Dominik Bettinger

Efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPSS) in 40 patients with hepatocellular carcinoma.

Portal hypertension and hepatocellular carcinoma (HCC) are major complications of advanced liver cirrhosis. Thus, patients are often affected by both complications. Transjugular intrahepatic portosystemic shunt (TIPSS) is an effective treatment for portal hypertension and its complications. However, no established guidelines for the treatment of symptomatic portal hypertension in HCC patients are currently available. In addition, only limited information exists about the consequence of TIPSS implantation in patients with HCC.

Procedural and shunt-related complications and mortality of the transjugular intrahepatic portosystemic shunt (TIPSS).

The implantation of a transjugular intrahepatic portosystemic shunt (TIPSS) is a complex angiographic procedure performed in patients with end‐stage liver disease. Numerous case reports and narrative reviews have been published so far; however, studies systematically investigating procedural and shunt‐related complications are lacking.

Excellent local control and tolerance profile after stereotactic body radiotherapy of advanced hepatocellular carcinoma

BackgroundTo evaluate the efficacy and toxicity of stereotactic body radiotherapy (SBRT) in the treatment of advanced hepatocellular carcinoma (HCC).Material and MethodsPatients with large HCCs (median diameter 7xa0cm, IQR 5-10xa0cm) with a Child-Turcotte-Pugh (CTP) score A (60%) or B (40%) and Barcelona-Clinic Liver Cancer (BCLC) classification stage B or C were treated with 3 to 12 fractions to allow personalized treatment according to the size of the lesions and the proximity of the lesions to the organs at risk aiming to give high biologically equivalent doses assuming an α/β ratio of 10xa0Gy for HCC. Primary end points were in-field local control and toxicity assessment.ResultsForty seven patients with 64 lesions were treated with SBRT (median 45xa0Gy in 3–12 fractions) with a median follow up for patients alive of 19xa0months. The median biological effective dose was 76xa0Gy (IQR 62–86xa0Gy). Tumor vascular thrombosis was present in 28% and an underlying liver disease in 87% (hepatitis B or C in 21%, alcohol related in 51%, nonalcoholic steatohepatitis in 13% of the patients, primary biliary cirrhosis 2%). Eighty three percent received prior and in most cases multiple therapies. Local control at 1xa0year was 77%. The median overall survival from the start of SBRT was 9xa0months (95% CI 7.7–10.3). Gastrointestinal toxicities gradexa0≥xa02 were observed in 3 (6.4%) patients. An increase in CTP score without disease progression was observed in 5 patients, of whom one patient developed a radiation induced liver disease. One patient died due to liver failure 4xa0months after treatment.ConclusionSBRT is an effective local ablative therapy which leads to high local control rates with moderate toxicity for selected patients with large tumors.

Treatment with proton pump inhibitors is associated with increased mortality in patients with pyogenic liver abscess

Proton pump inhibitors (PPI) are often used in patients with gastro‐esophageal reflux and peptic ulcer disease. A higher risk for infectious diseases and for pyogenic liver abscess has been reported in patients with prolonged PPI intake. Although many patients have ongoing PPI treatment after diagnosis of liver abscess, there are no data available that focus on the prognostic impact of PPI treatment in these patients.

The underdilation of nitinol stents at TIPS implantation: Solution or illusion?

PURPOSEnThis study investigates the behaviour of self-expanding nitinol stents at the time of TIPS-implantation and thereafter.nnnMETHODSnHundred consecutive patients with cirrhosis receiving a TIPS revision were included. The smallest stent diameter was measured radiologically immediately after implantation and before shunt revision. Accuracy of the measurement was assessed by comparing the nominal stent diameter with the largest stent diameter measured at the time of revision.nnnRESULTSnPearson correlation between largest measured and nominal diameters was excellent (r=0.952, p<0.001) showing that measurements are accurate. At TIPS implantation all stents were markedly underdilated reaching only 76-92% of their nominal diameter. Smallest measured diameters were similar (8mm) irrespective of the nominal diameter (8, 9, 10mm) of the stent. In addition, smallest diameters of 10mm stents were similar irrespective whether 8, 9 or 10mm balloons were used. During a mean follow-up of 12.7±17.8months (median 3 months, range 1-81) stents expanded by 0.5-1.6mm dependent on the nominal stent size (8, 9, 10mm) and the grade of primary underdilation. No significant difference was found between Viatorr and bare stents.nnnCONCLUSIONSnAt TIPS-implantation, the compliance of the surrounding tissue predominantly determines the stent diameter. The nominal size of the stent or the dilatation balloon has little influence. Accurate adjustment of a desired pressure gradient is, therefore, not possible. During follow-up, stents expand towards their nominal diameter questioning the usefulness of underdilation.

The role of albumin–bilirubin grade and inflammation-based index in patients with hepatocellular carcinoma treated with stereotactic body radiotherapy

PurposeWe evaluated the prognostic accuracy of the albumin–bilirubin (ALBI) grade and the inflammation-based index (IBI) in estimating overall survival (OS) and toxicity in patients with hepatocellular carcinoma (HCC) treated with stereotactic body radiotherapy (SBRT).Materials and methodsForty patients with 47xa0HCC lesions with axa0Barcelona Clinic Liver Cancer (BCLC) classification stagexa0B orxa0C were treated with SBRT in 3–12xa0fractions. The ALBI grade and the IBI were calculated at different time points (baseline, during, at the end of treatment and at follow-up) and compared with the Child-Pugh (CP) score as well as other patient- and treatment-related parameters, concerning OS and toxicity.ResultsThe median follow-up was 14.3xa0months for patients alive. The median OS from SBRT was 10 (95% confidence interval 8.3–11.6) months. The local control at 1xa0year was 79%. Axa0lower IBI during treatment was associated with better OS (pu202f=u20090.034) but not CP and ALBI. Higher C‑reactive protein levels as well as higher alpha-fetoprotein concentrations correlated with worse survival (pu202f=u20090.001). Both higher ALBI (pu202f=u20090.02) and CTP (pu202f=u20090.001) at baseline correlated with axa0higher incidence of acute and late toxicities (CTC ≥2). Neither the mean radiation dose to the liver nor the dose to 700u202fcc of the liver correlated with the occurrence of toxicities.ConclusionsIn this analysis, axa0higher ALBI grade as well as axa0higher CP were predictors of higher incidence of toxicity, whereas axa0lower IBI during treatment correlated with axa0better OS. These results should be further evaluated in prospective studies.ZusammenfassungHintergrundZiel war es, die Bedeutung der Rolle der objektiven Indizes Albumin-bilirubin Grade (ALBI) und Inflammation-based Index (IBI) für die Risikoabschätzung von Toxizität sowie für das Gesamtüberleben (OS) bei der stereotaktischen Strahlentherapie (SBRT) vom hepatozellulären Karzinom (HCC) zu untersuchen.Material und MethodenVierzig Patienten mit 47xa0Läsionen mit HCC im Stadiumxa0B oderxa0C nach der Barcelona-Clinic-Liver-Cancer(BCLC)-Klassifikation wurden in 3–12xa0Fraktionen stereotaktisch behandelt. Der ALBI-Grad und der IBI-Grad wurden zu verschiedenen Zeitpunkten berechnet (vor, während und nach Abschluss der Therapie sowie bei der ersten Nachsorge). Diese Ergebnisse wurden mit dem Child-Pugh(CP)-Score verglichen sowie mit anderen patienten- und therapierelevanten Faktoren, bezüglich des Überlebens und der Toxizität.ErgebnisseDas mediane Follow-up betrug 14,3xa0Monate. Die mediane Überlebenszeit(OS) ab SBRT war 10xa0Monate (95u202f%-Konfidenzintervall 8,3–11,6) und die lokale Kontrollrate nach 1xa0Jahr war 79u202f%. Weder der CP-Score noch der ALBI korrelierten mit einem besseren OS. Nur ein niedriger IBI während der Therapie (pu202f=u20090,03) war statistisch signifikant. Ein erhöhter Wert des C‑reaktiven Proteins sowie ein erhöhter Alpha-Fetoprotein-Wert im Serum korrelierten mit einer schlechteren Prognose (pu202f=u20090,001). Patienten mit erhöhtem ALBI-Grad (pu202f=u20090,02) und CP (pu202f=u20090,001) vor Therapie hatten ein höheres Risiko für höhergradige (CTC-Grad >2) Akut- und Spättoxizitäten. Weder die mediane Strahlendosis der Leber noch die Dosis an 700cc der Leber korrelierten mit dem Auftreten von Toxizitäten.SchlussfolgerungIn dieser Analyse waren ein höher CP-Score sowie ein höher ALBI Prädiktoren für das Auftreten von Toxizitäten und der IBI während der Therapie korrelierte mit einem besseren OS. Diese Ergebnisse sollten in prospektiven Studien evaluiert werden.

Survival benefit of transarterial chemoembolization in patients with metastatic hepatocellular carcinoma: a single center experience

BackgroundAs prognosis of patients with metastatic hepatocellular carcinoma (HCC) is mainly determined by intrahepatic HCC progression, local treatment with TACE may result in improved OS, although it is not recommended. The purpose of this study was to analyze retrospectively the efficacy of TACE and its impact on OS in patients with metastatic hepatocellular carcinoma (HCC).MethodsTwo hundred and fifteen patients with metastatic HCC who were treated at our Liver Center between 2003 and 2014 were included in this retrospective analysis. Medical records, laboratory parameters and imaging studies were analyzed. Treatment of metastatic HCC and OS were assessedResultsOne hundred and two patients (47.4%) did not receive any HCC specific treatment while 48 patients (22.3%) were treated with sorafenib, 42 patients (19.5%) with TACE and 23 patients (10.7%) received treatment with TACE and sorafenib in combination. Survival analyses and Cox regression models revealed that TACE and a combination therapy of TACE and sorafenib were significant prognostic factors in metastatic HCC. However, further analyses revealed that there was no additional prognostic effect of adding sorafenib to TACE treatment in this patient cohort.ConclusionsIn metastatic HCC, treatment of intrahepatic tumor by TACE may be associated with improved survival. These results support the prognostic importance of treating intrahepatic HCC even in patients with metastatic disease. Therefore, we suggest evaluating the technical feasibility of TACE in all metastatic patients.

Treatment with proton pump inhibitors increases the risk for development of hepatic encephalopathy after implantation of transjugular intrahepatic portosystemic shunt (TIPS)

Background and objective Treatment with proton pump inhibitors (PPIs) has been associated with development of hepatic encephalopathy (HE). As development of HE is a major complication after implantation of a transjugular intrahepatic portosystemic shunt (TIPS), we hypothesized that PPI treatment may be associated with a higher risk of post-TIPS HE. Methods We analyzed data of 397 patients with liver cirrhosis who received de novo TIPS implantation at the University Medical Center Freiburg, Germany. We assessed whether PPI medication and other patient characteristics are predictive factors for the development of post-TIPS HE. Results Patients with PPI treatment at the time of TIPS implantation showed significantly higher rates of post-TIPS HE than those without PPI medication (30.4% vs 11.7%, pu2009<u20090.001). The rate of post-TIPS HE increased in a dose-dependent manner. However, PPI medication did not directly affect transplant-free survival. Remarkably, in 59.1% of patients who received PPIs there was no clear indication. Conclusions PPI treatment may be an independent risk factor for the development of post-TIPS HE and the risk increases with PPI dose. Indication for PPI treatment should be assessed carefully prior to TIPS implantation in patients with liver cirrhosis.

Follicular T Helper Cell Signatures in Primary Biliary Cholangitis and Primary Sclerosing Cholangitis

Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are the most common cholestatic liver diseases. While PBC is generally accepted to be an autoimmune disorder characterized by pathognomonic autoantibodies against mitochondrial antigens, the pathogenesis of PSC is less precisely defined; however, some degree of altered immunity toward autoantigens has been suggested. Follicular T helper (Tfh) cells, a distinct clusters of differentiation (CD)4 T‐cell subset specialized in facilitating antibody responses, have been shown to contribute to humoral autoimmunity in various disorders; yet, there is only limited information on possible alterations of Tfh cells in the context of cholestatic liver diseases. Thus, we addressed this important question by analyzing the frequency, activation status, and function of Tfh cells and frequencies of regulatory follicular T helper (Tfr) cells in well‐defined cohorts of patients with PBC and patients with PSC. Interestingly, we observed a significant increase in circulating chemokine (C‐X‐C motif) receptor 5 (CXCR5)+programmed death 1 (PD‐1) +CD4+ Tfh cells in patients with PBC but not in those with PSC. Although the frequency of potentially pathogenic chemokine (C‐C motif) receptor 7 (CCR7)lowCXCR5+PD‐1+CD4+ Tfh cells was increased in both disorders compared to healthy donors, the increase was significantly more pronounced in PBC. Furthermore, in patients with PBC, Tfh cells displayed stronger expression of the activation markers OX40 and inducible costimulator of T cells, correlated with anti‐anti‐mitochondrial antibody M2 and immunoglobulin M titers, and were most significantly increased in patients with cirrhosis. Tfr cell numbers were similarly increased; however, Tfh/Tfr ratios were unaltered in PSC and PBC. These alterations did not correlate with increased secretion of the Tfh signature cytokine interleukin‐21 in sorted CD4 T cells. Conclusion: Significant alterations occur in the Tfh cell compartment in cholestatic liver diseases, suggesting that Tfh cells influence the pathogenesis of PBC and to a lesser extend PSC.

Over the Scope Clips are More Effective Than Standard Endoscopic Therapy for Patients With Recurrent Bleeding of Peptic Ulcers

BACKGROUND & AIMSnEndoscopic hemostasis is effective in treatment of bleeding peptic ulcers. However, rebleeding is difficult to treat and associated with substantial morbidity and mortality. We performed a prospective randomized trial to determine whether over-the-scope clips (OTSCs) are more effective than standard treatment of severe recurrent upper gastrointestinal bleeding.nnnMETHODSnWe performed our study at 9 academic referral centers (in Germany, Switzerland, and Hong Kong) from March 2013 through September 2016. Adult patients with recurrent peptic ulcer bleeding following initially successful hemostasis (66 patients in the intent-to-treat analysis) were randomly assigned to groups (1:1) that underwent hemostasis with either OTSC or standard therapy. Standard therapy was defined as hemostasis with through-the-scope clips (TTSC, nxa0= 31) or thermal therapy plus injection with diluted adrenaline (nxa0= 2). The primary endpoint was further bleeding (a composite endpoint of a persistent bleeding despite endoscopic therapy according to the protocol or recurrent bleeding within 7 days after successful hemostasis). Patients with further bleeding were allowed to cross over to OTSC therapy. Main secondary endpoints were mortality, necessity of surgical or angiographic salvage therapy, duration of stay in the hospital or intensive care, number of blood units transfused, and complications associated with endoscopic therapy.nnnRESULTSnPersistent bleeding after per-protocol hemostasis was observed in 14 patients (42.4%) in the standard therapy group and 2 patients (6.0%) in the OTSC group (Pxa0= .001). Recurrent bleeding within 7 days occurred in 5 patients (16.1%) in the standard therapy group vs 3 patients (9.1%) in the OTSC group (Pxa0= .468). Further bleeding occurred in 19 patients (57.6%) in the standard therapy group and in 5 patients (15.2%) in the OTSC group (absolute difference 42.4%; 95% confidence interval 21.6-63.2; Pxa0= .001) Within 30 days of follow-up, 1 patient in the standard therapy group (3.0%) and 1 patient in the OTSC group (3.0%) required surgical therapy (Pxa0= .999). Within 30 days of the procedure, 2 patients died in the standard therapy group (6.3%) and 4 patients died in the OTSC group (12.1%) (Pxa0= .672). There were no significant differences in the other secondary endpoints.nnnCONCLUSIONSnIn prospective randomized trial, we found endoscopic treatment with OTSCs to be superior to standard therapy with TTSCs for patients with recurrent peptic ulcer bleeding. STING Study, Clinicaltrials.gov no: NCT1836900.