Hepatic Biloma

Etiology

Bilomas are most commonly secondary to disruption of the biliary tree, whether iatrogenic or traumatic. Iatrogenic causes of biloma formation include laparoscopic cholecystectomy, endoscopic retrograde cholangiopancreatography, radiofrequency ablation, transcatheter arterial chemoembolization, liver transplant, resection, and biopsy.[8][9][10][11] While exceedingly rare, spontaneous rupture of the biliary tree and biloma formation have been recognized in the literature and can be associated with malignancy.[12][13][14]

The increased use of laparoscopic cholecystectomy over the past 3 decades has been linked with increased rates of disruption to the biliary tree. Laparoscopic cholecystectomy is associated with bile duct injuries in 0.6% to 1.5% of cases compared with 0.2% to 0.3% of open operations.[15] Biliary leaks following laparoscopic cholecystectomy can be attributed to damage of the common bile duct (CBD), unsuccessful cystic duct ligation, or anatomical variation leading to damaged or leaking accessory ducts.[16] The ducts of Luschka, small ducts that drain into the biliary system, are found in the gallbladder fossa in 25% to 35% of patients and are vulnerable to injury during cholecystectomy.[17] Fluid collection, including bile leakage, is more common following cholecystectomy than many clinicians realize. Results from a 1986 study demonstrated that small-volume bile leakage occurred in up to 44% of laparoscopic cholecystectomies. However, 95% of these did not require any further management.[18] 

In 1991, Kang et al showed that 53% of patients who underwent ultrasound 24 hours after laparoscopic cholecystectomy had small-volume fluid collections. However, they determined that a routine postoperative ultrasound did not change management and was unwarranted.[19] While small fluid collections are common postoperatively, these leaks are primarily small, asymptomatic, and often resolve without treatment. Most think that many small leaks go undetected. However, significant bile leaks and biloma formation must remain a key differential diagnosis in patients with a complicated recovery following laparoscopic cholecystectomy.[4]

Biloma has been demonstrated following perforation of the CBD during endoscopic retrograde cholangiopancreatography (ERCP).[20][21] Results from a prospective multicentre study of 5461 patients showed CBD perforation occurred in 0.4% of patients undergoing ERCP. Risk factors for biliary tree perforation included precut access to the CBD and malignancy.[21]

Biloma formation was identified in 3.3% of 3284 patients undergoing RFA of hepatocellular carcinoma. However, biloma formation during RFA is a minor complication. Chang et al examined 109 bilomas following radiofrequency ablation for hepatocellular carcinoma, with only 1 patient requiring percutaneous drainage of the biloma for infection.[22] Thermal ablation of hepatocellular carcinoma is also associated with biloma formation, with bile leaks identified in 0.1% to 12% of cases. Previous transarterial chemoembolization (TACE) procedures and a closer proximity to the biliary tree were both associated with an increased risk of bile leak and biloma formation in patients undergoing thermal ablation.[9] TACE procedures for hepatocellular carcinoma are also associated with biloma formation. Zhang et al demonstrated an incidence of 1.04% in 4695 patients undergoing TACE in 2017.[23]

Liver transplantation is known to be associated with biloma formation. Biloma forms part of a spectrum of posttransplant cholangiopathies. Posttransplant cholangiopathy is one of the most challenging complications following a liver transplant. The pathophysiology of posttransplant cholangiopathy is likely to involve ischemia-reperfusion injury, bile salt toxicity, or immune-mediated injury. Biloma formation after liver transplant can be associated with both anastomotic leakage and nonanastomotic strictures with associated bile duct necrosis and resulting intraparenchymal bile leakage.[11] Liver resection is also associated with biloma formation due to the disruption of intrahepatic bile ducts.[24]

Abdominal trauma has been associated with biloma formation. In most cases, this involves blunt trauma to the upper abdomen. Posttraumatic biloma can take 1 to 2 days to appear.[25][26] Spontaneous rupture of the biliary tree is very rare; however, it has been associated with underlying weakness in bile duct walls caused by cholelithiasis, cholangiocarcinoma, hepatic abscess, or tuberculosis.[27] Spontaneous rupture of the biliary tree is often a diagnosis of exclusion.[28] Biloma formation is also associated with sickle cell disease, likely due to hepatic infarction.[29] Bile leakage can occur without disrupting the biliary tree, for example, in leakage from the duodenal stump following Billroth II surgery.

Epidemiology

There is little epidemiological data regarding biloma formation. Most bilomas are secondary to iatrogenic disruption of the biliary tree; therefore, their incidence depends on the frequency of interventions. Biloma typically presents in patients aged 60 to 70. This likely reflects underlying etiological factors requiring invasive intervention rather than a predisposition to complications leading to biloma formation. No difference in biloma incidence has been observed between male and female patients.[30] Spontaneous biloma formation is exceedingly rare, and the literature on the subject consists solely of case reports. In 2007, Ahktar et al noted that 27 cases of spontaneous biloma had been reported since 1979.[31]

Pathophysiology

Disruption of the biliary tree and subsequent bile leakage is the cause of most bilomas. Encapsulation of the bile leak is thought to be via 2 mechanisms, depending on the rate of bile leakage. Most commonly, slow bile leakage causes mild inflammation of the surrounding abdominal tissues or the liver parenchyma, leading to fibrosis and encapsulation. Bile acids produce low-grade inflammation in surrounding tissues because of their detergent and tissue-destroying properties.[32] 

Biliary peritonitis can be present in large volumes, with rapid bile leaks. This may present with encapsulation; however, patients may present acutely before encapsulation has occurred. Intraperitoneally, the omentum and mesentery can form inflammatory adhesions, aiding encapsulation.[2] Biloma size and location depend on the mechanism of biliary tree disruption, the rate of bile leakage, and bile reabsorption by the surrounding liver parenchyma or peritoneum.[26] 

Extravasated bile follows abdominal anatomy, with its shape often demarcated by the diaphragm, liver margins, mesentery, and transverse mesocolon. Multiple bilomas in patients are not uncommon. Extrahepatic bilomas predominantly form in the right upper quadrant of the abdomen. However, in about 40% of cases, bile migrates over the anterior part of the liver to the left subphrenic or left subhepatic spaces.[2][31] 

Biloma content is typically greenish-yellow bile. However, they can contain blood or exudate, especially in the context of infection. Secondary infection can lead to a systemic inflammatory response, sepsis, and abscess formation. The natural history of abdominal bile collections from injured bile ducts is the progression from sterile bile collection to infection.[4]

History and Physical

Bilomas typically present with upper abdominal fullness and right upper quadrant discomfort following iatrogenic or traumatic disruption to the biliary tree. Nausea, vomiting, and fever are recognized symptoms, especially in cases of infected biloma. Jaundice may be present in cases of extrinsic compression of the bile duct. Key aspects required from the history include previous surgical or endoscopic interventions or abdominal trauma that may have caused biliary tree disruption. A history of hepatobiliary surgery or biliary tree disease also increases the risk of bile leak and biloma formation.[2]

While patients may present acutely unwell with septic shock from bilomas, many may be asymptomatic. The significant variation in presenting symptoms makes the diagnosis of biloma difficult. Bile peritonitis is a recognized presentation of bile leak and large biloma. However, Lee et al showed that this presentation is unusual, and most patients present with more subtle symptoms. They describe delayed diagnosis in 77% of 179 patients with abdominal bile collections and bile leaks following laparoscopic cholecystectomy. Significant abdominal pain and tenderness were observed in only 21% of patients. Initial peritonitis does not predict the severity of the disease, with many subtly symptomatic patients developing serious complications.[4] 

Following iatrogenic intervention or traumatic injury, physicians should be alert to persistent abdominal distention, bloating, or anorexia as early signs of bile leak and biloma. Clinicians should be aware that any delay in recovery from hepatobiliary surgery, especially laparoscopic cholecystectomy, is a possible early symptom of bile leak and biloma formation. Biloma remains an uncommon diagnosis, and other gastroenterological and hepatobiliary diagnoses should be considered for patients presenting with upper abdominal fullness and discomfort. However, in patients who have recently experienced surgical or endoscopic interventions in the region of the biliary tree, bile leak and biloma are essential differential diagnoses to exclude, as they can present subtly and have significant morbidity and mortality.[2][4]

Evaluation

Initial laboratory testing may reveal a systemic inflammatory response to a biloma. Blood tests may demonstrate elevated inflammatory markers, such as leucocytosis, neutrophilia, and elevated C-reactive protein. However, many patients with bilomas have no abnormalities in laboratory tests. Vazquez et al demonstrated normal blood results in 40% of 21 patients presenting with bilomas.[26] 

Liver function tests may be deranged in cases of bile duct compression. In cases of infected biloma, blood cultures may reveal gram-negative bacteremia. Wurstle et al showed positive blood cultures in 93% of 32 bilomas following iatrogenic injury to the biliary tree. The most common organisms found in a laboratory culture of biloma fluid were Enterobacteriaceae, followed by Enterococcus species. They demonstrated multidrug-resistant bacteria in 25% of biloma cultures.[33] 

The variable and often subtle presentation of bilomas makes radiological investigation the mainstay of diagnosis. MRI, computed tomography (CT), ultrasound, and hepatobiliary iminodiacetic acid are the main radiological modalities used to investigate bilomas. Abdominal imaging via ultrasound is often the first investigation due to the frequent presentation with right upper quadrant discomfort. Ultrasound imaging can frequently identify a cystic lesion. This modality can also demonstrate debris or blood clots within the biloma. The ultrasound may reveal a wide range of findings from well-circumscribed collections in the liver parenchyma to large loculated fluid collections throughout the abdomen. Heavily loculated bilomas seen on ultrasound imaging have been associated with an infection. Although ultrasound imaging is effective for identifying a cystic mass, further imaging is usually required to make a diagnosis.[2][34]

CT imaging typically shows bilomas as a well-circumscribed collection with clear margins. However, a well-defined capsule is not always present.[2] Bilomas are typically hypoechoic, hypoattenuated collections with CT attenuation of less than 20 Hounsfield units (see Image. Hepatic Biloma on Computed Tomography).[26][35] CT imaging has the benefit of precisely localizing the biloma and imaging the surrounding structures. While CT can provide a more detailed picture of bilomas, it cannot definitively differentiate between differential diagnoses such as postoperative seroma, hematoma, abscess, lymphocele, liver cyst, and pseudocyst.[36] Therefore, further imaging with MRI or hepatobiliary cholescintigraphy is often required, along with direct sampling of the biloma, to confirm the diagnosis.[2]

MRI, particularly magnetic resonance cholangiopancreatography (MRCP) in some cases, can further characterize a biloma. Biloma typically produces a low signal intensity on T1-weighted images and high signal intensity on T2-weighted images. While contrast rarely permeates the biloma, rim enhancement may be present due to reactive inflammation. Enhancing septations are often observed in superimposed infection. MRCP, particularly thin slab sequences, may demonstrate the source of a biliary leak.[37]

Hepatobiliary cholescintigraphy is an extremely effective noninvasive imaging modality for diagnosing and planning the treatment of bilomas. Cholescintigraphy uses the radiotracer Tc-99m iminodiacetic acid and is known as hepatobiliary iminodiacetic acid (HIDA) imaging. HIDA is very sensitive when looking for a bile leak. However, it does not provide detailed imaging of the surrounding anatomy. Single-photon emission computed tomography can provide more detailed imaging of potential leak locations and is more useful for planning percutaneous image-guided drains. Invasive imaging techniques, such as endoscopic retrograde cholangiopancreatography and percutaneous transhepatic cholangiogram, can provide further guidance for endoscopic, percutaneous, or surgical management.[2][28] Ultrasound or CT-guided sampling of the biloma, followed by laboratory analysis, may be required to confirm the diagnosis when prior imaging and clinical findings are inconclusive.[2]

Treatment / Management

Management varies depending on the clinical presentation, laboratory results, and radiological findings of the biloma. The 3 main options are percutaneous or endoscopic drainage, surgical drainage, or close monitoring. Ongoing bile leak, biloma size and position, superimposed infection, and patient fitness will determine the most appropriate management strategy.[2] Small, asymptomatic fluid collections may be reabsorbed and not require any intervention. However, Lee et al demonstrated that collections larger than 4 cm were rarely reabsorbed, and it was hard to predict whether patients would become symptomatic.[4]

Most bilomas can be managed successfully with radiologically guided percutaneous drainage. Fixation of the underlying disruption of the biliary tree is often unnecessary.[24][35] The ultrasound or CT-guided aspiration by an interventional radiologist is the preferred method. Due to the lack of radiation and real-time imaging, ultrasound is preferred over CT in most cases. Spectral Doppler and real-time color allow avoidance of vascular structures.(B2)

Interventional radiologists may access extrahepatic bilomas via the liver if no other clear window is available. Different methods of drainage include endoscopic ultrasound (EUS) guided drainage. For example, Shami et al described, in 2008, successful management of bilomas adjacent to bowel with EUS-guided drainage.[38] Tonozuka et al described, in 2015, the successful management of hepatic abscesses and infected bilomas with EUS-guided metal stents.[39] Most bilomas without ongoing bile leaks, when managed with percutaneous drainage, do not recur and have a good prognosis.(B3)

Ongoing bile leaks may require further management, with either surgical fixation or endoscopic stent placement. However, Lee et al recommend drainage of the biloma after laparoscopic cholecystectomy in the first case, especially in acutely unwell or symptomatic patients.[4] Percutaneous transhepatic cholangiography or percutaneous transhepatic biliary drainage is sometimes required to image the biliary tree further or decompress the gallbladder when there is an ongoing bile leak.[2]

Surgical management of biloma is sometimes indicated in cases of failed percutaneous drainage, multiloculated lesions, and ongoing bile leaks. Cases of bile leak identified intraoperatively during laparoscopic cholecystectomy or requiring surgical management of continuing bile leak are best managed in specialist tertiary centers.[40] The rarity of biloma formation means there is little reliable evidence beyond case reports and case series describing management strategies. However, percutaneous drainage has successfully managed biloma, and biloma patients have an excellent prognosis.(B2)

Differential Diagnosis

Because biloma formation is uncommon, it is essential to consider possible differential diagnoses. Right upper quadrant discomfort and abdominal fullness are nonspecific symptoms with a wide range of potential causes. Biloma should enter the differential where patients present secondary to an iatrogenic or traumatic event that could disrupt the biliary tree. Following this, appropriate imaging should be undertaken.

Differential diagnoses following radiological investigation include hepatic abscess, hepatic cyst, hepatic pseudocyst, and hepatic lymphocele. As most bilomas form postoperatively or postendoscopic investigation, seroma and hematoma are key differential diagnoses to consider. Identifying bilomas correctly is essential, as they often require drainage, whereas many differential diagnoses, such as hematoma, do not.[2][4]

Prognosis

Biloma prognosis varies depending on site, size, and etiology. Uncomplicated bilomas without underlying ongoing bile leaks have a good prognosis. Small, asymptomatic bilomas with no ongoing bile leak are often treated conservatively to good effect.[2] In patients with symptomatic bilomas, drainage via interventional radiology is an effective strategy, and patients generally have a good prognosis.[2][24] Lee et al have shown that prompt drainage of symptomatic bilomas significantly reduces morbidity and mortality, while reducing the risk of secondary infection and complications.[4] Most bilomas managed with percutaneous drainage do not recur and have a good prognosis. However, larger bile leaks into the peritoneum are associated with significant morbidity, often requiring urgent and invasive intervention to avoid deterioration.[4]

Complications

Complications of biloma include infection, septic shock, abscess formation, and cholestasis through impingement on the biliary tree. Lee et al also describe pancreatitis, respiratory failure, and transdiaphragmatic bile fistulation in patients with abdominal bile collections.[4] Risks of percutaneous drainage of bilomas include bleeding, infection, damage to surrounding structures, and failure to drain the biloma. Ongoing bile leaks may require further endoscopic or surgical management.[2]