Should we undertake surveillance for HCC in patients with MAFLD?
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ABSTRACT:
SUBMITTER: Norero B
PROVIDER: S-EPMC10052487 | biostudies-literature | 2023
REPOSITORIES: biostudies-literature
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Should we undertake surveillance for HCC in patients with MAFLD?
Norero Blanca B Dufour Jean-François JF
Therapeutic advances in endocrinology and metabolism 20230328
Over the last decade, metabolic-associated fatty liver disease (MAFLD) has become an important public health issue worldwide. In many countries, MAFLD has become the most common cause of chronic liver disease. On the contrary, hepatocellular carcinoma (HCC) mortality is rising. Liver tumors have become the third cause of cancer mortality worldwide. HCC is the most frequent liver tumor. While the burden of HCC related to viral hepatitis is declining, the prevalence of MAFLD-related HCC is rising ...[more]
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Project description:Background & aimsThere are conflicting data regarding the epidemiology of hepatocellular carcinoma (HCC) arising in the context of non-alcoholic and metabolic-associated fatty liver disease (NAFLD and MAFLD). We aimed to examine the changing contribution of NAFLD and MAFLD, stratified by sex, in a well-defined geographical area and highly characterised HCC population between 1990 and 2014.MethodsWe identified all patients with HCC resident in the canton of Geneva, Switzerland, diagnosed between 1990 and 2014 from the prospective Geneva Cancer Registry and assessed aetiology-specific age-standardised incidence. NAFLD-HCC was diagnosed when other causes of liver disease were excluded in cases with type 2 diabetes, metabolic syndrome, or obesity. Criteria for MAFLD included one or more of the following criteria: overweight/obesity, presence of type 2 diabetes mellitus, or evidence of metabolic dysregulation.ResultsA total of 76/920 (8.3%) of patients were diagnosed with NAFLD-HCC in the canton of Geneva between 1990 and 2014. Between the time periods 1990-1994 and 2010-2014, there was a significant increase in HCC incidence in women (standardised incidence ratio [SIR] 1.83, 95% CI 1.08-3.13, p = 0.026) but not in men (SIR 1.10, 95% CI 0.85-1.43, p = 0.468). In the same timeframe, the proportion of NAFLD-HCC increased more in women (0-29%, p = 0.037) than in men (2-12%, p = 0.010) while the proportion of MAFLD increased from 21% to 68% in both sexes and from 7% to 67% in women (p <0.001). From 2000-2004 to 2010-2014, the SIR of NAFLD-HCC increased to 1.92 (95% CI 0.77-5.08) for men and 12.7 (95% CI 1.63-545) in women, whereas it decreased or remained stable for other major aetiologies of HCC.ConclusionsIn a populational cohort spanning 25 years, the burden of NAFLD and MAFLD associated HCCs increased significantly, driving an increase in HCC incidence, particularly in women.Lay summaryHepatocellular carcinoma (HCC) is the most common type of liver cancer, increasingly arising in patients with liver disease caused by metabolic syndrome, termed non-alcoholic fatty liver disease (NAFLD) or metabolic-associated fatty liver disease (MAFLD). We assessed all patients with HCC between 1990 and 2014 in the canton of Geneva (western Switzerland) and found an increase in all HCC cases in this timeframe, particularly in women. In addition, we found that HCC caused by NAFLD or MAFLD significantly increased over the years, particularly in women, possibly driving the increase in overall HCC cases.
| S-EPMC7957147 | biostudies-literature
Project description:Outside of expert centres, surveillance programmes for hepatocellular carcinoma (HCC) are not well executed. There are deficiencies in every stage of the process. Overcoming these obstacles is the most important method for improving surveillance. However, even if these obstacles were overcome, there would still be room for improvement. Assessing who is at risk of developing HCC remains incompletely validated. At present, risk scores have been developed for different causes of liver disease, but scores developed in different parts of the world for the same disease do not always agree. Furthermore, most scores stratify patients by risk but do not examine what level of risk should trigger surveillance. Which surveillance tools to use remains controversial - schemes have been proposed that use biomarkers alone, ultrasound alone, or a combination of both. However, the requisite level of test sensitivity that would be associated with high cure rates has not been defined, so at this point it is not clear whether surveillance requires both ultrasound and biomarkers, or whether the use of biomarkers alone is sufficient. Finally, surveillance should result in the identification of HCC at a very early stage. Diagnosing these lesions is difficult and optimal algorithms for lesions that are atypical on radiology have yet to be developed. Algorithms for the follow-up of abnormal biomarkers in the absence of ultrasound have also not been developed yet.
| S-EPMC7005767 | biostudies-literature
Project description:Background and aimsMost patients with HCC are diagnosed at a late stage, highlighting the need for more accurate surveillance tests. Although biomarkers for HCC early detection have promising data in Phase 2 case-control studies, evaluation in cohort studies is critical prior to adoption in practice. We leveraged a prospective cohort of patients with Child-Pugh A or B cirrhosis who were followed until incident HCC, liver transplantation, death, or loss to follow-up. We used a prospective specimen collection, retrospective, blinded evaluation design for biomarker evaluation of GALAD (gender × age × log alpha-fetoprotein [AFP] × des-gamma-carboxy prothrombin), longitudinal GALAD, and the HCC Early Detection Screening (HES) algorithm-compared to AFP-using patient-level sensitivity and screening-level specificity.Approach and resultsOf 397 patients with cirrhosis, 42 developed HCC (57.1% early stage) over a median of 2.0 years. Longitudinal GALAD had the highest c-statistic for HCC detection (0.85; 95% CI, 0.77-0.92) compared to single-time point GALAD (0.79; 95% CI, 0.71-0.87), AFP (0.77; 95% CI, 0.69-0.85), and HES (0.76; 95% CI, 0.67-0.83). When specificity was fixed at 90%, the sensitivity for HCC of single-time point and longitudinal GALAD was 54.8% and 66.7%, respectively, compared to 40.5% for AFP. Sensitivity for HCC detection was higher when restricted to patients with biomarker assessment within 6 months prior to HCC diagnosis, with the highest sensitivities observed for single-time point GALAD (72.0%) and longitudinal GALAD (64.0%), respectively. Sensitivity of single-time point and longitudinal GALAD for early-stage HCC was 53.8% and 69.2%, respectively.ConclusionGALAD demonstrated high sensitivity for HCC detection in a cohort of patients with cirrhosis. Validation of these results is warranted in large Phase 3 data sets.
| S-EPMC8844059 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) can have viral or non-viral causes1-5. Non-alcoholic steatohepatitis (NASH) is an important driver of HCC. Immunotherapy has been approved for treating HCC, but biomarker-based stratification of patients for optimal response to therapy is an unmet need6,7. Here we report the progressive accumulation of exhausted, unconventionally activated CD8+PD1+ T cells in NASH-affected livers. In preclinical models of NASH-induced HCC, therapeutic immunotherapy targeted at programmed death-1 (PD1) expanded activated CD8+PD1+ T cells within tumours but did not lead to tumour regression, which indicates that tumour immune surveillance was impaired. When given prophylactically, anti-PD1 treatment led to an increase in the incidence of NASH-HCC and in the number and size of tumour nodules, which correlated with increased hepatic CD8+PD1+CXCR6+, TOX+, and TNF+ T cells. The increase in HCC triggered by anti-PD1 treatment was prevented by depletion of CD8+ T cells or TNF neutralization, suggesting that CD8+ T cells help to induce NASH-HCC, rather than invigorating or executing immune surveillance. We found similar phenotypic and functional profiles in hepatic CD8+PD1+ T cells from humans with NAFLD or NASH. A meta-analysis of three randomized phase III clinical trials that tested inhibitors of PDL1 (programmed death-ligand 1) or PD1 in more than 1,600 patients with advanced HCC revealed that immune therapy did not improve survival in patients with non-viral HCC. In two additional cohorts, patients with NASH-driven HCC who received anti-PD1 or anti-PDL1 treatment showed reduced overall survival compared to patients with other aetiologies. Collectively, these data show that non-viral HCC, and particularly NASH-HCC, might be less responsive to immunotherapy, probably owing to NASH-related aberrant T cell activation causing tissue damage that leads to impaired immune surveillance. Our data provide a rationale for stratification of patients with HCC according to underlying aetiology in studies of immunotherapy as a primary or adjuvant treatment.
| S-EPMC8046670 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer. Its incidence is rising faster than any other cancer in the United States and it remains one of the leading causes of cancer-related deaths worldwide. While advances in massive parallel sequencing and integration of 'omics information have transformed the field of oncology, tissue access is often limited in HCC and a single biopsy is poorly representative of the known genetic heterogeneity of tumours. Liquid biopsy has emerged as a promising strategy for analysing circulating tumour components including circulating tumour DNA. Cell-free DNA and tumour DNA are derived from necrotic, apoptotic and living eukaryotic cells. The profiling of genetic and epigenetic alterations in circulating cell-free DNA has potential clinical applications including early disease detection, prediction of treatment response and prognostication in real time. Novel biomarker candidates for disease detection and monitoring are under study. Of these, methylation analyses of circulating tumour DNA have shown promising performance for early HCC detection in at-risk patients. Assessments of assay performance in longitudinal validation cohorts are ongoing. Implementation of liquid biopsy for HCC will likely improve upon the current surveillance strategy. This review summarises the most recent developments on the role and utility of circulating cell-free DNA in the detection and management of HCC.
| S-EPMC8182265 | biostudies-literature
Project description:ObjectiveThere has been increased interest in interventions to promote hepatocellular carcinoma (HCC) surveillance given low utilization and high proportions of late stage detection. Accurate prediction of patients likely versus unlikely to respond to interventions could allow a cost-effective approach to outreach and facilitate targeting more intensive interventions to likely non-responders.DesignWe conducted a secondary analysis of a randomized clinical trial evaluating a mailed outreach strategy to promote HCC surveillance among 1200 cirrhosis patients at a safety-net health system between December 2014 and March 2017. We developed regularized logistic regression (RLR) and gradient boosting machine (GBM) algorithm models to predict surveillance completion during each of the 3 screening rounds in a training set (n = 960). Model performance was assessed using multiple performance metrics in an independent test set (n = 240).ResultsAmong 1200 patients, surveillance was completed in 41-47% of patients over the three rounds. The RLR and GBM models demonstrated good discriminatory accuracy, with area under receiver operating characteristic (AUROC) curves of 0.67 and 0.66 respectively in the first surveillance round and improved to 0.77 by the third surveillance round after incorporating prior screening behavior as a feature. Additional performance characteristics including the Brier score, Hosmer-Lemeshow test and reliability diagrams were also evaluated. The most important variables for the predictive model were prior screening completion status and past primary care contact.ConclusionsPredictive models can help stratify patients' likelihood to respond to surveillance outreach invitations, facilitating tailored strategies to maximize effectiveness and cost-effectiveness of HCC surveillance population health programs.
| S-EPMC9048842 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) surveillance is associated with early tumor detection and improved survival in patients with cirrhosis; however, effectiveness is limited by underuse. We compared the effectiveness of mailed outreach and patient navigation strategies to increase HCC surveillance in a racially diverse cohort of patients with cirrhosis. We conducted a pragmatic randomized clinical trial comparing mailed outreach for screening ultrasound (n = 600), mailed outreach plus patient navigation (n = 600), or usual care with visit-based screening (n = 600) among 1800 patients with cirrhosis at a large safety-net health system from December 2014 to March 2017. Patients who did not respond to outreach invitations within 2 weeks received reminder telephone calls. Patient navigation included an assessment of barriers to surveillance and encouragement of surveillance participation. The primary outcome was HCC surveillance (abdominal imaging every 6 months) over an 18-month period. All 1800 patients were included in intention-to-screen analyses. HCC surveillance was performed in 23.3% of outreach/navigation patients, 17.8% of outreach-alone patients, and 7.3% of usual care patients. HCC surveillance was 16.0% (95% confidence interval [CI]: 12.0%-20.0%) and 10.5% (95% CI: 6.8%-14.2%) higher in outreach groups than usual care (P < 0.001 for both) and 5.5% (95% CI: 0.9%-10.1%) higher for outreach/navigation than outreach alone (P = 0.02). Both interventions increased HCC surveillance across predefined patient subgroups. The proportion of HCC patients detected at an early stage did not differ between groups; however, a higher proportion of patients with screen-detected HCC across groups had early-stage tumors than those with HCC detected incidentally or symptomatically (83.3% versus 30.8%, P = 0.003). Conclusion: Mailed outreach invitations and navigation significantly increased HCC surveillance versus usual care in patients with cirrhosis.
| S-EPMC6324997 | biostudies-literature
Project description:BackgroundVietnam and Saudi Arabia have high disease burden of primary hepatocellular carcinoma (HCC). Early detection in asymptomatic patients at risk for HCC is a strategy to improve survival outcomes in HCC management. GALAD score, a serum-based panel, has demonstrated promising clinical utility in HCC management. However, in order to ascertain its potential role in the surveillance of the early detection of HCC, GALAD needs to be validated prospectively for clinical surveillance of HCC (i.e., phase IV biomarker validation study). Thus, we propose to conduct a phase IV biomarker validation study to prospectively survey a cohort of patients with advanced fibrosis or compensated cirrhosis, irrespective of etiologies, using semi-annual abdominal ultrasound and GALAD score for five years.MethodsWe plan to recruit a cohort of 1,600 patients, male or female, with advanced fibrosis or cirrhosis (i.e., F3 or F4) and MELD ≤ 15, in Vietnam and Saudi Arabia (n = 800 each). Individuals with a liver mass ≥ 1 cm in diameter, elevated alpha-fetoprotein (AFP) (≥ 9 ng/mL), and/or elevated GALAD score (≥ -0.63) will be scanned with dynamic contrast-enhanced magnetic resonance imaging (MRI), and a diagnosis of HCC will be made by Liver Imaging Reporting and Data System (LiRADS) assessment (LiRADS-5). Additionally, those who do not exhibit abnormal imaging findings, elevated AFP titer, and/or elevated GALAD score will obtain a dynamic contrast-enhanced MRI annually for five years to assess for HCC. Only MRI nearest to the time of GALAD score measurement, ultrasound and/or AFP evaluation will be included in the diagnostic validation analysis. MRI will be replaced with an abdominal computed tomography scan when MRI results are poor due to patient conditions such as movement etc. Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced MRI will not be carried out in study sites in both countries. Bootstrap resampling technique will be used to account for repeated measures to estimate standard errors and confidence intervals. Additionally, we will use the Cox proportional hazards regression model with covariates tailored to the hypothesis under investigation for time-to-HCC data as predicted by time-varying biomarker data.DiscussionThe present work will evaluate the performance of GALAD score in early detection of liver cancer. Furthermore, by leveraging the prospective cohort, we will establish a biorepository of longitudinally collected biospecimens from patients with advanced fibrosis or cirrhosis to be used as a reference set for future research in early detection of HCC in the two countries.Trial registrationName of the registry: ClinicalTrials.gov Registration date: 22 April 2022 Trial registration number: NCT05342350 URL of trial registry record.
| S-EPMC10506187 | biostudies-literature
Project description:BackgroundThe PAGE-B score (Platelet Age GEnder-HBV) selects chronic hepatitis B (cHB) patients showing no relevant 5-year risk for hepatocellular carcinoma (HCC). We, therefore, explored potential cost reduction following the introduction of a PAGE-B tailored ultrasound screening in a single center cohort of cHB patients receiving stable antiviral therapy.MethodscHB patients attending throughout the year 2018 were documented. Patients eligible for PAGE-B score were classified into high (≥18 points), intermediate (10-17 points) and low (≤9 points) HCC risk groups. Patients of the low HCC risk group could postpone HCC screening to reduce HCC screening expenses. Full costs for hepatic ultrasound were assessed.ResultsThroughout the year cHB patients (n = 607) attended our clinic, which included PAGE-B eligible patients (n = 227, 37.4%) of whom n = 94 (15.8%) were allocated to the low HCC risk group. Sonographic HCC screening during a median exam time of 12.4 min (IQR 9.2-17.2) resulted in total costs of 22.82 Euro/exam. Additional opportunistic expenses caused by patient's lost earnings or productivity were 15.6-17.5 €/exam and 26.7 €/exam, respectively. Following a PAGE-B tailored HCC screening at our institution annual full costs for cHB patients could be reduced by 15.51%, which equals a cost reduction by 1.91% for our total sonography unit. In comparison, 1.35% up to 7.65% of HBV-infected patients of Caucasian descent could postpone HCC screening according to population-based estimates from Germany.ConclusionsPAGE-B risk score adapted screening for HCC is an efficient and cost neutral tool to reduce costs for sonography in Caucasian patients with chronic hepatitis B receiving antiviral treatment.
| S-EPMC8379870 | biostudies-literature
Project description:Background & aimsThere is controversy regarding the overall value of hepatocellular carcinoma (HCC) surveillance in patients with cirrhosis given the lack of data from randomized-controlled trials. To address this issue, we conducted a systematic review and meta-analysis of cohort studies evaluating the benefits and harms of HCC surveillance in patients with cirrhosis.MethodsWe performed a search of the Medline and EMBASE databases and national meeting abstracts from January 2014 through July 2020 for studies reporting early-stage HCC detection, curative treatment receipt, or overall survival, stratified by HCC surveillance status, among patients with cirrhosis. Pooled risk ratios (RRs) and hazard ratios, according to HCC surveillance status, were calculated for each outcome using the DerSimonian and Laird method for random effects models.ResultsWe identified 59 studies including 145,396 patients with HCC, which was detected by surveillance in 41,052 (28.2%) cases. HCC surveillance was associated with improved early-stage detection (RR 1.86, 95% CI 1.73-1.98; I2 = 82%), curative treatment receipt (RR 1.83, 95% CI 1.69-1.97; I2 = 75%), and overall survival (hazard ratio 0.67, 95% CI 0.61-0.72; I2 = 78%) after adjusting for lead-time bias; however, there was notable heterogeneity in all pooled estimates. Four studies examined surveillance-related physical harms due to false positive or indeterminate surveillance results, but no studies examined potential financial or psychological harms. The proportion of patients experiencing surveillance-related physical harms ranged from 8.8% to 27.5% across studies, although most harms were mild in severity.ConclusionHCC surveillance is associated with improved early detection, curative treatment receipt, and survival in patients with cirrhosis, although there was heterogeneity in pooled estimates. Available data suggest HCC surveillance is of high value in patients with cirrhosis, although continued rigorous studies evaluating benefits and harms are still needed.Lay summaryThere has been ongoing debate about the overall value of hepatocellular carcinoma (HCC) screening in patients with cirrhosis given the lack of data from randomized-controlled trials. In a systematic review of contemporary cohort studies, we found that HCC screening is associated with improved early detection, curative treatment receipt, and survival in patients with cirrhosis, although there were fewer data quantifying potential screening-related harms. Available data suggest HCC screening is of high value in patients with cirrhosis, although continued studies evaluating benefits and harms are still needed.
| S-EPMC9232881 | biostudies-literature