| 1. |
- ALANKO BLOMÉ, MARIANNE, et al.
(författare)
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Minimal transmission of HIV despite persistently high transmission of hepatitis C virus in a Swedish needle exchange program.
- 2011
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Ingår i: Journal of Viral Hepatitis. - : Wiley. - 1365-2893 .- 1352-0504. ; 18, s. 831-839
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Tidskriftsartikel (refereegranskat)abstract
- Summary. The aim of this study was to examine the prevalence and incidence of HIV and hepatitis B and C (HBV and HCV) among injecting drug users in a Swedish needle exchange programme (NEP) and to identify risk factors for blood-borne transmission. A series of serum samples from NEP participants enrolled from 1997 to 2005 were tested for markers of HIV, HBV and HCV (including retrospective testing for HCV RNA in the last anti-HCV-negative sample from each anti-HCV seroconverter). Prevalence and incidence were correlated with self-reported baseline characteristics. Among 831 participants available for follow-up, one was HIV positive at baseline and two seroconverted to anti-HIV during the follow-up of 2433 HIV-negative person-years [incidence 0.08 per 100 person-years at risk (pyr); compared to 0.0 in a previous assessment of the same NEP covering 1990-1993]. The corresponding values for HBV were 3.4/100 pyr (1990-1993: 11.7) and for HCV 38.3/100 pyr (1990-1993: 27.3). HCV seroconversions occurred mostly during the first year after NEP enrolment. Of the 332 cases testing anti-HCV negative at enrolment, 37 were positive for HCV RNA in the same baseline sample (adjusted HCV incidence 31.5/100 pyr). HCV seroconversion during follow-up was significantly associated with mixed injection use of amphetamine and heroin, and a history of incarceration at baseline. In this NEP setting, HIV prevalence and incidence remained low and HBV incidence declined because of vaccination, but transmission of HCV was persistently high. HCV RNA testing in anti-HCV-negative NEP participants led to more accurate identification of timepoints for transmission.
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| 2. |
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| 3. |
- Lindh, Magnus, 1960, et al.
(författare)
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Hepatitis C treatment response kinetics and impact of baseline predictors.
- 2011
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Ingår i: Journal of Viral Hepatitis. - : Wiley. - 1365-2893 .- 1352-0504. ; 18:6, s. 400-407
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Tidskriftsartikel (refereegranskat)abstract
- Summary. The optimal duration of treatment for hepatitis C virus (HCV) infections is highly variable but critical for achieving cure (sustained virological response, SVR). We prospectively investigated the impact of age, fibrosis, baseline viraemia and genotype on the early viral kinetics and treatment outcome. Patients treated with peginterferon alfa-2a and ribavirin in standard dosing were included: 49 with genotype 1 treated for 48 weeks and 139 with genotype 2 or 3 treated for 24 weeks. The reduced SVR rates in patients older than 45 years, with severe liver fibrosis or pretreatment viraemia above 400 000 IU/mL were strongly associated with slower second phase declines of HCV RNA. Genotype 2/3 infections responded more rapidly than genotype 1, reaching week 4 negativity (RVR) in 59%vs 22%. We conclude that baseline response predictors such as age, fibrosis and viral load were well reflected by the early viral kinetics as assessed by repeated HCV RNA quantifications. The kinetic patterns and the high relapse rate in genotype 2/3 patients without RVR suggest that this group might benefit from treatment durations longer than 24 weeks.
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| 4. |
- Lindh, Magnus, 1960, et al.
(författare)
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IL28B polymorphisms determine early viral kinetics and treatment outcome in patients receiving peginterferon/ribavirin for chronic hepatitis C genotype 1
- 2011
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Ingår i: Journal of Viral Hepatitis. - : Wiley. - 1352-0504 .- 1365-2893. ; 18:7
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Tidskriftsartikel (refereegranskat)abstract
- Single nucleotide polymorphisms (SNPs) upstream of IL28B predict the outcome of treatment in chronic hepatitis C virus (HCV) infection, but their impact on viral kinetics and relation to other predictors are not well known. Here, two SNPs, rs12979860 and rs8099917, were analysed and related to early viral kinetics during treatment in 110 patients with HCV genotype 1 infection. The reduction of HCV RNA after 7days of therapy was more pronounced (P<0.0001) in patients with CC(rs12979860) or TT(rs8099917) than in patients carrying TT(rs12979860) or GG(rs8099917), respectively. The two SNPs were in linkage disequilibrium (d' =1, r2 = 0.44), but CC(rs12979860) was less common (43% vs. 71%) than TT(rs8099917). Patients carrying both CC(rs12979860) and TT(rs8099917) genotypes achieved lower levels of HCV RNA at week 4 than those with CT or TT at rs12979860 and TT(rs8099917) (P=0.0004). The viral elimination was significantly influenced by rs12979860 independently of baseline viral load, age or fibrosis. This translated into high rates of sustained viral response (SVR) among patients carrying CC(rs12979860) despite the presence of high viral load at baseline (SVR 74%), high age (SVR 79%) or severe liver fibrosis (SVR 83%). We conclude that the IL28B variability influences the antiviral efficiency of interferon/ribavirin therapy and has a strong impact on SVR, independently of traditional response predictors. A combined assessment of these SNPs in conjunction with other response predictors may better predict outcome in difficult-to-treat patients.
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| 5. |
- Love, A, et al.
(författare)
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Hepatitis G virus infections in Iceland
- 1999
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Ingår i: Journal of Viral Hepatitis. - : Wiley. - 1365-2893 .- 1352-0504. ; 6:3, s. 255-260
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Tidskriftsartikel (refereegranskat)abstract
- This study describes the prevalence of hepatitisG virus (HGV) in Iceland, in blood donors and in persons with parenteral risk factors. Among 370 randomly selected Icelandic blood donors, the prevalence of HGV viraemia was 3.8%, whereas the prevalence of HGV antibodies in the same donor group was found to be 13.2%, thus indicating that at least 17% of blood donors in Iceland had previously been exposed to HGV. Previous exposure was seen in all age groups and also in older blood donors. Among intravenous drug users (IVDUs), the prevalence of HGV was much higher. Among 109 hepatitisC virus (HCV) antibody-positive serum samples collected in the years 1992-1997, 33. 9% were polymerase chain reaction (PCR)-positive for HGV and 48.6% had HGV antibodies. Thus, the pattern of HGV in IVDUs was similar to findings among IVDUs in other western countries. HGV viraemia was detected neither in 10 patients with haemophilia nor in five dialysis patients. However, six of the 10 haemophilic patients and one of the five dialysis patients had HGV antibody. In conclusion, unlike hepatitis C, which seems to have been introduced into Iceland relatively recently and has remained virtually confined to IVDUs, exposure to HGV is common among all age groups in the general population, suggesting that the virus has been prevalent in Iceland for much longer, making additional routes of transmission probable.
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| 6. |
- Pradat, P., et al.
(författare)
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Long-term follow-up of the hepatitis CHENCORE cohort: response to therapy and occurrence of liver-related complications
- 2007
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Ingår i: Journal of Viral Hepatitis. - : Wiley. - 1365-2893 .- 1352-0504. ; 14:8, s. 556-563
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Tidskriftsartikel (refereegranskat)abstract
- The aims of the study were to verify the longterm effect of time on viral clearance in hepatitis C virus (HCV) patients and to find out factors possibly associated with disease progression. A total of 1641 patients recruited from eight European centres in 1996-1.997 were re-analysed 5-7 years after inclusion. The occurrence of decompensated cirrhosis, hepatocellular carcinoma (HCC) and liver transplantation was analysed in relation to different host and viral factors. Ninety-three per cent of the HCV patients who had cleared the virus (spontaneously or after antiviral therapy) remained HCV-RNA-negative during follow up and may be considered as 'cured'. Among patients who were sustained responders at inclusion, 2.3% developed liver complications during follow up, and 31% of non-responders did. Advanced age at infection and presence of the human leucocyte antigen (HLA) DRBI*1201-3 allele were possibly associated with a higher rate of progression to decompen- sated cirrhosis or HCC. Decompensated cirrhosis might be further associated with male gender, non-response to previous therapy, and lack of FILA DRBI*1301 allele, whereas HCC seems to be associated with the presence of the HLA DQ02 allele. Long-term follow up of HCV patients indicates that virological response persists over time and is associated with a very low incidence of liver complications. Advanced age at inclusion. advanced age at infection, viral genotype 1, non-response to previous therapy and possibly some specific HLA alleles are factors independently associated with a faster rate of progression towards liver complications. The large proportion of patients lost to follow up stresses the need for a strengthened and optimized management of HCV patients.
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| 7. |
- Verbaan, Hans, et al.
(författare)
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Factors associated with cirrhosis development in chronic hepatitis C patients from an area of low prevalence
- 1998
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Ingår i: Journal of Viral Hepatitis. - : Wiley. - 1365-2893 .- 1352-0504. ; 5:1, s. 43-51
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate the importance of different endogenous and exogenous factors associated with cirrhosis development among hepatitis C virus (HCV)-positive individuals from an area of low prevalence. We studied 106 consecutive HCV RNA positive patients who had undergone liver biopsy. Each patient was assessed with special attention to risk factors for hepatitis C infection, average daily alcohol consumption and analysis of plasma levels of alpha1-antitrypsin (alpha1AT) and alpha1-antichymotrypsin (alpha1ACT). Viral RNA, amplified from serum with the polymerase chain reaction (PCR) technique, was used for genotyping. Liver biopsies were assessed according to conventional histopathological criteria, and for necroinflammatory activity (grade) and fibrosis (stage) according to a numerical scoring system. The presence of cirrhosis (stage 4) was used as the dependent variable in multivariate logistic regression analysis. Alcohol abuse (P = 0.007), age at entry (P < 0.001), immigrant status (P = 0.017) and a low alpha1ACT level (P = 0.008) were all independent determinants of progression to cirrhosis whereas HCV genotype 1, estimated duration of HCV infection and positivity for antibodies to hepatitis B core antigen (HBcAb) were not. Cirrhosis occurred at a significantly younger age (P = 0.00(5) among alcohol abusers. Hence, both endogenous and exogenous factors such as subnormal alpha1ACT levels and alcohol appear to contribute to the rate of progression to cirrhosis among HCV-positive patients.
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| 8. |
- Yee, LJ, et al.
(författare)
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Antinuclear antibodies (ANA) in chronic hepatitis C virus infection: correlates of positivity and clinical relevance
- 2004
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Ingår i: Journal of Viral Hepatitis. - : Wiley. - 1365-2893 .- 1352-0504. ; 11:5, s. 459-464
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Tidskriftsartikel (refereegranskat)abstract
- We examined correlates of antinuclear antibody (ANA) positivity (ANA+) in individuals with chronic hepatitis C virus (HCV) infection and the effect of positivity on clinical outcome of HCV. Pretreatment sera from 645 patients from three centres in Sweden (n = 225), the UK (n = 207) and Italy (n = 213) were evaluated by indirect immunofluorescence on Hep-2 cells for ANA pattern and titre by a single laboratory. Liver biopsies were all scored by one pathologist. A total of 258 patients were subsequently treated with interferon monotherapy. There was a significant difference in the prevalence of ANA (1:40) by geographic location: Lund 4.4%, London 8.7%, Padova 10.3% [odds ratio (OR) = 0.66; 95% CI: 0.46-0.94; P = 0.023]. Duration of HCV infection, age at infection, current age, route of infection, viral genotype, alcohol consumption, fibrosis stage and inflammatory score were not correlated with ANA+ or ANA pattern. Female gender was correlated with ANA+ and this association persisted in multivariable analyses (OR = 3.0; P = 0.002). Increased plasma cells were observed in the liver biopsies of ANA-positive individuals compared with ANA-negative individuals, while a trend towards decreased lymphoid aggregates was observed [hazard ratio (HR) = 9.0, P = 0.037; HR = 0.291, P = 0.118, respectively]. No correlations were observed between ANA positivity and nonresponse to therapy (OR = 1.4; P = 0.513), although ANA+ was correlated with faster rates of liver fibrosis, this was not statistically significant (OR = 1.8; P = 0.1452). Low titre ANA+ should not be a contraindication for interferon treatment. Our observation of increased plasma cells in ANA+ biopsies might suggest B-cell polyclonal activity with a secondary clinical manifestation of increased serum immunoglobulins.
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| 9. |
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| 10. |
- Alavian, S.M., et al.
(författare)
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Virus-triggered autophagy in viral hepatitis - possible novel strategies for drug development
- 2011
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Ingår i: Journal of Viral Hepatitis. - : Blackwell Publishing. - 1352-0504 .- 1365-2893. ; 18:12, s. 821-830
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Forskningsöversikt (refereegranskat)abstract
- . Autophagy is a very tightly regulated process that is important in many cellular processes including development, differentiation, survival and homoeostasis. The importance of this process has already been proven in numerous common diseases such as cancer and neurodegenerative disorders. Emerging data indicate that autophagy plays an important role in some liver diseases including liver injury induced by ischaemia reperfusion and alpha-1 antitrypsin Z allele-dependent liver disease. Autophagy may also occur in viral infection, and it may play a crucial role in antimicrobial host defence against pathogens, while supporting cellular homoeostasis processes. Here, the latest findings on the role of autophagy in viral hepatitis B and C infection, which are both serious health threats, will be reviewed.
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