Hepatitis #C virus triggers #Golgi fragmentation and autophagy through the immunity-related GTPase M
http://m.pnas.org/content/114/17/E3462
Positive-stranded RNA viruses, such as hepatitis C virus (HCV), assemble their viral replication complexes by remodeling host intracellular membranes to a membranous web. The precise composition of these replication complexes and the detailed mechanisms by which they are formed are incompletely understood. Here we show that the human immunity-related GTPase M (IRGM), known to contribute to autophagy, plays a previously unrecognized role in this process.
We show that IRGM is localized at the Golgi apparatus and regulates the fragmentation of Golgi membranes in response to HCV infection, leading to colocalization of Golgi vesicles with replicating HCV. Our results show that IRGM controls phosphorylation of GBF1, a guanine nucleotide exchange factor for Arf-GTPases, which normally operates in Golgi membrane dynamics and vesicle coating in resting cells. We also find that HCV triggers IRGM-mediated phosphorylation of the early autophagy initiator ULK1, thereby providing mechanistic insight into the role of IRGM in HCV-mediated autophagy.
Collectively, our results identify IRGM as a key Golgi-situated regulator that links intracellular membrane remodeling by autophagy and Golgi fragmentation with viral replication
http://m.pnas.org/content/114/17/E3462
Positive-stranded RNA viruses, such as hepatitis C virus (HCV), assemble their viral replication complexes by remodeling host intracellular membranes to a membranous web. The precise composition of these replication complexes and the detailed mechanisms by which they are formed are incompletely understood. Here we show that the human immunity-related GTPase M (IRGM), known to contribute to autophagy, plays a previously unrecognized role in this process.
We show that IRGM is localized at the Golgi apparatus and regulates the fragmentation of Golgi membranes in response to HCV infection, leading to colocalization of Golgi vesicles with replicating HCV. Our results show that IRGM controls phosphorylation of GBF1, a guanine nucleotide exchange factor for Arf-GTPases, which normally operates in Golgi membrane dynamics and vesicle coating in resting cells. We also find that HCV triggers IRGM-mediated phosphorylation of the early autophagy initiator ULK1, thereby providing mechanistic insight into the role of IRGM in HCV-mediated autophagy.
Collectively, our results identify IRGM as a key Golgi-situated regulator that links intracellular membrane remodeling by autophagy and Golgi fragmentation with viral replication
Changes in #liver function and body composition by direct-acting antiviral therapy for hepatitis #C virus infection http://onlinelibrary.wiley.com/doi/10.1111/hepr.12999/full
Management of low skeletal #muscle mass (LSM) is a very important topic since LSM affects patient mortality in liver diseases. Changes in body composition are unexplored in chronic hepatitis C virus (HCV) patients, including those with liver cirrhosis, who receive direct-acting antiviral (DAA) therapy. Body composition measurements and liver function tests were performed before and after DAA therapy Serum albumin (Alb) levels were significantly increased at 48 weeks post DAA therapy, especially in patients with LSM. Skeletal muscle mass index (SMI) was significantly increased after DAA therapy (at 24 weeks and 48 weeks post DAA therapy) in patients with LSM (p<0.05). An increase in SMI was associated with an increase in body weight or a decrease in VFA.
Conclusions
We continuously measured body composition in HCV infected patients who received DAA therapy and found that skeletal muscle mass was significantly increased, associated with an elevation of serum Alb levels and/or body weight or reduction in VFA, but only in patients who presented with LSM before DAA therapy
Management of low skeletal #muscle mass (LSM) is a very important topic since LSM affects patient mortality in liver diseases. Changes in body composition are unexplored in chronic hepatitis C virus (HCV) patients, including those with liver cirrhosis, who receive direct-acting antiviral (DAA) therapy. Body composition measurements and liver function tests were performed before and after DAA therapy Serum albumin (Alb) levels were significantly increased at 48 weeks post DAA therapy, especially in patients with LSM. Skeletal muscle mass index (SMI) was significantly increased after DAA therapy (at 24 weeks and 48 weeks post DAA therapy) in patients with LSM (p<0.05). An increase in SMI was associated with an increase in body weight or a decrease in VFA.
Conclusions
We continuously measured body composition in HCV infected patients who received DAA therapy and found that skeletal muscle mass was significantly increased, associated with an elevation of serum Alb levels and/or body weight or reduction in VFA, but only in patients who presented with LSM before DAA therapy
Wiley
Changes in liver function and body composition by direct‐acting antiviral therapy for hepatitis C virus infection
Management of low skeletal muscle mass (LSM) is a very important topic as LSM affects patient mortality in liver diseases. Changes in body composition are unexplored in chronic hepatitis C virus (HCV)...
The risk of #hepatocellular carcinoma in cirrhotic patients with hepatitis #C and sustained viral response: role of the treatment regimen
http://www.journal-of-hepatology.eu/article/S0168-8278(17)32429-7/fulltext
857 patients met the study criteria, of whom 31.7% received an IFN-free regimen. Individuals receiving IFN-free therapy were more likely to be: older; of white ethnicity, Child-Turcotte-Pugh B/C vs. Child-Turcotte-Pugh A; thrombocytopenic; non-genotype 3; and treatment experienced. HCC occurrence was observed in 46 individuals during follow-up. In univariate analysis, IFN-free receipt was associated with a significantly increased risk of HCC (HR: 2.48; P=0.021). However after multivariate adjustment for baseline factors, no significant risk attributable to IFN-free therapy persisted (aHR: 1.15, P=0.744).
CONCLUSION
These findings suggest that the higher incidence of HCC following SVR with IFN-free therapy relates to baseline risk factors/patient selection, and not the use of IFN-free therapy per se
http://www.journal-of-hepatology.eu/article/S0168-8278(17)32429-7/fulltext
857 patients met the study criteria, of whom 31.7% received an IFN-free regimen. Individuals receiving IFN-free therapy were more likely to be: older; of white ethnicity, Child-Turcotte-Pugh B/C vs. Child-Turcotte-Pugh A; thrombocytopenic; non-genotype 3; and treatment experienced. HCC occurrence was observed in 46 individuals during follow-up. In univariate analysis, IFN-free receipt was associated with a significantly increased risk of HCC (HR: 2.48; P=0.021). However after multivariate adjustment for baseline factors, no significant risk attributable to IFN-free therapy persisted (aHR: 1.15, P=0.744).
CONCLUSION
These findings suggest that the higher incidence of HCC following SVR with IFN-free therapy relates to baseline risk factors/patient selection, and not the use of IFN-free therapy per se
Effectiveness of #ravidasvir plus #sofosbuvir in interferon-naïve and treated patients with chronic hepatitis #C genotype-4
http://www.journal-of-hepatology.eu/article/S0168-8278(17)32286-9/fulltext
•Ravidasvir is a new NS5A inhibitor for HCV.
•Sofosbuvir + Ravidasvir with or without RBV has achieved very high SVR rates.
•Results are comparable for both patients with and without cirrhosis.
•Serious adverse events were noticed in very few treated patients.
A total of 298 patients were enrolled: 149 in Group 1, 79 in Group 2 and 70 in Group 3. SVR12 was achieved in 95.3% of all patients who started the study, including 98% of patients without cirrhosis and 91% of patients with cirrhosis, whether treatment-naïve or interferon-experienced. Ribavirin intake and history of previous interferon therapy did not affect SVR12 rates. No virologic breakthroughs were observed and the study treatment was well tolerated.
Conclusions
Treatment with ravidasvir plus sofosbuvir, with or without ribavirin, was well tolerated and associated with high sustained virologic response rate for HCV-GT4 infected patients with and without cirrhosis, regardless of previous interferon-based treatments
http://www.journal-of-hepatology.eu/article/S0168-8278(17)32286-9/fulltext
•Ravidasvir is a new NS5A inhibitor for HCV.
•Sofosbuvir + Ravidasvir with or without RBV has achieved very high SVR rates.
•Results are comparable for both patients with and without cirrhosis.
•Serious adverse events were noticed in very few treated patients.
A total of 298 patients were enrolled: 149 in Group 1, 79 in Group 2 and 70 in Group 3. SVR12 was achieved in 95.3% of all patients who started the study, including 98% of patients without cirrhosis and 91% of patients with cirrhosis, whether treatment-naïve or interferon-experienced. Ribavirin intake and history of previous interferon therapy did not affect SVR12 rates. No virologic breakthroughs were observed and the study treatment was well tolerated.
Conclusions
Treatment with ravidasvir plus sofosbuvir, with or without ribavirin, was well tolerated and associated with high sustained virologic response rate for HCV-GT4 infected patients with and without cirrhosis, regardless of previous interferon-based treatments
Sofosbuvir and #velpatasvir for hepatitis #C virus infection in people with recent injection #drug use (SIMPLIFY): an open-label, single-arm, phase 4, multicentre trial
http://www.thelancet.com/journals/langas/article/PIIS2468-1253(17)30404-1/fulltext
Between March 29, and Oct 31, 2016, we enrolled 103 participants; 29 (28%) of whom were female, nine (9%) had cirrhosis, 36 (35%) had HCV genotype 1, five (5%) had genotype 2, 60 (58%) had genotype 3, and two (2%) had genotype 4. 61 (59%) participants were receiving opioid substitution therapy during the study, 76 (74%) injected in the past month, and 27 (26%) injected at least daily in the past month. 100 (97%) of 103 participants completed treatment; two people were lost to follow-up and one person died from an overdose. There were no virological failures. 97 (94%, 95% CI 88–98) of 103 people achieved SVR12. Three participants with an end-of-treatment response did not have a SVR; two were lost to follow-up and one had reinfection. Drug use before and during treatment did not affect SVR12. Treatment-related adverse events were seen in 48 (47%) patients (one grade 3, no grade 4). Seven (7%) patients had at least one serious adverse event; only one such event (rhabdomyolysis, resolved) was possibly related to the therapy. One case of HCV reinfection was observed.
Interpretation
HCV treatment should be offered to PWID, irrespective of ongoing drug use. Recent injection drug use should not be used as a reason to withhold reimbursement of HCV therapy
http://www.thelancet.com/journals/langas/article/PIIS2468-1253(17)30404-1/fulltext
Between March 29, and Oct 31, 2016, we enrolled 103 participants; 29 (28%) of whom were female, nine (9%) had cirrhosis, 36 (35%) had HCV genotype 1, five (5%) had genotype 2, 60 (58%) had genotype 3, and two (2%) had genotype 4. 61 (59%) participants were receiving opioid substitution therapy during the study, 76 (74%) injected in the past month, and 27 (26%) injected at least daily in the past month. 100 (97%) of 103 participants completed treatment; two people were lost to follow-up and one person died from an overdose. There were no virological failures. 97 (94%, 95% CI 88–98) of 103 people achieved SVR12. Three participants with an end-of-treatment response did not have a SVR; two were lost to follow-up and one had reinfection. Drug use before and during treatment did not affect SVR12. Treatment-related adverse events were seen in 48 (47%) patients (one grade 3, no grade 4). Seven (7%) patients had at least one serious adverse event; only one such event (rhabdomyolysis, resolved) was possibly related to the therapy. One case of HCV reinfection was observed.
Interpretation
HCV treatment should be offered to PWID, irrespective of ongoing drug use. Recent injection drug use should not be used as a reason to withhold reimbursement of HCV therapy
Remission of #Psoriasis After Treatment of Chronic Hepatitis #C Virus Infection With Direct-Acting Antivirals
http://annals.org/aim/article-abstract/2669850/remission-psoriasis-after-treatment-chronic-hepatitis-c-virus-infection-direct
Background: Hepatitis C virus (HCV) infection is a systemic disease with extrahepatic manifestations that include skin involvement, such as mixed cryoglobulinemia, lichen planus, and porphyria cutanea tarda (1). Some studies also suggest an association between HCV infection and psoriasis (2).
Objective: To provide additional information about the possible association between HCV infection and psoriasis.
http://annals.org/aim/article-abstract/2669850/remission-psoriasis-after-treatment-chronic-hepatitis-c-virus-infection-direct
Background: Hepatitis C virus (HCV) infection is a systemic disease with extrahepatic manifestations that include skin involvement, such as mixed cryoglobulinemia, lichen planus, and porphyria cutanea tarda (1). Some studies also suggest an association between HCV infection and psoriasis (2).
Objective: To provide additional information about the possible association between HCV infection and psoriasis.
Hepatitis #B virus reactivation during direct-acting antiviral therapy for hepatitis #C: a systematic review and meta-analysis
http://www.thelancet.com/journals/langas/article/PIIS2468-1253(18)30002-5/fulltext
Direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection might pose a risk for hepatitis B virus (HBV) reactivation in patients coinfected with chronic or resolved HBV infection. The need for HBV antiviral prophylaxis during DAA treatment remains controversial. The pooled proportion of patients who had HBV reactivation was 24% (95% CI 19–30) in patients with chronic HBV infection and 1·4% (0·8–2·4) in those with resolved HBV infection. In patients with chronic HBV infection, the pooled proportion of patients with HBV-reactivation-related hepatitis was 9% (95% CI 5–16) and the relative risk (RR) of HBV-reactivation-related hepatitis was significantly lower in patients with HBV DNA below the lower limit of quantification at baseline than in those with quantifiable HBV DNA (RR 0·17, 95% CI 0·06–0·50; p=0·0011). Three major clinical events related to HBV reactivation in patients with chronic HBV infection were reported (one patient had liver decompensation and two had liver failure, one of whom required liver transplantation). In patients with resolved HBV infection, no HBV-reactivation-related hepatitis was reported.
Interpretation
HBV reactivation occurs frequently in patients with chronic HBV and HCV coinfection receiving DAA therapy but is rare among patients with resolved HBV infection. Use of antiviral prophylaxis might be warranted in patients who test positive for hepatitis B surface antigen (HBsAg), particularly those with quantifiable HBV DNA
http://www.thelancet.com/journals/langas/article/PIIS2468-1253(18)30002-5/fulltext
Direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection might pose a risk for hepatitis B virus (HBV) reactivation in patients coinfected with chronic or resolved HBV infection. The need for HBV antiviral prophylaxis during DAA treatment remains controversial. The pooled proportion of patients who had HBV reactivation was 24% (95% CI 19–30) in patients with chronic HBV infection and 1·4% (0·8–2·4) in those with resolved HBV infection. In patients with chronic HBV infection, the pooled proportion of patients with HBV-reactivation-related hepatitis was 9% (95% CI 5–16) and the relative risk (RR) of HBV-reactivation-related hepatitis was significantly lower in patients with HBV DNA below the lower limit of quantification at baseline than in those with quantifiable HBV DNA (RR 0·17, 95% CI 0·06–0·50; p=0·0011). Three major clinical events related to HBV reactivation in patients with chronic HBV infection were reported (one patient had liver decompensation and two had liver failure, one of whom required liver transplantation). In patients with resolved HBV infection, no HBV-reactivation-related hepatitis was reported.
Interpretation
HBV reactivation occurs frequently in patients with chronic HBV and HCV coinfection receiving DAA therapy but is rare among patients with resolved HBV infection. Use of antiviral prophylaxis might be warranted in patients who test positive for hepatitis B surface antigen (HBsAg), particularly those with quantifiable HBV DNA
Population level outcomes and #cost-effectiveness of expanding the recommendation for age-based hepatitis #C testing in the United States
https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciy098/4840186
Expanded age-based testing strategies increased U.S. population lifetime case identification and cure rates. Greatest increases were observed in the ≥18 strategy. Compared to the SOC, this strategy resulted in an estimated 256,000 additional infected persons identified and 280,000 additional cures at the lowest cost per QALY gained (ICER = $28,000/QALY).
Conclusions
In addition to risk-based testing, one-time HCV testing of persons 18 and older appears to be cost-effective, leads to improved clinical outcomes and identifies more persons with HCV than the current birth cohort recommendations. These findings could be considered for future recommendation revisions
https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciy098/4840186
Expanded age-based testing strategies increased U.S. population lifetime case identification and cure rates. Greatest increases were observed in the ≥18 strategy. Compared to the SOC, this strategy resulted in an estimated 256,000 additional infected persons identified and 280,000 additional cures at the lowest cost per QALY gained (ICER = $28,000/QALY).
Conclusions
In addition to risk-based testing, one-time HCV testing of persons 18 and older appears to be cost-effective, leads to improved clinical outcomes and identifies more persons with HCV than the current birth cohort recommendations. These findings could be considered for future recommendation revisions
Direct-Acting Antiviral Prophylaxis in Kidney #Transplantation From Hepatitis #C Virus–Infected Donors to Noninfected Recipients: An Open-Label Nonrandomized Trial
http://annals.org/aim/article-abstract/2674335/direct-acting-antiviral-prophylaxis-kidney-transplantation-from-hepatitis-c-virus
Transplantation of kidneys from deceased donors aged 13 to 50 years with positive HCV RNA and HCV antibody test results. All recipients received a dose of grazoprevir (GZR), 100 mg, and elbasvir (EBR), 50 mg, immediately before transplantation. Recipients of kidneys from donors with genotype 1 infection continued receiving GZR–EBR for 12 weeks after transplantation; those receiving organs from donors with genotype 2 or 3 infection had sofosbuvir, 400 mg, added to GZR–EBR for 12 weeks of triple therapy
Among 10 HCV D+/R− transplant recipients, no treatment-related adverse events occurred, and HCV RNA was not detected in any recipient 12 weeks after treatment.
Pre- and posttransplantation HCV treatment was safe and prevented chronic HCV infection in HCV D+/R– kidney transplant recipients. If confirmed in larger studies, this strategy should markedly expand organ options and reduce mortality for kidney transplant candidates without HCV infection
http://annals.org/aim/article-abstract/2674335/direct-acting-antiviral-prophylaxis-kidney-transplantation-from-hepatitis-c-virus
Transplantation of kidneys from deceased donors aged 13 to 50 years with positive HCV RNA and HCV antibody test results. All recipients received a dose of grazoprevir (GZR), 100 mg, and elbasvir (EBR), 50 mg, immediately before transplantation. Recipients of kidneys from donors with genotype 1 infection continued receiving GZR–EBR for 12 weeks after transplantation; those receiving organs from donors with genotype 2 or 3 infection had sofosbuvir, 400 mg, added to GZR–EBR for 12 weeks of triple therapy
Among 10 HCV D+/R− transplant recipients, no treatment-related adverse events occurred, and HCV RNA was not detected in any recipient 12 weeks after treatment.
Pre- and posttransplantation HCV treatment was safe and prevented chronic HCV infection in HCV D+/R– kidney transplant recipients. If confirmed in larger studies, this strategy should markedly expand organ options and reduce mortality for kidney transplant candidates without HCV infection
The Role of Aging, Drug Dependence, and Hepatitis #C Comorbidity in #Alcoholism #Cortical Compromise
https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2674964
Given the high drug-dependence incidence (54.5%) in the alcoholism group, analysis examined drug subgroups (cocaine, cannabis, amphetamines, opiates) compared with drug-dependence–free alcoholism and control groups. Although the alcohol plus cocaine (t = −2.310, P = .04) and alcohol plus opiate (t = −2.424, P = .04) groups had smaller frontal volumes than the drug-dependence–free alcoholism group, deficits in precentral (t = −2.575, P = .01), supplementary motor (t = −2.532, P = .01), and medial (t = −2.800, P = .01) volumes endured in drug-dependence–free participants with alcoholism compared with control participants. Those with HCV infection had greater deficits than those without HCV infection in frontal (t = 3.468, P = .01), precentral (t = 2.513, P = .03), superior (t = 2.533, P = .03), and orbital (t = 2.506, P = .03) volumes, yet total frontal (t = 2.660, P = .02), insular (t = 3.526, P = .003), parietal (t = 2.414, P = .03), temporal (t = 3.221, P = .005), and precentral (t = 3.180, P = .01) volume deficits persisted in the uninfected participants with alcoholism compared with control participants with known HCV status.
Conclusions and Relevance Drug dependence and HCV infection compounded deleterious effects of alcohol dependence on frontal cortical volumes but could not account for the frontally distributed volume deficits in the drug-free participants with alcoholism. We speculate that age-alcohol interactions notable in frontal cortex put older adults at heightened risk for age-associated neurocompromise even if alcohol misuse is initiated later in life
https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2674964
Given the high drug-dependence incidence (54.5%) in the alcoholism group, analysis examined drug subgroups (cocaine, cannabis, amphetamines, opiates) compared with drug-dependence–free alcoholism and control groups. Although the alcohol plus cocaine (t = −2.310, P = .04) and alcohol plus opiate (t = −2.424, P = .04) groups had smaller frontal volumes than the drug-dependence–free alcoholism group, deficits in precentral (t = −2.575, P = .01), supplementary motor (t = −2.532, P = .01), and medial (t = −2.800, P = .01) volumes endured in drug-dependence–free participants with alcoholism compared with control participants. Those with HCV infection had greater deficits than those without HCV infection in frontal (t = 3.468, P = .01), precentral (t = 2.513, P = .03), superior (t = 2.533, P = .03), and orbital (t = 2.506, P = .03) volumes, yet total frontal (t = 2.660, P = .02), insular (t = 3.526, P = .003), parietal (t = 2.414, P = .03), temporal (t = 3.221, P = .005), and precentral (t = 3.180, P = .01) volume deficits persisted in the uninfected participants with alcoholism compared with control participants with known HCV status.
Conclusions and Relevance Drug dependence and HCV infection compounded deleterious effects of alcohol dependence on frontal cortical volumes but could not account for the frontally distributed volume deficits in the drug-free participants with alcoholism. We speculate that age-alcohol interactions notable in frontal cortex put older adults at heightened risk for age-associated neurocompromise even if alcohol misuse is initiated later in life
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Identification of a Novel Hepatitis #C Virus Genotype From Punjab, India: Expanding Classification of Hepatitis C Virus Into 8 #Genotypes
https://academic.oup.com/jid/advance-article-abstract/doi/10.1093/infdis/jiy401/5047409?redirectedFrom=fulltext
Four patients, previously classified as GT5 by LiPA or Abbott RealTime polymerase chain reaction assays, were identified as infected with a novel HCV GT. This novel HCV GT, GT8, is genetically distinct from previously identified HCV GT1–7 with >30% nucleotide sequence divergence to the established HCV subtypes. All 4 patients were originally from Punjab, India, but now reside in Canada and are epidemiologically unlinked. Despite presence of baseline resistance-associated substitutions within the GT8 virus of all 4 patients (NS3: V36L, Q80K/R; NS5A: Q30S, Y93S), all patients achieved a sustained virologic response; 2 treated with sofosbuvir/velpatasvir/voxilaprevir for 8 weeks, 1 with sofosbuvir/ledipasvir plus ribavirin for 24 weeks and 1 with sofosbuvir plus daclatasvir for 12 weeks.
Conclusions
The discovery of a novel HCV GT8 confirms the circulation of this newly identified lineage in the human population.
Identification of a Novel Hepatitis #C Virus Genotype From Punjab, India: Expanding Classification of Hepatitis C Virus Into 8 #Genotypes
https://academic.oup.com/jid/advance-article-abstract/doi/10.1093/infdis/jiy401/5047409?redirectedFrom=fulltext
Four patients, previously classified as GT5 by LiPA or Abbott RealTime polymerase chain reaction assays, were identified as infected with a novel HCV GT. This novel HCV GT, GT8, is genetically distinct from previously identified HCV GT1–7 with >30% nucleotide sequence divergence to the established HCV subtypes. All 4 patients were originally from Punjab, India, but now reside in Canada and are epidemiologically unlinked. Despite presence of baseline resistance-associated substitutions within the GT8 virus of all 4 patients (NS3: V36L, Q80K/R; NS5A: Q30S, Y93S), all patients achieved a sustained virologic response; 2 treated with sofosbuvir/velpatasvir/voxilaprevir for 8 weeks, 1 with sofosbuvir/ledipasvir plus ribavirin for 24 weeks and 1 with sofosbuvir plus daclatasvir for 12 weeks.
Conclusions
The discovery of a novel HCV GT8 confirms the circulation of this newly identified lineage in the human population.
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Approaches, Progress, and Challenges to Hepatitis #C #Vaccine Development
https://www.gastrojournal.org/article/S0016-5085(18)35035-2/fulltext?mobileUi=0
Risk factors for hepatitis C virus (HCV) infection vary, and there were an estimated 1.75 million new cases worldwide in 2015. The World Health Organization aims for a 90% reduction in new HCV infections by 2030. An HCV vaccine would prevent transmission, regardless of risk factors, and significantly reduce the global burden of HCV-associated disease. Barriers to development include virus diversity, limited models for testing vaccines, and our incomplete understanding of protective immune responses. Although highly effective vaccines could prevent infection altogether, immune responses that increase the rate of HCV clearance and prevent chronic infection may be sufficient to reduce disease burden.
Adjuvant envelope or core protein and virus-vectored non-structural antigen vaccines have been tested in healthy volunteers who are not at risk for HCV infection; viral vectors encoding non-structural proteins are the only vaccine strategy to be tested in at-risk individuals. Despite development challenges, a prophylactic vaccine is necessary for global control of HCV.
Approaches, Progress, and Challenges to Hepatitis #C #Vaccine Development
https://www.gastrojournal.org/article/S0016-5085(18)35035-2/fulltext?mobileUi=0
Risk factors for hepatitis C virus (HCV) infection vary, and there were an estimated 1.75 million new cases worldwide in 2015. The World Health Organization aims for a 90% reduction in new HCV infections by 2030. An HCV vaccine would prevent transmission, regardless of risk factors, and significantly reduce the global burden of HCV-associated disease. Barriers to development include virus diversity, limited models for testing vaccines, and our incomplete understanding of protective immune responses. Although highly effective vaccines could prevent infection altogether, immune responses that increase the rate of HCV clearance and prevent chronic infection may be sufficient to reduce disease burden.
Adjuvant envelope or core protein and virus-vectored non-structural antigen vaccines have been tested in healthy volunteers who are not at risk for HCV infection; viral vectors encoding non-structural proteins are the only vaccine strategy to be tested in at-risk individuals. Despite development challenges, a prophylactic vaccine is necessary for global control of HCV.
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#C-Reactive Protein Testing to Guide Antibiotic Prescribing for #COPD Exacerbations
https://www.nejm.org/doi/full/10.1056/NEJMoa1803185
Point-of-care testing of C-reactive protein (CRP) may be a way to reduce unnecessary use of antibiotics without harming patients who have acute exacerbations of chronic obstructive pulmonary disease (COPD).
A lower percentage of patients in the CRP-guided group than in the usual-care group received an antibiotic prescription at the initial consultation (47.7% vs. 69.7%, for a difference of 22.0 percentage points; adjusted odds ratio, 0.31; 95% CI, 0.21 to 0.45) and during the first 4 weeks of follow-up (59.1% vs. 79.7%, for a difference of 20.6 percentage points; adjusted odds ratio, 0.30; 95% CI, 0.20 to 0.46). Two patients in the usual-care group died within 4 weeks after randomization from causes considered by the investigators to be unrelated to trial participation.
CONCLUSIONS
CRP-guided prescribing of antibiotics for exacerbations of COPD in primary care clinics resulted in a lower percentage of patients who reported antibiotic use and who received antibiotic prescriptions from clinicians, with no evidence of harm.
#C-Reactive Protein Testing to Guide Antibiotic Prescribing for #COPD Exacerbations
https://www.nejm.org/doi/full/10.1056/NEJMoa1803185
Point-of-care testing of C-reactive protein (CRP) may be a way to reduce unnecessary use of antibiotics without harming patients who have acute exacerbations of chronic obstructive pulmonary disease (COPD).
A lower percentage of patients in the CRP-guided group than in the usual-care group received an antibiotic prescription at the initial consultation (47.7% vs. 69.7%, for a difference of 22.0 percentage points; adjusted odds ratio, 0.31; 95% CI, 0.21 to 0.45) and during the first 4 weeks of follow-up (59.1% vs. 79.7%, for a difference of 20.6 percentage points; adjusted odds ratio, 0.30; 95% CI, 0.20 to 0.46). Two patients in the usual-care group died within 4 weeks after randomization from causes considered by the investigators to be unrelated to trial participation.
CONCLUSIONS
CRP-guided prescribing of antibiotics for exacerbations of COPD in primary care clinics resulted in a lower percentage of patients who reported antibiotic use and who received antibiotic prescriptions from clinicians, with no evidence of harm.
The New England Journal of Medicine
C-Reactive Protein Testing to Guide Antibiotic Prescribing for COPD Exacerbations | NEJM
Point-of-care testing of C-reactive protein (CRP) may be a way to reduce unnecessary
use of antibiotics without harming patients who have acute exacerbations of chronic
obstructive pulmonary diseas...
use of antibiotics without harming patients who have acute exacerbations of chronic
obstructive pulmonary diseas...
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Draft Recommendation Statement
Hepatitis #C Virus Infection in Adolescents and Adults: #screening
https://www.uspreventiveservicestaskforce.org/Page/Document/draft-recommendation-statement/hepatitis-c-screening1
There is adequate evidence that HCV testing (screening for the anti-HCV antibody followed by confirmation of active infection by HCV RNA for persons who test positive) accurately detects HCV infection.
There is adequate evidence for one-time testing in all adults and periodic testing in persons at continued risk of new HCV infection.
There is inadequate evidence on the timing of repeat testing..
The USPSTF concludes with moderate certainty that screening for HCV infection in adults ages 18 to 79 years has substantial net benefit.
Draft Recommendation Statement
Hepatitis #C Virus Infection in Adolescents and Adults: #screening
https://www.uspreventiveservicestaskforce.org/Page/Document/draft-recommendation-statement/hepatitis-c-screening1
There is adequate evidence that HCV testing (screening for the anti-HCV antibody followed by confirmation of active infection by HCV RNA for persons who test positive) accurately detects HCV infection.
There is adequate evidence for one-time testing in all adults and periodic testing in persons at continued risk of new HCV infection.
There is inadequate evidence on the timing of repeat testing..
The USPSTF concludes with moderate certainty that screening for HCV infection in adults ages 18 to 79 years has substantial net benefit.
www.uspreventiveservicestaskforce.org
Draft Recommendation Statement: Hepatitis C Virus Infection in Adolescents and Adults: Screening - US Preventive Services Task…
This is a webpage on the US Preventive Services Task Force USPSTF site
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#C-reactive protein mediates the association between leisure-time physical #activity and #lung function in middle-aged and older adults
Although previous studies have reported the benefits of physical activity (PA) to lung function in middle-aged and older adults, the biological mechanisms are still unclear..
..Multiple linear regression models suggested that higher PA was associated with lower levels of CRP (β = − 0.048, P = 0.002 for moderate PA; β = − 0.108, P < 0.001 for high PA). CRP negatively correlated with FEV1 (β = − 0.180, P < 0.001) and FVC (β = − 0.181, P < 0.001). Higher levels of PA were associated with better FEV1 (β = 0.085, P < 0.001 for moderate PA; β = 0.150, P < 0.001 for high PA) and FVC (β = 0.131, P < 0.001 for moderate PA; β = 0.211, P < 0.001 for high PA)..
The association between PA and lung function is mediated by CRP, suggesting that this association may be partially explained by an inflammation-related biological mechanism. This finding highlights the possible importance of PA in systemic inflammation and lung function, thus, middle-aged and older adults should be encouraged to enhance PA levels.
https://bit.ly/2Re1GX9
#C-reactive protein mediates the association between leisure-time physical #activity and #lung function in middle-aged and older adults
Although previous studies have reported the benefits of physical activity (PA) to lung function in middle-aged and older adults, the biological mechanisms are still unclear..
..Multiple linear regression models suggested that higher PA was associated with lower levels of CRP (β = − 0.048, P = 0.002 for moderate PA; β = − 0.108, P < 0.001 for high PA). CRP negatively correlated with FEV1 (β = − 0.180, P < 0.001) and FVC (β = − 0.181, P < 0.001). Higher levels of PA were associated with better FEV1 (β = 0.085, P < 0.001 for moderate PA; β = 0.150, P < 0.001 for high PA) and FVC (β = 0.131, P < 0.001 for moderate PA; β = 0.211, P < 0.001 for high PA)..
The association between PA and lung function is mediated by CRP, suggesting that this association may be partially explained by an inflammation-related biological mechanism. This finding highlights the possible importance of PA in systemic inflammation and lung function, thus, middle-aged and older adults should be encouraged to enhance PA levels.
https://bit.ly/2Re1GX9
BMC Public Health
C-reactive protein mediates the association between leisure-time physical activity and lung function in middle-aged and older adults
Although previous studies have reported the benefits of physical activity (PA) to lung function in middle-aged and older adults, the biological mechanisms are still unclear. This study aimed to assess the extent to which C-reactive protein (CRP) mediates…
The Efficacy and Safety of Vitamin #C for Iron Supplementation in Adult Patients With Iron Deficiency #Anemia
https://2medical.news/2020/11/05/the-efficacy-and-safety-of-vitamin-c-for-iron-supplementation-in-adult-patients-with-iron-deficiency-anemia/
It remains uncertain whether vitamin C routinely used with oral iron supplements is essential for patients with iron deficiency anemia (IDA).. ..The primary outcome was the change in hemoglobin level from baseline to 2 weeks of treatment, and an equivalence margin of 1 g/dL in hemoglobin was chosen for the demonstration of comparable efficacy. Secondary outcomes included the change in the reticulocyte percentage after 2 …
https://2medical.news/2020/11/05/the-efficacy-and-safety-of-vitamin-c-for-iron-supplementation-in-adult-patients-with-iron-deficiency-anemia/
It remains uncertain whether vitamin C routinely used with oral iron supplements is essential for patients with iron deficiency anemia (IDA).. ..The primary outcome was the change in hemoglobin level from baseline to 2 weeks of treatment, and an equivalence margin of 1 g/dL in hemoglobin was chosen for the demonstration of comparable efficacy. Secondary outcomes included the change in the reticulocyte percentage after 2 …
The changing characteristics of patients infected with chronic hepatitis #C virus from 2014 to 2019: Real-world data from the German #Hepatitis C-Registry (DHC-R)
https://2medical.news/2021/08/07/the-changing-characteristics-of-patients-infected-with-chronic-hepatitis-c-virus-from-2014-to-2019-real-world-data-from-the-german-hepatitis-c-registry-dhc-r/
https://2medical.news/2021/08/07/the-changing-characteristics-of-patients-infected-with-chronic-hepatitis-c-virus-from-2014-to-2019-real-world-data-from-the-german-hepatitis-c-registry-dhc-r/
2Medical.News
The changing characteristics of patients infected with chronic hepatitis #C virus from 2014 to 2019: Real-world data from the German…
The number of patients diagnosed with hepatitis C virus (HCV) is markedly higher than the number initiating treatment indicating gaps in the care cascade, likely centered around reaching at-risk po…
Vitamin #C and scar strength: analysis of a historical trial and implications for #collagen-related pathologies
https://2medical.news/2021/09/07/vitamin-c-and-scar-strength-analysis-of-a-historical-trial-and-implications-for-collagen-related-pathologies/
https://2medical.news/2021/09/07/vitamin-c-and-scar-strength-analysis-of-a-historical-trial-and-implications-for-collagen-related-pathologies/
2Medical.News
Vitamin #C and scar strength: analysis of a historical trial and implications for #collagen-related pathologies
A double-blind controlled trial initiated in 1944 has led to the common narrative that a 10-mg daily vitamin C intake is adequate to prevent and treat impaired wound healing, and by inference, othe…
Hepatitis #C Virus Reactivation Following #COVID-19 Vaccination – A Case Report
https://2medical.news/2021/10/18/hepatitis-c-virus-reactivation-following-covid-19-vaccination-a-case-report/
https://2medical.news/2021/10/18/hepatitis-c-virus-reactivation-following-covid-19-vaccination-a-case-report/
2Medical.News
Hepatitis #C Virus Reactivation Following #COVID-19 Vaccination – A Case Report
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection impacted morbidity and mortality during the pandemic of 2020–2021. A number of anti-COVID-19 vaccines have been developed with…
Enhancing Vision: Exploring the Link Between Vitamin #C and Reduced #Cataract Risks – A Physician’s Perspective
https://2medical.news/2023/11/28/enhancing-vision-exploring-the-link-between-vitamin-c-and-reduced-cataract-risks-a-physicians-perspective/
https://2medical.news/2023/11/28/enhancing-vision-exploring-the-link-between-vitamin-c-and-reduced-cataract-risks-a-physicians-perspective/
2Medical.News
Enhancing Vision: Exploring the Link Between Vitamin #C and Reduced #Cataract Risks – A Physician’s Perspective
As physicians continually explore avenues for promoting overall health, recent research has shed light on a potential ally in the fight against cataracts – Vitamin C. This essential nutrient, long …