Lifestyle interventions for patients with non-alcoholic steato-hepatitis-Design, rationale and protocol of the study "target group-specific optimisation of lifestyle interventions for behavior change in non-alcoholic steato-hepatitis (OPTI-NASH)"

BACKGROUND: Non-alcoholic steato-hepatitis (NASH) is the inflammatory, progressive form of non-alcoholic fatty liver disease (NAFLD). A delayed diagnose interval is typical for the majority of the patients because of the asymptomatic natural course. However, serious sequelae may develop such as cirrhosis or hepatocellular carcinoma. NASH is also associated with an increased risk of metabolic diseases. Obesity developed due to a lack of exercise or a disadvantageous diet often leads to NAFLD or NASH, thereby interventions including enhanced physical activity and calorie reduction form the actual gold standard of treatment. To date, patients rarely use these. The project aims to model lifestyle interventions based on the preferences of the NASH patients. METHODS: Based on a systematic review and focus group discussions, two discrete choice experiments (DCE) will be designed, one on aspects influencing successful uptake of lifestyle interventions and one to analyses parameters contributing to long-term participation. An online survey will be used to elicit patient's preferences on program design and on motivational aspects in a cross-sectional design. The recruitment will take place in nine certified specialist practices and hospital outpatient clinics aiming to reach a sample size of n = 500 which is also required for the DCE design. DISCUSSION: The results will provide an overview of the NASH patient's preferences regarding the successful uptake and long-term implementation of lifestyle interventions. Recommendations for optimized lifestyle change programs will be derived and an intervention manual will be developed to facilitate target group-specific inclusion in programs in practice.</p

Cost-effectiveness of Triple Therapy with Telaprevir for Chronic Hepatitis C Virus Patients in Germany

**Background:** About 400,000-500,000 people are infected with hepatitis C in Germany. Long-term consequences are the development of liver cirrhosis and hepatocellular carcinoma. The introduction of first generation protease inhibitors has significantly improved the treatment of hepatitis C genotype 1 patients. The aim of the study was to assess the cost-effectiveness of triple therapy with telaprevir in Germany. **Methods:** We used a Markov model on disease progression and natural history to assess the cost-effectiveness of triple therapy with telaprevir compared to standard treatment with pegylated interferon and ribavirin. Model structure and inputs were discussed with clinical experts. Deterministic and probabilistic sensitivity analyses were performed to verify the robustness of results. **Results:** The base-case analyses shows that triple therapy results in higher costs (untreated patients: €48,446 vs. €30,691; previously treated patients: €63,228 vs. €48,603) and better outcomes (untreated patients: 16.85 qualily of life years [QALYs] vs. 15.97 QALYs; previously treated patients: 14.16 QALYs vs. 12.89 QALYs). The incremental cost-effectiveness ratio (ICER) was €20,131 per QALY and €30,567 per life year gained (LYG) for previously untreated patients. ICER in treatment experienced patients was €7,664 per QALY for relapse patients, €12,506 per QALY for partial responders and €28,429 per QALY for null responders. Results were robust in sensitivity analyses. **Conclusion:** Although triple therapy with telaprevir leads to additional costs, there is a high probability of being cost-effective for different thresholds. This health economic analysis makes an important contribution to current debates on cost savings and efficient resource allocation in the German healthcare sector

Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without D

Akute Exazerbation einer reaktivierten chronischen Hepatitis B nach Absetzen der antiviralen Therapie mit nachfolgendem Verlust des HBsAg

Zusammenfassung Anamnese und klinischer Befund Eine 66-jährige Patientin mit chronischer HBV-Infektion unter antiviraler Therapie stellte sich mit Ikterus und allgemeiner Schwäche 2 Wochen nach einem Infekt der oberen Atemwege vor. Die Therapie setzte die Patientin 6 Monate vor Vorstellung eigenständig ab. Die Leber war leicht vergrößert tastbar, das Abdomen sowie der weitere körperliche Untersuchungsstatus waren unauffällig. Untersuchungen und Diagnose Das Labor zeigte deutlich erhöhte Lebertransaminasen sowie ein erhöhtes Bilirubin. Der Hepatitis-B-Infektionsstatus bestätigte das Bild des chronisch-aktiven Verlaufs (HBsAg positiv), die Virusquantifizierung ergab Werte &gt; 21 Mio. IU/ml. Sonografisch zeigten sich keine Auffälligkeiten. Therapie und Verlauf Die antivirale Therapie wurde wieder aufgenommen mit nachfolgender Besserung der Lebertransaminasen und Abfall der Virusmenge. Nach 22 Wochen Behandlung traten eine Serokonversion (HBsAg negativ) und Ausheilung der Hepatitis ein. Folgerung Im Rahmen eines akuten Schubs einer chronischen Hepatitis B nach Beendigung der antiviralen Therapie ist eine Ausheilung mit Verlust des HBsAg möglich.</jats:p

Current management of intramural duodenal hematoma in alcohol induced pancreatitis

Intramural duodenal hematomas (IDH) have been rarely associated with pancreatic diseases. Conservative treatment is recommended, but course of disease can be life threatening, serious complications may occur (i.e. duodenal perforation) with imperative surgery. The management of diagnostic and treatment in IDH has improved over the years. Computed tomography (CT) and endoscopic ultrasound are excellent tools for diagnosis and follow up of IDH. We report a case of a 31-year-old alcoholic who presented with vomiting, exsiccosis, hypochondriac pain and positive shock index. Esophagogastroduodenoscopy showed gastric outlet obstruction caused by obliterating tumor of bulbus duodeni. Initial suspicion was malign tumor of the duodenum confirmed by native CT and histology. Further diagnostic using EUS-guided aspirate resulted in IDH. By conservative management with nasogastric decompression and digestive rest the patient recovered. In course of disease the hematoma got smaller, but parts were still seen in CT 6 month later