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Medicina (Kaunas, Lithuania) Aug 2022: Probiotic supplementation can prevent and alleviate gastrointestinal and respiratory tract infections in healthy individuals. Markers released from the site of... (Review)
Review
: Probiotic supplementation can prevent and alleviate gastrointestinal and respiratory tract infections in healthy individuals. Markers released from the site of inflammation are involved in the response to infection or tissue injury. Therefore, we measured the pre-exercise and postexercise levels of inflammation-related markers-tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, IL-10, interferon (IFN)-γ, salivary immunoglobulin A (IgA), IL-1β, IL-2, IL-4, and C-reactive protein (CRP)-in probiotic versus placebo groups to investigate the effects of probiotics on these markers in athletes. Probiotics contained multiple species (e.g., , etc.). : We performed a systematic search for studies published until May 2022 and included nine randomized clinical trials. Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline. Fixed-effects meta-analyses and sensitivity analyses were performed. Subgroup analyses were conducted on the basis of the period of probiotic intervention and timing of postassessment blood sampling. : The levels of IFN-γ and salivary IgA exhibited a significant positive change, whereas those of TNF-α and IL-10 demonstrated a negative change in the probiotic group. The subgroup analysis revealed that the probiotic group exhibited significant negative changes in TNF-α and IL-10 levels in the shorter intervention period. For the subgroup based on the timing of postassessment blood sampling, the subgroup whose blood sample collection was delayed to at least the next day of exercise exhibited significant negative changes in their TNF-α and IL-10 levels. The subgroups whose blood samples were collected immediately after exercise demonstrated negative changes in their TNF-α, IL-8, and IL-10 levels. : Probiotic supplementation resulted in significant positive changes in the IFN-γ and salivary IgA levels and negative changes in the IL-10 and TNF-α levels. No significant changes in the IL-1β, IL-2, IL-4, IL-6, IL-8, or CRP levels were observed after probiotic use in athletes.
Topics: Athletes; Biomarkers; C-Reactive Protein; Humans; Immunoglobulin A; Inflammation; Interferon-gamma; Interleukin-10; Interleukin-2; Interleukin-4; Interleukin-6; Interleukin-8; Probiotics; Randomized Controlled Trials as Topic; Tumor Necrosis Factor-alpha
PubMed: 36143865
DOI: 10.3390/medicina58091188 -
Jornal de Pediatria 2019Human immunodeficiency virus infection can result in the early impairment of anthropometric indicators in children and adolescents. However, combined antiretroviral...
OBJECTIVES
Human immunodeficiency virus infection can result in the early impairment of anthropometric indicators in children and adolescents. However, combined antiretroviral therapy has improved, in addition to the immune response and viral infection, the weight and height development in infected individuals. Therefore, the objective was to evaluate the effect of combined antiretroviral on the growth development of human immunodeficiency virus infected children and adolescents.
SOURCE OF DATA
A systematic review was performed. In the study, the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) strategy was used as the eligibility criterion. The MEDLINE-PubMed and LILACS databases were searched using these descriptors: HIV, children, growth, antiretroviral therapy. The objective was defined by the population, intervention, comparison/control, and outcome (PICO) technique. Inclusion and exclusion criteria were applied for study selection.
SYNTHESIS OF DATA
Of the 549 studies indexed in MEDLINE-PubMed and LILACS, 73 were read in full, and 44 were included in the review (33 showed a positive impact of combined antiretroviral therapy on weight/height development, ten on weight gain, and one on height gain in children and adolescents infected with human immunodeficiency virus). However, the increase in growth was not enough to normalize the height of infected children when compared to children of the same age and gender without human immunodeficiency virus infection.
CONCLUSIONS
Combined antiretroviral therapy, which is known to play a role in the improvement of viral and immunological markers, may influence in the weight and height development in children infected with human immunodeficiency virus. The earlier the infection diagnosis and, concomitantly, of malnutrition and the start of combined antiretroviral therapy, the lower the growth impairment when compared to healthy children.
Topics: Adolescent; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Body Height; Body Weight; Child; Child Development; Child, Preschool; Growth; HIV Infections; Humans; Infant; Infant, Newborn; Young Adult
PubMed: 29660296
DOI: 10.1016/j.jped.2018.02.006 -
Alimentary Pharmacology & Therapeutics Mar 2014Interferon lambda 3 (IFN-λ3) polymorphisms are the strongest genetic predictor of outcome of hepatitis C virus infection and of response to Pegylated interferon... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Interferon lambda 3 (IFN-λ3) polymorphisms are the strongest genetic predictor of outcome of hepatitis C virus infection and of response to Pegylated interferon (PegIFN)-based therapy. Whether this holds true for hepatitis B virus (HBV) infection is matter of controversy.
AIM
To review the association between host genomics and spontaneous or interferon-induced clearance of HBV with specific reference to the recently identified interleukin 28B gene now renamed IFN-λ3.
METHODS
A literature search was performed on MEDLINE, EMBASE and Web of Science for English articles and abstracts using free text words and combinations of the following terms 'IL28B', 'IFN lambda', 'genomics', 'hepatitis B virus', 'interferon' 'GWAS', 'treatment', 'SNPs', 'HLA', 'polymorphisms'.
RESULTS
Genome-wide association studies convincingly demonstrated an association between SNPs in the HLA locus and spontaneous resolution of HBV infection in subgroups of Asian patients, yet no information is available for Caucasians. The preliminary observations of an association between IFN-λ3 SNP and virological and serological responses to IFN in both HBeAg-positive and -negative patients could not be replicated by subsequent studies. Yet, majority of studies performed so far suffer several limitations in terms of sample size, selection of the patients, endpoints of therapy, treatment strategies and duration of follow-up.
CONCLUSIONS
While host genetics is associated with an increased likelihood of spontaneous clearance of HBV among genotype B/C patients, the relationship between IFN-λ3 polymorphisms and response to IFN has not been confirmed. Further studies in large cohorts of homogeneous patients are required, before this genetic test can be recommended in clinical practice.
Topics: Antiviral Agents; Genetic Testing; Genome-Wide Association Study; Genotype; Hepatitis B; Hepatitis B e Antigens; Hepatitis B virus; Humans; Interferons; Interleukins; Polymorphism, Single Nucleotide
PubMed: 24461198
DOI: 10.1111/apt.12631 -
Health Technology Assessment... Oct 2014Optimal therapy for children with chronic hepatitis C is unclear. Two treatment regimens are currently licensed in children. (Review)
Review
The clinical effectiveness and cost-effectiveness of peginterferon alfa and ribavirin for the treatment of chronic hepatitis C in children and young people: a systematic review and economic evaluation.
BACKGROUND
Optimal therapy for children with chronic hepatitis C is unclear. Two treatment regimens are currently licensed in children.
OBJECTIVES
To assess the clinical effectiveness and cost-effectiveness of peginterferon alfa-2a (Pegasys®, Roche) and peginterferon alfa-2b [ViraferonPeg®, Merck Sharp & Dohme (MSD)] in combination with ribavirin (RBV), within their licensed indications, for the treatment of chronic hepatitis C virus (HCV) in children and young people aged 3-17 years.
DATA SOURCES
Twelve electronic bibliographic databases, including The Cochrane Library, MEDLINE and EMBASE, were searched from inception to November 2012. Bibliographies of retrieved papers, key hepatitis C websites and symposia and manufacturers' submissions to the National Institute for Health and Care Excellence were also searched, and clinical experts were contacted.
REVIEW METHODS
Systematic reviews of clinical effectiveness and cost-effectiveness were conducted, including studies of health-related quality of life (HRQoL), following standard guidelines to ensure methodological rigour. Clinical effectiveness studies were included if they were in children and young people aged 3-17 years with chronic compensated HCV of any severity, including those with human immunodeficiency virus co-infection and those who were treatment naive or had been previously treated. Eligible interventions were peginterferon alfa-2a or peginterferon alfa-2b, each in combination with RBV, compared against best supportive care (BSC) or against each other, and study designs were randomised controlled trials (RCTs) or non-RCTs, or uncontrolled cohort studies. Outcomes included sustained virological response (SVR) and adverse events. Previously published Markov state-transition economic models of chronic HCV in adults were adapted to estimate the cost-effectiveness of peginterferon alfa-2a and -2b (in combination with RBV), compared with BSC and with one another in children. The model extrapolated the impact of SVR on life expectancy, quality-adjusted life expectancy and lifetime costs. Uncertainty was explored through probabilistic and deterministic sensitivity analyses.
RESULTS
Seven studies [two peginterferon alfa-2a and RBV (Copegus®, Roche), and five peginterferon alfa-2b and RBV (Rebetol®, MSD)] were included in the review of clinical effectiveness. Six were single-arm cohort studies and one was a RCT for which only those data for a single arm met the inclusion criteria. Overall, the studies were relatively small and of generally poor quality. SVR rates ranged from 53% to 66% (peginterferon alfa-2a) and 29% to 75% (peginterferon alfa-2b) (49% to 65% if excluding two studies with very small sample sizes). Rates of non-response and relapse were variable and adverse events were generally mild. No studies of cost-effectiveness or HRQoL in children and young people met the inclusion criteria. HRQoL, utilities and costs of treatment were therefore taken from studies of adults with chronic HCV. From this model, peginterferon alfa (-2a or -2b) in combination with RBV was more effective and had lower lifetime costs than BSC. Peginterferon alfa-2a had slightly lower lifetime costs and higher quality-adjusted life-years than peginterferon alfa-2b; therefore, peginterferon alfa-2b was dominated by peginterferon alfa-2a. Results were robust to changes in the sensitivity analyses.
LIMITATIONS
There were few good quality studies and parameter data had to be taken from adult studies, which is a limitation of the work.
CONCLUSIONS
Treatment of children and young people with peginterferon (alfa-2a or -2b) and RBV may be an effective therapy. Results from the independent Markov model suggest that peginterferon (alfa-2a or -2b) in combination with RBV is cost-effective compared with BSC. However, the available evidence is of poor quality. Future research into the impact of these treatments on growth and quality of life in children and young people is recommended.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42012002743.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Adolescent; Antiviral Agents; Biomarkers; Child; Child Development; Child, Preschool; Clinical Trials as Topic; Cost-Benefit Analysis; Drug Therapy, Combination; Female; Genotype; Hepatitis C, Chronic; Humans; Interferon alpha-2; Interferon-alpha; Liver; Male; Markov Chains; Models, Econometric; Polyethylene Glycols; Quality of Life; Quality-Adjusted Life Years; RNA, Viral; Recombinant Proteins; Ribavirin; Viral Load
PubMed: 25350588
DOI: 10.3310/hta18650 -
Clinical Therapeutics Jun 2022Heavily treatment-experienced (HTE) people with multidrug-resistant HIV-1 have limited treatment options. Treatment with the first-in-class attachment inhibitor...
PURPOSE
Heavily treatment-experienced (HTE) people with multidrug-resistant HIV-1 have limited treatment options. Treatment with the first-in-class attachment inhibitor fostemsavir in addition to optimized background therapy (OBT) resulted in sustained virologic and immunologic responses in HTE participants throughout 96 weeks in the BRIGHTE trial. In the absence of long-term direct comparative evidence between fostemsavir-based and other antiretroviral regimens, this analysis indirectly compares efficacy and safety across relevant available trials, adjusting for demographic and baseline characteristics.
METHODS
A systematic literature review was conducted to identify trials with designs and populations comparable to BRIGHTE. Using matching-adjusted indirect comparison analyses, individual participant data from BRIGHTE were reweighted to create balanced populations across trials, and efficacy and safety outcomes were compared.
FINDINGS
Three comparator trials were identified, 2 of which reflected an optimized therapy without fostemsavir (OBT alone): TMB-301 (ibalizumab and OBT), BENCHMRK-1/-2 (OBT alone), and VIKING-3 (OBT alone). Compared with ibalizumab and OBT (N = 40), fostemsavir and OBT (unadjusted, N = 347; adjusted, N = 236) were associated with numerically higher nonsignificant odds of virologic suppression (odds ratio [OR] = 1.44; 95% CI, 0.74-2.80; P = 0.284) and a similar increase in CD4 cell count of approximately 65 cells/mm from baseline through week 24 (mean difference = 7.05 cells/mm; 95% CI, -60.88 to 74.98 cells/mm; P = 0.834). Compared with OBT from BENCHMRK-1/-2 (N = 237), fostemsavir and OBT (adjusted, N = 126) were associated with significantly higher odds of virologic suppression (OR = 3.26; 95% CI, 2.08-5.11; P < 0.001) and increased CD4 cell count (135.78 cells/mm; 95% CI, 91.93-179.63 cells/mm; P < 0.001) at week 96. Compared with OBT from VIKING-3 (N = 183), fostemsavir and OBT (adjusted, N = 78) were associated with numerically higher odds of virologic suppression (OR = 1.34; 95% CI, 0.78-2.30; P = 0.297) and a modest CD4 cell count increase (26.86 cells/mm; 95% CI, -10.79 to 64.52; P = 0.162) through week 48; however, differences were not significant. All-cause discontinuations and safety comparisons varied across studies.
IMPLICATIONS
Although matching-adjusted indirect comparison analyses have limitations, these results support the use of fostemsavir and OBT as an important treatment option in HTE people with multidrug-resistant HIV-1.
Topics: Anti-HIV Agents; HIV Infections; HIV-1; Humans; Organophosphates; Piperazines; Viral Load
PubMed: 35610081
DOI: 10.1016/j.clinthera.2022.04.007 -
BMC Infectious Diseases Jan 2015The goal of chronic hepatitis C treatment is to remove the virus to avoid progression of HCV-related disease. Sustained virologic response (SVR) is the most widely used... (Review)
Review
BACKGROUND
The goal of chronic hepatitis C treatment is to remove the virus to avoid progression of HCV-related disease. Sustained virologic response (SVR) is the most widely used efficacy endpoint in clinical studies of hepatitis C, and represents the eradication of HCV from the body. The aim of the current review was to examine the long-term clinical, economic and quality of life benefits associated with achieving SVR.
METHODS
A systematic literature review was performed using the PubMed, EMBASE and Cochrane library databases to identify articles examining the clinical, economic and quality of life benefits associated with SVR, published in English language from 2002-2013. For inclusion studies were required to enroll ≥100 patients and to report clinical endpoints including hepatocellular carcinoma, overall- or liver-related mortality, or progression of disease/complications (e.g. portal hypertension, esophageal varices). Review of economic studies on cost/cost-effectiveness of achieving SVR were focused on studies assessing boceprevir/telaprevir plus pegIFN and ribavirin as this represents the current standard of care in several jurisdictions worldwide. Quality of life evidence was required to use validated quality of life instruments and provide a quantitative analysis of the impact of SVR versus no treatment or treatment failure.
RESULTS
SVR is durable with late relapse rates over 4-5 year periods being in the range of 1-2%. Patients who achieve SVR frequently demonstrate some regression of fibrosis/cirrhosis and have a substantially reduced risk for hepatocellular carcinoma (relative risk [RR] 0.1-0.25), liver-related mortality (RR 0.03-0.2) and overall mortality (RR 0.1-0.3) in comparison with no treatment or treatment failure. In the 5 years post-treatment, medical costs for patients achieving SVR are 13-fold lower than patients not achieving SVR. Patients who achieve SVR also have health state utility values that are 0.05 to 0.31 higher than non-responders to treatment.
CONCLUSIONS
SVR represents the fundamental goal of antiviral treatment for patients infected with chronic HCV, so as to reduce risk of liver disease progression. Achievement of SVR has implications beyond those of clearing viral infection; it is associated with improved long-term clinical outcomes, economic benefits and improved health-related quality of life.
Topics: Antiviral Agents; Cost-Benefit Analysis; Global Health; Health Care Costs; Hepatitis C, Chronic; Humans; Quality of Life
PubMed: 25596623
DOI: 10.1186/s12879-015-0748-8 -
The Cochrane Database of Systematic... Sep 2012Death is common in systemic inflammatory response syndrome (SIRS) or sepsis-induced multisystem organ failure and it has been thought that antioxidants such as... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Death is common in systemic inflammatory response syndrome (SIRS) or sepsis-induced multisystem organ failure and it has been thought that antioxidants such as N-acetylcysteine could be beneficial.
OBJECTIVES
We assessed the clinical effectiveness of intravenous N-acetylcysteine for the treatment of patients with SIRS or sepsis.
SEARCH METHODS
We searched the following databases: Cochrane Central Register of Clinical Trials (CENTRAL) (The Cochrane Library 2011, Issue 12); MEDLINE (January 1950 to January 2012); EMBASE (January 1980 to January 2012); CINAHL (1982 to January 2012); the NHS Trusts Clinical Trials Register and Current Controlled Trials (www.controlled-trials.com); LILACS; KoreaMED; MEDCARIB; INDMED; PANTELEIMON; Ingenta; ISI Web of Knowledge and the National Trials Register to identify all relevant randomized controlled trials available for review.
SELECTION CRITERIA
We included only randomized controlled trials (RCTs) in the meta-analysis.
DATA COLLECTION AND ANALYSIS
We independently performed study selection, quality assessment and data extraction. We estimated risk ratios (RR) for dichotomous outcomes. We measured statistical heterogeneity using the I(2) statistic.
MAIN RESULTS
We included 41 fully published studies (2768 patients). Mortality was similar in the N-acetylcysteine group and the placebo group (RR 1.06, 95% CI 0.79 to 1.42; I(2) = 0%). Neither did N-acetylcysteine show any significant effect on length of stay, duration of mechanical ventilation or incidence of new organ failure. Early application of N-acetylcysteine to prevent the development of an oxidato-inflammatory response did not affect the outcome, nor did late application that is after 24 hours of developing symptoms. Late application was associated with cardiovascular instability.
AUTHORS' CONCLUSIONS
Overall, this meta-analysis puts doubt on the safety and utility of intravenous N-acetylcysteine as an adjuvant therapy in SIRS and sepsis. At best, N-acetylcysteine is ineffective in reducing mortality and complications in this patient population. At worst, it can be harmful, especially when administered later than 24 hours after the onset of symptoms, by causing cardiovascular depression. Unless future RCTs provide evidence of treatment effect, clinicians should not routinely use intravenous N-acetylcysteine in SIRS or sepsis and academics should not promote its use.
Topics: Acetylcysteine; Adult; Antioxidants; Humans; Injections, Intravenous; Randomized Controlled Trials as Topic; Sepsis; Systemic Inflammatory Response Syndrome; Treatment Outcome
PubMed: 22972094
DOI: 10.1002/14651858.CD006616.pub2 -
BMJ (Clinical Research Ed.) Apr 2014To describe the potential benefits and harms of oseltamivir by reviewing all clinical study reports (or similar document when no clinical study report exists) of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To describe the potential benefits and harms of oseltamivir by reviewing all clinical study reports (or similar document when no clinical study report exists) of randomised placebo controlled trials and regulatory comments ("regulatory information").
DESIGN
Systematic review of regulatory information.
DATA SOURCES
Clinical study reports, trial registries, electronic databases, regulatory archives, and correspondence with manufacturers.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Randomised placebo controlled trials on adults and children who had confirmed or suspected exposure to natural influenza.
MAIN OUTCOME MEASURES
Time to first alleviation of symptoms, influenza outcomes, complications, admissions to hospital, and adverse events in the intention to treat population.
RESULTS
From the European Medicines Agency and Roche, we obtained clinical study reports for 83 trials. We included 23 trials in stage 1 (reliability and completeness screen) and 20 in stage 2 (formal analysis). In treatment trials on adults, oseltamivir reduced the time to first alleviation of symptoms by 16.8 hours (95% confidence interval 8.4 to 25.1 hours, P<0.001). There was no effect in children with asthma, but there was an effect in otherwise healthy children (mean difference 29 hours, 95% confidence interval 12 to 47 hours, P=0.001). In treatment trials there was no difference in admissions to hospital in adults (risk difference 0.15%, 95% confidence interval -0.91% to 0.78%, P=0.84) and sparse data in children and for prophylaxis. In adult treatment trials, oseltamivir reduced investigator mediated unverified pneumonia (risk difference 1.00%, 0.22% to 1.49%; number needed to treat to benefit (NNTB) 100, 95% confidence interval 67 to 451). The effect was not statistically significant in the five trials that used a more detailed diagnostic form for "pneumonia," and no clinical study reports reported laboratory or diagnostic confirmation of "pneumonia." The effect on unverified pneumonia in children and for prophylaxis was not significant. There was no significant reduction in risk of unverified bronchitis, otitis media, sinusitis, or any complication classified as serious or that led to study withdrawal. 14 of 20 trials prompted participants to self report all secondary illnesses to an investigator. Oseltamivir in the treatment of adults increased the risk of nausea (risk difference 3.66%, 0.90% to 7.39%; number needed to treat to harm (NNTH) 28, 95% confidence interval 14 to 112) and vomiting (4.56%, 2.39% to 7.58%; 22, 14 to 42). In treatment of children, oseltamivir induced vomiting (5.34%, 1.75% to 10.29%; 19, 10 to 57). In prophylaxis trials, oseltamivir reduced symptomatic influenza in participants by 55% (3.05%, 1.83% to 3.88%; NNTB 33, 26 to 55) and households (13.6%, 9.52% to 15.47%; NNTB 7, 6 to 11) based on one study, but there was no significant effect on asymptomatic influenza and no evidence of a reduction in transmission. In prophylaxis studies, oseltamivir increased the risk of psychiatric adverse events during the combined "on-treatment" and "off-treatment" periods (risk difference 1.06%, 0.07% to 2.76%; NNTH 94, 36 to 1538) and there was a dose-response effect on psychiatric events in two "pivotal" treatment trials of oseltamivir, at 75 mg (standard dose) and 150 mg (high dose) twice daily (P=0.038). In prophylaxis studies, oseltamivir increased the risk of headaches on-treatment (risk difference 3.15%, 0.88% to 5.78%; NNTH 32, 18 to 115), renal events with treatment (0.67%, -0.01% to 2.93%), and nausea while receiving treatment (4.15%, 0.86% to 9.51%; NNTH 25, 11 to 116).
CONCLUSIONS
In prophylactic studies oseltamivir reduces the proportion of symptomatic influenza. In treatment studies it also modestly reduces the time to first alleviation of symptoms, but it causes nausea and vomiting and increases the risk of headaches and renal and psychiatric syndromes. The evidence of clinically significant effects on complications and viral transmission is limited because of rarity of such events and problems with study design. The trade-off between benefits and harms should be borne in mind when making decisions to use oseltamivir for treatment, prophylaxis, or stockpiling.
Topics: Adult; Age Factors; Antiviral Agents; Child; Headache; Humans; Influenza, Human; Kidney Diseases; Nausea; Oseltamivir; Randomized Controlled Trials as Topic; Treatment Outcome; Vomiting
PubMed: 24811411
DOI: 10.1136/bmj.g2545 -
Journal of the National Medical... Feb 2016The African American/Black population in the United States (US) is disproportionately affected by hepatitis C virus (HCV) and has lower response rates to current... (Meta-Analysis)
Meta-Analysis Review
The African American/Black population in the United States (US) is disproportionately affected by hepatitis C virus (HCV) and has lower response rates to current treatments. This analysis evaluates the participation of African American/Blacks in North American and European HCV clinical trials. The data source for this analysis was the PubMed database. Randomized controlled clinical trials (RCT) on HCV treatment with interferon 2a or 2b between January 2000 and December 2011 were reviewed. Inclusion criteria included English language and participants 18 years or older with chronic HCV. Exclusion criteria included non-randomized trials, case reports, cohort studies, ethnic specific studies, or studies not using interferon-alfa or PEG-interferon. Of the 588 trials identified, 314 (53.4%) fit inclusion criteria. The main outcome was the rate of African American/ Black participation in North American HCV clinical trials. A meta-analysis comparing the expected and observed rates was performed. Of the RCT's that met search criteria, 123 (39.2%) reported race. Clinical trials in North America were more likely to report racial data than European trials. Racial reporting increased over time. There was a statistically significant difference among the expected and observed participation of African Americans in HCV clinical trials in North America based on the prevalence of this disease within the population. The burden of HCV among African Americans in North America is not reflected in those clinical trials designed to treat HCV. Research on minority participation in clinical trials and how to increase minority participation in clinical trials is needed.
Topics: Antiviral Agents; Drug Resistance, Viral; Drug Therapy, Combination; Hepatitis C; Humans; North America; Patient Participation; Quality of Life; Randomized Controlled Trials as Topic; Ribavirin
PubMed: 26928485
DOI: 10.1016/j.jnma.2015.12.004 -
Clinical Gastroenterology and... Jul 2023Hepatitis C virus (HCV) eradication with direct-acting antivirals reduces hepatocellular carcinoma (HCC) risk. Pooled HCC incidence rates by cirrhosis status and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND & AIMS
Hepatitis C virus (HCV) eradication with direct-acting antivirals reduces hepatocellular carcinoma (HCC) risk. Pooled HCC incidence rates by cirrhosis status and fibrosis stage have not been estimated using meta-analysis.
METHODS
We searched PubMed, Web of Science, Embase, and Cochrane Library from January 1, 2014 to December 31, 2020 to identify studies assessing HCC incidence or outcomes by cirrhosis status, in adults with HCV who achieved sustained virologic response (SVR) after direct-acting antivirals. Pooled estimates were obtained using random-effects modeling. Subgroup, sensitivity, and meta-regression analyses were performed to evaluate heterogeneity.
RESULTS
We included 31 studies involving 27,711 patients with cirrhosis (mean follow-up, 2.1 years) and 11 studies involving 32,123 patients without cirrhosis (mean follow-up, 2.6 years). HCC incidence was 2.99/100 person-years (95% confidence interval [CI], 2.52-3.54; I = 75%) in patients with cirrhosis, 0.47/100 person-years (95% CI, 0.32-0.70, I = 71%) in patients without cirrhosis, and 0.63/100 person-years (95% CI: 0.34-1.20, I = 0%) in stage 3 (F3) fibrosis. Among patients with cirrhosis, HCC incidence was highest in studies with <1 year of follow-up (6.17/100 person-years [95% CI, 3.73-10.19]) and progressively lower in studies with longer follow-up (1-2 years: 2.75/100 person-years [95% CI, 2.48-3.06]; 2-3 years: 2.90/100 person-years [95% CI, 1.90-4.44]; ≥3 years: 1.83/100 person-years [95% CI, 0.88-3.80]).
CONCLUSION
Pooled HCC incidence after SVR in patients with cirrhosis was very high (2.99/100 person-years) but may be declining as longer time accrues after SVR. In patients without cirrhosis, including F3 fibrosis, HCC incidence was lower than thresholds associated with cost-effective HCC screening. In patients with F3 fibrosis, the lack of between-study heterogeneity provides strong evidence that HCC screening may not be warranted.
Topics: Adult; Humans; Liver Neoplasms; Carcinoma, Hepatocellular; Antiviral Agents; Incidence; Hepacivirus; Hepatitis C, Chronic; Hepatitis C; Liver Cirrhosis; Sustained Virologic Response
PubMed: 35525392
DOI: 10.1016/j.cgh.2022.04.013