BACKGROUND:Endoscopic ultrasound-guided rendezvous (EUS-RV) endoscopic retrograde cholangiopancreatography (ERCP) is an alternative to interventional radiology-guided rendezvous ERCP in patients who failed biliary cannulation with conventional ERCP. However, there is significant variation in reported rates of success and adverse events associated with EUS-RV-assisted ERCP. We performed a systematic review and a proportion meta-analysis to reliably assess the effectiveness and safety of the EUS-RV-assisted ERCP. MATERIALS AND METHODS:We conducted a comprehensive search of multiple electronic databases and conference proceedings (from inception through August 2020) to identify studies reporting EUS-RV-assisted ERCP in patients who failed biliary cannulation with conventional ERCP techniques. Using the random-effects model described by DerSimonian and Laird, we calculated the pooled rates of technical success, clinical success, and adverse events of EUS-RV-assisted ERCP. RESULTS:Twelve studies reporting a total of 342 patients were included in the meta-analysis. The pooled rate of technical success (12 studies reporting a total of 342 patients) was 86.1% [95% confidence interval (CI): 78.4-91.3]. The pooled rate of clinical success (4 studies reporting a total of 94 patients) was 80.8% (95% CI: 64.1-90.8). The pooled rate of overall adverse events (12 studies; 42 events in 342 patients) was 14% (95% CI: 10.5-18.4). Low to moderate heterogeneity was noted in the analyses. CONCLUSIONS:EUS-RV-assisted ERCP appears to be effective and safe in patients who failed biliary cannulation with conventional ERCP. Given the risk of adverse events, it should be performed in centers with expertise in therapeutic endoscopic ultrasound.

Porto-sinusoidal vascular disease (PSVD) is a novel nomenclature to describe non-cirrhotic portal hypertension and characteristic histology without portal vein thrombosis (PVT). It is a more inclusive definition than the previously well-recognized entity idiopathic non-cirrhotic portal hypertension. There is a paucity of data on PSVD patients. A total of 33 patients diagnosed with PSVD and portal hypertension (PH) between 2005 and 2021 were included. Data were retrieved from electronic medical record system and analyzed. Of the 33 patients, 6 (18%) occurred in post-transplant allograft liver. After a median follow-up of 96 months (interquartile range, IQR [52, 139]), 14 deaths occurred (42%), 4 directly related to decompensated liver disease. The Kaplan–Meier survival estimates at 1, 5, and 10 years were 94%, 87% and 58%. PVT occurred in 10 patients (30%). The Nelson–Aalen cumulative risk estimate for PVT at 1, 5 and 10 years were 16%, 25% and 48%. The median model for end-stage liver disease and Child–Pugh score at initial presentation were 8 (IQR [7–12]) and 5 [5–6], and increased to 13 [8, 18] and 7 [5, 8], respectively, at the end of follow-up. Of the 11 patients who presented with splenomegaly and no specific sign of PH, 7 (64%) developed varices and 3 (27%) ascites at a median follow-up of 100 months. PSVD with PH is not a benign entity. Mortality, PVT and hepatic decompensation are common. Patients with PSVD must be closely monitored, including those who only have non-specific clinical signs (e.g., splenomegaly) of PH.

OBJECTIVES:Dysregulation of hepcidin-iron axis is presumed to account for abnormal iron status in patients with chronic liver disease (CLD). Our aim is to determine the effect of specific etiologies of CLD and of cirrhosis on serum hepcidin levels. METHODS:PubMed, Embase, Web of Science were searched for studies comparing serum hepcidin levels in patients with CLD to that in controls using enzyme-linked immunosorbent assay. The study was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Guidelines. Statistical analysis was carried out with STATA using random effects model to calculate the mean difference (MD) between two groups. RESULTS:Hepcidin levels were significantly lower in subjects with hepatitis C virus (16 studies) [MD -1.6 (95 % CI: -2.66 to -0.54), p<0.01] and alcoholic liver disease (3 studies) [MD -0.84 (95 % CI: -1.6 to -0.07), p=0.03] than controls. Serum hepcidin was significantly higher in subjects with non-alcoholic fatty liver disease (12 studies) [MD 0.62 (95 % CI: 0.21 to 1.03), p<0.01], but did not differ in subjects with hepatitis B and controls (eight studies) [MD -0.65 (95 % CI: -1.47 to 0.16), p=0.12]. Hepcidin levels were significantly lower in patients with cirrhosis of any etiology (four studies) [MD -1.02 (CI: -1.59 to -0.45), p<0.01] vs. controls (CI: confidence interval). CONCLUSIONS:Serum hepcidin levels are altered in common forms of CLD albeit not in a consistent direction. Additional study is needed to determine how changes in hepcidin levels are related to dysregulation of iron metabolism in CLD.

Background:. Controversy exists whether alpha-1 antitrypsin (A1AT) genotype testing should be performed as a first-line screening for A1AT heterozygous variants. Methods:. We calculated the median and interquartile range of A1AT level for each genotype in 4378 patients with chronic liver disease and “miss rate” of MZ genotype identification at various cutoff levels. Findings:. Significant overlap in A1AT level noted with Pi*MM, MZ, and MS variants. Miss rate of Pi*MZ at a cutoff level <100 was 29%, <110 was 18%, <120 was 8%, and <130 was 4%. We suggest simultaneous measurement of A1AT level and genotype in patients with chronic liver disease.

Video 1Colonoscopy findings of cecal mass as a lead point causing intussusception.

Introduction: Serum Hepcidin levels in chronic liver disease (CLD) are proposed biomarkers for hepatic iron load, inflammation, and fibrosis. Studies correlating serum hepcidin with these factors have yielded variable results. We carried out a meta-analysis to understand the effect on serum hepcidin levels on various aspects of CLD including systemic and hepatic iron levels, inflammation and liver synthetic capacity. Methods: We searched Pubmed, Embase and Web of Science for studies which measured serum hepcidin levels in patients with CLD from inception till 2020. We included studies where correlation of serum hepcidin levels with serum iron indices, inflammatory markers, grade of inflammation/fibrosis or iron score on liver biopsy was examined. Meta-analysis was done using STATA software applying the random effects model. Results: We found 1840 studies out of which 33 studies met inclusion criteria. Our meta-analysis showed that overall in patients with CLD, serum hepcidin levels (i) Correlated positively with iron indices, including serum ferritin (r50.41, p5, 0.0001), hemoglobin (r50.21, p5 0.011), transferrin saturation (r50.15, p50.01) and negatively with total iron binding capacity (r5-0.17, p50.048). There was no correlation with serum iron levels (r 5 0.07, p 50.333) (ii) Correlated positively with serum albumin levels (r50.19, p 50.007) (iii) Correlated positively with histological iron stores (r 5 0.46, p 5 0.001) (iv) Correlated positively with liver hepcidin mRNA levels (r50.51, p50.001) (v) Did not correlate with grade of inflammation or fibrosis on liver biopsy. On subgroup analysis chronic viral hepatitis differed significantly in that serum hepcidin levels had no correlation with iron indices such as hemoglobin (r50.14, p50.534), transferrin saturation (r50.13, p50.36) or total iron binding capacity (r5-0.01, p50.18). There continued to be a positive correlation with ferritin, albumin, hepcidin mRNA and histological iron score. (Figure) Conclusion: (i) Correlation with hepatic iron levels indicates that hepcidin iron axis is intact in CLD including viral hepatitis (ii) Lack of correlation with iron indices indicates that overall hepcidin production is suppressed in viral hepatitis (iii) Serum hepcidin levels likely depend on hepatic synthetic capacity as indicated by a positive correlation with serum albumin.

CASE REPORT A 72-year-old woman, without prior gastrointestinal disease, presented to clinic with abdominal pain, nausea, vomiting, poor appetite, fatigue, and weight loss. She denied melena or hematochezia. Her past colonoscopy, at the age of 55 years, was unremarkable. Upper endoscopy seemed normal. Colonoscopy demonstrated noninflamed colonic mucosa with multiple venous blebs throughout the colon (Figure 1). One small venous bleb was resected with a cold snare for histopathologic analysis. A clip was placed at the site of resection because of concern for bleeding. Hematoxylin and eosin staining revealed extensive submucosal band-like deposition of pink amorphous material involving the blood vessels in the lamina propria and muscularis propria (Figure 2). Congo red staining under polarized light revealed apple-green birefringence, consistent with amyloidosis (Figure 2). Random duodenal and colonic biopsies similarly revealed amyloidosis. There were no postprocedural complications.Figure 1.: Colonic venous blebs as noted on colonoscopy.Figure 2.: (A) Biopsy of colonic venous bleb stained with hematoxylin and eosin stain at ×10 shows amorphous material deposits in a band-like pattern in the lamina propria and extends to involve the blood vessels, consistent with amyloid. (B) Congo red stain of colonic venous bleb shows amyloid deposits in the lamina propria and around the blood vessels. (C) Congo red stain of colonic venous bleb under polarized light shows the classical apple-green birefringence.Serum protein electrophoresis showed a lambda free light chain of 8,429 mg/L and a kappa chain of 17.4 mg/L. Bone marrow biopsy of the left iliac crest demonstrated 20% monoclonal plasma cells. The patient was diagnosed with gastrointestinal amyloid light chain (AL) amyloidosis, secondary to multiple myeloma, and chemotherapy was initiated. After 1 month, the patient's lambda free light chain fell to 145 mg/L and her gastrointestinal symptoms improved. There were no follow-up colonoscopies. The patient ultimately developed progressive diastolic heart failure from cardiac amyloidosis (diagnosed based on clinical signs of heart failure and decreased global longitudinal left ventricular strain, with sparing of the apex, on echocardiogram). She unfortunately died a year after diagnosis. Approximately 10%–15% of multiple myeloma patients have AL amyloidosis.1 Gastrointestinal involvement of amyloidosis is not uncommon. In a study of 2,334 patients with amyloidosis of any subtype, 3% had biopsy-proven involvement of the gastrointestinal tract.2 Another analysis of 769 patients with AL amyloidosis indicated that biopsy-proven gastrointestinal amyloidosis was found in 8%.3 Among those with gastrointestinal AL amyloidosis, 50% had small bowel involvement, 44% had gastric involvement, 32% had colonic involvement, and 12% had esophageal involvement.2 Endoscopic findings of AL amyloidosis include submucosal hematomas, ulcerations, erosions, and inflammation.4 There are no reports of venous blebs associated with AL amyloidosis to date. This case suggests that diffuse colonic venous blebs may be a manifestation of gastrointestinal AL amyloidosis. Random colonic biopsies may reveal amyloidosis, and resection of venous blebs can be considered only when diagnosis is unclear. The differential diagnosis for colonic venous blebs includes blue rubber bleb nevus syndrome, arteriovenous malformations, cavernous hemangiomas, and vascular ectasias. DISCLOSURES Author contributions: S. Prakash wrote the article and compiled the endoscopy images. M. Obeidat provided and described the pathologic images. AR Murali revised, edited, and approved the final version of the article and is the article guarantor. Financial disclosures: None to report. Informed consent was obtained from the patient's next of kin.

Background:The NAFLD decompensation risk score (the Iowa Model) was recently developed to identify patients with nonalcoholic fatty liver disease (NAFLD) at highest risk of developing hepatic events using three variables-age, platelet count, and diabetes. Aims:We performed an external validation of the Iowa Model and compared it to existing non-invasive models. Methods:We included 249 patients with NAFLD at Boston Medical Center, Boston, Massachusetts, in the external validation cohort and 949 patients in the combined internal/external validation cohort. The primary outcome was the development of hepatic events (ascites, hepatic encephalopathy, esophageal or gastric varices, or hepatocellular carcinoma). We used Cox proportional hazards to analyze the ability of the Iowa Model to predict hepatic events in the external validation (https://uihc.org/non-alcoholic-fatty-liver-disease-decompensation-risk-score-calculator). We compared the performance of the Iowa Model to the AST-to-platelet ratio index (APRI), NAFLD fibrosis score (NFS), and the FIB-4 index in the combined cohort. Results:The Iowa Model significantly predicted the development of hepatic events with hazard ratio of 2.5 [95% confidence interval (CI) 1.7-3.9, P < 0.001] and area under the receiver operating characteristic curve (AUROC) of 0.87 (CI 0.83-0.91). The AUROC of the Iowa Model (0.88, CI: 0.85-0.92) was comparable to the FIB-4 index (0.87, CI: 0.83-0.91) and higher than NFS (0.66, CI: 0.63-0.69) and APRI (0.76, CI: 0.73-0.79). Conclusions:In an urban, racially and ethnically diverse population, the Iowa Model performed well to identify NAFLD patients at higher risk for liver-related complications. The model provides the individual probability of developing hepatic events and identifies patients in need of early intervention.

Introduction: Derangement of hepcidin-iron axis in chronic liver disease (CLD) has been implicated in the development of hepatic iron overload which is associated with accelerated progression of liver disease. Hepcidin is a proposed biomarker for monitoring CLD and has been shown to correlate with hepatic iron stores and histological activity index. Supplementing hepcidin has been suggested as a way of slowing down progression of liver disease. Studies comparing serum hepcidin in patients with CLD to that in controls have been fraught with discrepancies. We carried out a meta-analysis of these studies to gain a better understanding and investigate if serum hepcidin levels are affected by the underlying etiology of CLD. Methods: Pubmed, Embase and Web of Science were searched for studies comparing serum hepcidin in patients with CLD to controls from inception till November 2020. Meta-analysis was carried out using the STATA software applying the random effects model. Results: 1379 records were retrieved after removing duplicates. 24 studies met inclusion criteria. Compared to healthy controls, serum hepcidin was significantly lower in chronic hepatitis C (11 studies) [mean difference -0.93 (95% CI: -1.5 to -0.36), p< 0.01] [Figure A] and alcohol associated liver disease (3 studies) [mean difference -1.21 (95% CI: -1.97 to -0.46), p< 0.01] [Figure B]. There was a trend for lower serum hepcidin in chronic hepatitis B (6 studies) but this was not statistically significant [mean difference -0.61 (95% CI: -1.26 to 0.04), p=0.06] [Figure C]. There was a trend for higher serum hepcidin in non-alcoholic fatty liver disease (11 studies), but this was not statistically significant [mean difference 0.46 (CI: -0.02 to 0.94), p=0.06] [Figure D] [CI: confidence interval]. Conclusion: Serum hepcidin in CLD is influenced by several factors including systemic iron status, inflammation, liver synthetic capacity, presence of metabolic syndrome etc. Targeted therapy should be tailored based on the underlying mechanism.Figure 1.: Meta-analysis showing significantly lower serum hepcidin in CHC (11 studies) [mean difference -0.93 (95% CI: -1.5 to -0.36), p<0.01] [A]; AALD (3 studies) [mean difference -1.21 (95% CI: -1.97 to -0.46), p<0.01] [B]; trend for lower serum hepcidin in CHB (6 studies) [mean difference -0.61 (95% CI: -1.26 to 0.04), p=0.06] [C]; and trend for higher serum hepcidin in NAFLD (11 studies) [mean difference 0.46 (CI: -0.02 to 0.94), p=0.06] [D].Chronic hepatitis C (CHC), alcohol associated liver disease (AALD), Chronic hepatitis B (CHB), non-alcoholic fatty liver disease (NAFLD), number of patients (N), standard deviation (SD), confidence interval (CI).