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Purpose To assess the feasibility, safety and effectiveness of portal vein recanalization (PVR)–transjugular portosystemic shunt (TIPS) placement via splenic access using a balloon puncture technique. Materials and Methods In a single-center retrospective study from March 2017 to February 2021, 14 consecutive patients with portal hypertension, chronic liver disease and portal vein occlusion or near-complete (> 95%) occlusion were referred for PVR–TIPS placement. Feasibility, safety and effectiveness including procedural characteristics such as technical success, complication profile and splenic access time (SAT), balloon positioning time (BPT), conventional portal vein entry time (CPVET), overall procedure time (OPT), fluoroscopy time (FT), dose–area product (DAP) and air kerma (AK) were evaluated. Results Transsplenic PVR–TIPS using balloon puncture technique was technically feasible in 12 of 14 patients (8 men, 49 ± 13 years). In two patients without detectable intrahepatic portal vein branches, TIPS placement was not feasible and both patients were referred for further treatment with nonselective beta blockers and endoscopic variceal ligation. No complications grade > 3 of the Cardiovascular and Interventional Radiological Society of Europe classification system occurred. The SAT was 25 ± 21 min, CPVET was 33 ± 26 min, the OPT was 158 ± 54 min, the FT was 42 ± 22 min, the DAP was 167.84 ± 129.23 Gy*cm2 and the AK was 1150.70 ± 910.73 mGy. Conclusions Transsplenic PVR–TIPS using a balloon puncture technique is feasible and appears to be safe in our series of patients with obliteration of the portal vein. It expands the interventional options in patients with chronic PVT.

Background The latest research clearly indicates that diet plays an important role in the onset and course of inflammatory bowel diseases (IBD). But especially data on gender specific aspects of diet in IBD patients are still lacking even though we know from the general population that gender matters in case of diet. Methods We hypothesised an interaction of gender and diet in IBD patients and that this is linked to disease behaviour. In a subgroup analysis of a previously published prospective trial (Wiestler M. et al., Clinical and Translational Gastroenterology, 2019) 91 IBD patients were stratified into 4 groups (Crohn’s disease - CD [n=50] and ulcerative colitis – UC [n=41], female and male, respectively) to compare nutritional behaviour by sex and diagnosis. We evaluated disease-specific quality of life (IBDQ), physical activity (accelerometery), body composition (bioelectrical impedance analysis (BIA)), as well as clinical (HBI, SCCAI) and biochemical (CRP, faecal calprotectin) parameters of disease activity in comparison to nutritional behaviour (food frequency questionnaire (FFQ)). Results The nutritional behaviour of CD patients showed significant gender-related trends and differences in correlation with disease activity (Spearman correlation analysis). In male CD patients HBI significantly negatively correlated with the amount of fish (p=0.005, r=-0.612) and meat consumed per month (p=0.023, r=-0.519). In female CD patients the amount of fish consumed per month significantly negatively correlated with the IBDQ score (p=0.029, r=-0.438). The nutritional behaviour of UC patients showed significant gender-related trends and differences in correlation with disease activity as well. In female patients SCCAI significantly negatively correlated with the amount of cake, pie/ sweet baked goods (p= Conclusion In this subgroup analysis of a cross-sectional study, nutritional behaviour of IBD patients showed significant gender-related differences in correlation with disease activity and disease related quality of life. Due to the close correlation between IBD and nutrition and the different nutritional needs according to disease activity, our results illustrate the importance of gender-sensitive collection of a nutritional history as well as the need for gender-sensitive nutritional recommendations in IBD patients to further optimize individual patient care.

Data on the long-term persistence of HCV resistance-associated substitutions (RASs) after treatment with direct-acting antivirals (DAAs) are limited. This study evaluated the persistence of NS3, NS5A, and NS5B RASs for up to 5 years after the end of treatment (EOT).We included samples from 678 individuals with an HCV genotype (GT) 1 or 3 infection and virologic DAA treatment failure collected in the European Resistance Database. NS3, NS5A, and NS5B were sequenced, and clinical parameters were evaluated.A total of 242 individuals with HCV GT1a (36%), 237 with GT1b (35%), and 199 (29%) with GT3 and a DAA failure were included. After protease inhibitor failure, the frequencies of NS3 RASs were 40-90% after the EOT. NS3 RASs disappeared rapidly in GT1b and GT3 after follow-up month 3 but were stable (≥60%) in GT1a owing to Q80K. The SOF-resistant NS5B RAS S282T was only found in individuals with GT3a. Non-nucleoside NS5B RASs were frequent in GT1 (56-80%) and decreased to 30% in GT1a but persisted in GT1b. NS5A RASs were very common in all GTs after NS5A inhibitor failure (88-95%), and even after follow-up month 24, their frequency was 65% and higher. However, RASs in GT1b had a stable course, whereas RASs in GT1a and GT3 declined slightly after follow-up month 24 (GT1a, 68%; GT1b, 95%; and GT3, 65%), mainly because of the slow decline of high-level resistant Y93H.We found that low-to medium-level RASs persisted, whereas high-level resistant RASs disappeared over time. Different patterns of RAS persistence according to HCV subtype could have implications for retreatment with first-generation DAAs and for global HCV elimination goals.There are little data on the long-term persistence of HCV resistance-associated substitutions (RASs) after DAA treatment failure, and RASs could have an impact on the efficacy of a rescue treatment. Especially in countries with limited availability of VOX/VEL/SOF or G/P/SOF, different patterns of RAS persistence could have implications for retreatment with first-generation DAAs and for global HCV elimination goals. The different patterns of RAS persistence identified in this study can be used to derive general rules regarding the persistence of RASs after DAA failure that could be applied by physicians in less developed countries to plan individualized HCV retreatment.

Many cases of Clostridium perfringens sepsis prove to be fatal. We present a case of C. perfringens sepsis with a liver abscess as the focus of infection, which was successfully treated by an interdisciplinary intensive medical care management. The sepsis with this rare pathogen was favored by the presence of a bilioenteric anastomosis and immunosuppressive treatment of a pre-existing Crohn's disease. Antibiotic treatment with clindamycin and penicillin G was initiated and the abscess was drained. Hemodialysis with high cut-off filters was started because of acute kidney failure in the Acute Kidney Injury Network (AKIN) stage III, hemolysis and rhabdomyolysis. Therapeutic plasma exchange was performed due to sepsis and acute liver failure.Eine Clostridium-perfringens-Sepsis endet oft tödlich. Wir berichten über eine C.-perfringens-Sepsis mit einem Leberabszess als Fokus, die durch ein interdisziplinäres intensivmedizinisches Management erfolgreich behandelt wurde. Begünstigende Faktoren für die Sepsis mit diesem seltenen Keim waren eine vorliegende biliodigestive Anastomose und eine immunsuppressive Therapie bei Morbus Crohn. Es erfolgten eine antibiotische Therapie mit Clindamycin und Penicillin G, eine Abszessdrainage, eine Hämodialyse mit High-cut-off-Filter bei akutem Nierenversagen im Acute-Kidney-Injury-Network(AKIN)-Stadium III, Hämolyse und Rhabdomyolyse sowie ein Plasmaaustausch bei Sepsis und akutem Leberversagen.

The influence of a SARS-CoV-2 infection on inflammatory bowel disease (IBD) has not yet been well characterized and it is unclear whether this requires an adaptation of the immunosuppressive therapy.A national register was established for the retrospective documentation of clinical parameters and changes in immunosuppressive therapy in SARS-CoV-2 infected IBD patients.In total, only 3 of 185 IBD patients (1.6 %) were tested for SARS-CoV-2 infection because of abdominal symptoms. In the course of COVID-19 disease, 43.5 % developed diarrhea, abdominal pain or hematochezia (risk of hospitalization with vs. without abdominal symptoms: 20.0 % vs. 10.6 %, p 0.01). With active IBD at the time of SARS-CoV-2 detection, there was an increased risk of hospitalization (remission 11.2 %, active IBD 23.3 % p 0.05). IBD-specific therapy remained unchanged in 115 patients (71.4 %); the most common change was an interruption of systemic therapy (16.2 %).New abdominal symptoms often appeared in SARS-CoV-2 infected IBD patients. However, these only rarely led to SARS-CoV-2 testing. A high IBD activity at the time of SARS-CoV-2 detection was associated with an increased risk of hospitalization.Der Einfluss einer SARS-CoV-2-Infektion auf chronisch entzündliche Darmerkrankungen (CED) ist bislang nicht gut charakterisiert, und es ist unklar, ob diese eine Anpassung der immunsuppressiven Therapie erfordert.Für die retrospektive Dokumentation klinischer Parameter und Veränderungen einer immunsuppressiven Therapie von mit SARS-CoV-2 infizierten CED-Patienten wurde ein nationales Melderegister etabliert.Insgesamt wurden nur 3 von 185 CED-Patienten (1,6 %) wegen abdomineller Symptome auf eine SARS-CoV-2-Infektion getestet. Im COVID-19-Krankheitsverlauf entwickelten 43,5 % Durchfall, abdominelle Schmerzen oder Hämatochezie (Hospitalisierungsrisiko mit vs. ohne abdominelle Symptome: 20,0 % vs. 10,6 %, p 0,01). Bei aktiver CED zum Zeitpunkt des SARS-CoV-2-Nachweises bestand ein erhöhtes Hospitalisierungsrisiko (Remission 11,2 %, aktive CED 23,3 % p 0,05). Die CED-spezifische Therapie blieb bei 115 Patienten (71,4 %) unverändert; die häufigste Änderung bestand in einer Unterbrechung der systemischen Therapie (16,2 %).Bei mit SARS-CoV-2 infizierten CED-Patienten traten häufig neue abdominelle Symptome bei Infektion auf. Diese führten aber nur selten zur SARS-CoV-2-Testung. Eine hohe CED-Aktivität zum Zeitpunkt des SARS-CoV-2-Nachweises war mit einem erhöhten Hospitalisierungsrisiko assoziiert.

OBJECTIVES A combined lung and liver transplant in patients with cystic fibrosis (CF) is an uncommon procedure. The goal of this study was to compare long-term outcomes between patients with CF who underwent either a combined lung-liver or a lung-only transplant. METHODS This is a retrospective single-centre study of patients with CF who underwent a lung transplant between January 2005 and May 2020. Since 2006, our preference for a combined lung-liver transplant was to transplant the liver first and then the lung. Outcomes were compared using the Kaplan–Meier analysis and the log-rank test. Median follow-up was 53 (23–97) months. RESULTS During the study period, among 357 patients with CF who underwent a lung transplant, 14 (4%) required a lung-liver transplant whereas 343 (96%) had a lung-only transplant. Lung cold ischaemic time was longer in the lung-liver transplant group, but no patient in this group showed primary graft dysfunction at 72 h after the transplant. Prevalence of anti-human leucocyte antigen donor-specific antibodies was 7.1% vs 13.7% in the lung-liver versus the lung-only transplant group (P = 0.42). At 5 years, lung graft survival (78% vs 69%) and freedom from chronic lung allograft dysfunction (79% vs 62%) did not differ between the lung-liver versus the lung-only groups (P = 0.45 and P = 0.55, respectively). Freedom from lung biopsy-confirmed rejection was significantly higher in patients undergoing a lung-liver transplant (91% vs 50%; P = 0.027). CONCLUSIONS A lung-liver transplant did not impair lung graft function. The lower prevalence of donor-specific antibodies and the better freedom from lung biopsy-confirmed rejection suggest tolerogenic effects of the liver graft.

Acute liver failure (ALF) is a rare disease with high mortality. It is defined as coagulopathy and encephalopathy in a person with a previously healthy liver. The etiology of ALF is a decisive prognostic factor and varies depending on the country of origin of the patient. Although in many countries the main triggers are hepatotropic viruses, in western industrial countries toxic medicinal causes and autoimmune phenomena predominate. The course of ALF runs through various phases. The complete picture of ALF can mostly no longer be casually treated but necessitates in particular timely contact with a transplantation center. If a causal treatment exists, the effectiveness is greatly dependent on the timing of initiation. In the best case scenario this can completely avoid liver damage. In the complete picture of ALF the main focus is on the intensive medical care of a threatening multiorgan failure. In this context new standards of treatment were established by studies on plasmapheresis.Das akute Leberversagen (ALF) ist eine seltene Krankheit mit hoher Letalität. Es ist definiert als Koagulopathie und Enzephalopathie beim zuvor Lebergesunden. Die Ätiologie ist beim ALF ein entscheidender prognostischer Faktor und unterscheidet sich je nach Herkunftsland des Patienten. Während in vielen Ländern hepatotrope Viren Hauptauslöser sind, überwiegen in den westlichen Industrienationen medikamentös-toxische Ursachen sowie Autoimmunphänomene. Das ALF durchläuft verschiedene Phasen. Das Vollbild des ALF ist meist nicht mehr ursächlich behandelbar, sondern erfordert vor allem die rechtzeitige Kontaktaufnahme mit einem Transplantationszentrum. Sofern kausale Therapien existieren, ist ihre Wirksamkeit stark vom Zeitpunkt des Einsatzes abhängig. Bestenfalls wird durch sie der Leberschaden komplett verhindert. Intensivmedizinisch rückt im Vollbild des ALF die Behandlung des drohenden Multiorganversagens in den Mittelpunkt. Hier wurden durch Arbeiten zur Plasmapherese neue Therapiestandards etabliert.

Hepatitis C virus infection is causing chronic liver disease, cirrhosis, and hepatocellular carcinoma. By combining direct-acting antivirals (DAAs), high sustained virologic response rates (SVRs) can be achieved. Resistance-associated substitutions (RASs) are commonly observed after DAA failure, and especially nonstructural protein 5A (NS5A) RASs may impact retreatment options.1-3 Data on retreatment of DAA failure patients using first-generation DAAs are limited.4-7 Recently, a second-generation protease- and NS5A-inhibitor plus sofosbuvir (voxilaprevir/velpatasvir/sofosbuvir [VOX/VEL/SOF]) was approved for retreatment after DAA failure.8 However, this and other second-generation regimens are not available in many resource-limited countries or are not reimbursed by regular insurance, and recommendations regarding the selection of retreatment regimens using first-generation DAAs are very important. This study aimed to analyze patients who were re-treated with first-generation DAAs after failure of a DAA combination therapy.

Background Hepatitis C virus (HCV) infection is associated with a particularly poor outcome after liver transplantation. In December 2014, sofosbuvir/ledipasvir (SOF/LDV) fixed-dose combination (FDC) was approved for HCV genotype 1 and 4 in Europe. In orthotopic liver transplantation (OLT) recipients, the interferon-free treatment of HCV re-infection with novel direct-acting antivirals has been demonstrated to be safe and effective in clinical trials, but real-world data are missing. The aim of this study was to investigate the safety and efficacy of SOF/LDV FDC in OLT recipients in the real-life setting. Methods All consecutive OLT patients started on SOF/LDV FDC for 12 or 24 weeks at the University Medical Center Hamburg-Eppendorf and Medical School Hannover between October 2014 and August 2015 were retrospectively analyzed (n = 30). The primary efficacy endpoint was sustained virological response (SVR), i.e., absence of viremia 12 weeks after end of treatment (SVR 12). Liver function tests, creatinine, blood count, and HCV RNA (by polymerase chain reaction assay) were determined at each visit. Results SVR was achieved in 29/30 patients (96.67%) treated with SOF/LDV ± ribavirin (RBV) for 12 (n = 4) or 24 weeks (n = 25). Twenty-five patients (86.2%) received RBV. However, in 15 of the 25 patients, RBV administration had to be discontinued because of severe anemia (57.7%). One RBV-treated patient died of a myocardial infarction during antiviral therapy; this event was most likely not directly related to SOF/LDV. Aside from RBV-associated anemia, no severe side effects of the antiviral regimen were observed. Conclusion Antiviral treatment with SOF/LDV is highly effective, safe, and well tolerated in OLT recipients. The addition of RBV often results in severe anemia, requiring dose reduction or discontinuation.

Summary Hepatitis E virus (HEV) is the causative agent of hepatitis E in humans and a member of the genus Orthohepevirus in the family Hepeviridae. Infection usually leads to acute hepatitis that can become fulminant, particularly among pregnant women and in patients with preexisting liver disease, or may evolve to a chronic state, especially in immunosuppressed individuals. HEV has been shown to produce a range of extra-hepatic manifestations including aplastic anaemia, acute thyroiditis, glomerulonephritis as well as neurological disorders such as Guillain-Barre syndrome, neuralgic amyotrophy and encephalitis. The pathogenesis of these neurological injuries remains largely unknown, and it is also uncertain whether or not HEV can directly infect neuronal cells. In this study, we investigated whether HEV is capable of completing the viral life cycle in human neuronal-derived cell lines such as neuroepithelioma (SK-N-MC), desmoplastic cerebellar medulloblastoma (DAOY), glioblastoma multiforme (DBTRG), glioblastoma astrocytoma (U-373 MG) and oligodendrocytic (M03.13) cells. Following transfection of these cells with HEV Gaussia luciferase reporter virus, all tested cell lines supported HEV RNA replication. Furthermore, extra- and intracellular viral capsid was detected by an HEV antigen ELISA as a marker for virus assembly and release. Permissiveness for HEV cell entry could be demonstrated for the oligodendrocytic cell line M03.13. In conclusion, these results indicate that HEV tropism is not restricted to the liver and HEV can potentially complete the full viral life cycle in neuronal-derived tissues explaining neurologic disorders during HEV infection.

Treatment of chronic hepatitis C (HCV) has changed dramatically since the approval of the direct-acting antivirals (DAA). Depending on the HCV genotype and the stage of liver disease, sustained HCV clearance can be achieved in more than 95% of patients with a treatment duration of 8-12 weeks in most of the cases. The selection and combination of the drugs depends on previous antivirals therapies, the stage of liver fibrosis, HCV genotype and subtype, viral load at baseline, and renal function. Nowadays, potent antiviral therapy with minimal side effects can be offered to almost every patient. In the real-world setting, a high quality of HCV therapy considering economic aspects has been documented in the German Hepatitis C Registry. A reduction of clinical complications of chronic liver disease by clearance of HCV has already been documented.

BACKGROUND: Potent direct-acting antivirals (DAAs) for treatment of chronic hepatitis C virus (HCV) infection have reduced the need for on-treatment monitoring. Currently, on-treatment response and outcome are determined by HCV RNA testing. A less expensive alternative to verify viral replication is HCV core antigen (HCV Ag). AIMS: The aim of this study was to determine if HCV Ag can be used for initial confirmation of viremia, on-treatment monitoring and determination of SVR in patients with chronic HCV infection receiving DAA treatment. METHODS: To evaluate the role of HCV Ag in confirming SVR, patients treated with DAAs ±Peg-interferon (IFN)/RBV were included, for the purpose of assessing HCV Ag to determine relapse, patients treated with any regimen (including Peg-IFN/RBV) were included. Serum HCV RNA and HCV Ag levels were assessed at baseline (BL), on-treatment (OT), end of treatment (EOT) and week 12 and/or 24 of follow up (FU). HCV RNA was considered the gold standard. RESULTS: In total, 181 patients were included, 112 (62%) of whom achieved SVR. Mean age was 54 years (19–79), 115 (64%) patients were male. The majority of patients was infected with genotype 1 (68%) and treated with a sofosbuvir-based regimen (58%). Median HCV RNA level at BL was 6.1 Log10 IU/mL (2.7–7.4) and HCV Ag level was 2409 fmol/L (0.85-20000). At BL, 165 out of 167 (98.8%) viremic patients tested positive for HCV Ag. Of the two patients who tested HCV Ag negative, one patient had a low RNA level (2.67 log10 IU/mL), whereas in the second patient HCV RNA level was high (6.38 log10 IU/mL). Baseline HCV Ag and HCV RNA levels were significantly correlated (R=0.87, p

SummaryBackground Successful antiviral treatment of decompensated hepatitis B with HBV polymerase inhibitors is associated with improvement of liver function. To what extent liver function also improves in cirrhotic patients with chronic hepatitis C receiving novel interferon-free (IFN-free) therapies is unknown. Aim To study liver function in cirrhotic HCV patients receiving IFN-free therapies. Methods We here studied 80 consecutive patients with advanced HCV associated liver cirrhosis including 34 patients (43%) with Child B/C cirrhosis and 42 patients (53%) with platelet counts of