Biliary Obstruction

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Background

Disorders of the biliary tract affect a significant portion of the worldwide population, and the overwhelming majority of cases are attributable to cholelithiasis (gallstones). In the United States, 20% of persons older than 65 years have gallstones and 1 million newly diagnosed cases of gallstones are reported each year.

To better understand these disorders, a brief discussion of the normal structure and function of the biliary tree is needed. Bile is the exocrine secretion of the liver and is produced continuously by hepatocytes. It contains cholesterol and waste products, such as bilirubin and bile salts, which aid in the digestion of fats. Half the bile produced runs directly from the liver into the duodenum via a system of ducts, ultimately draining into the common bile duct (CBD). The remaining 50% is stored in the gallbladder. In response to a meal, this bile is released from the gallbladder via the cystic duct, which joins the hepatic ducts from the liver to form the CBD. The CBD runs in the hepatodudoenal ligament and then courses through the head of the pancreas for approximately 2 cm; it joins the terminal part of the pancreatic duct to form the ampulla of Vater before passing through the papilla of Vater into the duodenum.[1]

For patient education resources, see the Digestive Disorders Center and Cholesterol Center, as well as Gallstones and Cirrhosis.

Pathophysiology

Biliary obstruction refers to the blockage of any duct that carries bile from the liver to the gallbladder or from the gallbladder to the small intestine. This can occur at various levels within the biliary system. The major signs and symptoms of biliary obstruction result directly from the accumulation of bilirubin and bile salts in the blood and the failure of bile to reach its proper destination.

The clinical setting of cholestasis or failure of biliary flow may be due to biliary obstruction by mechanical means or by metabolic factors in the hepatic cells. For the sake of simplicity, the primary focus of this article is mechanical causes of biliary obstruction, further separating them into intrahepatic and extrahepatic causes. The discussion of intracellular/metabolic causes of cholestasis is very complex, the pathogenesis of which is not always clearly defined. Therefore, these causes are mentioned but are not discussed in detail.

Intrahepatic cholestasis generally occurs at the level of the hepatocyte or biliary canalicular membrane. Causes include hepatocellular disease (eg, viral hepatitis, drug-induced hepatitis), drug-induced cholestasis, biliary cirrhosis, and alcoholic liver disease. In hepatocellular disease, interference in the three major steps of bilirubin metabolism, ie, uptake, conjugation, and excretion, usually occurs. Excretion is the rate-limiting step and is usually impaired to the greatest extent. As a result, conjugated bilirubin predominates in the serum.

Extrahepatic obstruction to the flow of bile may occur within the ducts or secondary to external compression. Overall, gallstones are the most common cause of biliary obstruction. Other causes of blockage within the ducts include malignancy, infection, and biliary cirrhosis. External compression of the ducts may occur secondary to inflammation (eg, pancreatitis) and malignancy. Regardless of the cause, the physical obstruction causes a predominantly conjugated hyperbilirubinemia.

Accumulation of bilirubin in the bloodstream and subsequent deposition in the skin causes jaundice (icterus). Conjunctival icterus is generally a more sensitive sign of hyperbilirubinemia than generalized jaundice. Total serum bilirubin values are normally 0.2-1.2 mg/dL. Jaundice may not be clinically recognizable until levels are at least 3 mg/dL.[2] Urine bilirubin is normally absent. When it is present, only conjugated bilirubin is passed into the urine as it is water soluble. This may be evidenced by dark-colored urine seen in patients with obstructive jaundice or jaundice due to hepatocellular injury. However, reagent strips are very sensitive to bilirubin, detecting as little as 0.05 mg/dL. Thus, urine bilirubin may be found before serum bilirubin reaches levels high enough to cause clinical jaundice.

The lack of bilirubin in the intestinal tract is responsible for the pale stools typically associated with biliary obstruction. The cause of itching (pruritus) associated with biliary obstruction is not clear. Some believe it may be related to the accumulation of bile acids/bile salts in the skin. Others suggest it may be related to the release of endogenous opioids.

Etiology

Causes of biliary obstruction can be separated into intrahepatic and extrahepatic.

Intrahepatic causes

Mechanical or intrahepatic causes are most commonly hepatitis and cirrhosis. Drugs may also cause direct damage to hepatocytes and metabolic obstruction. Note the following:

Extrahepatic causes

Extrahepatic causes may be further subdivided into those that are intraductal and those that are extraductal.

Intraductal causes include stone disease, neoplasms, biliary stricture, parasites, primary sclerosing cholangitis (PSC), AIDS-related cholangiopathy, and biliary tuberculosis. Choledochal cysts cause functional biliary obstruction.

Extraductal obstruction caused by external compression of the biliary ducts may be secondary to neoplasms, pancreatitis (acute and chronic), pancreatic pseudocysts, collaterals of portal hypertension (portal biliopathy), or cystic duct stones with subsequent gallbladder distension.

Neoplasms are various tumors that may lead to biliary obstruction.

Stone disease is the most common cause of obstructive jaundice. Gallstones may pass through the CBD and cause obstruction and symptoms of biliary colic and cholangitis. Larger stones can become lodged in the CBD and cause complete obstruction, with increased intraductal pressure throughout the biliary tree. Mirizzi syndrome is the presence of a stone impacted in the cystic duct or the gallbladder neck, causing inflammation and external compression of the common hepatic duct and thus biliary obstruction.  A fistula may form between the gallbladder and the CBD and the gallstone may then come to lie in the CBD.

Of biliary strictures, 95% are due to surgical trauma and 5% are due to external injury to the abdomen or pancreatitis or erosion of the duct by a gallstone. Stone disease is the most common cause of biliary strictures in patients who have not undergone an operation. A tear in the duct causes bile leakage and predisposes the patient to a localized infection. In turn, this accentuates scar formation and the ultimate development of a fibrous stricture.

Of parasitic causes, adult Ascaris lumbricoides can migrate from the intestine into the bile ducts, thereby obstructing the extrahepatic ducts. Eggs of certain liver flukes (eg, Clonorchis sinensis, Fasciola hepatica) can obstruct the smaller bile ducts within the liver, resulting in intraductal cholestasis. This is more common in Asian countries (Oriental cholangiohepatitis [OCH]).[3]

PSC is most common in men aged 20-40 years, and the cause is unknown. However, PSC is commonly associated with inflammatory bowel disease (IBD), most commonly in patients with pancolitis. IBD (the vast majority being ulcerative colitis) is present in 60-80% of patients with PSC, and PSC is found in approximately 3% of patients with ulcerative colitis. PSC is characterized by diffuse inflammation of the biliary tract, causing fibrosis and stricture of the biliary system. It generally manifests as a progressive obstructive jaundice and is most readily diagnosed based on findings from endoscopic retrograde cholangiopancreatography (ERCP).

AIDS-related cholangiopathy manifests as abdominal pain and elevated liver function test results, suggesting obstruction. The etiology of this disorder in patients who are HIV-positive is thought to be infectious (cytomegalovirus, Cryptosporidium species, and microsporidia have been implicated). Direct cholangiography often reveals abnormal findings in the intrahepatic and extrahepatic ducts that may closely resemble PSC. IgG4-associated cholangiopathy may mimic cholangiocarcinoma.

Biliary tuberculosis is extremely rare. However, with the resurgence of tuberculosis and the emergence of Mycobacterium tuberculosis strains that are resistant to many drugs, biliary tuberculosis may be encountered more frequently in the future. Histopathologic evidence of caseating granulomatous inflammation with bile cytology revealing M tuberculosis is confirmatory. Polymerase chain reaction is useful to expedite the diagnosis if biliary tuberculosis is being considered.

Biliary obstruction associated with pancreatitis is observed most commonly in patients with dilated pancreatic ducts due to either inflammation with fibrosis of the pancreas or a pseudocyst.

Notably, intravenous feedings predispose patients to bile stasis and a clinical picture of obstructive jaundice. Consider this in the evaluation of biliary obstruction.

Sump syndrome is an uncommon complication of a side-to-side choledochoduodenostomy in which food, stones, or other debris accumulate in the CBD and thereby obstruct normal biliary drainage. Roux-en-Y limb stasis may manifest as biliary obstruction after a biliary-enteric anastomosis.

Epidemiology

United States data

The incidence of biliary obstruction is approximately 5 cases per 1000 people.

Race-related demographics

The racial predilection depends on the cause of the biliary obstruction. Gallstones are the most common cause of biliary obstruction. Persons of Hispanic origin and Northern Europeans have a higher risk of gallstones compared to people from Asia and Africa.

Native Americans (particularly Pima Indians) have an increased incidence of obesity and diabetes within their population and are especially prone to developing gallstones. Pima women have a lifetime chance of developing gallstones as high as 80%.

Gallbladder cancer is more common in Central and South America, Central and Eastern Europe, the northern Indian subcontinent and East Asia (Japan and Korea). Oriental cholangiohepatitis (OCH) is seen in the Far East.

Sex-related demographics

The sexual predilection also depends on the specific cause of the biliary obstruction. Gallstone disease is the most common cause of biliary obstruction. Women are much more likely to develop gallstones than men. By the sixth decade, almost 25% of American women develop gallstones, with as many as 50% of women aged 75 years developing gallstones. This increased risk is likely caused by the effect of estrogen on the liver, causing it to remove more cholesterol from the blood and diverting it into the bile. Gallbladder cancer is also more common in females than in males.[4]

Approximately 20% of men aged 75 years have gallstones, with more complicated disease courses occurring in those who have had cholecystectomies.

Prognosis

The prognosis as well as the mortality and morbidity of biliary obstruction depends on the cause.

Complications

Note the following:

History

Patients commonly complain of yellow skin and eyes, pale stools, dark urine, jaundice, and pruritus.

The following considerations are important:

Also, explore the use of alcohol, drugs, and medications.

Physical Examination

Upon physical examination, the patient may display signs of jaundice (skin and icterus). Look for signs of dissemination of cancer (eg, left supraclavicular lymph node, umbilical nodule, pelvic deposits on per rectal [P/R] or per vaginal [P/V] examination).

When the abdomen is examined, the gallbladder may be palpable (Courvoisier sign). This may be associated with underlying pancreatic malignancy. Also, look for signs of weight loss, adenopathies, and occult blood in the stool, suggesting a neoplastic lesion. In addition, note the presence or absence of splenomegaly, ascites, and collateral circulation associated with cirrhosis. Nodular enlarged liver suggests metastases in malignant biliary obstruction.

A high fever and chills suggest a coexisting cholangitis. Early recognition of primary sclerosing cholangitis is essential as fulminant sepsis may develop.[5]

Xanthomata are associated with primary biliary cirrhosis (PBC).

Excoriations suggest prolonged cholestasis or high-grade biliary obstruction.

Laboratory Studies

Serum bilirubin level

Regardless of the cause of cholestasis, serum bilirubin values (especially direct) are usually elevated. However, the degree of hyperbilirubinemia cannot help reliably distinguish between the causes of obstruction.

Extrahepatic obstruction

This is typically associated with considerable direct and indirect bilirubin elevation. However, in the early phases of obstruction and with incomplete or intermittent obstruction, serum bilirubin levels may only be mildly elevated. Initially, an increase in the conjugated bilirubin level occurs without affecting the unconjugated bilirubin level because obstruction of the CBD prevents excretion of already conjugated bilirubin into the duodenum. Conjugated bilirubin that does reach the intestine is deconjugated by intestinal bacteria. Unconjugated bilirubin, in contrast to the conjugated form, easily crosses the intestinal epithelial barrier into the blood. It accumulates in the blood because the uptake mechanism and the hepatic cells are overburdened by bilirubin that has already been conjugated but cannot be excreted. Therefore, indirect bilirubin levels rise even in persons with obstructive jaundice.

Intrahepatic obstruction

Both conjugated and unconjugated bilirubin fractions may increase in varying proportions. The unconjugated fraction may be increased because of the inability of the damaged cells to conjugate normal amounts of unconjugated serum bilirubin. The increase of the conjugated fraction usually results from metabolic deficiency in the excretory mechanism caused by the inflammatory process of the disease.

Alkaline phosphatase (ALP) level

A membrane-bound enzyme localized to the bile canalicular pole of hepatocytes, ALP is markedly elevated in persons with biliary obstruction. However, high levels of this enzyme are not specific to cholestasis. To determine whether the enzyme is likely to be of hepatic origin, measure gamma-glutamyl transpeptidase (GGT) or 5-prime-nucleotidase. These values tend to parallel the ALP levels in patients with liver disease. GGT is used most commonly. While it is part of the routine evaluation of biliary obstruction, the degree of elevation of ALP cannot be used to reliably discriminate between extrahepatic and intrahepatic causes of biliary obstruction.

Extrahepatic obstruction

ALP levels are elevated in nearly 100% of patients, except in some cases of incomplete or intermittent obstruction. Values are usually greater than 3 times the upper limit of the reference range, and in most typical cases, they exceed 5 times the upper limit. An elevation less than 3 times the upper limit is evidence against complete extrahepatic obstruction.

Intrahepatic obstruction

ALP levels are usually elevated, and they often are less than 3 times the upper limit of the normal reference range. However, 5-10% of patients have a greater degree of elevation.

Levels of serum transaminases

Levels of these are usually only moderately elevated in patients with cholestasis but occasionally may be markedly increased, especially if cholangitis is present.

Extrahepatic obstruction

Usually, serum aspartate aminotransferase (AST) levels are not elevated unless secondary acute parenchymal damage is present. When elevations occur, they are usually only mild to moderate (< 10 times the upper reference limit). However, when extrahepatic obstruction occurs acutely, AST values may quickly rise to more than 10 times the normal value, and then they fall after approximately 72 hours. With time and progressive hepatocyte damage caused by distended biliary ductules, an elevation in AST levels may be observed. A 3-fold or more increase in ALT strongly suggests pancreatitis.

Intrahepatic obstruction

Alanine aminotransferase (ALT) is predominantly found in the liver, and most elevations are due to intrahepatic disease. Although less specific to the liver, the AST level is also elevated in cases of intrahepatic cholestasis. ALT and AST levels are usually elevated to the same degree in patients with viral hepatitis and those with drug-induced liver damage. In association with alcoholic liver disease, cirrhosis, and metastatic lesions to the liver, the AST level is elevated more frequently than the ALT level. In general, AST levels are usually higher than ALT levels.

GGT levels

These levels are elevated in patients with diseases of the liver, biliary tract, and pancreas when the biliary tract is obstructed. Levels parallel the levels of ALP and 5-prime-nucleotidase in conditions associated with cholestasis. The extreme sensitivity of GGT, as opposed to ALP, limits its usefulness; however, the level helps distinguish hepatobiliary disease as the cause of an isolated rise in ALP.

Prothrombin time (PT)

This may be prolonged because of malabsorption of vitamin K. Correction of the PT by parenteral administration of vitamin K may help distinguish hepatocellular failure from cholestasis. Little or no improvement occurs in patients with parenchymal liver disease.

Hepatitis serology

Because differentiating viral hepatitis from extrahepatic obstructive causes may be difficult, include serologic assays for acute viral hepatitis B and C in the investigation of all patients with cholestasis.

Antimitochondrial antibody levels

The presence of antimitochondrial antibodies, usually in high titers, is indicative of PBC. They are usually absent in patients with mechanical biliary obstruction or PSC.

Urine bilirubin levels

Urine bilirubin normally is absent. When it is present, only conjugated bilirubin is passed into the urine. This may be evidenced by dark-colored urine seen in patients with obstructive jaundice or jaundice due to hepatocellular injury. However, reagent strips are very sensitive to bilirubin, detecting as little as 0.05 mg/dL. Thus, urine bilirubin may be found even in the absence of hyperbilirubinemia or clinical jaundice.

Imaging Studies

Plain radiographs are of limited utility to help detect abnormalities in the biliary system. Frequently, calculi are not visualized because few are radiopaque.

Ultrasonography (US)

Ultrasonography is the least expensive, safest, and most sensitive technique for visualizing the biliary system, particularly the gallbladder. Current accuracy is close to 95%.

This is the procedure of choice for the initial evaluation of cholestasis and for helping differentiate extrahepatic from intrahepatic causes of jaundice. Extrahepatic obstruction is suggested by the presence of dilated intrahepatic bile ducts, but the presence of normal bile ducts does not exclude obstruction that may be new or intermittent.

Visualization of the pancreas, kidney, and blood vessels is also possible.

Ultrasonography is considered somewhat limited in its overall ability to help detect the specific cause and level of obstruction. US is not as useful for CBD stones (bowel gas may obscure visualization of the CBD). The cystic duct is also poorly imaged. In addition, it is less useful diagnostically in individuals who are obese.

Computed tomography (CT) scanning

Traditional CT scanning

Traditional CT scanning is usually considered more accurate than US for helping determine the specific cause and level of obstruction. In addition, it helps visualize liver structures more consistently than US. The addition of intravenous contrast helps differentiate and define vascular structures and the biliary tract.

CT scanning has limited value in helping diagnose CBD stones because many of them are radiolucent and CT scanning can only image calcified stones. It is also less useful in the diagnosis of cholangitis because the findings that specifically suggest bile duct infection (increased attenuation due to pus, bile duct wall thickening, and gas) are seen infrequently.

Lastly, CT scanning is expensive and involves exposure to radiation, both of which lessen the routine use CT scans compared to US examinations.

Spiral CT scanning

Spiral (helical) CT scanning improves biliary tract imaging by providing several overlapping images in a shorter time than traditional CT scanning and by improving resolution by reducing the presence of respiratory artifacts.

CT cholangiography by the helical CT technique is used most often to image the biliary system and makes possible visualization of radiolucent stones and other biliary pathology.[9]

Limitations of helical CT cholangiography include reactions to the contrast, which are becoming less frequent. Also, as serum bilirubin levels increase, the ability to visualize the biliary tree diminishes and the ability to fully delineate tumors decreases. Patients are required to hold their breath while images are acquired.

Magnetic resonance cholangiopancreatography (MRCP)

MRCP is a noninvasive way to visualize the hepatobiliary tree. It takes advantage of the fact that fluid (eg, that found in the biliary tree) is hyperintense on T2-weighted images. The surrounding structures do not enhance and can be suppressed during image analysis. However, in its early stages, it was limited in its ability to detect nondilated bile ducts. The advent of rapid acquisition with relaxation enhancement (RARE) sequences and half-Fourier RARE (also known as half-Fourier acquisition single-shot turbo spin-echo or HASTE) sequences can reduce imaging time to a few seconds. This can facilitate imaging in different patient positions to distinguish air from a stone.

Note the following:

Procedures

Endoscopic retrograde cholangiopancreatography (ERCP)

ERCP is an outpatient procedure that combines endoscopic and radiologic modalities to visualize both the biliary and pancreatic duct systems. Endoscopically, the ampulla of Vater is identified and cannulated. A contrast agent is injected into these ducts, and x-ray images are taken to evaluate their caliber, length, and course.

It is especially useful for lesions distal to the bifurcation of the hepatic ducts. Besides being a diagnostic modality, ERCP has a therapeutic application because obstructions can potentially be relieved by the removal of stones, sphincterotomy, and the placement of stents and drains. The addition of cholangioscopy to the ERCP, by advancing a smaller "baby" scope through the endoscope into the common duct, allows for biopsies and brushings within the ducts and better identification of lesions seen on cholangiogram.

ERCP has a limited capacity to image the biliary tree proximal to the site of obstruction. Also, it cannot be performed if altered anatomy prevents endoscopic access to the ampulla (eg, Roux loop).

Complications of this technique include pancreatitis, perforation, biliary peritonitis, sepsis, hemorrhage, and adverse effects from the dye and the drug used to relax the duodenum. The risk of any complication is less than 10%. Severe complications occur in less than 1%.

The sensitivity and specificity of ERCP are 89-98% and 89-100%, respectively. ERCP is still considered the criterion standard for imaging the biliary system, particularly if therapeutic intervention is planned.

Percutaneous transhepatic cholangiogram (PTC)

PTC is performed by a radiologist using fluoroscopic guidance.[10] The liver is punctured to enter the peripheral intrahepatic bile duct system. An iodine-based contrast medium is injected into the biliary system and flows through the ducts. Obstruction can be identified on the fluoroscopic monitor. It is especially useful for lesions proximal to the common hepatic duct.

The technique is not easy and requires considerable experience. More than 25% of attempts fail (most often when the ducts cannot be well visualized because they are not dilated, ie, not obstructed.)

Complications of this procedure include the possibility of allergic reaction to the contrast medium, peritonitis with possible intraperitoneal hemorrhage, sepsis, cholangitis, subphrenic abscess, and lung collapse. Severe complications occur in approximately 3% of cases.

The accuracy of PTC in elucidating the cause and site of obstructive jaundice is 90-100% for causes within the biliary tract. The biliary tree can be successfully visualized in 99% of patients with dilated bile ducts and in 40-90% if the bile ducts are not dilated. Still, ERCP is generally preferred, and PTC is reserved for use if ERCP fails or when altered anatomy precludes accessing the ampulla.

Both ERCP and PTC are less frequently used for diagnosis (MRC is preferred) and are more commonly used for therapeutic intervention.

Endoscopic ultrasound (EUS)

EUS combines endoscopy and US to provide remarkably detailed images of the pancreas and biliary tree. It uses higher-frequency ultrasonic waves compared to traditional US (3.5 MHz vs 20 MHz) and allows diagnostic tissue sampling via EUS-guided fine-needle aspiration (EUS-FNA).[11]

Although endoscopic retrograde cholangiography is the procedure of choice for biliary decompression in obstructive jaundice, biliary access is not always achievable, in which case, interventional endoscopic ultrasound-guided cholangiography (IEUC) may offer an alternative to percutaneous transhepatic cholangiography (PTC). Maranki et al reported their 5-year experience with IEUC in patients who had unsuccessful treatment with ERCP.[12] The investigators used either a transgastric-transhepatic or transenteric-transcholedochal approach to the targeted biliary duct, then advanced a stent over the wire into the biliary tree.[12]

Of the 49 patients who underwent IEUC, the cause of biliary obstruction was a malignancy in 35, whereas 14 had a benign etiology.[12] Forty-one of the 49 patients (84%) had successful overall therapy with IEUC, with an overall complication rate of 16%. Resolution of obstruction had an 83% success rate (n = 29). The transenteric-transcholedochal approach was used in 14 patients, with successful biliary decompress in 86% (n = 12).[12] No procedure-related deaths were reported. Thus, overall, the intrahepatic approach was successful in 73% (29/40) of cases, and the extrahepatic approach was successful in 78% (7/9) cases.[12]

An international multicenter retrospective analysis found comparable short-term outcomes between EUS-guided biliary drainage and ERCP in 208 patients with malignant distal common bile duct obstruction who required the placement of self-expandable stents.[13] Ninety-seven of 104 patients (94.23%) who underwent EUS-guided biliary drainage and 98 of 104 patients (93.26%) who underwent ERCP had successful stent placement (P = 1.00); each group had an 8.65% frequency of adverse events, and the mean procedural times were similar (35.95 mins vs 30.10 mins, respectively; P = 0.05). However, the rates of postprocedure pancreatitis were higher in the ERCP group (4.8% vs 0%, P = 0.059).[13]

EUS has been reported to have up to a 98% diagnostic accuracy in patients with obstructive jaundice. This makes ERCP unnecessary in patients who are found to not have extrahepatic obstruction. In addition, those patients who may require operative biliary drainage are reliably identified and similarly need not undergo ERCP for further evaluation.[14]

EUS provides highly detailed imaging of the pancreas. The sensitivity of EUS for the identification of focal mass lesions has been reported to be superior to that of CT scanning, both traditional and spiral, particularly for tumors smaller than 3 cm in diameter.

Compared to MRCP for the diagnosis of biliary stricture, EUS has been reported to be more specific (100% vs 76%) and to have a much greater positive predictive value (100% vs 25%), although the two have equal sensitivity (67%).

Neither transabdominal US nor CT scanning can help reliably exclude the presence of choledocholithiasis. ERCP is highly accurate for this diagnosis but, because of the associated risk of pancreatitis, is generally reserved for patients with known common duct stones. EUS has been reported to have sensitivity approximately equal to both ERCP and MRCP for the detection of common duct stones, with minimal risks directly associated with the procedure.

EUS is more portable than ERCP or MRCP and is useful for patients in the intensive care unit. EUS (if performed in the fluoroscopy suite) can be followed immediately by therapeutic ERCP, which saves time.

The positive yield of EUS-FNA for cytology in patients with malignant obstruction has been reported to be as high as 96%.

PET CT is used to detect distant metastases and staging laparoscopy may be useful to detect small surface peritoneal deposits.

Approach Considerations

Admit the patient for prompt necessary diagnostic testing, supportive care, and surgical intervention if indicated. Transfer may be required for further diagnostic evaluation and treatment.

Treatment of the underlying cause is the objective of the medical treatment of biliary obstruction. Do not subject patients to surgery until the diagnosis is clear. Thus, make every effort to visualize the biliary tree in patients who are jaundiced, with appropriate use of noninvasive and invasive techniques. Importantly, however, a delay in moving on to more invasive therapeutic modalities in a patient who does not initially respond to medical and supportive care increases the risks of an adverse outcome (see Workup).

Consultations with a gastroenterologist, radiologist, and general surgeon are recommended.

Following discharge, monitor patients regularly to ensure that they respond to treatment and that the diagnosis is correct.

Medical Care

In cases of cholelithiasis in which either the patient refuses surgery or surgical intervention is not appropriate, an attempt to dissolve noncalcified calculi may occasionally be made by the administration of oral bile salts for as long as 2 years.

Because gallbladder emptying is an important determinant of stone clearance, normal gallbladder function must first be established via oral cholecystography.

Ursodeoxycholic acid (10 mg/kg/d) works to reduce biliary secretion of cholesterol. In turn, this decreases the cholesterol saturation of bile. In 30-40% of patients, this results in the gradual dissolution of cholesterol-containing stones. However, stones may recur within 5 years once the drug is stopped (50% of patients).

Extracorporeal shock-wave lithotripsy may be used as an adjunct to oral dissolution therapy. By increasing the surface-to-volume ratio of the stones, it both enhances dissolution of stones and makes clearing the smaller fragments easier. Contraindications include complications of gallstone disease (eg, cholecystitis, choledocholelithiasis, biliary pancreatitis), pregnancy, and coagulopathy or anticoagulant medications (ie, because of the risk of hematoma formation). Lithotripsy is associated with a 70% recurrence rate for gallstones, is not approved by the US Food and Drug Association, and is restricted to investigational programs only.

In cases of malignant biliary obstruction, a meta-analysis suggests that endoscopic nasobiliary drainage (ENBD) is more effective and safe than endoscopic biliary stenting (EBS) with regard to preoperative and postoperative complications such as the postoperative pancreatic fistula rate, the incidence of stent dysfunction, and morbidity.[15] However, the meta-analysis did not include data from randomized controlled trials.

Pharmacotherapy

Bile acid–binding resins, cholestyramine (4 g) or colestipol (5 g), dissolved in water or juice 3 times a day may be useful in the symptomatic treatment of pruritus associated with biliary obstruction. However, deficiencies of vitamins A, D, E, and K may occur if steatorrhea is present and can be aggravated by the use of cholestyramine or colestipol. Therefore, include an individualized regimen for replacement of these vitamins as needed in the patient's treatment.

Antihistamines may be used for the symptomatic treatment of pruritus, particularly as a sedative at night. Their effectiveness is modest. Endogenous opioids have been suggested as possibly playing a role in the development of pruritus of cholestasis. Treatment with parentally administered naloxone and, more recently, nalmefene, has improved pruritus in some patients.

Rifampin has been suggested as a medical adjunct to the treatment of cholestasis. By decreasing the intestinal flora, it slows the conversion of primary to secondary bile salts and may reduce serum bilirubin levels, ALP levels, and pruritus in certain patients.

Discontinuation of medications that may be causing or exacerbating cholestasis and/or biliary obstruction often leads to full recovery. Similarly, appropriate treatment of infections (eg, viral, bacterial, parasitic) is indicated.

Surgical Care

As with medical care, the need for surgical intervention depends on the cause of biliary obstruction.

Preoperative preparation includes nutritional support, hydration, correction of coagulopathy, and perioperative antibiotics.

Cholecystectomy is the recommended treatment in cases of symptomatic cholelithiasis because these patients have an increased risk of developing complications. Open cholecystectomy is relatively safe, with a mortality rate of 0.1-0.5 %.

Laparoscopic cholecystectomy remains the treatment of choice for symptomatic gallstones, partially because of the shorter recovery period (return to work in an average of 7 d), decreased postoperative discomfort, and improved cosmetic result. Approximately 5% of laparoscopic cases are converted to an open procedure secondary to difficulty in visualizing the anatomy or a complication. Risk of bile duct injury during laparoscopic cholecystectomy is around 0.4-0.6%.

Gallstones and common bile duct (CBD) stones can be treated with preoperative endoscopic removal of CBD stones followed by laparoscopic cholecystectomy or laparoscopic cholecystectomy and choledocholithotomy.

Choledochal cyst requires excision and hepaticojejunosotmy. Biliary obstruction in chronic pancreatitis may need a biliary-enteric anastomosis at the time of the drainage of the pancreatic duct.

Resectability of neoplastic causes of biliary obstruction varies with respect to the location and extent of the disease. Preoperative biliary drainage may be required before a major liver resection. Photodynamic therapy (PDT) has been shown to have good results in the palliative treatment of advanced biliary tract malignancies, particularly when used in conjunction with a biliary stenting procedure.[16, 17] PDT produces localized tissue necrosis by applying a photosensitizing agent, which preferentially accumulates in the tumor tissue, and then exposing the area to laser light, which activates the medication and results in destruction of tumor cells.

Endoscopic biliary stenting is considered first-line treatment for unresectable malignant hilar biliary obstruction and for distal biliary obstruction, with self-expandable metal stents (SEMSs) preferred over plastic stents in patients expected to live longer than 3 months.[18] Bilateral or unilateral stent insertion appear to be equally effective with similar long-term outcomes for patients with malignant hilar biliary obstruction.[19] Percutaneous transhepatic endobiliary radiofrequency ablation in combination with biliary stenting may hold potential for safely and effectively restoring biliary drainage in patients with malignant biliary obstruction based on the findings of a Turkish study in 21 patients.[20]

Findings from the WATCH-2 study appear to show comparable rates of recurrent biliary obstruction, time to recurrent biliary obstruction, and survival between patients with unresectable distal malignant biliary obstruction undergoing fully covered (n = 151) or partially covered (n = 141) SEMSs.[21] In addition, there was also no significant difference in the rate of stent migration between the two groups.

In a separate international multicenter study of endoscopic management of combined distal malignant biliary obstruction and duodenal obstruction in 110 patients, transpapillary or transmural endoscopic biliary drainage with a duodenal stent was effective in 95% of the patients, regardless of the timing or location of the duodenal obstruction.[22] Time to recurrent biliary obstruction was longer for metal versus plastic stents, and a higher rate of adverse events was associated with endoscopic ultrasonographic-guided biliary drainage relative to endoscopic retrograde cholangiopancreatography (ERCP).

In a single-center retrospective study (2013-2015) of 520 therapeutic ERCP, of which 45 cases failed ERCP, Nakai et al found similar technical success and ERCP-related adverse events among patients who underwent ERCP, rescue percutaneous transhepatic biliary drainage (PTBD), primary EUS-BD, and endoscopic ultrasonography-guided biliary drainage (EUS-BD).[23] Based on their findings, the investigators suggested that primary EUS-BD without failed ERCP may be a treatment option if it provides advantages over ERCP.

Liver transplantation may be considered in appropriate patients (eg, end-stage liver disease [ESLD], primary sclerosing cholangitis [PSC], hepatocellular carcinoma [HCC], secondary biliary cirrhosis and portal hypertension.

Diet and Activity

Obesity, excess energy intake, and rapid weight loss can lead to stone formation, with potential biliary obstruction as a consequence. Gradual and modest weight reduction may be of value in patients who are at risk.

Patients should reduce their intake of saturated fats and increase their fiber intake. High intake of fiber has been linked to a lower risk for gallstones.

Reduction in sugar intake is recommended, because a high intake of sugar may be associated with an increased risk of gallstones.

Regular exercise may reduce the risk of gallstones and gallstone complications.

Prevention

Awareness of the risk factors and clinical signs/symptoms of biliary obstruction is key to the prompt diagnosis and treatment of biliary obstruction, with the hope of preventing the potential complications it may cause.

In patients with risk factors for developing any of the conditions that lead to biliary obstruction, awareness of the signs and symptoms can improve chances for early diagnosis and improved outcome.

Gallstones are the most common cause of biliary obstruction. Estrogens cause an increase in the risk for formation of gallstones and may need to be avoided in patients with known gallstones or a strong family history of stone disease.

Medication Summary

Bile acid – binding resins and ursodeoxycholic acid are used to treat cholelithiasis when surgery is refused or is inappropriate. Normal gallbladder function must be established by oral cholecystography findings prior to the initiation of drug therapy.

Ursodiol (Actigall)

Clinical Context:  Used to treat biliary stasis and dissolve gallstones.

Class Summary

Ursodeoxycholic acid (ursodiol) is a naturally occurring bile acid present in small quantities in human bile. Suppresses liver synthesis and secretion of cholesterol. Inhibits intestinal cholesterol absorption.

Naloxone (Narcan)

Clinical Context:  Prevents or reverses opioid effects (eg, hypotension, respiratory depression, sedation, pruritus), possibly by displacing opiates from their receptors.

Class Summary

Endogenous opioids may effect pruritic development associated with cholestasis. Treatment with narcotic antagonists may attenuate pruritus.

Rifampin (Rifadin, Rifadin IV, Rimactane)

Clinical Context:  Inhibits DNA-dependent bacterial by binding to the beta subunit of DNA-dependent RNA polymerase, blocking RNA transcription.

Class Summary

Rifampin, in particular, has been suggested as a treatment for cholestasis in certain patients. By reducing intestinal flora, it slows conversion of primary to more toxic secondary bile salts. Has also been shown to decrease serum levels of bilirubin and ALP, perhaps in part contributing to its effectiveness in minimizing associated pruritus.

Cholestyramine (Questran)

Clinical Context:  Acts as a cholesterol-lowering agent. Forms a nonabsorbable complex with bile acids in the intestine, which inhibits enterohepatic reuptake of intestinal bile salts.

Colestipol (Colestid)

Clinical Context:  Binds bile acids in the intestine, facilitates partial removal of bile acids from enterohepatic circulation, and prevents their reabsorption.

Class Summary

Inhibit enterohepatic reuptake of intestinal bile salts.

What is the normal function of the biliary tree?What is biliary obstruction?What are the pathophysiological mechanisms of biliary obstruction?What is the pathophysiology of intrahepatic cholestasis in biliary obstruction?What is the pathophysiology of extrahepatic biliary obstruction?What is the pathophysiology of jaundice in biliary obstruction?What are the effects of lack of bilirubin in the pathophysiology of biliary obstruction?How are the causes of biliary obstruction categorized?What are the intrahepatic causes of biliary obstruction?How are extrahepatic causes of biliary obstruction further subdivided?Which neoplasms cause biliary obstruction?What is the role of stone disease in the etiology of biliary obstruction?What are parasitic causes of biliary obstruction?What is the role of primary sclerosing cholangitis (PSC) in the etiology of biliary obstruction?What is the role of tuberculosis in the etiology of biliary obstruction?What is the association between biliary obstruction and pancreatitis?What is the role of IV feeding in the etiology of biliary obstruction?What is Sump syndrome?What is the incidence of biliary obstruction in the US?What are the racial predilections of biliary obstruction?How does the prevalence of biliary obstruction vary by sex?What is the prognosis of biliary obstruction?What are potential complications of biliary obstruction?What is the signs and symptoms of biliary obstruction?What should be the focus of clinical history in the evaluation of biliary obstruction?Which physical findings are characteristic of biliary obstruction?When is double balloon enteroscopy (DBE) used in the evaluation of biliary obstruction?What should be included in the differential diagnoses for biliary obstruction?What are the differential diagnoses for Biliary Obstruction?What serum bilirubin level findings suggest biliary obstruction?What are serum bilirubin level findings suggestive of extrahepatic biliary obstruction?What are serum bilirubin level findings suggestive of intrahepatic biliary obstruction?What is the role of alkaline phosphatase (ALP) measurement in the workup of biliary obstruction?What alkaline phosphatase (ALP) level findings exclude a diagnosis of extrahepatic biliary obstruction?What are alkaline phosphatase (ALP) level findings suggestive of intrahepatic biliary obstruction?What levels of serum transaminases suggest biliary obstruction?What levels of serum transaminases suggest extrahepatic biliary obstruction?What levels of serum transaminases suggest intrahepatic biliary obstruction?What GGT levels suggest biliary obstruction?What is the role of prothrombin time (PT) in the workup of biliary obstruction?When is hepatitis serology indicated in the workup of biliary obstruction?What is the role of antimitochondrial antibody testing in the workup of biliary obstruction?What is the role of urine bilirubin testing in the workup of biliary obstruction?What is the role of radiography in the workup of biliary obstruction?What is the role of ultrasonography (US) in the workup of biliary obstruction?What is the role of CT scanning in the workup of biliary obstruction?What is the role of spiral CT scanning in the workup of biliary obstruction?What is the advantage of magnetic resonance cholangiopancreatography (MRCP) for the evaluation of biliary obstruction?What is the role of magnetic resonance cholangiopancreatography (MRCP) in the evaluation of biliary obstruction?What is the role of endoscopic retrograde cholangiopancreatography (ERCP) in the workup of biliary obstruction?What is the role of percutaneous transhepatic cholangiogram (PTC) in the workup of biliary obstruction?What is the role of endoscopic ultrasound (EUS) in the workup of biliary obstruction?What are the treatment options for biliary obstruction?What is the role of drug treatment for biliary obstruction?What is included in medical care for biliary obstruction?What is the role of surgery in the treatment of biliary obstruction?What dietary and activity restrictions are required for the treatment of biliary obstruction?How is biliary obstruction prevented?Which medications are used in the treatment of biliary obstruction?Which medications in the drug class Bile acid–binding resins are used in the treatment of Biliary Obstruction?Which medications in the drug class Antibiotics are used in the treatment of Biliary Obstruction?Which medications in the drug class Narcotic antagonists are used in the treatment of Biliary Obstruction?Which medications in the drug class Gallstone solubilizing agents are used in the treatment of Biliary Obstruction?

Author

Jennifer Lynn Bonheur, MD, Attending Physician, Division of Gastroenterology, Lenox Hill Hospital

Disclosure: Nothing to disclose.

Coauthor(s)

Peter F Ells, MD, Associate Professor, Division of Gastroenterology-Hepatology, Albany Medical Center

Disclosure: Nothing to disclose.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

BS Anand, MD, Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine

Disclosure: Nothing to disclose.

Chief Editor

Vinay Kumar Kapoor, MBBS, MS, FRCS, FAMS, Professor of Surgical Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India

Disclosure: Nothing to disclose.

Additional Contributors

Anil Minocha, MD, FACP, FACG, AGAF, CPNSS, Professor of Medicine, Director of Digestive Diseases, Medical Director of Nutrition Support, Medical Director of Gastrointestinal Endoscopy, Internal Medicine Department, University of Mississippi Medical Center; Clinical Professor, University of Mississippi School of Pharmacy

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Drugs & Diseases gratefully acknowledge the contributions of previous coauthor Flavio R Kamenetz, MD, PhD, to the development and writing of this article.

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