Liver transplantation has become an effective treatment for various end-stage liver diseases, improving the quality of life of patients. However, biliary complications after liver transplantation are still a weak link in the transplantation technique that is difficult to deal with, known as the Achilles’ heel, which seriously affects the quality of life and long-term survival of liver transplantation patients, and has attracted close attention from the global liver transplantation community. However, the incidence of biliary tract complications is reported differently in different centers, and its main causes are complicated, and the diagnosis and treatment methods are worth exploring further. I. Overview of biliary complications Since 1963, when Starzl performed the first human in situ liver transplantation, liver transplantation has become an effective means of treating various end-stage liver diseases. With the increasing maturity of liver transplantation technology, the number of transplantation cases gradually increased, and perioperative treatment was also gradually standardized, however, the incidence of biliary complications still ranged from 5.8 to 24.5%, with an average of 10%, and was more common at early postoperative period, which seriously affected the outcome of the liver transplantation. However, the incidence of biliary complications still ranges from 5,8 to 24,5%, with an average of about 10%, and is more common in the early postoperative period, which seriously affects the success of the operation and the recovery of the patient. Biliary complications mainly include biliary stenosis, bile leakage, bile duct stones, bile sludge, ductal pattern, cholangioma, biliary hemorrhage, and jugular abdominal dysfunction, etc. Among them, biliary stenosis and bile leakage are the most common, accounting for about 70% of the cases, which mainly occur in the early stage of postoperative liver transplantation, and are generally related to biliary reconstruction techniques; whereas, the causes of biliary stenosis and obstruction in the late stage are more complicated, which may be related to occlusion of hepatic artery, ischemia/reperfusion injury, and chronic rejection reaction. The causes of late biliary stenosis and obstruction are more complex and may be related to hepatic artery occlusion, ischemia-reperfusion injury, chronic rejection reaction, etc. Causes of biliary complications 1. Ischemic injury (including thermal ischemic injury, cold ischemic injury, and ischemia-reperfusion injury): With the shortage of liver supply becoming more and more prominent, no-heartbeat donors (NHBD) have received more and more attention as an organ source. Unlike brain-dead donors, donor livers from NHBD inevitably undergo a period of thermal ischemic injury, and then donor livers with pre-existing thermal ischemic injury are exposed to subsequent cold preservation ischemic injury. The aforementioned bile ducts experiencing cold and hot ischemia will inevitably undergo ischemia-reperfusion injury after restoration of blood perfusion. The biliary epithelial cells are sensitive to preservation and reperfusion injury, and studies have shown that biliary epithelial cells are more resistant to ischemic injury than hepatocytes, while their ability to tolerate reperfusion injury is much lower than that of hepatocytes, due to the fact that the biliary epithelial cells produce 5 times more toxic oxygen radicals than hepatocytes in the process of reperfusion, and the content of endogenous antioxidants, such as glutathione, is indeed 7 times less than that of hepatocytes. 2, Immune injury: Logistic regression analysis showed that among several common factors, acute rejection is an important risk factor. The target organ of rejection reaction is the biliary epithelium, which can directly cause biliary tract injury, followed by bile duct stenosis or gallstone formation, which is consistent with the observation of Turrion et al. 3. Hepatic artery tamponade (HAT): the single blood supply of the biliary tract is different from the dual blood supply to the liver, with the upper portion of extrahepatic bile ducts supplied by the branches of the right hepatic artery, and the lower portion of the extrahepatic bile ducts supplied by the posterior superior pancreaticoduodenal artery, and the direct bile ducts The blood supply mainly comes from the capillary plexus around the bile duct (PBVP), so once HAT occurs, it will definitely affect the blood supply of the bile duct, leading to poor healing of the biliary anastomosis, and ultimately causing bile leakage, biliary stenosis, and other complications.Zheng SS et al. reported that the incidence of HAT in the group of intermittent hepatic arterial anastomoses (1/102) was significantly lower than that of the group of consecutive hepatic arterial anastomoses (6/96). 4.Biliary tract reconstruction Technique: Biliary reconstruction has always been the weakest link in liver transplantation, and was called “Achilles’ ankle” by Calne as early as 1976. The biliary reconstruction technique has a direct impact on the occurrence of biliary complications after liver transplantation, and all major transplant centers are constantly improving the anastomosis method and anastomosis technique. Currently, bile duct to end anastomosis is still the main procedure. From the anastomotic technique point of view, the use of microsurgical anastomosis techniques and appropriate anastomotic materials are crucial. Whether intermittent or continuous anastomosis, the surgeon’s skillful microsurgical technique is required to ensure the biliary blood supply, fully grasp the alignment and chiasm.T, Bacchella [8] et al. through a group of clinical data retrospectively analyzed that the use of continuous anastomosis of the opposite end of the bile ducts, no case of bile leakage occurs in the postoperative period, and biliary complications are significantly reduced, and which jugular abdominal dysfunction accounted for 62,5% of the total. 5, liver and bile duct perfusion preservation fluid: adequate and effective biliary perfusion irrigation can make the biliary tract obtain the best protection during cold preservation. The reason is that bile salts have a toxic effect on the biliary epithelium under ischemia, the extent of which is based on the concentration and composition of the bile salts; 6. Infectious factors: damage to the biliary epithelium can cause bacterial, fungal, and viral cholangitis. starzl [et al. found that the occurrence of bile sludge and gallstones was closely related to infection, and believed that infection was also related to strictures, which could promote the aggravation of the strictures; 7. ABO blood type discrepancy: the liver because of its in immunological specificity, coupled with the limitations of the source of donor liver, there are repeated clinical reports of liver transplantation in which the donor-recipient’s ABO blood group is incompatible, and there are many long-term survivors. However, there is an increased incidence of biliary and vascular complications after transplantation in ABO dyscrasia patients, which can be as high as 56%. The main reason for this is that the recipient’s antibodies act on the donor antigens in endothelial cells and biliary epithelial cells, resulting in damage to these structures. Statistical data table ABO blood type incompatibility liver transplantation after the occurrence of acute rejection, hepatic lobe necrosis and vascular and biliary complications are more than the blood type compatible people; 8, other: cause biliary complications after liver transplantation of numerous and complex causes, there are primary disease recurrence, such as primary sclerosing cholangitis; drug damage, etc., post-transplantation anti-discharge, antiviral and antibiotic applications may cause bile duct damage of the Side effects. Diagnosis of biliary complications after liver transplantation is mainly diagnosed by clinical manifestations, laboratory tests and imaging tests. Imaging tests such as abdominal ultrasound, dynamic CT and MRCP should be routinely performed in the early postoperative period, and several large centers in the world advocate aggressive treatment. 1, clinical manifestations and biochemical examination: about 50% of biliary complications occur in 3 months after surgery, so liver function monitoring should be carried out closely in the early postoperative period after liver transplantation. If patients have abnormal liver function such as elevated aminotransferase, bilirubin, alkaline phosphatase and Y-glutamyl transpeptidase, especially when the latter three are elevated disproportionately to the elevation of aminotransferase, it suggests the possibility of biliary complications, and further imaging should be performed to clarify the diagnosis. The patient’s clinical presentation is determined by the nature and extent of the biliary complications. When bile leakage occurs, patients may present with signs of peritonitis such as abdominal muscle tension, abdominal pain, rebound pain, and bile-like fluid drainage from the abdominal drainage tube, and in severe cases, bile may overflow through the surgical incision or around the orifice of the drainage tube. Mild biliary stenosis may have no obvious symptoms and signs for a long period of time, and only mild stenosis or roughness of the bile duct lining can be detected during routine cholangiography. Moderate to severe bile duct stenosis may show progressive and severe liver function impairment and cholangitis symptoms, especially when accompanied by hepatic artery thrombosis, and even the transplanted liver loses its function. Cholangiography: Cholangiography is the gold standard for diagnosing biliary complications, which can accurately show the size, shape, distribution, stenosis and bile leakage of bile ducts. Including ERC, PTC and T-tube imaging, because the early stage of stenosis is often not accompanied by symptoms, especially for hepatic bile duct stenosis, ultrasound, MRCP diagnosis is more difficult, Mount Sinai Center advocates the early application of ERC and PTC, ERC and PTC can be directly placed stent drainage to lift the stenosis, because PTC is invasive, with a certain degree of risk, ERC is better than PTC, but for the biliary tract complications, it is better than PTC, but for the biliary ducts. Because PTC is invasive and has some risk, ERC is better than PTC to some extent, but PTC is the preferred diagnosis and treatment for patients with biliary-intestinal anastomosis. Magnetic resonance cholangiopancreatography (MRCP) and technetium hepato-biliary scintigraphy (HBS): MRCP is a recently developed method of examination, which is non-invasive and does not require contrast medium, its diagnostic value is especially prominent and its application is becoming more and more popular. Combined application of cholangiography and MRCP can improve the diagnostic accuracy, provide a full picture of the biliary tree, show whether there is any narrowing and dilatation of the bile ducts inside and outside the liver, as well as their location and degree, and provide an important basis for the diagnosis of cholestasis and bile leakage, and patients suspected of having biliary complications should be subjected to MRCP.MRCP has a specificity and sensitivity of close to 90%, and HBS can suggest cholestasis in the biliary system, with a sensitivity HBS can indicate biliary system cholestasis with a sensitivity and specificity of 75% and 100%, respectively. The main defect of these two diagnostic methods is that they cannot be used directly as a therapeutic method. 4, ultrasound, CT scan: ultrasound is not sensitive to the early diagnosis of biliary complications, biliary stenosis patients may have jaundice, itching, transaminase elevation, but early often not accompanied by obvious symptoms, the diagnosis should be based on abdominal ultrasound, ultrasound suggests that the bile ducts are obviously dilated after a high positive predictive value, but the sensitivity is low (38%-66%), and the further confirmation of the diagnosis can be relied on MRCP, HBS test, CT scan has certain diagnostic value for chronic biliary obstruction or biliary liver abscess. Treatment strategy for biliary complications Once complications of the biliary system appear, early diagnosis and treatment become more important. With the gradual replacement of biliary reconstruction by bile-intestinal anastomosis and the development of endoscopic techniques, reoperation has been relegated to the second line of treatment due to its high risk and trauma. Currently, the main treatment modalities used in most centers are conventional modalities, followed by surgical treatment for unsuccessful or contraindicated interventions. Interventional modalities mainly include PTC, ERC and T-tube modalities. Although the cure rate of PTC may be higher than that of ERC, the risk of bile leakage and bleeding is higher due to its invasive nature, and the ERC modality is generally used unless biliary anastomosis is indicated, and bile leakage is mainly treated by placing a nasobiliary drain to reduce the pressure of the biliary tract to promote healing, and biliary stricture is mainly corrected by placing a stent to drain the biliary tract and balloon dilatation. Biliary stenosis is mainly corrected by placing stent drainage and balloon dilatation. If bile duct infection and bile sludge formation occur repeatedly in a vicious circle, it can lead to further narrowing of the bile duct, causing segmental dilatation of the terminal bile ducts and bead-like changes, which is more difficult to deal with, and balloon dilatation and placement of stents in the bile ducts can not solve the fundamental problem, and according to the experience of our hospital, liver transplantation is often the only solution to the problem. 1.Treatment of bile leakage Bile leakage is an important complication after liver transplantation, the incidence rate varies from 2% to 21%, according to the site of occurrence, it can be divided into anastomotic and non-anastomotic bile leakage, the former is the most common, and surgical anastomosis technology and local ischemic necrosis related to the general occurrence of the early postoperative period, it has been reported that most of the bile leakage occurs in the postoperative period within one month, non-anastomotic bile leakage occurs in the position of the retained T-tube, Non-anastomotic bile leaks have been reported to occur within the first month after surgery, with non-anastomotic leaks occurring at the location of the indwelling T-tube, at the stump of the cystic duct, or at the liver section of the living donor liver. Multicenter reports have confirmed that bile leaks are an independent risk factor for stenosis in the late postoperative period. Bile leaks should be treated promptly before they lead to serious complications such as abdominal infection and sepsis. Any suspicious signs of bile leakage (abnormal drainage fluid, fluid encapsulation in the abdominal cavity, etc.) after liver transplantation are immediately excluded by ancillary tests or puncture, and ERCP is considered to be the gold standard for the diagnosis of bile leakage, and also provides excellent treatment, including papillary sphincterotomy and biliary stenting for about 2-3 months, which is capable of curing more than 90% of the leaks, and smaller leaks can be treated by just the sphincterotomy. In cases where ERCP is not feasible, other treatment options include PTC drainage or surgical reconstruction. Of course, surgical treatment is generally not advocated, and in our experience, reoperation is difficult to repair bile leaks. The Hong Kong transplantation group suggests that PTBD should be avoided as much as possible, and three people in this center died after PTBD for postoperative biliary stenosis, which resulted in damage to the arteries and portal veins. The Kyoto group suggests that PTBD is preferred in patients with biliary-intestinal anastomosis, and that surgery should be performed if the AMY of the drainage fluid is high or the patient’s condition is poor; if direct repair is difficult, Roux-en-Y enterostomy is feasible and a stent is placed at the anastomosis to drain the anastomosis; in patients with an end-to-side anastomosis, stenting is preferred to drain ERBD. However, it is difficult to treat ischemic bile leakage with endoscopic or radiological interventions, and surgical reconstruction is generally required. The incidence of biliary stenosis after liver transplantation is about 2-12%, with a higher incidence in living liver transplantation than in cadaveric liver transplantation, and it is more common in heartbeat-less donors than in brain-dead donors. Biliary strictures can occur at any time after liver transplantation, but are most prevalent from May to August postoperatively. Depending on the site of occurrence, biliary strictures can be categorized as anastomotic or non-anastomotic strictures. Anastomotic biliary strictures occur most often in the early postoperative period after liver transplantation and are usually associated with surgical techniques, including unsuitable anastomotic technique, small bile duct caliber, donor-recipient caliber mismatch, presence of tension at the anastomosis, excessive use of the electrosurgical knife for control of biliary bleeding, infection, and bile leakage. Treatment of anastomotic biliary strictures relies on ERCP, which is both diagnostic and therapeutic.During ERCP, a guidewire is passed through the stricture, the stricture is dilated by a balloon, and a plastic stent is inserted.ERCP is usually performed once every 2-3 months to dilate the stricture by balloon dilatation and to replace the stent.The procedure is usually performed once every 2-3 months to dilate the stricture and replace the stent. The incidence of non-anastomotic biliary stricture is about 0.5%-9.6%. The mechanism of occurrence is due to bile duct abnormalities, ranging from minor, localized mucosal irregularities to extensive diffuse bile duct stenosis, depending on the anatomic location, pathologic changes, and severity. Non-anastomotic bile duct stenosis can be further classified into 3 types: macrovascular lesions, microvascular lesions and immunogenic lesions; of which the macrovascular lesion type is mainly originated from insufficient hepatic arterial blood supply, such as hepatic artery embolism, and the microvascular lesion type mainly includes prolonged hot and cold ischemia time, heartless heartbeat supply with re-arterialization of the receptor leading to ischemia/reperfusion injury of the bile duct epithelial cells, and the bile duct epithelial or vascular epithelial immune injury mainly because of chronic rejection, ABO blood group incompatibility, cytomegalovirus infection, or recurrence of primary sclerosing cholangitis. Non-anastomotic biliary strictures secondary to early hepatic artery embolism usually require urgent revascularization or repeat liver transplantation, whereas those caused by late hepatic artery embolism or other causes can be treated endoscopically in a similar way to anastomotic biliary strictures, including removal of bile sludge and ductal patterns, balloon dilatation of all passable stenoses, and placement of a plastic stent that can be exchanged every 3-6 months for one year, with lower success rates than anastomotic biliary strictures, but not as high as those with anastomotic biliary strictures. success rate is lower than anastomotic biliary strictures. Non-anastomotic biliary strictures are more difficult to treat, including more complications such as graft failure or even death, and less favorable outcomes, with about 80% of patients needing repeat liver transplantation. 3, Biliary stones, biliary sludge and ductal pattern The incidence of biliary stones after liver transplantation is about 3,3-12,3%. The main causes of stone and bile sludge formation after transplantation may be mechanical obstruction at the site of stenosis, bacterial infection, bile reflux, and biliary mucosal inflammation. Removal of stones or debris by ERCP papillary sphincterotomy can be very successful in 90-100% of almost all cases. The main causes of biliary ductal pattern formation include necrotic breakdown of the biliary epithelium caused by prolonged cold ischemia, transient or progressive ischemia, chronic rejection, infection, cholestasis, and changes in the biliary environment. Ductal patterns usually occur within one year of liver transplantation and are more challenging to treat, sometimes requiring multiple approaches such as papillary sphincterotomy, balloon dilatation, mesh basket removal, stenting, lithotripsy, and PTC. Surgical resolution may be required if endoscopic treatment is unsuccessful, and approximately 22% of patients with biliary ductal syndromes will require repeat liver transplantation. Sphincter of Oddi dysfunction The incidence of sphincter of Oddi dysfunction after liver transplantation is about 5%, and the reason for its occurrence is unknown. It may be related to the excessive freeing of the nerves of the bile duct pudendal region during transplantation, which leads to abnormal relaxation of the pudendal region and increases the pressure of bile in the bile ducts, and the persistent elevation of transaminases in the presence of cholestasis is suspected to be sphincter of Oddi dysfunction. In the absence of evidence of biliary obstruction due to anastomosis, the diagnostic accuracy can be further improved by loosening the T-tube if it is left in place, and by cholangiography showing marked dilatation of the common bile duct greater than 10 mm in diameter and delayed excretion of contrast medium (greater than 15 min).Thuluvath et al. reported that CMV and other opportunistic infections also play an important role in the pathogenesis of Sphincter of Odi dysfunction after liver transplantation. Pathologic etiology also plays an important role. Hepatobiliary scintigraphy, sphincter or T-tube manometry may be utilized as diagnostic methods. endoscopic sphincterotomy or biliary stenting under ERCP is a routine and usually successful treatment. Cholangioma is a limited collection of bile-like fluid in or near the liver due to ischemia secondary to anastomotic leakage. There is limited data on the incidence of cholangioma after liver transplantation. Since cholangioma is an important infectious complication, patients with fever, abdominal pain or transaminase abnormality should be considered for cholangioma after liver transplantation. Cholangiomas appear as scattered, rounded hypoechoic tumors on ultrasound and low-density fluid collections on CT; most cholangiomas that are connected to the biliary tree structure disappear spontaneously or require endoscopic stent placement, while those that are not usually require a combination of antibiotics and percutaneous perforation and drainage. Biliary complications are important complications after liver transplantation, although the incidence has been significantly reduced in the past few years, biliary stenosis and bile leakage are still an important source of morbidity and mortality, therefore, in order to improve the success rate of early intervention and treatment, exploring the discovery of early and efficient diagnostic indexes and methods seems to be crucial; the current treatment strategies for biliary complications mainly include non-surgical and surgical means, combining several domestic reports and the experience of our center, we believe that: ERCP is the most effective treatment for biliary complications. Combined with many domestic reports and our center’s experience, we believe that ERCP is a more effective means of treating biliary strictures and biliary obstruction due to gallstones, bile sludge and sphincter of Oddi dysfunction, and that surgical treatment or even re-transplantation is mandatory if endoscopic treatment is infeasible or unsuccessful. However, it must be pointed out that the clinical research on liver transplantation in China is still mostly limited to retrospective analysis and lack of prospective research, which requires further efforts from domestic liver transplantation workers. There is a long way to go to prevent postoperative complications in all aspects of liver transplantation and to improve the long-term survival rate of liver transplant patients. Not only do we need to absorb the advanced experience of foreign countries in time, but we also hope that our liver transplantation physicians can explore courageously, strive for excellence, and carry out systematic basic and clinical research, so that clinical liver transplantation can better benefit mankind.