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Background: This study aimed to investigate the characteristics of severe hepatitis (SH), acute liver injury (ALI), and acute liver failure trt patients with mushroom-induced hepatotoxicity. Methods: Data of patients between 2010 and 2019 were retrospectively reviewed. Twenty-four patients with mushroom-induced hepatotoxicity were included and divided into 3 groups: SH, ALI, and ALF. SH was defined as transaminase level >= 10 times ULN, international normalized ratio (INR) 1.5, presumed acute illness onset, and the absence of HE. ALF was diagnosed based on the presence of HE of any degree, with INR> 1.5, presumed acute illness onset, and the absence of cirrhosis. Results: The mean age of the patients was 51.6 years; 13 (54.2%) were female. At admission, 18 patients (75%) had SH, 5 (21%) had ALI, and 1 (4.1%) had ALF. During follow-up, 6 of the 18 SH (33%) patients progressed to All and 2 of the 5 ALI (40%) patients progressed to ALF. No progression to ALI or ALF was observed in the 8 SH cases with a baseline MELD score of

Introduction and aim. Sofosbuvir (SOF)-based regimen has been shown to have high efficacy even in patients with decompensated cirrhosis. Treated patients may experience various degrees of hepatic recovery ranging from stabilization of liver function, to removal from liver transplant wait lists. The frequency of these occurrences in larger transplant eligible patient populations is unknown. The aim of this study was to assess the efficacy of SOF-based therapy in HCV infected transplant eligible patients and to evaluate short term changes in liver function and the effect on their liver transplant status. Material and methods. A retrospective multicenter Canadian study of liver transplant candidates with advanced HCV cirrhosis treated with SOF-based therapy. Outcomes included sustained virologic response (SVR), and liver transplant status. Results. 105 liver transplant candidates with advanced liver disease due to HCV were evaluated. The overall SVR was 83.8%. Hepatocellular carcinoma was diagnosed in 39 (37.1%) prior to transplant evaluation. In short term follow-up, 14 (13.3%) remained active on the list at the time of SVR12, 22 (20.9%) patients underwent liver transplantation, 7 (6.6%) patients were deactivated due to clinical improvement, 3 patients were delisted, and 10 deaths were reported. Conclusions. SOF-based therapy for patients progressing to liver transplantation leads to high SVR rates, short term stability in liver function, and deactivation from the transplant list.

Introduction Hepatitis E virus (HEV), the most common cause of acute hepatitis in many European countries, is transmitted through consumption of processed pork but also via blood transfusion and transplantation. HEV infection can become persistent in immunocompromised individuals. Aim We aimed to determine the incidence and epidemiology of HEV infection in English blood donors since the introduction of donation screening in 2016. Methods Between March 2016 and December 2017, 1,838,747 blood donations were screened for HEV RNA. Donations containing HEV RNA were further tested for serological markers, RNA quantification and viral phylogeny. Demographics, travel and diet history were analysed for all infected donors. Results We identified 480 HEV RNA-positive blood donations during the 22-month period, most (319/480; 66%) donors were seronegative. Viral loads ranged from 1 to 3,230,000 IU/ml. All sequences belonged to genotype 3, except one which likely represents a new genotype. Most viraemic donors were over 45 years of age (279/480; 58%), donors aged between 17 and 24 years had a seven-times higher incidence of HEV infection than other donors between March and June 2016 (1:544 donations vs 1:3,830). HEV-infected blood donors were evenly distributed throughout England. Screening prevented 480 HEV RNA-positive blood donations from reaching clinical supply. Conclusion HEV screening of blood donations is a vital step in order to provide safer blood for all recipients, but especially for the immunosuppressed. The unusually high rates of HEV infection in young blood donors may provide some insight into specific risks associated with HEV infection in England.

Post-transplant lymphoproliferative disorder (PTLD) is a serious and still frequently observed complication of solid organ transplantation. Despite the recent introduction of anti B-cell monoclonal antibody therapy (rituximab) for treatment of PTLD, mortality rates remain high. Because PTLD often presents in a nonspecific way in clinically unsuspected patients, it is a major challenge to diagnose PTLD at an early stage. Epstein-Barr virus (EBV)-DNA load monitoring is a promising tool for the identification of patients at risk for PTLD development. However, there are some limitations of this method, and not all patients at risk for PTLD can be identified by EBV-DNA measurements alone. Therefore, it is of major importance to recognize early clinical signs and symptoms of PTLD. In this review, risk factors for PTLD development, disease presentation, and methods for early detection will be discussed. Special attention is given to allograft and digestive tract localization and the relation with time of onset of PTLD. The value and pitfalls of EBV-DNA load monitoring are discussed. In addition, because fluorodeoxyglucose (FDG)-positron emission tomography (PET) has shown to be a powerful tool for staging and response evaluation of malignant lymphoma, the role of FDG-PET for early diagnosis and staging of PTLD is addressed.

Post-transplant lymphoproliferative disorder (PTLD) is a serious and still frequently observed complication of solid organ transplantation. Despite the recent introduction of anti B-cell monoclonal antibody therapy (rituximab) for treatment of PTLD, mortality rates remain high. Because PTLD often presents in a nonspecific way in clinically unsuspected patients, it is a major challenge to diagnose PTLD at an early stage. Epstein-Barr virus (EBV)-DNA load monitoring is a promising tool for the identification of patients at risk for PTLD development. However, there are some limitations of this method, and not all patients at risk for PTLD can be identified by EBV-DNA measurements alone. Therefore, it is of major importance to recognize early clinical signs and symptoms of PTLD. In this review, risk factors for PTLD development, disease presentation, and methods for early detection will be discussed. Special attention is given to allograft and digestive tract localization and the relation with time of onset of PTLD. The value and pitfalls of EBV-DNA load monitoring are discussed. In addition, because fluorodeoxyglucose (FDG)-positron emission tomography (PET) has shown to be a powerful tool for staging and response evaluation of malignant lymphoma, the role of FDG-PET for early diagnosis and staging of PTLD is addressed.

Der progrediente Verlauf einer chronisch entzündlichen Darmerkrankung (CED) bleibt eine therapeutische Herausforderung. Kontrovers diskutiert werden immunsuppressive, immunmodu-latorische und immunstimulierende Therapiemodelle. Vor diesem Hintergrund interessierten die Auswirkungen der chronisch immunsuppressiven Therapie im Vergleich zur konventionell antientzündlichen Therapie. Der Erkrankungsverlauf von 41 CED-Patienten (CU 30, MC 6, CI 5), die sich überwiegend auf-grund einer fortgeschrittenen PSC einer Lebertransplantation unterzogen hatten, wurde mit einer Kontrollgruppe von 42 (CU 29, MC 11, CI 2) nicht-transplantierten CED-Patienten mittels retrospektiver Datenerhebung, standardisiertem Fragebogen und aktualisierender telefonischer Befragung verglichen. Posttransplantär kamen die oralen immunsuppressiven Medikamente Ciclosporin A, Tacrolimus und Mycophenolat Mofetil (MMF) zur Anwendung. Analysiert wurde einerseits entsprechend kurzzeitiger Therapieschemata mit patienten-unabhängigen Zeit-abschnitten (6 Monats-Intervalle) mittels nichtparametrischer Testverfahren, andererseits, bei Zeiträumen von mehr als 6 Monaten (Langzeittherapie), fand die Kaplan- Meier-Methode Anwendung. In der Längsschnittanalyse waren in der Transplantiertengruppe nach 14,5 Jahren 22 von 41 der Patienten versus 14 von 42 der Kontrollpatienten dauerhaft in Remission (p=0,0295). Alle drei immunsuppressiven Medikamente standen im Zusammenhang mit Remissionsinduktionen (Ciclosporin: p=0,000, Tacrolimus: p=0,000, MMF: p=0,001), eine stabile Remission nach 14,5 Jahren war aber nur während einer MMF-Therapie (p=0,000) zu beobachten. In der Immunsuppressivagruppe wurden im Verlauf 3 Kolektomien (CU-Patienten) versus 7 innerhalb der Kontrollgruppe (3 CU-, 4 MC-Patienten) notwendig. Weiterhin kam es im gesamten Verlauf in der Immunsuppressivagruppe zu 5 Carzinomen, davon zu einem kolo-rektalen Carzinom bei CU (2,4%) und 2 Cholangiocellulären Carzinomen, in der Kontrollgruppe zu 4 Carzinomen, darunter ebenfalls einem kolorektalen Carzinom bei CU (2,4%) und 1 Cholangiocellulären Carzinomen. Extraintestinale Manifestationen traten als Arthropathien während Ciclosporin- (p=0,000) und Tacrolimus-Therapie (p=0,000) auf, Nebenwirkungen waren unter Ciclosporin dermatologischer (p=0,005), unter Tacrolimus kardiovaskulärer (p=0,000) und während MMF dermatologischer (p=0,011) und pulmonologischer (p=0,006) Klassifikation zu beobachten. Bei 16 Patienten dominierte direkt nach der Transplantation eine völlige CED- Symptomfreiheit, später als 1 Jahr nach der Transplantation noch bei 9 Patienten. Eine Progredienz der CED-Symptome nach Lebertransplantation fiel ausschließlich unter CI-Patienten auf (4 Patienten bei zuvor 1 Patient). Schlussfolgernd war zum einen im Vergleich zu anderen Arbeiten die Inzidenz kolorektaler Karzinome unter Langzeitimmunsuppression im Vergleich zur Kontrollgruppe nicht erhöht, zum anderen die Kolektomierate in der Transplantiertengruppe nur halb so hoch wie in den Kontrollen, und letztendlich ließ sich bei Beobachtungseinheiten von bis zu 14,5 Jahren ein Vorteil im rezidivfreien Überleben für die Patienten mit chronischer Immunsuppression gegenüber den Kontroll-Patienten in Bezug auf einen stabilen Remissionserhalt erkennen, wobei im Einzelnen im Zusammenhang mit dem Immunsuppressivum MMF relevante Ergebnisse zu beobachten waren., The progressive course of chronic inflammatory bowel disease (IBD) remains a challenge to treat. Immunosuppressive, immunomodulatory and immunostimulatory therapy models are the subject of controversial debate. Against this background, the effects of chronic immunosuppressive therapy as compared with conventional anti-inflammatory therapy were of interest. The disease progression of 41 IBD patients ulcerative colitis (UC) 30, crohn`s disease (CD) 6, indeterminate colitis (CI) 5, who, on account of advanced primary sclerosing cholangitis (PSC), had predominantly undergone a liver transplant, was compared with a control group consisting of 42 (UC 29, CD 11, CI 2) IBD patients, who did not undergo a transplant, assessed by means of retrospective data collection, standardised surveys and updated telephone interviews. After the transplant, oral types of immunosuppressive medication, such as cyclosporine A, tacrolimus, and mycophenolate mofetil (MMF), were applied. On the one hand, analyses were carried out by means of non-parametric test procedures, according to short-term schemes of treatment at time intervals (6 month-intervals) irrespective of the patient; on the other hand, the Kaplan- Meier method was applied at time intervals of more than 6 months (long-term therapy). In the longitudinal analysis, after 14.5 years, 22 out of 41 patients in the transplant group remained permanently in remission (p = 0.0295) in comparison with 14 out of 42 of the control group patients. All three types of immunosuppressive medication were associated with remission inductions (cyclosporine: p =0.000, tacrolimus: p =0.000, MMF: p =0.001). However, stable remission after 14.5 years was observed only during MMF therapy (p =0.000). In the immunosuppressive group, over the course, 3 colectomies (UC patients) were necessary, compared with 7 within the control group (3 UC, 4 CD patients). Furthermore, in the immunosuppressive group, over the entire course, 5 cases of carcinoma arose, consisting of one case of colorectal carcinoma in those with UC (2.4%) and 2 cases of cholangiocellular carcinoma. In the control group, 4 cases of carcinoma occurred, among which there was also one case of colorectal carcinoma in those with UC (2.4%) and one case of cholangiocellular carcinoma. Extra intestinal symptoms occurred as arthropathies during cyclosporine (p=0.000) and tacrolimus therapy (p=0.000). Side effects observed in cyclosporine were attributed to dermatological (p=0.005) classification, in tacrolimus to cardiovascular (p=0.000) classification and during MMF medication, to dermatological (p=0.011) and pulmonological (p=0.006) classification. 16 patients were completely free from IBD symptoms immediately after the transplant; more than a year after the transplant there were only 9 patients. Progression of the IBD symptoms following liver transplant was only evident in CI patients (4 patients, while initially 1 patient). By deduction, on the one hand, in comparison with other studies, the incidence of colorectal carcinoma in long-term immunosuppression, as compared with the control group, did not increase. On the other hand, the colectomy rate in the transplant group was only half as high as in the control group. Finally, in the observation periods of up to 14.5 years, an advantage with reference to stable retention of remission was identified in relapse-free survival for patients with chronic immunosuppression, compared with control group patients, in the course of which relevant results associated with immunosuppressive MMF were observed in detail.