Recurrent Pyogenic Cholangitis 

Updated: Jul 24, 2015
Author: Praveen K Roy, MD, AGAF; Chief Editor: Julian Katz, MD 

Overview

Background

Cholangiohepatitis, or recurrent pyogenic cholangitis (RPC), is characterized by a recurrent syndrome of bacterial cholangitis that occurs in association with intrahepatic pigment stones and intrahepatic biliary obstruction. It was first described in 1930 and has been called by different names, including Hong Kong disease, Oriental cholangitis, and Oriental infestational cholangitis.

Pathophysiology

Recurrent episodes of cholangitis develop as a result of pyogenic bile duct infection. Predominantly coliform-type bacteria are seeded into the biliary system, and, as a consequence, a cascade of stone formation and recurrent cholangitis is initiated. The bile ducts of patients with cholangiohepatitis are thought to be increasingly susceptible to bacterial seeding as a result of helminthic infections or as a consequence of malnutrition.

Malnutrition results in a relative deficiency of enzymes, such as beta-glucuronidase inhibitor glucaro-1,4-lactone, that inhibit deconjugation of conjugated bilirubin. The relatively unopposed deconjugation favors breakdown of conjugated bilirubin to its unconjugated form, which then complexes with calcium to form calcium bilirubinate. Calcium bilirubinate acts as the nidus for the formation of pigmented stones. Pigment stone formation then leads to recurrent biliary obstruction with the characteristic consequence of suppurative cholangitis. This theory of nutrition associated deficiency of beta-glucuronide has been called into question as definite differences in enzyme levels between patients with gallstones and control subjects are difficult to demonstrate.

Infection in the biliary system from Ascaris lumbricoides or from trematodes, such as Clonorchis sinensis and Opisthorchis viverrini, often results in significant epithelial damage. Clinical and experimental data suggest that coliforms may then result in portal bacteremia by bacterial translocation as a result of this epithelial damage. Repeated portal bacteremia, in turn, results in the cascade of events characterized by biliary stasis, obstruction, and stone formation, which consequently result as RPC.

However, it is more likely that infection and malnutrition act in concert to give rise to RPC.

Etiology

The underlying mechanism of RPC is unclear. Most experts believe that RPC is initiated by helminthic infection of the bile ducts and/or sludge/stone formation from deficient glucuronidation as a consequence of profound malnutrition. The initial insult(s) to the bile ducts precipitates a cycle of biliary stone formation and infection that results in recurrent episodes of pyogenic cholangitis.

Epidemiology

Frequency

United States

The condition is rare. It often is observed in immigrants from Southeast Asia or from other regions of the world where trematode infections are endemic. Patients who have RPC develop it over time; hence, there does not appear to be a risk of developing RPC for visitors to endemic areas.

International

The worldwide prevalence of cholangiohepatitis is unclear largely because of the paucity of disease statistics in many parts of the world where this disease is endemic. RPC is prevalent in Hong Kong and East Asia. A case in Turkey was successfully treated with surgery.[1]

Although the arrival of Asian immigrants in the United Kingdom, Australia, Europe, and the United States has resulted in more cases reported in nonendemic areas, the overall incidence in East Asia has been in decline over the last 20 years. Population surveys confirm this trend. The decline in incidence has been credited to the improved economic situation and living standards with the associated westernization of diet.

Prognosis

The prognosis is variable and is directly related to the presence or absence of comorbidities, the presence or absence of liver dysfunction, and the presence or absence of malignancy. In general, the prognosis of patients with cholangiohepatitis is not well documented; however, death occurs in approximately 15-20% of patients over 5-6 years.

Morbidity/mortality

Morbidity is related to recurrent biliary infection and may manifest as pancreatobiliary abnormalities, such as pancreatitis, biliary fistulae, hepatic abscesses, and suppurative cholangitis. Consequences of systemic infections and remote foci of infections account for distant or nonpancreatobiliary morbidity.

Complications

The complications of RPC are protean; acutely, patients may experience systemic sepsis with all of the potential complications of single and multisystem organ failure and hemostatic dysfunction. Over time, patients may develop cirrhosis with portal hypertension and parenchymal insufficiency. Cholangiocarcinoma is an increasingly well-recognized long-term complication of cholangiohepatitis.

 

Presentation

History

Patients may present with the following: (1) an acute attack of cholangitis, (2) a history of recurrent attacks of cholangitis typified by fevers and right upper quadrant (RUQ) abdominal pain, or (3) complications of pyogenic cholangitis. As the disease progresses, patients may develop cholangiocarcinoma and present with constitutional symptoms, including weight loss, easy fatigability, and jaundice.[2, 3]

Roughly one third of patients present with an initial episode of RPC. The typical presentation is a patient older than 30 years who is from an endemic region and reports with complaints of fevers, RUQ abdominal pain, and jaundice (Charcot triad). Atypical presentations without all of the components of the triad are somewhat infrequent but may confound the diagnosis, and a high index of suspicion for RPC in the appropriate setting cannot be overemphasized.

Patients who have experienced recurrent episodes typically report 1-2 episodes of fevers, jaundice, and RUQ abdominal pain per year and a history of prior biliary surgery, endoscopic procedures, or percutaneous biliary drainage procedures.

Patients may present to the hospital with any sequelae of the complications of RPC, including gram-negative bacteremia/sepsis and organ failure. Perforations of the bile duct can occur with rupture into potential spaces, including the pericardium and the peritoneum. Acute pancreatitis is an infrequent but often-described consequence of recurrent bouts of pyogenic cholangitis. In patients presenting with acute pancreatitis, the pain may be in the epigastrium, as opposed to the RUQ. A pyogenic hepatic abscess may be one presentation of RPC, as is biliary malignancy.

Physical

No specific physical findings are evident in RPC. The history is cardinal in prompting the diagnosis.

Patients often appear ill, frequently are jaundiced, and usually have tenderness in the RUQ of the abdomen. Not infrequently in RPC, upon careful physical examination, an enlarged tender gallbladder can be palpated in the RUQ.

Other findings are specific to local and systemic complications of RPC, which can include the following:

  • Rupture into the peritoneum can precipitate an acute abdomen.

  • Rupture or fistulization into the abdominal wall often presents with pus drainage from cutaneous fistulae.

  • Rupture into the pericardium may present with tamponade.

 

DDx

Diagnostic Considerations

Other conditions to consider in the differential diagnosis of recurrent pyogenic cholangitis include the following:

  • Biliary infection with Opisthorchis species

  • Biliary ascariasis

  • Cholangiocarcinoma

  • Pyogenic liver abscess

Differential Diagnoses

 

Workup

Laboratory Studies

Diagnostic testing in the workup of recurrent pyogenic cholangitis includes the following:

  • Complete blood count: A leukocytosis with a left shift is typical in patients with pyogenic cholangitis.

  • Liver function tests: Aminotransferases, serum bilirubin, and alkaline phosphatase typically are elevated in patients with RPC. As with most biliary problems, no predictive or discriminant levels are available to help guide a diagnosis. In other words, any abnormal values in the appropriate clinical setting should prompt a suspicion of RPC, regardless of the degree of liver function test abnormality.

  • Prothrombin time: This may become prolonged if persistent cholestasis with consequent fat malabsorption and vitamin K deficiency is present. This is important to exclude because hypoprothrombinemia can impact the safety of invasive procedures and is easily correctible with parenteral vitamin K in this setting.

  • Blood cultures: These are mandatory because many patients are bacteremic. The blood culture results often help guide antibiotic choice.

  • Ova and parasites: Clonorchis infection frequently is associated with RPC and should be sought and treated when present.

Imaging Studies

Noninvasive imaging studies

Noninvasive imaging studies include transabdominal ultrasonography, computed tomography (CT) scanning, and magnetic resonance cholangiopancreatography (MRCP).

Ultrasonography is the preferred initial test during the primary workup. This imaging modality may demonstrate segmental biliary dilatation, hepatolithiasis, and liver abscesses, if present. Ultrasonography findings often determines the choice of supplemental axial imaging techniques.

CT scanning may demonstrate centrally dilated bile ducts with peripheral tapering. Cholangiohepatitis has a predilection for the left lobe of the liver, and predominantly left-sided findings should prompt consideration of this diagnosis in patients from endemic areas. Other potential findings on CT scans include bile duct stones and pyogenic liver abscesses.

The role of MRCP in the investigation of biliary disease continues to evolve in spite of the poor availability of magnetic resonance imaging (MRI) facilities in many regions of the world where RPC is endemic. MRI produces axial images and can be performed to evaluate the portal and hepatic venous system. Note the following:

  • MR cholangiography may quickly replace endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography as the imaging modality of choice for delineating the biliary tree.

  • In a recent study of 45 patients with RPC who underwent direct cholangiography and MR cholangiography, MR cholangiography demonstrated 100% of all dilated segments, 96% of all strictures, and 98% of all calculi, whereas direct cholangiography demonstrated significantly less, reportedly 44% of all strictures and 45% of all calculi.

  • The role of MRCP is complementary to direct cholangiography, as MRCP, at present, does not offer any therapeutic opportunities.[4, 5, 6]

MRI has been effective in differential diagnosis of malignant versus benign hepatic masses.[7]

Invasive imaging techniques

Cholangiography in the management of RPC is pivotal.

The choice of endoscopic (ie, ERCP) versus percutaneous cholangiography hinges on the patient's anatomy and general health status and on the availability of local expertise.

Very often, a combination of both techniques is necessary to achieve complete ductal clearance of stones and to ensure that drainage of the biliary tree has been optimized.

 

Treatment

Approach Considerations

Patients must be treated with a multidisciplinary approach by multiple subspecialists; therefore, referral to a tertiary center is prudent. Preferably, care should be rendered by individuals who are regional experts in interventional endoscopy, radiology, and hepatobiliary surgery.

Medical care generally involves parenteral antibiotics, avoidance, and/or prompt recognition and treatment of complications. Patients who are malnourished require nutritional rehabilitation.

A biliary drainage procedure is necessary to achieve resolution of the initial infection and to pursue the ultimate goal of preventing further attacks of recurrent cholangitis. The choice of biliary drainage procedure should hinge on patient presentation, comorbidities, cholangiographic findings, and local expertise. To prevent further attacks of cholangitis, these patients are best treated using a multidisciplinary approach of interventional gastroenterology, interventional radiology, and gastrointestinal surgery. Referral to an institution with considerable experience in the management of complex biliary disease is prudent.

Initial biliary decompression is achieved at ERCP, which also allows for the delineation of the biliary tree, an essential step in the planning of the definitive decompressive procedure. Sphincterotomy, stricture dilatation, and placement of a biliary endoprosthesis (stent) often are necessary to achieve biliary decompression and, when appropriate, to alleviate stasis or luminal compromise in the biliary tree, thus preventing further episodes of pyogenic cholangitis. The results of endotherapy appear to be durable in well-selected patients.

Following hospital discharge, careful follow-up with meticulous imaging studies and serial liver function tests is prudent. These studies often provide the first clue that full clearance of the bile ducts has not been achieved or that stone formation has recurred.

Little or no data are available on prevention; however, an overall improvement in living standards appears to parallel a decline in incidence of this disease.

Surgical Care

In some patients, initial medical management may fail and patients may require emergency surgery. These patients often have acute suppurative cholecystitis and require emergent cholecystectomy or percutaneous cholecystotomy (as a temporizing measure). Definitive surgery is directed toward optimizing biliary outflow and is determined by the anatomical extent of involvement. For information on follow-up care, see Further Inpatient Care.

Surgery is necessary in patients who have concomitant cholelithiasis or complex hepatolithiasis.[8, 9] The surgical approach is based on the appearance at cholangiography and on axial imaging or MRCP. Note the following:

  • The usual surgical approach includes the following: (1) cholecystectomy, (2) intraoperative stone clearance by ERCP, (3) percutaneous cholangiography, (4) lithotripsy (ie, mechanical, laser, electrohydraulic), and (5) a definitive biliary drainage procedure.

  • Definitive drainage procedures include operative sphincteroplasty and appropriate biliodigestive bypass.

  • Many surgeons favor performing a Roux-en-Y choledochojejunostomy. Access to the Roux limb for reintervention (if necessary) is achieved percutaneously or endoscopically.

In a retrospective analysis, Lee et al looked at the outcomes of 85 patients who underwent any of the following treatments for recurrent pyogenic cholangitis: hepatectomy (65.9%); hepatectomy combined with drainage (9.4%); drainage alone (14.1%), and percutaneous choledochoscopy (10.6%).[10]

No operative moralities occurred, although 40% of patients suffered complications, half of them involving wound infections. Over a median follow-up period of 45.4 months, patients experienced a residual stone (21.2%), stone recurrence (16.5%), and biliary sepsis recurrence (21.2%), with the greatest incidence of these being in patients who had undergone drainage alone or had been treated with percutaneous choledochoscopy.[10]

In patients who had undergone hepatectomy alone or in combination with drainage, over a median follow-up period of 42.7 months, the frequency of residual stone was 15.6%, stone recurrence was 7.8%, and biliary sepsis recurrence was 9.4%.[10] Based on the study results, the authors recommended that hepatectomy should be considered the treatment of choice for suitable patients with recurrent pyogenic cholangitis.[10]

Consultations

Optimal management of these cases usually requires many consultants who must work in a synergistic fashion to achieve the desired optimal outcome. Potential consultants include interventional gastroenterologists, interventional radiologists, and hepatobiliary surgeons.

Infectious disease experts often help guide the investigation for and the treatment of concurrent helminthic infection.

In the minority of patients who present with the complication of cholangiocarcinoma, consultation with an oncology specialist is prudent.

 

Medication

Medication Summary

Resolution of active infections occurring during acute episodes of RPC requires biliary drainage (ie, surgical, endoscopic, radiologic) and administration of antibiotics.

Broad-spectrum antibiotics

Class Summary

Combination agents (eg, beta-lactam plus beta-lactamase inhibitor) provide excellent gram-negative and anaerobic coverage. Antibiotic selection is guided by blood culture sensitivity whenever feasible. In patients who are allergic to penicillin, a fluoroquinolone is acceptable alternative therapy.

Piperacillin and tazobactam (Zosyn)

Antipseudomonal penicillin plus beta-lactamase inhibitor. Inhibits biosynthesis of cell wall mucopeptide and is effective during the stage of active multiplication.

Ciprofloxacin (Cipro)

Fluoroquinolone with activity against pseudomonads, streptococci, MRSA, Staphylococcus epidermidis, and most gram-negative organisms but no activity against anaerobes. Inhibits bacterial DNA synthesis and, consequently, growth. Continue treatment for at least 2 d (7-14 d typical) after signs and symptoms have disappeared