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- Ackefors, Malin
(författare)
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Natural course and treatment outcome in hepatitis C recurrence after liver transplantation
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hepatitis C virus (HCV) infection post-liver transplantation (post-LT) is associated with an increased rate of fibrosis progression compared to non-transplanted patients. Thus, 25% of the recipients will progress to cirrhosis within 5 years after LT. Antiviral treatment after LT with peg-INF and ribavirin (RBV) yields lower sustained viral response (SVR) than in nontransplanted patients. In many LT-recipients non-response to treatment will eventually lead to progression to cirrhosis. The aim of this thesis was to study the natural course and treatment outcome in liver transplant patients with hepatitis C recurrence, and the influence of baseline factors on the course of the HCV recurrence and antiviral treatment, with particular emphasis on HCV genotype and IL28B gene polymorphism. In paper I we conducted a pilot-study on 21 hepatitis C LT recipients with the aim to increase adherence and tolerance to antiviral treatment. All recipients were pre-treated with Darbepoetin (EPO) starting 2 weeks before the initiation of Peg-IFN and RBV. RBV was dosed taking weight and kidney function into account, with a target serum concentration set to10 μM/L by using a formula to calculate the dose. A majority of patients achieved the target concentration, and 90% could stay adherent to a full treatment course. SVR was reached in 18% recipients with genotype 1 and 60% with genotype non-1. Recipients with mild fibrosis achieved SVR in 67%. In paper II we studied the influence of IL28B gene polymorphism on fibrosis progression and treatment outcome in 54 LT recipients, who had received antiviral treatment, and in 45 of their donors. The most favorable IL28B genotype CC was associated with slower fibrosis progression and better treatment outcome. Patients with HCV genotype non-1 and the IL28B CC gene achieved SVR in 71%, whereas patients with genotype 1 and IL28B non-CC did so in only 23%, p < 0,016. Patients with mild fibrosis (F1-2) had better treatment outcome than patients with advanced fibrosis. In paper III we treated 46 Swedish and 8 Norwegian patients with the treatment regimen evaluated in paper I. 94% stayed adherent to the treatment course. SVR was achieved in 82% of recipients with HCV genotype 2/3 versus in only 22% with genotype 1, p < 0.002. Patients with IL28B CC achieved SVR in 73% and patients with non-CC in 33%, p < 0.001. Patients with mild fibrosis achieved SVR in 56% and patients with advanced fibrosis in 26% p < 0.01. Thus, with favorable HCV genotype and IL28B genotype, LT recipients have a good chance to achieve SVR, when treated before advanced fibrosis has developed. In paper IV we evaluated the utility of an early liver biopsy post-LT to detect and predict fibrosis progression of recurrent HCV infection post-LT. 35 HCV RNA positive, and 11 HCV RNA negative LT recipients, who underwent protocolled liver biopsies 6 and 12 months post-LT, were studied. Histological recurrence with fibrosis stage ≥ F1was noted in 56% of the HCV positive LT recipients at 6 months, and in 82% 12 months post-LT. Acute cellular rejection (ACR) and IL28B genotype CC were associated with a more pronounced fibrosis progression 12 months post-LT. Fibrosis was absent in all eleven recipients who were HCV RNA negative directly after LT. Thus, a 6 months biopsy post-LT is a valuable tool for detection of an early HCV recurrence, which makes an early treatment intervention for HCV possible.
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| 2. |
- Ivarsson, Sten-A., et al.
(författare)
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Glutamate decarboxylase antibodies in non-diabetic pregnancy precedes insulin-dependent diabetes in the mother but not necessarily in the offspring
- 1997
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Ingår i: Autoimmunity. - 0891-6934. ; 26:4, s. 261-269
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Tidskriftsartikel (refereegranskat)abstract
- We studied the risk for diabetes of glutamate decarboxylase (GAD65Ab) and islet cell (ICA) autoantibodies in non-diabetic pregnant mothers and their children. Pregnancy and cord blood sera were collected in 1970-87 from about 35,000 mothers who delivered a child in the city of Malmo, Sweden. A total of 42 mothers were identified in 1988 who, 1-18 years after their pregnancies, had developed either insulin-dependent (n = 22) or non-insulin dependent (n = 20) diabetes mellitus. First, in 123 pregnant mothers selected as controls, 0.8% had GAD65Ab and 0.8% ICA. Second, among the mothers with non-insulin dependent diabetes, 7/20 (35%) had GAD65Ab eight months to 13 years, 10 months before clinical diagnosis. Third, in mothers who later developed insulin-dependent diabetes, 12/22 (55%) had GAD65Ab and 10/22 (45%) had ICA in pregnancies preceding the clinical diagnosis by 13 months to 9 years, 4 months. In 1996, none of the children born to the 42 mothers have developed diabetes. GAD65Ab and ICA in non-diabetic pregnancies may predict insulin-dependent diabetes in the mother but not necessarily in the offspring.
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| 3. |
- Remberger, Mats, et al.
(författare)
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Improved survival after allogeneic hematopoietic stem cell transplantation in recent years : A single-center study
- 2011
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Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 17:11, s. 1688-1697
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Tidskriftsartikel (refereegranskat)abstract
- We analyzed the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) over the past 2 decades. Between 1992 and 2009, 953 patients were treated with HSCT, mainly for a hematologic malignancy. They were divided according to 4 different time periods of treatment: 1992 to 1995, 1996 to 2000, 2001 to 2005, and 2006 to 2009. Over the years, many factors have changed considerably regarding patient age, diagnosis, disease stage, type of donor, stem cell source, genomic HLA typing, cell dose, type of conditioning, treatment of infections, use of granulocyte-colony stimulating factor (G-CSF), use of mesenchymal stem cells, use of cytotoxic T cells, and home care. When we compared the last period (2006-2009) with earlier periods, we found slower neutrophil engraftment, a higher incidence of acute graft-versus-host disease (aGVHD) of grades II-IV, and less chronic GVHD (cGHVD). The incidence of relapse was unchanged over the 4 periods (22%-25%). Overall survival (OS) and transplant-related mortality (TRM) improved significantly in the more recent periods, with the best results during the last period (2006-2009) and a 100-day TRM of 5.5%. This improvement was also apparent in a multivariate analysis. When correcting for differences between the 4 groups, the hazard ratio for mortality in the last period was 0.59 (95% confidence interval [CI]: 0.44-0.79; P < .001) and for TRM it was 0.63 (CI: 0.43-0.92; P = .02). This study shows that the combined efforts to improve outcome after HSCT have been very effective. Even though we now treat older patients with more advanced disease and use more alternative HLA nonidentical donors, OS and TRM have improved. The problem of relapse still has to be remedied. Thus, several different developments together have resulted in significantly lower TRM and improved survival after HSCT over the last few years.
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