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PLoS Medicine Mar 2023Current guidelines do not recommend routine antiviral prophylaxis to prevent hepatitis B virus (HBV) reactivation in non-liver solid organ transplant (SOT) recipients... (Meta-Analysis)
Meta-Analysis
Incidence, risk factors, and clinical outcomes of HBV reactivation in non-liver solid organ transplant recipients with resolved HBV infection: A systematic review and meta-analysis.
BACKGROUND
Current guidelines do not recommend routine antiviral prophylaxis to prevent hepatitis B virus (HBV) reactivation in non-liver solid organ transplant (SOT) recipients with resolved HBV infection, even in anti-hepatitis B surface antigen (anti-HBs)-negative recipients and those receiving intense immunosuppression. This systematic review and meta-analysis aimed to determine the incidence, risk factors, and clinical outcomes of HBV reactivation in non-liver SOT recipients.
METHODS AND FINDINGS
Three databases (PubMed, Embase, and Cochrane Library) were systematically searched up to December 31, 2022. Clinical studies reporting HBV reactivation in non-liver SOT recipients were included. Case reports, case series, and cohort studies with a sample size of less than 10 patients were excluded. Random-effects analysis was used for all meta-analyses. We included 2,913 non-liver SOT recipients with resolved HBV infection from 16 retrospective cohort studies in the analysis. The overall HBV reactivation rate was 2.5% (76/2,913; 95% confidence interval [95% CI 1.6%, 3.6%]; I2 = 55.0%). Higher rates of reactivation were observed in recipients with negative anti-HBs (34/421; 7.8%; 95% CI [5.2%, 10.9%]; I2 = 36.0%) by pooling 6 studies, experiencing acute rejection (13/266; 5.8%; 95% CI [2.3%, 14.5%]; I2 = 63.2%) by pooling 3 studies, receiving ABO blood type-incompatible transplantation (8/111; 7.0%; 95% CI [2.9%, 12.7%]; I2 = 0%) by pooling 3 studies, receiving rituximab (10/133; 7.3%; 95% CI [3.4%, 12.6%]; I2 = 0%) by pooling 3 studies, and receiving anti-thymocyte immunoglobulin (ATG, 25/504; 4.9%; 95% CI [2.5%, 8.1%]; I2 = 49.0%) by pooling 4 studies. Among recipients with post-transplant HBV reactivation, 11.0% (7/52; 95% CI [4.0%, 20.8%]; I2 = 0.3%) developed HBV-related hepatic failure, and 11.0% (7/52; 95% CI [4.0%, 20.8%]; I2 = 0.3%) had HBV-related death. Negative anti-HBs (crude odds ratio [OR] 5.05; 95% CI [2.83, 9.00]; p < 0.001; I2 = 0%), ABO blood type-incompatible transplantation (crude OR 2.62; 95% CI [1.05, 6.04]; p = 0.040; I2 = 0%), history of acute rejection (crude OR 2.37; 95% CI [1.13, 4.97]; p = 0.022; I2 = 0%), ATG use (crude OR 3.19; 95% CI [1.48, 6.87]; p = 0.003; I2 = 0%), and rituximab use (crude OR 3.16; 95% CI [1.24, 8.06]; p = 0.016; I2 = 0%) increased the risk of reactivation. Adjusted analyses reported similar results. Limitations include moderate heterogeneity in the meta-analyses and that most studies were conducted in kidney transplant recipients.
CONCLUSIONS
Non-liver SOT recipients with resolved HBV infection have a high risk of HBV-related hepatic failure and HBV-related death if HBV reactivation occurs. Potential risk factors for HBV reactivation include rituximab use, anti-thymocyte immunoglobulin use, anti-HBs negative status, acute rejection history, and ABO blood type-incompatible transplantation. Further research on monitoring and routine antiviral prophylaxis of non-liver SOT recipients at higher risk of HBV reactivation is required.
Topics: Humans; Hepatitis B virus; Rituximab; Retrospective Studies; Incidence; Antiviral Agents; Hepatitis B; Risk Factors; Hepatitis B Antibodies; Organ Transplantation
PubMed: 36920988
DOI: 10.1371/journal.pmed.1004196 -
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 -
The Cochrane Database of Systematic... Nov 2014Influenza is an acute respiratory illness caused by influenza A and B viruses. Complications may occur, especially among children and the elderly. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Influenza is an acute respiratory illness caused by influenza A and B viruses. Complications may occur, especially among children and the elderly.
OBJECTIVES
To assess the effectiveness and safety of amantadine and rimantadine in preventing, treating and shortening the duration of influenza A in children and the elderly.
SEARCH METHODS
We searched CENTRAL (2014, Issue 9), MEDLINE (1966 to September week 4, 2014) and EMBASE (1980 to October 2014).
SELECTION CRITERIA
Randomised controlled trials (RCTs) or quasi-RCTs comparing amantadine and/or rimantadine with no intervention, placebo, other antivirals or different doses or schedules of amantadine or rimantadine in children and the elderly with influenza A.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the search results. We extracted and analysed data using the standard Cochrane methodology.
MAIN RESULTS
We identified 12 studies (2494 participants: 1586 children and 908 elderly) comparing amantadine and rimantadine with placebo, paracetamol (one trial: 69 children) or zanamivir (two trials: 545 elderly) to treat influenza A.Amantadine was effective in preventing influenza A in children (773 participants, risk ratio (RR) 0.11; 95% confidence interval (CI) 0.04 to 0.30). The assumed risk of influenza A in the control group was 10 per 100. The corresponding risk in the rimantadine group was one per 100 (95% CI 0 to 3). Nevertheless, the quality of the evidence was low and the safety of the drug was not well established.For treatment, rimantadine was beneficial in abating fever on day three of treatment in children: one selected study with low risk of bias, moderate evidence quality and 69 participants (RR 0.36; 95% CI 0.14 to 0.91). The assumed risk was 38 per 100. The corresponding risk in the rimantadine group was 14 per 100 (95% CI 5 to 34).Rimantadine did not show any prophylactic effect in the elderly. The quality of evidence was very low: 103 participants (RR 0.45; 95% CI 0.14 to 1.41). The assumed risk was 17 per 100. The corresponding risk in the rimantadine group was 7 per 100 (95% CI 2 to 23).There was no evidence of adverse effects caused by treatment with amantadine or rimantadine.We found no studies assessing amantadine in the elderly.
AUTHORS' CONCLUSIONS
The quality of the evidence combined with a lack of knowledge about the safety of amantadine and the limited benefits of rimantadine, do not indicate that amantadine and rimantadine compared to control (placebo or paracetamol) could be useful in preventing, treating and shortening the duration of influenza A in children and the elderly.
Topics: Adolescent; Aged; Amantadine; Antiviral Agents; Child; Humans; Influenza A Virus, H1N1 Subtype; Influenza A virus; Influenza, Human; Randomized Controlled Trials as Topic; Rimantadine; Sex Factors; Young Adult
PubMed: 25415374
DOI: 10.1002/14651858.CD002745.pub4 -
Immunity, Inflammation and Disease Dec 2021To provide the latest evidence for the efficacy and safety of arbidol (umifenovir) in COVID-19 treatment. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To provide the latest evidence for the efficacy and safety of arbidol (umifenovir) in COVID-19 treatment.
METHODS
A literature systematic search was carried out in PubMed, Cochrane Library, Embase, and medRxiv up to May 2021. The Cochrane risk of bias tool and Newcastle-Ottawa scale were used to assess the quality of included studies. Meta-analysis was performed using RevMan 5.3.
RESULTS
Sixteen studies were met the inclusion criteria. No significant difference was observed between arbidol and non-antiviral treatment groups neither for primary outcomes, including the negative rate of PCR (NR-PCR) on Day 7 (risk ratio [RR]: 0.94; 95% confidence interval (CI): 0.78-1.14) and Day 14 (RR: 1.10; 95% CI: 0.96-1.25), and PCR negative conversion time (PCR-NCT; mean difference [MD]: 0.74; 95% CI: -0.87 to 2.34), nor secondary outcomes (p > .05). However, arbidol was associated with higher adverse events (RR: 2.24; 95% CI: 1.06-4.73). Compared with lopinavir/ritonavir, arbidol showed better efficacy for primary outcomes (p < .05). Adding arbidol to lopinavir/ritonavir also led to better efficacy in terms of NR-PCR on Day 7 and PCR-NCT (p < .05). There was no significant difference between arbidol and chloroquine in primary outcomes (p > .05). No remarkable therapeutic effect was observed between arbidol and other agents (p > .05).
CONCLUSION
The present meta-analysis showed no significant benefit of using arbidol compared with non-antiviral treatment or other therapeutic agents against COVID-19 disease. High-quality studies are needed to establish the efficacy and safety of arbidol for COVID-19.
Topics: Antiviral Agents; Humans; Indoles; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34347937
DOI: 10.1002/iid3.502 -
Medicine Mar 2016All possible direct-acting antiviral agent (DAA) regimens for treatment-naive hepatitis C genotype 1 were evaluated by many randomized controlled trials (RCTs). However,... (Meta-Analysis)
Meta-Analysis Review
Systematic Review and Network Meta-Analysis of Randomized Controlled Trials: Comparative Effectiveness and Safety of Direct-Acting Antiviral Agents for Treatment-Naive Hepatitis C Genotype 1.
All possible direct-acting antiviral agent (DAA) regimens for treatment-naive hepatitis C genotype 1 were evaluated by many randomized controlled trials (RCTs). However, the optimum regimen remains inconclusive. We aim to compare interventions in terms of sustained virological response at 12 (SVR12) and 24 (SVR24) weeks after the end of treatment and adverse effects (AEs) (fatigue, headache, nausea, insomnia). PubMed, Embase, and the Cochrane Library were searched for RCTs until July 31, 2015. We estimated odds ratios (ORs) between treatments on clinical outcomes. Twenty-two eligible RCTs were included. Compared with peginterferon-ribavirin (PR), daclatasvir plus PR (OR 8.90, P < 0.001), faldaprevir plus PR (OR 3.72, P < 0.001), simeprevir plus PR (OR 3.59, P < 0.001), sofosbuvir plus PR (OR 4.69, P < 0.001) yield a significant effect in improving SVR12. Consistently, simeprevir plus PR (OR 3.49, P < 0.001), sofosbuvir plus PR (OR 4.51, P < 0.001), daclatasvir plus PR (OR 4.77, P < 0.001) also improved the rates of SVR24 significantly compared with PR. With respect to AEs, compared with PR, ledipasvir plus sofosbuvir plus PR (OR 2.13, P < 0.001) confer a significant AE in nausea, whereas daclatasvir plus PR (OR 0.20, P < 0.001 and OR 0.18, P < 0.001, respectively) lowered the incidence of fatigue and nausea significantly when compared with ledipasvir plus sofosbuvir plus PR. Daclatasvir plus PR was the most effective in SVR12 and SVR24, but caused an increased AEs profile (headache and insomnia). Combined ledipasvir with sofosbuvir or combination of PR was associated with higher incidence of fatigue and nausea.
Topics: Antiviral Agents; Comparative Effectiveness Research; Drug Therapy, Combination; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Odds Ratio; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 26945424
DOI: 10.1097/MD.0000000000003004 -
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 -
Alimentary Pharmacology & Therapeutics Nov 2011The indications and endpoints for treatment of chronic hepatitis B continue to evolve. The aim of the therapy for chronic hepatitis B is to achieve a long-term continued... (Review)
Review
BACKGROUND
The indications and endpoints for treatment of chronic hepatitis B continue to evolve. The aim of the therapy for chronic hepatitis B is to achieve a long-term continued suppression of the hepatitis B virus (HBV) DNA to prevent disease progression leading to the development of cirrhosis and hepatocellular carcinoma.
AIM
To summarise current literature on therapy of chronic hepatitis B, with a focus on indications for therapy, preferred treatment options, and management of resistance and partial responders.
METHODS
A systematic review of the literature, with a focus on international guidelines, was performed.
RESULTS
Seven drugs are licensed for the treatment of chronic hepatitis B in many countries. The selection of a drug with high potency and low rate of resistance is essential to achieve rapid and long-term viral suppression. The prevention of the sequelae of antiviral drug resistance and appropriate management of viral breakthrough are major goals of current management. The addition or change to an antiviral agent that is not cross-resistant is critical to restore suppression of viral replication for patients with breakthrough resistance. Patient adherence to medication is essential to achieve adequate HBV DNA suppression.
CONCLUSIONS
The current treatment strategy of chronic hepatitis B is now standard: initial selection of entecavir, tenofovir, or peginterferon alfa-2a. Future studies are required to determine if combination therapy using two oral agents or peginterferon with an oral agent with a high genetic barrier to resistance might be superior to standard current monotherapy.
Topics: Antiviral Agents; Carcinoma, Hepatocellular; Drug Resistance, Viral; Hepatitis B virus; Hepatitis B, Chronic; Humans; Liver Cirrhosis; Liver Neoplasms; Patient Compliance; Practice Guidelines as Topic
PubMed: 21978243
DOI: 10.1111/j.1365-2036.2011.04869.x -
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 -
Clinical Infectious Diseases : An... Aug 2023In a hepatitis C virus (HCV)-controlled human infection model (CHIM), healthy volunteers are inoculated with HCV and then treated. Residual hepatocellular carcinoma...
Risk of Hepatocellular Carcinoma After Spontaneous Clearance of Hepatitis C Virus and in Noncirrhosis Chronic Hepatitis C Patients With Sustained Virological Response: A Systematic Review.
In a hepatitis C virus (HCV)-controlled human infection model (CHIM), healthy volunteers are inoculated with HCV and then treated. Residual hepatocellular carcinoma (HCC) risk after viral clearance is an important consideration when evaluating the CHIM. We estimate HCC risk in spontaneously cleared HCV and in noncirrhosis after sustained virological response (SVR) to HCV treatment in a systematic review and using data from 3 cohorts: German anti-D, Taiwan, and US Veterans Affairs (VA). For noncirrhosis SVR, the overall HCC rate is 0.33 per 100 patient-years in meta-analysis. HCC rates for the German, Taiwan, and US Veterans Affairs cohorts are 0, 0.14, and 0.02 per 100 patient-years, respectively. Past hepatitis B virus exposure was not accounted for in the Taiwan cohort, while VA patients were likely tested based on liver disease/risk factors, which may confound HCC outcomes. The German cohort with no HCC after 44 years is most comparable to the CHIM participants. Although it is difficult to precisely estimate HCC risk from an HCV CHIM, the data suggest the risk to be very low or negligible.
Topics: Humans; Antiviral Agents; Carcinoma, Hepatocellular; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Liver Neoplasms; Sustained Virologic Response
PubMed: 37579210
DOI: 10.1093/cid/ciad380 -
Liver Transplantation : Official... Jan 2013Cyclosporine A (CSA), but not tacrolimus (TAC), inhibits hepatitis C virus (HCV) replication in vitro. Clinical reports on the efficacy of interferon-α (IFNα)-based... (Meta-Analysis)
Meta-Analysis Review
Cyclosporine A (CSA), but not tacrolimus (TAC), inhibits hepatitis C virus (HCV) replication in vitro. Clinical reports on the efficacy of interferon-α (IFNα)-based antiviral therapy (AVT) for recurrent HCV after liver transplantation (LT) with CSA and TAC are conflicting. Our aim was to assess whether AVT for recurrent HCV after LT is more effective with CSA or TAC. We performed an electronic database search (1995-2012) and a manual abstract search (2005-2012). The a priori defined eligibility criteria included the use of AVT for recurrent HCV with IFN (standard or pegylated) and ribavirin and the reporting of sustained virological response (SVR) rates with CSA and TAC (the primary outcome). Two authors identified and extracted data independently. Dichotomous data were expressed as relative risks (RRs) and 95% confidence intervals (CIs) with a random effects model. In all, 5058 references were retrieved, and 1 randomized controlled trial (RCT) and 17 observational studies (13 full-text articles) met the eligibility criteria; the meta-analysis was based on the latter studies. The pooled SVR rates were 42% (395/945) with CSA and 35% (471/1364) with TAC (RR = 1.18, 95% CI = 1.00-1.39, P = 0.05). Although the pooled data contained significant heterogeneity (I(2) = 45%, P = 0.02), the SVR rates in the RCT were comparable (39% with CSA and 35% with TAC). Limiting the analysis to the 7 studies reporting on 40 or more patients in each group (with 1634 patients in all) favored CSA (RR = 1.23, 95% CI = 1.09-1.38, P < 0.001), and heterogeneity disappeared (I(2) = 0%, P = 0.62). In conclusion, IFN-based AVT for recurrent HCV after LT seems marginally more effective with CSA versus TAC; the study heterogeneity, however, limits firm conclusions.
Topics: Antiviral Agents; Cyclosporine; Female; Hepatitis C; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Middle Aged; Tacrolimus
PubMed: 22821730
DOI: 10.1002/lt.23516