This study aimed to report our experience with the use of sirolimus in pediatric liver transplant patients with chronic rejection or steroid-resistant rejection with hepatic fibrosis, focusing on their histological evolution. All pediatric liver transplant recipients who received off-label treatment with sirolimus for chronic ductopenic rejection or cortico-resistant rejection between July 2003 and July 2022 were included in the study. All nine patients included in the study showed improvement in liver enzymes and cholestasis parameters as soon as 1-month after postsirolimus introduction. A decrease in fibrosis stage was observed in 7/9 (77.7%) patients at 36 months. All but one patient experienced an improvement in the Rejection Activity Index and ductopenia at 12 months. A single patient had to discontinue sirolimus treatment owing to nephrotic proteinuria. In conclusion, sirolimus may be a safe and effective treatment for chronic and steroid-resistant rejection and may improve allograft rejection-related fibrosis and ductal damage.

The transjugular intrahepatic portosystemic shunt is a rising interventional procedure with multiple indications and high technical success but with risks of biliary injuries, an underreported scenario. We present an 11-year-old patient with biliary injury with a leak, biloma formation, and biliary obstruction caused by the percutaneous procedure. Interventional radiology drainages addressed these complications by resolving the leak and biloma. These biliary complications in percutaneous procedures and their management are rarely reported in the medical literature, making their management not standard. We highlight drainage management and the importance of sharing it to add experience to this clinical scenario and encourage sharing cases with similar diagnoses.

Gallbladder rupture caused by blunt abdominal trauma is an uncommon injury, particularly in children. This condition occurs even less frequently in children with common bile duct cysts. The history is difficult to obtain, the clinical symptoms are indistinct, and their assessment is obscured by a slew of other lesions. Radiography cannot produce clear images. Thus, the diagnosis is frequently delayed and confirmed only during surgery. Case reports of gallbladder injury after abdominal trauma are relatively rare and there are only 50 case reports in literature for 100 years. Herein, we present the case of an 18-month-old girl who had a ruptured gallbladder funnel due to blunt abdominal trauma caused by domestic violence, with an early clinical presentation of septic shock and chylous effusion. The patient underwent surgery after being diagnosed with chylous ascites that had not responded to medical treatment. Based on the findings, single-stage laparoscopic surgery is confirmed to aid in the diagnosis and treatment of gallbladder injury in the presence of a common bile duct cyst.

Iatrogenic bile duct injury during laparoscopic cholecystectomy is a known complication of low incidence. The outcome can be devastating if not recognized and managed timely and properly. In cases of iatrogenic biliary injury due to cholecystectomy, the management depends on the level of injury, the timing of discovery (intraoperative or postoperative), and the patient\'s condition. If discovered intraoperatively, the injury should be managed immediately. In case expertise is lacking, a surgical drain with external biliary drainage can provide a temporary alternative solution to allow for referral to a tertiary care center. If the patient is septic or not fit for surgery, a percutaneous internal-external biliary drainage (PTBD) catheter can be placed until the patient\'s condition improves. We report a case of complete transection of the common hepatic duct during laparoscopic cholecystectomy managed by extra-anatomic PTBD.

BACKGROUND: Ischemia of the bile duct is a common feature in liver disease and transplantation, which represents a major cause of morbidity and mortality, especially after liver transplantation. Detailed knowledge of its pathogenesis remains incomplete due to the lack of appropriate in vitro models.
METHODS: To recapitulate biliary damage induced by ischemia and reperfusion in vitro, human intrahepatic cholangiocyte organoids (ICOs) were grown at low oxygen levels of 1% up to 72 h, followed by re-oxygenation at normal levels.
RESULTS: ICOs stressed by ischemia and subsequent re-oxygenation represented the dynamic change in biliary cell proliferation, upregulation of epithelial-mesenchymal transition (EMT)-associated markers, and the evocation of phase-dependent cell death programs similar to what is described in patients. Clinical-grade alpha-1 antitrypsin was identified as a potent inhibitor of both ischemia-induced apoptosis and necroptosis.
CONCLUSIONS: These findings demonstrate that ICOs recapitulate ischemic cholangiopathy in vitro and enable drug assessment studies for the discovery of new therapeutics for ischemic cholangiopathies.
BACKGROUND: Dutch Digestive FoundationMLDS D16-26; TKI-LSH (Topconsortium Kennis en Innovatie-Life Sciences & Health) grant RELOAD, EMC-LSH19002; Medical Delta program \"Regenerative Medicine 4D\"; China Scholarship Council No. 201706230252.

Clonorchiasis caused by Clonorchis sinensis is a mainly foodborne parasitic disease. It can lead to hepatobiliary duct inflammation, fibrosis, obstructive jaundice, liver cirrhosis, and even cholangiocarcinoma. Interleukin (IL)-10 is an immune-regulatory cytokine which plays an immunosuppressive role during infection. Our previous study found that IL-10 was increased in mice with C. sinensis infection. However, the role and mechanism of IL-10 playing in hepatobiliary injury induced by C. sinensis infection remain unknown. Herein, Il10+/+ mice and Il10+/- C57BL/6J mice were infected with C. sinensis. It was found that IL-10 deficiency aggravated biliary hyperplasia and exacerbated periductal fibrosis induced by C. sinensis infection. Moreover, IL-10 deficiency increased CD4+T cells and CD8+T cells but not macrophages in the liver of mice with infection. There were no apparent differences in Th1 and Treg cells between Il10+/+ and Il10+/- mice infected with C. sinensis. However, the proportion of Th17 cells in CD4+T cells in Il10+/- infected mice was significantly higher than that in Il10+/+ infected mice. IL-10 deficiency also enhanced the increase of Th17 cells induced by ESPs stimulation in vitro. Taken together, our results suggest that IL-10 plays a protective role in hepatobiliary injury in C57BL/6J mice induced by C. sinensis infection via inhibiting Th17 cells, which could deepen our understanding of the immunopathology of clonorchiasis.

BACKGROUND: Clonorchiasis caused by Clonorchis sinensis is a zoonotic parasitic disease characterized by cholangitis, biliary proliferation, biliary fibrosis, and even cholangiocarcinoma. Our previous study showed that the expression of interleukin (IL)-33 is increased in both humans and mice infected by C. sinensis, suggesting that IL-33 is potentially involved in the pathogenesis of clonorchiasis. However, the roles and potential mechanism of IL-33 underlying remain unknown.
METHODS: Wild-type (WT) and IL-33 knockout (KO) mice (BALB/c female mice) were orally infected with 45 metacercariae of C. sinensis for 8 weeks. Biliary injuries and fibrosis were extensively evaluated. Hepatic type II cytokines (IL-4, IL-13, and IL-10) were detected by ELISA.
RESULTS: For wild-type mice, we found that the mice infected with C. sinensis showed severe biliary injuries and fibrosis compared with the normal mice that were free from worm infection. In addition, the levels of type II cytokines such as IL-4, IL-13, and IL-10 in infected wild-type mice were significantly higher than in the control mice without infection (P < 0.05). However, IL-33 deficiency (IL-33 KO) prevents the augmentation of biliary injuries and fibrosis caused by C. sinensis infection. Furthermore, the increased levels of these type II cytokines induced by worm infection were also reversed in IL-33 KO mice.
CONCLUSIONS: Our present study demonstrates that IL-33 contributes to the pathogenesis of C. sinensis-induced biliary injuries and repair, which can potentially orchestrate type 2 responses. These findings highlight the pathophysiological role of IL-33 in the progression of clonorchiasis.

UNASSIGNED: Every year, worldwide, the celebration for patient safety is carried out; since about 2.6 million people are documented who die each year from events that can potentially be avoided during their medical care, it is even estimated that around 15% of hospital costs can be attributed to treatment resulting in patient safety. As an important part of its dissemination in the medical-surgical community, we present the following article in relation to the critical vision of safety in the bile duct, promoted and published initially by Dr Steven Strasberg, which aims to reduce the number of complications during laparoscopic cholecystectomies.
UNASSIGNED: A bibliographic search was carried out in PubMed, Medline, Clinical Key, and Index Medicus. From May 2020 to July 2021 in Spanish and English with the following.
UNASSIGNED: Strasberg\'s critical view is a proposed strategy to minimize the risk to zero during laparoscopic gallbladder surgery. It consists of obtaining a plane in which the surgeon can visualize the anatomical structures that make up the bile duct, as well as its irrigation and drainage. Being able to clearly observe these structures allows the surgeon to cut freely and safely to avoid bile duct injuries which are not so uncommon during this procedure.
UNASSIGNED: Montalvo-Javé EE, Contreras-Flores EH, Ayala-Moreno EA, et al. Strasberg\'s Critical View: Strategy for a Safe Laparoscopic Cholecystectomy. Euroasian J Hepato-Gastroenterol 2022;12(1):40-44.

In recent years, significant progress has been made in the field of liver machine perfusion. Many large transplant centers have implemented machine perfusion strategies in their clinical routine. Normothermic machine perfusion (NMP) is primarily used to determine the quality of extended criteria donor (ECD) organs and for logistical reasons. The vast majority of studies, which assessed the viability of perfused grafts, focused on hepatocellular injury. However, biliary complications are still a leading cause of post-transplant morbidity and the need for re-transplantation. To evaluate the extent of biliary injury during NMP, reliable criteria that consider cholangiocellular damage are needed. In this review, different approaches to assess damage to the biliary tree and the current literature on the possible effects of NMP on the biliary system and biliary injury have been summarized. Additionally, it provides an overview of novel biomarkers and therapeutic strategies that are currently being investigated. Although expectations of NMP to adequately assess biliary injury are high, scant literature is available. There are several biomarkers that can be measured in bile that have been associated with outcomes after transplantation, mainly including pH and electrolytes. However, proper validation of those and other novel markers and investigation of the pathophysiological effect of NMP on the biliary tree is still warranted.

Biloma is an intrahepatic or extrahepatic collection of bile within the abdominal cavity. It can occur spontaneously, or as a result of trauma to the biliary tree. The clinical presentation can be variable and non-specific. Early diagnosis is crucial given the high mortality rate. Diagnostic modalities include abdominal ultrasound, hepatobiliary scintigraphy, computerized tomography (CT), and magnetic resonance imaging (MRI). Treatment options include interventional radiology (IR)-guided drainage, endoscopic drainage, or surgical drainage with a bile leak repair. We report a case of a middle-aged non-cirrhotic patient who presented with abdominal pain and was noted to have extensive portal vein thrombosis. She underwent transjugular intrahepatic portosystemic shunt (TIPS) with thrombectomy and the hospital course was complicated by elevated liver enzymes and found to have intrahepatic biloma requiring IR-guided drainage.