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- Lindh, Magnus, 1960, et al.
(author)
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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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In: Journal of Viral Hepatitis. - : Wiley. - 1352-0504 .- 1365-2893. ; 20:4
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Journal article (peer-reviewed)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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| 2. |
- Andersson, Maria Eva, et al.
(author)
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Rapid Clearance and Frequent Reinfection With Enteric Pathogens Among Children With Acute Diarrhea in Zanzibar.
- 2017
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In: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 65:8, s. 1371-1377
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Journal article (peer-reviewed)abstract
- Background: Acute infectious gastroenteritis is an important cause of illness and death among children in low-income countries. In addition to rotavirus vaccination, actions to improve nutrition status, sanitation, and water quality are important to reduce enteric infections, which are frequent also among asymptomatic children. The aim of this study was to investigate if the high prevalence of these infections reflects that they often are not cleared properly by the immune response or rather is due to frequent pathogen exposure.Methods: Rectal swabs were collected at time of acute diarrhea and 14 days later from 127 children, aged 2-59 months and living in rural Zanzibar, and were analyzed by real-time polymerase chain reaction targeting multiple pathogens.Results: At baseline, detection rates >20% were found for each of enterotoxigenic Escherichia coli, Shigella, Campylobacter, Cryptosporidium, norovirus GII, and adenovirus. At follow-up, a large proportion of the infections had become cleared (34-100%), or the pathogen load reduced, and this was observed also for agents that were presumably unrelated to diarrhea. Still, the detection frequencies at follow-up were for most agents as high as at baseline, because new infections had been acquired. Neither clearance nor reinfection was associated with moderate malnutrition, which was present in 21% of the children.Conclusions: Children residing in poor socioeconomic conditions, as in Zanzibar, are heavily exposed to enteric pathogens, but capable of rapidly clearing causative and coinfecting pathogens.
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| 4. |
- Björkman, Eleonora, 1981, et al.
(author)
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Angiotensin IV and the human esophageal mucosa: An exploratory study in healthy subjects and gastroesophageal reflux disease patients.
- 2015
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In: Journal of the renin-angiotensin-aldosterone system : JRAAS. - : Hindawi Limited. - 1752-8976 .- 1470-3203. ; 16:3, s. 570-577
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Journal article (peer-reviewed)abstract
- The human esophageal mucosa expresses various components of the renin-angiotensin system (RAS), e.g. the main effector peptide angiotensin II (AngII). The aim of this study was to investigate the esophageal presence of angiotensin III (AngIII) and angiotensin IV (AngIV) forming enzymes and the AngIV receptor (AT4R). The aim was also to study the actions of AngIV and to look for aberrations in patients with gastroesophageal reflux disease (GERD).
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| 6. |
- Waldenström, Jesper, 1985, et al.
(author)
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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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In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 56:7
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Journal article (peer-reviewed)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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