| 1. |
- Duberg, Ann-Sofi, 1957-, et al.
(författare)
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The future disease burden of hepatitis C virus infection in Sweden and the impact of different treatment strategies
- 2015
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Ingår i: Scandinavian Journal of Gastroenterology. - London : Informa Healthcare. - 0036-5521 .- 1502-7708. ; 50:2, s. 233-244
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Recently, new highly effective direct-acting antivirals (DAAs) against hepatitis C virus (HCV) were introduced. Whether these will alleviate the anticipated increase of liver disease burden in Sweden is unknown, partly because high costs may restrict the use. The objectives were to model the HCV epidemic in Sweden, the burden of disease, and the potential impact of different treatment strategies.Material and methods: HCV disease progression was modeled to 2030. Scenarios were simulated using new DAAs with sustained annual treatment rate (n = 1130), reduced treatment rate (n = 380) to maintain budget, and increased treatment rates (n = 1430 or 2260) to reduce HCV infections.Results: With today's triple therapies, the estimated number of serious liver complications and death are expected to peak in 2021. Using new DAAs among F0-F4 patients, an unchanged annual treatment rate can reduce the number of HCV infections by 10% by 2030; however, hepatocellular carcinoma (HCC) and mortality will remain unchanged. By reducing to 380 treatments annually and focusing on patients with advanced fibrosis (F3-F4), serious complications will remain constant but the total number of HCV infections will increase. By doubling the number of DAA treatments, HCC-incidence and liver-related deaths would decrease by 65-70% by 2030.Conclusion: Mortality and HCC can be reduced with new DAAs and sustained treatment uptake when restricted to F2-F4 patients, or with increased uptake in F0-F4 patients. Treatment restrictions to limit cost may reduce the positive effects and increase the burden of HCV infection. These results may be important for the future strategies of HCV management.
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| 2. |
- Falconer, Karolin
(författare)
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HIV-1/HCV co-infection : immunity and viral dynamics
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Human immunodeficiency virus-1 (HIV-1) and hepatitis C virus (HCV) are the agents behind two viral epidemics causing huge morbidity and mortality worldwide. HCV infection is a leading cause of end-stage liver disease. Co-infection with HIV leads to faster progression to cirrhosis and lower clearance rate of HCV infection following current standard treatment with pegylated interferon alpha (peg-IFNalpha) and ribavirin. The overall aims of the studies described in this thesis were to gain knowledge of how to best manage HIV/HCV co-infection in clinical practice, to study immunological features in co-infected patients, to search for immunological host factors affecting HCV treatment outcome, and to identify possible predictive markers of treatment response. In paper I we investigated the feasibility of treating HIV/HCV co-infected patients with peg-IFNalpha and ribavirin in a Swedish HIV outpatient clinic. We found that only a small fraction of the patients were suitable treatment candidates when following international guidelines. However, in those treated the response was good and correlated to HCV RNA kinetics during initial treatment. One of the patients, who was among those screened for participation in the abovementioned study, spontaneously cleared her chronic HCV infection. Since this is a very rare event we further investigated the immune response of this patient, as described in paper II. She displayed a low level of T cell activation and a high level of T cell function comparedto HIV/HCV co-infected control subjects, thus resembling a healthy individual. In paper III we investigated the impact of chronic HIV/HCV co-infection and the effects of treatment with peg-IFNalpha and ribavirin on NK cells and on NKT cells by flow cytometry. Conventional NK cells were largely unaffected by the co-infection, with only a slight decrease in perforin content in CD56dim cells and an increased CD56bright immunoregulatory population. In contrast, the NKT cells were severely reduced in the co-infected patients and were not restored by HCV therapy. Interestingly, we observed a significant accumulation of unconventional CD56-CD16+ NK cells in these subjects. The expansion of CD56- NK cells was rapidly reverted when HCV replication was suppressed by HCV treatment. In paper IV, we observed that the CD56- NK cells in HCV infected patients were functionally skewed, with poor IFNgamma production but retained MIP-1beta expression. In addition, we found that pretreatment levels of CD56- NK cells in peripheral blood correlated with peg-IFNalpha and ribavirin treatment outcome. Patients with low levels of CD56- NK cells were more likely to clear the HCV infection, and this was not directly linked to other viral and host factors known to influence treatment outcome. In paper V we measured the chemokine IP-10 in plasma from HIV/HCV co-infected patients. We found that lower pretreatment plasma IP-10 levels were associated with faster clearance of the virus. This effect was more pronounced on the first phase viral reduction (day 0-2), than on the second (day 7-28). In summary, this thesis increases our knowledge of the immune system s interaction with HCV and HIV, and identifies an immunological biomarker that correlates with HCV treatment outcome. In addition, it highlights the need for further implementation of HCV treatment in the HIV/HCV co-infected patient group.
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| 3. |
- Falconer, Karolin, et al.
(författare)
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IP-10 predicts the first phase decline of HCV RNA and overall viral response to therapy in patients co-infected with chronic hepatitis C virus infection and HIV.
- 2010
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Ingår i: Scandinavian journal of infectious diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 42:11-12, s. 896-901
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the utility of baseline plasma interferon-gamma inducible protein-10 (IP-10) levels in human immunodeficiency virus (HIV)-hepatitis C virus (HCV) co-infected patients. Baseline IP-10 was monitored during HCV combination therapy in 21 HIV-HCV co-infected patients (HCV genotype 1 (n = 16), 2 (n = 2), and 3 (n = 3)). Lower baseline IP-10 was significantly associated with a rapid decline in HCV RNA, in particular with the first phase reduction, and similar cut-off levels (< 150 and > 600 pg/ml) as in HCV mono-infected patients apply. In conclusion, baseline IP-10 < 150 pg/ml is predictive of a favourable viral response to HCV therapy in HIV-HCV co-infected patients, and may thus be useful in encouraging such difficult-to-treat patients to initiate therapy.
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