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BMC Infectious Diseases Oct 2023To compare the effectiveness of seven major interventions [Bulevirtide (BLV), Interferon (IFN), Nucleoside analogs (NAs), BLV + IFN, BLV + NAs, IFN + NAs,... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To compare the effectiveness of seven major interventions [Bulevirtide (BLV), Interferon (IFN), Nucleoside analogs (NAs), BLV + IFN, BLV + NAs, IFN + NAs, and Placebo] to treat chronic hepatitis D.
METHODS
We followed PRISMA-NMA guidelines, searched databases (Cochrane Library, PubMed, EMBASE, and Web Of Science) for eligible randomized controlled trials (RCTs), and applied STATA17.0 software to execute the meta-analysis.
RESULTS
We included 14 randomized controlled trials (814 patients) comparing seven different interventions. The results of the network meta-analysis showed that: ① Sustained virological response (after 24 weeks of follow-up): Four intervention groups (BLV + IFN, IFN alone, IFN + NAs, and NAs alone) were effective (relative risk (RR) = 13.30, 95% confidence interval (Cl) [1.68,105.32], RR = 12.13, 95% Cl [1.46,101.04], RR = 5.05, 95% Cl [1.68,15.19], RR = 5.03, 95% Cl [1.66,15.20]), with no statistically significant differences between the four groups. The top three in probability rankings were: BLV + NAs, BLV + IFN, and BLV alone (surface under the cumulative ranking curve (SUCRA) = 86.8%, 80.3%, and 48.4%; ② Sustained biochemical response (after 24 weeks of follow-up): BLV + IFN and IFN were superior to BLV (RR = 14.71, 95% Cl [1.14,189.07], RR = 16.67, 95% Cl [1.39,199.52]). The top three were BLV alone, BLV + NAs, and BLV + IFN (SUCRA = 86.9%,81.2%, and 64.3%). ③ Histological response: NAs were superior to BLV (RR = 2.08, 95% Cl [1.10,3.93]), whereas the difference between other treatment regimens was not statistically significant, and the top three in the probability ranking were BLV alone, BLV + NAs, and BLV + IFN (SUCRA = 75.6%, 75.6%, and 61.8%).
CONCLUSIONS
IFN, IFN + BLV, and IFN + NAs were effective in clearing HDV RNA and normalizing alanine aminotransferase levels; however, IFN and IFN + NAs had a high rate of viral relapse at 24 weeks post-treatment follow-up. There was no additional benefit of adding NAs to IFN therapy for chronic hepatitis D; however, the combination of IFN + BLV significantly improved short-term HDV RNA clearance, which showed strong synergistic effects. The seven regimens included in the study did not contribute significantly to liver histological improvement. Therefore, the IFN + BLV combination has the most potential as a treatment option to improve the long-term prognosis or even cure chronic hepatitis D.
TRIAL REGISTRATION
This systematic evaluation and meta-analysis was registered with PROSPERO under the registration number: CRD42022314544.).
Topics: Humans; Network Meta-Analysis; Hepatitis D, Chronic; Randomized Controlled Trials as Topic; Interferons; RNA; Antiviral Agents
PubMed: 37880598
DOI: 10.1186/s12879-023-08718-7 -
Hepatology (Baltimore, Md.) May 2024Studies have suggested that patients with chronic hepatitis B, either co- or superinfected, have more aggressive liver disease progression than those with the HDV. This... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Studies have suggested that patients with chronic hepatitis B, either co- or superinfected, have more aggressive liver disease progression than those with the HDV. This systematic literature review and meta-analysis examined whether HDV RNA status is associated with increased risk of advanced liver disease events in patients who are HBsAg and HDV antibody positive.
APPROACH AND RESULTS
A total of 12 publications were included. Relative rates of progression to advanced liver disease event for HDV RNA+/detectable versus HDV RNA-/undetectable were extracted for analysis. Reported OR and HRs with 95% CI were pooled using the Hartung-Knapp-Sidik-Jonkman method for random-effects models. The presence of HDV RNA+ was associated with an increased risk of any advanced liver disease event [random effect (95% CI): risk ratio: 1.48 (0.93, 2.33); HR: 2.62 (1.55, 4.44)]. When compared to the patients with HDV RNA- status, HDV RNA+ was associated with a significantly higher risk of progressing to compensated cirrhosis [risk ratio: 1.74 (1.24, 2.45)] decompensated cirrhosis [HR: 3.82 (1.60, 9.10)], HCC [HR: 2.97 (1.87, 4.70)], liver transplantation [HR: 7.07 (1.61, 30.99)], and liver-related mortality [HR: 3.78 (2.18, 6.56)].
CONCLUSIONS
The patients with HDV RNA+ status have a significantly greater risk of liver disease progression than the patients who are HDV RNA-. These findings highlight the need for improved HDV screening and linkage to treatment to reduce the risk of liver-related morbidity and mortality.
Topics: Humans; Hepatitis Delta Virus; Carcinoma, Hepatocellular; Liver Neoplasms; Hepatitis B Surface Antigens; Liver Cirrhosis; Morbidity; RNA, Viral; Disease Progression; Hepatitis B virus
PubMed: 37870278
DOI: 10.1097/HEP.0000000000000642 -
Frontiers in Public Health 2023Hepatitis C virus (HCV) infection is an independent risk factor associated with adverse outcomes in patients with end-stage renal disease (ESRD). Due to the wide variety... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hepatitis C virus (HCV) infection is an independent risk factor associated with adverse outcomes in patients with end-stage renal disease (ESRD). Due to the wide variety of direct-acting antiviral regimens (DAAs) and the factor of renal insufficiency, careless selection of anti-hepatitis C treatment can lead to treatment failure and safety problems. The integrated evidence for optimized therapies for these patients is lacking. This study would conduct comparisons of different DAAs and facilitate clinical decision-making.
METHODS
We conducted a systematic literature search in multiple databases (PubMed, Ovid, Embase, Cochrane Library, and Web of Science) up to 7 August 2023. Study data that contained patient characteristics, study design, treatment regimens, intention-to-treat sustained virologic response (SVR), and adverse event (AE) data per regimen were extracted into a structured electronic database and analyzed. The network meta-analysis of the estimation was performed by the Bayesian Markov Chain Monte Carlo methods.
RESULTS
Our search identified 5,278 articles; removing the studies with duplicates and ineligible criteria, a total of 62 studies (comprising 4,554 patients) were included. Overall, the analyses contained more than 2,489 male individuals, at least 202 patients with cirrhosis, and no less than 2,377 patients under hemodialysis. Network meta-analyses of the DAAs found that receiving ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (R) plus dasabuvir (DSV), glecaprevir (G)/pibrentasvir (P), and sofosbuvir (SOF)/ledipasvir (LDV) ranked as the top three efficacy factors for the HCV-infected ESRD patients. Stratified by genotype, the G/P would prioritize genotype 1 and 2 patients with 98.9%-100% SVR, the SOF/DCV regimen had the greatest SVR rates (98.7%; 95% CI, 93.0%-100.0%) in genotype 3, and the OBV/PTV/R regimen was the best choice for genotype 4, with the highest SVR of 98.1% (95% CI, 94.4%-99.9%). In the pan-genotypic DAAs comparison, the G/P regimen showed the best pooled SVR of 99.4% (95% CI, 98.6%-100%). DAA regimens without Ribavirin or SOF showed the lowest rates of AEs (49.9%; 95% CI, 38.4%-61.5%) in HCV-infected ESRD patients.
CONCLUSION
The G/P could be recommended as the best option for the treatment of pan-genotypic HCV-infected ESRD patients. The OBV/PTV/R plus DSV, SOF/Velpatasvir (VEL), SOF/Ledipasvir (LDV), and SOF/DCV would be reliable alternatives for HCV treatment with comparable efficacy and safety profiles.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/#searchadvanced, PROSPERO: CRD42021242359.
Topics: Humans; Male; Antiviral Agents; Network Meta-Analysis; Hepacivirus; Bayes Theorem; Hepatitis C, Chronic; Treatment Outcome; Ritonavir; Hepatitis C; Kidney Failure, Chronic
PubMed: 37841743
DOI: 10.3389/fpubh.2023.1179531 -
International Journal of Medical... Nov 2023Machine learning (ML) prediction models to support clinical management of blood-borne viral infections are becoming increasingly abundant in medical literature, with a... (Review)
Review
BACKGROUND
Machine learning (ML) prediction models to support clinical management of blood-borne viral infections are becoming increasingly abundant in medical literature, with a number of competing models being developed for the same outcome or target population. However, evidence on the quality of these ML prediction models are limited.
OBJECTIVE
This study aimed to evaluate the development and quality of reporting of ML prediction models that could facilitate timely clinical management of blood-borne viral infections.
METHODS
We conducted narrative evidence synthesis following the synthesis without meta-analysis guidelines. We searched PubMed and Cochrane Central Register of Controlled Trials for all studies applying ML models for predicting clinical outcomes associated with hepatitis B virus (HBV), human immunodeficiency virus (HIV), or hepatitis C virus (HCV).
RESULTS
We found 33 unique ML prediction models aiming to support clinical decision making. Overall, 12 (36.4%) focused on HBV, 10 (30.3%) on HCV, 10 on HIV (30.3%) and two (6.1%) on co-infection. Among these, six (18.2%) addressed the diagnosis of infection, 16 (48.5%) the prognosis of infection, eight (24.2%) the prediction of treatment response, two (6.1%) progression through a cascade of care, and one (3.03%) focused on the choice of antiretroviral therapy (ART). Nineteen prediction models (57.6%) were developed using data from high-income countries. Evaluation of prediction models was limited to measures of performance. Detailed information on software code accessibility was often missing. Independent validation on new datasets and/or in other institutions was rarely done.
CONCLUSION
Promising approaches for ML prediction models in blood-borne viral infections were identified, but the lack of robust validation, interpretability/explainability, and poor quality of reporting hampered their clinical relevance. Our findings highlight important considerations that can inform standard reporting guidelines for ML prediction models in the future (e.g., TRIPOD-AI), and provides critical data to inform robust evaluation of the models.
Topics: Humans; Hepatitis C; HIV Infections; Prognosis
PubMed: 37820561
DOI: 10.1016/j.ijmedinf.2023.105244 -
Annals of Hepatology 2024Occult HBV infection (OBI) is a specific form of hepatitis B virus (HBV) infection and has the possibility of developing into hepatocellular carcinoma (HCC) in adults.... (Meta-Analysis)
Meta-Analysis
INTRODUCTION AND OBJECTIVES
Occult HBV infection (OBI) is a specific form of hepatitis B virus (HBV) infection and has the possibility of developing into hepatocellular carcinoma (HCC) in adults. This study aimed to estimate the global prevalence of occult HBV infection in children and adolescents.
MATERIALS AND METHODS
We systematically searched PubMed, Embase, Web of Science, and Cochrane databases for relevant studies on the prevalence of OBI in children and adolescents. Meta-analysis was performed using STATA 16 software.
RESULTS
Fifty studies were included. The overall prevalence of OBI in children and adolescents was 7.5% (95% CI: 0.050-0.103). In different risk populations, OBI prevalence was remarkably high in the HIV-infected population (24.2%, 95% CI: 0.000-0.788). The OBI prevalence was 0.8% (95% CI:0.000-0.029) in the healthy population, 3.8% (95% CI:0.012-0.074) in the general population, and 6.4% (95% CI: 0.021-0.124) in children born to HBsAg-positive mothers. Based on different serological profiles, the prevalence of OBI in HBsAg-negative and anti-HBc-positive patients was 6.6% (95% CI: 0.016-0.136), 3.0% (95% CI: 0.009-0.059) in HBsAg-negative and anti-HBc-negative patients, 4.6% (95% CI: 0.015-0.088) in HBsAg-negative and anti-HBs-positive patients, and 3.7% (95% CI: 0.001-0.102) in HBsAg-negative and anti-HBs-negative patients.
CONCLUSIONS
Despite HBV vaccination and hepatitis B immunoglobulin (HBIG), OBI is common in children and adolescents in high-risk groups.
Topics: Adolescent; Child; Humans; Carcinoma, Hepatocellular; DNA, Viral; Hepatitis B; Hepatitis B Antibodies; Hepatitis B Surface Antigens; Hepatitis B virus; Liver Neoplasms; Prevalence
PubMed: 37748752
DOI: 10.1016/j.aohep.2023.101158 -
International Journal of Surgery... Nov 2023Hepatocellular carcinoma (HCC) is the third-most lethal malignant tumor worldwide. The rapid development of immunotherapy utilizing immune checkpoint inhibitors for... (Meta-Analysis)
Meta-Analysis
Clinico-characteristics of patients which correlated with preferable treatment outcomes in immunotherapy for advanced hepatocellular carcinoma: a systematic review and meta-analysis.
BACKGROUND AND AIMS
Hepatocellular carcinoma (HCC) is the third-most lethal malignant tumor worldwide. The rapid development of immunotherapy utilizing immune checkpoint inhibitors for advanced HCC patients has been witnessed in recent years, along with numerous randomized clinical trials demonstrating the survival benefits for these individuals. This systematic review and meta-analysis aimed to identify specific clinico-pathological characteristics of advanced HCC patients that may lead to preferable responses to immunotherapy in terms of overall survival (OS), progression-free survival (PFS), and objective response rate (ORR).
METHODS
The included clinical trials were retrieved from PubMed, Embase, the Cochrane library, and the Web of Science databases published in English between 1 January 2002 and 20 October 2022. A systematic review and meta-analysis for first-line and second-line phase II/III studies were conducted on immunotherapy for patients with advanced HCC by using OS as the primary outcome measure, and PFS and ORR as the secondary outcome measures to obtain clinico-pathological characteristics of patients which might be preferable responses to programmed death-1 (PD-1) and programmed cell death-Ligand 1 (PD-L1) inhibitors. Toxicity and specific treatment-related adverse events (TRAEs) were also determined.
RESULTS
After screening 1392 relevant studies, 12 studies were included in this systematic review and meta-analysis to include 5948 patients. Based on the analysis of interaction, the difference in OS after first-line immunotherapy between the subgroups of viral hepatitis [hazard ratio (HR)=0.73 vs 0.87, P for interaction=0.02] and macrovascular invasion and/or extrahepatic spread (HR=0.73 vs 0.89, P for interaction=0.02) were significant. The difference in PFS between the subgroups of viral hepatitis was highly significant (pooled HR=0.55 vs 0.81, P for interaction=0.007). After second-line immunotherapy, the difference in ORR between the subgroups of Barcelona Clinic Liver Cancer was significant (pooled ES=0.12 vs 0.23, P for interaction=0.04). Compared with PD-L1 inhibitors, PD-1 inhibitors may have a higher probability to cause TRAEs. Diarrhea, increased aspartate aminotransferase, and hypertension were the top three TRAEs.
CONCLUSIONS
This systematic review and meta-analysis represents the first pilot study aimed at identifying crucial clinico-pathological characteristics of patients with advanced HCC that may predict favorable treatment outcomes in terms of OS, PFS, and ORR to immunotherapy. Findings suggest that patients with viral hepatitis positivity (especially hepatitis B virus) and macrovascular invasion and/or extrahepatic spread may benefit more in OS when treated with PD-1/PD-L1 immune checkpoint inhibitors.
Topics: Humans; Carcinoma, Hepatocellular; B7-H1 Antigen; Immune Checkpoint Inhibitors; Pilot Projects; Programmed Cell Death 1 Receptor; Liver Neoplasms; Treatment Outcome; Immunotherapy; Hepatitis, Viral, Human; Lung Neoplasms
PubMed: 37598406
DOI: 10.1097/JS9.0000000000000652 -
The Lancet. Global Health Sep 2023The epidemiology of human papillomavirus (HPV) in women has been well documented. Less is known about the epidemiology of HPV in men. We aim to provide updated global... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The epidemiology of human papillomavirus (HPV) in women has been well documented. Less is known about the epidemiology of HPV in men. We aim to provide updated global and regional pooled overall, type-specific, and age-specific prevalence estimates of genital HPV infection in men.
METHODS
We conducted a systematic review and meta-analysis to assess the prevalence of genital HPV infection in the general male population. We searched Embase, Ovid MEDLINE, and the Global Index Medicus for studies published between Jan 1, 1995, and June 1, 2022. Inclusion criteria were population-based surveys in men aged 15 years or older or HPV prevalence studies with a sample size of at least 50 men with no HPV-related pathology or known risk factors for HPV infection that collected samples from anogenital sites and used PCR or hybrid capture 2 techniques for HPV DNA detection. Exclusion criteria were studies conducted among populations at increased risk of HPV infection, exclusively conducted among circumcised men, and based on urine or semen samples. We screened identified reports and extracted summary-level data from those that were eligible. Data were extracted by two researchers independently and reviewed by a third, and discrepancies were resolved by consensus. We extracted only data on mucosal α-genus HPVs. Global and regional age-specific prevalences for any HPV, high-risk (HR)-HPV, and individual HPV types were estimated using random-effects models for meta-analysis and grouped by UN Sustainable Development Goals geographical classification.
FINDINGS
We identified 5685 publications from database searches, of which 65 studies (comprising 44 769 men) were included from 35 countries. The global pooled prevalence was 31% (95% CI 27-35) for any HPV and 21% (18-24) for HR-HPV. HPV-16 was the most prevalent HPV genotype (5%, 95% CI 4-7) followed by HPV-6 (4%, 3-5). HPV prevalence was high in young adults, reaching a maximum between the ages of 25 years and 29 years, and stabilised or slightly decreased thereafter. Pooled prevalence estimates were similar for the UN Sustainable Development Goal geographical regions of Europe and Northern America, Sub-Saharan Africa, Latin America and the Caribbean, and Australia and New Zealand (Oceania). The estimates for Eastern and South-Eastern Asia were half that of the other regions.
INTERPRETATION
Almost one in three men worldwide are infected with at least one genital HPV type and around one in five men are infected with one or more HR-HPV types. Our findings show that HPV prevalence is high in men over the age of 15 years and support that sexually active men, regardless of age, are an important reservoir of HPV genital infection. These estimates emphasise the importance of incorporating men in comprehensive HPV prevention strategies to reduce HPV-related morbidity and mortality in men and ultimately achieve elimination of cervical cancer and other HPV-related diseases.
FUNDING
Instituto de Salud Carlos III, European Regional Development Fund, Secretariat for Universities and Research of the Department of Business and Knowledge of the Government of Catalonia, and Horizon 2020.
TRANSLATIONS
For the Spanish and French translations of the abstract see Supplementary Materials section.
Topics: Young Adult; Humans; Female; Male; Adult; Human Papillomavirus Viruses; Papillomavirus Infections; Prevalence; Sexually Transmitted Diseases; Uterine Cervical Neoplasms; Papillomaviridae
PubMed: 37591583
DOI: 10.1016/S2214-109X(23)00305-4 -
BMJ Open Aug 2023To synthesise the available evidence on the reporting of conflicts of interest (COI) by individuals posting health messages on social media, and on the reporting of...
OBJECTIVES
To synthesise the available evidence on the reporting of conflicts of interest (COI) by individuals posting health messages on social media, and on the reporting of funding sources of studies cited in health messages on social media.
DATA SOURCES
MEDLINE (OVID) (2005-March 2022), Embase (2005-March 2022) and Google Scholar (2005-August 2022), supplemented with a review of reference lists and forward citation tracking.
DESIGN
Reviewers selected eligible studies and abstracted data in duplicate and independently. We appraised the quality of the included studies using the Mixed Methods Appraisal Tool. We summarised the results in both narrative and tabular formats. We followed the PRISMA 2020 checklist for reporting our study.
RESULTS
Of a total of 16 645 retrieved citations, we included 17 eligible studies. The frequency of reporting of conflicts of interest varied between 0% and 60%, but it was mostly low. In addition, a significant proportion, ranging between 15% and 80%, of healthcare professionals using social media have financial relationships with industry. However, three studies assessed the proportion of conflicts of interest of physicians identified through Open Payment Database but not reported by the authors. It was found that 98.7-100% of these relationships with industry are not reported when communicating health-related information. Also, two studies showed that there is evidence of a potential association between COI and the content of posting. No data was found on the reporting of funding sources of studies cited in health messages on social media.
CONCLUSIONS
While a significant proportion of healthcare professionals using social media have financial relationships with industry, lack of reporting on COI and undisclosed COI are common. We did not find studies on the reporting of funding sources of studies cited in health messages on social media.
TRIAL REGISTRATION
dx.doi.org/10.17504/protocols.io.5jyl8jj4rg2w/v1.
Topics: Humans; Conflict of Interest; Health Communication; Social Media; Physicians; Industry
PubMed: 37580091
DOI: 10.1136/bmjopen-2023-072258 -
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 -
Veterinary Medicine and Science Sep 2023Rift Valley fever (RVF) is a severe zoonotic mosquito-borne disease that represents an important threat to human and animal health, with major public health and... (Meta-Analysis)
Meta-Analysis
Rift Valley fever (RVF) is a severe zoonotic mosquito-borne disease that represents an important threat to human and animal health, with major public health and socioeconomic impacts. This disease is endemic throughout many African countries and the Arabian Peninsula. This systematic review with meta-analysis was conducted to determine the RVF prevalence in humans, mosquitoes and other animal species in Africa. The review also provides contemporary data on RVF case fatality rate (CFR) in humans. In this systematic review with meta-analysis, a comprehensive literature search was conducted on the PubMed, Embase, Web of Science and Global Index Medicus databases from January 2000 to June 2022 to identify relevant studies. Pooled CFR and prevalence estimates were calculated using the random-effects model. Subgroup analysis and sensitivity analysis were performed, and the I -statistic was used to investigate a potential source of heterogeneity. A total of 205 articles were included in the final analysis. The overall RVF CFR in humans was found to be 27.5% [95% CI = 8.0-52.5]. The overall pooled prevalence was 7.8% [95% CI = 6.2-9.6] in humans and 9.3% [95% CI = 8.1-10.6] in animals, respectively. The RVF prevalence in individual mosquitoes ranged from 0.0% to 25%. Subgroup analysis showed substantial heterogeneity with respect to geographical regions and human categories. The study shows that there is a correspondingly similar prevalence of RVF in human and animals; however, human CFR is much higher than the observed prevalence. The lack of a surveillance programme and the fact that this virus has subclinical circulation in animals and humans could explain these observations. The implementation of a One Health approach for RVF surveillance and control would be of great interest for human and animal health.
Topics: Animals; Humans; Africa; Culicidae; Disease Outbreaks; Rift Valley Fever; Rift Valley fever virus
PubMed: 37548116
DOI: 10.1002/vms3.1238