intrahepatic changes to AIDS cholangiopathy. This observation has led to its experimental use in patients with AIDS cholangiopathy; results in a small number of patients have found an improvement in symptoms and a fall in levels of serum alkaline phosphatase and gamma-glutamyl transpeptidase. The authors recommend giving UDCA in a dose 300 mg 3 times daily, primarily in patients who have intrahepatic ductal disease and markedly elevated liver function test results.
Vanishing bile duct syndrome
This is a rare syndrome affecting the intrahepatic bile ducts. Most patients are asymptomatic, but some may present with pruritus and, rarely, jaundice. The alkaline phosphatase level usually is elevated, along with GGT, which may exceed 600 IU/L. Obtaining a wedge liver biopsy often is necessary to make the diagnosis. The cause of ductopenia may be related to developmental abnormalities of the intrahepatic biliary system, as in Alagille syndrome. On physical examination, frontal bossing and triangular facies may be noted, and tests that are more specific can reveal butterfly vertebrae and posterior embryotoxon of the eye. Progressive familial intrahepatic cholestasis is another type, caused by a genetic mutation of the membrane transporter for phospholipids (MDR3).
Other types are acquired and are associated with cystic fibrosis, systemic mastocytosis, histiocytosis-X, Hodgkin disease, and drug-induced hepatotoxicity. Patients without a clear association are diagnosed with idiopathic adult ductopenia.
Bilirubin, Impaired Conjugation
Yun EJ, Choi CS, Yoon DY, et al. Combination of magnetic resonance cholangiopancreatography and computed tomography for preoperative diagnosis of the Mirizzi syndrome. J Comput Assist Tomogr. 2009 Jul-Aug. 33(4):636-40. [Medline].
American Liver Foundation. Primary biliary cholangitis (PBC, primary biliary cirrhosis). Available at http://www.liverfoundation.org/abouttheliver/info/pbc/. Updated March 29, 2016; Accessed: June 3, 2016.
Solis Herruzo JA, Solis Munoz P, Munoz Yague T. The pathogenesis of primary biliary cirrhosis. Rev Esp Enferm Dig. 2009 Jun. 101(6):413-423. [Medline].
Uibo R, Kisand K, Yang CY, Gershwin ME. Primary biliary cirrhosis: a multi-faced interactive disease involving genetics, environment and the immune response. APMIS. 2012 Nov. 120(11):857-71. [Medline].
Berg CP, Kannan TR, Klein R, et al. Mycoplasma antigens as a possible trigger for the induction of antimitochondrial antibodies in primary biliary cirrhosis. Liver Int. 2009 Jul. 29(6):797-809. [Medline].
Cavallaro A, Cavallaro V, Di Vita M, Cappellani A. Main bile duct carcinoma management. Our experience on 38 cases. Ann Ital Chir. 2009 Mar-Apr. 80(2):107-11. [Medline].
Allison RR, Zervos E, Sibata CH. Cholangiocarcinoma: an emerging indication for photodynamic therapy. Photodiagnosis Photodyn Ther. 2009 Jun. 6(2):84-92. [Medline].
Belli G, Limongelli P, Fantini C, et al. Laparoscopic and open treatment of hepatocellular carcinoma in patients with cirrhosis. Br J Surg. 2009 Sep. 96(9):1041-8. [Medline].
Drebber U, Mueller JJ, Klein E, et al. Liver biopsy in primary biliary cirrhosis: clinicopathological data and stage. Pathol Int. 2009 Aug. 59(8):546-54. [Medline].
US Food and Drug Administration. FDA approves Ocaliva for rare, chronic liver disease [press release]. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm503964.htm. May 31, 2016; Accessed: June 1, 2016.
Edwards JE, LaCerte C, Pheng LH, et al. Sa1576 Exposure-response relationship of obeticholic acid for alkaline phosphatase and total bilirubin in patients with primary biliary cirrhosis (PBC). Poster presented at Digestive Disease Week; San Diego, California; May 21, 2016.
Kageoka M, Watanabe F, Maruyama Y, et al. Long-term prognosis of patients after endoscopic sphincterotomy for choledocholithiasis. Dig Endosc. 2009 Jul. 21(3):170-5. [Medline].
Ohashi A, Tamada K, Wada S, et al. Risk factors for recurrent bile duct stones after endoscopic papillary balloon dilation: long-term follow-up study. Dig Endosc. 2009 Apr. 21(2):73-7. [Medline].
Gurusamy K, Sahay SJ, Burroughs AK, Davidson BR. Systematic review and meta-analysis of intraoperative versus preoperative endoscopic sphincterotomy in patients with gallbladder and suspected common bile duct stones. Br J Surg. 2011 Jul. 98(7):908-16. [Medline].
Castaing D, Vibert E, Bhangui P, et al. Results of percutaneous manoeuvres in biliary disease: The Paul Brousse experience. Surg Endosc. 2011 Jun. 25(6):1858-65. [Medline].
Catena F, Ansaloni L, Di Saverio S, et al. Prospective analysis of 101 consecutive cases of laparoscopic cholecystectomy for acute cholecystitis operated with harmonic scalpel. Surg Laparosc Endosc Percutan Tech. 2009 Aug. 19(4):312-6. [Medline].
Murphy MM, Shah SA, Simons JP, et al. Predicting major complications after laparoscopic cholecystectomy: a simple risk score. J Gastrointest Surg. 2009 Aug 12. epub ahead of print. [Medline].
Sultan AM, El Nakeeb A, Elshehawy T, Elhemmaly M, Elhanafy E, Atef E. Risk Factors for Conversion during Laparoscopic Cholecystectomy: Retrospective Analysis of Ten Years' Experience at a Single Tertiary Referral Centre. Dig Surg. 2013 Apr 26. 30(1):51-55. [Medline].
Moody FG, Vecchio R, Calabuig R. Transduodenal sphincteroplasty with transampullary septectomy for stenosing papillitis. Am J Surg. 1991 Feb. 161(2):213-8. [Medline].
Acosta JM, Civantos F, Nardi GL. Fibrosis of the papilla of Vater. Surg Gynecol Obstet. 1967 Apr. 124(4):787-94. [Medline].
Afdhal NH, Smith BF. Cholesterol crystal nucleation: a decade-long search for the missing link in gallstone pathogenesis. Hepatology. 1990 Apr. 11(4):699-702. [Medline].
Bennion LJ, Grundy SM. Risk factors for the development of cholelithiasis in man (second of two parts). N Engl J Med. 1978 Nov 30. 299(22):1221-7. [Medline].
Boey JH, Way LW. Acute cholangitis. Ann Surg. 1980 Mar. 191(3):264-70. [Medline].
Bolondi L, Gaiani S, Testa S. Gall bladder sludge formation during prolonged fasting after gastrointestinal tract surgery. Gut. 1985 Jul. 26(7):734-8. [Medline].
Broome U, Olsson R, Loof L, et al. Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis. Gut. 1996 Apr. 38 (4):610-5. [Medline].
Burnstein MJ, Ilson RG, Petrunka CN. Evidence for a potent nucleating factor in the gallbladder bile of patients with cholesterol gallstones. Gastroenterology. 1983 Oct. 85(4):801-7. [Medline].
Carey MC, Small DM. The physical chemistry of cholesterol solubility in bile. Relationship to gallstone formation and dissolution in man. J Clin Invest. 1978 Apr. 61(4):998-1026. [Medline].
Castiella A, Iribarren JA, Lopez P. Ursodeoxycholic acid in the treatment of AIDS-associated cholangiopathy. Am J Med. 1997 Aug. 103(2):170-1.
Csendes A, Burdiles P, Maluenda F. Simultaneous bacteriologic assessment of bile from gallbladder and common bile duct in control subjects and patients with gallstones and common duct stones. Arch Surg. 1996 Apr. 131(4):389-94.
Denman ST. A review of pruritus. J Am Acad Dermatol. 1986 Mar. 14(3):375-92. [Medline].
Everhart JE, Khare M, Hill M. Prevalence and ethnic differences in gallbladder disease in the United States. Gastroenterology. 1999 Sep. 117(3):632-9.
Gallinger S, Taylor RD, Harvey PR. Effect of mucous glycoprotein on nucleation time of human bile. Gastroenterology. 1985 Sep. 89(3):648-58. [Medline].
Gerecht WB, Henry NK, Hoffman WW, et al. Prospective randomized comparison of mezlocillin therapy alone with combined ampicillin and gentamicin therapy for patients with cholangitis. Arch Intern Med. 1989 Jun. 149 (6):1279-84. [Medline].
Graziadei IW, Wiesner RH, Batts KP. Recurrence of primary sclerosing cholangitis following liver transplantation. Hepatology. 1999 Apr. 29(4):1050-6. [Medline].
Harnois DM, Angulo P, Jorgensen RA, Larusso NF, Lindor KD. High-dose ursodeoxycholic acid as a therapy for patients with primary sclerosing cholangitis. Am J Gastroenterol. 2001 May. 96 (5):1558-62. [Medline].
Harnois DM, Lindor KD. Primary sclerosing cholangitis: evolving concepts in diagnosis and treatment. Dig Dis. 1997 Jan-Apr. 15 (1-2):23-41. [Medline].
Heathcote EJ. Management of primary biliary cirrhosis. The American Association for the Study of Liver Diseases practice guidelines. Hepatology. 2000 Apr. 31 (4):1005-13. [Medline].
Hendrickse MT, Rigney E, Giaffer MH, et al. Low-dose methotrexate is ineffective in primary biliary cirrhosis: long-term results of a placebo-controlled trial. Gastroenterology. 1999 Aug. 117 (2):400-7. [Medline].
Holzbach RT. Recent progress in understanding cholesterol crystal nucleation as a precursor to human gallstone formation. Hepatology. 1986 Nov-Dec. 6(6):1403-6. [Medline].
Izumi Y, Teramoto K, Ohshima M. Endoscopic resection of duodenal ampulla with a transparent plastic cap. Surgery. 1998 Jan. 123(1):109-10. [Medline].
Jones DE, Gray JC, Newton J. Perceived fatigue is comparable between different disease groups. QJM. 2009 Sep. 102(9):617-24. [Medline].
Kaplan MM. Primary biliary cirrhosis. N Engl J Med. 1996 Nov 21. 335 (21):1570-80. [Medline].
Krishnamurthy GT, Turner FE. Pharmacokinetics and clinical application of technetium 99m-labeled hepatobiliary agents. Semin Nucl Med. 1990 Apr. 20(2):130-49. [Medline].
Lam SK, Wong KP, Chan PK. Recurrent pyogenic cholangitis: a study by endoscopic retrograde cholangiography. Gastroenterology. 1978 Jun. 74(6):1196-1203. [Medline].
Levy PF, Smith BF, LaMont JT. Human gallbladder mucin accelerates nucleation of cholesterol in artificial bile. Gastroenterology. 1984 Aug. 87(2):270-5. [Medline].
Liermann Garcia RF, Evangelista Garcia C, McMaster P. Transplantation for primary biliary cirrhosis: retrospective analysis of 400 patients in a single center. Hepatology. 2001 Jan. 33(1):22-7. [Medline].
Lim JH. Oriental cholangiohepatitis: pathologic, clinical, and radiologic features. Am J Roentgenol. 1991 Jul. 157(1):1-8. [Medline].
Mazer NA, Carey MC. Quasi-elastic light-scattering studies of aqueous biliary lipid systems. Cholesterol solubilization and precipitation in model bile solutions. Biochemistry. 1983 Jan 18. 22(2):426-42. [Medline].
Moody FG. Pathogenesis and treatment of inflammatory lesions of the papilla of Vater. Jpn J Surg. 1985 Sep. 15(5):341-7. [Medline].
Nijhawan PK, Therneau TM, Dickson ER, Boynton J, Lindor KD. Incidence of cancer in primary biliary cirrhosis: the Mayo experience. Hepatology. 1999 May. 29 (5):1396-8. [Medline].
O'Connor MJ, Schwartz ML, McQuarrie DG, Sumer HW. Acute bacterial cholangitis: an analysis of clinical manifestation. Arch Surg. 1982 Apr. 117(4):437-41. [Medline].
O'Connor MJ, Sumner HW, Schwartz ML. The clinical and pathologic correlations in mechanical biliary obstruction and acute cholangitis. Ann Surg. 1982 Apr. 195(4):419-23. [Medline].
Palazzo L, Girollet PP, Salmeron M. Value of endoscopic ultrasonography in the diagnosis of common bile duct stones: comparison with surgical exploration and ERCP. Gastrointest Endosc. 1995 Sep. 42(3):225-31. [Medline].
Pomeranz IS, Shaffer EA. Abnormal gallbladder emptying in a subgroup of patients with gallstones. Gastroenterology. 1985. 88:801. [Medline].
Quirk DM, Rattner DW, Fernandez-del Castillo C. The use of endoscopic ultrasonography to reduce the cost of treating ampullary tumors. Gastrointest Endosc. 1997 Oct. 46(4):334-7. [Medline].
Ransohoff DF, Gracie WA, Wolfenson LB. Prophylactic cholecystectomy or expectant management for silent gallstones. A decision analysis to assess survival. Ann Intern Med. 1983 Aug. 99(2):199-204. [Medline].
Ros E, Zambon D. Postcholecystectomy symptoms. A prospective study of gall stone patients before and two years after surgery. Gut. 1987 Nov. 28(11):1500-4. [Medline].
Ruffolo TA, Sherman S, Lehman GA. Gallbladder ejection fraction and its relationship to sphincter of Oddi dysfunction. Dig Dis Sci. 1994 Feb. 39(2):289-92. [Medline].
Sampliner RE, Bennett PH, Comess LJ. Gallbladder disease in Pima Indians. Demonstration of high prevalence and early onset by cholecystography. N Engl J Med. 1970 Dec 17. 283(25):1358-64. [Medline].
Schoenfield LJ, Carey MC, Marks JW. Gallstones: an update. Am J Gastroenterol. 1989 Sep. 84(9):999-1007. [Medline].
Sievers MS, Marquis JR. The Southwest American Indian's burden: biliary disease. JAMA. 1962. 182:570-2.
Strauch GO. Primary carcinoma of the gall bladder: presentation of seventy cases from the Rhode Island Hospital and a cumulative review of the last ten years of the American literature. Surgery. 1960 Mar. 47:368-83. [Medline].
Strom BL, Soloway RD, Rios-Dalenz JL, et al. Risk factors for gallbladder cancer. An international collaborative case-control study. Cancer. 1995 Nov 15. 76 (10):1747-56. [Medline].
Thistle JL, Cleary PA, Lachin JM, Tyor MP, Hersh T. The natural history of cholelithiasis: the National Cooperative Gallstone Study. Ann Intern Med. 1984 Aug. 101 (2):171-5. [Medline].
Wienser RH, Porayko MK, LaRusso NF, et al. In: Schiff L, Schiff ER, eds. Diseases of the Liver. 7th ed. Philadelphia, Pa: JB Lippincott; 1993: 411-26.
Wolfhagen FH, Sternieri E, Hop WC. Oral naltrexone treatment for cholestatic pruritus: a double-blind, placebo-controlled study. Gastroenterology. 1997 Oct. 113(4):1264-9. [Medline].
Yap L, Wycherley AG, Morphett AD. Acalculous biliary pain: cholecystectomy alleviates symptoms in patients with abnormal cholescintigraphy. Gastroenterology. 1991 Sep. 101(3):786-93. [Medline].
Yoshida J, Chijuwa K. Practical classification of the branching types of the biliary tree: an analysis of 1094 consecutive direct cholangiograms. J Am Coll Surg. 1997. 185:274-82. [Medline].
Zeman RK. Cholelithiasis and cholecystitis. In: Gore RM, Levine MS, Laufer I, eds. Text of Gastrointestinal Radiology. Philadelphia, Pa: WB Saunders.; WB Saunders. 1994: 1654-5.