Cholangitis

What is cholangitis?

Acute cholangitis, also called ascending cholangitis, is a bacterial infection of the biliary system, due to partial or complete obstruction of the bile duct or hepatic ducts. The most common cause of biliary obstruction is gallstone or malignant stricture, but obstruction caused by primary sclerosing cholangitis, amyloid depositions or parasite biliary invasions also occur.¹

Acute cholecystitis is an acute inflammatory disease of the gallbladder, often caused by gallstones; however, many factors (eg, ischaemia, motility disorders, chemical injury, infections by micro-organism, protozoon and parasites, collagen disease and allergic reactions) are also involved.

The term hepatic fever was used for the first time by Charcot in his report published in 1887. Intermittent fever accompanied by chills, right upper quadrant abdominal pain, and jaundice have been established as Charcot's triad.

Bile is normally sterile; however, if the common bile duct (CBD) is obstructed the flow of bile is reduced (biliary stasis) and infection can occur. Infection can also flow in a retrograde direction up the CBD as a result of acute cholecystitis or instrumentation such as endoscopic retrograde cholangiopancreatography (ERCP).

The most common in the UK are Klebsiella spp., Escherichia coli, Enterobacter spp., enterococci and streptococci. More than one organism may be involved. Outside the UK, cholangitis can be caused by roundworm and liver fluke² .

NB: primary sclerosing cholangitis is an aetiologically unrelated idiopathic condition which is dealt with in a separate article.

See also the separate articles Primary Biliary Cholangitis and Choledochal Cysts.

How common is cholangitis? (Epidemiology)

• Up to 9% of patients admitted to hospital with gallstone disease have acute cholangitis.³

• Approximately 1% of patients develop cholangitis after ERCP.⁴

• The racial distribution pattern follows to some extent the races in which there is a high prevalence of gallstones - ie fair-skinned people of Northern European descent, Hispanics, native Americans and Pima Indians.

• The male-to-female ratio is equal.

• The median age of presentation is 50-60 years.

• Malignant disease (bile duct tumours, gallbladder tumours, ampullary tumours, pancreatic tumours and duodenal tumours) accounts for 10-30% of cases with acute cholangitis.

Cholangitis causes^{5 6}

• Obstruction of the gallbladder or bile duct due to stones.

• ERCP.

• Tumours - pancreatic cancer, cholangiocarcinoma, ampullary cancer, porta hepatis tumours or metastasis.

• Bile duct stricture or stenosis.

• Choledochocele (cyst or diverticulum of the CBD).

• AIDS cholangiopathy.

• Parasitic infection - roundworm, liver fluke.

Cholangitis symptoms

• 50-70% of patients present with classic Charcot's triad of jaundice, fever and right upper quadrant pain.

• In elderly patients, the abdominal pain may be poorly localised.

• Acute cholangitis is graded in severity from grade I (mild), grade II (moderate) and grade III (severe). Severe acute cholangitis is acute cholangitis associated with at least one of cardiovascular, neurological, respiratory, renal, hepatic and/or haematological dysfunction.

• 10-20% of patients also present with the additional features of hypotension due to septic shock and mental confusion - the Reynolds' pentad.

• The patient may also report acholic (putty-coloured) stools and pruritus.

• A history of gallstones, CBD stones, recent cholecystectomy, ERCP or other invasive procedures, HIV or AIDS may assist the diagnosis and management.

• Some patients present with several attacks, usually in association with untreated biliary stones (recurrent pyogenic cholangitis).

• Physical signs may include fever, right upper quadrant tenderness, jaundice, mental status changes, hypotension and tachycardia. Peritonism is an unusual sign and should stimulate the search for an alternative diagnosis.

Diagnostic criteria for acute cholangitis⁷

Clinical features:

1. Previous biliary disorder.

2. Fever and/or chills.

3. Jaundice.

4. Abdominal pain.

Laboratory features:

1. Presence of inflammation indicators (elevated leukocyte count, positivity for C-reactive protein).

2. Elevated liver enzymes.

Imaging findings:

1. Biliary dilatation, other abnormalities suggesting hepatobiliary disorder.

Suspected diagnosis: two or more items of clinical features.
Definite diagnosis: either Charcot’s triad (clinical features 2+3+4) or two items in the clinical features along with both items in the laboratory and imaging findings.

Differential diagnosis

• Gallstones and cholecystitis.

• Diverticular disease.

• Hepatitis - eg, viral hepatitis, drug-induced hepatitis.

• Mesenteric ischaemia.

• Pancreatitis.

• Other causes of septic shock.

• Cirrhosis.

• Liver failure.

• Liver abscess.

• Acute appendicitis.

• Perforated peptic ulcer.

• Pyelonephrosis.

Investigations^{7 8}

Endoscopic retrograde cholangiography (ERCP) is the gold standard for diagnosis of cholangitis. ERCP may also be performed as a therapeutic procedure for biliary drainage in cholangitis.

Magnetic resonance cholangiopancreatography and endoscopic ultrasonography are also frequently used as diagnostic tools.

Blood tests

• FBC: the white cell count is usually raised.

• Inflammatory markers: ESR and CRP may be raised.

• LFTs: typically show pattern of obstructive jaundice.

• Kidney function tests and electrolytes: associated renal dysfunction.

• Blood cultures.

• Amylase may be raised and then often indicates involvement of the lower part of the common bile duct.

• If bile fluid is available (eg, biliary drainage through intervention has occurred), a sample should be sent for culture.

Imaging

When acute cholangitis is suspected, diagnostic assessment includes abdominal X-ray (kidneys, ureters and bladder (KUB)) and abdominal ultrasound. Contrast-enhanced dynamic CT is the best method of diagnosing acute cholangitis, followed by MRI. Magnetic resonance cholangiopancreatography (MRCP) may also be necessary to detect non-calcified biliary stones.

Cholangitis treatment and management¹

Acute cholangitis diagnosis and management should be considered as an emergency because it may be responsible for life-threatening organ failure and death.

The initial management consists of fluid resuscitation, correction of coagulopathy, and administration of broad-spectrum antibiotics.

• Resuscitation may be required for patients with septic shock and due attention should be given to oxygenation and correction of fluid and electrolyte imbalance. Vital signs should be monitored.

• Parenteral antibiotics should be administered once blood cultures have been taken. The drugs selected should be effective against anaerobes and Gram-negative organisms.

Most patients with acute cholangitis respond to antibiotic therapy but endoscopic biliary drainage is ultimately required to treat the underlying obstruction.⁵

• Prevailing guidelines recommend treatment according to severity. By assessing the clinical picture, blood test results and imaging against the criteria laid down in the 2007 guidelines (and updated in 2013), it is possible to classify the severity of the condition as follows:
  

  • Stage I - mild

  • Stage II - moderate

  • Stage III - severe

• The 2013 Tokyo guidelines furthermore acknowledged that determining severity against criteria could create some difficulty in reality. They advised that emergency biliary drainage should be carried out at any time when the condition becomes severe, as indicated by the development of:

  • Shock (reduced blood pressure).

  • Consciousness disturbance.

  • Acute lung injury.

  • Acute renal injury.

  • Hepatic injury.

  • Disseminated intravascular coagulation (DIC).

• Treatment for sepsis should be instituted according to prevailing guidelines.

• Management according to severity is as follows:

  • Stage 1 - antimicrobial therapy, percutaneous, endoscopic or operative intervention for non-responders, depending on aetiology.

  • Stage 2 - early percutaneous or endoscopic drainage with a T-tube. Endoscopic biliary drainage is recommended for acute cholangitis. More definitive surgery depending on aetiology will be required once the patient is stabilised.

  • Stage 3 - treatment of organ failure (respiratory/circulatory) with ventilatory support, vasopressors, etc. Urgent percutaneous or endoscopic drainage or, in severe cases, decompression of the bile duct with a T-tube. Definitive treatment will be required once the clinical picture improves.

Complications⁷

• Patients with severe sepsis can develop liver abscesses and liver failure, bacteraemia and Gram-negative sepsis.

• Severe acute cholangitis may cause septic shock, acute kidney injury and cardiovascular, neurological, respiratory, renal, hepatic and/or haematological dysfunction.

• Patients treated with percutaneous or endoscopic drainage can develop intra-abdominal or percutaneous bleeding, sepsis, fistulae and bile leakage.

• Severe obstructions of bile ducts can cause extreme infected bile reflux and sepsis.

Prognosis^{7 9}

The mortality rate is reported to be between 17% and 40%, depending on accompanying medical problems and age. Early endoscopic drainage after stabilisation of the patient significantly improves the prognosis. Failure to respond to conservative therapy and underlying malignant aetiology are unfavourable factors.

Hypoalbuminaemia along with a prolonged prothrombin time (INR above 1.5) are associated with poorer prognosis and refractory disease. Adverse predictive factors also include hyperbilirubinaemia, high fever, leukocytosis, advanced age, low blood pressure, high CRP and long period of antibiotic therapy.