Intrahepatic Bile Duct Injury Research Articles

Rupture of intrahepatic bile duct after ERCP for common bile duct stone: A case report of rare complications.

Complications after endoscopic retrograde cholangiopancreatography (ERCP) are diverse and usually treated with nonoperative management or percutaneous drainage; however, there are still some rare, life-threatening complications. This is an extremely rare case of biliary peritonitis caused by rupture of the intrahepatic bile duct after ERCP. A 63-year-old male underwent ERCP for common bile duct stones. On the second day after the procedure, the patient developed sepsis and abdominal distention. Contrast-enhanced computed tomography revealed a subcapsular hepatic fluid collection attached to the bile duct of segment VII. Sepsis resulted in liver parenchyma rupture and intrahepatic bile duct injury after ERCP. Intraoperative cholangiography revealed a connection between a hole in the liver parenchymal surface and the intrahepatic bile duct. Surgeons performed the cholecystectomy, inserted a T-tube into the common bile duct stones, sutured the defect, and put 2 drainage tubes around the lesion. Postoperative recovery was uneventful, and the patient was discharged on the 17th postoperative day. Intrahepatic bile duct perforation after ERCP can lead to rupture of the liver parenchyma, biloma, or abdominal peritonitis. Multidisciplinary management is necessary to achieve favorable outcomes.

IL-21, not IL-17A, exacerbates murine primary biliary cholangitis.

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease caused by intrahepatic bile duct injuries, resulting in fibrosis, cirrhosis, and eventually liver failure. T helper (Th) 17 cells are proposed to involve in the pathogenesis of PBC. However, how and which Th17 cell-derived cytokines affect PBC remains unclear. In this study, we investigated the effects of Th17 effector cytokines, including interleukin (IL)-17A, IL-17F, and IL-21 in PBC using a xenobiotic-induced mouse model of autoimmune cholangitis (inducible chemical xenobiotic models of PBC) treated with cytokine-expressing adeno-associated virus. Our results showed that administration of IL-17A, the well-known main cytokine produced by Th17 cells, did not augment liver inflammation or fibrosis. In contrast, we noted IL-17A-treated mice had lower hepatic Th1 cell numbers and higher hepatic CD11b+Ly6G+ polymorphonuclear myeloid-derived suppressor cell numbers. IL-17F did not alter liver inflammation or fibrosis. However, the administration of IL-21 exacerbated liver inflammatory responses and portal cell infiltration. IL-21 markedly increased the numbers of activated CD8+ T cells and liver tissue-resident memory CD8+ T cells. Moreover, IL-21 aggravates liver fibrosis in mice with autoimmune cholangitis. These results emphasized that not IL-17A but IL-21 in Th17 cell-derived cytokines affected the pathogenesis of PBC. IL-21 enhanced liver inflammation and progression to fibrosis by enhancing the numbers and effector activities of CD8+ T cells. Delineation of the effects of different Th17 effector cytokines in PBC offers clues for developing new therapeutic approaches.

Combined endoscopic and surgical management of a right intrahepatic bile duct injury during laparoscopic cholecystectomy.

Combined endoscopic and surgical management of a right intrahepatic bile duct injury during laparoscopic cholecystectomy.

RRV-induced biliary atresia in neonatal mice involves CD8 + T lymphocyte killer cells and the Notch signaling pathway.

Persistent inflammation induced by viral infection may contribute to the pathogenesis of biliary atresia (BA). Moreover, CD4+ helper cells and CD8+ killer cells are the main effector cells involved in BA and intrahepatic bile duct injuries. Thus, we aimed to explore the dynamics of inflammatory cell infiltration and inflammation-regulated pathways in liver-specific inflammatory responses. Neonatal Balb/C mice were intraperitoneally infected with 1 × 106 PFU rhesus rotavirus (RRV; BA + group), 1 × 105 PFU RRV (BA- group), or DMEM (control group). Mice were sacrificed 7 or 14days post-infection and their bile ducts, livers, and spleen-derived tissues were examined via H & E staining. The number of CD4+T lymphocytes helper cells (CD4+Th), CD8+T lymphocytes killer cells (CD8+Tc), natural killer (NK) cells, and macrophages (Mac) in the liver and spleen were quantified by flow cytometry. The expression of inflammatory genes was analyzed via a PCR-array. Western blotting was conducted to quantify the protein expression of Notch receptor active fragments (NICD). Finally, some mice were injected with DAPT (a γ-secretase inhibitor) 12h post-infection followed by analysis of liver and bile duct tissues after 14days. The numbers of CD4+Th cells were increased in the livers of BA- mice after 14days (P < 0.05). After RRV infection, the number of CD8+Tc, CD4+Th, NK, and Mac were increased in the livers of BA + mice after 7 and 14days. Notably, NK cell numbers remained elevated in the BA + group, but the number of Mac first increased and then decreased in both the treatment groups. PCR-array analyses indicated that the expression of many genes related to T cell proliferation and differentiation significantly increased in the livers of BA. The most upregulated gene was Jagged2 (20.34-fold). Increased NICD (Notch receptor active fragments) protein expression was found in the BA + group. Finally, DAPT injection could reduce inflammation, CD8+Tc infiltration, NICD expression, and bile duct damage after RRV infection. We found that CD8+Tc played the most important role in damaging bile ducts and promoting BA. The DAPT-based intervention could reduce expression of CD8+Tc and bile duct damage in BA mouse livers post-RRV infection. We believe that the Notch signaling pathway regulates CD8+Tc functions and inflammatory dynamics in BA mouse livers.

Centrally Mediated Abdominal Pain Syndrome

Centrally mediated abdominal pain syndrome (CAPS), known as functional abdominal pain syndrome in the Rome III criteria of functional gastrointestinal diseases, has a reported population prevalence of between 0.5% and 2.1%, with a female preponderance. The pathogenesis of CAPS has not been completely established, and various studies are being conducted. On the other hand, central nervous system sensitization with disinhibition of the pain signaling pathways appears to play a more important role than the up-regulation of peripheral afferent neuronal excitability. The diagnosis of CAPS is based on the Rome IV criteria (2016) and is established around the gastrointestinal symptoms combination. Various new treatment trials and effective patient-physician relationships showed progressive results.

Long-term outcomes in the repair of intrahepatic iatrogenic bile duct lesions using a combined intraglissonian and extraglissonian approach.

Iatrogenic bile duct injuries (IBDI) with intrahepatic involvement are a serious and challenging surgical complication that can have disastrous consequences in terms of morbidity and mortality. We collected the patients with IBDI type (E4) between January 1991 and March 2020 in our hospital. The objective of the study was to present the long-term results of a extraglissonian approach and intraglissonian biliary reconstruction in a series of patients with intrahepatic bile duct injuries after cholecystectomy. We also detail our preoperative management and the standardization of the technique. An extraglissonian approach with partial hepatic resection of the base of segments 4b and 5 and intraglissonian Roux-en-Y hepaticojejunostomy for biliary reconstruction using to several branches was performed in 10 patients with E4 Strassberg type intrahepatic lesions. Only one patient had postoperative bile leak (Clavien 3a). Surgical time was 260 min (IQR, 210-490). We left transanastomotic catheter (between 2 and 5) in situ for 3 and 6 months after surgery. The patients remained asymptomatic over a median follow-up of 169 months (IQR 129-234). This biliary reconstruction technique obtains positive long-term outcomes in patients with severe intrahepatic lesions.

Protective Mechanism of MIF Inhibitor ISO-1 on Intrahepatic Bile Duct Cells in Rats with Severe Acute Pancreatitis.

This study aimed to explore the protection mechanism of ISO-1 on severe acute pancreatitis-associated intrahepatic bile duct (IBD) injury in rats. Forty-eight specific-pathogen-free male Wistar rats were randomly divided into four groups (N = 12): a sham operation group (SO group), a severe acute pancreatitis model group (SAP group), a ISO-1 treatment group (ISO-1 + SAP group), and a ISO-1 control group (ISO-1 + SO group). All rats were killed after 12h of being made models. Immunohistochemistry was used to detect the expression of MIF and P38 in IBD cells. MIF mRNA expression in IBD cells was observed using real-time fluorescent quantitative polymerase chain reaction (real-time PCR). In addition, Western blotting was performed to detect the protein expression of P38, phosphorylated P38 (P-P38), nuclear factor-κB (NF-κB p65), and tumor necrosis factor alpha (TNF-α). Enzyme-linked immunosorbent assays were used to analyze the levels of TNF-α, IL-1β, and IL-6 in the IBD of rats. Compared with SAP, after treatment with ISO-1, the pathological injuries of pancreas, liver, and IBD cells in ISO-1 treatment group remarkably relieved. The expression of MIF in the IBD cells was significantly downregulated both at mRNA and at protein levels in ISO-1 treatment group. Besides, the protein expression levels of P38, P-P38, NF-κBp65, TNF-α, IL-1β, and IL-6 in the IBD in rats were also significantly decreased in ISO-1 treatment group (all P < 0.05). ISO-1 may protect the IBD cells, reduce pathological injuries, and reduce the inflammatory response in SAP rats. Its mechanisms may be via inhibiting the expression of MIF and then blocking the activation of p38-MAPK and NF-κB signaling pathway.

RANK/RANKL Acts as a Protective Factor by Targeting Cholangiocytes in Primary Biliary Cholangitis.

Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by the highly selective autoimmune injury of small intrahepatic bile ducts. Studies reported that the cholangiocytes from PBC patients expressed significantly higher levels of both receptor activator of nuclear factor-kappa B (RANK) and its ligand RANKL. However, the accurate role of RANK/RANKL axis in PBC remains unclear. Forty patients with PBC were enrolled according to the inclusion criteria. The biochemical parameters (alkaline phosphatase, ALP; gamma-glutamyltransferase, GGT; alanine aminotransferase, ALT; aspartate transaminase, AST; total bilirubin, TB) were collected at baseline and followed-up after 6months of treatment with ursodeoxycholic acid (UDCA, 15mg/kgd). Stages of PBC were diagnosed based on liver biopsy histopathology according to Nakanuma's criteria. RANK expression in hepatic tissues was detected by immunohistochemistry. The cellular immunofluorescence method was used to locate the distribution of RANK in the human intrahepatic biliary epithelial cells (HIBECs) cultured in vitro. HIBECs were treated with RANKL at a concentration of 100ng/ml or transfected with RANK-overexpressing lentivirus (LV-RANK). CCK-8 assay and cell cycle assay were used to detect the cell proliferation. Real-time PCR was used to detect the expression of IL-6, E-cadherin, VCAM, ICAM-1, TNF-α, and CD80. RANK expression in liver biopsies from early PBC patients (stage I + stage II) was significantly lower than that from advanced PBC patients (stage III + stage IV) (1.7 ± 0.63 vs. 2.3 ± 0.45 scores, P < 0.05). High-RANK patients seemed to have better response to UDCA than low-RANK patients (88.9% vs. 40.9%, P < 0.05). The baseline biochemical parameters between the two groups were comparable. The decline percentages of ALP and GGT after UDCA treatment were more obvious in high-RANK patients than those in low-RANK patients (53.90% ± 9.82% vs. 23.93% ± 6.24%, P < 0.05; 74.11% ± 7.18% vs. 48.00% ± 8.17%, P < 0.05, respectively). HIBECs proliferation was significantly inhibited after treatment of RANKL or transfection with LV-RANK. Increased expression of IL-6 and E-cadherin was observed in HIBECs treated with RANKL or LV-RANK. The overall hepatic RANK expression was associated with disease severity and biochemical response in PBC patients. Activation of RANK/RANKL signaling pathway inhibited cholangiocytes proliferation in vitro. Our study suggested that RANK/RANKL pathway might be a potential target of immunotherapy of PBC based on its involvement in the occurrence and development of the disease.

Intra and extraglissonian approach with partial resection of IV-V segments for intrahepatic bile duct injuries

Background: Laparoscopic bile duct injuries (LBDI) are more often intrahepatic, with associated vascular injury and disappearance of the bile duct segments than in open surgery. Their repair is a difficult challenge for the surgeon. Methods: Between January 1991 and March 2016, 11 patients with LBDI (E4) were satisfactorily resolved by an extra and intraglissonian approach developed by our unit. We performed a combined intraglissonian and extraglissonian approach resecting the base of the IVb and V segment, in search of the intrahepatic bile radicals to the uninjured zone. We performed and intrahepatic HY-Roux in all cases and due to the low caliber of intrahepatic bile radicals we left transanastomotic tutors (between 2 and 5), which were maintained between 3 and 6 months after surgery. In 4 cases they had RHA injury. Nine patients were treated at their hospital with HY-Roux. Four patients were diagnosed of secondary biliary cirrhosis candidate to liver transplant. Three patients had acute diffuse peritonitis requiring urgent surgery. Results: There was no mortality. One patient had a biliary leakage treated with percutaneous radiological drainage. Surgical time was 270 min (range 200–480 min). Patients are asymptomatic with a median follow up of 6 years (range: 10 months–19 years). Conclusion: Our technique in severe intrahepatic lesions associated with vascular lesions obtained satisfactory results.

Intra and extraglissonian approach with partial resection of IV-V segments for intrahepatic bile duct injuries

Intra and extraglissonian approach with partial resection of IV-V segments for intrahepatic bile duct injuries

Macrophage Migration Inhibitor Promoted the Intrahepatic Bile Duct Injury in Rats with Severe Acute Pancreatitis.

Macrophage migration inhibitory factor (MIF) is involved in many acute and chronic inflammatory diseases. However, its role in intrahepatic bile duct (IBD) cell damage associated with severe acute pancreatitis (SAP) remains unclear. This study was aimed to identify the role of MIF and its underlying mechanisms in SAP complicated by IBD cell damage. Forty-eight specific-pathogen-free male Wistar rats were randomly divided into four groups (N = 12): a sham operation group (SO group) and three SAP model groups (SAP-3h, SAP-6h, and SAP-12h). Immunohistochemistry was used to detect the expression of MIF and P38 in IBD cells. MIF mRNA expression in IBD cells was observed using real-time fluorescent quantitative polymerase chain reaction (real-time PCR). In addition, Western blotting was performed to detect the protein expression of P38, phosphorylated P38 (P-P38), nuclear factor-κB (NF-κB p65), and tumor necrosis factor alpha (TNF-α). Enzyme-linked immunosorbent assays were used to analyze the levels of TNF-α, IL-1β, and IL-6 in the IBD of rats. Compared with the SO group, the expression of MIF in the IBD was significantly upregulated both at mRNA and at protein levels in the SAP group. Besides, the protein expression levels of P38, P-P38, NF-κB, p65, TNF-α, IL-1β, and IL-6 in the IBD in rats were also significantly increased in the SAP group and the levels increased gradually as acute pancreatitis progressed (all P < 0.05). MIF may promote the IBD injury and inflammatory reaction in SAP via activating the P38-MAPK and NF-κB signaling pathways.

Management of traumatic bile duct injuries in children.

Pediatric experience with biliary tract injuries (BTI) is limited and mostly consists of case presentations. The purpose of this study is to evaluate clinical and radiological findings of possible BTI, treatment strategies, and results. The records of nine patients with the diagnosis of BTI between July 2009 and November 2017 were reviewed retrospectively. There were seven boys and two girls (mean 8.05 ± 4.39years). The mechanisms were motor vehicle occupant, fall, crush and gunshot wound. Hepatic laceration routes that extended into the porta hepatis and contracted the gall bladder were demonstrated on computerized tomography (CT). Bile duct injury was diagnosed with bile leakage from the thoracic tube (n = 2), from the abdominal drain (n = 2) and by paracentesis (n = 5). Extrahepatic (n = 8) and intrahepatic (n = 1) bile duct injuries were diagnosed by cholangiography. Endoscopic retrograde cholangiography, sphincterotomy, and stent placement were successfully completed in five patients. Peritoneal drainage stopped after 3-17days of procedure in four patients. The fifth patient was operated with the diagnosis of cystic duct avulsion. Cholecystectomies, primary repair of laceration, cystic duct ligation, and Roux-en-Y hepatoportoenterostomy were performed in the remaining four patients. All patients presented with clinically normal findings, normal liver functions, and normal ultrasonographic findings in the follow-up period. The presentation of the parenchymal injury extending to the porta hepatis with contracted gall bladder on CT and diffuse homogenous abdominal fluid should be considered as signs of BTI. We suggest a multi-disciplinary approach for the diagnosis and treatment of BTIs. Surgery may be indicated according to the patient's clinical condition, radiological findings and failure of non-operative treatment.

Secondary sclerosing cholangitis in critically ill patients: current perspectives.

Secondary sclerosing cholangitis (SSC) is a term used for a group of chronic cholestatic disease affecting the intra- and/or extrahepatic biliary tree with inflammation and progressive stricture formation, which can lead to biliary cirrhosis. A newly recognized form of SSC is secondary sclerosing cholangitis in critically ill patients (SSC-CIP). Pathogenesis is believed to involve ischemic injury of intrahepatic bile ducts associated with prolonged hypotension, vasopressors administration, and/or mechanical ventilation in patients treated in the intensive care unit (ICU). Patients diagnosed with SSC-CIP have no prior history of liver disease and no known pathologic process or injury responsible for bile duct obstruction prior to ICU treatment. Reasons leading to ICU treatment are many including multitrauma, burn injury, cardiac surgery, severe pneumonia, other infections, or bleeding after abdominal surgery. Patients have in common prolonged ICU admission. SSC-CIP is associated with rapid progression to liver cirrhosis and poor survival with limited treatment options except a liver transplantation. Transplant-free survival is around 17–40 months, which is lower than in other SSC patients. During the initial stages of the disease, the clinical symptoms and biochemical profile are not specific and easily missed. Biliary casts formation may be considered pathognomonic for SSC-CIP since most patients have them in early stages of the disease. Increased awareness and early detection of the disease and its complications is considered to be crucial to improve the poor prognosis.

Risk Factors for Bile Duct Injury After Percutaneous Thermal Ablation of Malignant Liver Tumors: A Retrospective Case-Control Study.

Bile duct injury after ablation of malignant liver tumors (MLTs) was not unusual and should be avoided. However, few studies have focused on evaluating the risk factors for intrahepatic bile duct injury. To evaluate the risk factors for intrahepatic bile duct injury after ablation of MLTs and to evaluate the minimum safe distance for ablating tumors abutting bile ducts. Sixty-five patients with intrahepatic bile duct injury after ablation of MLTs, and 65 controls were recruited. Risk factors for intrahepatic bile duct injury were analyzed. Tumor location was recorded as ≤5mm (group A), 5-10mm (group B), and >10mm (group C) from the right/left main duct or segmental bile duct. Ascites history (P<0.001), TACE treatment history (P=0.025), intrahepatic bile duct dilatation before ablation (P<0.001), and tumor location (P=0.000) were identified as significant risk factors for intrahepatic bile duct injury. Significant differences in the risk of intrahepatic bile duct injury were found between groups B and C (P=0.000), but not between groups A and B (P=0.751). Ascites history (P=0.002) and tumor location (P<0.001) were independent predictors with the OR (95% confidence interval) of 39.31(3.95-391.69) and 16.56 (5.87-46.71), respectively. Bile duct injury after ablation of MLTs was the result of local treatment-related factors combined with the patients' general condition. The minimum safe distance for ablation of tumor abutting a bile duct was 10mm.

The dendritic cell-T helper 17-macrophage axis controls cholangiocyte injury and disease progression in murine and human biliary atresia.

These findings identify the dendritic cell-T helper 17-macrophage axis as a target for the development of strategies to block progression of intrahepatic bile duct injury in patients with BA. (Hepatology 2017;65:174-188).

Dose-dependent effects of alpha-naphthylisothiocyanate disconnect biliary fibrosis from hepatocellular necrosis.

Exposure of rodents to the xenobiotic α-naphthylisothiocyanate (ANIT) is an established model of experimental intrahepatic bile duct injury. Administration of ANIT to mice causes neutrophil-mediated hepatocellular necrosis. Prolonged exposure of mice to ANIT also produces bile duct hyperplasia and liver fibrosis. However, the mechanistic connection between ANIT-induced hepatocellular necrosis and bile duct hyperplasia and fibrosis is not well characterized. We examined impact of two different doses of ANIT, by feeding chow containing ANIT (0.05%, 0.1%), on the severity of various liver pathologies in a model of chronic ANIT exposure. ANIT-elicited increases in liver inflammation and hepatocellular necrosis increased with dose. Remarkably, there was no connection between increased hepatocellular necrosis and bile duct hyperplasia and peribiliary fibrosis, as these pathologies increased similarly in mice exposed to either dose of ANIT. The results indicate that the severity of hepatocellular necrosis does not dictate the extent of bile duct hyperplasia/fibrosis in ANIT-exposed mice.

Primary biliary cirrhosis is a generalized autoimmune epithelitis.

Primary biliary cirrhosis (PBC) is a chronic progressive autoimmune cholestatic liver disease characterized by highly specific antimitochondrial antibodies (AMAs) and the specific immune-mediated injury of small intrahepatic bile ducts. Unique apoptotic feature of biliary epithelial cells (BECs) may contribute to apotope presentation to the immune system, causing unique tissue damage in PBC. Perpetuation of inflammation may result in senescence of BECs, contributing to irreversible loss of bile duct. In addition to the classic liver manifestations, focal inflammation and tissue damage are also seen in salivary glands and urinary tract in a significant proportion of PBC patients. These findings provide potent support to the idea that molecular mimicry may be involved in the breakdown of autoimmune tolerance and mucosal immunity may lead to a systematic epithelitis in PBC patients. Thus, PBC is considered a generalized epithelitis in clinical practice.

Low doses of CMV induce autoimmune-mediated and inflammatory responses in bile duct epithelia of regulatory T cell-depleted neonatal mice

Recent studies have indicated that perinatal infection with cytomegalovirus (CMV) may promote bile duct damage in biliary atresia (BA) and that the decreased regulatory T cell (Treg) percentage associated with BA may further amplify the bile duct damage. Although a majority of BA patients have had previous CMV infections and lower percentages of Tregs, it is unknown whether an initial exposure to a low dose of CMV could induce exaggerated and progressive biliary injury. A Treg-depleted neonatal mouse was infected with low-dose CMV (LD-CMV) as a model to study BA patients. LD-CMV infection in Treg-depleted mice induced extensive inflammation in both the intrahepatic and extrahepatic bile ducts, accompanied with injury to and atresia of intrahepatic bile ducts and partial obstruction of the extrahepatic bile ducts. Serum total and direct bilirubin amounts were also elevated. Evidence for the involvement of cellular and humoral autoimmune responses in LD-CMV-infection of Treg-depleted mice was also obtained through detection of increased percentages of CD3 and CD8 mononuclear cells and serum autoantibodies reactive to bile duct epithelial proteins, one of which was identified as α-enolase. Depletion of Tregs that can lead to the decreased inhibition of aberrantly activated hepatic T-lymphocytes and generation of autoantibodies may lead to further injury. Increased hepatic expression of Th1-related genes (TNF-α), IFN-γ-activated genes (STAT-1) and Th1 cytokines (TNF-α, lymphotactin, IL-12p40 and MIP −1γ) were also identified. In conclusion, autoimmune-mediated and inflammatory responses induced by LD-CMV infection in Treg-depleted mice results in increased intrahepatic and extrahepatic bile duct injury and contributed to disease progression.

Delayed rearterialization unlikely leads to nonanastomotic stricture but causes temporary injury on bile duct after liver transplantation.

Nonanastomotic strictures (NAS) are common biliary complications after liver transplantation (LT). Delayed rearterialization induces biliary injury in several hours. However, whether this injury can be prolonged remains unknown. The correlation of this injury with NAS occurrence remains obscure. Different delayed rearterialization times were compared using a porcine LT model. Morphological and functional changes in bile canaliculus were evaluated by transmission electron microscopy and real-time PCR. Immunohistochemistry and TUNEL were performed to validate intrahepatic bile duct injury. Three months after LT was performed, biliary duct stricture was determined by cholangiography; the tissue of common bile duct was detected by real-time PCR. Bile canaliculi were impaired in early postoperative stage and then exacerbated as delayed rearterialization time was prolonged. Nevertheless, damaged bile canaliculi could fully recover in subsequent months. TNF-α and TGF-β expressions and apoptosis cell ratio increased in the intrahepatic bile duct only during early postoperative period in a time-dependent manner. No abnormality was observed by cholangiography and common bile duct examination after 3 months. Delayed rearterialization caused temporary injury to bile canaliculi and intrahepatic bile duct in a time-dependent manner. Injury could be fully treated in succeeding months. Solo delayed rearterialization cannot induce NAS after LT.

The Long-Term Prognosis and Treatments of Biliary Complications After Living Donor Liver Transplantation.

Purpose: Biliary complications after living donor liver transplantation (LDLT) are classified as hepaticojejunostomy anastomotic strictures (HJS) and non-anastomotic biliary strictures (NAS). We present a retrospective analysis of the long-term prognosis and treatsments of biliary complications in hepaticojejunostomy. Methods: Between May 2001 and May 2011, 199 LDLTs were performed using S2 monosegment, lateral segment or left lobe grafts. The median age and body weight at LDLT were 1.6 years (0.1-19.5 years) and 9.8 kg (2.6-65.0 kg), respectively. The median observation period was 6.8 years (2.7-12.7 years) after LDLT. Results: The overall incidence of HJS was 18.1% (36/199). Multivariate analysis revealed that left lobe grafts were an independent risk factor for HJS (p=0.034). There were 2 surgical reconstructions, 18 percutaneous biliary drainages (PTBD), 14 double balloon enteroscopies (DBE) and 2 rendezvous penetration procedures were performed for recipients with HJS. The incidence of recurrent HJS was 36.1% (13/36). The graft survival of recipients with and without HJS was 97.2% and 91.4% (p=0.532), respectively, and the graft failures were not due to complications associated with HJS. The overall incidence of NAS was 2.5% (5/199). The causes of NAS were hepatic arterial thrombosis in 1 recipient, intrahepatic bile duct injury associated with ABO-incompatible LDLT in 1 recipient, intrahepatic bile duct injury associated with acute cellular rejection in 2 recipients and unknown etiology in 1 recipient. PTBD were performed for all recipients with NAS, but 1 recipient underwent re-transplantation eight months after the first LDLT due to graft failure secondary to refractory cholangitis. Four recipients were able to undergo PTBD tube removal, but 2 recipients suffered from liver dysfunction. Conclusions: Although HJS occurs even in a late period after LDLT, the long-term prognosis is good because graft failure can be avoided by early diagnosis and treatment. However, NAS can develop into graft failure and suffers from a poor long-term prognosis.