CHOLANGITIS
Acute cholangitis is the result of bacterial infection superimposed on partial or complete obstruction of the biliary system. It occurs
in 6% to 9% of patients admitted with cholelithiasis. In the past, about 80% of cases were related to choledocholithiasis. However, due to the
increase in endoscopic and radiological intervention and prolonged survival in patients with malignant disease, more patients with cholangitis
are related to malignant biliary obstruction. The disease can present with a wide range of severity, from lowgrade fever to severe sepsis and
shock with frank pus within the biliary tree, which is also known as acute suppurative cholangitis. The reported mortality rate for acute
suppurative cholangitis was as high as 88%. The infecting organism is usually one of the gut flora and gram-negative bacillus are commonly
encountered. These include Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae, Pseudomonas, Streptococcus, Proteus and
Enterobacter species. Anaerobes including Bacteroides and Clostridium species can be detected in about 25% of patients. In about 20% of
patients, two organisms are isolated but there are rarely more than two. Sepsis from cholangitis can be particularly severe because there is no
endothelial lining between the bile canaliculi and the capillary system in the liver. Elevated intraductal pressure leads to bacteremia and about
50% of the patients have positive blood cultures.
Possible etiology of acute cholangitis

Biliary stones
o
Choledocholithiasis
o
Hepatolithiasis (recurrent pyogenic
cholangitis)
o
Mirizzi syndrome

Benign biliary condition
o
Benign stricture
o
Anastomotic stricture
o
Ampullary stenosis
o
Choledochal cyst
o
Periampullary diverticulum
o
Primary sclerosing cholangitis




Malignant stricture
o
Cholangiocarcinoma
o
Carcinoma of pancreas
o
Carcinoma of ampulla
o
Carcinoma of gallbladder
Indwelling tubes or stents
Cholangiography
o
T-tube
o
Percutaneous transhepatic
o
Endoscopic retrograde
Parasitic infestation
o
Clonorchis sinensis
o
Ascaris lumbricoides
DIAGNOSIS
Clinical features
The diagnosis of acute cholangitis is usually made, or at least suspected, on the basis of the history and physical examination.
Charcot's triad of fever, jaundice and right upper quadrant abdominal pain is the classical presentation of acute cholangitis. However, only 50%
to 70% of the patients exhibit all the three features. The most frequent symptom is fever, which is present in over 90% of the patients.
Abdominal pain occurs in about 80% of the patients and clinical jaundice occurs in similar incidence. In severe acute cholangitis, patients may
develop shock and an altered mental status known as Reynolds’ pentad. Other possible presenting symptoms include paralytic ileus and occult
sepsis. The principal abdominal conditions that confuse with acute cholangitis are acute cholecystitis, acute pancreatitis, acute hepatitis, liver
abscess, acute pyelonephritis and perforated peptic ulcers.
Blood tests
Blood tests may show elevated white cell count, serum bilirubin, alkaline phosphatase and transaminases. Serum amylase may be
elevated in about onethird of the patients and is markedly raised in about 10% of the patients when concomitant acute pancreatitis is present.
Radiological investigations
Percutaneous ultrasonography of the abdomen usually reveals dilated biliary tree and detects the presence of cholecystolithiasis but
it can only detect about 35% of the choledocholithiasis. Compared with ultrasonography, computed tomography is more effective in
demonstrating the cause and the level of biliary obstruction. It can visualize the distal common bile duct and demonstrate common bile duct
stones if they have a higher calcium density. Direct cholangiography including percutaneous transhepatic cholangiography (PTC) or endoscopic
retrograde cholangiopancreatography (ERCP) can demonstrate the biliary tree properly. However, direct cholangiography can exacerbate the
cholangitis leading to severe sepsis and should always be combined with therapeutic drainage procedure whenever biliary obstruction is
demonstrated.
Poor prognostic factors
Poor prognostic factors include old age, female sex, acute renal failure, concomitant medical problems, pH < 7.4, bilirubin > 90
μmol/L, albumin < 30 g/L, platelet count < 150 × 109/L, preexisting cirrhosis, presence of liver abscess and malignant biliary obstruction.
MANAGEMENT
Antibiotics and supportive treatment
Initial management of all patients with acute cholangitis should include intravenous fluid resuscitation and antibiotics. Supportive
measures may also include invasive monitoring, intensive care, inotropic and ventilation support in patients with severe cholangitis. Because of
the wide range of possible infecting organisms and the possibility of mixed infection, broad-spectrum antibiotic is required, which should be
able to cover gram-negative bacilli. In the past, the antibiotic frequently administered in acute cholangitis was ampicillin together with an
aminoglycoside. Mezlocillin alone was found more effective and has fewer adverse effects than the combination of ampicillin and gentamicin.
However, mezlocillin is ineffective against Pseudomonas. Trials comparing various antibiotics have not shown the superiority of any agent. A
reasonable choice for initial antibiotic treatment of acute cholangitis is ticarcillin and clavulanante (Timentin) or piperacillin and tazobactam
(Tazocin). About 90% of patients with acute cholangitis respond to antibiotics and other supportive treatment within 24 to 48 hours. Response
is usually measured by improvement of clinical signs and body temperature, normalizing liver function tests, and subjective improvement. In
patients who respond to antibiotics and supportive treatment, definitive treatment of biliary obstruction, including endoscopic or radiological
intervention and surgery, can be delayed until the patients have recovered from cholangitis. However, in patients with severe acute cholangitis
and septicemia or patients who failed conservative management, emergency biliary decompression is crucial for treatment.
Surgical drainage
Before the advent of interventional radiology and therapeutic endoscopy, surgical decompression of the biliary tree was the only
treatment for patients with severe cholangitis. Surgical interventions for drainage include stone extraction, T-tube insertion, transhepatic
intubation of bile duct or bilio-enteric bypass. Open surgery, however, has been associated with high morbidity and mortality. The reported
mortality rate of emergency surgery for acute cholangitis varied from 20% to 60%. Age, comorbidities, jaundice, renal failure, acidosis,
thrombocytopenia and malignant diseases are risk factors associated with increased perioperative mortality.
Percutaneous transhepatic biliary drainage (PTBD)
Traditionally, emergency PTC has been avoided in patients with acute suppurative cholangitis because of the association of a high
complication rate of about 50%. However, with the development of interventional radiological technique including fine-needle
cholangiography, the procedure-related complications have been much reduced and PTBD is a valuable tool in treating patients with
cholangitis. Care must be taken, however, in avoiding injection of contrast into the biliary system with pressure during the procedure in the
setting of acute cholangitis because it will exacerbate septicemia. The primary aim of emergency PTBD is to establish drainage rather than
definitive cholangiography in the acute phase of cholangitis. In recent reported series, emergency PTBD for patients with acute cholangitis
could achieve a successful biliary drainage rate close to 100% with a complication rate less than 10% and mortality around 5%. The major
advantage of PTBD compared with surgery or endoscopic treatment is that there is no need for systemic sedation or anesthesia, which can
result in hemodynamic instability and respiratory complications. The disadvantage of PTBD includes the need to puncture the liver which may
result in serious complications, especially in patients with severe sepsis, clotting derangement and thrombocytopenia. These include bile
peritonitis, hemoperitoneum and hemobilia. In view of a higher complication rate and an inferior successful rate when compared with
endoscopic drainage procedure, PTBD is reserved for patients who have strong contraindication for endoscopic intervention (for example,
previous Billroth II gastrectomy) and who have failed endoscopic intervention or hilar cholangiocarcinoma.
Endoscopic drainage
Since the description of endoscopic sphincterotomy and stone extraction in 1973, endoscopic management has become the optimal
mode of treatment for many patients with various conditions including acute cholangitis. Numerous studies have reported the use of
endoscopic treatment for patients with acute cholangitis and the association with low morbidity and mortality. Leese et al. reported in 1986
that endoscopic treatment was superior to both medical management and surgery in a retrospective, nonrandomized analysis of the outcome
of 82 patients with acute cholangitis related to choledocholithiasis. Patients undergoing endoscopic sphincterotomy had significantly lower
mortality (4.7%) than patients undergoing surgery (21.4%), despite the fact that patients in the endoscopic group were significantly older and
with poorer surgical risks than those treated surgically. In another retrospective study, Lai et al. (1990) found that endoscopic drainage using a
nasobiliary catheter after performing a small sphincterotomy led to lower morbidity (40% versus 65%) and lower mortality (6.7% versus 20%)
compared with surgery. These retrospective studies suggested that endoscopic treatment was superior to surgery in the management of
patients with acute cholangitis.
The advantages of endoscopic treatment over surgery in patients with severe cholangitis were first demonstrated in a prospective
randomized trial reported by Lai et al. from Hong Kong in 1992. In this study, 82 critically ill patients with severe cholangitis were randomized to
either endoscopic drainage or emergency surgery after choledocholithiasis was confirmed with endoscopic cholangiography. Endoscopic
drainage consisted of small papillotomy and placement of a 7 Fr. nasobiliary catheter. No attempt was made to extract the stones in initial
endoscopic procedure. After resolution of cholangitis, 16 patients underwent definitive surgery and 25 underwent definitive endoscopic
treatment. Patients treated surgically underwent emergency laparotomy and choledochotomy. It was found that patients who were treated
surgically had significantly higher incidence of complications (64% versus 34%) and hospital mortality (32% versus 10%) compared with those
who underwent endoscopic treatment. It was therefore concluded that endoscopic biliary drainage was a safe and effective measure for the
initial control of severe acute cholangitis due to choledocholithiasis and in reducing mortality associated with the condition.
Further studies also confirmed that endoscopic drainage can be performed with a much lower mortality rate and fewer
complications than open surgical drainage and can effectively relieve the endotoxemia associated with acute cholangitis. In a recent large
series, ERCP was utilized to treat 898 patients with cholangitis due to gallstone obstruction and 49 with cholangitis due to ductal stenosis. All
patients were successfully treated endoscopically with a mortality rate of 0.42% and a complication rate of 6%. Only two patients in the series
required open surgery: one for pancreatitis and one for perforation. Both morbidity and mortality increase with increasing delay from the onset
of cholangitis to the time of biliary drainage; therefore patients with severe acute cholangitis or those who have shown a poor response to
conservative measures require urgent endoscopic biliary decompression.
SUMMARY
Acute cholangitis is a serious infective condition of the biliary tract that requires prompt treatment. The application of therapeutic
endoscopy and interventional radiology has significantly improved the morbidity and mortality associated with the condition. Endoscopic
treatment plays a major role in both the acute phase of acute cholangitis and the definitive treatment of choledocholithiasis. However, it must
be emphasized that if endoscopic intervention is unsuccessful or if the patients do not recover after endoscopic intervention, surgical or
radiological intervention must be performed before the patients deteriorate further. The definitive treatment of the biliary stones depends on
surgical risks of the patients and the availability of endoscopic and surgical expertise at different centers.