Improvement of health‐related quality of life (HRQoL) is frequently reported as a benefit when treating hepatitis C virus infection (HCV) with direct acting antivirals (DAA). As most of the available data were obtained from clinical trials, limited generalizability to the real‐world population might exist. This study aimed to investigate the impact of DAA therapy on changes in HRQoL in a real‐world setting. HRQoL of 1180 participants of the German Hepatitis C‐Registry was assessed by Short‐Form 36 (SF‐36) questionnaires. Scores at post‐treatment weeks 12–24 (FU12/24) were compared to baseline (BL). Changes of ≥2.5 in mental and physical component summary scores (MCS and PCS) were defined as a minimal clinical important difference (MCID). Potential predictors of HRQoL changes were analysed. Overall, a statistically significant increase in HRQoL after DAA therapy was observed, that was robust among various subgroups. However, roughly half of all patients failed to achieve a clinically important improvement in MCS and PCS. Low MCS ( p < .001, OR = 0.925) and PCS ( p < .001, OR = 0.899) BL levels were identified as predictors for achieving a clinically important improvement. In contrast, presence of fatigue ( p = .023, OR = 1.518), increased GPT levels ( p = .005, OR = 0.626) and RBV containing therapy regimens ( p = .001, OR = 1.692) were associated with a clinically important decline in HRQoL after DAA therapy. In conclusion, DAA treatment is associated with an overall increase of HRQoL in HCV‐infected patients. Nevertheless, roughly half of the patients fail to achieve a clinically important improvement. Especially patients with a low HRQoL seem to benefit most from the modern therapeutic options.

Only limited data are available, regarding the influence of IFN-free, DAA-mediated therapy on patient reported outcomes (PROs) and clinical symptoms in patients with chronic hepatitis C infection. Therefore, we longitudinally assessed Short-Form 36 (SF-36) scores in HCV patients antivirally treated in a real world setting and focused on the identification of subgroups especially profiting from DAA regimens with respect to self-reported quality of life (QoL).

BACKGROUND:Direct-acting antiviral agents (DAAs) have revolutionized treatment of chronic hepatitis C in patients with normal glomerular filtration rate (GFR). However, patients with impaired kidney function have been excluded from several clinical trials. We, therefore, investigated the use, effectiveness, and tolerability of DAAs in patients with GFR less than 30 ml/min in the real-world setting.PATIENTS AND METHODS:An analysis was done within the German Hepatitis C-Registry on 5733 patients including 46 individuals with a baseline GFR less than 30 ml/min treated with sofosbuvir-based (61%) or paritaprevir/ritonavir-based (39%) regimens.RESULTS:Sustained virological response 12 rates did not differ significantly between patients with baseline GFR less than 30 versus more than 30 ml/min (91 vs. 96%). Nine individuals with a baseline GFR more than 30 ml/min presented with a GFR less than 30 ml/min at the end of treatment. GFR improvement from less than 30 ml/min to more than 30 ml/min was observed in 9/46 cases. Adverse events did not differ in patients with GFR less than 30 versus more than 30 ml/min. However, serious adverse events were significantly more frequent in individuals with GFR less than 30 ml/min and associated with ribavirin.CONCLUSION:Different DAA therapies can be safely used with high sustained virological response rates in patients with GFR less than 30 ml/min. Ribavirin has to be avoided because of poor tolerability.

Während die Wirksamkeit der ab 2014 verfügbaren direkt-antiviralen HCV Medikamente (DAA) im Alltag bestätigt wurde, gibt es kaum Daten, die den Einfluss einer DAA-basierten Heilung (SVR12) auf das Wohlbefinden und die klinische Symptomatik in einer breiten Patientenpopulation außerhalb klinischer Studien zeigen.

Aim The utility of noninvasive serum markers to longitudinally monitor liver fibrosis is not established. Methods A total of 70 patients with chronic hepatitis C who had previously failed antiviral therapy were randomized to receive pegylated interferon with or without silymarin for 24 months. Enhanced Liver Fibrosis (ELF) tests (hyularonic acid, terminal peptide of procollagen III, tissue inhibitor of matrix metaloproteinase-1) were performed on patient sera obtained before, during and at the end of the study (0, 12, 24 months) and liver histology obtained before and at the end of the study. Results At 24 months, absolute changes in Ishak fibrosis stage and ELF ranged from −4 to +4 and from −2.41 to +2.68, respectively. Absolute changes in ELF at 12 months were significantly associated with changes in both ELF and histology at 24 months. A model combining both baseline ELF and change of ELF at 12 months could predict the 24-month ELF ( R 2 =0.609, P <1×10 –11 ), a decrease in ELF at 24 months [area under the curve (AUC): 0.80–0.85] and an increase in ELF at 24 months (AUC: 0.81–0.85). Furthermore, a model combining both baseline histologic stage and ELF together with the change of ELF at 12 months could predict 24-month histology ( R 2 =0.601, P <1×10 –11 , AUC: 0.88–0.92), histologic fibrosis regression (AUC: 0.81–0.84) and progression (AUC: 0.86–0.91). Conclusion Our observations suggest that a change in the serum marker ELF predicts changes in liver fibrosis over a longer period. These data support the use of ELF as a surrogate marker of liver fibrosis evolution in monitoring antifibrotic treatments, thus permitting ‘response-guided’ therapy by the early identification of patients who will benefit from prolonged treatment.

Während die Wirksamkeit der ab 2014 verfügbaren direkt-antiviralen Medikamente (DAA) im Alltag bestätigt wurde, gibt es kaum Daten, die die Heilungsraten (SVR-12), das Wohlbefinden und die klin. Symptomatik von HCV Patienten mit Migrationshintergrund beschreiben.

BACKGROUND:Advancing fibrosis is regarded as the most important factor when stratifying patients with chronic hepatitis C for retreatment.GOALS:(1) To compare the performance of 10 biomarkers of fibrosis, including patented tests, among patients with chronic hepatitis C and treatment failure; and (2) to assess the impact on biomarker performance of using 2 different assays of hyaluronic acid (HA).STUDY:For 80 patients, liver histology (Metavir) was compared with biomarker scores using sera obtained within 6 months of liver biopsy (indirect biomarkers: AST:ALT ratio, APRI, Forns index, FIB-4, Fibrometer V3G; direct biomarkers: ELF, Fibrospect II, Hyaluronic acid-HA, Fibrometer V2G, Hepascore). Direct biomarker scores were calculated using 2 validated assays for HA (ELISA and radiometric).RESULTS:Using the ELISA assay for HA to calculate the direct panels, all 10 of the biomarkers exhibited comparable overall discriminatory performance (unweighted Obuchowski measure, ordROC 0.92-0.94, P-value>0.05) except AST:ALT ratio and APRI (ordROC 0.86-0.88, P-value<0.05). For the detection of moderate (F2-4) and advanced (F3-4) fibrosis, the AUROC of Fibrometer 2G were significantly higher than AST:ALT ratio and APRI but none of the other biomarkers. Good correlation was observed between the 2 HA assays (intraclass correlation coefficient=0.873) with the ELISA assay exhibiting superior diagnostic performance (ordROC 0.92 vs. 0.88, P-value=0.003). Importantly, the performance of many of the direct biomarkers at their diagnostic thresholds was heavily influenced by the choice of HA assay.CONCLUSIONS:Although many biomarkers exhibited good diagnostic performance for the detection of advancing fibrosis, our results indicate that diagnostic performance may be significantly affected by the selection of individual component assays.

Hintergrund/Einleitung: Die Therapie des hepatozellulären Karzinoms (HCC) mit konventionellen Chemotherapeutika wie 5-Fluoruracil (5-FU) und Irinotecan (ITC) ist wenig effektiv. Wir konnten zeigen, dass Hemmer der Histondeacetylase (HDAC) bereits in mik-romolaren Konzentrationen Apoptose in verschiedenen Tumorzellen in vitro induzie-ren. Zur Kombination von Suberoylanilidhydroxaminsäure (SAHA), einem oralen HDAC-Inhibitor, mit 5-FU und ITC liegen bislang keine Daten vor.

Hintergrund/Einleitung: Histondeazetylase (HDAC) Hemmer gelten wegen ihrer redifferenzierenden und pro-apoptotischen Effekte als vielversprechende Medikamente in der experimentellen Tumortherapie. HDAC Hemmer führen über eine Hyperacetylierung der Histone zur vermehrten Expression bestimmter Gen-Loci. Es gibt bislang keine vergleichendenDaten hinsichtlich der anit-tumoralen Potenz verschiedener HDAC-Hemmer.

Einleitung: Das hepatozelluläre Karzinom (HCC) gilt als chemo-resistent.Wir konnten zellkulturell eine anti-proliferative und pro-apoptotische Effektivität des Anti-Östrogens Tamoxifen (TAM) und des Retinoids 9cis Retinsäure (CRA) nachweisen. Eine Kom-bination der beiden Substanzen zeigte über-additive Effekte. Es gibt bislang keine in vivo Daten zur Wirkung von TAM und/oder CRA in einem Tiermodell des HCC.

P1043 REAL-LIFE PERSISTENCE AND ADHERENCE IN ETV TREATED CHRONIC HEPATITIS B PATIENTS: RESULTS OF A GERMAN PROSPECTIVE MULTICENTER OBSERVATIONAL STUDY J. Petersen, T. Wilke, S. Mauss, R. Heyne, C. Herold, M. Wiese, K. Boeker, T. Pichl, D. Hueppe. ifi – Institut fur Interdisziplinare Medizin, Hamburg, IPAM Wismar, Wismar, Medizinisches Versorgungszentrum, Duesseldorf, Leberzentrum Checkpoint, Berlin, Internisten am Ring, Nuernberg, Gesellschaft fur Klinische Studien, Leipzig, Leberpraxis Hannover, Hannover, BristolMyers Squibb GmbH & Co. KGaA, Munich, Gastroenterologische Gemeinschaftspraxis Herne, Herne, Germany E-mail: petersen@ifi-medizin.de Background and Aims: Entecavir (ETV) is a very effective and safe treatment option in chronic hepatitis B (CHB) patients. However, some patients show only a partial virologic response. The most reasonable explanation is non-persistence/non-adherence. Persistence and adherence measurement is underrepresented in clinical trials. Therefore, the extent of non-persistence (NP), nonadherence (NA) and clinical outcomes of any NP/NA were measured in ETV-treated patients in a real-life study. Methods: In a prospective observational multicenter study, persistence and adherence were measured based on documented ETV prescriptions within a 12 month period. A patient was defined as NP if he missed all treatment doses in >30 subsequent days. Adherence was measured based on medication possession ratio (MPR) between first and last documented prescription (NA if MPR 30 subsequent days (NP group), 30% of patients in the NP group (n =9) and none of the persistent patients were classified as non-adherent. Mean MPR for all patients was 95.3%. 84.4% of persistent/adherent patients and 63.0% of patients in the NP group reached undetectable HBV-DNA levels (p = 0.022). So far no significantly correlating factors for NP/NA could be detected.

Introduction The detection of advancing fibrosis in patients with CHC and prior treatment failure is important for ascertaining prognosis. HA has been used alone and as a constituent component of fibrosis marker panels. The aim of this study was to compare the performance of 4 marker panels in the detection of moderate-to-severe fibrosis (Metavir F2–4) and to assess the influence on diagnostic performance of using 2 different validated assays for HA. Methods 80 patients with CHC, all non-responders or relapsers to IFN-based treatment, were included in this study. Sera obtained within 6 months of liver biopsy were used to measure 4 biomarker panels incorporating HA (ELF, Fibrospect-II, Hepascore, Fibrometer-2G) using 2 validated assays for HA (ELISA-Siemens, radiometric-Pharmacia). Diagnostic performance for the detection of moderate-to-severe fibrosis was assessed by AUROC and by evaluating biomarker performance at published thresholds. Results The prevalence of moderate-to-severe fibrosis was 63% (F0–8%, F1–29%, F2–24%, F3–30%, F4–9%). The AUROC of the Siemens HA assay was higher than the Pharmacia assay (0.80 Vs. 0.69, P = 0.005). Incorporating the Siemens assay for HA, the performance of the panels were not statistically significantly different but Fibrometer 2G generated the highest AUROC. Using the Siemens assay, ELF and Fibrometer 2G had the highest PPV and NPV respectively (88% and 100% using published thresholds). The use of the Pharmacia assay for HA to calculate the biomarkers did not reduce the discriminatory ability of the 4 panels (p = NS). However whereas the other panels were largely unaffected, the use of the Pharmacia assay resulted in a dramatic reduction in the performance of published thresholds of the ELF test with the a priori and a posteriori probability of fibrosis being equal. View this table: Abstract PWE-140 Table Conclusion In this study the performance of the 4 biomarker panels to detect moderate-to-severe fibrosis was comparable. The diagnostic performance of biomarker panels may be significantly effected by the selection of the individual component assays as demonstrated by comparison of the results obtained with different HA assays. Disclosure of Interest None Declared.

Objective Minimal hepatic encephalopathy (MHE) is one of the possible complications of liver cirrhosis. In this study, a potassium–iron–phosphate–citrate complex was analyzed for its efficacy and safety in the treatment of MHE, as this complex is supposed to bind to the major pathogenic factor of MHE: intestinal ammonia. Materials and methods In this placebo-controlled, double-blind clinical trial, 51 patients with MHE were randomized into two groups at a ratio of 1 : 1 and treated for 4 weeks either with a potassium–iron–phosphate–citrate complex or a placebo. The efficacy of treatment was assessed according to changes in the portosystemic encephalopathy (PSE) score. Further assessments included alterations in quality of life and safety evaluations. Results Significantly more patients showed improvements in the PSE syndrome test from pathological to nonpathological PSE scores in the potassium–iron–phosphate–citrate-treated group (72.0%) than in the placebo group (26.9%; P=0.0014). Furthermore, quality of life improved at a higher grade in the verum group (by 0.7±0.6 U) compared with the placebo group (by 0.2±0.6 U; P=0.0036). Adverse events occurring in 28.0% of potassium–iron–phosphate–citrate-treated patients were generally mild or moderate and affected mainly the gastrointestinal tract. Conclusion Treatment with potassium–iron–phosphate–citrate significantly improved PSE scores and quality of life in patients with MHE. The potassium–iron–phosphate–citrate complex is a well-tolerated treatment option in MHE.