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: Patient reported-outcomes [PROs] are becoming a major therapeutic goal in IBD, both in clinical trials and in daily clinical care. Moreover, it has recently been shown that in patients with UC the absence of rectal bleeding (Mayo Clinic endoscopic Score (MCSe)=0) shows high sensitivity for detecting mucosal healing. [1] We therefore investigated the efficacy of vedolizumab, a humanized monoclonal antibody against α4 β7-integrins, in achieving PROs, especially with regard to rectal bleeding (MCSe=0). Methods: A consecutive cohort of 60 adult IBD patients with ulcerative colitis (partial Mayo score >4) receiving vedolizumab was prospectively recruited from 9 German tertiary IBD centers. Primary endpoint was the absence of rectal bleeding (MCSe=0) as determined at week 2, 6, 14, 30 and 54, resp. Secondary endpoints included a combined endpoint (absence of rectal bleeding and stool frequency of 1 or 2, respectively, according to the Mayo Clinic Scoring system (MCSsf)). Quality of life (QoL) was evaluated by use of a visual analogue scale (VAS; 0–100). This data represents a subgroup analysis from a larger prior observational study. [2] [3] Results: 81.7% of patients had received prior treatment with anti-TNF-antibodies, 40% of patients had been hospitalized within one year prior to vedolizumab treatment initiation. 53.4% of patients received corticosteroids at week 0 (median 20 mg; range 0–60 mg). At week 54 20/60 patients (33.3%) reported absence of rectal bleeding, 17/60 patients (28.3%) achieved steroid-free cessation of rectal bleeding. A combined endpoint of MCSe=0 and normal stool frequency (MCSsf=0) was achieved by 16.7% of patients, while 26.7% of patients experienced absence of rectal bleeding (MCSe=0) and a mild increase in stool frequency (MCSsf=1) (Table 1). Quality of life increased from 47,5 at week 0 to 70 at week 14, 72.5 at week 30 and 70 at week 54, resp. Table 1. Response to vedolizumab treatment Conclusions: In UC patients with a severe disease course vedolizumab treatment results in a rapid and persistent absence of rectal bleeding in one third of patients. Normalization of stool frequency occurs less frequently and may reflects chronic alterations/damages of the bowel that may not be reverted by anti-inflammatory treatment strategies in this severely ill patient population. Absence of rectal bleeding is associated with a substantial improvement in patients quality of life. However, a substantial percentage of patients still required steroid-treatment to achieve these endpoints. References: [1] Colombel-JF et al. (2016), Discrepancies between patient-reported outcomes, and endoscopic and histological appearance in UC. [2] Baumgart-DC et al. (2016), Vedolizumab induction therapy for inflammatory bowel disease in clinical practice–a nationwide consecutive German cohort study. [3] Stallmach-A et al. (2016), Vedolizumab provides clinical benefit over 1 year in patients with active inflammatory bowel disease - a prospective multicenter observational study.

BACKGROUND:Vedolizumab, a monoclonal antibody targeting the α4β7-integrin, is effective in inducing and maintaining clinical remission in Crohn's disease and ulcerative colitis according to randomised clinical trials.AIM:To determine the long-term effectiveness of vedolizumab in a real-world clinical setting.METHODS:This observational registry assessed the clinical outcome in patients treated with vedolizumab for clinically active Crohn's disease (n = 67) or ulcerative colitis (n = 60). Primary endpoint was clinical remission (HBI ≤ 4/pMayo ≤ 1) at week 54. Secondary endpoints included clinical response rates (HBI/pMayo score drop ≥3) and steroid-free clinical remission at weeks 30 and 54.RESULTS:Vedolizumab was stopped in 69/127 (56%) patients after a median time of 18 weeks (range 2-49) predominantly owing to lack or loss of response. Using nonresponder imputation analysis, clinical remission and steroid-free remission rates were 21% and 15% in Crohn's disease and 25% and 22% in ulcerative colitis, respectively. Lack of clinical remission was associated with prior treatment with anti-TNF or with steroids for more than 3 months in the last 6 months in ulcerative colitis. At week 14, the absence of remission in Crohn's disease or nonresponse in ulcerative colitis indicated a low likelihood of clinical remission at week 54 [2/31 (7%) in Crohn's disease, 4/41 (10%) in ulcerative colitis]. Accordingly, declining C-reactive protein in inflammatory bowel disease and/or lower faecal calprotectin in ulcerative colitis at week 14 predicted remission at week 54.CONCLUSION:Among patients who started vedolizumab for active inflammatory bowel disease, clinical remission rates are 21-25% after 54 weeks.

Einleitung: Mit Vedolizumab (VDZ) ist ein neuer monoklonaler Antikörper gegen α4β7-Integrine zur Therapie der CED in Deutschland seit Mai 2014 zugelassen. Die Langzeitwirkung von VDZ in der klinischen Routinepraxis ist unbekannt.

Einleitung: Eine chronische Hepatitis C Virusinfektion beeinflusst die Mortalität bei Patienten mit angeborenen Gerinnungsstörungen, Daten zu Interferon-freien Behandlungen liegen bei diesen Patienten allerdings bisher kaum vor. Es wurden lediglich Ergebnisse von 14 Patienten einer Substudie im Sofosbuvir/Ledipasvir Entwicklungsprogramm publiziert (Stedman, Haemophilia 2015).

Sofosbuvir (SOF) ist ein nukleotidischer Inhibitor der RNA-abhängigen RNA-Polymerase NS5B, der in Deutschland zur Behandlung der chronischen Hepatitis C (HCV) zugelassen ist. Da das aktive Zentrum der NS5B-Polymerase eine hoch-konservierte Region darstellt, hat SOF prinzipiell pangenotypische Wirksamkeit und weist zudem eine hohe Resistenzbarriere auf. Dennoch konnte kürzlich aufgezeigt werden, dass Patienten mit HCV Genotyp (GT)1b-Infektion in den SOF-Zulassungsstudien geringere Ansprechraten als GT 1a-Patienten aufwiesen.

Kasuistik: Ein 46-jähriger Mann hat seit August 2012 intermittierend belastungsabhängigen Husten und stellt sich im Dezember 2012 in der pulmonologischen Abteilung zur weiteren Abklärung vor. Klinisch ist er in einem guten Allgemein- und Kräftezustand. Es findet sich ein ca. 1 cm großer Lymphknoten rechts cervical. Der Befund wird auf ein im letzten Jahr durchgemachtes Pfeiffersches Drüsenfieber zurückgeführt. Die Laborparameter sind unauffällig. Wegen einer linksparatrachealen Raumforderung wird der Patient in der gastroenterologischen Abteilung vorgestellt.

H.W. Zimmermann, P.A. Reuken, A. Koch, M. Bartneck, D.H. Adams, C. Trautwein, A. Stallmach, F. Tacke, T. Bruns Department of Medicine III, University Hospital Aachen, Germany, NIHR Biomedical Research Unit and Centre for Liver Research, University of Birmingham, UK, Department of Internal Medicine IV, Jena University Hospital, Germany, Center for Sepsis Control and Care (CSCC), Jena University Hospital, Germany

Der heute 55-jährige Patient stellte sich im Juni 2009 wegen Verschlechterung des Allgemeinzustandes bei Z.n erweiterter Pneumektomie rechts und Z.n. kombinierter Radiochemotherapie wegen eines zentralen nichtkleinzelligen Bronchialkarzinoms (5/2004) vor. Es wurde als Ursache ein Pneumektomieresthöhlenempyem diagnostiziert. Endoskopisch zeigte sich eine ösophago-tracheale Fistel mit eitriger Sekretion. Hinweise auf ein Tumorrezidiv fanden sich im Verlauf nicht. Es erfolgten verschiedene Therapieversuche des Fistelverschlusses (Fibrinklebung, OTSC-Clip, Stenting) ohne dass eine ausreichende Verbesserung der klinischen Situation erreicht werden konnte. Deshalb entschlossen wir uns zur Platzierung eines Doppelschirm-Devices zum Verschluss eines Vorhofseptumdefekts unter kombiniert ösophagoskopischer und bronchoskopischer Kontrolle. Damit konnte ein Verschluss der Fistel erzielt werden. Der Patient profitierte klinisch im Verlauf. Allerdings kam es dann zur Dislokation dieses Devices. Eine operative Intervention war nicht möglich, so dass wir uns erneut zur Stent-Implantation entschlossen. Der Fall zeigt die endoskopische Platzierung des Doppelschirm-Devices und die in diesem Zusammenhang möglichen Komplikationen.

The watery diarrhea, hypokalemia and achlorhydria (WHDA) syndrome due to vasoactive intestinal polypeptide (VIP)-producing extra-pancreatic tumors is rare. We report on a 45-year-old woman who suffered from persistent secretory diarrhea for six years and who was admitted to hospital with complaints of muscular weakness and myalgia. Biochemical testing revealed pronounced rhabdomyolysis due to severe hypokalemia. Gastrointestinal evaluation of long-standing diarrhea including endoscopy of the upper and lower gastrointestinal tract and the small intestine did not show any pathologies. An abdominal computed tomography scan revealed a mass of 4 × 5 cm in the left adrenal gland demonstrating a strong uptake in the 123I-labelled metaiodobenzylguanidine scintigraphy. Plasma levels of chromogranin A, calcitonin, parathormone, basal renin and most prominently VIP were increased in line with a increased 24 hour urinary secretion of noradrenaline, dopamine, normetanephrine and vanillymandelic acid. A WDHA (watery diarrhea, hypokalaemia, achlorhydria) syndrome with hypokalemic rhabdomyolysis due to a VIP-producing adrenal tumor was diagnosed that was removed surgically. The histological evaluation demonstrated a composite pheochromocytoma. Diarrhea stopped immediately after surgery together with a normalization of laboratory parameters. In conclusion, this case report focuses on the rare clinical presentation of secretory diarrhea and electrolyte disturbances in combination with hypokalemic rhabdomyolysis which was caused by a VIP-producing composite pheochromocytoma.