Showing papers by "Beat Müllhaupt published in 2013"

Faldaprevir and deleobuvir for HCV genotype 1 infection.

Abstract: The primary end point was met in 59% of patients in the TID16W group, 59% of patients in the TID28W group, 52% of patients in the TID40W group, 69% of patients in the BID28W group, and 39% of patients in the TID28W-NR group. The sustained virologic response 12 weeks after the completion of therapy did not differ significantly according to treatment duration or dosage among ribavirin-containing regimens. This response was significantly higher with TID28W than with TID28W-NR (P = 0.03). Rates of a sustained virologic response 12 weeks after the completion of therapy were 56 to 85% among patients with genotype 1b infection versus 11 to 47% among patients with genotype 1a infection and 58 to 84% among patients with IL28B CC versus 33 to 64% with non-CC genotypes. Rash, photosensitivity, nausea, vomiting, and diarrhea were the most common adverse events. CONCLUSIONS The rate of a sustained virologic response 12 weeks after the completion of therapy was 52 to 69% among patients who received interferon-free treatment with faldaprevir in combination with deleobuvir plus ribavirin. (Funded by Boehringer Ingelheim; SOUND-C2 ClinicalTrials.gov number, NCT01132313.)

IL28B expression depends on a novel TT/-G polymorphism which improves HCV clearance prediction

Abstract: Approximately 3% of the world population is chronically infected with the hepatitis C virus (HCV), with potential development of cirrhosis and hepatocellular carcinoma. Despite the availability of new antiviral agents, treatment remains suboptimal. Genome-wide association studies (GWAS) identified rs12979860, a polymorphism nearby IL28B, as an important predictor of HCV clearance. We report the identification of a novel TT/-G polymorphism in the CpG region upstream of IL28B, which is a better predictor of HCV clearance than rs12979860. By using peripheral blood mononuclear cells (PBMCs) from individuals carrying different allelic combinations of the TT/-G and rs12979860 polymorphisms, we show that induction of IL28B and IFN-γ-inducible protein 10 (IP-10) mRNA relies on TT/-G, but not rs12979860, making TT/-G the only functional variant identified so far. This novel step in understanding the genetic regulation of IL28B may have important implications for clinical practice, as the use of TT/G genotyping instead of rs12979860 would improve patient management.

Genetic analyses reveal a role for vitamin D insufficiency in HCV-associated hepatocellular carcinoma development.

Abstract: Background: Vitamin D insufficiency has been associated with the occurrence of various types of cancer, but causal relationships remain elusive. We therefore aimed to determine the relationship between genetic determinants of vitamin D serum levels and the risk of developing hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). Methodology/Principal Findings: Associations between CYP2R1, GC ,a ndDHCR7 genotypes that are determinants of reduced 25-hydroxyvitamin D (25[OH]D3) serum levels and the risk of HCV-related HCC development were investigated for 1279 chronic hepatitis C patients with HCC and 4325 without HCC, respectively. The well-known associations between CYP2R1 (rs1993116, rs10741657), GC (rs2282679), and DHCR7 (rs7944926, rs12785878) genotypes and 25(OH)D3 serum levels were also apparent in patients with chronic hepatitis C. The same genotypes of these single nucleotide polymorphisms (SNPs) that are associated with reduced 25(OH)D3 serum levels were found to be associated with HCV-related HCC (P=0.07 [OR=1.13, 95% CI=0.99–1.28] for CYP2R1, P=0.007 [OR=1.56, 95% CI=1.12–2.15] for GC, P=0.003 [OR=1.42, 95% CI=1.13–1.78] for DHCR7; ORs for risk genotypes). In contrast, no association between these genetic variations and liver fibrosis progression rate (P.0.2 for each SNP) or outcome of standard therapy with pegylated interferon-a and ribavirin (P.0.2 for each SNP) was observed, suggesting a specific influence of the genetic determinants of 25(OH)D3 serum levels on hepatocarcinogenesis. Conclusions/Significance: Our data suggest a relatively weak but functionally relevant role for vitamin D in the prevention of HCV-related hepatocarcinogenesis.

Faldaprevir (BI 201335), BI 207127 and ribavirin oral therapy for treatment-naive HCV genotype 1: SOUND-C1 final results

Abstract: BackgroundFaldaprevir (BI 201335) and deleobuvir (BI 207127) are direct-acting antiviral agents under development for the treatment of chronic HCV infection. This article describes the final result...

Liver Transplantation during Pregnancy for Acute Liver Failure due to HBV Infection: A Case Report

Abstract: Acute hepatic failure during pregnancy is a life-threatening situation for the mother and fetus and might need a super-urgent liver transplantation. Many pregnancies with positive outcomes are reported after a previous liver transplantation before the pregnancy, but only a few of them are mentioned with transplantation during pregnancy. In these few cases, fetal outcome is mostly adverse. Experience with liver failure during pregnancy and its management is still deficient and needs to be approved. For sure, patients need to be treated in highly qualified centers in a multidisciplinary approach. We present a case of successful super-urgent liver transplantation during the second trimester of pregnancy after acute hepatic failure due to an acute hepatitis B infection with positive maternal and fetal outcome. Liver transplantation during pregnancy due to an acute liver failure can be a life-saving procedure for the mother and fetus. An early initiated maternal therapy with antiviral drugs and immunoglobulins seems to be safe and able to prevent fetal infection and immunosuppressive therapy after transplantation seems to be well tolerated. Nevertheless, fetal outcome differs widely and long-term outcome is deficiently known.

Successful Salvage Chemotherapy with FOLFIRINOX for Recurrent Mixed Acinar Cell Carcinoma and Ductal Adenocarcinoma of the Pancreas in an Adolescent Patient.

Abstract: Pancreatic tumors are rare in children and adolescents. Here, we report the case of a 15-year-old boy who presented with a mixed acinar cell carcinoma/ductal adenocarcinoma with blastomatous components. He received multimodal treatment including various chemotherapy regimens and multistep surgery including liver transplantation. Introduction of FOLFIRINOX after relapse repeatedly achieved a durable metabolic and clinical response with good quality of life.

[Gastro-highlights 2012].

Abstract: The annual Gastro Highlights training event, held at the university Hospital Zurich last autumn, also celebrated the 60th birthday of prof.Dr.med. Michael Fried, who initiated this widely recognized event 17 years ago. Featured at the symposium was a round up of the most important new discoveries in the field of gastroenterology and hepatology to be published during the course of the previous year or represented at the Digestive Disease Week (DDW). To mark the birthday of Prf. Dr. med. Michael Fried, two international experts made a special report on the key developments in the gastroenterology to emerge over the past decades.

Notfallbehandlung bei Varizenblutung

Abstract: Die Varizenblutung ist eine gefurchtete Komplikation einer portalen Hypertension und assoziiert mit einer hohen Mortalitat. Risikofaktoren sind ein hoher Pfortaderdruck, ein hoherer Schweregrad der Zirrhose sowie das Vorliegen sogenannter Red Whale Marks.