Hepatitis C: The beginning of the end-key elements for successful European and national strategies to eliminate HCV in Europe.

Hepatitis C virus (HCV) infection is a major public health problem in the European Union (EU). An estimated 5.6 million Europeans are chronically infected with a wide range of variation in prevalence across European Union countries. Although HCV continues to spread as a largely "silent pandemic," its elimination is made possible through the availability of the new antiviral drugs and the implementation of prevention practices. On 17 February 2016, the Hepatitis B & C Public Policy Association held the first EU HCV Policy Summit in Brussels. This summit was an historic event as it was the first high-level conference focusing on the elimination of HCV at the European Union level. The meeting brought together the main stakeholders in the field of HCV: clinicians, patient advocacy groups, representatives of key institutions and regional bodies from across European Union; it served as a platform for one of the most significant disease elimination campaigns in Europe and culminated in the presentation of the HCV Elimination Manifesto, calling for the elimination of HCV in Europe by 2030. The launch of the Elimination Manifesto provides a starting point for action in order to make HCV and its elimination in Europe an explicit public health priority, to ensure that patients, civil society groups and other relevant stakeholders will be directly involved in developing and implementing HCV elimination strategies, to pay particular attention to the links between hepatitis C and social marginalization and to introduce a European Hepatitis Awareness Week.

[Current drug treatment of hepatitis C : Useful therapy algorithms taking into consideration economical aspects]. / Aktuelle Arzneimitteltherapie der Hepatitis C : Sinnvolle Therapiealgorithmen unter Berücksichtigung ökonomischer Aspekte.

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.

[From the national competence network for viral hepatitis (HepNet) emerged the German Liver Foundation (Deutsche Leberstiftung)]. / Vom Kompetenznetz Hepatitis (HepNet) zur Deutschen Leberstiftung.

The competence network for viral hepatitis (HepNet) was founded in 2002 with funding from the German government and has influenced the research on viral hepatitis in Germany. HepNet collaborator sites have been involved in numerous national and international investigator-initiated, as well as industry-sponsored, phase 1-3 studies. Within the HepNet Study-House, many groundbreaking investor-initiated trials have been completed and are still ongoing. For example, the acute hepatitis C trials and trials on chronic hepatitis D (delta), which led to therapy optimization. Continuation of the competence network on viral hepatitis has been achieved by the foundation of the German Liver Foundation, which has been an external cooperation partner of the German Center for Infection Research (DZIF) for two years. The well-established HepNet Study-House acts here as the clinical trial platform for all DZIF hepatitis trials.

The state of hepatitis B and C in the Mediterranean and Balkan countries: report from a summit conference.

The burden of disease due to chronic viral hepatitis constitutes a global threat. In many Balkan and Mediterranean countries, the disease burden due to viral hepatitis remains largely unrecognized, including in high-risk groups and migrants, because of a lack of reliable epidemiological data, suggesting the need for better and targeted surveillance for public health gains. In many countries, the burden of chronic liver disease due to hepatitis B and C is increasing due to ageing of unvaccinated populations and migration, and a probable increase in drug injecting. Targeted vaccination strategies for hepatitis B virus (HBV) among risk groups and harm reduction interventions at adequate scale and coverage for injecting drug users are needed. Transmission of HBV and hepatitis C virus (HCV) in healthcare settings and a higher prevalence of HBV and HCV among recipients of blood and blood products in the Balkan and North African countries highlight the need to implement and monitor universal precautions in these settings and use voluntary, nonremunerated, repeat donors. Progress in drug discovery has improved outcomes of treatment for both HBV and HCV, although access is limited by the high costs of these drugs and resources available for health care. Egypt, with the highest burden of hepatitis C in the world, provides treatment through its National Control Strategy. Addressing the burden of viral hepatitis in the Balkan and Mediterranean regions will require national commitments in the form of strategic plans, financial and human resources, normative guidance and technical support from regional agencies and research.

[Costs of guideline-based treatment of hepatitis B patients in Germany]. / Kosten einer leitliniengerechten Versorgung von Hepatitis-B-Patienten in Deutschland.

The costs of guideline-based treatment are unknown for most diseases. This also applies for economically significant infectious diseases like viral hepatitis and HIV. On the basis of the "German Guidelines for the Management of HBV Infection" from 2011 patients were grouped into HBsAg-positive, immuntolerant and chronic hepatitis patients with and without cirrhosis. Costs were divided in baseline diagnostics, monitoring and medical treatment according to the guideline. The calculation was modelled for a period of five years. Costs for virological diagnostics and imaging account for a large proportion of diagnostic costs. The main cost factors are expenses for pharmaceutical treatment with interferon or HBV polymerase inhibitors. On the assumption that only 25 % of the infected patients are diagnosed, 5-year total costs in Germany account for more than 2.5 billion Euros. Therefore, chronic hepatitis B is a disease with a very high economic burden. The aim of a guideline treatment is to prevent the development of cirrhosis with all its complications as well as the development of liver-cell carcinoma. Prophylactic vaccination against hepatitis B should be advised also considering the potential economic impact.

[Transcutaneous perianal ultrasound (PAUS) for the imaging of fistulas and abscesses in Crohn's disease]. / Aktuelle Sonographie: Transkutaner, perianaler Ultraschall (PAUS) zur Diagnostik von Fisteln und Abszessen bei M. Crohn.

Pelvic MRI and transanal ultrasound constitute the gold standard for the imaging of perianal inflammatory lesions in Crohn's disease. Perianal ultrasound (PAUS), however, is rarely considered in recent literature. In contrast to the established methods, perianal ultrasound represents an easy, cost-effective and at the same time sensitive method for the imaging of perianal abscesses and fistulas. This article illustrates the performance of perianal ultrasound and shows typical images of pathological findings such as abscesses and fistulas. PAUS is especially useful for acute diagnostics to rule out perianal abscesses and for follow-up evaluation of fistula treatment. For example, complications such as abscesses can be detected in a timely manner.

[Liver transplantation: deciding between need and donor allocation]. / Lebertransplantation zwischen Indikation und Spenderallokation.

Liver transplantation represents an established therapeutic option for advanced liver diseases. The spectrum of indications encompasses infectious, vascular, immunological and toxic diseases leading to cirrhosis, in addition to genetic, metabolic, developmental and selected neoplastic diseases. On the one hand the timing of liver transplantation is determined by the disease specific course until decompensation and the disease manifestation involving bile ducts or hepatocytes. On the other hand it represents gene therapy of diseases affecting the liver, or entities where the genetic defect lies in the liver. In view of the shortage of donor organs and an increasing requirement for liver transplantation the challenge is to provide an effective and fair waiting list management. Reform of allocation criteria has put the focus on urgency. This in turn leads to an increase in waiting time for elective transplantations, inclusion of end stage diseases and critical patients, higher perioperative costs, problems with the matching of organs and the problem of an effective use of organ resources. Fair allocation and medical necessity therefore define the challenges surrounding the indications for liver transplantation.

[Encoding of diagnosis by medical documentation assistant or ward physician. Influence on the mapping of Diagnostic Related Group (DRG) performance]. / Diagnosenverschlüsselung durch Medizinische Dokumentationsassistentin oder Stationsarzt. Einfluss auf die Abbildung der DRG-Leistung.

BACKGROUND AND OBJECTIVE: Starting in 2004 the patient budget in Germany will be calculated according to the Diagnosis Related Group (DRG) system, by which system the monetary reward of a unit will be directly related to the quality of documentation e. g. diagnosis and procedures. The aim of this study was to compare the quality of documentation by a medical documentation assistant (MDA) with the usual practice of documentation by the ward physician (WP). Additionally, the effect of introducing a completely changed organizational process was tested. METHODS: In a prospective study on the ward of a gastroenterology unit two different approaches of medical documentation were compared. In a first six-month period diagnosis and procedures were encoded by WP. In the following six months an MDA was introduced and involved in the encoding process. RESULTS: In the first six months 221 patients (mean age 55 +/- 16,2 years, 55,7 % males) were evaluated, whereas in the following six months 305 patients (mean age 53 +/- 15,4 years, 59,9 % males) were included. The introduction of an MDA improved medical documentation and economical reference numbers: with an increase of diagnosis per case to 7,43 (in first six months 5,53), patient complexity and comorbidity level (PCCL) to 2,5 (in first six months 2,13), case-mix index to 1,04 (in first six months 0,98). Additionally the medial hospitalization time decreased from 11,2 to 8,1 days. The average daily reimbursement increased in the MDA group from 423 Euro to 603 Euro. This was calculated on the basis of a basic case factor of 2900 Euro. CONCLUSION: Introduction of an MDA in a gastroenterology ward increases the quality of documentation and results in an improved presentation of DRG-relevant efforts with a better reimbursement of medical costs.

Cost effectiveness of peginterferon alpha-2b plus ribavirin versus interferon alpha-2b plus ribavirin for initial treatment of chronic hepatitis C.

BACKGROUND: Peginterferon alpha-2b plus ribavirin therapy in previously untreated patients with chronic hepatitis C yields the highest sustained virological response rates of any treatment strategy but is expensive. AIMS: To estimate the cost effectiveness of treatment with peginterferon alpha-2b plus ribavirin compared with interferon alpha-2b plus ribavirin for initial treatment of patients with chronic hepatitis C. METHODS: Individual patient level data from a randomised clinical trial with peginterferon plus ribavirin were applied to a previously published and validated Markov model to project lifelong clinical outcomes. Quality of life and economic estimates were based on German patient data. We used a societal perspective and applied a 3% annual discount rate. RESULTS: Compared with no antiviral therapy, peginterferon plus fixed or weight based dosing of ribavirin increased life expectancy by 4.2 and 4.7 years, respectively. Compared with standard interferon alpha-2b plus ribavirin, peginterferon plus fixed or weight based dosing of ribavirin increased life expectancy by 0.5 and by 1.0 years with incremental cost effectiveness ratios of 11,800 euros and 6600 euros per quality adjusted life year (QALY), respectively. Subgroup analyses by genotype, viral load, sex, and histology showed that peginterferon plus weight based ribavirin remained cost effective compared with other well accepted medical treatments. CONCLUSIONS: Peginterferon alpha-2b plus ribavirin should reduce the incidence of liver complications, prolong life, improve quality of life, and be cost effective for the initial treatment of chronic hepatitis C.

Prevention of hepatocellular carcinoma in chronic liver disease: molecular markers and clinical implications.

The development of hepatocellular carcinoma is generally preceded by chronic liver damage leading to cirrhosis. Prevention of chronic liver diseases can decrease the incidence of hepatic cancer impressively. Many recent investigations have also explored the power of secondary and tertiary prevention in established liver cirrhosis. Screening programs for patients at high risk, antiviral treatment of patients with progressed hepatitis, and adjuvant interventions after curative resection are some of the approaches. However, the cost effectiveness and benefits of such procedures and the prognosis is also dependent on the remaining liver function, there is no consensus to date on how patients should be handled. In the future molecular markers and prognostic scores may help better define the group at risk of developing. To give a perspective to these patients, it is necessary to improve the treatment of hepatocellular carcinoma as well as cirrhosis.

Elevated bound leptin correlates with energy expenditure in cirrhotics.

BACKGROUND & AIMS: Leptin, found to be elevated in patients with liver cirrhosis, may contribute to the inadequate energy expenditure and malnutrition associated with a negative prognosis for these patients. Our aim was to characterize leptin components and their relationships to body composition, resting energy expenditure (REE), and substrate use in patients with posthepatic liver cirrhosis. METHODS: Using specific radioimmunoassays, we measured free leptin and bound leptin in 27 cirrhotics and 27 matched control subjects. In the cirrhotic group, body composition and REE were determined. RESULTS: Free leptin was not different in cirrhotics and control subjects and was related to body mass index (controls: r = 0.34, P < 0.05; cirrhotics: r = 0.55, P < 0.005) and to fat mass (cirrhotics: r = 0.76, P < 0.0001). Bound leptin was significantly higher in cirrhotic subjects than in controls (P < 0.001) and was related to REE x fat-free mass(-1) (r = 0.57, P < 0.005) or to the difference between measured and estimated REE (r = 0.55, P < 0.005). CONCLUSIONS: Free leptin reflects fat mass in controls and cirrhotics. Increased serum leptin in cirrhotics is a result of increased bound leptin serum concentrations, which are positively related to energy expenditure. Moreover, bound leptin may be a useful marker for inadequate energy expenditure in patients with liver cirrhosis.

[Peritoneal carcinosis in appendiceal carcinoma--at what price can the prognosis be improved?]. / Peritonealkarzinose beim Appendixkarzinom--um welchen Preis kann die Prognose verbessert werden?

BACKGROUND AND AIM: Many patients with appendix carcinoma develop peritoneal carcinomatosis with poor prognosis. The purpose of this study was to look for results of multimodality treatment in these patients. PATIENTS AND METHODS: Data of 13 patients (11 men, 2 women, median age 58 years) with proven peritoneal carcinomatosis from appendiceal carcinoma, operated between 07/1995 and 10/1998 were analysed retrospectively with special regard to extent of resection, postoperative morbidity and mortality, survival. RESULTS: A macroscopically complete cytoreduction could be achieved in all patients by multivisceral resection with peritonectomy. Intraoperatively, after resection, an open, hyperthermic intraperitoneal chemotherapy with Cisplatin was performed. Morbidity and 90-days-mortality were 62% and 15%, respectively. After a median follow-up of 36 months all patients survived the therapy (excepting two postoperative deaths). CONCLUSIONS: In selected patients with advanced appendix carcinoma and peritoneal carcinomatosis prognosis can be improved by peritonectomy with intraperitoneal hyperthermic chemotherapy. This results in high mortality and morbidity.

Immunnohistological assessment of intestinal eosinophil activation in patients with eosinophilic gastroenteritis and inflammatory bowel disease.

OBJECTIVE: To assess the activation grade of intestinal eosinophils in patients with eosinophilic gastroenteritis (EOG), ulcerative colitis (UC), Crohn's disease (CD), and controls by immunohistochemistry. METHODS: Cecal biopsies were collected from healthy controls and from patients with EOG, CD, UC, and other noninflammatory GI diseases. Immunohistochemistry was performed in sequential sections stained with monoclonal antibodies directed against eosinophil cationic protein (ECP) or eosinophil protein X (EPX) stored in eosinophil granules (EG1) and that secreted by activated eosinophils (EG2). The ratio of EG1 to EG2-positive eosinophils expressed as percentage of lamina propria cells was calculated. ECP and EPX were measured in serum and feces. RESULTS: The percentage of EG1 and EG2-positive lamina propria cells was elevated in EOG and slightly, but not significantly, in UC. The ratio of EG1 to EG2-positive cells was decreased in CD, UC, and other patients as compared to healthy controls. Particularly low EG1 to EG2 ratios were found in EOG. Correspondingly, fecal and serum levels of ECP and EPX, respectively, were highest in patients with EOG. The EG1 to EG2 ratio was negatively correlated with fecal ECP and EPX levels. At sites of actively inflamed mucosa, the EG1 to EG2 ratio was lower than in noninflamed tissue. CONCLUSIONS: Our data strongly suggest that the EG1 to EG2 ratio may be a marker of tissue eosinophil activation. Low ratios (<1) indicate eosinophil activation, whereas ratios > or =1 are found in healthy controls. Furthermore, we show that EOG is characterized by a pronounced intestinal eosinophil accumulation and activation, whereas in CD and UC, eosinophils seem to be activated but their number is not or only slightly elevated compared to controls.

The number connection tests A and B: interindividual variability and use for the assessment of early hepatic encephalopathy.

BACKGROUND/AIMS: The number connection tests A and B are regarded as sensitive psychometric measures for the assessment of early hepatic encephalopathy. Review of the studies dealing with the diagnostic sensitivity of the number connection tests, however, shows that the scoring of the number connection tests results differs between studies. Most groups define the limits of the normal range by studying small control groups. Others use scores given in the literature without ensuring the comparability of the test versions used. Thus, there is a need for normative data for the number connection test results and for re-evaluation of the sensitivity of the tests using valid scores. METHODS: In this study the number connection tests A and B were administered to 249 healthy volunteers (age: 18 to 76 years) to analyze the influence of age, education and occupation on their results. In addition, the age-corrected normative data were applied to 169 patients with grade 0-I hepatic encephalopathy. The specificity and sensitivity of age-corrected and age-independent normative data of the number connection tests were compared. RESULTS: There was a significant influence of age and education on the number connection test results, but only a negligible effect of occupation. Application of the age-corrected normative data to the test results of the patients with grade I hepatic encephalopathy significantly decreased the sensitivity of the number connection tests for hepatic encephalopathy compared to widely used age-independent normal ranges, but also increased the specificity. CONCLUSION: The use of standardized versions of the number connection tests and age-related normative data is recommended.

[Approaches to objective assessment of differences in tissue textures by ultrasound equipment as a contribution to quality assurance]. / Ansätze zur Objektivierung der Gewebeunterscheidbarkeit von Ultraschallgeräten als Beitrag zur Qualitätssicherung.

PURPOSE: For clinical investigators the increasing number of ultrasonic machines with different technological equipment makes it difficult to reliably assess their ability to differentiate between the textures of various tissues. We investigated a procedure for a standardised method to measure the tissue texture when using different ultrasonic machines. METHODS: The texture parameters concern brightness, standard deviation, coefficient of variation and spatial coefficient of variation. These were calculated for three tissue phantoms with changing levels of gain and distance. These parameters, well established in literature for speckle detection, texture differentiation and contrast monitoring were useful for rapid comparison of the texture differentiation achieved by several ultrasonic machines. RESULTS: A linear relationship between standard deviation and mean image brightness seems to be an important factor for the detection of small changes in ultrasonic textures. We noticed great differences between the various ultrasonic machines tested by us. The best parameter in our set was the spatial coefficient of variation. CONCLUSION: The method allows rapid orientation regarding the ability of a machine to distinguish between several textures depending on the brightness, and offers an opportunity of determining the best working point for a given machine.