Biliary Disease

The most commonly encountered biliary diseases are cholelithiasis (gallstones in the gallbladder), cholecystitis (inflammation of the gallbladder), choledocholithiasis (gallstones in the common bile duct), and gallstone pancreatitis (inflammation of the pancreas from gallstone blockage of the pancreas duct). Although 10%-15% of adults develop cholelithiasis in their lifetime, only about 1% of cases per year become symptomatic. These patients are commonly managed as inpatients. In this section, we review the following biliary diseases:

• Cholelithiasis

• Biliary Strictures

• Primary Sclerosing Cholangitis

(Source: Biliary Tract. USMLEMD 2008.)

Cholelithiasis

Gallstone-Related Complications

• Biliary colic occurs when the gallbladder contracts against a gallstone that has passed into the cystic duct. This leads to steady cramping pain in the right upper quadrant that may last for 30 to 60 minutes, then dissipate and return. Biliary pain often begins a few hours after ingesting fatty food and resolves within several hours.

• Cholecystitis occurs when an impacted gallstone in the cystic duct leads to gallbladder distention and subsequent ischemia and inflammation of the gallbladder wall. Prolonged ischemia and inflammation of the gallbladder can result in bacterial translocation and infection; thus, management of cholecystitis includes:

  • intravenous antibiotics: with coverage of gram-positive, gram-negative, and anaerobic bacteria

  • pain control and volume replacement

  • surgical intervention: usually early laparoscopic cholecystectomy (as early as possible during hospitalization) unless the patient is at high risk for surgical complications, in which case initial nonoperative management is preferred

• Choledocholithiasis occurs when a gallstone is impacted in the common bile duct. Sometimes the stone will pass spontaneously. However, in some cases an endoscopic retrograde cholangiopancreatography (ERCP) is required to extract the sludge and stones from the duct. Choledocholithiasis can lead to acute ascending cholangitis.

• Acute ascending cholangitis is a medical emergency associated with high morbidity and mortality if it is not diagnosed and treated promptly. It is characterized by inflammation and infection that involves the whole biliary tree. Cholangitis can also develop as a result of other causes of biliary obstruction. The classic presentation of septic cholangitis is Charcot triad (right-upper-quadrant pain, jaundice, and fever) or Reynolds pentad (with added altered mental status and hypotension).

  • Management includes broad-spectrum antibiotics to cover biliary organisms.

  • Emergency ERCP is required to remove obstructing stones and allow pus to drain into the duodenum. In certain situations, a stent is placed in the distal common bile duct, with or without sphincterotomy, to allow ongoing drainage of pus and debris.

Diagnosis

The following table outlines the diagnostic criteria for acute cholecystitis. Diagnosis requires one local sign or symptom (e.g., right-upper-quadrant pain), one systemic sign (e.g., fever), and confirmation on an imaging test.

(Source: Acute Calculous Cholecystitis. N Engl J Med 2008.)

Management

Management of gallstone disease depends on whether the patient is symptomatic. In many patients who undergo abdominal imaging for other reasons, asymptomatic gallstones are detected in the gallbladder. In the absence of symptoms, cholecystectomy is usually not recommended. However, in specific circumstances (e.g., patients with hemolytic anemia), detection of asymptomatic gallstones may require surgical intervention.

Surgery: Surgery is indicated in symptomatic patients with complications related to cholelithiasis, and particularly in patients with acute cholecystitis. The following table summarizes the advantages and disadvantages of surgical interventions for complications of gallstones.

(Source: Interventional Approaches to Gallbladder Disease. N Engl J Med 2015.)

Biliary Strictures

Biliary strictures can predispose to cholangitis and result from chronic choledocholithiasis, chronic pancreatitis, primary sclerosing cholangitis, or biliary tract malignancies (e.g., cholangiocarcinoma or ampullary carcinoma). In adults, biliary strictures tend to be malignant when an etiologic cause is not apparent (e.g., postoperative stricture or external compression) and often require tissue sampling via endoscopic ultrasound (EUS) or ERCP to make a definitive diagnosis. These procedures are often performed in a single session for concurrent diagnosis and drainage.

Management

• Management of benign biliary strictures is generally via ERCP with dilatation, stent placement, or both.

• Malignant strictures, however, more often require biliary stenting and specific therapies directed at treating malignancies. Current guidelines on diagnosis and management of biliary strictures can be accessed here.

Primary Sclerosing Cholangitis

Primary sclerosing cholangitis (PSC) is an idiopathic, chronic, cholestatic liver disease characterized by persistent, progressive biliary inflammation and fibrosis of intrahepatic and extrahepatic bile ducts that lead to multifocal bile-duct strictures, consequent inflammation, and even cirrhosis.

Clinically, PSC manifests as insidious, worsening cholestasis with progressive jaundice. Approximately 70%-80% of patients with PSC also have inflammatory bowel disease (IBD); two-thirds have ulcerative colitis and one-third have Crohn disease or indeterminate colitis. The vast majority of patients (90%) with PSC have the classic subtype. The several subtypes of PSC are described in the following table:

(Source: Primary Sclerosing Cholangitis. N Engl J Med 2016.)

Diagnosis

PSC should be considered in all patients with cholestasis, particularly those who also have IBD. Diagnosis of PSC is based on laboratory, imaging, and histologic findings, and after careful exclusion of secondary causes.

• Laboratory testing: serum alkaline phosphatase

  • increased serum alkaline phosphatase level that persists for >6 months

• Imaging: Initial imaging with magnetic resonance cholangiopancreatography [MRCP] is recommended over ERCP due to the invasive nature of ERCP and associated serious complications.

  • MRCP reveals intra- and/or extrahepatic bile-duct strictures alternating with normal or dilatated segments.

• Histology: Histology is useful in diagnosing small-duct PSC (when large bile ducts appear normal on MRCP) and an overlap syndrome with autoimmune hepatitis.

  • Characteristic histologic features include periductal fibrosis, fibro-obliterative duct lesions, biliary pattern of interface activity, and chronic cholestatic changes in periportal hepatocytes.

  • Histology can exclude sclerosing cholangitis (e.g., amyloidosis, iatrogenic biliary strictures, IgG4-associated cholangitis, ischemic cholangitis, recurrent pyogenic cholangitis)

Management

Pharmacotherapy:

• No effective pharmacologic treatment for PSC exists.

• Low-dose ursodiol should be considered, especially if it reduces alkaline phosphatase and symptoms. However, treatment is not associated with improved survival or reduced need for liver transplantation.

  • High-dose ursodiol is not recommended. In a 2009 randomized, placebo-controlled trial, long-term high-dose ursodiol was associated with twice the risk of liver transplantation, cirrhosis, and death.

• Antibiotics are required in patients with bacterial cholangitis. In recurrent cases, rotating antibiotic prophylaxis may keep overt cholangitis at bay.

Disease surveillance:

• In patients with PSC without IBD, colonoscopy with biopsies should be performed at diagnosis and at 5-year intervals.

• In patients will small-duct PSC, MRCP should be performed every 3-5 years to monitor for the development of large-duct disease.

Surveillance for malignancy:

• Adult patients with large-duct PSC should undergo annual surveillance for cholangiocarcinoma and gallbladder cancer with MRI/MRCP (with contrast) and serum carbohydrate antigen (CA 19-9).

• For relevant strictures, intraductal sampling should be performed during ERCP for cytology, fluorescent in-situ hybridization, or both.

• Cholecystectomy should be performed in patients with gallbladder polyps ≥8 mm.

• Screening for hepatocellular carcinoma with imaging and alpha-fetoprotein (AFP) testing should be performed every six months in patients with cirrhosis.

• Patients with PSC and IBD should undergo high-definition surveillance colonoscopy every 1-2 years (starting at age 15 years) to evaluate for colonic dysplasia.

Management of biliary strictures:

• ERCP can be considered for patients with recurrent or treatment-resistant bacterial cholangitis, new-onset pruritus, imaging suspicious for cholangiocarcinoma, unexplained weight loss, or elevated CA 19-9 level.

• Multidisciplinary decision-making is recommended for dilatation or stenting of strictures.

Management of coexisting conditions:

The treatment of complications of end-stage liver disease in patients with PSC and the management of associated and coexisting conditions are summarized in the following table:

(Source: Primary Sclerosing Cholangitis. N Engl J Med 2016.)

Liver transplantation:

Due to the lack of treatment options and the progressive nature of PSC, approximately 40% of patients require liver transplantation. Median time to death or transplant-free survival is between 9 and 21 years. However, the disorder may recur after transplantation in about 10%-37% of patients.