Endoscopic management of post-transplant biliary strictures

Biliary tract strictures are the most common postoperative biliary complication of orthotropic liver transplantation, with an estimated overall incidence of 16 percent — down from nearly 60 percent just two decades ago. At that time, strictures were managed surgically, often with relatively high rates of morbidity and mortality. Today, increasingly sophisticated endoscopic techniques and advances in interventional radiology have greatly improved outcomes by limiting the need for surgical repair or re-transplant.

Strictures can occur anytime post-transplant, but most present in the first five to eight months and are classified as anastomotic or nonanastomotic, depending on their location in the biliary tract. An anastomotic stricture is a single narrowing around an anastomosis, often due to fibrotic healing. Nonanastomotic strictures are frequently multiple, occurring in the donor bile ducts proximal to the anastomosis. They are longer and occur earlier than anastomotic strictures and are believed to result from ischemia.

Risk factors vary, depending on the type of stricture, but generally include hepatic artery thrombosis, an older, female or living donor, the surgical reconstruction technique — Roux-en-Y choledochojejunostomy versus duct-to-duct anastomosis — size mismatch between donor and recipient bile ducts, prolonged warm and cold ischemia times, and a prior diagnosis of primary sclerosing cholangitis.

Diagnosis

Diagnosing post-transplant biliary strictures can be challenging. Patients are often asymptomatic or have nonspecific symptoms, such as fever, jaundice and elevated cholestatic enzymes that overlap with symptoms of transplant rejection or hepatic artery stenosis. An accurate diagnosis is crucial to avoid unnecessary procedures and the risk of more complications, frequent readmissions and increased trauma to patients.

Although evaluation for suspected biliary strictures typically begins with transabdominal ultrasound with Doppler studies, ultrasound may not be sensitive enough to detect bile duct obstruction in liver transplant patients. Dilation doesn't always occur in these patients — perhaps because post-surgical fibrosis makes the donor bile ducts less pliable — and ultrasound doesn't easily detect a stricture without associated dilation.

The most effective noninvasive imaging test — and the one increasingly used after liver transplant — is MRI with magnetic resonance cholangiopancreatography (MRCP), according to Frank Lukens, M.D., a gastroenterologist specializing in therapeutic endoscopy for hepatobiliary and pancreatic disease at Mayo Clinic's campus in Jacksonville, Florida.

"MRCP, which has an overall accuracy of 95 percent, has become the imaging modality of choice to detect biliary strictures after liver transplant and is usually the second test ordered after ultrasound," he explains. "The gold standard is still endoscopic retrograde cholangiography (ERC) or percutaneous cholangiography (PTC), but these tests are invasive and no longer necessarily used solely for diagnostic purposes. If they are used, ERC is preferred because it is less invasive, better for patients and has a lower complication rate."

M. Edwyn Harrison, M.D., a gastroenterologist specializing in endoscopist specializing in liver transplant and medical therapy of liver disease at Mayo Clinic's campus in Arizona, notes that percutaneous cholangiography is usually reserved for patients in whom ERC has failed or who have a choledochojejunostomy and Roux-en-Y anastomosis. Although experienced centers may attempt ERC in Roux-en-Y patients using balloon enteroscopy, Dr. Harrison says the technical difficulty of the procedure, high failure rate, and increased risks and costs make it a less proven option than PTC.

Treatment

Endoscopy is now the standard therapy for managing most post-transplant biliary strictures. It is widely available, safe and effective. PTC-guided therapy is an option after unsuccessful ERC; surgical revision and re-transplant are choices of last resort for failed percutaneous approaches or patients with multiple inaccessible intrahepatic strictures or Roux-en-Y anastomoses.

Dr. Lukens says early anastomotic strictures — those occurring in the first four weeks after transplant, usually as a result of inflammation or edema — may not require treatment or are managed with a 7or 8.5French stent placed in the bile duct without dilation. The stent is later removed and the patient is reassessed. But for later occurring anastomotic strictures, balloon dilation with multiple side-by-side stent placement is the current standard of care.

"To treat an anastomotic stricture, balloon dilation of 6 to 10 millimeters is followed by the placement of at least two 10French plastic stents in the bile duct. In about three months, when postoperative inflammation has gone down, we bring patients back, and if they still have the stricture, we repeat the balloon dilation, progressively placing more stents at repeat visits, if necessary.

"More than 80 percent of patients undergo treatment for up to a year. This may achieve patency rates of 75 to 90 percent by the end of treatment, although the success rate for living donor transplants is not as good," he says.

Plastic stents tend to occlude at about three months, and repeat ERC procedures can cause complications such as cholangitis and pancreatitis, but the risks are considerably less than for surgical revision. Recurrence rates are about 10 to 20 percent and are more likely in patients who have very tight, nonanastomotic or delayed onset (6 months or more post-transplant) strictures.

Repeat strictures may require more aggressive dilation and the use of additional stents or even covered self-expandable metal stents (CSEMS) to improve patency and prevent recurrence. Dr. Lukens says there is limited experience with CSEMS for biliary strictures in transplant patients, and studies have shown mixed results.

Bret T. Petersen, M.D., a gastroenterologist specializing in therapeutic endoscopy at Mayo Clinic's campus in Minnesota, says, "We tend to use plastic first and foremost. We do use covered removable metal, especially for recurrent strictures or recalcitrant strictures that don't seem to be responding well. This largely applies to orthotropic donation livers — not living related — as they tend to have larger ducts that can accommodate metal, if used. Most living related transplants use intrahepatic ducts that can't accommodate stents well."

He also notes that use of metal stents in long Roux-en-Y limb patients depends on the endoscope used. "If experience in a given patient suggests we can reach it with a colonoscope, then covered SEMS become an option — typically at a later second or third procedure rather than the first time. If we are only using single balloon enteroscopy, then SEMS are often too large. There is lots of nuance, hence no true algorithm, though we could probably construct one," he says.