Background and Study Aims: Endoscopic ultrasound-directed transgastric ERCP (EDGE) is an alternative to enteroscopy- and laparoscopy-assisted ERCP in patients with Roux-en-Y gastric bypass anatomy. Although short-term results are promising, the long-term outcomes are not known. Aims of this study were 1) to determine rates of long-term adverse events (AEs) after EDGE, with a focus on rates of persistent gastrogastric or jejunogastric fistula; 2) identify predictors of persistent fistula; 3) assess outcomes of endoscopic closure when persistent fistula is encountered. Patients and Methods: This was a multicenter, retrospective study involving 13 centers between 1/2014 and 3/2019. AEs were defined according to ASGE lexicon. Persistent fistula was defined as upper GI series or EGD showing evidence of fistula. Results: A total of 178 patients (mean age 58 years, 79% F) underwent EDGE. Technical success was achieved in 98% of cases (175/178) with a mean procedure time of 92 min. Periprocedural AEs occurred in 28 patients (15.7%; mild 10.1%, moderate 3.3%, severe 2.2%). The 4 severe adverse events were managed laparoscopically. Persistent fistula was diagnosed in 10% of those sent for objective testing (9/90). Following identification of fistula, 5/9 patients underwent endoscopic closure procedures, which were successful in all cases. Conclusions: The EDGE procedure is associated with high clinical success rates, and an acceptable risk profile. Persistent fistula after lumen apposing stent removal are uncommon, but objective testing is recommended to identify their presence. When persistent fistula are identified, endoscopic treatment is warranted, and should be successful in closing the fistula.

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Over the past several years, more so recently, treatment options for hepatitis C virus (HCV) have seemed to exponentially grow. Up until recently, the regimen of pegylated interferon (peg-IFN) and ribavirin (RBV) stood as the standard of care. Direct acting antivirals, which target nonstructural proteins involved in replication and infection of HCV were first approved in 2011 as an addition to the peg-IFN and RBV regimen and with them have come increased sustained virological response rates (SVR). The previously reported 50%-70% SVR rates using the combination of peg-IFN and RBV are no longer the standard of care with direct acting antiviral (DAA) based regimens now achieving SVR of 70%-90%. Peg-IFN free as well as "all oral" regimens are also available. The current randomized controlled trials available show favorable SVRs in patients who are naive to treatment, non-cirrhotic, and not human immunodeficiency virus (HIV)-co-infected. What about patients who do not fit into these categories? In this review, we aim to discuss the currently approved and soon to be approved DAAs while focusing on their roles in patients that are treatment experienced, cirrhotic, or co-infected with HIV. In this discussion, review of the clinical trials leading to recent consensus guidelines as well as discussion of barriers to treatment will occur. A case will attempt will be made that social services, including financial support and drug/alcohol treatment, should be provided to all HCV infected patients to improve chances of cure and thus prevention of late stage sequela.

We have analyzed the antibody response against either AAV2 or canine F.IX (cF.IX) in parental C57BL/6 (B6) and DBA/2 (D2) and 18 strains of B6 x D2 (BXD) recombinant inbred (RI) strains of mice after iv administration of AAV2-(ApoE)4/hAAT-cF.IX. There was a higher anti-AAV2 capsid response in B6 compared to D2 mice, with IgG2b being the major isotype separating the high and low responders in these two strains. In contrast, the antibody response to cF.IX was lower than the response to the AAV2 capsid and was limited to the IgG1 isotype in both strains. Genetic linkage analysis of the IgG2b anti-AAV2 antibody response in BXD RI strains revealed a significant locus at D4Mit164 (29 cM, LRS=15.3) and two suggestive loci at D6Mit16 (30.5 cM, LRS=11.2) and D17Mit187 (47.4 cM, LRS=13.1). Genetic linkage analysis of the IgG1 anti-cF.IX antibody response revealed a suggestive locus at D1Mit218 (67 cM, LRS=14.1). Significant epistatic interaction was found between two loci (D8Mit45 and D16Mit47; LOD=6.54) for anti-AAV2 and two other loci (D5Mit348 and D15Mit161; LOD=7.66) for anti-cF.IX. These results indicate that multiple genetic loci independently regulate the isotype-specific antibody response to the AAV2 capsid and the cF.IX transgene.