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The Lancet. Infectious Diseases Dec 2016Advances in therapy for hepatitis B virus (HBV) and hepatitis C virus (HCV) have ushered in a new era in chronic hepatitis treatment. To maximise the effectiveness of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Advances in therapy for hepatitis B virus (HBV) and hepatitis C virus (HCV) have ushered in a new era in chronic hepatitis treatment. To maximise the effectiveness of these medicines, individuals must be engaged and retained in care. We analysed operational interventions to enhance chronic viral hepatitis testing, linkage to care, treatment uptake, adherence, and viral suppression or cure.
METHODS
We did a systematic review of operational interventions, and did meta-analyses for sufficiently comparable data. We searched PubMed, Embase, WHO library, International Clinical Trials Registry Platform, PsycINFO, and CINAHL for randomised controlled trials and controlled non-randomised studies that examined operational interventions along the chronic viral hepatitis care continuum, published in English up to Dec 31, 2014. We included non-pharmaceutical intervention studies with primary or secondary outcomes of testing, linkage to care, treatment uptake, treatment adherence, treatment completion, treatment outcome, or viral endpoints. We excluded dissertations and studies of children only. Data were extracted by two independent reviewers, with disagreements resolved by a third reviewer. Studies were assessed for bias. Data from similar interventions were pooled and quality of evidence was assessed using GRADE. This study was registered in PROSPERO (42014015094).
FINDINGS
We identified 7583 unduplicated studies, and included 56 studies that reported outcomes along the care continuum (41 for HCV and 18 for HBV). All studies except one were from high-income countries. Lay health worker HBV test promotion interventions increased HBV testing rates (relative risk [RR] 2·68, 95% CI 1·82-3·93). Clinician reminders to prompt HCV testing during clinical visits increased HCV testing rates (3·70, 1·81-7·57). Nurse-led educational interventions improved HCV treatment completion (1·14, 1·05-1·23) and cure (odds ratio [OR] 1·93, 95% CI 1·44-2·59). Coordinated mental health, substance misuse, and hepatitis treatment services increased HCV treatment uptake (OR 3·03, 1·24-7·37), adherence (RR 1·22, 1·05-1·41), and cure (RR 1·21, 1·07-1·38) compared with usual care.
INTERPRETATION
Several simple, inexpensive operational interventions can substantially improve engagement and retention along the chronic viral hepatitis care continuum. Further operational research to inform scale-up of hepatitis services is needed in low-income and middle-income countries.
FUNDING
World Health Organization and US Fulbright Program.
Topics: Continuity of Patient Care; Health Promotion; Hepatitis B; Hepatitis C; Hepatitis, Viral, Human; Humans; Medication Adherence
PubMed: 27615026
DOI: 10.1016/S1473-3099(16)30208-0 -
World Journal of Gastroenterology Oct 2023Noninvasive methods have been developed to detect fibrosis in many liver diseases due to the limits of liver biopsy. However, previous studies have focused primarily on... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Noninvasive methods have been developed to detect fibrosis in many liver diseases due to the limits of liver biopsy. However, previous studies have focused primarily on chronic viral hepatitis and nonalcoholic fatty liver disease. The diagnostic value of transient elastography for autoimmune liver diseases (AILDs) is worth studying.
AIM
To compare the diagnostic accuracy of imaging techniques with serum biomarkers of fibrosis in AILD.
METHODS
The PubMed, Cochrane Library and EMBASE databases were searched. Studies evaluating the efficacy of noninvasive methods in the diagnosis of AILDs [autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC)] were included. The summary area under the receiver operating characteristic curve (AUROC), diagnostic odds ratio, sensitivity and specificity were used to assess the accuracy of these noninvasive methods for staging fibrosis.
RESULTS
A total of 60 articles were included in this study, and the number of patients with AIH, PBC and PSC was 1594, 3126 and 501, respectively. The summary AUROC of transient elastography in the diagnosis of significant fibrosis, advanced fibrosis and cirrhosis in patients with AIH were 0.84, 0.88 and 0.90, respectively, while those in patients with PBC were 0.93, 0.93 and 0.91, respectively. The AUROC of cirrhosis for patients with PSC was 0.95. However, other noninvasive indices (aspartate aminotransferase to platelet ratio index, aspartate aminotransferase/alanine aminotransferase ratio, fibrosis-4 index) had corresponding AUROCs less than 0.80.
CONCLUSION
Transient elastography exerts better diagnostic accuracy in AILD patients, especially in PBC patients. The appropriate cutoff values for staging advanced fibrosis and cirrhosis ranged from 9.6 to 10.7 and 14.4 to 16.9 KPa for PBC patients.
Topics: Humans; Elasticity Imaging Techniques; Liver Cirrhosis; Fibrosis; Hepatitis, Autoimmune; ROC Curve; Non-alcoholic Fatty Liver Disease; Aspartate Aminotransferases; Liver
PubMed: 37900994
DOI: 10.3748/wjg.v29.i39.5503 -
Human Vaccines & Immunotherapeutics Nov 2022With 583 million inhabitants, the Eastern Mediterranean Region (EMR) is a worldwide hub for travel, migration, and food trade. However, there is a scarcity of data on...
INTRODUCTION
With 583 million inhabitants, the Eastern Mediterranean Region (EMR) is a worldwide hub for travel, migration, and food trade. However, there is a scarcity of data on the epidemiology of the hepatitis A virus (HAV).
METHODS
The MEDLINE and grey literature were systematically searched for HAV epidemiological data relevant to the EMR region published between 1980 and 2020 in English, French, or Arabic.
RESULTS
Overall, 123 publications were extracted. The proportion of HAV cases among acute viral hepatitis cases was high. HAV seroprevalence rate ranged from 5.7% to 100.0% and it was decreasing over time while the average age at infection increased.
CONCLUSION
In the EMR, HAV remains a significant cause of acute viral hepatitis. The observed endemicity shift will likely increase disease burden as the population ages. Vaccinating children and adopting sanitary measures are still essential to disease prevention; vaccinating at-risk groups might reduce disease burden even further.
Topics: Child; Humans; Hepatitis A; Seroepidemiologic Studies; Hepatitis A virus; Hepatitis A Antibodies; Travel; Acute Disease
PubMed: 35617508
DOI: 10.1080/21645515.2022.2073146 -
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 -
Clinical and Molecular Hepatology Jul 2023Chronic hepatitis B (CHB) and fatty liver (FL) often co-exist, but natural history data of this dual condition (CHB-FL) are sparse. Via a systematic review, conventional... (Meta-Analysis)
Meta-Analysis
BACKGROUND/AIMS
Chronic hepatitis B (CHB) and fatty liver (FL) often co-exist, but natural history data of this dual condition (CHB-FL) are sparse. Via a systematic review, conventional meta-analysis (MA) and individual patient-level data MA (IPDMA), we compared liver-related outcomes and mortality between CHB-FL and CHB-no FL patients.
METHODS
We searched 4 databases from inception to December 2021 and pooled study-level estimates using a random- effects model for conventional MA. For IPDMA, we evaluated outcomes after balancing the two study groups with inverse probability treatment weighting (IPTW) on age, sex, cirrhosis, diabetes, ALT, HBeAg, HBV DNA, and antiviral treatment.
RESULTS
We screened 2,157 articles and included 19 eligible studies (17,955 patients: 11,908 CHB-no FL; 6,047 CHB-FL) in conventional MA, which found severe heterogeneity (I2=88-95%) and no significant differences in HCC, cirrhosis, mortality, or HBsAg seroclearance incidence (P=0.27-0.93). IPDMA included 13,262 patients: 8,625 CHB-no FL and 4,637 CHB-FL patients who differed in several characteristics. The IPTW cohort included 6,955 CHB-no FL and 3,346 CHB-FL well-matched patients. CHB-FL patients (vs. CHB-no FL) had significantly lower HCC, cirrhosis, mortality and higher HBsAg seroclearance incidence (all p≤0.002), with consistent results in subgroups. CHB-FL diagnosed by liver biopsy had a higher 10-year cumulative HCC incidence than CHB-FL diagnosed with non-invasive methods (63.6% vs. 4.3%, p<0.0001).
CONCLUSION
IPDMA data with well-matched CHB patient groups showed that FL (vs. no FL) was associated with significantly lower HCC, cirrhosis, and mortality risk and higher HBsAg seroclearance probability.
Topics: Humans; Carcinoma, Hepatocellular; Hepatitis B Surface Antigens; Hepatitis B, Chronic; Liver Neoplasms; Hepatitis B virus; Antiviral Agents; Liver Cirrhosis; Fatty Liver; DNA, Viral
PubMed: 37157776
DOI: 10.3350/cmh.2023.0004 -
Annals of Internal Medicine Jan 2016Solid tumor chemotherapy regimens pose a risk for hepatitis B virus (HBV) reactivation, but screening and antiviral prophylaxis remains controversial because of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Solid tumor chemotherapy regimens pose a risk for hepatitis B virus (HBV) reactivation, but screening and antiviral prophylaxis remains controversial because of insufficient evidence.
PURPOSE
To determine the risk for HBV reactivation with and without antiviral prophylaxis and the effectiveness of prophylaxis in adults with solid tumors and chronic or resolved HBV infection.
DATA SOURCES
MEDLINE through 1 July 2015 and Web of Science, Cochrane Central Register of Controlled Trials, TOXNET, and Scopus through 1 March 2015.
STUDY SELECTION
26 English-language observational studies and randomized, controlled trials in patients with chronic or resolved HBV receiving chemotherapy for solid tumors.
DATA EXTRACTION
Study characteristics, quality, and risk of bias were assessed by 1 researcher and verified by another independent researcher.
DATA SYNTHESIS
Random-effects model meta-analyses were used to estimate the risk and odds ratio (OR) of reactivation with versus without antiviral prophylaxis. Reactivation in chronic HBV without prophylaxis ranged from 4% to 68% (median, 25%) with substantial heterogeneity. Prophylaxis reduced the risk for HBV reactivation (OR, 0.12 [95% CI, 0.06 to 0.22]), HBV-related hepatitis (OR, 0.18 [CI, 0.10 to 0.32]), and chemotherapy interruption (OR, 0.10 [CI, 0.04 to 0.27]). In 3 studies of patients with resolved HBV infection, none received HBV prophylaxis and reactivation risk ranged from 0.3% to 9.0%.
LIMITATIONS
Significant heterogeneity in underlying study populations and treatment regimens, incomplete baseline data, possibility of publication bias, and limited study quality. Most studies were observational and from Asia.
CONCLUSION
In patients with chronic HBV receiving solid tumor chemotherapy, the risk for HBV reactivation is similar to the risk with other types of immunosuppressive therapy. Results support HBV screening and antiviral prophylaxis before initiation of chemotherapy for solid tumors.
PRIMARY FUNDING SOURCE
National Center for Advancing Translational Sciences and National Institutes of Health.
Topics: Adult; Antiviral Agents; Hepatitis B; Hepatitis B virus; Hepatitis B, Chronic; Humans; Neoplasms; Risk Factors; Virus Activation
PubMed: 26595058
DOI: 10.7326/M15-1121 -
Clinical Infectious Diseases : An... Oct 2023Many people who have a positive hepatitis C virus (HCV) antibody (Ab) test never receive a confirmatory HCV RNA viral load (VL) test. Reflex VL testing may help address... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Many people who have a positive hepatitis C virus (HCV) antibody (Ab) test never receive a confirmatory HCV RNA viral load (VL) test. Reflex VL testing may help address this problem. We undertook a systematic review to evaluate the effectiveness of reflex VL testing compared with standard nonreflex approaches on outcomes across the HCV care cascade.
METHODS
We searched 4 databases for studies that examined laboratory-based reflex or clinic-based reflex VL testing approaches, with or without a nonreflex comparator, and had data on the uptake of HCV RNA VL test and treatment initiation and turnaround time between Ab and VL testing. Both laboratory- and clinic-based reflex VL testing involve only a single clinic visit. Summary estimates were calculated using random-effects meta-analyses.
RESULTS
Fifty-one studies were included (32 laboratory-based and 19 clinic-based reflex VL testing). Laboratory-based reflex VL testing increased HCV VL test uptake versus nonreflex testing (RR: 1.35; 95% CI: 1.16-1.58) and may improve linkage to care among people with a positive HCV RNA test (RR: 1.47; 95% CI: .81-2.67) and HCV treatment initiation (RR: 1.03; 95% CI: .46-2.32). The median time between Ab and VL test was <1 day for all laboratory-based reflex studies and 0-5 days for 13 clinic-based reflex testing.
CONCLUSIONS
Laboratory-based and clinic-based HCV reflex VL testing increased uptake and reduced time to HCV VL testing and may increase HCV linkage to care. The World Health Organization now recommends reflex VL testing as an additional strategy to promote access to HCV VL testing and treatment.
CLINICAL TRIALS REGISTRATION
PROSPERO CRD42021283822.
Topics: Humans; Hepatitis C; Hepacivirus; Viral Load; Reflex; RNA
PubMed: 37648655
DOI: 10.1093/cid/ciad126 -
Journal of Evidence-based Medicine Feb 2018Hepatitis C virus (HCV) infection is one of the most common causes of chronic liver disease. Several epidemiologic studies have suggested that patients with HCV... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND/OBJECTIVES
Hepatitis C virus (HCV) infection is one of the most common causes of chronic liver disease. Several epidemiologic studies have suggested that patients with HCV infection might have a higher risk of osteoporotic fracture. However, the data are inconclusive. This systematic review and meta-analysis was conducted with the aims to summarize all available evidence.
METHODS
A literature search was performed using MEDLINE and EMBASE database from inception to June 2016. Studies that reported relative risks, odd ratios, or hazard ratios comparing the risk of osteoporotic fracture among HCV-infected patients versus subjects without HCV infection were included. Pooled risk ratio (RR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method.
RESULTS
Three studies with 362,285 participants met our eligibility criteria and were included in analysis. We found a significantly higher risk of osteoporotic fracture among patients with HCV infection with RR of 1.53 (95% CI 1.09 to 2.14).
CONCLUSIONS
Our study demonstrated an increased risk of osteoporotic fracture among HCV-infected patients. Further studies are required to clarify how this risk should be addressed in clinical practice.
Topics: Hepatitis C, Chronic; Humans; Osteoporotic Fractures
PubMed: 29322660
DOI: 10.1111/jebm.12286 -
Virology Journal Jul 2021The relationship between psoriasis and hepatitis C was previously controversial, so our purpose is to investigate this connection. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The relationship between psoriasis and hepatitis C was previously controversial, so our purpose is to investigate this connection.
METHODS
We conducted a systematic review of the case-control, cross-sectional and cohort studies examining the association between psoriasis and hepatitis C in PubMed, EMBASE and Cochrane library databases and investigated the overlapping genes between psoriasis targets and hepatitis C targets using bioinformatics analysis. Based on overlapping genes and hub nodes, we also constructed the protein-protein interaction (PPI) network and module respectively, followed by the pathway enrichment analysis.
RESULTS
We included 11 publications that reported a total of 11 studies (8 cross-sectional and 3 case-control). The case-control and cross-sectional studies included 25,047 psoriasis patients and 4,091,631 controls in total. Psoriasis was associated with a significant increase of prevalent hepatitis C (OR 1.72; 95% confidence interval [CI] (1.17-2.52)). A total of 389 significant genes were common to both hepatitis C and psoriasis, which mainly involved IL6, TNF, IL10, ALB, STAT3 and CXCL8. The module and pathway enrichment analyses showed that the common genes had the potential to influence varieties of biological pathways, including the inflammatory response, cytokine activity, cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway, which play an important role in the pathogenesis of hepatitis C and psoriasis.
CONCLUSION
Patients with psoriasis display increased prevalence of hepatitis C and the basic related mechanisms between hepatitis C and psoriasis had been preliminarily clarified.
Topics: Computational Biology; Cross-Sectional Studies; Hepatitis C; Humans; Protein Interaction Maps; Psoriasis
PubMed: 34215260
DOI: 10.1186/s12985-021-01606-z -
Frontiers in Immunology 2021Immune checkpoint inhibitors (ICIs) have been widely used in hepatocellular carcinoma (HCC), while only a subset of patients experience clinical benefit. We aimed to... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIM
Immune checkpoint inhibitors (ICIs) have been widely used in hepatocellular carcinoma (HCC), while only a subset of patients experience clinical benefit. We aimed to investigate the effects of viral etiology on response to ICIs in HCC and depict the tumor immune microenvironment (TIME) of virally infected and uninfected HCC.
METHODS
A systematic search was conducted in PubMed, Web of Science, Embase, and the Cochrane central register of controlled trials up to August 2021. Clinical trials reporting the efficacy of ICIs in HCC were eligible. Baseline characteristics including first author, year of publication, National Clinical Trials (NCT) registry number, study region, sample sizes, interventions, line of treatment, and viral status were extracted. Meta-analysis was conducted to generate combined odds ratios (ORs) with 95% confidence intervals (CI) based on random or fixed effect model, depending on heterogeneity. Tumor immune microenvironment was depicted using ESTIMATE and CIBERSORT algorithm.
RESULTS
Eight studies involving 1,520 patients were included. Combined data suggested that there was no significant difference of objective response rate (ORR) between virally infected HCC and non-viral HCC patients [OR = 1.03 (95% CI, 0.77-1.37; I = 30.9%, p = 0.152)]. Similarly, difference was not observed on ORR between HBV-HCC and HCV-HCC patients [OR = 0.74 (95% CI, 0.52-1.06; I = 7.4%, p = 0.374)]. The infiltration of immune cells in the tumor microenvironment did not differ by etiology except for M0 macrophages, M2 macrophages, regulatory T cells, naive B cells, follicular helper T cells, activated dendritic cells, activated mast cells, and plasma cells. Despite differences in infiltration observed in specific cell types, the immune score and stromal score were generally comparable among etiology groups.
CONCLUSION
Viral etiology may not be considered as the selection criteria for patients receiving ICIs in HCC, and viral status has little impact on TIME remodeling during HCC tumorigenesis.
Topics: Animals; Carcinoma, Hepatocellular; Hepacivirus; Hepatitis C; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Liver Neoplasms; Tumor Microenvironment
PubMed: 34659220
DOI: 10.3389/fimmu.2021.733530