Ameliorative Effects of Larazotide Acetate on Intestinal Permeability and Bacterial Translocation in Acute Pancreatitis Model in Rats.

BACKGROUND: Intestinal barrier dysfunction in acute pancreatitis (AP) may progress to systemic inflammatory response syndrome (SIRS) and multi-organ failures by causing bacterial translocation. Larazotide acetate (LA) is a molecule that acts as a tight junction (TJ) regulator by blocking zonulin (Zo) receptors in the intestine. AIMS: In our study, we aimed to investigate the effects of LA on intestinal barrier dysfunction and bacterial translocation in the AP model in rats. METHODS: Thirty-two male Sprague-Dawley rats were divided into 4 groups; control, larazotide (LAR), AP, and AP + LAR. The AP model was created by administering 250 mg/100 g bm L-Arginine intraperitoneally 2 times with an hour interval. AP + LAR group received prophylactic 0.01 mg/mL LA orally for 7 days before the first dose of L-Arginine. For intestinal permeability analysis, fluorescein isothiocyanate-dextran (FITC-Dextran) was applied to rats by gavage. The positivity of any of the liver, small intestine mesentery, and spleen cultures were defined as bacterial translocation. Histopathologically damage and zonulin immunoreactivity in the intestine were investigated. RESULTS: Compared to the control group, the intestinal damage scores, anti-Zo-1 immunoreactivity H-Score, serum FITC-Dextran levels and bacterial translocation frequency (100% versus 0%) in the AP group were significantly higher (all p < 0.01). Intestinal damage scores, anti-Zo-1 immunoreactivity H-score, serum FITC-Dextran levels, and bacterial translocation frequency (50% versus 100%) were significantly lower in the AP + LAR group compared to the AP group (all p < 0.01). CONCLUSIONS: Our findings show that LA reduces the increased intestinal permeability and intestinal damage by its effect on Zo in the AP model in rats, and decreases the frequency of bacterial translocation as a result of these positive effects.

The efficacy and tolerability of glecaprevir/pibrentasvir treatment in a real-world chronic hepatitis C patients cohort.

Background and Aim: The aims of the present study were to evaluate the real-life efficacy and tolerability of glecaprevir (GLE)/pibrentasvir (PIB) in the treatment of patients with chronic hepatitis C (CHC). Materials and Methods: Between May 2019 and May 2022, 686 patients with CHC, treated with GLE/PIB combination from 21 participating centers in Turkiye, were enrolled in the study. Results: All patients were Caucasian, and their median age was 56 years. At the start of GLE/PIB treatment, the median serum Hepatitis C virus RNA and serum alanine amino transaminase (ALT) levels were 6.74 log10 IU/mL and 47 U/L, respectively. Fifty-three percent of the patients were infected with genotype 1b, followed by genotype 3 (17%). Diabetes was the more common concomitant disease. The sustained virological response (SVR12) was 91.4% with intent-to-treat analysis and 98.5% with per protocol analysis. The SVR12 rates were statistically significant differences between the patients who were i.v. drug users and non-user (88.0% vs. 98.8%, p=0.025). From the baseline to SVR12, the serum ALT levels and Model for End-Stage Liver Disease score were significantly improved (p<0.001 and p=0.014, respectively). No severe adverse effect was observed. Conclusion: GLE/PIB is an effective and tolerable treatment in patients with CHC.

Fingolimod induced fulminant liver failure requiring liver transplantation: A case report.

Fingolimod has been used for about ten years to treat multiple recurrent sclerosis. It has been reported that Fingolimod causes an elevation in liver enzymes. In this case report, the clinical and laboratory parameters improved after discontinuation of the drug. However, there is no publication in the literature regarding acute liver failure and liver transplantation following Fingolimod treatment. In this article, we presented a 33 - year - old female patient who developed acute liver failure and underwent liver transplantation after Fingolimod treatment for recurrent multiple sclerosis.

Endoscopic treatment of biliary complications in donors after living donor liver transplantation in a high volume transplant center.

BACKGROUND/AIMS: Although living donor liver transplantation (LDLT) has been accepted as a primary treatment for adults with end-stage liver disease, concerns about donor health have been emerged. As LDLT is technically complex, it creates perioperative morbidity and mortality risk in donors. Biliary complications such as stricture and leakage are seen most frequently in donors after liver transplantation. While some of these complications get treated with conservative approach, endoscopic, surgical, and percutaneous interventions may be required in some others. We aimed to present endoscopic retrograde cholangiography (ERC) results in donors who developed biliary complications after LDLT. MATERIALS AND METHODS: Between June 2010 and January 2018, a total of 1521 donors (1291 right lobe grafts, 230 left lobe grafts) of patients who underwent LDLT, were retrospectively reviewed. 63 donors who underwent ERC due to biliary complication, were included in the study. RESULTS: Biliary stricture was found in 1.6% (25/1521), biliary leakage in 2.1% (33/1521), and stricture and leakage together in 0.3% (5/1521) donors. Our endoscopic success rates in patients with biliary leakage, biliary stricture, and stricture and leakage were 85% (28/33), 92% (23/25), and 80% (4/5), respectively. Surgical treatment was performed on 12.6% (8/63) donors who failed ERC. CONCLUSION: We found that ERC is a successful treatment for post-LDLT donors who have biliary complications.

Endoscopic treatment of biliary complications in left lobe living donor liver transplantation.

PURPOSE: Almost all of the publications regarding the treatment of biliary complications after liver transplantation are related to biliary complications after right lobe living donor liver transplantation (LDLT) and cadaveric liver transplantation (LT). The number of publications regarding endoscopic treatment of biliary complications after left lobe LDLT is negligible. In this study, we aimed to present the results of endoscopic treatments applied in the management of biliary complications developed in left-lobe duct-to-duct LDLT patients. PATIENTS AND METHODS: Between 2008 and 2018, patients with duct-to-duct anastomosis who underwent ERCP due to biliary complication after left lobe LDLT were included in the study. Clinical data included patient demographics, indications for LDLT, duration till the first ERCP after LDLT, number of ERCP procedures, ERCP indications (stricture or leak), and treatment outcomes, including the need for percutaneous and surgical interventions. RESULTS: Among 13 patients who underwent ERCP, 2 (15%) had biliary leakage and 11 (8%) had an anastomotic stricture. Our endoscopic success rate was 100% in patients with biliary stricture. Despite the implementation of ERCP on two patients with leakage, they died due to the biliary complication. CONCLUSION: Our results suggest that endoscopic treatment methods are successful in the management of biliary stricture complication in patients with left lobe LDLT and duct-to-duct anastomosis. Although our findings show that endoscopic treatments fail when there is a leakage after left lobe LDLT, there is a need for further studies that include more patients to reach a definite conclusion.