Proceedings of the 28th Annual Congress of the International Liver Transplantation Society.

The 2023 Joint International Congress of the International Liver Transplantation Society (ILTS), the European Liver and Intestine Transplant Association (ELITA), and the Liver Intensive Care Group of Europe (LICAGE) held in Rotterdam, the Netherlands, marked a significant recovery milestone for the liver transplant community after COVID-19. With 1159 participants and a surge in abstract submissions, the event focused on "Liver Disorders and Transplantation: Innovations and Evolving Indications." This conference report provides a comprehensive overview of the key themes discussed during the event, encompassing Hepatology, Anesthesia and Critical Care, Acute Liver Failure, Infectious Disease, Immunosuppression, Pediatric Liver Transplantation, Living Donor Liver Transplantation, Transplant Oncology, Surgical Approaches, and Machine Perfusion. The congress provided a platform for extensive discussions on a wide range of topics, reflecting the continuous advancements and collaborative efforts within the liver transplant community.

Five-year follow-up of 96 weeks peginterferon plus tenofovir disoproxil fumarate in hepatitis D.

BACKGROUND & AIMS: Until recently, pegylated interferon-alfa-2a (PEG-IFNa) therapy was the only treatment option for patients infected with hepatitis D virus (HDV). Treatment with PEG-IFNa with or without tenofovir disoproxil fumarate (TDF) for 96 weeks resulted in HDV RNA suppression in 44% of patients at the end of therapy but did not prevent short-term relapses within 24 weeks. The virological and clinical long-term effects after prolonged PEG-IFNa-based treatment of hepatitis D are unknown. METHODS: In the HIDIT-II study patients (including 40% with liver cirrhosis) received 180 µg PEG-IFNa weekly plus 300 mg TDF once daily (n = 59) or 180 µg PEG-IFNa weekly plus placebo (n = 61) for 96 weeks. Patients were followed until week 356 (5 years after end of therapy). RESULTS: Until the end of follow-up, 16 (13%) patients developed liver-related complications (PEG-IFNa + TDF, n = 5 vs PEG-IFNa + placebo, n = 11; p = .179). Achieving HDV suppression at week 96 was associated with decreased long-term risk for the development of hepatocellular carcinoma (p = .04) and hepatic decompensation (p = .009). Including complications irrespective of PEG-IFNa retreatment status, the number of patients developing serious complications was similar with (3/18) and without retreatment with PEG-IFNa (16/102, p > .999) but was associated with a higher chance of HDV-RNA suppression (p = .024, odds ratio 3.9 [1.3-12]). CONCLUSIONS: Liver-related clinical events were infrequent and occurred less frequently in patients with virological responses to PEG-IFNa treatment. PEG-IFNa treatment should be recommended to HDV-infected patients until alternative therapies become available. Retreatment with PEG-IFNa should be considered for patients with inadequate response to the first course of treatment. CLINICAL TRIAL REGISTRATION: NCT00932971.

A rare benign tumor of the liver mimicking angiosarcoma: Anastomosing hemangioma.

Anastomosing hemangioma of the liver (AHL) is a very rare condition and limited to a few cases. It is often confused with well-differentiated angiosarcomas and causes overtreatment. In this report, we present a 53-year-old female patient diagnosed with AHL. Since the tumor is rarely seen, it is important to define well the imaging and pathological features for preventing unnecessary surgeries and related morbidities.

Risk of Bleeding After Percutaneous Endoscopic Gastrostomy in Patients Using Antithrombotic Drugs.

BACKGROUND: The rate of using antithrombotic (AT) drugs is frequently high in patients who require percutaneous endoscopic gastrostomy (PEG). The aim of this study was to determine whether the risk of bleeding after PEG increases in patients whose AT drugs were discontinued according to the European Society Gastrointestinal Endoscopy guidelines (warfarin for 5 d, low molecular weight heparin for 24 h, DOAC for 3 d, and clopidogrel for 7 d). PATIENTS AND METHODS: Data from 243 patients, who underwent PEG tube placement and received AT drugs and 206 patients who did not between 2018 and 2021 in our hospital, were evaluated retrospectively. Bleeding was defined as requiring blood transfusion, hematemesis and/or melena, decreased hemoglobin, or bleeding from PEG. RESULTS: A total of 243 (54.1%) patients (121 (49.7%), women, mean age (75.7 y) who underwent PEG and received AT drugs, and 206 (45.9%) patients who did not (92 (44.6%), women, mean age (63.15 y). The medications and bleeding rates of the patients are given in Table 1. The rate of bleeding in patients using AT medication was significantly higher than that in patients not using medication (Table 2) ( P = 0.007). When the AT drugs were compared among themselves, the bleeding risk did not differ. Bleeding was detected in 10 patients with bleeding from the PEG tube in 4 with melena. Bleeding detected in 14 patients was controlled with adrenaline injections. None of the patients required transfusion or repeat endoscopies. No bleeding-related deaths were reported. CONCLUSION: Even if patients receiving AT drugs are treated as recommended by international guidelines, it should be kept in mind that bleeding may occur after PEG, and the patients should be followed accordingly.

Proceedings of the 27th Annual Congress of the International Liver Transplantation Society.

After a virtual congress in 2021 and a previous absence in 2020 because of the coronavirus disease 2019 pandemic, the 27th Annual Congress of the International Liver Transplantation Society was held from May 4 to 7, 2022, in a hybrid format in Istanbul, with 1123 (58% on-site) liver transplant professionals from 61 countries attending the meeting. The hybrid format successfully achieved a balance of much yearned-for "in-person interaction" and global online participation. Almost 500 scientific abstracts were presented. In this report, the Vanguard Committee aims to present a summary of key invited lectures and selected abstracts for the liver transplant community.

A case report of reversible intracranial lesions after long-term Azathioprine therapy in an autoimmune hepatitis patient.

This study is written to report a case of 67-year-old female with known autoimmune hepatitis (AIH) who developed balance and walking difficulties. Clinical and imaging investigations were more suggestive of AIH suffering from lymphoproliferative disease. To identify the underlying suspected lymphoproliferative disease, series of brain scans were performed, which showed multiple brain lesions. This is a report on a striking case of multiple contrast enhanced brain lesions discovered in an AIH patient that was resolved upon withdrawal of azathioprine. Many side effects of azathioprine are acknowledged around the world; however, to the very best of our knowledge, an article on azathioprine inducing suspected malignancy was never reported.

Quality-of-life scores improve after 96 weeks of PEG-IFNa-2a treatment of hepatitis D: An analysis of the HIDIT-II trial.

BACKGROUND & AIMS: Infection with the hepatitis D virus (HDV) causes the most severe form of viral hepatitis with a high risk to develop clinical complications of liver disease. In addition, hepatitis delta has been shown to be associated with worse patient-reported outcomes. Until recently, only pegylated interferon alfa could be used to treat hepatitis delta. METHODS: Here, we investigated quality of life (QOL) as assessed by the Short Form 36 Health Survey (SF-36) in patients undergoing antiviral therapy with pegylated interferon alfa (PEG-IFNa-2a)-based treatment in the HIDIT-II trial. HIDIT-II was a randomized prospective trial exploring PEG-IFNa-2a with tenofovir disoproxil (TDF) or placebo for 96 weeks in patients with compensated hepatitis delta. Surveys completed by 83 study participants before, during, and after treatments were available. RESULTS: Overall, we observed a reduced QOL of HDV patients compared with a reference population, both in physical as well as mental scores. Interestingly, PEG-IFNa-2a treatment showed only minor impairment of the QOL during therapy. Moreover, HDV-RNA clearance was not associated with relevant changes in physical or social SF-36 scores, whereas an improvement of fibrosis during treatment was associated with increased QOL. Overall, slight improvements of the QOL scores were observed 24 weeks after the end of treatment as compared with baseline. TDF co-treatment had no influence on QOL. CONCLUSIONS: Overall, our findings suggest that PEG-IFNa-2a was reasonably tolerated even over a period of 96 weeks by hepatitis D patients reporting SF-36 questionnaires. Of note, several patients may benefit from PEG-IFNa-2a-based therapies with off-treatment improvements in quality of life.

Emerging drugs for hepatitis D.

INTRODUCTION: Chronic hepatitis delta (CHD) is the most severe form of chronic viral hepatitis. Until recently, its treatment consisted of pegylated interferon alfa (pegIFN) use. AREAS COVERED: Current and new drugs for treating CHD. Virus entry inhibitor bulevirtide has received conditional approval by the European Medicines Agency. Prenylation inhibitor lonafarnib and pegIFN lambda are in phase 3 and nucleic acid polymers in phase 2 of drug development. EXPERT OPINION: Bulevirtide appears to be safe. Its antiviral efficacy increases with treatment duration. Combining bulevirtide with pegIFN has the highest antiviral efficacy short-term. The prenylation inhibitor lonafarnib prevents hepatitis D virus assembly. It is associated with dose-dependent gastrointestinal toxicity and is better used with ritonavir which increases liver lonafarnib concentrations. Lonafarnib also possesses immune modulatory properties which explains some post-treatment beneficial flare cases. Combining lonafarnib/ritonavir with pegIFN has superior antiviral efficacy. Nucleic acid polymers are amphipathic oligonucleotides whose effect appears to be a consequence of phosphorothioate modification of internucleotide linkages. These compounds led to HBsAg clearance in a sizable proportion of patients. PegIFN lambda is associated with less IFN typical side effects. In a phase 2 study it led to 6 months off treatment viral response in one third of patients.

The DETAIL questionnaire is a useful and effective tool to assess spondyloarthritis in patients with inflammatory bowel disease.

Introduction: This study aimed to determine the effectiveness of adding a simple questionnaire related to musculoskeletal system to routine outpatient examination to detect undiagnosed axial and peripheral arthropathy in patients with inflammatory bowel disease (IBD). Materials and methods: A musculoskeletal symptom questionnaire was given to all patients with IBD during their follow-up examinations between January 2020 and November 2021. The DETAIL questionnaire consisting of six questions about the musculoskeletal system was administered by asking the patients with IBD. All patients who answered yes to at least one of these questions were directed to specialists in the rheumatology department to undergo a detailed examination. The patients who were diagnosed with rheumatological disease after further investigation were recorded. Patients with a known diagnosis of rheumatological disease were excluded from the study. Findings: There were 333 patients with IBD included in the study. Of these patients, 41 (12.3%) had a previously diagnosed rheumatological disease and were excluded from the evaluation. Of the remaining 292 patients (147 with ulcerative colitis, 139 with Crohn's disease and six with indeterminate colitis; mean age 42 years), 67 (23%) answered yes to at least one of the questions and were referred to a rheumatology consultation. Rheumatological examination was completed in 52 patients. As a result of the evaluations, 24 patients (8.2%) were diagnosed with enteropathic arthritis (14 axial, 9 peripheral, and 1 axial plus peripheral). Patients with newly diagnosed enteropathy had a lower median disease age than patients without enteropathy. Conclusion: The DETAIL questionnaire is an effective and easy tool for identifying missed cases of SpA in patients with IBD.

Non-invasive fibrosis markers for assessment of liver fibrosis in chronic hepatitis delta.

Assessment of liver fibrosis by non-invasive means is clinically important. Studies in chronic hepatitis delta (CHD) are scarce. We evaluated the performance of eight serum fibrosis markers [fibrosis-4 score (FIB-4), aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AAR), age-platelet index (API), AST-to platelet-ratio-index (APRI), Goteborg University Cirrhosis Index (GUCI), Lok index, cirrhosis discriminant score (CDS) and Hui score] in CHD and chronic hepatitis B (CHB). Liver stiffness was assessed by transient elastography (TE) in CHD. The ability of fibrosis markers to detect significant fibrosis and cirrhosis were evaluated in 202 CHB and 108 CHD patients using published and new cut-offs through receiver operating characteristics (ROC) analysis. The latter was also applied to obtain cut-offs for TE. APRI, Fib-4, API and Hui score were assessed for significant fibrosis, and APRI, GUCI, Lok index, CDS and AAR for cirrhosis determination. Fibrosis markers displayed weak performance in CHB for significant fibrosis with area under ROC (AUROC) curves between 0.62 and 0.71. They did slightly better for CHD. TE displayed an AUROC of 0.92 and performed better than serum fibrosis markers (p < 0.05 for fibrosis markers). For cirrhosis determination, CDS and Lok Index displayed an AUROC of 088 and 0.89 in CHB and GUCI, Lok index and APRI displayed AUROCs around 0.90 in CHD. TE displayed the best AUROC (0.95). Hence TE is superior to serum fibrosis markers for diagnosing significant liver fibrosis and cirrhosis. GUCI, Lok index and APRI displayed a reasonable performance in CHD, which needs further confirmation.

Outcomes of Surgical Strategies for Living Donor Liver Transplantation in Patients With Portal Vein Thrombosis: A Cohort Study.

BACKGROUND: Adequate portal flow to the liver graft is the requirement of a successful liver transplant (LT). Historically, portal vein thrombosis (PVT) was a contraindication for LT, especially for living donor LT (LDLT), demanding technically more difficult operations and advanced technique. In this study, the outcomes of patients with and without PVT after LDLT were compared. METHODS: Adult LDLTs performed by 2 centers (n = 335) between 2013 and 2020 were included into this large cohort study. PVT was classified based on Yerdel classification grade 1 to 4. RESULTS: Sixty-two patients with PVT constituted 19% of the study cohort of 335 recipients. While mean platelet count was found to be lower (P = .011) in the PVT group, patient age (P = .035), operation duration (P = .001), and amount of intraoperative blood transfusion (P = .010) were found to be higher. Incidence of PVT was higher in female patients than males (22.7% vs 16.1%, P = .037). There was no significant difference in survival between patients with and without PVT on 30-day (P = .285), 90-day (P = .565), 1-year (P = .777), and overall survival (P = .917). Early thrombosis did not show a better survival rate than Grades 2, 3, or 4 PVT. Thrombosis limited to portal vein was not found to bring a survival advantage compared with Grade 3 and 4 thromboses. Eversion thrombectomy was the most common procedure (66%) to overcome PVT intraoperatively. CONCLUSION: Although technically more challenging, PVT is not a contraindication of LDLT. Similar outcomes can be achieved in LDLT in patients with PVT after proper restoration of portal flow, which eliminates the default survival disadvantage of patients with PVT.

Behçet's Disease-related Budd-Chiari Syndrome Successfully Managed with anti-TNF Antibody: A Case Report and Review of the Literature.

Behçet's disease (BD) is multisystemic vasculitis with heterogeneous clinical manifestations. We describe the case of a 26-year-old man who presented with Budd-Chiari syndrome (BCS) related to BD. The patient received infliximab (IFX) due to the severity of vascular involvement. Subsequently, after IFX therapy, hospital-acquired pneumonia, trapped lung, and fungal infection of the lung and central nervous system developed as complications. The patient benefited from a second course of IFX and clinical remission was achieved following early identification and treatment of complications. Data on the presentation and prognosis of BCS related to BD are extremely limited. Our case report supports the growing evidence that anti-TNF antibody is a promising treatment for BD-related BCS. LEARNING POINTS: Behçet's disease-related Budd-Chiari syndrome is a rare form of vascular involvement that severely affects mortality.Behçet's disease-related Budd-Chiari syndrome is frequently confused with idiopathic thrombosis and may be underdiagnosed.Infliximab could be a therapeutic option for refractory Behçet's disease with major vascular involvement, but the increased risk of opportunistic infections should be kept in mind.

Clinical and Endoscopic Consequences of Delay in Stent Exchange Procedures With ERCP During the Covid-19 Pandemic.

INTRODUCTION: During the COVID-19 pandemic, elective endoscopic retrograde cholangiopancreatography (ERCP) procedures have been postponed as recommended by international guidelines. In this study, the results of biliary and pancreatic ERCP procedures that had to be postponed during the pandemic process were investigated. MATERIALS AND METHODS: Forty-seven patients whose stent exchange procedures with ERCP were postponed between March 2020 and June 2020 due to the COVID-19 pandemic were included in the study. Patients were evaluated in 2 groups as delayed biliary procedures (n: 32) and delayed pancreatic procedures (n: 15). Clinical problems (biliary or pancreatic pain, itching, cholangitis, etc.) and technical problems encountered during the procedure (stent migration, abundant stone sludge in the bile ducts, etc.) were compared with 46 patients who could be treated without delay (39 interventions for the biliary system and seven interventions for the pancreas). FINDINGS: Considering the procedures for the biliary system, there was no difference in age and sex between the groups. Although clinical problems in biliary procedures were more common in the group with delay than in those without delay, this difference was not significant (34% vs. 20%; P : 0.14). The technical problems encountered during the procedures in the group with delay were significantly higher than those without delay (21% vs. 2.5%; P : 0.019), with stent migration being the most common problem (n: 5). Age and sex did not differ in the patients who had pancreatic interventions with and without delay. The clinical problems that developed in the patients did not differ between the groups with and without delay (26% vs. 28%; P : 0.8). Although technical problems were encountered in 1 out of 15 patients in the group with delay, no technical problem was experienced in the group without delay ( P : 0.68). CONCLUSION: Postponing elective ERCP procedures for the biliary system not for the pancreatic system during the COVID-19 pandemic brings technical problems.

Proceedings of the 26th Annual Virtual Congress of the International Liver Transplantation Society.

After a 1-y absence due to the coronavirus disease 2019 pandemic, the 26th Annual Congress of the International Liver Transplantation Society was held from May 15 to 18, 2021, in a virtual format. Clinicians and researchers from all over the world came together to share their knowledge on all the aspects of liver transplantation (LT). Apart from a focus on LT in times of coronavirus disease 2019, featured topics of this year's conference included infectious diseases in LT, living donation, machine perfusion, oncology, predictive scoring systems and updates in anesthesia/critical care, immunology, radiology, pathology, and pediatrics. This report presents highlights from invited lectures and a review of the select abstracts. The aim of this report, generated by the Vanguard Committee of International Liver Transplantation Society, is to provide a summary of the most recent developments in clinical practice and research in LT.

The role of preoperative psychosocial counseling on the improvement of the recipient compliance and speed of recovery after liver transplantation - A systematic review of the literature and expert panel recommendations.

BACKGROUND: Psychosocial disorders ranging from anxiety to severe psychiatric diseases and active alcohol/substance abuse are frequent in liver transplant candidates and potentially associated with worse post- transplant outcomes. Therefore, psychosocial evaluation is mandatory to optimize success after liver transplantation. However, how to carry out this evaluation, the type of intervention needed and its potential impact on patient outcome remain unclear. OBJECTIVES: To investigate whether psychosocial assessment may help in predicting risks of poor outcome; and to investigate whether psychosocial interventions may mitigate these risks and improve posttransplant outcomes, in particular compliance and speed of recovery. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. The protocol was registered on PROSPERO CRD42021238361. Main outcomes assessed were mortality, alcohol relapse, rejection, and medication compliance. RESULTS: Fifteen studies were analyzed including five observational comparative and ten observational noncomparative studies. Preoperative psychosocial evaluation of LT candidates was associated with higher concordance with the treatment plan (i.e., higher adherence to treatment and lower alcohol relapse) and lower rates of rejection. Psychosocial assessment tools were used in some studies to guide the evaluation, but their predictive ability remains debated, and they should not be used in isolation. Most of the interventions were studied in patients with alcohol related issues. In this context, support by specialized teams was associated with better posttransplant outcome, especially through a decrease in post-transplant alcohol relapse. CONCLUSIONS: Preoperative psychosocial assessment should be provided in order to detect patients at increased risk of poorer post-transplant outcome, in particular in terms of concordance to the treatment plan (Quality of Evidence; Low | Grade of Recommendation; Strong/For). The experts suggest that, when possible, provision of preoperative psychological assessment and concomitant interventions aimed at improving the concordance to treatment plans will positively impact the success of liver transplantation. (Quality of Evidence; Very Low | Grade of Recommendation; Strong/For].

A phase 2 dose-finding study of lonafarnib and ritonavir with or without interferon alpha for chronic delta hepatitis.

BACKGROUND AND AIMS: Proof-of-concept studies demonstrated lonafarnib (LNF), a first-in-class oral prenylation inhibitor, efficacy in patients infected with HDV. The lonafarnib with ritonavir for HDV-2 (LOWR-2) study's aim was to identify optimal combination regimens of LNF + ritonavir (RTV) ± pegylated interferon alpha (PEG-IFNα) with efficacy and tolerability for longer-term dosing. Here we report the safety and efficacy at end of treatment for up to 24 weeks. APPROACH AND RESULTS: Fifty-five patients with chronic HDV were consecutively enrolled in an open-label, single-center, phase 2 dose-finding study. There were three main treatment groups: high-dose LNF (LNF ≥ 75 mg by mouth [po] twice daily [bid] + RTV) (n = 19, 12 weeks); all-oral low-dose LNF (LNF 25 or 50 mg po bid + RTV) (n = 24, 24 weeks), and combination low-dose LNF with PEG-IFNα (LNF 25 or 50 mg po bid + RTV + PEG-IFNα) (n = 12, 24 weeks). The primary endpoint, ≥2 log10 decline or < lower limit of quantification of HDV-RNA from baseline at end of treatment, was reached in 46% (6 of 13) and 89% (8 of 9) of patients receiving the all-oral regimen of LNF 50 mg bid + RTV, and combination regimens of LNF (25 or 50 mg bid) + RTV + PEG-IFNα, respectively. In addition, multiple patients experienced well-tolerated transient posttreatment alanine aminotransferase increases, resulting in HDV-RNA negativity and alanine aminotransferase normalization. The proportions of grade 2 and 3 gastrointestinal adverse events in the high-dose versus low-dose groups were 49% (37 of 76) and only 22% (18 of 81), respectively. CONCLUSIONS: LNF, boosted with low-dose RTV, is a promising all-oral therapy, and maximal efficacy is achieved with PEG-IFNα addition. The identified optimal regimens support a phase 3 study of LNF for the treatment of HDV.

The impact of COVID-19 disease on the natural course of cirrhosis: Before and after starting vaccination.

Background: Cirrhosis has been reported as an important risk factor for death in coronavirus disease 2019 (COVID-19) disease. In this study, we aimed to investigate the effects of COVID-19 on the natural course of cirrhosis before and after starting vaccination. Methods: The cirrhosis patients in our cohort (n: 140; median age:56; 71 female) were included in this study. The median MELD (Model For End-stage Liver Disease) score was 11 (6-25) and CCI (Charlson Comorbidity Index) score was 4 (1-11). In total, 85 had CTP (Child-Turcotte-Pugh)-A, 44 had CTP-B and 11 had CTP-C cirrhosis. The course of COVID-19 in this patient group was evaluated before and after COVID-19 vaccination. Results: Between March 2020 and January 2021, 36 of the 140 cirrhosis patients had developed COVID-19. Cirrhosis (+)/COVID-19 (+) and Cirrhosis (+)/COVID-19 (-) groups did not differ in terms of age, CCI and MELD-Na scores, or gender. There were six deaths in the Cirrhosis (+)/COVID-19 (+) group and five in the Cirrhosis (+)/COVID-19 (-) group [6/36 (16.6%) vs. 5/104 (4.8%); p: 0.03]. Patients who died were older, had higher CCI and MELD-Na scores, and lower albumin levels. Having had COVID-19 [6.45 (1.43-29.4); p: 0.015], higher MELD-Na score [1.35 (1.18-1.60); p: 0.001] and higher CCI score [1.65 (1.14-2.39); p: 0.008] were found to be independent predictors of mortality. After effective vaccination started in Turkey, only 11 of the remaining 129 patients developed COVID-19, and only one patient died, who was unvaccinated. Discussion: In our cirrhotic cohort, COVID-19 disease was associated with 16% mortality in the pre-vaccination period. COVID-19 vaccination prevents serious illness and death due to COVID-19 in cirrhotic patients.