| 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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| 11. |
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| 12. |
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| 13. |
- Carlsson, T., et al.
(författare)
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HCV RNA levels during therapy with amantadine in addition to interferonand ribavirin in chronic hepatitis C patients with previous nonresponse orresponse/relapse to interferon and ribavirin
- 2000
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Ingår i: Journal of Viral Hepatitis. - : Wiley. - 1352-0504 .- 1365-2893. ; 7:6, s. 409-413
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Tidskriftsartikel (refereegranskat)abstract
- Interferon (IFN) alpha in combination with ribavirin (RIB) is standard therapy for patients with chronic hepatitis C virus (HCV) infection. However, many patients do not respond with sustained HCV clearance to this therapy. At present, no accepted treatment strategy exists for these patients. Recent preliminary data have suggested that amantadine (AMA) is effective against HCV infection. In a pilot study, we treated 13 nonresponders and 10 response/ relapsers to previous IFN/RIB therapy with AMA 200 mg per day in combination with IFN 3 MU thrice weekly, and RIB 1000 mg per day for 24 weeks, with a 24-week follow-up period after end-of-treatment. At the end-of-treatment, 1 previous nonresponder and 5 previous response/relapsers were HCV RNA negative. At the end of follow-up, only 1 previous response/relapser remained HCV RNA negative and had a sustained response. During therapy, serum HCV RNA became undetectable in 4 previous nonresponders, of whom 3 had a breakthrough at week 24. Twenty-one patients continued therapy without dose reductions. One patient discontinued therapy prematurely due to sleeping disturbances, and another patient was withdrawn from therapy due to heavy alcohol intake. We conclude that the addition of AMA to IFN and RIB was well tolerated but had little, if any, impact on HCV RNA eradication in nonresponders or response/relapsers to previous IFN/RIB combination therapy.
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| 14. |
- Duberg, Ann-Sofi, et al.
(författare)
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Cause of death in individuals with chronic HBV and/or HCV infection, a nationwide community-based register study
- 2008
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Ingår i: Journal of Viral Hepatitis. - : Wiley. - 1352-0504 .- 1365-2893. ; 15:7, s. 538-550
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Tidskriftsartikel (refereegranskat)abstract
- Studies on chronic viral hepatitis and mortality have often been made on selected populations or in high-endemic countries. The aim of this study was to investigate the causes of death and the mortality rates in the nationwide cohorts of people chronically infected with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) in Sweden, a low-endemic country. All notifications on chronic HBV infection and HCV infection 1990-2003 were linked to the Cause of Death Register. A total of 9517 people with chronic HBV infection, 34 235 people with HCV infection and 1601 with chronic HBV-HCV co-infection were included, and the mean observation times were 6.4, 6.3 and 7.9 years, respectively. The mortality in the cohorts was compared with age- and gender-specific mortality in the general population and standardized mortality ratios (SMR) were calculated. All-cause mortality was significantly increased, SMR 2.3 (HBV), 5.8 (HCV) and 8.5 (HBV-HCV), with a great excess liver-related mortality in all cohorts, SMR 21.7, 35.5 and 46.2, respectively. In HCV and HBV-HCV infected there was an increased mortality due to drug-related psychiatric diagnoses (SMR: 20.7 and 27.6) and external causes (SMR: 12.4 and 11.4), predominantly at younger age. To conclude, this study demonstrated an increased all-cause mortality, with a great excess mortality from liver disease, in all cohorts. In people with HCV infection the highest excess mortality in younger ages was from drug-related and external reasons.PMID: 18397223 [PubMed - indexed for MEDLINE]
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| 15. |
- Duberg, Ann-Sofi, et al.
(författare)
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The burden of hepatitis C in Sweden : a national study of inpatient care
- 2011
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Ingår i: Journal of Viral Hepatitis. - : Wiley-Blackwell Publishing Inc.. - 1352-0504 .- 1365-2893. ; 18:2, s. 106-118
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Tidskriftsartikel (refereegranskat)abstract
- The spread of hepatitis C virus (HCV) in Sweden in the 1970s indicated that serious liver complications (SLC) would increase in the 2000s. The aim of this study was to analyse the burden of HCV-associated inpatient care in Sweden, to demonstrate the changes over time and to compare the findings with a noninfected population. The HCV-cohort (n: 43 000) was identified from the national surveillance database 1990-2006, and then linked to national registers to produce an age-, sex-, and region-matched noninfected comparison population (n: 215 000) and to obtain information on demographics, cancers, inpatient care and prescriptions. Cox regression was used to estimate the likelihood (hazard ratios) for admission to hospital in the HCV compared with the noninfected cohort. The hazard ratios were 4.03 (95% CI: 3.98-4.08) for all care, 77.52 (71.02-84.60) for liver-related care and 40.74 (30.58-54.27) for liver cancer care. The admission rate in the HCV-cohort compared with the noninfected cohort, the rate ratio (age- and sex-adjusted) for all inpatient care was 5.91 (95% CI: 5.87-5.94), and the rate ratio for liver-related care was 70.05 (66.06-74.28). In the HCV-cohort, 45% of all episodes were for psychiatric, mostly drug-related, care. Inpatient care for SLC increased in the 2000s. To conclude, drug-related care was common in the HCV-infected cohort, the demand for liver-related care was very high, and SLC increased notably in the 2000s, indicating that the burden of inpatient care from serious liver disease in HCV-infected individuals in Sweden is an increasing problem.
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| 16. |
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| 17. |
- Garson, J. A., et al.
(författare)
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Virological, biochemical and histological effects of human lymphoblastoid interferon in Swedish patients with chronic hepatitis
- 1997
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Ingår i: Journal of Viral Hepatitis. - : Wiley. - 1352-0504 .- 1365-2893. ; 4:5, s. 325-331
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Tidskriftsartikel (refereegranskat)abstract
- Thirty-eight Swedish patients with chronic hepatitis C were randomly assigned to receive either 3 million units (MU) or 5 MU of human lymphoblastoid interferon-alpha-n1 (Wellferon) three times per week for either 6 or 12 months. The patients were monitored biochemically, histologically and by quantitative polymerase chain reaction for circulating HCV RNA, during therapy and for the following year. Overall, 22 (58%) of the patients lost detectable hepatitis C virus (HCV) viraemia during therapy but eight of these patients relapsed during follow-up, leaving 14 (37%) sustained responders. Patients infected with HCV non-type 1 genotypes were significantly more likely to achieve a sustained response than were those infected with HCV type 1 (63% vs 10.5%, P = 0.001). Sustained virological responses were also associated with lower pretreatment viraemia level, younger age, absence of cirrhosis and the higher interferon dosage regimens but these associations failed to reach statistical significance. In 97% of patients there was concordance between virological and biochemical responses, and a statistically significant (P = 0.005) improvement in the Knodell histological activity index was observed in the virological sustained responders.
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| 18. |
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| 19. |
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| 20. |
- Pedersen, C., et al.
(författare)
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Ribavirin plasma concentration is a predictor of sustained virological response in patients treated for chronic hepatitis C virus genotype 2/3 infection
- 2011
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Ingår i: Journal of Viral Hepatitis. - : Wiley. - 1352-0504 .- 1365-2893. ; 18:4, s. 245-51
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Tidskriftsartikel (refereegranskat)abstract
- In hepatitis C virus (HCV) genotype 1 infection, the likelihood of obtaining sustained virological response (SVR) is associated with higher ribavirin exposure. Such an association has not been demonstrated for HCV genotype 2/3 infection, where a fixed 800 mg daily dosing of ribavirin is generally recommended. The primary aim of this study was to investigate the correlation between ribavirin concentration at day 29 and therapeutic response in patients with HCV genotype 2/3 infection. A total of 382 patients were randomized to 12 or 24 weeks of treatment with pegylated interferon-alfa 2a 180 μg weekly and 800 mg ribavirin daily. Trough plasma concentration of ribavirin was measured at day 29 and week 12 and the primary outcome was SVR (HCV-RNA undetectable 24 weeks after treatment). Of the 382 patients, 355 had a ribavirin concentration available at day 29. SVR was 84% among patients with a ribavirin concentration ≥2 mg/L at day 29 compared to 66% in those with concentrations <2 mg/L (P = 0.002). The corresponding figures in the 12-week treatment group were 74% and 57% (P = 0.12), and in the 24-week treatment group 91% and 75% (P = 0.02), respectively. In a multivariate analysis, ribavirin concentration at day 29 was an independent predictor of SVR (P = 0.002). In conclusion, a higher plasma ribavirin concentration is associated with an increased likelihood of achieving SVR in HCV genotype 2/3 infection. Individualization of ribavirin dosing may be helpful in improving outcome, especially in the presence of unfavourable baseline characteristics. This, however, requires evaluation in a prospective trial.
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| 21. |
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| 22. |
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| 23. |
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| 24. |
- Strauss, Reinhild, et al.
(författare)
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Hepatocellular carcinoma and other primary liver cancers in hepatitis C patients in Sweden : a low endemic country
- 2008
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Ingår i: Journal of Viral Hepatitis. - : Wiley. - 1352-0504 .- 1365-2893. ; 15:7, s. 531-537
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to assess the risk of hepatocellular carcinoma (HCC) and other primary liver cancers (PLC) in the nationwide cohort of hepatitis C virus (HCV) infected patients in Sweden. The basis was the total HCV-cohort notified in 1990-2004, after excluding 3238 people also reported with hepatitis B, the study cohort consisted of 36 126 people contributing an observation time of 246 105 person-years. The most common route of transmission was intravenous drug use (57%). The national Cancer Registry was used for follow-up, and 354 developed PLC (mainly HCC), of whom 234 were eligible for statistical analysis. The PLC incidence in the HCV cohort was compared with the incidence in the general population, and a standardized incidence ratio (SIR) was calculated for six different strata according to estimated duration of infection. The highest relative risk, SIR: 46 (95% CI: 36-56) was found in the stratum 25-30 years with HCV infection and SIR: 40 (95% CI: 31-51) in the stratum 30-35 years with infection. In the entire community-based HCV cohort in Sweden we found a highly increased risk of liver cancer compared to the general population. The highest relative risk was among people who had been infected for more than 25 years.PMID: 18397224 [PubMed - indexed for MEDLINE]
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| 25. |
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| 26. |
- Westin, Johan, 1965, et al.
(författare)
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Are FoxP3(+) cells involved in hyporesponsiveness to interferon/ribavirin therapy in chronic hepatitis C?
- 2011
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Ingår i: Journal of viral hepatitis. - : Wiley. - 1365-2893 .- 1352-0504. ; 18:2, s. 149-151
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Tidskriftsartikel (refereegranskat)abstract
- Summary. We aimed to clarify the role of liver-infiltrating FoxP3(+)T cells for the response to therapy in chronic hepatitis C. Liver biopsies from 52 patients were collected prior to the start of interferon/ribavirin treatment, and the kinetics of viral decay during treatment were compared in patients with high and low infiltration of FoxP3(+) cells. These groups did not differ with respect to the effectiveness of early viral clearance or the frequency of sustained viral response. Our data imply that FoxP3(+) cell-mediated immunosuppression is not a major mechanism of hyporesponsiveness to interferon-based therapy in chronic hepatitis C.
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| 27. |
- Westin, Johan, 1965, et al.
(författare)
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Impact of hepatic steatosis on viral kinetics and treatment outcome during antiviral treatment of chronic HCV infection
- 2007
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Ingår i: J Viral Hepat. - : Wiley. - 1352-0504. ; 14:1, s. 29-35
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Tidskriftsartikel (refereegranskat)abstract
- Liver steatosis is highly prevalent in chronic hepatitis C virus (HCV) infection, especially in patients infected with genotype 3 virus, but its significance for the outcome of antiviral treatment is not fully understood. We have monitored steatosis in liver biopsies from 231 patients with chronic HCV infection who received pegylated recombinant interferon-alpha and ribavirin in a phase III study (DITTO trial). The degree of steatosis, along with relevant metabolic parameters, was correlated with the early disappearance of virus and with the final outcome of treatment. Our data suggest that the presence of steatosis impairs the early reduction of viral load during treatment in patients infected with HCV genotype 3 and non-3. Steatosis negatively affected the final outcome of treatment mainly in patients infected with HCV genotype non-3 virus. Based on these findings, we propose that interventions aiming at reducing hepatic steatosis prior to the onset of antiviral therapy may be of benefit to patients infected with HCV of the non-3 genotypes. Patients infected with genotype 3, on the other hand, should be offered early antiviral treatment.
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| 28. |
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| 29. |
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| 30. |
- Bruggmann, P., et al.
(författare)
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Historical epidemiology of hepatitis C virus (HCV) in selected countries
- 2014
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Ingår i: Journal of Viral Hepatitis. - Hoboken : Wiley-Blackwell. - 1352-0504 .- 1365-2893. ; 21, s. 5-33
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Tidskriftsartikel (refereegranskat)abstract
- Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6358000 cases in 2008 and Brazil with 2106000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV-infected populations are critical for addressing HCV-related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.
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| 31. |
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| 32. |
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| 33. |
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| 34. |
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| 35. |
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| 36. |
- Kamal, Habiba, et al.
(författare)
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Risk of hepatocellular carcinoma in hepatitis B and D virus co-infected patients : A systematic review and meta-analysis of longitudinal studies
- 2021
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Ingår i: Journal of Viral Hepatitis. - : John Wiley & Sons. - 1352-0504 .- 1365-2893. ; 28:10, s. 1431-1442
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Forskningsöversikt (refereegranskat)abstract
- Hepatitis D virus (HDV) infection causes a severe chronic viral hepatitis with accelerated development of liver cirrhosis and decompensation, but whether it further increases the risk of hepatocellular carcinoma (HCC) is unclear. We performed a comprehensive systematic review of the published literature and meta-analysis to assess the risk of HCC in HDV and hepatitis B virus (HBV) co-infected, compared to HBV mono-infected patients. The study was conducted per a priori defined protocol, including only longitudinal studies, thus excluding cross-sectional studies. Random-effects models were used to determine aggregate effect sizes (ES) with 95% confidence intervals (CI). Meta-regression was used to examine the associations among study level characteristics. Twelve cohort studies comprising a total of 6099 HBV/HDV co-infected and 57,620 chronic HBV mono-infected patients were analysed. The overall pooled ES showed that HBV/HDV co-infected patients were at 2-fold increased risk of HCC compared to HBV mono-infected patients (ES = 2.12, 95% CI 1.14-3.95, I2 = 72%, N = 12). A six-fold significant increased risk of HCC was noted among HIV/HBV/HDV triple-infected, compared to HIV/HBV co-infected patients. The magnitude of ES did not differ significantly after adjustment for study design and quality, publication year and follow-up duration in univariable meta-regression analysis. This systematic review and meta-analysis shows that infection with HDV is associated with a 2-fold higher risk of HCC development compared to HBV mono-infection. HCC surveillance strategies taking this increased risk into account, and new treatment options against HDV, are warranted.
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| 37. |
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| 38. |
- Lindh, Magnus, 1960, et al.
(författare)
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Dynamic tailoring of treatment durations improves efficiency of hepatitis C treatment with pegylated interferon and ribavirin
- 2013
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Ingår i: Journal of Viral Hepatitis. - : Wiley. - 1352-0504 .- 1365-2893. ; 20:4
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Tidskriftsartikel (refereegranskat)abstract
- The treatment durations for hepatitis C are guided by the analysis of hepatitis C virus (HCV) RNA in blood at certain time points. This multicentre, randomized open label trial evaluated the utility and performance of individualized treatment durations guided by viral decline rates in 103 patients with HCV genotype 1 infection. Pegylated interferon 2a and ribavirin were given as standard of care (SOC) for 24, 48 or 72 weeks or as dynamic treatment (DT) for 24–72 weeks. The DT duration was based on the time point when log HCV RNA would reach 0 log copies/mL, as estimated by the second-phase decline. The rate of sustained virologic response was 63% for SOC and 54% for DT, but this difference was not significant in multiple regression analysis taking predictive factors such as interleukin-28B genotypes, age and baseline viremia into account (P = 0.45). The mean required treatment time per cured patient was 51 weeks for DT as compared with 58 weeks for SOC (P = 0.22) when given per protocol (n = 95) and was significantly shorter (42 vs 51 weeks) among patients who achieved undetectable HCV RNA (P = 0.01). We conclude that DT was feasible and increased efficiency. The estimated time point for 0 log viral copies/mL is a new and quantitative response variable, which may be used as a complement to the qualitative variable rapid virologic response. The outcome parameter treatment weeks per cured patient could become a useful tool for comparing treatment efficiency also in the era of directly acting antivirals.
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| 39. |
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| 40. |
- Oltmanns, Carlos, et al.
(författare)
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Elevation of S2-bound a1-acid glycoprotein is associated with chronic hepatitis C virus infection and hepatocellular carcinoma
- 2024
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Ingår i: Journal of Viral Hepatitis. - : WILEY. - 1352-0504 .- 1365-2893.
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Tidskriftsartikel (refereegranskat)abstract
- There is an urgent need for new high-quality markers for the early detection of hepatocellular carcinoma (HCC). angstrom strom et al. suggested that S2-bound alpha 1-acid glycoprotein (AGP) might be a promising marker. Consequently, we evaluated the predictive advantage of S2-bound AGP in the early detection of HCC. In a retrospective case-control study of patients chronically infected with hepatitis C virus (HCV) and treated with direct-acting antiviral agents (n = 93), we measured S2-bound AGP using the HepaCheC (R) ELISA kit (Glycobond AB, Linkoping, SE) at the start of treatment, end of treatment and follow-up (maximum: 78 months). Patients were retrospectively propensity score matched (1:2). Thirty-one patients chronically infected with HCV developed HCC after a sustained virological response, while 62 did not. In addition, samples of patients with chronic hepatitis B virus infection, metabolic dysfunction-associated steatotic liver disease and HCC of different etiologies were analysed. S2-bound AGP elevation in HCC patients was confirmed. However, we did not observe a predictive advantage of S2-bound AGP for the early detection of HCC during treatment and follow-up. Interestingly, S2-bound AGP levels correlated with aspartate aminotransferase (rho = .56, p = 9.5x10-15) and liver elastography (rho = .67, p = 2.2x10-16). Of note, S2-bound AGP decreased in patients chronically infected with HCV after treatment-induced HCV clearance. Fucosylated S2-bound AGP levels were elevated in patients with chronic HCV and HCC. The potential role of S2-bound AGP as a novel tumour marker requires further investigation.
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| 41. |
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| 42. |
- Razavi, H., et al.
(författare)
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The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm
- 2014
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Ingår i: Journal of Viral Hepatitis. - Hoboken : Wiley-Blackwell. - 1352-0504 .- 1365-2893. ; 21:Suppl. 1, s. 34-59
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Tidskriftsartikel (refereegranskat)abstract
- The disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. In addition, the model was used to estimate the change in the total number of HCV infections, the disease progression and mortality in 2013-2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today's treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries studied. However, in the same time period, the number of individuals with late-stage liver disease is projected to increase. This study concluded that the current treatment rate and efficacy are not sufficient to manage the disease burden of HCV. Thus, alternative strategies are required to keep the number of HCV individuals with advanced liver disease and liver-related deaths from increasing.
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| 43. |
- Ringlander, Johan, et al.
(författare)
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Deep sequencing of liver explant transcriptomes reveals extensive expression from integrated hepatitis B virus DNA
- 2020
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Ingår i: Journal of Viral Hepatitis. - : Wiley. - 1352-0504 .- 1365-2893. ; 27:11, s. 1162-1170
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Tidskriftsartikel (refereegranskat)abstract
- Hepatitis B virus (HBV) is a major cause of hepatocellular carcinoma (HCC). Integration of HBV DNA into the human genome may contribute to oncogenesis and to the production of the hepatitis B surface antigen (HBsAg). Whether integrations contribute to HBsAg levels in the blood is poorly known. Here, we characterize the HBV RNA profile of HBV integrations in liver tissue in patients with chronic HBV infection, with or without concurrent hepatitis D infection, by transcriptome deep sequencing. Transcriptomes were determined in liver tissue by deep sequencing providing 200 million reads per sample. Integration points were identified using a bioinformatic pipeline. Explanted liver tissue from five patients with end-stage liver disease caused by HBV or HBV/HDV was studied along with publicly available transcriptomes from 21 patients. Almost all HBV RNA profiles were devoid of reads in the core and the 3 ' redundancy (nt 1830-1927) regions, and contained a large number of chimeric viral/human reads. Hence, HBV transcripts from integrated HBV DNA rather than from covalently closed circular HBV DNA (cccDNA) predominated in late-stage HBV infection, in particular in cases with hepatitis D virus co-infection. The findings support the suggestion that integrated HBV DNA can be a significant source of HBsAg in humans.
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| 44. |
- Wedemeyer, H., et al.
(författare)
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Strategies to manage hepatitis C virus (HCV) disease burden
- 2014
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Ingår i: Journal of Viral Hepatitis. - Hoboken : Wiley-Blackwell. - 1352-0504 .- 1365-2893. ; 21, s. 60-89
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Tidskriftsartikel (refereegranskat)abstract
- The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV-related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3-5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical.
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| 45. |
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| 46. |
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| 47. |
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| 48. |
- Guedj, H., et al.
(författare)
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The impact of fibrosis and steatosis on early viral kinetics in HCV genotype 1-infected patients treated with Peg-IFN-alfa-2a and ribavirin
- 2012
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Ingår i: Journal of Viral Hepatitis. - : Wiley. - 1352-0504. ; 19:7, s. 488-496
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Tidskriftsartikel (refereegranskat)abstract
- . Hepatitis C viral (HCV) kinetics after initiation of interferon-based therapy provide valuable insights for understanding virus pathogenesis, evaluating treatment antiviral effectiveness and predicting treatment outcome. Adverse effects of liver fibrosis and steatosis on sustained virological response have been frequently reported, yet their impacts on the early viral kinetics remain unclear. In this study, associations between histology status and early viral kinetics were assessed in 149 HCV genotype 1infected patients treated with pegylated interferon alfa-2a and ribavirin (DITTO trial). In multivariate analyses adjusted for critical factors such as IL28B genotype and baseline viral load, presence of significant fibrosis (Ishak stage > 2) was found to independently reduce the odds of achieving an initial reduction (calculated from day 0 to day 4) in HCV RNA of =2 logIU/mL (adjusted OR 0.03, P = 0.004) but was not associated with the second-phase slope of viral decline (calculated from day 8 to day 29). On the contrary, presence of liver steatosis was an independent risk factor for not having a rapid second-phase slope, that is, =0.3 logIU/mL/week (adjusted OR 0.22, P = 0.012) but was not associated with the first-phase decline. Viral kinetic modelling theory suggests that significant fibrosis primarily impairs the treatment antiviral effectiveness in blocking viral production by infected cells, whereas the presence of steatosis is associated with a lower net loss of infected cells. Further studies will be necessary to identify the biological mechanisms underlain by these findings.
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| 49. |
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| 50. |
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