EASL Clinical Practice Guidelines on genetic cholestatic liver diseases.

Genetic cholestatic liver diseases are caused by (often rare) mutations in a multitude of different genes. While these diseases differ in pathobiology, clinical presentation and prognosis, they do have several commonalities due to their cholestatic nature. These Clinical Practice Guidelines (CPGs) offer a general approach to genetic testing and management of cholestatic pruritus, while exploring diagnostic and treatment approaches for a subset of genetic cholestatic liver diseases in depth. An expert panel appointed by the European Association for the Study of the Liver has created recommendations regarding diagnosis and treatment, based on the best evidence currently available in the fields of paediatric and adult hepatology, as well as genetics. The management of these diseases generally takes place in a tertiary referral centre, in order to provide up-to-date approaches and expertise. These CPGs are intended to support hepatologists (for paediatric and adult patients), residents and other healthcare professionals involved in the management of these patients with concrete recommendations based on currently available evidence or, if not available, on expert opinion.

Intraduodenal fecal microbiota transplantation ameliorates gut atrophy and cholestasis in a novel parenteral nutrition piglet model.

Total parenteral nutrition (TPN) provides lifesaving nutritional support intravenously; however, it is associated with significant side effects. Given gut microbial alterations noted with TPN, we hypothesized that transferring fecal microbiota from healthy controls would restore gut-systemic signaling in TPN and mitigate injury. Using our novel ambulatory model (US Patent: US 63/136,165), 31 piglets were randomly allocated to enteral nutrition (EN), TPN only, TPN + antibiotics (TPN-A), or TPN + intraduodenal fecal microbiota transplant (TPN + FMT) for 14 days. Gut, liver, and serum were assessed through histology, biochemistry, and qPCR. Stool samples underwent 16 s rRNA sequencing. Permutational multivariate analysis of variance, Jaccard, and Bray-Curtis metrics were performed. Significant bilirubin elevation in TPN and TPN-A versus EN (P < 0.0001) was prevented with FMT. IFN-G, TNF-α, IL-ß, IL-8, and lipopolysaccharide (LPS) were significantly higher in TPN (P = 0.009, P = 0.001, P = 0.043, P = 0.011, P < 0.0001), with preservation upon FMT. Significant gut atrophy by villous-to-crypt ratio in TPN (P < 0.0001) and TPN-A (P = 0.0001) versus EN was prevented by FMT (P = 0.426 vs. EN). Microbiota profiles using principal coordinate analysis demonstrated significant FMT and EN overlap, with the largest separation in TPN-A followed by TPN, driven primarily by Firmicutes and Fusobacteria. TPN-altered gut barrier was preserved upon FMT; upregulated cholesterol 7 α-hydroxylase and bile salt export pump in TPN and TPN-A and downregulated fibroblast growth factor receptor 4, EGF, farnesoid X receptor, and Takeda G Protein-coupled Receptor 5 (TGR5) versus EN was prevented by FMT. This study provides novel evidence of prevention of gut atrophy, liver injury, and microbial dysbiosis with intraduodenal FMT, challenging current paradigms into TPN injury mechanisms and underscores the importance of gut microbes as prime targets for therapeutics and drug discovery.NEW & NOTEWORTHY Intraduodenal fecal microbiota transplantation presents a novel strategy to mitigate complications associated with total parenteral nutrition (TPN), highlighting gut microbiota as a prime target for therapeutic and diagnostic approaches. These results from a highly translatable model provide hope for TPN side effect mitigation for thousands of chronically TPN-dependent patients.

Endoscopic Ultrasound-Guided vs Endoscopic Retrograde Cholangiopancreatography-Guided Biliary Drainage as Primary Approach to Malignant Distal Biliary Obstruction: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Endoscopic ultrasound-guided biliary drainage (EUS-BD) is an alternative to endoscopic retrograde cholangiopancreatography (ERCP)-guided transpapillary drainage in malignant distal biliary obstruction (MDBO). This meta-analysis of randomized controlled trials (RCTs) aims to compare the outcomes of these 2 approaches. METHODS: Electronic databases from January 2005 through December 2023 were searched for RCTs comparing outcomes of EUS-BD and ERCP for treating MDBO. Pooled proportions, risk ratio (RR), and odds ratio were calculated using random-effects models. RESULTS: Five RCTs comprising 519 patients were included in the final analysis. The pooled RR for overall technical success with EUS-BD compared with ERCP was 1.05 (95% confidence interval [CI] = 0.96-1.16, P = 0.246, I2 = 61%) and for clinical success was 0.99 (95% CI = 0.95-1.04, P = 0.850, I2 = 0%). The pooled rate of procedure-related pancreatitis was 7.20% (95% CI = 3.60-13.80, I2 = 34%) in the ERCP group compared with zero in the EUS-BD group. The pooled RR for stent dysfunction with EUS-BD compared with ERCP was 0.48 (95% CI = 0.28-0.83, P = 0.008, I2 = 7%). The weighted mean procedure time was 13.43 (SD = 10.12) minutes for EUS-BD compared with 21.06 (SD = 6.64) minutes for ERCP. The mean stent patency was 194.11 (SD = 52.12) days in the EUS-BD group and 187 (SD = 60.70) days in the ERCP group. DISCUSSION: EUS-BD is an efficient and safe alternative to ERCP in MDBO. An almost nonexistent risk of procedure-related pancreatitis, lower procedure time, and ease of use make this an attractive primary approach to biliary decompression in centers with expertise.

Risk factors and treatment strategies for cholecystitis after metallic stent placement for malignant biliary obstruction: a multicenter retrospective study.

BACKGROUND AND AIMS: Cholecystitis can occur after self-expandable metallic stent (SEMS) placement for malignant biliary obstruction (MBO), but the best treatment option for cholecystitis has not been determined. Here, we aimed to identify the risk factors of cholecystitis after SEMS placement and determine the best treatment option. METHODS: Incidence, treatments, and predictive factors of cholecystitis were retrospectively evaluated in 1084 patients with distal MBO (DMBO) and 353 patients with hilar MBO (HMBO) who underwent SEMS placement at 12 institutions from January 2012 to March 2021. RESULTS: Cholecystitis occurred in 7.5% of patients with DMBO and 5.9% of patients with HMBO. The recurrence rate was significantly lower (P = .043) and the recurrence-free period significantly longer (P = .039) in endoscopic procedures than in percutaneous procedures for cholecystitis treatment. EUS-guided gallbladder drainage (EUS-GBD) was better in terms of technical success, procedure time, and recurrence-free period than endoscopic transpapillary gallbladder drainage. Obstruction across the cystic duct orifice by tumor (P = .015) and by stent (P = .037) were independent risk factors for cholecystitis in DMBO. Cases with multiple SEMS placements (odds ratio [OR], 11; 95% confidence interval [CI], 0.68-190; P = .091) and with gallbladder stones (OR, 2.3; 95% CI ,0.92-5.6; P = .075) had a higher risk for cholecystitis in HMBO. CONCLUSIONS: The incidences of cholecystitis after SEMS placement for DMBO and HMBO were similar. EUS-GBD is the optimal treatment option for patients with cholecystitis after SEMS placement for MBO.

American Society for Gastrointestinal Endoscopy guideline on the role of endoscopy in the management of chronic pancreatitis: summary and recommendations.

This clinical practice guideline from the American Society for Gastrointestinal Endoscopy (ASGE) provides an evidence-based approach for the role of endoscopy in the management of chronic pancreatitis (CP). This document was developed using the Grading of Recommendations Assessment, Development and Evaluation framework. The guideline addresses effectiveness of endoscopic therapies for the management of pain in CP, including celiac plexus block, endoscopic management of pancreatic duct (PD) stones and strictures, and adverse events such as benign biliary strictures (BBSs) and pseudocysts. In patients with painful CP and an obstructed PD, the ASGE suggests surgical evaluation in patients without contraindication to surgery before initiation of endoscopic management. In patients who have contraindications to surgery or who prefer a less-invasive approach, the ASGE suggests an endoscopic approach as the initial treatment over surgery, if complete ductal clearance is likely. When a decision is made to proceed with a celiac plexus block, the ASGE suggests an EUS-guided approach over a percutaneous approach. The ASGE suggests indications for when to consider ERCP alone or with pancreatoscopy and extracorporeal shock wave lithotripsy alone or followed by ERCP for treating obstructing PD stones based on size, location, and radiopacity. For the initial management of PD strictures, the ASGE suggests using a single plastic stent of the largest caliber that is feasible. For symptomatic BBSs caused by CP, the ASGE suggests the use of covered metal stents over multiple plastic stents. For symptomatic pseudocysts, the ASGE suggests endoscopic therapy over surgery. This document clearly outlines the process, analyses, and decision processes used to reach the final recommendations and represents the official ASGE recommendations on the above topics.

Biliary drainage in palliative and curative intent European patients with hilar cholangiocarcinoma and malignant hilar obstruction: a retrospective single center analysis.

BACKGROUND AND AIMS: Relief of cholestasis in hilar cholangiocarcinoma is commonly undertaken in both curative and palliative treatment plans. There are numerous open questions with regard to the ideal biliary drainage strategy - including what constitutes clinical success (CS). In the existing data, curative patients and patients from the Western world are underrepresented. PATIENTS AND METHODS: We performed a retrospective analysis of patients with complex malignant hilar obstruction (Bismuth-Corlette II and higher) due to cholangiocarcinoma who underwent biliary drainage at a German referral center between 2010 and 2020. We aimed to define CS and complication rates and directly compare outcomes in curative and palliative patients. RESULTS: 56 curative and 72 palliative patients underwent biliary drainage. In patients with curative intent, CS was achieved significantly more often regardless of what definition of CS was applied (e.g., total serum bilirubin (TSB) < 2 mg/dl: 66.1% vs. 27.8%, p = < 0.001, > 75% reduction of TSB: 57.1% vs. 29.2%, p = 0.003). This observation held true only when subgroups with the same Bismuth-Corlette stage were compared. Moreover, palliative patients experienced a significantly greater percentage of adverse events (33.3% vs. 12.5%, p = 0.01). Curative intent treatment and TSB at presentation were predictive factors of CS regardless of what definition of CS was applied. The observed CS rates are comparable to published studies involving curative patients, but inferior to reported CS rates in palliative series mostly from Asia. CONCLUSIONS: Biliary drainage in complex malignant hilar obstruction due to cholangiocarcinoma is more likely to be successful and less likely to cause adverse events in curative patients compared to palliative patients.

Inside stent placement is suitable for preoperative biliary drainage in patients with perihilar cholangiocarcinoma.

BACKGROUND/PURPOSE: Endoscopic biliary stenting (EBS) is commonly used for preoperative drainage of localized perihilar cholangiocarcinoma (LPHC). This study retrospectively compared the utility of inside stent (IS) and conventional stent (CS) for preoperative EBS in patients with LPHC. METHODS: EBS was performed in 56 patients with LPHC. EBS involved the placement of a CS (n = 32) or IS (n = 24). Treatment outcomes were compared between these two groups. RESULTS: Preoperative recurrent biliary obstruction (RBO) occurred in 23 patients (71.9%) in the CS group and 7 (29.2%) in the IS group, with a significant difference (p = 0.002). The time to RBO (TRBO) was significantly longer in IS than in CS (log-rank: p < 0.001). The number of stent replacements was significantly lower in IS than CS [0.38 (0-3) vs. 1.88 (0-8), respectively; p < 0.001]. Gemcitabine-based neoadjuvant chemotherapy (NAC) was administered to 26 patients (46.4%). Among patients who received NAC, TRBO was longer in IS than in CS group (log-rank: p < 0.001). The IS group had a significantly shorter preoperative and postoperative hospital stay than the CS group (20.0 vs. 37.0 days; p = 0.024, and 33.5 vs. 41.5 days; p = 0.016).　 Both the preoperative and the postoperative costs were significantly lower in the IS group than in the CS group (p = 0.049 and p = 0.0034, respectively). CONCLUSION: Compared with CS, IS for preoperative EBS in LPHC patients resulted in fewer complications and lower re-intervention rates. The fact that the IS group had shorter preoperative and postoperative hospital stays and lower costs both preoperatively and postoperatively compared to the CS group may suggest that the use of IS has the potential to benefit not only the patient but also the healthcare system.

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.

Use of therapeutic plasma exchange to remove lipoprotein X in a patient with vanishing bile duct syndrome presenting with cholestasis, pseudohyponatremia, and hypercholesterolemia: A case report and review of literature.

INTRODUCTION: Lipoprotein X (Lp-X) is an abnormal lipoprotein found in multiple disease conditions, including liver dysfunction and cholestasis. High Lp-X concentrations can interfere with some laboratory testing that may result in spurious results. The detection of Lp-X can be challenging, and there is currently a lack of consensus regarding the management of Lp-X other than treating the underlying disease. CASE PRESENTATION: A 42-year-old female with Hodgkin's lymphoma treated with dexamethasone, high dose cytarabine and cisplatin and vanishing bile duct syndrome confirmed by liver biopsy presented with cholestasis, pseudohyponatremia (sodium, 113 mmol/L; reference range 136-146 mmL/L; serum osmolality, 303 mOsm/kg), and hypercholesterolemia (> 2800 mg/dL, reference range < 200 mg/dL). Lp-X was confirmed by lipoprotein electrophoresis (EP). Although she did not manifest any specific signs or symptoms, therapeutic plasma exchange (TPE) was initiated based on laboratory findings of extreme hypercholesterolemia, spuriously abnormal serum sodium, and HDL values, and the potential for short- and long-term sequelae such as hyperviscosity syndrome, xanthoma, and neuropathy. During the hospitalization, she was treated with four 1.0 plasma volume TPE over 6 days using 5% albumin for replacement fluid. After the first TPE, total cholesterol (TC) decreased to 383 mg/dL and sodium was measured at 131 mmol/L. The patient was transitioned into outpatient maintenance TPE to eliminate the potential of Lp-X reappearance while the underlying disease was treated. Serial follow-up laboratory testing with lipoprotein EP showed the disappearance of Lp-X after nine TPEs over a 10-week period. LITERATURE REVIEW: There are seven and four case reports of Lp-X treated with TPE and lipoprotein apheresis (LA), respectively. While all previous case reports showed a reduction in TC levels, none had monitored the disappearance of Lp-X after completing a course of therapeutic apheresis. CONCLUSION: Clinicians should have a heightened suspicion for the presence of abnormal Lp-X in patients with cholestasis, hypercholesterolemia, and pseudohyponatremia. Once Lp-X is confirmed by lipoprotein EP, TPE should be initiated to reduce TC level and remove abnormal Lp-X. Most LA techniques are not expected to be beneficial since Lp-X lacks apolipoprotein B. Therefore, we suggest that inpatient course of TPE be performed every other day until serum sodium, TC and HDL levels become normalized. Outpatient maintenance TPE may also be considered to keep Lp-X levels low while the underlying disease is treated. Serum sodium, TC, and HDL levels should be monitored while on maintenance TPE.

A therapeutic ERCP in an only 5.9 kg infant with obstruction jaundice using JF-260V duodenoscope.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) has found extensive use in pediatric patients; however, challenges persist in the application of therapeutic ERCP in infants. CASE PRESENTATION: This case report details the presentation of a 5.9-kilogram infant with obstructive jaundice and suspected hemolytic anemia who underwent ERCP to alleviate biliary obstruction. The infant was admitted due to clay-colored stools, jaundice, and liver injury. Ultrasound and magnetic resonance cholangiopancreatography (MRCP) revealed dilation of the common bile duct (CBD) accompanied by the presence of stones. ERCP was conducted using a JF-260V duodenoscope under general anesthesia. Successful stone extraction and biliary drainage were achieved. CONCLUSIONS: In centers with considerable expertise in ERCP and pediatric anesthesia, the use of a conventional adult duodenoscope for therapeutic ERCP in infants can be considered safe and feasible, provided careful and stringent patient selection criteria are applied. In the future, clear guidelines and standardized protocols for the indications and procedures of pediatric ERCP should be established.

Hepatic dysfunction in patients receiving intravenous lipid emulsions.

PURPOSE OF REVIEW: Until recently, intravenous lipid emulsions (ILEs) have consisted of soybean oil (SO) only. This review addresses recent developments in the field, including the problem of intestinal failure associated liver disease (IFALD) that can occur with the use of ILEs in children and adults, and newer ILEs that may minimize and reverse IFALD. RECENT FINDINGS: Cholestasis is the primary manifestation of IFALD in premature infants receiving ILEs, whereas in older children and adults, steatosis is predominant. Two alternative ILEs have been extensively investigated for both safety and efficacy. SMOF, an ILE containing medium chain triglyceride, soybean oil, olive oil and fish oil (FO), is now widely used in both children and adults. A newer FO ILE is approved for use in children only. However, in case reports FO ILE has been shown to improve IFALD in adults. A number of new studies suggest that cholestasis from ILEs is dose-related. IFALD does not improve in many patients after transition from SO to SMOF, but partial or complete replacement with FO can halt and reverse IFALD. SUMMARY: Adverse hepatic effects from ILEs are to some extent dose-related. Overfeeding with fat or with carbohydrate, or simply providing excessive calories in general, may be responsible. More research is needed investigating dose-related effects of macronutrients on liver injury.

Effect of ursodeoxycholic acid after self-expandable metal stent placement in malignant distal biliary obstruction: a propensity score-matched cohort analysis.

BACKGROUND AND AIMS: Sludge occlusion is a primary reason for recurrent biliary obstruction (RBO) after self-expandable metallic stent (SEMS) placement. However, the efficacy of ursodeoxycholic acid (UDCA) for SEMS occlusion remains unexplored to date. This study aimed to evaluate the efficacy of UDCA after SEMS placement for malignant distal biliary obstruction (MDBO). METHODS: Three hundred fifty-four patients were included, of which 60 received UDCA. Additionally, we conducted a propensity score-matched cohort analysis on 110 patients with SEMS placement for MDBO to reduce selection bias. Patients were categorized into 2 groups of 55 each, based on whether they received UDCA. In the UDCA group, the treatment was administered for more than a month. The primary endpoint was the time to RBO (TRBO) after SEMS placement. The secondary endpoint was to evaluate SEMS occlusion rate and early adverse events (AEs). RESULTS: The cumulative SEMS occlusion rate was 41.8% and 18.2% in the groups with and without UDCA, respectively (P = .0119). Median TRBO was significantly longer in the control group than in the UDCA group (528 vs 154 days, P = .0381). In the multivariate analysis, UDCA administration was identified as the independent risk factor for reducing TRBO (hazard ratio, 2.28; 95% confidence interval, 1.06-4.88; P = .0348). The overall early AE rate showed insignificant differences between groups. CONCLUSIONS: Administering UDCA after SEMS placement was not efficacious for prolonging the TRBO in MDBO. Moreover, administering UDCA beyond a month might increase the risk of stent sludge occlusion. (Clinical trial registration number: UMIN000046862.).

Impact of cholangitis on survival of patients with malignant biliary obstruction treated with percutaneous transhepatic biliary drainage.

PURPOSE: To evaluate the impact of cholangitis on survival of patients with gastrointestinal cancer and malignant biliary obstruction treated with percutaneous transhepatic biliary drainage (PTBD). METHODS: A retrospective registry study was performed at a tertiary center from 2000 to 2016 in Northern Finland. RESULTS: The study included 588 patients, 258 (43.9%) patients with pancreatic cancer, 222 (37.7%) with biliary tract cancer, and 108 (18.4%) with metastasis from gastrointestinal cancers. Patient mean age was 70 years, range 26 - 93 years. There were 288 [49.0%] women. The 30-day mortality rate was 30.8% for 156 patients with cholangitis before PTBD, 19.5% for 215 patients with cholangitis after PTBD and 25.8% for 217 patients without cholangitis (P = 0.039). The median survival was 1.8 months for patients with cholangitis before PTBD, 3.0 months for patients with cholangitis after PTBD, and 3.2 months for patients without cholangitis (P = 0.002). The hazard ratio (HR) for 1-year mortality for patients with cholangitis before PTBD was 1.3 (95% CI 1.06 - 1.67, P = 0.015) compared to patients with cholangitis after PTBD. After successful PTBD, 54 out of 291 patients received chemotherapy; the median survival was 5.2 months with cholangitis before PTBD, 9.4 months with cholangitis after PTBD and 15.3 months without cholangitis. CONCLUSION: In gastrointestinal cancers with malignant biliary obstruction, survival is poorer if cholangitis occurs before PTBD compared to cholangitis after PTBD. An oncologist's consultation is essential for assessing the possibility of chemotherapy in successfully treated PTBD patients, because of the notable survival benefit.

Internal versus external biliary drainage in malignant biliary obstructions: is there a difference in the rate of infection?

BACKGROUND: Percutaneous biliary drainage is a frequently used method to provide biliary decompression in patients with biliary obstruction. PURPOSE: To investigate the between drainage type and infection risk in patients treated with internal-external and external biliary drainage catheterization for malignant biliary obstruction. MATERIAL AND METHODS: A total of 410 patients with malignant biliary obstruction who underwent internal-external or external biliary drainage catheterization between January 2012 and October 2016 were retrospectively evaluated. We investigated the correlation between percutaneous biliary drainage technique and infection frequency by evaluating patients with clinical findings, bile and blood cultures, complete blood counts, and blood biochemistry. RESULTS: There was no statistically significant difference between the selected patient groups (internal-external or external biliary drainage catheter placed) in terms of age, sex, primary diagnosis, receiving chemotherapy, catheter sizes, and outpatient-patient status. After catheterization, catheter-related infection was observed in 49 of 216 (22.7%) patients with internal-external and 18 of 127 (14.2%) patients with external biliary drainage catheters, according to the defined criteria. There was no difference in infection rate after the biliary drainage in the two groups (P > 0.05). There was also no difference concerning frequently proliferating microorganisms in bile cultures. CONCLUSION: Internal-external biliary drainage catheter placement does not bring an additional infection risk for uninfected cholestatic patients whose obstruction could be passed easily in the initial drainage.

Pathogenesis and Treatment of Pruritus Associated with Chronic Kidney Disease and Cholestasis.

Itching is an unpleasant sensation that provokes the desire to scratch. In general, itching is caused by dermatologic diseases, but it can also be caused by systemic diseases. Since itching hampers patients' quality of life, it is important to understand the appropriate treatment and pathophysiology of pruritus caused by systemic diseases to improve the quality of life. Mechanisms are being studied through animal or human studies, and various treatments are being tested through clinical trials. We report current trends of two major systemic diseases: chronic kidney disease and cholestatic liver disease. This review summarizes the causes and pathophysiology of systemic diseases with pruritus and appropriate treatments. This article will contribute to patients' quality of life. Further research will help understand the mechanisms and develop new strategies in the future.

Effect of Percutaneous Biliary Drainage on Enzyme Activity of Serum Matrix Metalloproteinase-9 in Patients with Malignant Hilar Obstructive Hyperbilirubinemia.

Background and Objectives. Cholestasis activates complex mechanisms of liver injury and as a result has an increased production of matrix metalloproteinases (MMP). Depending on the stage of liver disease, different matrix metalloproteinases expressions have been detected and could serve as indirect biomarkers as well as therapeutic targets. MMP-9 proteolytic activity has a proven role in both liver regeneration and neoplastic cell invasion in various malignancies. The purpose of this prospective cohort study was to evaluate the effect of external biliary drainage on enzyme activity of MMP-9 in the serum of patients with malignant hilar biliary obstruction. Materials and Methods. Between November 2020 and April 2021, 45 patients with malignant hilar biliary obstruction underwent percutaneous biliary drainage following determination of serum MMP-9 enzyme activity (before treatment and 4 weeks after the treatment) by gelatin zymography. Results. MMP-9 values decreased statistically significantly 4 weeks after percutaneous biliary drainage (p = 0.028) as well as the value of total bilirubin (p < 0.001), values of direct bilirubin (p < 0.001), aspartate aminotransferase (AST) (p < 0.001), alanine transaminase (ALT) (p < 0.001), and gamma-glutamyl transferase (GGT) (p < 0.001). Conclusions. In patients with malignant hilar biliary obstruction treated by external percutaneous biliary drainage for cholestasis resolution, a significant reduction in MMP-9 serum values was noted 4 weeks after the treatment.

[Diagnosis and treatment of hereditary cholestasis].

With China's outstanding achievements in the prevention and treatment of hepatitis, hereditary cholestasis caused by genetic variants has gradually become an important cause of death or transplantation in children with liver disease. The continuous identification of new pathogenic genes expands the disease spectrum and clinician's understanding of disease. The disease characteristics and clinical manifestations of hereditary cholestasis caused by different gene variants vary, and the severity of diseases caused by the same gene variants and the response to treatment are also significantly different. Therefore, early genetic diagnosis is of great value for improving the clinical management of patients. In terms of treatment, in addition to traditional drugs and surgery, targeted therapy and gene therapy are also gradually moving towards clinical application. Advances in metabolomics, gene editing technology, and structural biology have made it possible to provide personalized and precise treatment of children with hereditary cholestasis in the future; however, this which will put forward higher requirements for on relevant practitioners.

Post-Transplant Biliary Strictures: An Updated Review.

Liver transplantation (LT) is the only curative therapy in patients with end-stage liver disease with excellent long-term survival; however, LT recipients are at risk of significant complications. Among these complications are biliary complications with an incidence ranging from 5 to 32% and associated with significant post-LT morbidity and mortality. Prompt recognition and management are critical as these complications have been associated with mortality rates up to 19% and retransplantation rates up to 13%. An important limitation of published studies is that a large proportion does not discriminate between anastomotic strictures and nonanastomotic strictures. This review aims to summarize our current understanding of risk factors and natural history, diagnostic testing, and treatment options for post-LT biliary strictures.

Fully Covered Self-Expanding Metal Stent vs Multiple Plastic Stents to Treat Benign Biliary Strictures Secondary to Chronic Pancreatitis: A Multicenter Randomized Trial.

BACKGROUND & AIMS: Benign biliary strictures (BBS) are complications of chronic pancreatitis (CP). Endotherapy using multiple plastic stents (MPS) or a fully covered self-expanding metal stent (FCSEMS) are acceptable treatment options for biliary obstructive symptoms in these patients. METHODS: Patients with symptomatic CP-associated BBS enrolled in a multicenter randomized noninferiority trial comparing 12-month treatment with MPS vs FCSEMS. Primary outcome was stricture resolution status at 24 months, defined as absence of restenting and 24-month serum alkaline phosphatase not exceeding twice the level at stenting completion. Secondary outcomes included crossover rate, numbers of endoscopic retrograde cholangiopancreatography (ERCPs) and stents, and stent- or procedure-related serious adverse events. RESULTS: Eighty-four patients were randomized to MPS and 80 to FCSEMS. Baseline technical success was 97.6% for MPS and 98.6% for FCSEMS. Eleven patients crossed over from MPS to FCSEMS, and 10 from FCSEMS to MPS. For MPS vs FCSEMS, respectively, stricture resolution status at 24 months was 77.1% (54/70) vs 75.8% (47/62) (P = .008 for noninferiority intention-to-treat analysis), mean number of ERCPs was 3.9 ± 1.3 vs 2.6 ± 1.3 (P < .001, intention-to-treat), and mean number of stents placed was 7.0 ± 4.4 vs 1.3 ± .6 (P < .001, as-treated). Serious adverse events occurred in 16 (19.0%) MPS and 19 (23.8%) FCSEMS patients (P = .568), including cholangitis/fever/jaundice (9 vs 7 patients respectively), abdominal pain (5 vs 5), cholecystitis (1 vs 3) and post-ERCP pancreatitis (0 vs 2). No stent- or procedure-related deaths occurred. CONCLUSIONS: Endotherapy of CP-associated BBS has similar efficacy and safety for 12-month treatment using MPS compared with a single FCSEMS, with FCSEMS requiring fewer ERCPs over 2 years. (ClinicalTrials.gov, Number: NCT01543256.).

Percutaneous Cholangioscopy for the Diagnosis and Management of Biliary Pathology in Pediatric Patients: A Single-Center Experience.

Transhepatic percutaneous cholangioscopy (PC) can be used for the diagnosis and treatment of biliary pathology. It allows for direct visualization of the biliary system to identify pathologic changes, perform biopsies, and treat biliary obstruction. The effectiveness and safety of PC in adults have been established. However, the data on the use of PC in pediatric patients are limited. In this case series, the outcomes in 4 pediatric patients (3 girls; mean age, 4 [range, 1-8] years) who underwent 6 PC procedures were examined. Three out of the 6 (50%) PC procedures were performed for diagnostic visualization of the biliary tree and/or small intestine, whereas the remaining 3 (50%) were performed for the treatment of biliary obstruction causing chronic cholestasis. The technical and procedural success rate was 100%, and no complications were encountered during or 30 days after the procedure. This study supports the feasibility and safety of PC in pediatric patients for the management of biliary pathology.