The Course of Endoscopic Treatment Success in Biliary Complications After Living Donor Liver Transplantation.

Objective: Our aim was to present the results of endoscopic retrograde cholangiopancreatography (ERCP) after living donor liver transplantation (LDLT) between February 2015 and June 2021. Methods: Clinical data included LDLT indications, time to perform ERCP after LDLT, number of ERCP procedures, indications for ERCP, and all treatment outcomes, including ERCP, percutaneous, and surgical interventions. We compared the obtained data with our previous study published by our team in 2018, which included 446 patients who underwent ERCP for biliary complications after LDLT between 2005 and 2015. Results: We performed ERCP in 283 of 1506 patients with LDLT who underwent duct-to-duct anastomosis during transplantation and then developed biliary complications. Our endoscopic success rates were 60.9% and 71.0% in the previous and present studies, respectively. Conclusions: Our findings suggest that the success rate of endoscopic treatment of biliary complications in patients with LDLT increases in correlation with the increasing experience of clinicians treating these patients.

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.

SARS-CoV-2 vaccination and risk of severe COVID-19 outcomes in patients with autoimmune hepatitis.

BACKGROUND: Data regarding outcome of Coronavirus disease 2019 (COVID-19) in vaccinated patients with autoimmune hepatitis (AIH) are lacking. We evaluated the outcome of COVID-19 in AIH patients who received at least one dose of Pfizer- BioNTech (BNT162b2), Moderna (mRNA-1273) or AstraZeneca (ChAdOx1-S) vaccine. PATIENTS AND METHODS: We performed a retrospective study on AIH patients with COVID-19. The outcomes of AIH patients who had acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection after at least one dose of COVID-19 vaccine were compared to unvaccinated patients with AIH. COVID-19 outcome was classified according to clinical state during the disease course as: (i) no hospitalization, (ii) hospitalization without oxygen supplementation, (iii) hospitalization with oxygen supplementation by nasal cannula or mask, (iv) intensive care unit (ICU) admission with non-invasive mechanical ventilation, (v) ICU admission with invasive mechanical ventilation or (vi) death, and data was analyzed using ordinal logistic regression. RESULTS: We included 413 (258 unvaccinated and 155 vaccinated) patients (81%, female) with a median age of 52 (range: 17-85) years at COVID-19 diagnosis. The rates of hospitalization were (36.4% vs. 14.2%), need for any supplemental oxygen (29.5% vs. 9%) and mortality (7% vs. 0.6%) in unvaccinated and vaccinated AIH patients with COVID-19. Having received at least one dose of SARS-CoV-2 vaccine was associated with a significantly lower risk of worse COVID-19 severity, after adjusting for age, sex, comorbidities and presence of cirrhosis (adjusted odds ratio [aOR] 0.18, 95% confidence interval [CI], 0.10-0.31). Overall, vaccination against SARS-CoV-2 was associated with a significantly lower risk of mortality from COVID-19 (aOR 0.20, 95% CI 0.11-0.35). CONCLUSIONS: SARS-CoV-2 vaccination significantly reduced the risk of COVID-19 severity and mortality in patients with AIH.

Autoimmune hepatitis and liver transplantation: Indications, and recurrent and de novo autoimmune hepatitis.

Autoimmune hepatitis is a chronic inflammatory disease of the liver that is characterized by circulating autoantibodies and elevated serum globulin levels. Liver transplantation may be required for patients with acute liver failure, decompensated cirrhosis, and hepatocellular carcinoma. Recurrence is defined as development of the same disease in the allograft following liver transplantation. Autoimmune hepatitis recurs in 36%-68% of the recipients 5 years after liver transplantation. De novo autoimmune hepatitis is the development of autoimmune hepatitis like clinical and laboratory characteristics in patients who had undergone liver transplantation for causes other than autoimmune hepatitis. Diagnostic work up for recurrent and de novo autoimmune hepatitis is similar to the diagnosis of the original disease, and it is usually difficult. Predniso(lo)ne with or without azathioprine is the main treatment for recurrent and de novo autoimmune hepatitis. Early diagnosis and treatment are vital for patient prognosis because de novo autoimmune hepatitis and recurrent autoimmune hepatitis cause graft loss and result in subsequent retransplantation if medical treatment fails.

Risk factors and outcomes associated with recurrent autoimmune hepatitis following liver transplantation.

BACKGROUND & AIMS: Autoimmune hepatitis can recur after liver transplantation (LT), though the impact of recurrence on patient and graft survival has not been well characterized. We evaluated a large, international, multicenter cohort to identify the probability and risk factors associated with recurrent AIH and the association between recurrent disease and patient and graft survival. METHODS: We included 736 patients (77% female, mean age 42±1 years) with AIH who underwent LT from January 1987 through June 2020, among 33 centers in North America, South America, Europe and Asia. Clinical data before and after LT, biochemical data within the first 12 months after LT, and immunosuppression after LT were analyzed to identify patients at higher risk of AIH recurrence based on histological diagnosis. RESULTS: AIH recurred in 20% of patients after 5 years and 31% after 10 years. Age at LT ≤42 years (hazard ratio [HR] 3.15; 95% CI 1.22-8.16; p = 0.02), use of mycophenolate mofetil post-LT (HR 3.06; 95% CI 1.39-6.73; p = 0.005), donor and recipient sex mismatch (HR 2.57; 95% CI 1.39-4.76; p = 0.003) and high IgG pre-LT (HR 1.04; 95% CI 1.01-1.06; p = 0.004) were associated with higher risk of AIH recurrence after adjusting for other confounders. In multivariate Cox regression, recurrent AIH (as a time-dependent covariate) was significantly associated with graft loss (HR 10.79, 95% CI 5.37-21.66, p <0.001) and death (HR 2.53, 95% CI 1.48-4.33, p = 0.001). CONCLUSION: Recurrence of AIH following transplant is frequent and is associated with younger age at LT, use of mycophenolate mofetil post-LT, sex mismatch and high IgG pre-LT. We demonstrate an association between disease recurrence and impaired graft and overall survival in patients with AIH, highlighting the importance of ongoing efforts to better characterize, prevent and treat recurrent AIH. LAY SUMMARY: Recurrent autoimmune hepatitis following liver transplant is frequent and is associated with some recipient features and the type of immunosuppressive medications use. Recurrent autoimmune hepatitis negatively affects outcomes after liver transplantation. Thus, improved measures are required to prevent and treat this condition.

Post COVID-19 irritable bowel syndrome.

OBJECTIVES: The long-term consequences of COVID-19 infection on the gastrointestinal tract remain unclear. Here, we aimed to evaluate the prevalence of gastrointestinal symptoms and post-COVID-19 disorders of gut-brain interaction after hospitalisation for SARS-CoV-2 infection. DESIGN: GI-COVID-19 is a prospective, multicentre, controlled study. Patients with and without COVID-19 diagnosis were evaluated on hospital admission and after 1, 6 and 12 months post hospitalisation. Gastrointestinal symptoms, anxiety and depression were assessed using validated questionnaires. RESULTS: The study included 2183 hospitalised patients. The primary analysis included a total of 883 patients (614 patients with COVID-19 and 269 controls) due to the exclusion of patients with pre-existing gastrointestinal symptoms and/or surgery. At enrolment, gastrointestinal symptoms were more frequent among patients with COVID-19 than in the control group (59.3% vs 39.7%, p<0.001). At the 12-month follow-up, constipation and hard stools were significantly more prevalent in controls than in patients with COVID-19 (16% vs 9.6%, p=0.019 and 17.7% vs 10.9%, p=0.011, respectively). Compared with controls, patients with COVID-19 reported higher rates of irritable bowel syndrome (IBS) according to Rome IV criteria: 0.5% versus 3.2%, p=0.045. Factors significantly associated with IBS diagnosis included history of allergies, chronic intake of proton pump inhibitors and presence of dyspnoea. At the 6-month follow-up, the rate of patients with COVID-19 fulfilling the criteria for depression was higher than among controls. CONCLUSION: Compared with controls, hospitalised patients with COVID-19 had fewer problems of constipation and hard stools at 12 months after acute infection. Patients with COVID-19 had significantly higher rates of IBS than controls. TRIAL REGISTRATION NUMBER: NCT04691895.

Prevalence of Gastrointestinal Symptoms in Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Results of the Prospective Controlled Multinational GI-COVID-19 Study.

INTRODUCTION: Gastrointestinal (GI) symptoms in coronavirus-19 disease (COVID-19) have been reported with great variability and without standardization. In hospitalized patients, we aimed to evaluate the prevalence of GI symptoms, factors associated with their occurrence, and variation at 1 month. METHODS: The GI-COVID-19 is a prospective, multicenter, controlled study. Patients with and without COVID-19 diagnosis were recruited at hospital admission and asked for GI symptoms at admission and after 1 month, using the validated Gastrointestinal Symptom Rating Scale questionnaire. RESULTS: The study included 2036 hospitalized patients. A total of 871 patients (575 COVID+ and 296 COVID-) were included for the primary analysis. GI symptoms occurred more frequently in patients with COVID-19 (59.7%; 343/575 patients) than in the control group (43.2%; 128/296 patients) (P < 0.001). Patients with COVID-19 complained of higher presence or intensity of nausea, diarrhea, loose stools, and urgency as compared with controls. At a 1-month follow-up, a reduction in the presence or intensity of GI symptoms was found in COVID-19 patients with GI symptoms at hospital admission. Nausea remained increased over controls. Factors significantly associated with nausea persistence in COVID-19 were female sex, high body mass index, the presence of dyspnea, and increased C-reactive protein levels. DISCUSSION: The prevalence of GI symptoms in hospitalized patients with COVID-19 is higher than previously reported. Systemic and respiratory symptoms are often associated with GI complaints. Nausea may persist after the resolution of COVID-19 infection.

Effects of larazotide acetate, a tight junction regulator, on the liver and intestinal damage in acute liver failure in rats.

BACKGROUND AND AIM: The epithelial cells are the strongest determinants of the physical intestinal barrier. Tight junctions (TJs) hold the epithelial cells together and allow for selective paracellular permeability. Larazotide acetate (LA) is a synthetic octapeptide that reduces TJ permeability by blocking zonulin receptors. In this study, we aimed to investigate the effects of LA, a TJ regulator, on the liver and intestinal histology in the model of acute liver failure (ALF) in rats. MATERIALS AND METHODS: The thioacetamide (TAA) group received intraperitoneal (ip) injections of 300 mg/kg TAA for 3 days. The TAA+LA(dw) (drinking water) group received prophylactic 0.01 mg/mL LA orally for 7 days before the first dose of TAA. The LA(dw) group received 0.01 mg/mL LA orally. The TAA + LA(g) (gavage) group received prophylactic 0.01 mg/mL LA via oral gavage for 7 days before the first dose of TAA. The LA(g) group received 0.01 mg/mL LA via oral gavage. While liver tissue was evaluated only with light microscopy, intestinal samples were examined with light and electron microscopy. RESULTS: Serum ammonia, AST, and ALT levels in the TAA group were significantly higher than in control groups (all p < 0.01). Serum ALT levels in the TAA + LA(dw) group were significantly lower than in the TAA group (p < 0.05). However, serum ammonia and ALT levels did not differ between the TAA and other groups. Serious liver damage in the TAA group was accompanied by marked intestinal damage. There was no significant difference between the TAA and TAA + LA(dw) groups and TAA and TAA + LA(g) groups for liver damage scores. However, intestinal damage scores significantly decreased in the TAA + LA(dw) group compared to the TAA group. In the TAA + LA(dw) group, fusion occurred between the surface epithelial cells of neighboring villi and connecting regions formed as epithelial bridges between the villi. CONCLUSION: Our findings suggest that LA reduced intestinal damage by acting on TJs in the TAA-induced ALF model in rats.

Analysis of risk factors affecting the development of peptic ulcer perforation: case-control study.

AIM: The aim of the to determine the risk factors associated with increased risk of peptic ulcer perforation (PUP). MATERIAL AND METHODS: The demographic, clinic, and biochemical parameters of 65 patients (PUP group) who underwent PUP surgery at our clinic between June 2009 and September 2016 were compared with the data of 134 patients (control group) who underwent endoscopy at a gastroenterology clinic for dyspeptic complaints. The control group were matched at random in a 1 : 2 ratio with the PUP group. Univariate analyses were used to compare different variables and variables with clinical significance, and p ≤ 0.05 was used in the backward stepwise logistic regression model. RESULTS: This study included 65 patients with peptic ulcer perforation aged 17 to 92 years (PUP group) and 134 patients with dyspeptic complaints aged 18 to 87 years (control group). Univariate analysis showed that statistically significant differences were found between groups in terms of non-steroidal anti-inflammatory drugs usage (p = 0.042; OR = 1.868), smoking (p < 0.001; OR = 5.124), old age (p = 0.003), low body mass index (BMI) (p < 0.001), and low hemoglobin (Hb) (p = 0.002). However multivariate analysis showed that increasing age (p = 0.004; OR = 1.035), smoking (p = 0.007; OR = 3.591), decreasing Hb (p = 0.042; OR = 1.277), and decreasing BMI (p < 0.001; OR = 1.669) were independent clinically significant risk factors for development of PUP. CONCLUSIONS: This study showed that decreased BMI, decreased Hb, increased age, and smoking were independent risk factors for development of PUP. Thus, this group of patients needs particular attention paid to suggestive symptoms with early diagnosis and optimal management of peptic ulcer disease.

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.

Feasibility of telehealth in the management of autoimmune hepatitis before and during the COVID-19 pandemic.

OBJECTIVES: We aimed to evaluate the feasibility of telehealth in the management of patients with autoimmune hepatitis (AIH). The COVID-19 outbreak during the study period provided an opportunity to evaluate any pandemic influence on how telehealth was perceived by patients and physicians. METHODS: We included patients with AIH who were followed in the Harran University hospital, Turkey. Patients were managed by either remote telehealth or standard care. RESULTS: A total of 46 (telehealth, n=19 and standard care, n= 27) patients (40 female) with a median age of 32 (range 17-74) years at diagnosis were included in the study. Until the start of the COVID-19 pandemic, the rates of biochemical remission and relapse after remission were similar in the telehealth and standard care groups (89.5% vs. 89.1% and 15.8% vs. 25.9%, p=ns, for both). The telehealth group maintained remission significantly better than the standard care group (100% vs. 77.3%, p=0.035) during the COVID-19 period. All relapses were due to non-adherence to therapy. Psychiatric problems, pregnancy-related issues and drug side-effects could all be managed remotely by telehealth. CONCLUSIONS: In this study, we show for the first time that telehealth is a feasible alternative for managing AIH, both under normal circumstances and during the COVID-19 pandemic. EXPERT OPINION: Autoimmune hepatitis (AIH) requires long-life lifelong immunosuppression and follow-up for most patients. The use of telehealth may be an alternative way to evaluate these patients remotely. We show for the first time that telehealth is effective and useful in the management of AIH in regular time as well during COVID-19. We hope that our study can extend use of telehealth in the evaluation of patients with other causes of chronic liver disease.

Validation of Risk Scoring Systems in Ursodeoxycholic Acid-Treated Patients With Primary Biliary Cholangitis.

INTRODUCTION: Risk stratification based on biochemical variables is a useful tool for monitoring ursodeoxycholic acid (UDCA)-treated patients with primary biliary cholangitis (PBC). Several UDCA response criteria and scoring systems have been proposed for risk prediction in PBC, but these have not been validated in large external cohorts. METHODS: We performed a study on data of 1746 UDCA-treated patients with PBC from 25 centers in Europe, United States, and Canada. The prognostic performance of the risk scoring systems (GLOBE and UK-PBC) and the UDCA response criteria (Barcelona, Paris I, Paris II, Rotterdam, and Toronto) were evaluated. We regarded cirrhosis-related complications (ascites, variceal bleeding, and/or hepatic encephalopathy) as clinical end points. RESULTS: A total of 171 patients reached a clinical end point during a median 7 years (range 1-16 years) of follow-up. The 5-, 10- and 15-year adverse outcome-free survivals were 95%, 85%, and 77%. The GLOBE and UK-PBC scores predicted cirrhosis-related complications better than the UDCA response criteria. The hazard ratio (HR) for a 1 standard deviation increase was HR 5.05 (95% confidence interval (CI): 4.43-5.74, P < 0.001) for the GLOBE score and HR 3.39 (95% CI: 3.10-3.72, P < 0.001) for the UK-PBC score. Overall, the GLOBE and UK-PBC risk scores showed similar and excellent prognostic performance (C-statistic, 0.93; 95% CI: 0.91%-95% vs 0.94; 95% CI: 0.91%-0.96%). DISCUSSION: In our international, multicenter PBC cohort, the GLOBE and UK-PBC risk scoring systems were good predictors of future cirrhosis-related complications.