Publications by authors named "Forton D"
Article Synopsis
- There is evidence that inhibitory killer cell immunoglobulin-like receptors (iKIRs) can influence T cell responses and survival, particularly in chronic viral infections.
- In a study with humans, it was found that individuals with more iKIR-ligand gene pairs had significantly longer-lasting memory CD8+ T cells, with lifespans increasing from 125 days to 250 days.
- The research suggests that iKIR-ligand genotypes play a crucial role in T cell survival and immune aging, independent of iKIR expression on the T cells themselves.
The World Health Organization (WHO) has identified the need for a better understanding of which patients with hepatitis C virus (HCV) can be cured with ultrashort course HCV therapy. A total of 202 individuals with chronic HCV were randomised to fixed-duration shortened therapy (8 weeks) vs variable-duration ultrashort strategies (VUS1/2). Participants not cured following first-line treatment were retreated with 12 weeks' sofosbuvir/ledipasvir/ribavirin.
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- - The study analyzed antibody responses (IgG) in 177 individuals with SARS-CoV-2 infection in London from March to May 2020, linking antibody levels to patient demographics and outcomes.
- - Findings revealed that 2.0%-8.5% of participants did not develop antibodies after 3-6 weeks, and those who did were generally older, had more health issues, and higher inflammatory markers.
- - Additionally, non-White participants had stronger antibody responses that persisted over time, suggesting that serologic assays could help monitor immune responses and inform public health strategies.
Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited.
Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19.
Design, Setting, And Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin.
Article Synopsis
- The endocannabinoid (eCB) system is involved in regulating immune responses and has been linked to depressive behaviors, especially after treatments like IFN-α for hepatitis C.
- Researchers conducted a study to examine how endocannabinoids (anandamide and 2-arachidonoylglycerol) were affected by IFN-α treatment and their potential role in depression among hepatitis C patients.
- Findings showed that while 2-AG levels increased early during treatment, AEA levels rose later and remained elevated, and HCV patients had lower baseline AEA levels compared to healthy individuals, linking AEA changes to depressive symptoms.
Article Synopsis
- In England, the effectiveness of hepatitis C treatments varies over time, as national contracts dictate therapy choices, and the population has many rare viral genotypes.
- Aim of the study was to analyze real-world data from a national registry to assess the success rates (SVR) of direct-acting antiviral treatments.
- Results showed that among 14,603 patients, the overall SVR rate was 95.59%, with certain treatments being more effective for specific genotypes, and even partial completion of treatment led to significant success rates.
The role of immune or infective triggers in the pathogenesis of Chronic Fatigue Syndrome (CFS) is not yet fully understood. Barriers to obtaining immune measures at baseline (i.e.
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- Neurological issues related to HCV infection, such as fatigue, depression, and cognitive problems, are often overlooked in clinical settings.
- Evidence suggests a potential link between HCV and an increased risk of developing Parkinson's disease, though the exact mechanisms are still unclear.
- Treatment for HCV has shown to improve neuropsychiatric symptoms, leading to a better overall quality of life for patients.
Unlabelled: Many direct-acting antiviral regimens have reduced activity in people with hepatitis C virus (HCV) genotype (GT) 3 infection and cirrhosis. The C-ISLE study assessed the efficacy and safety of elbasvir/grazoprevir (EBR/GZR) plus sofosbuvir (SOF) with and without ribavirin (RBV) in compensated cirrhotic participants with GT3 infection. This was a phase 2, randomized, open-label study.
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- Concerns have been raised about the potential for increased recurrence of hepatocellular carcinoma (HCC) in patients undergoing direct-acting antiviral (DAA) therapy for hepatitis C while on the liver transplant waitlist.
- A study at Padua Liver Transplant Center compared HCC patients treated with DAAs to controls, finding similar dropout rates and progression in HCC characteristics between the two groups during follow-up.
- The results indicate that treating hepatitis C with DAAs does not significantly raise the risk of HCC recurrence or affect transplant eligibility, suggesting viral eradication may be safe for these patients.
An association between hepatitis C virus infection and neuropsychiatric symptoms has been proposed for some years. A variety of studies have been undertaken to assess the nature and severity of these symptoms, which range from fatigue and depression to defects in attention and verbal reasoning. There is evidence of mild neurocognitive impairment in some patients with HCV infection, which is not fully attributable to liver dysfunction or psychosocial factors.
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- Directly acting antiviral drugs (DAAs) show over 90% success in curing hepatitis C, but treatment failure often occurs due to the emergence of resistance-associated variants (RASs).
- Research has identified specific amino acid changes in the virus that can reduce DAA effectiveness; these RASs may not always lead to treatment failure but can persist long after therapy.
- Current guidelines suggest using optimal treatment strategies tailored to individual patient characteristics to minimize resistance, while next-generation DAAs are expected to be more effective and serve as backup options for those who experience treatment failure.
Development of psychiatric symptoms during interferon-alpha therapy may be influenced by psychological factors. We examined illness perceptions using the Revised Illness Perceptions Questionnaire in 55 patients with chronic hepatitis C virus infection, due to receive interferon-alpha. The Hospital Anxiety and Depression Scale was used to assess the development of symptoms.
View Article and Find Full Text PDFOwing to the unique opportunity to assess individuals before and after they develop depression within a short timeframe, interferon-α (IFN-α) treatment for chronic hepatitis C virus (HCV) infection is an ideal model to identify molecular mechanisms relevant to major depression, especially in the context of enhanced inflammation. Fifty-eight patients were assessed prospectively, at baseline and monthly over 24 weeks of IFN-α treatment. New-onset cases of depression were determined using the Mini International Neuropsychiatric Interview (MINI).
View Article and Find Full Text PDFFaldaprevir, a hepatitis C virus (HCV) NS3/4A protease inhibitor, was evaluated in HCV genotype 1-infected patients who failed peginterferon and ribavirin (PegIFN/RBV) treatment during one of three prior faldaprevir trials. Patients who received placebo plus PegIFN/RBV and had virological failure during a prior trial were enrolled and treated in two cohorts: prior relapsers (n = 43) and prior nonresponders (null responders, partial responders and patients with breakthrough; n = 75). Both cohorts received faldaprevir 240 mg once daily plus PegIFN/RBV for 24 weeks.
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- Chronic hepatitis C virus (HCV) infection can cause various extrahepatic issues like mixed cryoglobulinemia, diabetes, and neurological problems, affecting overall patient health.
- Successful treatment with interferon and ribavirin has shown improvements in these extrahepatic effects, including reduced insulin resistance and better cognitive function.
- New interferon-free treatments could expand patient access and may significantly improve associated health conditions, possibly leading to treatment focusing on these extrahepatic effects, even without liver disease.
Article Synopsis
- Hepatitis C virus (HCV) not only causes liver damage but can also lead to neuropsychiatric symptoms, prompting investigation into the role of the APOE gene in brain function among HCV-infected patients.
- A study of 100 HCV-infected patients with mild liver disease revealed that those carrying the APOE-ε4 allele showed lower instances of working memory impairments and attention deficits.
- These findings suggest that the APOE-ε4 allele may have a protective effect against cognitive issues in HCV-infected individuals, offering insights into potential mechanisms behind neuropsychiatric symptoms associated with the infection.
Background & Aims: We conducted an open-label, randomized, phase 3 trial to determine the efficacy and safety of sofosbuvir and ribavirin, with and without peginterferon-alfa, in treatment-experienced patients with cirrhosis and hepatitis C virus (HCV) genotype 2 infection and treatment-naïve or treatment-experienced patients with HCV genotype 3 infection.
Methods: The study was conducted at 80 sites in Europe, North America, Australia, and New Zealand Patients were randomly assigned (1:1:1) to groups given sofosbuvir and ribavirin for 16 weeks (n = 196); sofosbuvir and ribavirin for 24 weeks (n = 199); or sofosbuvir, peginterferon-alfa, and ribavirin for 12 weeks (n = 197). The primary end point was the percentage of patients with HCV RNA <15 IU/mL 12 weeks after stopping therapy (sustained virologic response [SVR12]).
Background & Aims: The efficacy and tolerability of faldaprevir, a potent hepatitis C virus (HCV) NS3/4A protease inhibitor, plus peginterferon (PegIFN) and ribavirin (RBV) was assessed in a double-blind, placebo-controlled phase 3 study of treatment-naïve patients with HCV genotype-1 infection.
Methods: Patients were randomly assigned (1:2:2) to PegIFN/RBV plus: placebo (arm 1, n = 132) for 24 weeks; faldaprevir (120 mg, once daily) for 12 or 24 weeks (arm 2, n = 259); or faldaprevir (240 mg, once daily) for 12 weeks (arm 3, n = 261). In arms 2 and 3, patients with early treatment success (HCV-RNA <25 IU/ml at week 4 and undetectable at week 8) stopped all treatment at week 24.