Ola Weiland group
Antiviral therapy, immunology and long-term follow-up in chronic viral hepatitis C and B infections
Our overall goal is to improve therapy for chronic viral hepatitis in HBV and HCV mono-infected, HCV/HIV co-infected and liver transplanted patients.
We conduct phase 1-3 clinical trials on new DAA drugs in combination with peg-IFN and ribavirin, and evaluate therapeutic DNA based vaccine therapy for chronic HCV. We further investigate the immunological background for chronic evolution versus spontaneous resolution of viral hepatitis and the long-term clinical outcome. Finally we have developed a database Infcare Hepatitis as an instrument for research on a national basis.
Our research aims to:
- Evaluate the immunological background for chronicity versus spontaneous resolution of acute and chronic viral hepatitis B and C.
- Evaluate the potential of new DAA drugs (protease and polymerase inhibitors) for treatment of chronic HCV.
- Evaluate the usefulness of a therapeutic DNA based HCV vaccine delivered by electroporation for treatment of chronic HCV
- Evaluates the long-term outcome of chronic HCV and HBV related to antiviral treatment outcome.
- Evaluate new treatments for liver transplant patients and HIV/HCV co-infected patients
Keywords: Chronic hepatitis C, Chronic hepatitis B, IFN, ribavirin, protease inhibitors, polymerase inhibitors, liver transplantation, HCV/HIV co-infection, therapeutic vaccination.
Ola Weiland, Group Leader, Professor, MD, Chief Liver section Dpt of ID
Member of EASL, AASLD, IDSA, SILK, Svenska Infektionsläkar-och Tropikläkarföreningen.
Published more than 200 articles on chronic viral hepatitis and treatment with antivirals. Has conducted peg-IFN, ribavirin, and DAA studies in chronic hepatitis B and C since more than 20 years.
Phone: +46 8-585 82273
|Karolin Falconer, MD, PhD, lecturer specialist in ID and HIV/HCV co-infections and NK cell immunology.|
|Malin Ackefors, MD, Senior consultant, specialist in ID and post transplant and hematological infections. PhD studies on chronic viral hepatitis in Liver transplant recipients.|
|Magnus Hedenstierna, MD, ID specialist with studies on long-term consequences of chronic viral hepatitis after SVR in HCV mono- and HIV/HCV co infected patients.|
|Rebecka Theve, ID specialist nurse|
|Susanne Cederberg, ID specialist nurse|
1. T - and NK - cell response
Studies on T - and NK - cell response in patients treated with SOC (peg-IFN + ribavirin) in collaboration with professor Matti Sällbergs and Hans-Gustav Ljunggrens groups with PhD students in collaboration. Recently Niklas Björkström, H-G Ljunggren the main tutor, defended his theisis on the importance of NK cells in infection in particular chronic HCV August 2011.
Large patient materials have been collected: among these 100 mono-infected patients with HCV, 50 liver transplant patients, and 30 HCV/HIV co-infected all treated with SOC (peg-IFN + ribavirin). PBMCs and serum have ben collected before, during and after treatment and during long-term follow-up.
2. IL28B SNPs importance for spontaneous clearence versus chronicity
Studies on IL28B SNPs importance for spontaneous clearence versus chronicity in HCV and HCV- HIV co-infected patients with a PhD student JS as responsible. She also investigate the total Swedish HIV cohort with data from the national registers, InfCare HIV and InfCare Hepatitis created by the group.
Furthermore the importance of IL28B snp for the outcome of SOC treatment in liver transplant patients with HCV relapse is studied by the PhD student MA. IL28B snp seem to be of importance both in the recipient and the donor. These studies ar performed on a unique material of treated patients in collaboration the Transplantation and Pathology Clinics at Karolinska and the division of Infectious Diseases, Karolinska University hospital.
We also study the IL28B SNPs importance for HCV viral kinetics during SOC treatment in HCV patients HCV mono-infected, HIV/HCV co-infected, and transplanted utilizing our unique materials. Analyses of IL28B snp are performed at the division of Virologi, Karolinska University hospital. The rs 12979860 SNP genotyping is performed with an allel-specific Taqman-based test for the CC, C/T or TT genotypes.
The histological evaluation in liver transplant patients with HCV relapse is performed on liver biopsies taken 6 and 12 months after liver transplantation as follows.
All protocol liver biopsies were fixed in 4% paraformaldehyde, dehydrated and embedded in paraffin according to standard procedures. 2-3 um thick sections were cut on a microtome and stained with hematoxylin/eosin (HE) and Sirius staining, 8 and 4 section levels respectively.
3. Long-term outcome in patients successfully treated with SOC (peg-IFN + ribavirin)
Studies on the long-term outcome histological, virological and immunological in patients successfully treated with SOC (peg-IFN + ribavirin) for chronic hepatitis C.
A unique patient material has been collected comprising of 50 patients who cleared their HCV infection after SOC treatment mor than 10 years ago. This EC approved study evaluates these 50 patients, and the histological studies are based on liver biopsies taken prior to the original SOC treatment and again in mean 10 years after the infection was cleared. These studies are part of a PhD project for PhD student MH. A preliminary report was given at the AASLD meeting November 2011 in San Francisco which showed tremendous improvement and normalisation of the fibrosis stage.
We also perform virological and immunological studies on the material from these patients. These comprise HCV RNA, antigen and serological determinations as follows: Cobas Amplicor, HCV antibodies EIA and by Western blot using separated HCV antigens, Amplified HCV RNA will be sequenced, the 5´-non coding region is the first target, HCV proteins in the liver will be analyzed by immuno-precipitation western blot and histological. T helper cells are determined in PBMC and liver tissue using ELISpot. Proliferation is determined. gIFN producing cells are quantified. Cytotoxic T lymphocytes (CTLs) are determined in liver tissue and PBMC using ELISpot assays and by tetramer staining by flow cytometry. Specific cells are then analysed by Vantage flow cytometer (BDB) and analyzed by the Cell Quest software (BDB).
4. Construction of a national hepatitis-data base InfCare Hepatitis
This has been developed in collaboration with Health Solutions and is owned by The Infectious Disease Clinic Karolinska. The system is now fully in operation (natinally 6000 patients, a majority from Karolinska, have been included Nov 2011). More than 20 of 29 ID clinics in Sweden are connected and the system is now introduced in all Gast/Hepatological clinics in Sweden. It is expected to cover 100 % of these clinics within 1 year. This InfCare Hepatitis data base is a very strong research instrument.
5. DAA antiviral therapy
DAA antiviral therapy in national and international studies on patients with chronic HCV infection in collaboration with and for major Pharma Industries, Roche, Janssen, BMS, MSD, Gilead and ChronTech Pharma. All studies are preformed with highly qualifies personnel according to GCP. The hospital laboratories are all qualified as is the hospital Pharmacy.
All these Phase I - III studies are headed by the group leader Ola Weiland as principal investigator for Sweden and Scandinavia.