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Background Non-alcoholic fatty liver disease (NAFLD) affects more than 18 million individuals in Germany. Real-world data help to better characterize the natural history of disease and standard of care. Methods The German NAFLD-Registry is a prospective non-interventional study initiated by the German Liver Foundation and aims to describe clinical characteristics and observe outcomes in patients with NAFLD recruited in secondary and tertiary care. Results From this ongoing study, baseline data of the first 501 patients (mean age 54 years, 48% women) were analysed. 13 % of the study population had a high risk for advanced fibrosis (FIB-4 ≥2.67), approximately one-third had a liver stiffness value ≥9.6kPa measured by transient elastography, and the clinical diagnosis of liver cirrhosis was present in 10%. Typical comorbidities were more prevalent in high risk as compared to low risk patients (FIB-4 Conclusion First data of the German NAFLD registry show that approximately every 10th patient has advanced NAFLD, highlights T2DM patients as a high-risk group and gives insights in the use of comedication and life-style interventions in secondary and tertiary care.

Die Einfuhrung der neuen direkt antiviral wirksamen Medikamente hat die Therapie der chronischen Hepatitis C revolutioniert. Dank dieser Entwicklung sind wir heute in der Lage, den uberwiegenden Teil unserer Hepatitis-C-Patienten dauerhaft zu heilen. Fur die tagliche Praxis ist daher eine gezielte Diagnostik bezuglich einer Hepatitis C von groser Bedeutung, um infizierte Patienten identifizieren und behandeln zu konnen.

Sufficient bowel preparation is crucial for successful screening and surveillance colonoscopy. However, rates of inadequate preparation are still high. We investigated the effects of reinforced patient education using a smartphone application software (APP) for colonoscopy preparation in participants in a CRC screening program.We performed a prospective, endoscopist-blinded study of 500 patients undergoing split-dose bowel preparation for CRC screening or surveillance colonoscopies at multiple centers in Germany, from November 2017 through January 2019. Participants (n = 500) were given oral and written instructions during their initial appointment and then randomly assigned (1:1) to groups that received reinforced education starting 3 days before the colonoscopy (APP group) or no further education (controls). The primary outcome was quality of bowel preparation according to the Boston bowel preparation scale. Secondary outcomes included polyp and adenoma detection rates, compliance with low-fiber diet, split-dose laxative intake, perceived discomfort from the preparation procedure.The mean Boston bowel preparation scale score was significantly higher in the APP-group (7.6 ± 0.1) than in the control group (6.7 ± 0.1) (P.0001). The percentage of patients with insufficient bowel preparation was significantly lower in the APP group (8%) than in the control group (17%) (P = .0023). The adenoma detection rate was significantly higher in the APP group (35% vs 27% in controls) (P = .0324). Use of the APP was accompanied by a lower level of non-compliance with correct laxative intake (P =.0080) and diet instructions (P = .0089). The APP group reported a lower level of discomfort during preparation (P.0001).In a randomized trial, reinforcing patient education with a smartphone application optimized bowel preparation in the 3 days before colonoscopy, increasing bowel cleanliness, adenoma detection, and compliance in patients undergoing CRC screening or surveillance. ClinicalTrials.gov no: NCT03290157.

Current surveillance strategies for colorectal cancer following polypectomy are determined by endoscopic and histopathological factors. Such a distinction has been challenged. The present study was designed to identify molecular parameters in colonic polyps potentially defining new sub-groups at risk.One hundred patients were enrolled in this multicentre study. Polyps biopsies underwent formalin-free processing (PAXgene, PreAnalytiX) and targeted next generation sequencing (38 genes (QIAGEN), NextSeq 500 platform (Illumina)). Genetic and histopathological analyses were done blinded to other data.In 100 patients, 224 polyps were removed. Significant associations of genetic alterations with endoscopic or histological polyp characteristics were observed forAssessment of the mutational landscape of polyps can be integrated in the workflow of current colonoscopy practice. There are distinct genetic patterns related to polyp size and location. These results suffice to optimise individual risk calculation and may help to better define surveillance intervals.

Sufficient bowel preparation is crucial for successful screening and surveillance colonoscopy. However, the rates of inadequate preparation are still high. We investigated the effects of reinforcing patient education and guidance by using the short message service (SMS).In this prospective, endoscopist-blinded, multicenter study, standard instructions pertaining to split-dose preparation were provided in a verbal and written format to all patients during the initial appointment. Patients were randomly assigned (1:1) to a group that received reinforced education starting 4 days before the colonoscopy (SMS group) or to the control group which did not receive further education. The primary outcome was the percentage of insufficient preparation results (Boston Bowel Preparation Scale [BBPS] score 6). The secondary outcomes included quality of bowel preparation according to the BBPS, polyp and adenoma detection rates, and patients' perceived discomfort in the preparation procedure.The percentage of patients with insufficient bowel preparation was significantly lower in the SMS group (9%) than in the control group (19%) (P = .0013). The mean BBPS score was significantly higher in the SMS group (7.4 ± 0.1) than in the control group (6.5 ± 0.1) (P .0001). Each colon segment had significantly higher BBPS scores in the SMS group. The adenoma detection rate and number of detected adenomas in the right segment of the colon were higher in the SMS group. SMS messages were accompanied by a lower level of discomfort during preparation (numeric rating scale) (5.2 SMS vs 5.8 controls) (P = .0042).Reinforced patient education by using SMS messages during the 4 days before colonoscopy increased bowel cleanliness, adenoma detection in the right segment of the colon, and reduced discomfort. (Clinical trial registration number: NCT02272036.).

Colonoscopy, either performed as screening or as a therapeutic proceedure, is, in general, very safe with only a few cases of serious complications. Most cases of bleeding after endoscopic polypectomy can be safely managed endoscopically. The rare cases of colonic perforations still have to be managed by surgical intervention. The postpolypectomy-coagulation syndrome and a cecal volvulus are very rare complicatoions after colonoscopy. In the current manuscript, we describe a rare case of a cecal volvulus after routine colonoscopy due to an unknown mobile coecum as a predisposition. We discuss the endoscopic, clinical and radiological findings of the patient. Moreover, we describe the performed surgical procedure and the further clinical course of the patient. A cecal volvulus should always be considered as a possible rare, but serious, complication in the differential diagnosis of abdominal pain after colonoscopy. The standard therapy of a cecal volvulus is the right hemicolectomy. As an alternative, a coecopexy without resection could be performed as long as the colonic wall is still vital.Die Koloskopie ist sowohl als Vorsorgeuntersuchung als auch als therapeutische Endoskopie mit Polypektomie eine sichere Untersuchung. Ernsthafte Komplikationen sind sehr selten. Blutungen oder Nachblutungen können in der Mehrzahl der Fälle durch eine endoskopische Intervention beherrscht werden, wohingegen bei iatrogener Darmperforation zumeist eine operative Therapie erforderlich ist. Weitaus seltenere Komplikationen stellen das Post-Polypektomie-Koagulationssyndrom sowie als Rarität ein Volvulus nach Koloskopie dar. Wir beschreiben den seltenen Fall eines Patienten mit Volvulus des Coecums nach Koloskopie bei vorbestehendem, aber nicht vorbekanntem Coecum mobile. Die spezifischen Befunde der koloskopischen Untersuchung, die klinische, bildgebende und laborchemische Diagnostik sowie die operative Therapie dieser seltenen Krankheitsentität werden dargestellt und diskutiert. Ein Volvulus des Kolons sollte bei abdominalen Schmerzen nach Koloskopie immer als mögliche seltene aber ernsthafte Komplikation differenzialdiagnostisch in Erwägung gezogen werden. Bei Volvulus des Coecums stellt die Hemikolektomie rechts das operative Verfahren der Wahl dar, alternativ ist bei noch vitalem Darm die Coecopexie ohne Resektion möglich.

Background/Aim: The assessment of advanced chronic liver disease (ACLD) is a prerequisite for therapy and surveillance in patients with chronic hepatitis C infection. Mini-laparoscopy-assisted liver biopsies facilitate both histological and macroscopical evaluation of liver fibrosis. This study is aimed at investigating the prognostic significance of the laparoscopic assessment for the cumulative incidence of ACLD-related events. Patients and Methods: We performed a single center, retrospective analysis of 94 patients with either macroscopically or/and microscopically assessed advanced fibrosis/cirrhosis caused by chronic hepatitis C infection. The patients' data, the respective laboratory results, and follow-up period were evaluated in the outpatient clinic. Results: The group with both macro- and microscopic diagnosed ACLD showed a significantly higher number of decompensating events (n = 7) compared with the other 2 groups (n = 0 in the group with only histological and n = 1 in the group with only laparoscopic diagnosis of advanced liver disease). The results were not affected by the successful treatment of the hepatitis C virus. In the Cox-regression analysis, the spleen size (>120 mm) was significantly associated with the incidence of ACLD-related events. Conclusions: Assessment of ACLD in chronic hepatitis C by mini-laparoscopy-assisted liver biopsies may facilitate the selection of patients with a poor prognosis, irrespective of achieving a sustained virological response following treatment. Follow-up of these patients should be intensified to treat decompensation early. �� In Copyright http://rightsstatements.org/vocab/InC/1.0/, publishedVersion

The likelihood of a sustained virological response (SVR) is the most important factor for physicians and patients in the decision to initiate and continue therapy for chronic hepatitis C (CHC) infection. This study identified predictive factors for SVR with peginterferon plus ribavirin (RBV) in patients with CHC treated under 'real-life' conditions. The study cohort consisted of patients from a large, retrospective German multicentre, observational study who had been treated with peginterferon alfa-2a plus RBV or peginterferon alfa-2b plus RBV between the years 2000 and 2007. To ensure comparability regarding peginterferon therapies, patients were analysed in pairs matched by several baseline variables. Univariate and multivariate logistic regression analyses were used to determine the effect of nonmatched baseline variables and treatment modality on SVR. Among 2378 patients (1189 matched pairs), SVR rates were 57.9% overall, 46.5% in HCV genotype 1/4-infected patients and 77.3% in genotype 2/3-infected patients. In multivariate logistic regression analysis, positive predictors of SVR were HCV genotype 2 infection, HCV genotype 3 infection, low baseline viral load and treatment with peginterferon alfa-2a. Negative predictors of SVR were higher age (≥40 years), elevated baseline gamma-glutamyl transpeptidase (GGT) and low baseline platelet count (

We present the case of a 25-year-old woman with a history of weakness, weight loss, anemia, and elevated liver enzymes. Outpatient diagnostic evaluation, including abdominal ultrasound and endoscopies, revealed no conclusive explanation for the clinical picture and the patient was admitted to our clinic. Because of the hepatosplenomegaly together with the elevated liver enzymes, one of our differential diagnoses was that of liver disease. To clarify this, we performed a minilaparoscopy, which showed multiple diffuse distributed spots of livid color without clear margins distributed all over both liver lobes. A biopsy taken from these areas revealed the diagnosis of peliosis hepatis with irregular and diffusely enlarged hepatic sinusoids with an irregular structure. Peliosis hepatis is associated with numerous infectious and neoplastic diseases, but also occurs as a result of toxic liver damage. Further evaluation of our patient with an x-ray and a computed tomography (CT) scan revealed a mediastinal mass and a CT-guided biopsy showed classical Hodgkin’s lymphoma. After completing further screening, a definitive diagnosis of Hodgkin’s lymphoma stage II/N/B (Ann-Arbor) was established and chemotherapy according to the German Hodgkin’s study group protocol with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (the BEACOPP regimen) was initiated. After the first chemotherapy cycle, the patient’s symptoms and laboratory values improved rapidly. Taken together, we present the case of a patient with peliosis hepatis as an uncommon manifestation of Hodgkin’s lymphoma. Despite an extensive literature search, we could not find any case of peliosis hepatis associated with a de novo diagnosis of classical Hodgkin’s disease.

Background/Aims The immunomodulatory active hepatitis C virus (HCV) has been shown to interfere with antiviral interferon (IFN) type I functions. The aim of the study was to determine whether further basic innate immunologic functions are influenced by HCV. Methods The acute phase response (APR) was induced in HCV transgenic (tg) mice and C57BL/6J control mice using lipopolysaccharide. Activation of transcription factors, mRNA expression and production of cytokines and acute phase proteins (APP) were determined. IFN type I and tumor necrosis factor (TNF) α signalling were investigated after polyI:C or TNF-α treatment. Results HCV tg mice showed an attenuated APR: hepatic activation of nuclear factor κ B (NFκB) and interferon-stimulated gene factor 3 (ISGF3), hepatic expression of interleukin (IL) 6, IL-10, and IFN-γ mRNA, serum concentrations of IL-6 and IFN-γ and production of type II acute phase proteins were reduced compared to wild-type mice. While no differences in NFκB activation could be detected after TNF-α injection, HCV tg mice showed reduced activation of ISGF3 and reduced transactivation of IFN target genes after polyI:C treatment. Conclusions Besides antiviral defence mechanisms, interruption of IFN type I signalling by HCV modulates the APR which is aimed at a variety of pathogens.

Background/Aims Hepatitis C virus leads to chronic hepatitis in the majority of infected individuals. The mechanism of viral persistence is not completely understood. Hepatitis C virus core protein is produced within hepatocytes and is secreted during HCV infection. Our study characterizes the effects of core protein on T cell priming in mice. Methods We used a system of antigen-specific in vitro priming of CD4 + and CD8 + T cells by myeloid dendritic cells, hepatoma cells or primary hepatocytes. Core protein was either added to the cultures or expressed by antigen-presenting cells. Results Antigen-presenting cells treated with core protein showed reduced surface expression of major histocompatibility molecules. Myeloid dendritic cells showed also reduced expression of costimulatory molecules. CD4 + and CD8 + T cells primed by these cells showed defects in activation, proliferation, and cytokine production. Importantly, CD4 + and also CD8 + T cells primed in the presence of core protein showed an increase in interleukin-10 production resembling the phenotype of regulatory T cells. Conclusions Hepatitis C virus core protein inhibits priming of antigen-specific CD4 + and CD8 + T cell responses by downregulation of major histocompatibility molecules and costimulatory molecules on antigen-presenting cells and induces development of IL-10-producing T cells.

Background/Aims The biological functions of the recently discovered IL-10-related cytokines IL-19, IL-20, IL-22, IL-24 and their receptors IL-20R1, IL-20R2 and IL-22R are not clear. Therefore, the expression of these cytokines and their receptors in the hepatic acute phase response to LPS was analysed. Type I interferons have important immunomodulatory functions in bacterial infections. We investigated if they influence release and organ-specific expression of TNF, IL-6 and IL-10 and the responsiveness of liver to IL-10 related cytokines during the reaction to LPS in vivo . Methods B6 and congenic IFNAR −/− mice were intraperitoneally injected with 5mg/kg LPS. Systemic release of cytokines was quantified by ELISA. Organ-specific expression of cytokines and their receptors was evaluated by (semi quantitative or quantitative) RT-PCR. Results The cytokines IL-19, IL-22 and the IL-20R2 receptor subunit are up-regulated by LPS in the liver of normal mice. IFNα/β enhance the secretion and expression of IL-6 and IL-10 during the response to LPS, but also the up-regulation of IL-20R2 expression. Conclusions We show that the liver is a potential target for IL-19, IL-20 and IL-24. During an LPS response, IFNα/β influence cytokine secretion and expression and possibly the response to IL-19 and IL-24.

Background Ischemic preconditioning (I/P) and methylprednisolone (MP) have been suggested to protect against ischemia-reperfusion (IR) injury, which results in an increased tolerance against organ hypoxia. Methods Before 45 minutes of hepatic ischemia, male Wistar rats were pretreated with either I/P (5/30 minutes) or MP (30 mg/kg BW). The degree of IR injury and the postischemic inflammatory (leukocyte infiltration, myeloperoxidase, intercellular adhesion molecule-1) and apoptotic (TUNEL, caspase 3, cytochrome C) activity was measured in both groups and compared with non-pretreated (ischemic) animals. Results Histology and enzyme release revealed that I/P and MP treatment provided significant protection as compared with ischemic controls. TUNEL-positive cells, as well as caspase 3 and cytochrome C expression, were clearly reduced in hepatic tissue of MP-treated animals and partially reduced in I/P-treated animals when compared with ischemic animals. The inflammatory response was considerably reduced in MP- and I/P-treated animals, especially in the early period after ischemia. NF-κB/Rel–binding activity was increased after I/P and decreased in MP-treated animals, whereas ischemic controls showed a constant binding activity. Conclusions MP (probably by downregulation of NF-κB–binding activity) and I/P attenuated the postischemic apoptotic and inflammatory response. Both treatments equally reduced IR-related hepatocellular damage, and, thus, may also be applied equally in surgery involving warm organ hypoxia.

Background : The liver efficiently eliminates activated CD8 + T blasts. It is unknown if vaccine-primed CD8 + T blasts migrate to and establish functional CD8 + T cell immunity in the liver post-immunization. Aims : We tested, if functional CD8 + T cell populations can be detected in the liver post-vaccination. Methods : Murine CD8 + T cells with different epitope/restriction specificities were primed by intramuscular injection of protein- or DNA-based vaccines. The kinetics of appearance in the liver, as well as the surface phenotype and functional competence of intrahepatic, specific CD8 + T cell populations was tested. Results : High numbers of specific CD8 + T cells appear in the liver after vaccination that are activated (CD69 + CD44 + ), express effector functions (CD27 lo /CD28 lo phenotype, interferon γ secretion, specific cytolytic reactivity), but show no evidence of apoptosis (annexin V − , B220 lo , similar numbers/kinetics in primed, congenic lpr/lpr mice). Specific CD8 + T cells from the liver adoptively transferred into a naive, syngeneic host successfully reconstitute specific CD8 + T cell immunity. Conclusions : Specific, functionally competent CD8 + effector/memory T cell populations are established in the liver for months post-vaccination.

Background Inflammatory states such as hepatitis and sepsis are frequently associated with alterations of bile acid synthesis. These conditions are mediated by bacterial wall products like lipopolysaccharide (LPS). Cholesterol 7-alpha hydroxylase is the rate-limiting enzyme of bile acid synthesis. Hydrophobic bile acids repress cholesterol 7-alpha hydroxylase transcription via binding to the farnesoid X receptor and interaction with the bile acid response element II in the cholesterol 7-alpha hydroxylase promoter. Methods We tested the effect of LPS on hepatic expression of cholesterol 7-alpha hydroxylase in C57BL/6 mice and Wistar rats. Further, we analyzed the binding activity of hepatic nuclear extracts to the bile acid response element II and the binding site for farnesoid X receptor heterodimers (ecdysone response element). Result Lipopolysaccharide caused a 100-fold reduction of cholesterol 7-alpha hydroxylase mRNA levels in mice and a 10-fold reduction in rats. Protein levels of cholesterol 7-alpha hydroxylase also decreased in both species. These changes inversely correlated with the increased binding activity of nuclear proteins to the bile acid response element II and the ecdysone response element. Conclusion Lipopolysaccharide-induced repression of cholesterol 7-alpha hydroxylase occurs at the transcriptional level. The underlying mechanism involves an increased binding activity of nuclear proteins to the bile acid response element II and the ecdysone response element. In conclusion, the farnesoid and retinoid X receptors participate in LPS-induced cholesterol 7-alpha hydroxylase repression.

Background Different parameters have been determined for prediction of treatment outcome in hepatitis c virus genotype 1 infected patients undergoing pegylated interferon, ribavirin combination therapy. Results on the importance of vitamin D levels are conflicting. In the present study, a comprehensive analysis of vitamin D levels before and during therapy together with single nucleotide polymorphisms involved in vitamin D metabolism in the context of other known treatment predictors has been performed. Methods In a well characterized prospective cohort of 398 genotype 1 infected patients treated with pegylated interferon-α and ribavirin for 24–72 weeks (INDIV-2 study) 25-OH-vitamin D levels and different single nucleotide polymorphisms were analyzed together with known biochemical parameters for a correlation with virologic treatment outcome. Results Fluctuations of more than 5 (10) ng/ml in 25-OH-vitamin D-levels have been observed in 66 (39) % of patients during the course of antiviral therapy and neither pretreatment nor under treatment 25-OH-vitamin D-levels were associated with treatment outcome. The DHCR7-TT-polymorphism within the 7-dehydrocholesterol-reductase showed a significant association (P = 0.031) to sustained viral response in univariate analysis. Among numerous further parameters analyzed we found that age (OR = 1.028, CI = 1.002–1.056, P = 0.035), cholesterol (OR = 0.983, CI = 0.975–0.991, P

The role of nitric oxide (NO) in the pathophysiology of inflammatory bowel diseases (IBD) is controversially discussed. The aim of the present study was to investigate the role of NO inhibition in the acute phase of rat 2,4,6-trinitrobenzenesulphonic acid (TNB)-colitis. To inhibit NO synthesis we used aminoguanidine (AG) as a selective inhibitor of inducible nitric oxide synthase (iNOS). TNB-colitis was induced in rats with and without pretreatment with AG (200 mg kg-1 body weight in the drinking water). The severity of colitis was observed over a period of 7 days. On days 1 and 2, AG reduced concentrations of plasma nitrate and nitrite as well as of portal 6-keto-prostaglandin 1alpha. AG pretreatment increased colonic damage and inflammatory response, assessed by colonic myeloperoxidase and serum lactate dehydrogenase activity, macroscopic damage score, tumour necrosis factor-alpha concentration in stool and colonic glutathione content. The AG-treated group showed a higher and prolonged nuclear factor kappaB (NF-kappaB)/Rel binding activity in the colon. We conclude that NOS inhibition by AG is not beneficial in acute intestinal inflammation. With regard to appropriate therapeutic strategies, NF-kappaB/Rel activation might be a more suitable target.

BI 207127 is a potent non-nucleoside hepatitis C virus (HCV) NS5B polymerase inhibitor in vitro.In this double-blind, placebo-controlled study, 57 HCV genotype (GT)-1 patients (n=27 treatment-naïve [TN]; n=30 treatment-experienced [TE]) with compensated liver disease were randomised for 28-day treatment with 400, 600, or 800 mg BI 207127 three times daily (TID) or placebo (only TN) in combination with peginterferon alfa 2a and ribavirin (PegIFN/RBV). Plasma HCV RNA was measured by Roche COBAS TaqMan assay.HCV RNA decreased in a dose-dependent manner with little difference between 600 mg (TN 5.6 log(10), TE 4.2 log(10)) and 800 mg (TN 5.4 log(10), TE 4.5 log(10)). Rapid virological response (RVR; HCV RNA15 IU/ml) at day 28 occurred in 11/19 TN and 4/30 TE patients treated with BI 207127. GT-1b patients had stronger reductions in HCV RNA than GT-1a (RVR: TN 64% vs. 43%; TE 33% vs. 5%). There were no breakthroughs (HCV RNA rebound1 log(10) from nadir) in the TN groups, whereas 3/30 TE patients experienced breakthrough due to P495-mutations. Gastrointestinal adverse events (AEs) and rash were the major AEs and most frequent at higher doses. One and four patients discontinued due to AEs in the 600 and 800 mg groups, respectively. Overall, tolerability was good and better at 600 mg than 800 mg.BI 207127 in combination with PegIFN/RBV demonstrated strong antiviral activity with a favourable safety and tolerability profile. The best benefit/risk ratio was observed at 600 mg.

We report on a 19-year-old male patient with chronic HBeAg-positive hepatitis B-infection and agranulocytosis as a severe side effect of pegylated interferon alpha therapy. Within the first six months of therapy the hepatitis B virus DNA became undetectable in parallel with a significant decrease of the HBsAg serum concentration. After a six-month course of therapy the patient was admitted to our emergency unit. He appeared significantly ill and reported that he had fever for two days, painful oral mucosa, throat pain and general fatigue and discomfort. A complete blood cell count was performed and revealed a complete agranulocytosis with no detectable neutrophilic granulocytes in the blood smear. Antiviral therapy was immediately stopped and he was admitted to our clinic where a supportive therapy and an empirical course of broadband antibiotics were initiated. A few days later an additional treatment with intravenous prednisolone was started. Within the next week the agranulocytosis resolved and the neutrophil count was completely restored. In parallel, the clinical status improved quickly. This case demonstrates the need for our awareness of agranulocytosis as a rare but severe and potentially life-threatening side effect of interferon alpha therapy.

SUMMARY. In randomized clinical trials, treatment with peginterferon plus ribavirin (RBV) results in a sustained virological response (SVR) in around half of hepatitis C virus genotype 1-infected and 80% of genotype 2/3-infected individuals. This study aimed to evaluate efficacy and tolerability of peginterferon alfa-2a plus RBV compared with peginterferon alfa-2b plus RBV for the treatment of chronic hepatitis C in routine clinical practice. The intent-to-treat cohort consisted of 3414 patients treated with either peginterferon alfa-2a plus RBV (Group A) or peginterferon alfa-2b plus RBV (Group B) in 23 centres participating in the large, multicentre, observational PRACTICE study. Collected data included baseline characteristics, treatment regimen, RBV dose and outcome. Rates of early virological response, end of treatment response and SVR were 76.6%, 75.7% and 52.9% in Group A, and 70.2%, 65.6% and 50.5% in Group B, respectively. In patients matched by baseline parameters, 59.9% of patients in Group A and 55.9% in Group B achieved an SVR (P £ 0.051). In genotype 1-infected patients matched by baseline parameters and cumulative RBV dose, SVR rates were 49.6% and 43.7% for Group A and Group B, respectively (P £ 0.047); when matched by baseline parameters and RBV starting dose, SVR rates were 49.9% and 44.6%, respectively (P = 0.068). Overall, 21.8% of group A and 29.6% of group B patients discontinued treatment (P £ 0.0001). The efficacy and tolerability of peginterferon plus RBV in this large cohort of patients treated in routine daily practice was similar to that in randomized clinical trials. In matched pairs analyses, more patients achieved an SVR with peginterferon alfa-2a compared with peginterferon alfa-2b.

Aims: The current treatment of choice is a combination of pegylated interferon-alfa (PegIFN-alfa) plus ribavirin. Prediction of IFN efficacy before treatment has been mainly based on viral characteristics such as viral load and genotype. We therefore analyzed data from a large multicentric German surveillance study in order to identify additional host- related predictors of nonresponse. Methods: Between 9/2003 and 8/2008, 279 active sites treated a total of 4039 patients with weight-based PegIFN-alfa2b and ribavirin. As this is an ongoing surveillance trial, we have performed an interim analysis of formerly untreated noncirrhotic patients with HCV-genotype 1 and nonresponse defined as HCV-RNA-positivity at end of treatment (EOT) as well as at the end of follow-up (EOF) 6 months after end of treatment. Results: 455 treated patients with genotype 1 failed to achieve HCV-RNA-negativity at EOT and EOF, while 614 patients experienced sustained virological response after 6 months of follow-up (SVR). Baseline data and rapid virologic response (RVR) in both groups are shown in the table. Because data were not available in all patients the number of patients fluctuates throughout the subgroups analyzed. No dose reductions of either PegIFN-alfa2b or ribavirin were performed in 437 (71.2%) of patients with SVR and 324 (71.2%) in the nonresponder-group. Reductions of ribavirin have been made in 69 (11.2%) of SVR-patients and 31 (6.8%) of patients with nonresponse, respectively. Only 7/209 (3.3%) nonresponding patients, who were tested for HCV-RNA at week 4, experienced an RVR, while 21.4% of all SVR-patients exhibited an RVR. Conclusions: Regarding baseline predictive values, there is a significant difference in age as well as baseline viral load while other factors such as body weight and BMI seem not to predict nonresponse in noncirrhotic patients. In contrast, RVR may predict low nonresponse rates, as break through after week 4 are rare events. Data were analyzed using standard summary statistics and two-sided 95% confidence intervals.