Discrimination of Etiologically Different Cholestasis by Modeling Proteomics Datasets.

Cholestasis is characterized by disrupted bile flow from the liver to the small intestine. Although etiologically different cholestasis displays similar symptoms, diverse factors can contribute to the progression of the disease and determine the appropriate therapeutic option. Therefore, stratifying cholestatic patients is essential for the development of tailor-made treatment strategies. Here, we have analyzed the liver proteome from cholestatic patients of different etiology. In total, 7161 proteins were identified and quantified, of which 263 were differentially expressed between control and cholestasis groups. These differential proteins point to deregulated cellular processes that explain part of the molecular framework of cholestasis progression. However, the clustering of different cholestasis types was limited. Therefore, a machine learning pipeline was designed to identify a panel of 20 differential proteins that segregate different cholestasis groups with high accuracy and sensitivity. In summary, proteomics combined with machine learning algorithms provides valuable insights into the molecular mechanisms of cholestasis progression and a panel of proteins to discriminate across different types of cholestasis. This strategy may prove useful in developing precision medicine approaches for patient care.

Percutaneous biliary stent removal for benign biliary stricture post hepaticojejunostomy.

This case report presents the percutaneous extraction of a biliary stent in a patient with a history of liver transplant and Whipple procedure, suffering from benign biliary stricture post hepaticojejunostomy. After failed management with conventional benign biliary protocol, a fully covered WallFlex biliary stent was percutaneously placed and later removed using a balloon catheter technique. The procedure demonstrated anastomosis patency without complications, providing a drain-free option for complex anatomy where endoscopic management was not feasible. This case contributes valuable insights to the limited literature on percutaneous stent removal for benign biliary strictures, emphasising the importance of considering alternative approaches in challenging clinical scenarios.

Perioperative outcomes after open biliary bypass for malignant biliary obstruction (MBO) in resource-limited setups; a multicenter prospective cohort study, 2023.

INTRODUCTION: Obstructive jaundice is the most common symptom of malignant diseases of the extrahepatic biliary system and necessitates either non-operative or operative biliary bypass. Because of percutaneous and endoscopic approaches, the use of palliative surgical procedures has decreased in recent years. However, in resource-limited situations, open biliary bypasses remain a viable option. This study aimed to identify factors associated with adverse perioperative outcomes following open biliary bypass. METHODS: From June 2022 to May 2023, 69 patients underwent open biliary bypass for malignant biliary obstruction. Postoperative morbidity and mortality within 30 days of surgery were assessed. A Kaplan-Meier was used for categorical variables, and a log-rank test was used to determine the statistically significant difference between variables. A Cox regression analysis was conducted to identify factors associated to time to develop complications. RESULTS: The hazard of developing complications among those with preoperative cholangitis was 2.49 times higher than those without preoperative cholangitis (HR 2.49, 95% CI [1.06, 5.84]). For every hour increment in the length of surgery, the hazard of getting complications increased by 2.47 times (HR 2.47, 95% CI [1.28, 4.77]). As serum bilirubin increased by 1 mg/dl, the hazard of developing complications increased by 14% (HR 1.14, 95% CI [1.03, 1.17]). CONCLUSION: Patients who had long operation times, preoperative cholangitis, and elevated total bilirubin levels are at increased risk for poor perioperative outcomes. Clinicians may use these results to optimize these patients to decrease their elevated risk of serious morbidity and mortality.

Safety of skipping the tract dilation step for EUS-guided biliary drainage in patients with unresectable malignant biliary obstruction (with video).

BACKGROUND: Thin delivery system stents can be inserted directly without the need for a tract dilation step and are expected to reduce bile leakage during endoscopic ultrasound-guided biliary drainage (EUS-BD). The present study retrospectively compared the safety and efficacy of EUS-BD using a thin metal stent (< 7.5 Fr) with those of EUS-BD using a conventional stent (≥ 7.5 Fr). METHODS: The present study enrolled 112 patients who underwent EUS-BD using metal stents for unresectable malignant biliary obstruction between April 2016 and July 2022. The primary endpoint was the rate of adverse events (AEs). The secondary endpoints were clinical success rate, procedure time, procedure success rate in the absence of the tract dilation step, recurrent biliary obstruction rate, time to biliary obstruction, and overall survival. Risk factors associated with early AEs were also evaluated. RESULTS: The rate of early AEs was significantly lower (12% vs. 35%, P = 0.013) and the procedure success without the tract dilation step was significantly higher (82% vs. 33%, P < 0.001) in the thin than in the conventional delivery system stent group. None of the other secondary endpoints differed significantly between the two groups. Multivariate analysis showed that employing the tract dilation step during EUS-BD was a significant independent risk factor for early AEs (skipping vs. employing; HR, 9.66; 95% CI, 1.13-83.0, P = 0.028). CONCLUSION: Employing the tract dilation step during EUS-BD was a significant risk factor for early AEs. Metal stents with a delivery diameter < 7.5 Fr can be inserted directly without the tract dilation step, resulting in lower early AE rates.

Percutaneous placement of a retrievable fully covered metal stent with anchoring flaps for the treatment of biliary anastomotic stricture following LDLT.

To investigate the outcomes following percutaneous placement of a retrievable fully covered self-expanding metal stent (fcSEMS) with anchoring flaps at proximal and distal ends for the treatment of biliary anastomotic strictures following living-donor liver transplantation (LDLT). We retrospectively reviewed the medical records of nine patients who underwent this procedure at our centre between April 2020 and March 2021. Percutaneous stent placement was technically successful in 100% patients, and all stents were successfully retrieved. No proximal or distal stent migration or occlusion was observed during the mean (±SD) stent indwelling period of 191(± 77) days. Clinical success was 89%. There was one major bleeding complication related to the biliary approach and one minor stent-related complication of calculus/sludge. During the mean (±SD) follow-up period of 595 ± 207 days after stent retrieval, only one patient developed recurrent clinical biliary stricture and symptoms. Percutaneous placement of a retrievable fcSEMS with anchoring flaps is safe and feasible for the treatment of biliary anastomotic strictures following LDLT.

Factors affecting survival in patients undergoing percutaneous transhepatic biliary drainage for malignant biliary obstruction.

OBJECTIVE: The general approach to malignant biliary obstruction (MBO) is to provide drainage in all patients with jaundice. However, the procedure is often palliative, and its contribution to survival is debated. This study aimed to investigate prognostic factors in patients undergoing percutaneous transhepatic biliary drainage (PTBD) for MBO. PATIENTS AND METHODS: All laboratory values were divided into two groups based on median values: low and high. Chi-square analysis was performed for dichotomous data. The time from the PTBD procedure to the date of death or last follow-up was considered overall survival (OS). Univariate and multivariate analyses were calculated using the Cox regression model. RESULTS: A total of 152 patients were included in the study, of whom 84 (55.3%) were male. The median OS was 71 ± 12.6 days (95% CI: 46.3-95.7). The 1, 3, 6, and 12-month OS rates were 74.3%, 45.2%, 29.2%, and 13%, respectively. In the multivariate analysis, comorbidity (p=0.029), Eastern cooperative oncology group performance status (ECOG PS) (p=0.007), pre-PTBD albumin (p=0.025), post-PTBD aspartate aminotransferase (p=0.025), chemo naive (p<0.001), and post-PTBD chemotherapy (CT) (p=0.01) were found to be independent prognostic factors. CONCLUSIONS: In patients with poor prognosis MBO, the decision for PTBD should be made multidisciplinarily, taking into consideration ECOG PS, comorbidities, albumin levels, and prior CT status.

A Novel Method of Calculating the Drained Liver Volume Using a 3D Volume Analyzer for Biliary Drainage of Unresectable Malignant Hilar Biliary Obstruction.

OBJECTIVES: In patients with unresectable malignant hilar biliary obstruction (UMHBO), drainage of ≥ 50% liver volume correlates with better clinical outcomes. Accurately measuring the liver volume to be drained by biliary stents is required. We aimed to develop a novel method for calculating the drained liver volume (DLV) using a 3D volume analyzer (3D volumetry), and assess the usefulness for drainage in patients with UMHBO. METHODS: Three-dimensional volumetry comprises the following steps: (1) manual tracing of bile duct using 3D imaging system; (2) 3D reconstruction of bile duct and liver parenchyma; and (3) calculating DLV according to the 3D distribution of bile ducts. Using 3D volumetry, we reviewed data of patients who underwent biliary drainage for UMHBO, calculated the DLV, and determined the association between DLV and biliary drainage outcome. RESULTS: There were 104 eligible cases. The mean DLV was 708 ± 393 ml (53% ± 21%). and 65 patients (63%) underwent drainage of ≥50% liver volume. The clinical success rate was significantly higher in patients with DLV ≥ 50% than in patients with DLV < 50% (89% vs. 28%, P < 0.001). The median time to recurrence of biliary obstruction (TRBO) and survival time were significantly longer in patients with DLV ≥ 50% than in patients with DLV < 50% (TRBO, 292 vs. 119 days, P = 0.03; survival, 285 vs. 65days, P = 0.004, log-rank test, respectively). CONCLUSIONS: Three-dimensional volumetry, a novel method to calculate DLV accurately according to bile duct distribution was useful for drainage in UMHBO patients.

Update on the diagnosis and management of neonatal intrahepatic cholestasis caused by citrin deficiency: Expert review on behalf of the Asian Pan-Pacific Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

Citrin deficiency is an autosomal recessive metabolic liver disease caused by mutations in the SLC25A13 gene. The disease typically presents with cholestasis, elevated liver enzymes, hyperammonemia, hypercitrullinemia, and fatty liver in young infants, resulting in a phenotype known as "neonatal intrahepatic cholestasis caused by citrin deficiency" (NICCD). The diagnosis relies on clinical manifestation, biochemical evidence of hypercitrullinemia, and identifying mutations in the SLC25A13 gene. Several common mutations have been found in patients of East Asian background. The mainstay treatment is nutritional therapy in early infancy utilizing a lactose-free and medium-chain triglyceride formula. This approach leads to the majority of patients recovering liver function by 1 year of age. Some patients may remain asymptomatic or undiagnosed, but a small proportion of cases can progress to cirrhosis and liver failure, necessitating liver transplantation. Recently, advancements in newborn screening methods have improved the age of diagnosis. Early diagnosis and timely management improve patient outcomes. Further studies are needed to elucidate the long-term follow-up of NICCD patients into adolescence and adulthood.