| 1. |
- Grander, D, et al.
(författare)
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Factors influencing the response to interferon therapy in chronic hepatitis C. Studies on viral genotype and induction of 2',5'-oligoadenylate synthetase in the liver and peripheral blood cells
- 1996
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 31:6, s. 604-611
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The mechanism behind the antiviral action of interferon (IFN) therapy in chronic hepatitis C virus (HCV) infection is not well understood, and, furthermore, few factors have been shown to be good predictors of a favourable response to IFN treatment in chronic HCV infection. METHODS: Freshly explanted liver cells and peripheral blood mononuclear cells (PBMC) from 80 patients with chronic HCV infection were used to study the capacity of IFN to induce the enzyme 2',5'-oligoadenylate synthetase (2'5'-AS) in vitro. The HCV genotype was determined in 53 patients. The induction of 2'5'-AS was correlated to the results of IFN-alpha treatment in 36 patients. RESULTS: Normalization of transaminases during IFN treatment was significantly associated with 2'5'-AS levels in liver cells cultured in the absence of IFN. A similar tendency, although not statistically significant, was found for IFN-induced levels of 2'5'-AS in liver cells. No such associations were found when PBMC were analysed. Six patients showed a sustained biochemical response. These six did not deviate significantly from the remaining patients with regard to base-line or IFN-induced levels of 2'5'-AS in liver cells or PBMC. Eradication of HCV RNA during IFN treatment did not correlate with 2'5'-AS levels in liver cells. Comparison of HCV genotype and clinical response showed that patients with genotype 3a had the most favourable outcome. No association was found between liver histology and treatment outcome. CONCLUSION: These data imply that direct effects of IFN on liver cells are of importance for the response to IFN treatment.
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| 2. |
- Brändström, U., et al.
(författare)
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Results from the intercalibration of optical low light calibration sources 2011
- 2012
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Ingår i: Geoscientific Instrumentation, Methods and Data Systems. - : Copernicus GmbH. - 2193-0856 .- 2193-0864. ; 1:1, s. 43-51
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Tidskriftsartikel (refereegranskat)abstract
- Following the 38th Annual European Meeting onAtmospheric Studies by Optical Methods in Siuntio in Finland,an intercalibration workshop for optical low light calibrationsources was held in Sodankyl¨a, Finland. The mainpurpose of this workshop was to provide a comparable scalefor absolute measurements of aurora and airglow. All sourcesbrought to the intercalibration workshop were compared tothe Fritz Peak reference source using the Lindau CalibrationPhotometer built by Wilhelm Barke and Hans Lauche in1984. The results were compared to several earlier intercalibrationworkshops. It was found that most sources were fairlystable over time, with errors in the range of 5–25 %. To furthervalidate the results, two sources were also intercalibratedat UNIS, Longyearbyen, Svalbard. Preliminary analysis indicatesagreement with the intercalibration in Sodankyl¨a withinabout 15–25 %.
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| 3. |
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| 4. |
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| 5. |
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| 6. |
- 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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| 7. |
- Lindstedt, Göran, 1937, et al.
(författare)
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[New service for laboratory investigation of problematic cases. Four patients illustrate the value of EQUALIS]
- 2005
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Ingår i: Läkartidningen. - 0023-7205. ; 102:5
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Tidskriftsartikel (refereegranskat)abstract
- In 1996, the Endocrinology Group in EQUALIS, in collaboration with The Thyroid Unit at The Section of Endocrinology at Sahlgrenska University Hospital, introduced a "patient-related" quality assurance program. Serum samples from patients with established or suspected thyroid disorder and/or results from thyroid-related biochemical measurements which were at variance with the clinical presentation, were analyzed by the participants of an external quality assurance program in endocrinology. The results from this program were informative as regards capacity, in the individual laboratories, for the evaluation of analytical and/or biological factors causing unexpected results from the measurement of thyroid-related serum components. We now present four clinical cases, which had offered diagnostic problems. EQUALIS, in collaboration with the participants of the external quality assurance program in endocrinology and on the basis of experiences from this program, now offers a diagnostic service for clinical chemistry laboratories and physicians when they are confronted with unexpected results from the immunochemical measurement of analytes included in the program.
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| 8. |
- Shev, S, et al.
(författare)
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GBV-C/HGV infection in hepatitis C virus-infected deferred Swedish blood donors
- 1998
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Ingår i: Journal of Medical Virology. - 1096-9071 .- 0146-6615. ; 54:2, s. 75-79
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Tidskriftsartikel (refereegranskat)abstract
- Sera from 62 hepatitis C virus (HCV)-infected Swedish blood donors were tested by a nested polymerase chain reaction using primers targeting the 5'-noncoding region of the GB virus-C/hepatitis G (GBV-C/HGV) genome and an enzyme-linked immunosorbent assay that detects antibodies to the envelope protein E2 of GBV-C/HGV (anti-E2). Fourteen (22%) and 21 (34%) of the 62 blood donors were found to be GBV-C/HGV RNA and anti-E2 positive, respectively. None of the blood donors was positive for both GBV-C/HGV RNA and anti-E2. Thus, 35 of 62 (56%) HCV-infected donors had been exposed to GBV-C/HGV infection. At sequencing of the 14 GBV-C/HGV isolates, 12 were identified as subtype 2a and 2 as subtype 2b. One of 7 (14%) donors with mild liver disease such as steatosis and nonspecific reactive hepatitis had been exposed to GBV-C/HGV vs. 34 of 55 (62%) with chronic hepatitis with or without cirrhosis (P = 0.04). All other differences in histology were small between HCV and dual HCV GBV-C/HGV-infected donors. In conclusion, more than half of HCV-infected Swedish blood donors in this study were positive for either GBV-C/HGV RNA or anti-E2. GBV-C/HGV viremia and seropositivity were mutually exclusive.
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| 9. |
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| 10. |
- Shev, S, et al.
(författare)
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HCV genotypes in Swedish blood donors as correlated to epidemiology, liver disease and hepatitis C virus antibody profile
- 1995
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Ingår i: Infection. - 1439-0973 .- 0300-8126. ; 23:5, s. 253-257
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Tidskriftsartikel (refereegranskat)abstract
- Sixty-two anti-HCV and HCV-RNA positive Swedish blood donors (44 men, 18 women; median age 34 years) were studied. HCV genotypes were correlated to parenteral risk factors, liver morphology, serum alanine aminotransferase (ALAT) levels and HCV antibody profile. Forty percent of the donors were infected with HCV genotype 1a, 10% with 1b, 21% with 2b, and 29% with 3a. Intravenous drug use (IVDU) was more common in donors with genotype 3a than in those with genotype 1a (p = 0.024), and prior blood transfusion more common in genotype 2b than in 3a (p = 0.012). Chronic active hepatitis with and without cirrhosis was found in 38% of donors infected with genotype 2b as compared to 8% of donors infected with 1a (p = 0.034). Forty percent of donors with genotype 1a had normal ALAT at the time of liver biopsy versus 11% with genotype 3a (p = 0.046). Antibodies to C33c and C22-3 were present in nearly all donors whereas reactivity to C100-3 and 5-1-1 was detected more often in donors with genotypes 1a and 1b as compared to donors with genotypes 2b and 3a. In conclusion, genotype 3a was correlated to IVDU or tattooing as parenteral risk factors for the acquisition of HCV infection, and genotype 2b to prior blood transfusion. Donors with genotypes 1a seemed to have less severe liver disease than those infected with genotypes 2b and 3a.
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| 11. |
- Shev, S, et al.
(författare)
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Second-generation hepatitis C Elisa antibody tests confirmed by the four-antigen recombinant immunoblot assay correlate well with hepatitis C viremia and chronic liver disease in Swedish blood donors
- 1993
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Ingår i: Vox Sanguinis. - 1423-0410. ; 65:1, s. 32-37
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Tidskriftsartikel (refereegranskat)abstract
- Seventy-three Swedish blood donors (52 men, 21 women; median age 36 years) repeatedly reactive for hepatitis C antibodies (anti-HCV C-100-3) were tested with a second-generation (2nd-gen) anti-HCV Elisa and a 4-band recombinant immunoblot assay (RIBA 2). These results were correlated to serum alanine aminotransferase (S-ALAT), liver morphology and viremia as detected by 'nested' polymerase chain reaction (PCR) based on primers from a 5'-noncoding sequence of the HCV genome. Thirty-five of 46 (76%) donors with positive 2nd-gen Elisa tests confirmed by RIBA 2 were PCR positive whereof 27 had histological findings compatible with chronic persistent hepatitis (CPH) and 7 had chronic active hepatitis (CAH). Ten of 56 (18%) 2nd-gen Elisa-positive donors were RIBA 2 negative (or indeterminate) and none of these had chronic hepatitis nor were PCR positive. Seventeen of 73 (23%) donors were 1st-gen Elisa positive but 2nd-gen Elisa negative. All of these were PCR negative and only 1 (6%) had chronic hepatitis (CPH). An elevated S-ALAT level (reference < 0.7 mu kat/l) was found in 26 2nd-gen Elisa and RIBA 2-positive donors of which 18 had CPH and 7 had CAH and all 25 were PCR positive. A normal S-ALAT level was found in 9 of 34 (26%) donors with chronic hepatitis (all had CPH) and positive PCR. We have found that blood donors with positive 2nd-gen anti-HCV Elisa tests confirmed by RIBA-2 and especially with a concomitant elevated S-ALAT are highly likely to be viremic as demonstrated by PCR and to have chronic hepatitis.
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| 12. |
- Simmonds, P, et al.
(författare)
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Consensus proposals for a unified system of nomenclature of hepatitis C virus genotypes
- 2005
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Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3350 .- 0270-9139. ; 42:4, s. 962-973
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Tidskriftsartikel (refereegranskat)abstract
- International standardization and coordination of the nomenclature of variants of hepatitis C virus (HCV) is increasingly needed as more is discovered about the scale of HCV-related liver disease and important biological and antigenic differences that exist between variants. A group of scientists expert in the field of HCV genetic variability, and those involved in development of HCV sequence databases, the Hepatitis Virus Database (Japan), euHCVdb (France), and Los Alamos (United States), met to re-examine the status of HCV genotype nomenclature, resolve conflicting genotype or subtype names among described variants of HCV, and draw up revised criteria for the assignment of new genotypes as they are discovered in the future. A comprehensive listing of all currently classified variants of HCV incorporates a number of agreed genotype and subtype name reassignments to create consistency in nomenclature. The paper also contains consensus proposals for the classification of new variants into genotypes and subtypes, which recognizes and incorporates new knowledge of HCV genetic diversity and epidemiology. A proposal was made that HCV variants be classified into 6 genotypes (representing the 6 genetic groups defined by phylogenetic analysis). Subtype name assignment will be either confirmed or provisional, depending on the availability of complete or partial nucleotide sequence data, or remain unassigned where fewer than 3 examples of a new subtype have been described. In conclusion, these proposals provide the framework by which the HCV databases store and provide access to data on HCV, which will internationally coordinate the assignment-of-new genotypes and subtypes in the future.
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| 13. |
- Waldenström, Jesper, 1985, et al.
(författare)
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Absence of interferon-lambda 4 enhances spontaneous clearance of acute hepatitis C virus genotypes 1-3 infection
- 2021
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 56:7
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Absence of a functional interferon-lambda 4 (IFN-lambda 4) gene (IFNL4) predicts spontaneous resolution of acute hepatitis C virus (HCV) infections in regions with a predominance of genotype 1, whereas variants of the inosine triphosphate pyrophosphatase (ITPase) gene (ITPA) entailing reduced activity associate with increased sustained virologic response rates following some therapeutic regimens. This study aimed at investigating the impact of IFNL4 on acute HCV genotype 2 or 3 infections, and whether ITPase activity influenced outcome. Materials and Methods Two hundred and seven people who injected drugs (PWID) with documented anti-HCV seroconversion, and 57 PWID with reinfection with HCV were analyzed regarding IFNL4 (rs368234815 and rs12979860) and ITPA (rs1127354 and rs7270101), and longitudinally followed regarding HCV RNA. Results The spontaneous clearance of HCV infection in anti-HCV seronegative PWID was enhanced when IFN-lambda 4 was absent (44% vs. 20% for IFNL4 TT/TTrs1368234815 and Delta G(rs1368234815) respectively, p < .001; OR 3.2) across genotypes 1-3. The proportion lacking IFN-lambda 4 was further increased following resolution of repeated re-exposure to HCV (74% among re-infected participants who had cleared at least two documented HCV infections). ITPA genetic variants did not independently impact on the outcome, but among males lacking IFN-lambda 4, reduced ITPase activity markedly augmented the likelihood of resolution (65% vs. 29% for <100% and 100% ITPase activity, p = .006). Conclusions Absence of IFN-lambda 4 entails an enhanced likelihood of spontaneous resolution both following primary acute infection and repeated re-exposure to HCV across genotypes 1-3. Among men lacking IFN-lambda 4, reduced ITPase activity improved outcome.
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| 14. |
- Weiland, O, et al.
(författare)
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Efficacy of human leucocyte alpha-interferon treatment for chronic hepatitis C virus infection
- 1995
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 27:5, s. 319-324
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Tidskriftsartikel (refereegranskat)abstract
- A total of 42 Swedish patients with biopsy-proven chronic hepatitis C virus (HCV) infection were treated with a natural human leucocyte alpha-interferon (HuIFN-alpha-Le), Alfanative (BioNative AB, Umeå, Sweden) in an open uncontrolled study. Two patients were withdrawn from treatment within 2 weeks due to non-compliance and were omitted from further analysis, and 40 patients (17 females), mean age 39 years (range 24-71) completed the study. All patients were HCV RNA-positive in serum prior to treatment, with raised alanine aminotransferase (ALT) levels > 1.5 times the upper normal limit known for more than 6 months. Interferon was given at a dose of 3 MU t.i.w. for an intended 24 weeks and follow-up was a further 24 weeks after treatment. Biochemical non-responders were withdrawn from treatment within 12-16 weeks but continued follow-up. Overall 21/40 (52.5%) patients had a complete biochemical response with normal ALT levels at the end of treatment. Sustained response during follow-up was seen in 8 (20%) whereas 13 (32.5%) had a non-sustained response. At the end of treatment 23 (58%) patients had undetectable serum HCV RNA and 9 (23%) at follow-up. Patients with sustained, non-sustained and non-response had a mean pretreatment HCV RNA level of 3.2 x 10(5), 2.5 x 10(6) and 3.2 x 10(6) genomes/ml, respectively, differences that did not reach statistical significance. Of the patients 3, 9, 10 and 14 had genotype 1b, 3a, 1a, and 2b, respectively, and 4 had mixed genotypes. Of the 23 patients with genotype 2b or 3a, 7 had a sustained response vs. none of the 13 patients with genotype 1a or 1b (p = 0.03). No patients with cirrhosis had a sustained response whereas 4/18 with chronic persistent and 4/18 with chronic active hepatitis had such a response. It is concluded that some 50% of patients treated with HuIFN-alpha-Le responded with normalisation of ALT levels but that only 20% had a durable response 24 weeks post-treatment, and that patients with genotypes 3a or 2b seem to respond better than patients with other genotypes.
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| 15. |
- Weiland, O, et al.
(författare)
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Serum HCV RNA levels in patients with chronic hepatitis C given a second course of interferon alpha-2b treatment after relapse following initial treatment
- 1993
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Ingår i: Scandinavian Journal of Infectious Diseases. - 1651-1980. ; 25:1, s. 25-30
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Tidskriftsartikel (refereegranskat)abstract
- 10 patients with chronic hepatitis C virus (HCV) infection who previously had responded temporarily to 9 months interferon alpha-2b treatment with normalization of ALT levels during treatment but later relapse were given a second 6-month treatment course. All patients were positive for anti-HCV by a second generation ELISA confirmed by second generation RIBA and positive for HCV RNA in serum before retreatment with interferon. Serum HCV RNA titers and ALT levels were monitored before, during and after treatment. ALT levels fell significantly from mean 1.95 mu kat/l before treatment to mean 0.96 and 0.85 mu kat/l after 4 and 24 weeks treatment, respectively (p < 0.005-p < 0.009). Six patients had normal ALT levels (< 0.07 mu kat/l) at treatment stop. 12 weeks post treatment cessation, however, the mean ALT level, 2.29 mu kat/l, was not significantly changed from the pretreatment level and all patients had raised ALT levels. The mean pretreatment HCV RNA titer in serum 10(5) (range 10(7)-10(3.5)) fell in all patients to mean 10(1.3) (range 10(3)-10(0)) already after 4 weeks treatment and became undetectable at treatment cessation in 5 patients, of whom 4 had normal ALT levels. ALT levels, however, were also normal in 2/5 patients who continued to have detectable HCV RNA titers at treatment cessation. After treatment was stopped HCV RNA titers rose again and 12 weeks post treatment the mean titer was 10(4.7) (range 10(3.5)-10(5.5)).(ABSTRACT TRUNCATED AT 250 WORDS)
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| 16. |
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