Clinical profile of adult and pediatric patients with hepatic Wilson's disease.

BACKGROUND: The clinical profile varies in patients with Wilson's disease (WD). There is paucity of data regarding adult and pediatric patients with hepatic WD. METHODS: As many as 140 consecutive patients diagnosed with hepatic WD between December 2006 and January 2021 were included in the study. Data was collected regarding the demographic parameters, clinical presentation, extrahepatic organ involvement, liver histology and laboratory investigations. Adult and children (0-14 years) with hepatic WD were compared regarding these features. RESULT: Eighty-eight adults and 52 children were included in the study. The median age of presentation was 17 years (range: 1.1-42 years). Male preponderance was seen (adult 68/88, 69%; children 40/52, 77%). Adults as compared to children presented more commonly as cirrhosis (52/88 vs. 15/52, p = 0.0005) and with hepatic decompensation (35/88 vs. 9/52, p = 0.005). Presentation with acute-on-chronic liver failure (ACLF) was more common in children (10/52 vs. 2/88, p = 0.0005). Twenty-eight-day mortality was 50% (5/10) in children and none in adults presenting with ACLF. Nazer's Prognostic Index (≥ 7) and New Wilson Index were more accurate in predicting mortality among children with ACLF with AUROC 1, while AARC (APASL ACLF Research Consortium) was less accurate with AUROC 0.45. Liver histology findings were similar in adults and children. Extrahepatic involvement was also similar. (8/88 in adults vs. 3/52 children, p value 0.48). CONCLUSION: Most patients with WD present as cirrhosis in adulthood. ACLF is more common in children. Nazer's prognostic index and new Wilson Index score are accurate in predicting mortality in children with ACLF.

Safety and efficacy of endoscopic retrograde cholangiopancreatography in pediatric pancreatic and biliary disorders.

INTRODUCTION: There is sparse data from India on indications, technical success, safety and outcomes of endoscopic retrograde cholangiopancreatography (ERCP) using standard adult duodenoscope in the pediatric population. METHODS: Retrospective analysis of prospectively maintained electronic endoscopy and clinical database was performed to identify pediatric patients (age ≤ 18 years) who underwent ERCP between January 2017 and December 2022. Demographics and procedural details including indications, cholangio-pancreatogram findings, endotherapy type performed, technical and clinical success and complications were noted. RESULTS: As many as 150 pediatric patients were included of whom 88 had pancreatic (mean age-13.7 years) and 62 had biliary disease (mean age- 14.9 years). Common pancreatic ERCP indications were chronic pancreatitis (n = 45 [51.1%]), pancreatic duct disruption fistula (n = 21 [23.9%]) and recurrent acute pancreatitis (n = 16 [18.2%]). Among biliary indications were choledocholithiasis (n = 29 [46.8%]), benign bile duct strictures (n = 13 [21%]), bile duct injury/leak and biliary stent removal (n = 7 [11.3%]) , choledochal cyst (n = 5  [8.1%]) and pancreatic mass causing biliary compression (n = 1 [1.6%]). Technical success in pancreatic and biliary ERCP was 94.3% and 95.2%, respectively, and clinical success was 84.1% and 93.5%, respectively. Most common complications following pancreatic ERCPs were acute pancreatitis (n = 9 [10.2%]) (mild = 5, moderate = 4) patients and post sphincterotomy bleed in one (1.1%). Among biliary ERCPs, post ERCP pancreatitis was seen in (n = 3 [4.8%]) (mild = 2, moderate = 1). CONCLUSION: ERCP can be safely and effectively performed in children using standard duodenoscope. Chronic pancreatitis, choledocholithiasis and pancreatic divisum are common pediatric ERCP indications.

Exploring the utility of EUS in Budd-Chiari syndrome: a multicenter multiobserver prospective cohort study.

BACKGROUND AND AIMS: The diagnosis of Budd-Chiari syndrome (BCS) is essentially radiologic and is needed to plan appropriate therapy. We therefore conducted this proof of concept study to assess the utility of EUS in assessing the anatomy of BCS. METHODS: This prospective, multicenter, observational study enrolled 50 consecutive patients with a diagnosis of BCS. All patients underwent a detailed EUS examination by 3 independent endosonographers, blinded to the anatomic details of BCS and others' findings. The EUS examination was compared between the endosonographers and with conventional angiography (where available) or magnetic resonance venography (MRV). Outcomes assessed were interobserver agreement, sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy in diagnosing pathologic lesions of BCS. RESULTS: Fifty BCS patients (mean age, 34 years [range, 13-65]) underwent EUS. Results showed good agreement among endosonographers for diagnosing right hepatic vein (κ = .716) and left hepatic vein lesions (κ = .722), moderate agreement for middle hepatic vein lesions (κ = .660), and very good agreement for inferior vena cava (IVC) lesions (κ = .823). EUS demonstrated high sensitivity and positive predictive value, low interobserver variability, and overall diagnostic accuracy for BCS lesions. CONCLUSIONS: EUS is a safe and accurate diagnostic tool for BCS. It can provide accurate mapping of hepatic veins, intrahepatic collaterals, and the IVC.

Utility of gastroscopy in the left lateral semi-recumbent position: A blood-free coup!

Background and study aims The utility of esophagogastroduodenoscopy (EGD) in the left lateral semi-recumbent position in the setting of acute upper gastrointestinal bleeding (UGIB) with a persistent fundal pool of blood for adequate visualization and effective endotherapy has not been studied. This study aimed to evaluate the feasibility, efficacy, and safety of this position in such settings. Patients and methods A prospective study of patients presenting with acute UGIB with an uncleared fundal pool of blood was conducted. All underwent EGD in the left lateral decubitus and secondary left lateral semi-recumbent positions. Outcomes in secondary position in terms of adequate visualization of the fundus, identification of new or additional sources of bleeding, and effectiveness of endotherapy were studied. Results We screened 860 patients and included 44 patients (5.11%) with a persistent fundal pool of blood. Endoscopy in the primary position revealed the source of bleeding in 37 of 44 patients (84%). The source of the bleeding was not identified in seven of 44 patients (16%). Endoscopy in the secondary position showed clearance of fundal pool in all 44 patients (100%). A new source of bleeding was identified in all seven patients (100%) and an additional source could be identified in another five patients (13.6%). Endotherapy was performed in the secondary position for all 44 patients with 100% technical success and 94% clinical success. Conclusions These data show that endotherapy in the left lateral semi-recumbent position is feasible, safe, and effective. It should be done when endoscopy in the left lateral decubitus position reveals a pool of blood in the fundus and there is inadequate visualization of the fundus.

Outcomes and predictors of response to endotherapy in pancreatic ductal disruptions with refractory internal and high-output external fistulae.

Backgrounds/Aims: Endoscopic retrograde cholangiopancreatography (ERCP) remains the primary treatment for a subset of patients with pancreatic fistulae. The objective of this study was reporting outcomes of ERCP and predictors of resolution in patients with pancreatic fistulae refractory to conservative therapy. Methods: Retrospective review of patients who underwent ERCP and pancreatic stent placement for pancreatic fistula not responding to medical therapy was performed. Clinical features, laboratory parameters, radiological features and pancreatogram findings were noted. Clinical resolution of fistula was the primary outcome measure. Results: Sixty-eight patients underwent ERCP for high-output pancreatic fistula (Mean age 34.1 years, 91.1% males, 35/68 chronic pancreatitis, 52.9% alcohol etiology). Internal fistulae (pancreatic ascites, pleural effusion, or pericardial effusion) were seen in 55 (80.9%) patients and external fistula in 13 (19.1%) patients. Technical success for ERCP was 92.6% (63/68). Leak was seen in 98.4% (62/63). The most common leak site was body (69.8%). Multiple leak sites were seen in 23.1%. Pancreatic stricture was found in 36.5%. In 44 (69.4%) patients, stent was placed beyond the site of the leak. Resolution at six weeks was achieved in 76.4% (52/68). On univariate and multivariate analyses, placement of stent beyond site of leak was significantly associated with resolution of high-output fistulae (3/41 [7.3%] vs. 5/19 [26.3%], p = 0.03; odds ratio: 6.5, 95% confidence interval: 1.211-34.94). Conclusions: In our experience, ERCP was successful in 76% of patients with pancreatic fistulae refractory to conservative therapy. Stent placement beyond the site of leak was associated with higher resolution of fistulae.

Adverse Events with D-penicillamine Therapy in Hepatic Wilson's Disease: A Single-Center Retrospective Audit.

BACKGROUND AND OBJECTIVE: There are limited data on the adverse events of D-penicillamine in Wilson's disease (WD) that can result in dose modification or treatment discontinuation. The objective of this study was to observe the adverse events related to D-penicillamine in patients with hepatic WD. METHODS: A retrospective audit of prospectively registered hepatic WD patients at a tertiary care center between December 2006 and January 2020 was carried out. Demographic variables, laboratory parameters, and details of treatment were noted. Adverse events (AEs) related to D-penicillamine treatment, the timing and management of these AEs were analysed. RESULTS: The study included 112 patients with hepatic WD on D-penicillamine. D-penicillamine intolerance was seen in 28/112 (25%) over 179 person-years. Of the 28 AEs, severe AEs leading to permanent D-penicillamine discontinuation occurred in 16 (57%) [never reintroduced 12 (43%), discontinued after intolerant to rechallenge, 4 (14%)], temporary cessation followed by reintroduction to initial dose 13 (46%) and continuation with reduced dose in 3 (11%) patients. Overall, most common AEs were hematological [16, 57% (pancytopenia n = 8, bicytopenia n = 5 and hemolytic anemia n = 3)] while renal adverse events (n = 7, 25%) constituted the most common indication for permanent discontinuation. Cytopenias developed beyond 12 months of D-penicillamine initiation whereas hemolytic anemia developed within first 3 months. Following D-penicillamine discontinuation in 25 patients, it was reintroduced to initial dose in 13/25 (52%), switched to trientine due to neurological worsening in 2/25 (8%) and switched to zinc in 10/25 (40%). In patients with reintroduction, gradual dose escalation was tolerated in 9/13 (69%) with a recurrence of AEs leading to permanent discontinuation in 4/13 (31%). CONCLUSION: D-penicillamine treatment is associated with significant AEs mainly related to blood, kidney, and skin. Temporary cessation of drug with reintroduction at a lower dose is an effective and safe option.

Evaluation of non-invasive marker of esophageal varices in cirrhosis of liver.

INTRODUCTION: Esophageal varices develop as a consequence of portal hypertension (PHT) in patients with chronic liver disease. Hence, screening of all cirrhotic patients with upper gastrointestinal endoscopy to detect the presence of significant esophageal varices implies a number of unnecessary endoscopies and has its limitation where such facilities are not available, especially in the rural part of country. METHOD: Patients with either sex, aged between 18 and 60 years with diagnosis of cirrhosis were studied. Detailed history, physical examination along with relevant investigations were recorded and upper gastrointestinal endoscopy was done within 2-3 days of investigation. Esophageal varices were graded as I-IV, using the Paquet grading system and patients were classified dichotomously either as having large esophageal varices (LEV) group A (Grade III-IV) and no varices group B (grade I-II). RESULT: A total of 50 patients with cirrhosis of liver were recruited in the study. Among hematological markers, only low platelet count was significantly associated with the presence of LEV (P value <0.05). None of the biochemical markers were found to be significantly associated with LEV. All the ultrasonographic parameters, i.e. spleen size, splenic vein size, portal vein size, and the presence of portosystemic collaterals were found to be significantly associated with the presence of LEV (P value <0.05). CONCLUSION: Though upper gastrointestinal endoscopy remains the gold standard for the diagnosis of esophageal varices in cirrhotic patients,those patients at high risk of having LEV can be screened by using clinical, hematological, biochemical, and radiological markers.