Biliary complications after liver transplantation are one of the most common complications of liver transplantation and are currently one of the main problems affecting clinical outcomes after liver transplantation, with a high incidence, which is reported in the literature to be between 10% and 30% due to the different criteria for defining biliary complications. They include biliary fistula (anastomosis, bile duct), biliary sludge or gallstone formation, sphincter of Oddi dysfunction, and biliary stricture (anastomosis, non-anastomosis), and the most difficult to manage clinically are biliary stricture and biliary sludge or gallstone formation. Biliary strictures are divided into anastomotic strictures and non-anastomotic strictures depending on the site of occurrence, cause and treatment. Due to the lack of cadaveric organs and the expanding indications for liver transplantation, the conflict between supply and demand has become more and more prominent. In 1988, the world’s first living liver transplantation using the left lateral lobe was performed by Raia in Brazil for pediatric patients, and the first successful living liver transplantation was completed by Strong in 1989. However, since the introduction of living liver transplantation, biliary complications have become the “Achilles’ heel” of this procedure. How to prevent and treat biliary stenosis after liver transplantation is of great significance to improve the survival rate and long-term prognosis after liver transplantation in China. Biliary strictures in cadaveric liver transplantation 1. Biliary tract classification: Biliary strictures are divided into anastomotic strictures and non-anastomotic strictures depending on the site and cause. Anastomotic stenosis is mostly caused by surgical anastomosis techniques such as over-sutured ischemia, scar contracture or bile leak,
With the increasing awareness of biliary complications after liver transplantation and the improvement of anastomotic techniques, the technical causes of anastomotic strictures are decreasing, while non-anastomotic biliary strictures have become the main cause of biliary strictures after transplantation,
It is called the “Achilles’ heel” reproduction. Non-anastomotic biliary strictures are classified according to their etiology: cold preservation/reperfusion injury (cold ischemic injury, reperfusion injury, biliary toxicity injury), intraoperative thermal ischemic injury, immune injury (chronic rejection, ABO incompatible transplantation, primary biliary sclerosis), cytomegalovirus infection, and donor age, etc. Moench proposes to classify them into 3 categories, 1. embolization of HAT), 2, when NAS secondary to microvascular lesions (preservation injury, prolonged cold ischemia and prolonged thermal ischemia, donation of cardiogenic death, and longer donor application of vasopressors), and 3, when NAS of immunologic origin (chronic rejection, ABO blood group incompatibility, autoimmune hepatitis, and primary sclerosing cholangitis). NAS is usually multiple, with long lesions located in the intrahepatic bile duct and/or in the donor bile duct close to the anastomosis. The reported incidence varies between 1% and 19%. In contrast, anastomotic strictures are located at the anastomotic site and are shorter in length. Its incidence varies between 4% and 9%. The intrahepatic bile ducts are structurally different from the extrahepatic bile ducts in that they have a smooth muscle layer near the porta hepatis, but the inner layer is covered with bile duct endothelial cells, whose damage and detachment can cause inflammation and fibrosis, resulting in stenosis. Various injuries directly damage the bile duct endothelium through their respective underlying mechanisms, ultimately leading to the occurrence of non-anastomotic bile duct stenosis. This is one of the important causes of non-anastomotic stenosis after liver transplantation.Risk factors for NAS include HAT, chronic rejection, ABO blood group incompatibility, primary sclerosing cholangitis as the primary pathological change leading to recurrent or ischemic stenosis, cardiac death donor donation, prolonged donor application of vasopressor drugs, elderly donors, preservation injury, cold ischemia and prolonged thermal ischemia. Although stenosis can occur at any time after surgery and the mean time to manifest is 5-8 months after liver transplantation, with the vast majority occurring within 1 year after surgery, recent studies suggest that its incidence increases with time after transplantation. nas occurs 3.3-5.9 months earlier than the mean time to AS. buis et al. further reported that nas is caused by ischemia within 1 year after transplantation, while 1 year later is usually associated with immune factors. Since most of our country belongs to cadaveric donor liver, there is a long period of thermal ischemia and a special donor excision environment with hasty perfusion and biliary vascularization, all of which aggravate biliary complications, we performed a multivariate analysis of factors influencing biliary strictures after liver transplantation through a prospective study of a large number of cases in our center. The main factors associated with biliary stricture in our existing donor excision setting were found to be the duration of portal vein block and cytomegalovirus infection, and not related to the placement of T-tubes, the use of UW preservation fluid or HTK preservation fluid. 3. Prevention and treatment Historically, the solution to biliary stricture after liver transplantation was surgical Roux-en-Y hepatico-intestinal anastomosis. However, recently, due to the development of interventional and endoscopic techniques, trans-T-tubular sinusoidal intervention and endoscopic treatment is also a treatment method for biliary strictures. Although the success rate of percutaneous treatment is in the range of 40%-85%, it is still used as a second-line treatment because of its invasive nature, bleeding, bile leakage and significant mortality. Surgery is only used to treat patients who have failed interventional and endoscopic treatment and is the last line of defense in alternative treatment options. The conventional approach to interventional, endoscopic treatment consists of identifying the opening of the stricture under guide wire guidance, balloon dilation of the stricture, followed by placement of a plastic stent. The stent is then replaced every 3 months with a thicker plastic stent to prevent occlusion, cholangitis or stone formation. Double or multiple stents allow for a thicker expansion and better results compared to single stents. Treatment is usually completed within 1 year and usually requires 3-4 stent replacements over time. The success rate of biliary anastomotic strictures is in the range of 70-100%. When anastomotic strictures are treated appropriately, their patient and graft survival rates do not differ compared to those of matched control patients without anastomotic strictures. Treatment of non-anastomotic stenosis is difficult and it is difficult to decide which treatment is better to recommend. Non-anastomotic stenoses due to early hepatic artery embolism require urgent revascularization or re-grafting. Non-anastomotic stenoses due to advanced hepatic artery embolism can be treated endoscopically. As multiple stenoses are present, additional endoscopic procedures are required, including balloon dilation, stenting, and longer treatment times. The success of interventional, endoscopic treatment depends on the severity of the stenosis, the number of stenoses, and the location of the stenosis. Endoscopic treatment of non-anastomotic stenoses is slightly less effective, with a reported success rate of 50-75%. The consequences of inappropriate treatment of strictures are recurrent biliary cholangitis, and biliary cirrhosis or atrophy of the corresponding liver lobe. Ultimately, close to 50% of patients with non-anastomotic strictures may require retransplantation. The mortality rates reported in the literature are particularly variable. Based on our experience in treating biliary strictures after liver transplantation, we classify them into anastomotic strictures and non-anastomotic strictures depending on the site of occurrence and treatment. Non-anastomotic strictures are further divided into three types, type I: strictures located in the liver; type II: strictures located outside the liver; and type III: strictures located inside and outside the liver. Prevention of biliary stenosis after liver transplantation is more important than treatment. CMV infection is more common before and after liver transplantation, and the incidence of CMV infection can be reduced by effective treatment; the combined donor liver and kidney excision technique effectively improves perfusion, protects the variant artery, and reduces the risk of artificial damage or loss of the hepatic artery, which can effectively reduce the occurrence of biliary stenosis after liver transplantation. For the treatment of biliary stenosis after liver transplantation, the treatment should be individualized for different degrees of disease to avoid medically induced injury or aggravation of the disease. The corresponding biliary support therapy, placement of biliary stents, biliary support external drainage, bile ductoscopic lithotripsy, biliary dilatation and multi-stage and multi-level treatment of re-liver transplantation should be performed for different grades. ① Prevention and treatment of biliary anastomotic stenosis after liver transplantation: anastomotic stenosis is mainly related to anastomotic technique, specific prevention and treatment measures are to leave as little as possible in the donor bile duct, not to do excessive dissection around the bile duct, to protect the trophoblastic vessels of the bile duct, the anastomosis should be tension-free and the needle distance should not be too dense and tight, and to reasonably choose T
tube. If there are no clinical symptoms, the bile can be treated symptomatically; if there is jaundice, fever and itching, interventional treatment is feasible; via T
Ductal sinusoid, gastroduodenal cholangiopancreatography (ERCP), magnetic resonance cholangiopancreatography (MRCP) or percutaneous hepatic puncture cholangiography (PTC) to support dilation, which requires repeated treatment because of easy recurrence; if the above treatment is ineffective, anastomotic resection and reanastomosis or Roux-en-Y bile-intestinal anastomosis is feasible. (2) Prevention and treatment of non-anastomotic biliary strictures after liver transplantation: for type II and part of type I can be relieved by non-surgical treatment, which includes trans-T
ductal sinus support, choledochoscopy to remove the cast, ERCP, implantation of biliary stents, and PTC support for external drainage. If conditions allow, trans-T-tubular sinus tract treatment is preferred, followed by ERCP.
Non-surgical treatment is easily complicated by infection, so anti-infective treatment is particularly important. For type III diffuse biliary strictures, conservative treatment is often unsuccessful, but cholangioscopy can be used to visualize the extent of bile duct destruction, and in combination with T-tube imaging, the diagnosis can be confirmed as early as possible, and retransplantation can be performed in good general condition with good results.