Biliary Research Articles

063. Characteristics and Predisposing Factors of Bile Duct Injury in Hasan Sadikin General Hospital

Background: Iatrogenic bile duct injuries (BDI) are associated with fatal complications and increased mortality. Bile duct injuries can be caused by imprecise bile duct cutting, dislodged surgical clips, tearing or obstruction by fibrosis as a result of thermal injury by electrocautery resulting in biliary leakage and/or stricture. The aim of this study is to identify characteristics and predisposing factors of bile duct injury in our center. Methods: This study is a cohort retrospective study, with 42 cases of iatrogenic BDI following cholecystectomy (after both open and laparoscopic approaches); both happened in or were referred to Hasan Sadikin Hospital from September 2023 to September 2024. Patients were classified according to age, gender, BMI, Strasberg – Bismuth classification, laboratory values, and imaging findings. Results: In this study, there were 43 subjects, with majority of subjects aged ?40 years old (58%). There was no difference in gender, with 22 males and 21 females. The mean BMI was 26.1 ± 5.1 kg/m2. Majority of the cases were type E2 Strasberg – Bismuth classification (76.7%). This study found age ?40 years old (p value = 0.00), abnormal preoperative liver function (p value = 0.01), and gallbladder wall thickening (p value = 0.01) as significant predisposing factors of BDI. Conclusion: Age ?40 years old, abnormal preoperative liver function, and gallbladder wall thickening are significant predisposing factors of BDI. Data of anatomical variations and surgeon’s expertise should be beneficial for improvement of future studies.

Taurocholic acid represents an earlier and more sensitive biomarker and promotes cholestatic hepatotoxicity in ANIT-treated rats.

Bile acid homeostasis is crucial for the normal physiological functioning of the liver. Disruptions in bile acid profiles are closely linked to the occurrence of cholestatic liver injury. As part of our diagnostic and therapeutic approach, we aimed to investigate the disturbance in bile acid profiles during cholestasis and its correlation with cholestatic liver injury. Before the occurrence of liver injury, alterations in bile acid profiles were detected in both plasma and liver between 8 and 16 h, persisting up to 96 h. TCA, TCDCA, and TUDCA in the plasma, as well as TCA, TUDCA, TCDCA, TDCA, TLCA, and THDCA in the liver, emerged as early sensitive and potential markers for diagnosing ANIT-induced cholestasis at 8-16 h. The distinguishing features of ANIT-induced liver injury were as follows: T-BAs exceeding G-BAs and serum biochemical indicators surpassing free bile acids. Notably, plasma T-BAs, particularly TCA, exhibited higher sensitivity to cholestatic hepatotoxicity compared with serum enzyme activity and liver histopathology. Further investigation revealed that TCA exacerbated ANIT-induced liver injury by elevating liver function enzyme activity, inflammation, and bile duct proliferation and promoting the migration of bile duct epithelial cell. Nevertheless, no morphological changes or alterations in transaminase activity indicative of liver damage were observed in the rats treated with TCA alone. Additionally, there were no changes in bile acid profiles or inflammatory responses under physiological conditions with maintained bile acid homeostasis. In summary, our findings suggest that taurine-conjugated bile acids in both plasma and liver, particularly TCA, can serve as early and sensitive markers for predicting intrahepatic cholestatic drugs and can act as potent exacerbators of cholestatic liver injury progression. However, exogenous TCA does not induce liver injury under physiological conditions where bile acid homeostasis is maintained.

Gallstones increase the risk of nonalcoholic fatty liver: A case-control study.

Nonalcoholic fatty liver disease (NAFLD) and gallstones are generally seen together, and many of the risk factors for fatty liver and gallstones are common and similar. Therefore, this study aims to investigate the relationship between NAFLD and gallstones. This case-control study was conducted in patients referred to Imam Khomeini and Golestan hospitals of Ahvaz University of Medical Sciences in 2023, whose ultrasound showed fatty liver. Patients who were diagnosed with NAFLD by ultrasound were considered as the case group, and patients who did not have diagnostic findings of fatty liver in ultrasound were considered as the control group. Finally, the information recorded in the checklists was statistically analyzed using SPSS version 26 (SPSS Inc.). Three hundred patients were included in our study, 150 as cases and 150 as controls. There was no significant difference between the groups in terms of gender and age (gender P-value: 0.817/age P-value: 0.102). A statistically significant relationship was found between obesity, diabetes mellitus (DM), the presence of gallstones, and NAFLD (weight p-value < 0.001/DM p-value < 0.001/gallstones P-value: 0.03). In addition, based on binary logistic regression analysis, the presence of gallstones increases the odds of NAFLD by 2.33 times (P-value: 0.035). Furthermore, having DM and increasing each BMI unit increases the odds of NAFLD by 16 times and 30%, respectively (BMI p-value < 0.001/DM p-value < 0.001). Based on the results of our study, gallstones are an important risk factor for NAFLD. The possible mechanisms are the existence of common risk factors between gallstones and NAFLD and the reduction of motility and flow of bile in the bile ducts with the presence of gallstones.

Hepatoprotective and neuroprotective effects of quinacrine against bile duct ligation-induced hepatic encephalopathy in rats: Role of bone morphogenetic proteins signaling

AimsThis study aimed to assess the potential protective effect of quinacrine, an FDA approved antimalarial drug with reported anti-inflammatory effects, on hepatic encephalopathy (HE) in a bile duct ligation (BDL) experimental model and to investigate the mechanisms responsible for this effect, namely those associated with the liver-brain axis, particularly, bone morphogenetic protein 2 (BMP2) signaling. Materials and methodsFive groups of rats were selected at random: sham, BDL, (BDL+ quinacrine 5), (BDL+ quinacrine 10), and (quinacrine 10 + sham). Daily Intraperitoneal (I.P.) administration of quinacrine was initiated on the surgery day and continued for 28 days. Key findingsResults showed that rats that underwent BDL exhibited marked elevation of serum liver enzymes, ammonia, total bilirubin, together with oxidative stress, inflammation, dysregulated farnesoid x receptor (FXR), dysregulated BMP2 signaling and escalated fibrotic markers indicating hepatotoxicity, cholestasis and fibrosis. Besides, neurotoxicity was detected as manifested by cognitive deficits and dysregulation of hippocampal FXR, BMP2 signaling, WNT3A signaling, brain derived neurotrophic factor (BDNF), phospholipase A2 (PLA2) and glial fibrillary acidic protein (GFAP). In contrast, co-treatment with quinacrine mitigated BDL-induced hepatotoxicity, cholestasis, fibrosis, and neurotoxicity. Notably, quinacrine improved learning and memory and restored FXR, BMP2 signaling in the liver and hippocampus. In addition, quinacrine restored hippocampal WNT3A signaling, BDNF, whereas it downregulated expression of hippocampal PLA2 and GFAP. SignificanceThese findings demonstrated implication of BMP2 signaling in the molecular process of BDL-induced HE and proposed that quinacrine has potential hepatoprotective and neuroprotective properties against HE.

Clinical significance of CA 19-9 elevation during postoperative surveillance for extrahepatic bile duct cancer: a nomogram-based approach for the prediction of short-term recurrence

BackgroundThis study aimed to assess the significance of elevated carbohydrate antigen (CA) 19-9 in postoperative surveillance of extrahepatic bile duct cancer and to identify short-term recurrence predictors. MethodsThis retrospective study included patients with elevated CA 19-9 post-curative surgery. Patients were categorized into positive and negative CT groups based on the detection of recurrence at CA 19-9 elevation. Short-term recurrence was defined as recurrence within 6 months in the negative CT group. We identified the factors associated with short-term recurrence and devised a predictive nomogram. ResultsAmong the 190 patients, 91 (47.9%) exhibited tumor recurrence with CA 19-9 elevation (CT-positive group), whereas 99 (52.1%) showed no recurrence (CT-negative group). In the CT-negative group (n=99), 22 (22.2%) experienced short-term tumor recurrence within 6 months. Preoperative CA 19-9 (odds ratio [OR]: 1.5, p=0.016), postoperative CA 19-9 (OR: 1.9, p=0.047), adjuvant treatment (OR: 3.5, p=0.032), and the absence of inflammation (OR: 3.5, p=0.045) were predictors of short-term recurrence. The area under the curve of the nomogram was 0.80 (95% CI: 0.69–0.90). DiscussionDespite elevated CA 19-9 levels, approximately 50% of patients exhibited no recurrence during postoperative surveillance for extrahepatic bile duct cancer. Factors influencing short-term recurrence encompass pre- and postoperative CA 19-9, adjuvant treatment, and inflammatory status.

Postoperative continuation of antibiotic prophylaxis beyond 24 h is unnecessary for abdominal surgeries in children and neonates

PurposeDespite recent WHO recommendations, antibiotic prophylaxis is routinely continued for several days after surgery. We conducted a retrospective study to evaluate the safety and efficacy of antibiotic prophylaxis cessation within 24 h after abdominal surgeries MethodsWe retrospectively reviewed the charts of patients who underwent 3 representative gastrointestinal surgeries (1; transumbilical small bowel procedure for intestinal atresia or stenosis, 2; extrahepatic bile duct resection, and hepaticojejunostomy for congenital biliary dilatation, 3; stoma closure for intestinal perforation, anorectal malformation, or inflammatory bowel disease) at our institution between 2011 and 2023. The demographic data collected included age, preoperative hemoglobin level, albumin level, body mass index, and ASA class. Intraoperative and postoperative data were also collected. The patients were divided into 2 groups according to the duration of perioperative antibiotics (‘within 24 h’ and ‘beyond 24 h’), and the incidence of superficial incisional SSI (siSSI) was compared between the 2 groups in each procedure ResultsDuring the study period, 25 cases underwent transumbilical small bowel procedure, 23 cases underwent hepaticojejunostomy, and 45 cases underwent stoma closure. The preoperative care bundle including bowel preparation, cleansing, and operative procedures has not changed during the study period. First- and third-generation cephalosporins were administered to all the patients. All patients received their first single dose of antibiotics within 60 min before the skin incision. In particular, 14 patients who underwent small-bowel procedures received only a single dose. The SSI rates for small bowel procedures, hepaticojejunostomy, and stoma closure were 0%, 4.4%, and 4.4%, respectively. No SSIs were observed in any of the procedures in the 'within 24 h' group ConclusionBased on our study, we conclude that ≤24 h of postoperative continuation of antibiotic prophylaxis is sufficient for siSSI prevention in hepaticojejunostomy and stoma closure. Additionally, single-dose antibiotic prophylaxis is adequate for neonatal small bowel procedures.

New criteria for preoperative liver function assessment with safety margins to avoid postoperative mortality during liver resection for hilar cholangiocarcinoma.

BackgroundDespite recent medical advancements, surgery for hilar cholangiocarcinoma is associated with high complication and mortality rates. This may be partly attributed to the absence of established preoperative liver evaluation criteria for safe surgery. This study aimed to propose a reliable indicator for safe and well-planned management of major hepatectomy with extrahepatic bile duct resection. MethodsWe included 150 patients who underwent major hepatectomy with extrahepatic bile duct resection between 2013 and 2021 in Japan. The risk factors for post-hepatectomy liver failure (PHLF) were retrospectively analyzed. ResultsPHLF was observed in 24 (16.0%) patients who underwent major hepatectomy with extrahepatic bile duct resection. In the multivariate analysis, the identified risk factors for PHLF were the ratio of future remnant liver volume to total liver volume (FRLV/TLV) ≤ 42% and indocyanine green clearance fraction of the future remnant liver (ICGK-F) ≤ 0.07. Patients with these two factors were significantly associated with PHLF compared with those with either one or none of the risk factors (60.0% vs 15.1% and 8.1%, respectively). ConclusionsThe combinational use of ICGK-F and FRLV/TLV is useful for preoperative liver function assessment with a safety margin to avoid PHLF and postoperative mortality in hepatectomy for hilar cholangiocarcinoma.

Lessons learned from implementing laparoscopic common bile duct exploration at a safety net hospital

BackgroundMounting evidence favors one-stage laparoscopic cholecystectomy with common bile duct exploration over endoscopic retrograde cholangiopancreatography with cholecystectomy for choledocholithiasis. However, laparoscopic cholecystectomy with common bile duct exploration remains underused. In 2020, our center initiated a laparoscopic cholecystectomy with common bile duct exploration program for choledocholithiasis. This study compares the experience and outcomes of laparoscopic cholecystectomy with common bile duct exploration compared with endoscopic retrograde cholangiopancreatography with cholecystectomy at a safety net hospital. MethodsThis single-center, retrospective study analyzed data from 179 patients admitted with choledocholithiasis from 2019 to 2023. Demographics, preoperative investigations, intraoperative details, and postoperative outcomes were evaluated. ResultsThe study included 179 patients (55.6 ± 21.0 years, 66% female) with American Society of Anesthesiologists Physical Status Classification System score III (II–III) and body mass index 29 kg/m2 (25.8–35.5 kg/m2). Of these, 148 underwent endoscopic retrograde cholangiopancreatography with cholecystectomy and 31 underwent laparoscopic cholecystectomy with common bile duct exploration. Demographic and preoperative data were similar between groups. Laparoscopic cholecystectomy with common bile duct exploration achieved a 74.2% success rate. Laparoscopic cholecystectomy with common bile duct exploration’s average operative time was 180 (139–213) minutes, with a 3.2% postoperative bile leak and 35.4% requiring postoperative ERCP. Median lengths of stay were 3 (1–4) for laparoscopic cholecystectomy with common bile duct exploration and 4 days (3–7) for endoscopic retrograde cholangiopancreatography with cholecystectomy (Z = –3.16, P = .002). The number of readmissions were 1.2 ± 0.4 for laparoscopic cholecystectomy with common bile duct exploration and 1.9 ± 1.3 for endoscopic retrograde cholangiopancreatography with cholecystectomy (t = 1.43, P = .08). Additional procedures for choledocholithiasis were performed in 36% of laparoscopic cholecystectomy with common bile duct exploration and 79% of ERCP + LC cases (χ2 = 21.7, P < .0001). ConclusionThe study highlights challenges in implementing laparoscopic cholecystectomy with common bile duct exploration at a safety net hospital. Results support laparoscopic cholecystectomy with common bile duct exploration over endoscopic retrograde cholangiopancreatography, with cholecystectomy, with shorter stays, fewer readmissions, and fewer additional procedures reported. Laparoscopic cholecystectomy with common bile duct exploration remains underused, with only 17.3% of patients who underwent one-stage laparoscopic cholecystectomy with common bile duct exploration. Further research is needed for laparoscopic cholecystectomy with common bile duct exploration’s expansion as the superior choledocholithiasis treatment.

MAPK signaling pathway induced LOX-1+ polymorphonuclear myeloid-derived suppressor cells in biliary atresia

Biliary atresia (BA) is a severe pediatric liver disease characterized by progressive bile duct destruction and fibrosis, leading to significant liver damage and frequently necessitating liver transplantation. This study elucidates the role of LOX-1+ polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in BA pathogenesis and assesses their potential as non-invasive early diagnostic biomarkers. Using flow cytometry, immunofluorescence, and molecular profiling, we analyzed the expression and activity of these cells in peripheral blood and liver tissues from BA patients and controls. Our findings reveal a significant increase in the frequencies and function of LOX-1+PMN-MDSCs in BA patients, along with MAPK signaling pathway upregulation, indicating their involvement in disease mechanisms. Additionally, the frequencies of LOX-1+PMN-MDSC in peripheral blood significantly positively correlate with liver function parameters in BA patients, demonstrating diagnostic performance comparable to traditional serum markers. These findings suggest that LOX-1+PMN-MDSCs contribute to the immunosuppressive environment in BA and could serve as potential diagnostic targets.

056. Impacted CBD Stones in Ampula Vater Evacuated by Transduodenal Approach in A 48-year-old Patient at Prof. Dr. IGNG Ngoerah Hospital in 2024

Background: Cholecystolithiasis and choledocholithiasis are common biliary disorders that can lead to significant complications if left untreated. Among these complications, the formation of impacted CBD stones, particularly at the Ampulla of Vater, poses a unique clinical challenge. The Ampulla of Vater is the anatomical site where the common bile duct (CBD) and pancreatic duct converge, and its obstruction can lead to biliary colic, cholangitis, or pancreatitis. Urgent stone removal is critical for improving the patient’s condition. Case: A 48-year-old male patient presents to the emergency department with right upper abdominal pain since 10 days ago accompanied with icteric sclera since 10 days ago. There was nausea and vomiting when eating high-fat foods. The stools were brownish in color, the urine color was similar to tea color. The patient regularly takes UDCA 3 x 250 mg IO, simvastatin 1 x 20mg IO, curcuma 3 x1 tab IO, lansoprazole 2 x 30mg IO. Physical examination showed icteric eyes, jaundice, liver enlargement 2 fingers below costae arch with positive Murphy's sign. Complete blood examination showed leukocytosis, decreased hemoglobin, hypokalemia, as well as increased direct bilirubin, total bilirubin, and indirect bilirubin. BOF result showed sentinel loop on the right umbilical region suspected inflammatory process. MRI impression of choledocholithiasis causing dilatation of EHBD and IHBD proximal aspect without signs of cholangitis, hepatomegaly, simple cyst of left kidney (Bosniak I). Abdominal ultrasound with the conclusion of cholecystitis with dilatation and thickening of the ductus cysticus wall suspicious of inflammation, dilatation of the right and left IHBD, common hepatic duct, to the proximal common biliary duct, the presence of distal obstruction cannot be evaluated because it is covered by intestinal shadows, mild prostatic hypertrophy accompanied by prostate calcification. After Cholecystectomy and Explore CBD transduodenal, the patient was placed with thoracic drain with good outcome. Conclusion: The transduodenal approach to evacuating impacted CBD stones at the Ampulla of Vater is a valuable technique that can yield excellent outcomes in select cases. This case report underscores the importance of a tailored approach based on individual patient anatomy and stone characteristics.

Liver transcriptome analysis reveals PSC-attributed gene set associated with fibrosis progression

BackgroundPrimary Sclerosing Cholangitis (PSC) is a chronic heterogenous cholangiopathy with unknown etiology where chronic inflammation of the bile ducts leads to multifocal biliary strictures and biliary fibrosis with consecutive cirrhosis development. We here aimed to identify a PSC-specific gene signature associated with biliary fibrosis development. MethodsWe performed RNA-sequencing of 47 liver biopsies from people with PSC (n = 16), primary biliary cholangitis (PBC, n = 15), and metabolic dysfunction-associated steatotic liver disease (MASLD, n = 16) with different fibrosis stages to identify a PSC-specific gene signature associated with biliary fibrosis progression. For validation, we compared an external transcriptome data set of liver biopsies from people with PSC (n = 73) with different fibrosis stages (DOI: 10.1002/hep.31488; baseline samples from NCT01672853). ResultsDifferential gene expression analysis of the liver transcriptome from PSC patients with advanced versus early fibrosis revealed 431 genes associated with fibrosis development. Of those, 367 were identified as PSC-associated when compared to PBC or MASLD. Validation against an external data set of 73 liver biopsies from PSC patients with different fibrosis stages led to a condensed set of 150 (out of 367) DEGs. Cell type specificity assignment of those genes by using published single cell RNA-seq data revealed genetic disease drivers expressed by cholangiocytes (e.g. CXCL1, SPP1), fibroblasts, innate and adaptive immune cells while deconvolution along fibrosis progression of the PSC, PBC, MASLD samples highlighted an early involvement of macrophage- and neutrophil-associated genes in PSC fibrosis. ConclusionWe reveal a PSC-attributed gene signature associated with biliary fibrosis development that may enable the identification of potential new biomarkers and therapeutic targets in PSC-related fibrogenesis. IMPACT AND IMPLICATIONSPrimary sclerosing cholangitis (PSC) is an inflammatory liver disease that is characterized by multifocal inflammation of bile ducts and subsequent biliary fibrosis. Herein, we identify a PSC-specific gene set of biliary fibrosis progression attributing to a uniquely complex milieu of different cell types, including innate and adaptive immune cells while neutrophils and macrophages showed an earlier involvement in fibrosis initiation in PSC in contrast to PBC and MASLD. Thus, our unbiased approach lays an important groundwork for further mechanistic studies for research into PSC-specific fibrosis.

Ginsenoside compound K restrains hepatic fibrotic response by dual-inhibition of GLS1 and LDHA

BackgroundLiver fibrosis is a dynamic process marked by the accumulation of extracellular matrix due to hepatic stellate cells (HSCs) activation. Ginsenoside compound K (CK), a rare derivative of its parent ginsenosides, is known to significantly ameliorate metabolic disorders. PurposeThe aim of this study was to elucidate the protective effects of CK against liver fibrosis with a focus on metabolic regulation. MethodsWe established liver fibrosis models in mice using carbon tetrachloride (CCl4) challenge, bile duct ligation, or a methionine-choline deficient diet, with continuous oral administration of CK at specified doses and intervals. Simultaneously, we examined the impact of CK on metabolic regulation in cultured HSCs and investigated the associated mechanisms. ResultsCK was found to alleviate liver injury and curb fibrotic responses in mouse models, as well as decrease elevated levels of liver enzyme. Metabolomic analysis in vitro highlighted the crucial roles of pyruvate and glutamine metabolism in metabolic remodeling. Immunohistochemical staining indicated significantly elevated expressions of lactate dehydrogenase A (LDHA) (p = 0.014) and glutaminase 1 (GLS1) (p = 0.024) in liver cirrhosis patients. Comparable alterations were noted in the liver of model mice and in cultured HSCs. Molecular docking and bio-layer interferometry demonstrated that CK interacts with and inhibits the activities of LDHA and GLS1. As expected, CK attenuated glycolysis and glutaminolysis, reducing HSC growth dependently on lactate and α-ketoglutarate (α-KG). Upon HSC activation, metabolism is reprogrammed with Myc as a key regulator, transcriptionally controlling LDHA, GLS1, and glutamine transporters SLC1A5 and SLC38A5. CK inhibited Myc induction, integrating glycolysis and glutaminolysis regulation to counteract the fibrotic response. ConclusionCK inhibited LDHA and GLS1 activities, thereby inhibiting hepatic fibrosis. These findings offer new insights into the role of ginsenosides in liver protection, especially regarding metabolic disorders.

High-Risk Biliary Anastomosis During Robotic Pancreaticoduodenectomy: Initial Experience with Biodegradable Biliary Stent

Background and Objectives: Biliary fistulas (BFs) occur in approximately 3–8% of patients undergoing pancreaticoduodenectomy (PD), and the bile duct diameter ≤ 5 mm is the most important risk factor. The aim of this study was to evaluate the efficacy of biodegradable biliary stents (BSs) in reducing complications in patients undergoing robotic pancreaticoduodenectomy (RPD) with a bile duct diameter of ≤5 mm. Materials and Methods: A retrospective single-centre observational study was conducted. Patients undergoing RPD after the completion of the robotic biliary anastomosis learning curve were included in this study. Only patients with a bile duct diameter ≤ 5 mm were included in the analysis. A prospectively held database was used. The intraoperative time for biliary anastomosis was extracted from surgical videos. Results: Of 30 patients, 20 received no biliary stent (nBS) and 10 received a biodegradable stent (BS). The decision to use a stent was based on product availability. The median operative time for biliary anastomosis was significantly shorter in the BS group compared to the nBS group, at 15 min versus 24 min (p &lt; 0.001). Three patients in the nBS group developed a BF, whereas none were observed in the BS group. No stent migration was observed in any of the patients. Conclusions: The use of biodegradable biliary stents in high-risk biliary anastomosis in RPD appears to effectively reduce the incidence of BFs and may serve as a viable strategy to mitigate early biliary complications. The use of biodegradable stents facilitates a faster and easier biliary anastomosis. These findings suggest a potential benefit of using biodegradable stents in complex biliary reconstruction. However, larger studies are needed to confirm these results.

Oleanolic acid induces hepatic injury by disrupting hepatocyte tight junction and dysregulation of farnesoid X receptor-mediated bile acid efflux transporters.

Oleanolic acid (OA) is a naturally occurring pentacyclic triterpene compound that has been reported to cause cholestatic liver injury. However, the regulation and pathogenic role of bile acids in OA-induced development of cholestatic liver injury remains largely unclear. Farnesoid X receptor (FXR) is a metabolic nuclear receptor that plays an important role in bile acid homeostasis in the liver by regulating efflux transporters bile salt export pump (BSEP) and multidrug resistance-associated protein 2 (MRP2). The aim of this study was to investigate the effect of OA on hepatocyte tight junction function and determine the role of FXR, BSEP, and MRP2 in the mechanism of impairment of transport of bile acids induced by OA. Both in vivo and in vitro models were used to characterize the OA-induced liver injury. The liquid chromatography-tandem mass spectrometry (LC-MS) was employed to characterize the efflux function of the transporters, and the results showed that OA caused a blockage of bile acids efflux. OA treatment resulted in decreased expression levels of the tight junction proteins zonula occludens-1 and occludin. Immunofluorescence results showed that OA treatment significantly reduced the number of bile ducts and the immunofluorescence intensity. Pretreatment with agonists of FXR and MRP2, respectively, in animal experiments attenuated OA-induced liver injury, while pretreatment with inhibitors of BSEP and MRP2 further aggravated OA-induced liver injury. These results suggest that OA inhibits FXR-mediated BSEP and MRP2, leading to impaired bile acid efflux and disruption of tight junctions between liver cells, resulting in liver damage.

Overexpression of SULT1E1 alleviates salt-processed Psoraleae Fructus-induced cholestatic liver damage

ObjectiveSalt-processed Psoraleae fructus (SPF) is widely used as a phytoestrogen-like agent in the treatment of osteoporosis. However, due to improper clinical use or misuse, resulting in liver damage. In this study, network pharmacology was employed to analyze the mechanism of cholestatic liver damage. An adeno-associated virus overexpressing SULT1E1 (rAAV8-SULT1E1) was constructed and the hepatotoxicity of SPF, psoralen, and isopsoralen was determined. MethodsBy utilizing three databases inclding TCMSP, TCMID, and BATMAN- TCM, the targets of the three databases were summarized, and a total of 45 psoralen compounds were included. Network pharmacology analysis was then performed. The adenoviral vectors were injected into the tail vein of C57BL6 mice to elucidate the role of SULT1E1 in SPF-induced cholestasis-mediated hepatotoxicity in vivo. SPF (10 g/kg), psoralen, and isopsoralen (50 mg/kg each) were intragastrically administered to mice for 30 d. B-ultrasound and samples were collected and examined for follow-up experiments. ResultsA total of 854 targets were predicted for 45 active components, with 151 cholestasis-mediated hepatotoxicity-related disease targets obtained for SPF. A total of 126 pathways were enriched based on KEGG pathway analysis, with the “estrogen signaling pathway” identified as one of the top 20 pathways. In terms of pathological hepatic changes, treated mice had visually swollen hepatocytes, dilated bile ducts, and elevated serum biochemical markers, which were more prominent in mice treated with isopsoralen than in those treated with other compounds. Notably, the overexpression of SULT1E1 could reverse liver damage in each treatment group. B-ultrasound was used to observe the size of the gallbladder in vivo. The size of the gallbladder was found to significantly increase on day 30 after treatment in the SPF-, psoralen-, and isopsoralen-treated groups, especially the SPF group. Compared with the expression levels in the negative control group (rAAV8-empty+con), the expression levels of FXR, Mrp2, Bsep, SULT1E1, SULT2A1, Ntcp, and Nrf2 decreased, whereas those of CYP7a1 and IL-6 increased in the SPF-, psoralen-, and isopsoralen-treated groups. ConclusionThe overexpression of SULT1E1 could alleviate the decreased or increased expression of indicators, indicating that SULT1E1 is an important target gene for SPF-induced liver damage. The severity of liver damage was significantly lower in the rAAV8-SULT1E1 groups than in the rAAV8-empty groups.

064. Overview of Bacterial Patterns and Antibiotic Resistance on Cholangitis Patients at Hasan Sadikin General Hospital from January to December 2023

Background: Cholangitis is a serious infection of the bile ducts that requires prompt treatment, often with antibiotic therapy. Although antibiotic use, especially ceftriaxone and metronidazole, is vital in treatment, antibiotic resistance remains a significant challenge. Unfortunately, data on bacterial resistance patterns in cholangitis patients treated at Doctor Hasan Sadikin Hospital in Bandung is still limited. This study aims to describe the bacterial patterns and antibiotic resistance in cholangitis patients at Doctor Hasan Sadikin General Hospital. Another objective is to assess the effectiveness of ceftriaxone and metronidazole therapy in patients with moderate to severe cholangitis. Methods: This research employed a retrospective descriptive design by collecting data from the medical records of acute cholangitis patients treated at Doctor Hasan Sadikin General Hospital from January to December 2023. A total of 126 patient samples meeting the inclusion criteria were analyzed through blood cultures, and sensitivity tests were conducted against various antibiotics. Data were analyzed using SPSS software. Results: The results showed that Escherichia coli (26.3%) was the most commonly found bacterium, followed by Staphylococcus haemolyticus and Klebsiella pneumoniae (each at 13.2%). The highest resistance was observed against ampicillin (78.9%), while the most effective antibiotic was tigecycline (92.1% sensitivity). Conclusion: In conclusion, ceftriaxone and metronidazole as empiric therapy remains effective for most cholangitis patients, although resistance to certain antibiotics like ampicillin warrants attention. This study highlights the importance of regular monitoring of antibiotic resistance patterns to ensure proper treatment and reduce morbidity and mortality rates among cholangitis patients.

P08 Vanishing bile duct syndrome in haemophagocytic lymphohistiocytosis precipitated by Stevens-Johnson syndrome: a rare case report

P08 Vanishing bile duct syndrome in haemophagocytic lymphohistiocytosis precipitated by Stevens-Johnson syndrome: a rare case report

Perioperative Complications After Pediatric Liver Transplantation-A Retrospective Analysis of 421 Cases.

Due to the low incidence of pediatric liver transplantations, short- and long-term data regarding their outcome, details on early postoperative complications and their risk factors are under-represented in the literature. We retrospectively reviewed 1645 LTx performed at Hannover Medical School between January 2005 and December 2021. Of these, 421 transplantations were performed in 405 pediatric recipients. Univariate and multivariate binary logistic regressions were performed to identify independent risk factors for the onset of selected perioperative complications requiring intervention within the first 30 days following transplantation and their influence on graft and patient survival. Pleural effusions represent the most common postoperative complication observed in 49.4% (n = 208) of cases, followed by vascular complications in 22.6% (n = 95) and biliary complications in 20.0% (n = 84) of cases. Donor age (OR: 1.019; p = 0.010) and recipient age between 3 and 12 years (OR: 1.849; p = 0.008) were identified as independent risk factors for the onset of pleural effusions. Retransplantations within the first year after LTx were necessary in 11.4% of all cases (n = 48). Twenty (4.8%) patients died within the first year after LTx. Pleural effusions requiring postoperative intervention were observed in approximately half of the pediatric recipients. Therefore, the preemptive intraoperative placement of a chest drain under sterile conditions and general anesthesia should be considered. Our data further indicate that a two-stage procedure for biliary reconstruction may be the preferred procedure in patients at risk of early bile duct complications and retransplantation within the first year.

A microsystem for in vivo wireless monitoring of plastic biliary stents using magnetoelastic sensors.

With an interest in monitoring the patency of stents that are used to treat strictures in the bile duct, this paper reports the investigation of a wireless sensing system to interrogate a microsensor integrated into the stent. The microsensor is comprised of a 28-μm-thick magnetoelastic foil with 8.25-mm length and 1-mm width. Magnetic biasing is provided by permanent magnets attached to the foil. These elements are incorporated into a customized 3D polymeric package. The system electromagnetically excites the magnetoelastic resonant sensor and measures the resulting signal. Through shifts in resonant frequency and quality factor, the sensor is intended to provide an early indication of sludge accumulation in the stent. This work focuses on challenges associated with sensor miniaturization and placement, wireless range, drive signal feedthrough, and clinical use. A swine specimen in vivo experiment is described. Following endoscopic implantation of the sensor enabled plastic stent into the bile duct, at a range of approximately 17 cm, the signal-to-noise ratio of ~106 was observed with an interrogation time of 336 s. These are the first reported signals from a passive wireless magnetoelastic sensor implanted in a live animal.

Revised Clinical Practice Guideline of Korean Pancreatobiliary Association for Common Bile Duct Stones: Endoscopic Management of Difficult Common Bile Duct Stones

Difficult common bile duct (CBD) stones are difficult to remove using conventional stone clearance methods such as endoscopic papillary sphincterotomy. In this guideline, we present several recommendations and relevant information on the endoscopic treatment of difficult CBD stones. For the primary treatment of large CBD stones in patients without distal bile duct stricture, we recommend limited endoscopic sphincterotomy followed by endoscopic papillary large balloon dilation. For large CBD stones that are difficult to remove with conventional endoscopic treatment methods, we recommend electrohydraulic or laser lithotripsy under cholangioscopy. Short-term biliary stenting is recommended in patients with CBD stones that are difficult to remove by these methods. Finally, endoscopic treatment via small bowel enteroscopy or percutaneous transhepatic cholangioscopy may be an option in patients with surgically altered anatomy.