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Journal of Viral Hepatitis Jul 2024The impact of concurrent fatty liver (FL) on response to antiviral therapy in chronic hepatitis B (CHB) patients has not been well characterized. We aimed to... (Meta-Analysis)
Meta-Analysis
The impact of concurrent fatty liver (FL) on response to antiviral therapy in chronic hepatitis B (CHB) patients has not been well characterized. We aimed to systematically review and analyse antiviral treatment response in CHB patients with and without FL. We searched PubMed, Embase, Web of Science and the Cochrane Library databases from inception to 31 May 2023 for relevant studies. Biochemical response (BR), complete viral suppression (CVS) and hepatitis B e antigen (HBeAg) seroconversion in CHB patients with FL (CHB-FL) and without FL (non-FL CHB) were compared. In an initial pool of 2101 citations, a total of 10 studies involving 2108 patients were included. After 12 weeks of treatment, CHB-FL patients as compared with non-FL CHB patients had lower BR rate (48.37% [108/227] vs. 72.98% [126/174], p = .04) but similar trend for CVS (36.86% [80/227] vs. 68.81% [114/174], p = .05) and similar rates of HBeAg seroconversion (6.59% [7/103] vs. 7.40% [7/110], p = .89). However, at week 48, there were no statistically significant differences between CHB-FL and non-FL CHB patients in any of the outcomes, including BR (60.03% [213/471] vs. 69.37% [314/717], p = .67), CVS (65.63% [459/746] vs. 73.81% [743/1132], p = .27) and HBeAg seroconversion (10.01% [30/275] vs. 14.06% [65/453], p = .58) with similar findings for week 96. BR rate was lower in CHB-FL patients after 12 weeks of antiviral treatment. However, after a longer follow-up of either 48 or 96 weeks, no statistically significant differences were observed in BR, CVS or HBeAg seroconversion rates between CHB patients with and without FL.
Topics: Humans; Hepatitis B, Chronic; Antiviral Agents; Hepatitis B e Antigens; Treatment Outcome; Fatty Liver; Seroconversion; Hepatitis B virus; DNA, Viral
PubMed: 38590002
DOI: 10.1111/jvh.13942 -
The American Journal of Medicine Jun 2015We conducted a systematic review with meta-analysis to evaluate the efficacy of antiviral agents on complete recovery of Bell's palsy. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
We conducted a systematic review with meta-analysis to evaluate the efficacy of antiviral agents on complete recovery of Bell's palsy.
METHODS
We searched CENTRAL, Embase, MEDLINE, International Pharmaceutical Abstracts, and sources of unpublished literature to November 1, 2014. Primary and secondary outcomes were complete and satisfactory recovery, respectively. To evaluate statistical heterogeneity, we performed subgroup analysis of baseline severity of Bell's palsy and between-study sensitivity analyses based on risk of allocation and detection bias.
RESULTS
The 10 included randomized controlled trials (2419 patients; 807 with severe Bell's palsy at onset) had variable risk of bias, with 9 trials having a high risk of bias in at least 1 domain. Complete recovery was not statistically significantly greater with antiviral use versus no antiviral use in the random-effects meta-analysis of 6 trials (relative risk, 1.06; 95% confidence interval, 0.97-1.16; I(2) = 65%). Conversely, random-effects meta-analysis of 9 trials showed a statistically significant difference in satisfactory recovery (relative risk, 1.10; 95% confidence interval, 1.02-1.18; I(2) = 63%). Response to antiviral agents did not differ visually or statistically between patients with severe symptoms at baseline and those with milder disease (test for interaction, P = .11). Sensitivity analyses did not show a clear effect of bias on outcomes.
CONCLUSIONS
Antiviral agents are not efficacious in increasing the proportion of patients with Bell's palsy who achieved complete recovery, regardless of baseline symptom severity.
Topics: Antiviral Agents; Bell Palsy; Humans
PubMed: 25554380
DOI: 10.1016/j.amjmed.2014.11.033 -
Obesity Reviews : An Official Journal... Dec 2015There is evidence that certain infections may induce obesity. Obese persons may also have more severe infections and have compromised response to therapies. The... (Review)
Review
There is evidence that certain infections may induce obesity. Obese persons may also have more severe infections and have compromised response to therapies. The objective of this study is to review the available literature identifying infections that potentially contribute to greater body mass index (BMI) and differential responses of overweight and obese persons to infections. A systematic literature review of human studies examining associations between infections and weight gain, differential susceptibility, severity, and response to prevention and treatment of infection according to BMI status (January 1980-July 2014) was conducted. Three hundred and forty-three studies were eligible for inclusion. Evidence indicated that viral infection by human adenovirus Ad36 and antibiotic eradication of Helicobacter pylori were followed by weight gain. People who were overweight or obese had higher susceptibility to developing post-surgical infections, H1N1 influenza and periodontal disease. More severe infections tended to be present in people with a larger BMI. People with a higher BMI had a reduced response to vaccinations and antimicrobial drugs. Higher doses of antibiotics were more effective in obese patients. Infections may influence BMI, and BMI status may influence response to certain infections, as well as to preventive and treatment measures. These observations have potential clinical implications.
Topics: Adenoviridae; Adenovirus Infections, Human; Anti-Bacterial Agents; Antibodies, Bacterial; Antibodies, Viral; Antiviral Agents; Body Mass Index; Disease Susceptibility; Helicobacter Infections; Helicobacter pylori; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Obesity; Severity of Illness Index; Surgical Wound Infection; Weight Gain
PubMed: 26354800
DOI: 10.1111/obr.12320 -
Pathogens (Basel, Switzerland) Nov 2023Host genetic factors significantly influence susceptibility to SARS-CoV-2 infection and COVID-19 severity. Among these genetic factors are single-nucleotide variants... (Review)
Review
Host genetic factors significantly influence susceptibility to SARS-CoV-2 infection and COVID-19 severity. Among these genetic factors are single-nucleotide variants (SNVs). and genes have been associated with severe COVID-19 in populations from the United Kingdom, Africa, and Latin America. IFNAR1 and IFNAR2 are subunits forming the type I interferon receptor (IFNAR). SNVs in the genes impact protein function, affecting antiviral response and disease phenotypes. This systematic review aimed to describe and variants associated with COVID-19 susceptibility and severity. Accordingly, the current review focused on and studies published between January 2021 and February 2023, utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) protocol. The electronic search was conducted in PubMed databases using Boolean operators and inclusion and exclusion criteria. Of the 170 literature pieces, 11 studies were included. We include case reports of rare SNVs, defined by minor allele frequency (MAF) < 1%, and genome-wide associated studies (GWAS). Variants in and could potentially be new targets for therapies that limit the infection and the resulting inflammation by SARS-CoV-2 infection.
PubMed: 38003785
DOI: 10.3390/pathogens12111320 -
Journal of Hepatology Sep 2019The effect of hepatocellular carcinoma (HCC) on the response to interferon-free direct-acting antiviral (DAA) therapy in patients with chronic hepatitis C (CHC)... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
The effect of hepatocellular carcinoma (HCC) on the response to interferon-free direct-acting antiviral (DAA) therapy in patients with chronic hepatitis C (CHC) infection remains unclear. Using a systematic review and meta-analysis approach, we aimed to investigate the effect of DAA therapy on sustained virologic response (SVR) among patients with CHC and either active, inactive or no HCC.
METHODS
PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from 1/1/2013 to 9/24/2018. The pooled SVR rates were computed using DerSimonian-Laird random-effects models.
RESULTS
We included 49 studies from 15 countries, comprised of 3,341 patients with HCC and 35,701 without HCC. Overall, the pooled SVR was lower in patients with HCC than in those without HCC (89.6%, 95% CI 86.8-92.1%, I = 79.1% vs. 93.3%, 95% CI 91.9-94.7%, I = 95.0%, p = 0.0012), translating to a 4.8% (95% CI 0.2-7.4%) SVR reduction by meta-regression analysis. The largest SVR reduction (18.8%) occurred in patients with active/residual HCC vs. inactive/ablated HCC (SVR 73.1% vs. 92.6%, p = 0.002). Meanwhile, patients with HCC who received a prior liver transplant had higher SVR rates than those who did not (p <0.001). Regarding specific DAA regimens, patients with HCC treated with ledipasvir/sofosbuvir had lower SVR rates than patients without HCC (92.6%, n = 884 vs. 97.8%, n = 13,141, p = 0.026), but heterogeneity was high (I = 84.7%, p <0.001). The SVR rate was similar in patients with/without HCC who were treated with ombitasvir/paritaprevir/ritonavir ± dasabuvir (n = 101) (97.2% vs. 94.8%, p = 0.79), or daclatasvir/asunaprevir (91.7% vs. 89.8%, p = 0.66).
CONCLUSION
Overall, SVR rates were lower in patients with HCC, especially with active HCC, compared to those without HCC, though heterogeneity was high. Continued efforts are needed to aggressively screen, diagnose, and treat HCC to ensure higher CHC cure rates.
LAY SUMMARY
There are now medications (direct-acting antivirals or "DAAs") that can "cure" hepatitis C virus, but patients with hepatitis C and liver cancer may be less likely to achieve cure than those without liver cancer. However, patients with liver cancer are also more likely to have advanced liver disease and risk factors that can decrease cure rates, so better controlled studies are needed to confirm these findings.
Topics: 2-Naphthylamine; Adolescent; Adult; Anilides; Antiviral Agents; Benzimidazoles; Carbamates; Carcinoma, Hepatocellular; Cyclopropanes; Female; Fluorenes; Hepacivirus; Hepatitis C, Chronic; Humans; Isoquinolines; Lactams, Macrocyclic; Liver Neoplasms; Liver Transplantation; Macrocyclic Compounds; Male; Proline; Ritonavir; Sofosbuvir; Sulfonamides; Sustained Virologic Response; Uracil; Valine; Young Adult
PubMed: 31096005
DOI: 10.1016/j.jhep.2019.04.017 -
Alimentary Pharmacology & Therapeutics Jun 2016The burden of HCV cirrhosis is high and projected to increase significantly over the next decade. While interferon therapy is problematic in HCV cirrhosis, the era of... (Review)
Review
BACKGROUND
The burden of HCV cirrhosis is high and projected to increase significantly over the next decade. While interferon therapy is problematic in HCV cirrhosis, the era of direct-acting anti-viral (DAA) therapy provides effective treatment for patients with cirrhosis.
AIM
To systematically review the results of DAA therapy to date in patients with HCV cirrhosis, and highlight the ongoing challenges for DAA therapy in this population.
METHODS
A structured Medline search was conducted to obtain phase II and III HCV trials in patients with cirrhosis. Citations from review articles were cross-referenced and conference abstracts from EASL and AASLD liver meetings for the preceding 3 years were reviewed manually. Keywords used included hepatitis C, cirrhosis and the DAA's: sofosbuvir, ledipasvir, velpatasvir, grazoprevir, elbasvir, daclatasvir, beclabuvir, asunaprevir, simeprevir, paritaprevir, ombitasvir and dasabuvir.
RESULTS
Successful direct-acting anti-viral treatment is now possible in patients with HCV-related cirrhosis including those with liver decompensation with several regimens now offering sustained virological response (SVR) of 90-95%. Overall success rates in GT1 cirrhosis are excellent while GT3-infected patients with cirrhosis remain hard to cure. The pangenotypic combination of sofosbuvir and velpatasvir holds promise for GT3 cirrhosis achieving SVR of ~90%.
CONCLUSIONS
Potent DAA therapies provide much needed, safe and highly effective treatment options for persons with HCV cirrhosis including those previously deemed unsuitable for treatment. Combination therapy with two or more classes of drug is essential to achieve high efficacy and minimise viral resistance, with the role of ribavirin still under evaluation. However, several challenges remain including the hard-to-cure groups of GT3 cirrhosis and direct-acting anti-viral failures, and managing drug-drug interactions.
Topics: Antiviral Agents; Hepatitis C; Humans; Interferons; Liver Cirrhosis
PubMed: 27087015
DOI: 10.1111/apt.13633 -
BMC Gastroenterology Apr 2017The long-term clinical outcomes of antiviral therapy for patients with chronic hepatitis C are uncertain in terms of hepatitis C virus (HCV)-related morbidity and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The long-term clinical outcomes of antiviral therapy for patients with chronic hepatitis C are uncertain in terms of hepatitis C virus (HCV)-related morbidity and mortality according to the response to antiviral therapy. This study aimed to assess the impact of antiviral treatment on the development of HCC and mortality in patients with chronic HCV infection.
METHODS
A systematic review was conducted for studies that evaluated the antiviral efficacy for patients with chronic hepatitis C or assessed the development of HCC or mortality between SVR (sustained virologic response) and non-SVR patients. The methodological quality of the enrolled publications was evaluated using Risk of Bias table or Newcastle-Ottawa scale. Random-effect model meta-analyses and meta-regression were performed. Publication bias was assessed.
RESULTS
In total, 59 studies (4 RCTs, 15 prospective and 40 retrospective cohort studies) were included. Antiviral treatment was associated with reduced development of HCC (vs. no treatment; OR 0.392, 95% CI 0.275-0.557), and this effect was intensified when SVR was achieved (vs. no SVR, OR: 0.203, 95% CI 0.164-0.251). Antiviral treatment was associated with lower all-cause mortality (vs. no treatment; OR 0.380, 95% CI 0.295-0.489) and liver-specific mortality (OR 0.363, 95% CI 0.260-0.508). This rate was also intensified when SVR was achieved [all-cause mortality (vs. no SVR, OR 0.255, 95% CI 0.199-0.326), liver-specific mortality (OR 0.126, 95% CI 0.094-0.169)]. Sensitivity analyses revealed robust results, and a small study effect was minimal.
CONCLUSIONS
In patients with chronic hepatitis C, antiviral therapy can reduce the development of HCC and mortality, especially when SVR is achieved.
Topics: Antiviral Agents; Carcinoma, Hepatocellular; Hepatitis C, Chronic; Humans; Liver Neoplasms; Mortality; Sustained Virologic Response; Treatment Outcome
PubMed: 28376711
DOI: 10.1186/s12876-017-0606-9 -
Journal of Hepatology Dec 2017The risk of hepatocellular carcinoma (HCC) occurrence or recurrence following direct-acting antiviral (DAA) hepatitis C virus (HCV) therapy remains unclear. The aims of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND & AIMS
The risk of hepatocellular carcinoma (HCC) occurrence or recurrence following direct-acting antiviral (DAA) hepatitis C virus (HCV) therapy remains unclear. The aims of this study were to compare the rate of HCC occurrence in patients with HCV-related cirrhosis, following DAA vs. interferon (IFN)-based cure, and to compare the rate of HCC recurrence in patients who received curative HCC treatment, following DAA vs. IFN-based cure.
METHODS
A search was conducted for reports published between January 2000 and February 2017. Studies were included if they assessed HCC outcomes by type and response to HCV therapy. Random-effects meta-analyses were undertaken to determine a combined estimate of HCC incidence rate per 100/person-years (py) among patients with a sustained virological response (SVR).
RESULTS
A total of 41 studies (n=13,875 patients), including 26 on HCC occurrence (IFN=17, DAA=9; prospective=19, retrospective=5, retrospective-prospective=2), and 17 on HCC recurrence (IFN=7, DAA=10; prospective=11, retrospective=5 and retrospective-prospective=1) were included. In studies assessing HCC occurrence, average follow-up was shorter (1.0 vs. 5.5years), and average age older (60 vs. 52years) in DAA studies. In studies assessing HCC recurrence, average follow-up was shorter (1.3 vs. 5.0years), but average age similar (64 vs. 66years) in DAA studies. HCC occurrence was 1.14/100 py (95% CI 0.86-1.52) and 2.96/100 py (95% CI 1.76-4.96) in IFN and DAA studies respectively. HCC recurrence was 9.21/100 py (95% CI 7.18-11.81) and 12.16/100 py (95% CI 5.00-29.58) in IFN and DAA studies respectively. In meta-regression adjusting for study follow-up and age, DAA therapy was not associated with higher HCC occurrence (RR 0.68; 95% CI 0.18-2.55; p=0.55) or recurrence (RR 0.62, 95% CI 0.11-3.45, p=0.56).
CONCLUSION
There is no evidence for differential HCC occurrence or recurrence risk following SVR from DAA and IFN-based therapy.
LAY SUMMARY
The risk of hepatocellular carcinoma (HCC) occurrence or recurrence following direct-acting antiviral (DAA) hepatitis C virus (HCV) therapy remains unclear. We conducted a meta-analysis to compare occurrence and recurrence of HCC in patients receiving either DAA or interferon (IFN) therapy. There is no evidence that HCC occurrence or recurrence is different between patients receiving DAA or IFN therapy.
Topics: Aged; Antiviral Agents; Carcinoma, Hepatocellular; Female; Hepatitis C, Chronic; Humans; Interferons; Liver Neoplasms; Male; Middle Aged; Risk
PubMed: 28802876
DOI: 10.1016/j.jhep.2017.07.025 -
Clinical Gastroenterology and... Jan 2018We performed a systematic review and meta-analysis to estimate the decrease in liver stiffness, measured by vibration-controlled transient elastrography (VCTE), in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND & AIMS
We performed a systematic review and meta-analysis to estimate the decrease in liver stiffness, measured by vibration-controlled transient elastrography (VCTE), in patients with hepatitis C virus infection who achieved a sustained virologic response (SVR).
METHODS
We searched the literature through October 2016 for observational studies or randomized controlled trials of adults with hepatitis C virus infection who received antiviral therapy (either direct-acting antiviral agents or interferon-based therapies), underwent liver stiffness measurement using VCTE before starting therapy, and had at least 1 follow-up VCTE after completion of therapy; studies also provided data on mean or median liver stiffness measurements for patients who did and did not achieve an SVR. We identified 24 studies, and estimated weighted mean difference (and 95% confidence interval) in liver stiffness in patients with versus without SVR using random-effects meta-analysis.
RESULTS
In patients who achieved SVR, liver stiffness decreased by 2.4 kPa at the end of therapy (95% CI, -1.7 to -3.0), by 3.1 kPa 1-6 months after therapy (95% CI, -1.6 to -4.7), by 3.2 kPa 6-12 months after therapy (90% CI, -2.6 to -3.9), and 4.1 kPa 12 months or more after therapy (95% CI, -3.3 to -4.9) (median decrease, 28.2%; interquartile range, 21.8-34.8). In contrast, there was no significant change in liver stiffness in patients who did not achieve an SVR (at 6-12 months after therapy, decrease of 0.6 kPa; 95% CI, -1.7 to 0.5). Decreases in liver stiffness were significantly greater in patients treated with direct-acting antiviral agents than with interferon-based therapy (decrease of 4.5 kPa vs decrease of 2.6 kPa; P = .03), cirrhosis at baseline (decrease of 5.1 kPa vs decrease of 2.8 kPa in patients with no cirrhosis; P = .02), or high pretreatment levels of alanine aminotransferase (P < .01). Among patients with baseline liver stiffness >9.5 kPa, 47% (95% CI, 27%-68%) achieved posttreatment liver stiffness of <9.5 kPa.
CONCLUSIONS
In a systematic review and meta-analysis, we associated eradication of hepatitis C virus infection (SVR) with significant decreases in liver stiffness, particularly in patients with high baseline level of inflammation or patients who received direct-acting antiviral agents. Almost half the patients considered to have advanced fibrosis, based on VCTE, before therapy achieved posttreatment liver stiffness levels <9.5 kPa. Clinical Trial Registration no: CRD42016051034.
Topics: Antiviral Agents; Elasticity Imaging Techniques; Hepatitis C, Chronic; Humans; Liver; Sustained Virologic Response; Time Factors; Treatment Outcome
PubMed: 28479504
DOI: 10.1016/j.cgh.2017.04.038 -
Journal of Hepatology Apr 2023Hepatitis B core-related antigen (HBcrAg) is a new biomarker for chronic hepatitis B (CHB) whose performance has not been critically or systematically appraised. Herein,...
BACKGROUND & AIMS
Hepatitis B core-related antigen (HBcrAg) is a new biomarker for chronic hepatitis B (CHB) whose performance has not been critically or systematically appraised. Herein, we performed a systematic review to determine its clinical utility.
METHODS
We evaluated the biological pathway of HBcrAg and performed a systematic review of PubMed for clinical trials, cohort studies, and case-control studies that evaluated the clinical utility of HBcrAg. The effectiveness of HBcrAg in predicting HBV-specific clinical events (e.g. HBeAg seroconversion, phases of CHB, HBsAg loss, treatment response, and relapse after stopping therapy) was examined using receiver-operating characteristic curves. The correlation coefficients of HBcrAg with HBV DNA, quantitative HBsAg (qHBsAg), HBV RNA, and cccDNA were summarised from published studies. Median values were used as estimates.
RESULTS
HBcrAg consists of three precore/core protein products: HBcAg, HBeAg, and a 22 kDa precore protein. HBcrAg assays have been associated with false-positive rates of 9.3% and false-negative rates of between 12-35% for CHB. The new iTACT-HBcrAg is more sensitive but does not reduce the false-positive rate. A PubMed search found 248 papers on HBcrAg, of which 59 were suitable for analysis. The clinical performance of HBcrAg was evaluated using AUROC analyses, with median AUROCs of 0.860 for HBeAg seroconversion, 0.867 for predicting HBeAg(-) hepatitis, 0.645 for HBsAg loss, 0.757 for treatment response, and 0.688 for relapse after stopping therapy. The median correlation coefficient (r) was 0.630 with HBV DNA, 0.414 with qHBsAg, 0.619 with HBV RNA and 0.550 with cccDNA. Correlation decreased during antiviral therapy, but combined biomarkers improved performance.
CONCLUSIONS
HBcrAg has a mixed performance and has a poor correlation with HBsAg loss and antiviral therapy, hence HBcrAg results should be interpreted with caution.
IMPACT AND IMPLICATIONS
Hepatitis B core-related antigen (HBcrAg) has been used to assess management of patients with chronic hepatitis B (CHB) without a systematic and critical Sreview of its performance. Our finding that HBcrAg had a false-positive rate of 9% and a false-negative rate of 12-35% raises concerns, although larger studies are needed for validation. A systematic review showed that the performance of HBcrAg was variable depending on the CHB endpoint; it was excellent at predicting HBeAg seroconversion and HBeAg-negative chronic hepatitis (vs. chronic infection), which should be its main use, but it was poor for relapse after stopping antiviral therapy and for HBsAg loss. HBcrAg results should be interpreted with considerable caution, particularly by physicians, researchers, guideline committees and agencies that approve diagnostic tests.
Topics: Humans; Hepatitis B Core Antigens; Hepatitis B, Chronic; Hepatitis B Surface Antigens; Hepatitis B e Antigens; DNA, Viral; Biomarkers; Antiviral Agents; RNA; Hepatitis B virus
PubMed: 36586590
DOI: 10.1016/j.jhep.2022.12.017