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The Lancet. Gastroenterology &... Sep 2022Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and the leading cause of liver-related morbidity and mortality. We aimed to predict... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and the leading cause of liver-related morbidity and mortality. We aimed to predict the burden of NAFLD by examining and estimating the temporal trends of its worldwide prevalence and incidence.
METHODS
In this systematic review and meta-analysis, we searched MEDLINE, EMBASE, Scopus, and Web of Science without language restrictions for reports published between date of database inception and May 25, 2021. We included observational cross-sectional or longitudinal studies done in study populations representative of the general adult population, in whom NAFLD was diagnosed using an imaging method in the absence of excessive alcohol consumption and viral hepatitis. Studies were excluded if conducted in paediatric populations (aged <18 years) or subgroups of the general population. Summary estimates were extracted from included reports by KR and independently verified by HA using the population, intervention, comparison, and outcomes framework. Primary outcomes were the prevalence and incidence of NAFLD. A random-effects meta-analysis was used to calculate overall and sex-specific pooled effect estimates and 95% CIs.
FINDINGS
The search identified 28 557 records, of which 13 577 records were screened; 299 records were also identified via other methods. In total, 72 publications with a sample population of 1 030 160 individuals from 17 countries were included in the prevalence analysis, and 16 publications with a sample population of 381 765 individuals from five countries were included in the incidence analysis. The overall prevalence of NAFLD worldwide was estimated to be 32·4% (95% CI 29·9-34·9). Prevalence increased significantly over time, from 25·5% (20·1-31·0) in or before 2005 to 37·8% (32·4-43·3) in 2016 or later (p=0·013). Overall prevalence of NAFLD was significantly higher in men than in women (39·7% [36·6-42·8] vs 25·6% [22·3-28·8]; p<0·0001). The overall incidence of NAFLD was estimated to be 46·9 cases per 1000 person-years (36·4-57·5); 70·8 cases per 1000 person-years (48·7-92·8) in men and 29·6 cases per 1000 person-years (20·2-38·9) in women (p<0·0001). There was considerable heterogeneity between studies of both NAFLD prevalence (I=99·9%) and NAFLD incidence (I=99·9%).
INTERPRETATION
Worldwide prevalence of NAFLD is considerably higher than previously estimated and is continuing to increase at an alarming rate. Incidence and prevalence of NAFLD are significantly higher among men than among women. Greater awareness of NAFLD and the development of cost-effective risk stratification strategies are warranted to address the growing burden of NAFLD.
FUNDING
Canadian Institutes of Health.
Topics: Adult; Canada; Child; Cross-Sectional Studies; Female; Humans; Incidence; Male; Non-alcoholic Fatty Liver Disease; Prevalence
PubMed: 35798021
DOI: 10.1016/S2468-1253(22)00165-0 -
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 -
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 -
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 -
RMD Open Nov 2022To conduct a systematic literature review (SLR) on the screening and prophylaxis of opportunistic and chronic infections in autoimmune inflammatory rheumatic diseases... (Review)
Review
Systematic literature review informing the 2022 EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in adults with autoimmune inflammatory rheumatic diseases.
OBJECTIVE
To conduct a systematic literature review (SLR) on the screening and prophylaxis of opportunistic and chronic infections in autoimmune inflammatory rheumatic diseases (AIIRD).
METHODS
SLR (inception-12/2021) based on the following search domains: (1) infectious agents, (2) AIIRD, (3) immunosuppressives/immunomodulators used in rheumatology, (4) screening terms and (5) prophylaxis terms. Articles were retrieved having the terms from (1) AND (2) AND (3) plus terms from (4) OR(5). Databases searched: PubMed, Embase and Cochrane Library.
EXCLUSION CRITERIA
studies on postoperative infections, paediatric AIIRD, COVID-19, vaccinations and non-Εnglish literature. Study quality was assessed with Newcastle-Ottawa scale for non-randomised controlled trials (RCTs), RoB-Cochrane for RCTs, AMSTAR2 for SLRs.
RESULTS
From 5641 studies were retrieved, 568 full-text articles were assessed for eligibility, with 194 articles finally included. For tuberculosis, tuberculin skin test (TST) is affected by treatment with glucocorticoids and conventional synthetic disease modifying anti-rheumatic drugs (DMARDs) and its performance is inferior to interferon gamma release assay (IGRA). Agreement between TST and IGRA is moderate to low. For hepatitis B virus (HBV): risk of reactivation is increased in patients positive for hepatitis B surface antigen. Anti-HBcore positive patients are at low risk for reactivation but should be monitored periodically with liver function tests and/or HBV-viral load. Risk for Hepatitis C reactivation is existing but low in patients treated with biological DMARDs. For , prophylaxis treatment should be considered in patients treated with prednisolone ≥15-30 mg/day for >2-4 weeks.
CONCLUSIONS
Different screening and prophylaxis approaches are described in the literature, partly determined by individual patient and disease characteristics.
Topics: Adult; Child; Humans; Antirheumatic Agents; COVID-19; Hepatitis B virus; Opportunistic Infections; Rheumatic Diseases
PubMed: 36323488
DOI: 10.1136/rmdopen-2022-002726 -
Przeglad Gastroenterologiczny 2022There are discordant reports on N-acetylcysteine (NAC) efficacy in non-acetaminophen acute liver failure (ALF). (Review)
Review
INTRODUCTION
There are discordant reports on N-acetylcysteine (NAC) efficacy in non-acetaminophen acute liver failure (ALF).
AIM
To determine whether NAC is beneficial in non-acetaminophen ALF.
MATERIAL AND METHODS
We performed a systemic review and meta-analysis of published data to address the question. PubMed and MEDLINE were searched using the terms non-acetylcysteine and ALF due to non-acetaminophen, viral infection, drug-induced or autoimmune hepatitis. The primary outcome was overall mortality. Secondary outcomes were transplant-free survival and length of hospital stay. Risk ratios were calculated using a random model for meta-analysis.
RESULTS
A total of 672 patients were included in this meta-analysis from 5 prospective studies (NAC group: = 334; control group: = 338). Viral hepatitis (45.8% vs. 32.8%) followed by drug-induced liver injury (24.6% vs. 27.5%), indeterminate cause (13.2% vs. 21.6%) and autoimmune hepatitis (6.6% vs. 8.9%) were the most common etiologies of ALF in the treatment group and control group respectively. Treatment with N-acetylcysteine improved the transplant-free survival significantly (55.1% vs. 28.1%; RR = 0.56; 95% CI: 0.33-0.94) whereas the overall survival was not improved with NAC (71% vs. 59.8%; RR = 0.73; 95% CI: 0.48-1.09). The NAC treatment was associated with shorter hospital stay (standard difference in means (SMD) = -1.62; 95% CI: -1.84 to -1.40, p < 0.001).
CONCLUSIONS
The treatment of patients with acute liver failure with N-acetylcysteine improved transplant-free survival and length of stay.
PubMed: 35371352
DOI: 10.5114/pg.2021.107797 -
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 -
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 -
Gastroenterology Sep 2021Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, with a rapidly changing landscape of treatments. In the past 20 years, numerous randomized... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, with a rapidly changing landscape of treatments. In the past 20 years, numerous randomized controlled trials (RCTs) have aimed at improving outcomes across disease stages. We aimed to analyze the current evidence and identify potential factors influencing response to therapies.
METHODS
We conducted a systematic review of phase III RCTs (2002-2020) across disease stages. A meta-analysis was designed to examine the relationship between etiology and outcome after systemic therapies with either tyrosine-kinase inhibitor (TKI)/antiangiogenic or immune checkpoint inhibitor (ICI) therapy.
RESULTS
Out of 10,100 studies identified, 76 were phase III RCTs. Among them, a rigorous screening algorithm identified 49 with high quality including a total of 22,113 patients undergoing adjuvant (n = 7) and primary treatment for early (n = 2), intermediate (n = 7), and advanced (first-line, n = 21; second-line, n = 12) stages of disease. Nine of these trials were positive, 6 treatments have been adopted in guidelines (sorafenib [2 RCTs], lenvatinib, atezolizumab+bevacizumab, regorafenib, cabozantinib and ramucirumab), but 2 were not (adjuvant CIK cells and sorafenib plus hepatic arterial infusion with FOLFOX). Meta-analysis of 8 trials including 3739 patients revealed ICI therapy to be significantly more effective in patients with viral hepatitis compared with nonviral-related HCC, whereas no differences related to etiology were observed in patients treated with TKI/anti-vascular endothelial growth factor.
CONCLUSIONS
Among 49 high-quality RCTs conducted in HCC during 2002-2020, 9 resulted in positive results. A meta-analysis of systemic therapies suggests that immunotherapies may be more effective in viral etiologies.
Topics: Ablation Techniques; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Chemotherapy, Adjuvant; Clinical Trials, Phase III as Topic; Disease Progression; Evidence-Based Medicine; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Liver Neoplasms; Neoadjuvant Therapy; Neoplasm Staging; Progression-Free Survival; Radiopharmaceuticals; Randomized Controlled Trials as Topic; Time Factors
PubMed: 34126063
DOI: 10.1053/j.gastro.2021.06.008