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Journal of Hepatology Sep 2020There are uncertainties about the epidemic patterns of HDV infection and its contribution to the burden of liver disease. We estimated the global prevalence of HDV... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
There are uncertainties about the epidemic patterns of HDV infection and its contribution to the burden of liver disease. We estimated the global prevalence of HDV infection and explored its contribution to the development of cirrhosis and hepatocellular carcinoma (HCC) among HBsAg-positive people.
METHODS
We searched Pubmed, EMBASE and Scopus for studies reporting on total or IgG anti-HDV among HBsAg-positive people. Anti-HDV prevalence was estimated using a binomial mixed model, weighting for study quality and population size. The population attributable fraction (PAF) of HDV to cirrhosis and HCC among HBsAg-positive people was estimated using random effects models.
RESULTS
We included 282 studies, comprising 376 population samples from 95 countries, which together tested 120,293 HBsAg-positive people for anti-HDV. The estimated anti-HDV prevalence was 4.5% (95% CI 3.6-5.7) among all HBsAg-positive people and 16.4% (14.6-18.6) among those attending hepatology clinics. Worldwide, 0.16% (0.11-0.25) of the general population, totalling 12.0 (8.7-18.7) million people, were estimated to be anti-HDV positive. Prevalence among HBsAg-positive people was highest in Mongolia, the Republic of Moldova and countries in Western and Middle Africa, and was higher in injecting drug users, haemodialysis recipients, men who have sex with men, commercial sex workers, and those with HCV or HIV. Among HBsAg-positive people, preliminary PAF estimates of HDV were 18% (10-26) for cirrhosis and 20% (8-33) for HCC.
CONCLUSIONS
An estimated 12 million people worldwide have experienced HDV infection, with higher prevalence in certain geographic areas and populations. HDV is a significant contributor to HBV-associated liver disease. More quality data are needed to improve the precision of burden estimates.
LAY SUMMARY
We combined all available studies to estimate how many people with hepatitis B also have hepatitis D, a viral infection that only affects people with hepatitis B. About 1 in 22 people with hepatitis B also have hepatitis D, increasing to 1 in 6 when considering people with liver disease. Hepatitis D may cause about 1 in 6 of the cases of cirrhosis and 1 in 5 of the cases of liver cancer that occur in people with hepatitis B. Hepatitis D is an important contributor to the global burden of liver disease.
Topics: Adult; Carcinoma, Hepatocellular; Coinfection; Female; Genotype; Hepatitis Antibodies; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis D; Hepatitis Delta Virus; Homosexuality, Male; Humans; Immunoglobulin G; Liver Cirrhosis; Liver Neoplasms; Male; Prevalence; RNA, Viral; Renal Dialysis; Sex Workers; Sexual and Gender Minorities; Substance Abuse, Intravenous
PubMed: 32335166
DOI: 10.1016/j.jhep.2020.04.008 -
Hepatology (Baltimore, Md.) Jan 2016Chronic hepatitis B viral (HBV) infection remains a significant global health problem. Evidence-based guidelines are needed to help providers determine when treatment... (Meta-Analysis)
Meta-Analysis Review
UNLABELLED
Chronic hepatitis B viral (HBV) infection remains a significant global health problem. Evidence-based guidelines are needed to help providers determine when treatment should be initiated, which medication is most appropriate, and when treatment can safely be stopped. The American Association for the Study of Liver Diseases HBV guideline methodology and writing committees developed a protocol a priori for this systematic review. We searched multiple databases for randomized controlled trials and controlled observational studies that enrolled adults ≥18 years old diagnosed with chronic HBV infection who received antiviral therapy. Data extraction was done by pairs of independent reviewers. We included 73 studies, of which 59 (15 randomized controlled trials and 44 observational studies) reported clinical outcomes. Moderate-quality evidence supported the effectiveness of antiviral therapy in patients with immune active chronic HBV infection in reducing the risk of cirrhosis, decompensated liver disease, and hepatocellular carcinoma. In immune tolerant patients, moderate-quality evidence supports improved intermediate outcomes with antiviral therapy. Only very low-quality evidence informed the questions about discontinuing versus continuing antiviral therapy in hepatitis B e antigen-positive patients who seroconverted from hepatitis B e antigen to hepatitis B e antibody and about the safety of entecavir versus tenofovir. Noncomparative and indirect evidence was available for questions about stopping versus continuing antiviral therapy in hepatitis B e antigen-negative patients, monotherapy versus adding a second agent in patients with persistent viremia during treatment, and the effectiveness of antivirals in compensated cirrhosis with low-level viremia.
CONCLUSION
Most of the current literature focuses on the immune active phases of chronic HBV infection; decision-making in other commonly encountered and challenging clinical settings depends on indirect evidence.
Topics: Adult; Antiviral Agents; Hepatitis B e Antigens; Hepatitis B, Chronic; Humans; Liver Cirrhosis
PubMed: 26566246
DOI: 10.1002/hep.28280 -
Journal of Hepatology Jan 2020Cholangiocarcinoma (CCA) carries a poor prognosis, is increasing in incidence and its causes are poorly understood. Although some risk factors are known, they vary...
BACKGROUND & AIMS
Cholangiocarcinoma (CCA) carries a poor prognosis, is increasing in incidence and its causes are poorly understood. Although some risk factors are known, they vary globally and collectively account for a minority of cases. The aim of this study was to perform a comprehensive meta-analysis of risk factors for intrahepatic (iCCA) and extrahepatic cholangiocarcinoma (eCCA), from Eastern and Western world studies.
METHODS
A literature search of case-control studies was performed to identify potential risk factors for iCCA and eCCA. Pooled odds ratios (ORs) with 95% CIs and heterogeneity were calculated. Funnel plots were used to assess publication bias, and meta-regression was used to select risk factors for comparison between Eastern and Western studies.
RESULTS
A total of 13 risk factors were selected from 25 case-control studies in 7 geographically diverse countries. The strongest risk factors for both iCCA and eCCA were biliary cysts and stones, cirrhosis, hepatitis B and hepatitis C. Choledochal cysts conferred the greatest risk of both iCCA and eCCA with pooled ORs of 26.71 (95% CI 15.80-45.16) and 34.94 (24.36-50.12), respectively. No significant associations were found between hypertension and obesity for either iCCA or eCCA. Comparing Eastern and Western populations, there was a difference for the association of hepatitis B with iCCA (coefficient = -0.15195; 95% CI -0.278 to -0.025; p = 0.022).
CONCLUSION
This is the most comprehensive meta-analysis of CCA risk factors to date. Some risk factors, such as diabetes, although less strong, are increasing globally and may be contributing to rising rates of this cancer.
LAY SUMMARY
Cholangiocarcinoma (CCA) is a cancer arising in the bile ducts inside (intrahepatic CCA) and connected to the liver (extrahepatic CCA). It is a very aggressive cancer: 95% of patients die within 5 years. CCA rates are increasing globally, but the causes of CCA are poorly understood. The few risk factors that are known account for only a minority of cases. In this study, we found that the strongest risk factors for both intrahepatic and extrahepatic CCA are cysts and stones in the bile ducts, cirrhosis, and hepatitis B and C viruses. Some risk factors for CCA, such as diabetes, although less strong, are increasing globally and may be contributing to rising rates of CCA.
Topics: Alcohol Drinking; Bile Duct Neoplasms; Bile Ducts, Extrahepatic; Bile Ducts, Intrahepatic; Case-Control Studies; Cholangiocarcinoma; Hepacivirus; Hepatitis B; Hepatitis B virus; Hepatitis C; Humans; Incidence; Liver Cirrhosis, Biliary; Risk Factors
PubMed: 31536748
DOI: 10.1016/j.jhep.2019.09.007 -
The Lancet. Gastroenterology &... Oct 2022Despite growing concerns about transmissibility and clinical impact, occult hepatitis B virus (HBV) infection has received little attention in the hepatitis elimination... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite growing concerns about transmissibility and clinical impact, occult hepatitis B virus (HBV) infection has received little attention in the hepatitis elimination agenda. We aimed to estimate the prevalence of occult HBV infection at a global and regional scale and in specific populations.
METHODS
For this systematic review and meta-analysis, we searched the MEDLINE, Embase, Global Health, and Web of Science databases for articles published in any language between Jan 1, 2010, and Aug 14, 2019. We included original articles and conference abstracts of any study design that reported the proportion of HBsAg-negative adults (aged ≥18 years) who are positive for HBV DNA (ie, people with occult HBV infection). The prevalence of occult HBV infection was pooled, using the DerSimonian-Laird random-effects model, in the general population and specific groups defined by the type of study participants (blood donors; other low-risk populations; high-risk populations; and people with advanced chronic liver disease), and stratified by HBV endemicity in each country. We also assessed the performance of anti-HBc as an alternative biomarker to detect occult HBV infection. The study was registered with PROSPERO, CRD42019115490.
FINDINGS
305 of 3962 articles were eligible, allowing a meta-analysis of 140 521 993 individuals tested for HBV DNA. Overall, only two studies evaluated occult HBV infection in the general population, precluding unbiased global and regional estimates of occult HBV infection prevalence. In blood donors, occult HBV infection prevalence mirrored HBV endemicity: 0·06% (95% CI 0·00-0·26) in low-endemicity countries, 0·12% (0·04-0·23) in intermediate-endemicity countries, and 0·98% (0·44-1·72), in high-endemicity countries (p=0·0012). In high-risk groups, occult HBV infection prevalence was substantial, irrespective of endemicity: 5·5% (95% CI 2·9-8·7) in low-endemicity countries, 5·2% (2·5-8·6) in intermediate-endemicity countries, and 12·0% (3·4-24·7) in high-endemicity countries. The pooled sensitivity of anti-HBc to identify occult HBV infection was 77% (95% CI 62-88) and its specificity was 76% (68-83).
INTERPRETATION
A substantial proportion of people carry occult HBV infection, especially among high-risk groups across the globe and people living in highly endemic countries. Occult HBV infection should be part of the global viral hepatitis elimination strategy.
FUNDING
None.
Topics: Adolescent; Adult; DNA, Viral; Hepatitis B; Hepatitis B Antibodies; Hepatitis B virus; Hepatitis B, Chronic; Humans; Prevalence
PubMed: 35961359
DOI: 10.1016/S2468-1253(22)00201-1 -
The Lancet. Gastroenterology &... Aug 2022Empirical, updated country-level estimates on the proportion of cirrhosis attributable to viral hepatitis are required. We estimated the prevalence of hepatitis B virus...
BACKGROUND
Empirical, updated country-level estimates on the proportion of cirrhosis attributable to viral hepatitis are required. We estimated the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in patients with cirrhosis at country, regional, and global levels as an approximation for the fractions of cirrhosis attributable to viral hepatitis.
METHODS
In this systematic review, we searched MEDLINE, Embase, Web of Science, and Scielo between Jan 1, 1993, and Aug 1, 2021. Studies were eligible if they reported on the prevalence of both HBV and HCV infection in representative studies of at least 20 patients with cirrhosis. Studies were excluded if they used first-generation HCV assays or were from a selected population of patients with cirrhosis (eg, patients selected based on specific causes, veterans, injecting drug users). Two authors (CJA and CdM) selected and extracted aggregated data from the selected publications. Data were extracted for study recruitment period, age, sex, and cause of cirrhosis, among others. Data about heavy alcohol consumption and non-alcoholic fatty liver disease (NAFLD) were also extracted when available. Aggregated data from studies from key publications were requested from the authors of the original study if selection of patients was unclear or information on causes was missing. We estimated the country-specific prevalence of causes of cirrhosis by pooling study-level data from the same country using a random-effects model. Subsequently, we estimated the regional (WHO region and UN subregion) and global prevalence by weighting the country-specific prevalence by the number of new liver cancer cases that occurred in 2020, as estimated in GLOBOCAN. The study was registered with PROSPERO, CRD42020149323.
FINDINGS
Our database searches identified 21 338 records, and a further nine records were identified by scanning references of key publications. After excluding duplicates and assessing full-text articles for eligibility, 520 publications from 86 countries or territories (and reporting on 1 376 503 patients with cirrhosis) were included in the systematic review. The prevalence of HBV infection was lower among patients with cirrhosis in Europe, the Americas, and Oceania (UN subregional prevalence ranges 3-14%) than in Africa and Asia (8-61%). HCV infection prevalence was heterogenous, even within regions (12-83%). The combined prevalence of HBV and HCV infection exceeded 50% in most Asian and African regions. Globally, among patients with cirrhosis, 42% had HBV infection and 21% had HCV infection. The contribution of heavy alcohol use was highest in Europe (country range 16-78%), the Americas (17-52%), and Oceania (15-37%) and lowest in Asia (0-41%). Data on NAFLD were limited.
INTERPRETATION
HBV and HCV could account for almost two thirds of the global burden of cirrhosis. With the availability of effective interventions for the prevention or treatment of HBV and HCV, the data presented in this study will help to effectively allocate resources towards viral hepatitis elimination and to design interventions at the country level.
FUNDING
International Agency for Research on Cancer, World Health Organization.
Topics: Hepacivirus; Hepatitis B; Hepatitis B virus; Hepatitis C; Hepatitis, Viral, Human; Humans; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease; Prevalence; United States
PubMed: 35576953
DOI: 10.1016/S2468-1253(22)00050-4 -
Vaccine Jan 2019Coverage levels for many recommended adult vaccinations are low. The cost-effectiveness research literature on adult vaccinations has not been synthesized in recent...
BACKGROUND
Coverage levels for many recommended adult vaccinations are low. The cost-effectiveness research literature on adult vaccinations has not been synthesized in recent years, which may contribute to low awareness of the value of adult vaccinations and to their under-utilization. We assessed research literature since 1980 to summarize economic evidence for adult vaccinations included on the adult immunization schedule.
METHODS
We searched PubMed, EMBASE, EconLit, and Cochrane Library from 1980 to 2016 and identified economic evaluation or cost-effectiveness analysis for vaccinations targeting persons aged ≥18 years in the U.S. or Canada. After excluding records based on title and abstract reviews, the remaining publications had a full-text review from two independent reviewers, who extracted economic values that compared vaccination to "no vaccination" scenarios.
RESULTS
The systematic searches yielded 1688 publications. After removing duplicates, off-topic publications, and publications without a "no vaccination" comparison, 78 publications were included in the final analysis (influenza = 25, pneumococcal = 18, human papillomavirus = 9, herpes zoster = 7, tetanus-diphtheria-pertussis = 9, hepatitis B = 9, and multiple vaccines = 1). Among outcomes assessing age-based vaccinations, the percent indicating cost-savings was 56% for influenza, 31% for pneumococcal, and 23% for tetanus-diphtheria-pertussis vaccinations. Among age-based vaccination outcomes reporting $/QALY, the percent of outcomes indicating a cost per QALY of ≤$100,000 was 100% for influenza, 100% for pneumococcal, 69% for human papillomavirus, 71% for herpes zoster, and 50% for tetanus-diphtheria-pertussis vaccinations.
CONCLUSIONS
The majority of published studies report favorable cost-effectiveness profiles for adult vaccinations, which supports efforts to improve the implementation of adult vaccination recommendations.
Topics: Adult; Age Factors; Canada; Cost-Benefit Analysis; Diphtheria; Diphtheria-Tetanus-Pertussis Vaccine; Hepatitis B; Humans; Immunization Schedule; Influenza Vaccines; Influenza, Human; Pneumococcal Vaccines; Pneumonia, Pneumococcal; Tetanus; United States; Vaccination
PubMed: 30527660
DOI: 10.1016/j.vaccine.2018.11.056 -
Hepatology (Baltimore, Md.) Nov 2020Chronic hepatitis B virus (HBV), hepatitis C virus (HCV), nonalcoholic fatty liver disease (NAFLD), and alcohol-associated liver disease (ALD) are main causes of chronic...
BACKGROUND AND AIMS
Chronic hepatitis B virus (HBV), hepatitis C virus (HCV), nonalcoholic fatty liver disease (NAFLD), and alcohol-associated liver disease (ALD) are main causes of chronic liver disease. We assessed the global incidence, mortality, and disability-adjusted life-years (DALYs) related to chronic liver disease (primary liver cancer [LC] and cirrhosis).
APPROACH AND RESULTS
We obtained data from the 2017 Global Burden of Disease study. In 2017, there were 2.14 million liver-related deaths (2.06-2.30 million), representing an 11.4% increase since 2012 (16.0% increase in LC deaths; 8.7% increase in cirrhosis deaths). LC and cirrhosis accounted for 38.3% and 61.7%, respectively, of liver deaths (LC and cirrhosis deaths were related to HBV [39% and 29%], HCV [29% and 26%], ALD [16% and 25%], and NAFLD [8% and 9%]). Between 2012 and 2017, age-standardized incidence rate, age-standardized death rate (ASDR), and age-standardized DALY rate increased for LC from 11.1 to 11.8, 10.1 to 10.2, and 250.4 to 253.6 per 100,000, respectively. Although age-standardized incidence rate for cirrhosis increased from 66.0 to 66.3, ASDR and age-standardized DALY rate decreased from 17.1 to 16.5 and 532.9 to 510.7, respectively. The largest increase in ASDR for LC occurred in Eastern Europe (annual percent change [APC] = 2.18% [0.89%-3.49%]), whereas the largest decrease occurred in high-income Asia Pacific (APC = -2.88% [-3.58 to -2.18%]). ASDR for LC-NAFLD and ALD increased annually by 1.42% (1.00%-1.83%) and 0.53% (0.08-0.89), respectively, whereas there were no increases for HBV (P = 0.224) and HCV (P = 0.054). ASDR for cirrhosis-NAFLD increased (APC = 0.29% [0.01%-0.59%]) but decreased for ALD (APC = -0.44% [-0.78% to -0.40%]), HCV (APC = -0.50% [-0.81% to -0.18%]), and HBV (APC = -1.43% [-1.71% to -0.40%]).
CONCLUSIONS
From 2012 to 2017, the global burden of LC and cirrhosis has increased. Viral hepatitis remains the most common cause of liver deaths, and NAFLD is the most rapidly growing contributor to liver mortality and morbidity.
Topics: Disease Progression; Global Burden of Disease; Hepatitis B, Chronic; Hepatitis C, Chronic; Humans; Incidence; Liver Cirrhosis; Liver Diseases, Alcoholic; Liver Neoplasms; Mortality; Non-alcoholic Fatty Liver Disease; Quality-Adjusted Life Years; Risk Factors
PubMed: 32043613
DOI: 10.1002/hep.31173 -
The Journal of Infectious Diseases Apr 2020Hepatitis delta virus (HDV) coinfects with hepatitis B virus (HBV) causing the most severe form of viral hepatitis. However, its exact global disease burden remains... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hepatitis delta virus (HDV) coinfects with hepatitis B virus (HBV) causing the most severe form of viral hepatitis. However, its exact global disease burden remains largely obscure. We aim to establish the global epidemiology, infection mode-stratified disease progression, and clinical outcome of HDV infection.
METHODS
We conducted a meta-analysis with a random-effects model and performed data synthesis.
RESULTS
The pooled prevalence of HDV is 0.80% (95% confidence interval [CI], 0.63-1.00) among the general population and 13.02% (95% CI, 11.96-14.11) among HBV carriers, corresponding to 48-60 million infections globally. Among HBV patients with fulminant hepatitis, cirrhosis, or hepatocellular carcinoma, HDV prevalence is 26.75% (95% CI, 19.84-34.29), 25.77% (95% CI, 20.62-31.27), and 19.80% (95% CI, 10.97-30.45), respectively. The odds ratio (OR) of HDV infection among HBV patients with chronic liver disease compared with asymptomatic controls is 4.55 (95% CI, 3.65-5.67). Hepatitis delta virus-coinfected patients are more likely to develop cirrhosis than HBV-monoinfected patients with OR of 3.84 (95% CI, 1.79-8.24). Overall, HDV infection progresses to cirrhosis within 5 years and to hepatocellular carcinoma within 10 years, on average.
CONCLUSIONS
Findings suggest that HDV poses a heavy global burden with rapid progression to severe liver diseases, urging effective strategies for screening, prevention, and treatment.
Topics: Developing Countries; Global Health; Hepatitis D; Hepatitis Delta Virus; Humans; Prevalence; Risk Factors
PubMed: 31778167
DOI: 10.1093/infdis/jiz633 -
International Journal of Medical... Nov 2023Lack of accurate and timely diagnosis of hepatitis poses obstacles to effective treatment, disease progression prevention, complication reduction, and life-saving... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Lack of accurate and timely diagnosis of hepatitis poses obstacles to effective treatment, disease progression prevention, complication reduction, and life-saving interventions of patients. Utilizing machine learning can greatly enhance the achievement of timely and precise disease diagnosis. Therefore, we carried out this systematic review and meta-analysis to explore the performance of machine learning algorithms in predicting viral hepatitis.
METHODS
Using an extensive literature search in PubMed, Scopus, and Web of Science databases until June 15, 2023, English publications on hepatitis prediction using machine learning algorithms were included. Two authors independently extracted pertinent information from the selected studies. The PRISMA 2020 checklist was followed for study selection and result reporting. The risk of bias was checked using the International Journal of Medical Informatics (IJMEDI) checklist. Data were analyzed using the 'metandi' command in Stata 17.
RESULTS
Twenty-one original studies were included, covering 82 algorithms. Sixteen studies utilized five algorithms to predict hepatitis B. Ten studies used five algorithms for hepatitis C prediction. For hepatitis B prediction, the SVM algorithms demonstrated the highest sensitivity (90.0%; 95% confidence interval (CI): 77.0%-96.0%), specificity (94%; 95% CI: 90.0%-97.0%), and a diagnostic odds ratio (DOR) of 145 (95% CI: 37.0-559.0). In the case of hepatitis C, the KNN algorithms exhibited the highest sensitivity (80%; 95% CI:30.0%-97.0%), specificity (95%; 95% CI: 58.0%-99.0%), and DOR (72; 95% CI: 3.0-1644.0) for prediction.
CONCLUSION
SVM and KNN demonstrated superior performance in predicting hepatitis. The proper algorithm along with clinical practice could improve hepatitis prediction and management.
Topics: Humans; Hepatitis, Viral, Human; Machine Learning; Hepatitis C; Hepatitis B
PubMed: 37806178
DOI: 10.1016/j.ijmedinf.2023.105243 -
Viruses Nov 2023Acute hepatitis B infection is associated with severe liver disease and chronic sequelae in some cases. The purpose of this review was to determine the efficacy of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acute hepatitis B infection is associated with severe liver disease and chronic sequelae in some cases. The purpose of this review was to determine the efficacy of nucleoside analogues (NA) (lamivudine versus entecavir) compared to placebo or no intervention for treating acute primary HBV infection.
METHODS
A meta-analysis for drug intervention was performed, following a fixed-effect model. Randomized controlled trials (RCTs) and quasi-randomized studies that evaluated the outcomes of NA in acute hepatitis B infection were included. The following outcomes were considered: virological cure (PCR negative), elimination of acute infection (seroconversion of HBsAg), mortality, and serious adverse events.
RESULTS
Five trials with 627 adult participants with severe acute hepatitis B defined by biochemical and serologic parameters were included. Virological cure did not favor any intervention: OR 0.96, 95% CI 0.54 to 1.7 ( = 0.90), I2 = 58%. Seroconversion of HBsAg to negative favored placebo/standard-of-care compared to lamivudine: OR 0.54, 95% CI 0.33 to 0.9 ( = 0.02), I2 = 31%. The only trial that compared entecavir and lamivudine favored entecavir over lamivudine (OR: 3.64, 95% CI 1.31-10.13; 90 participants). Adverse events were mild.
CONCLUSION
There is insufficient evidence that NA obtain superior efficacy compared with placebo/standard-of-care in patients with acute viral hepatitis, based on low quality evidence.
Topics: Adult; Humans; Lamivudine; Antiviral Agents; Hepatitis B Surface Antigens; Hepatitis B; Hepatitis B virus; Hepatitis B, Chronic; Treatment Outcome; DNA, Viral
PubMed: 38005918
DOI: 10.3390/v15112241