Hepatocellular Carcinoma Screening Process Failures in Patients with Cirrhosis.
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ABSTRACT:
SUBMITTER: Marquardt P
PROVIDER: S-EPMC8435280 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background & aimsHepatocellular carcinoma (HCC) screening of patients with cirrhosis is recommended by professional societies to increase detection of early stage tumors and survival, but is underused in clinical practice.MethodsWe conducted a retrospective cohort study of 13,714 patients diagnosed with HCC from 2003 through 2013 included in the Surveillance, Epidemiology, and End Results Program-Medicare database. We characterized receipt of HCC screening in the 3 years before HCC diagnosis using mutually exclusive categories (consistent vs inconsistent vs no screening) and the proportion of time covered with screening. Correlates for screening receipt were assessed using a multivariable 2-part regression model. We examined the association between screening receipt and early detection of tumors using multivariable logistic regression. We evaluated associations between screening receipt and overall survival using a Cox proportional hazards model, after adjustments for effects of lead-time bias and length-time bias on survival rate estimators.ResultsMost patients with cirrhosis (51.1%) did not receive any screening in the 3 years before a diagnosis of HCC, and only 6.8% of patients underwent consistent annual screening. The proportion with consistent screening increased from 5.4% in 2003 to 2006 to 8.8% in 2011 to 2013 (P < .001). The mean proportion of time covered was 13.4% overall, which increased from 11.7% in 2003 to 2006 to 15.2% in 2011 to 2013. Receipt of consistent screening was associated with detection of early stage tumors (odds ratio, 1.98; 95% CI, 1.68-2.33) and a reduced risk of death after correction for lead-time bias (hazard ratio, 0.76; 95% CI, 0.70-0.83). Inconsistent screening was associated with a slightly smaller increase in early detection of HCC (odds ratio, 1.31; 95% CI, 1.20-1.43) and a reduced risk of death (hazard ratio, 0.86; 95% CI, 0.83-0.90). After correction for lead- and length-time biases, higher proportions of patients with consistent (23%; 95% CI, 21%-25%) and inconsistent screening (19%; 95% CI, 19%-20%) survived for 3 years compared with patients without screening (13%; 95% CI, 12%-14%).ConclusionsIn an analysis of the Surveillance, Epidemiology, and End Results Program-Medicare database, we found HCC screening to be underused for patients with cirrhosis. This contributes to detection of liver tumors at later stages and shorter times of survival. However, the proportion of patients screened for HCC has increased over time.
| S-EPMC6431264 | biostudies-literature
Project description:Background & aimsIdentifying patients in whom ultrasound may be inadequate to exclude the presence of hepatocellular carcinoma (HCC) can inform interventions to improve screening effectiveness. We aimed to characterize correlates of suboptimal ultrasound quality and changes in ultrasound quality over time in patients with cirrhosis undergoing HCC screening.MethodsWe performed a retrospective cohort study of patients with cirrhosis who underwent ultrasound examination at 2 large health systems between July 2016 and July 2019. Exam adequacy was graded by radiologists using the LI-RADS Visualization Score (A, B, C); we evaluated changes in visualization over time among patients with >1 ultrasound exams. We performed multivariable logistic regression to identify characteristics associated with limited ultrasound visualization (scores B or C).ResultsOf 2053 cirrhosis patients, 1685 (82.1%) had ultrasounds with score A, 262 (12.8%) had score B, and 106 (5.2%) had score C. Limited visualization was associated with alcohol-related or nonalcoholic fatty liver disease cirrhosis and presence of class II-III obesity. Among 1546 patients with >1 ultrasounds, 1129 (73.0%) had the same visualization score on follow-up (1046 score A, 60 score B, 23 score C). However, 255 (19.6%) of 1301 with score A at baseline had limited visualization when repeated (230 score B, 25 score C), and 130 (53.1%) of 245 patients with baseline limited visualization had good visualization when repeated.ConclusionsNearly 1 in 5 patients with cirrhosis had moderately-severely limited ultrasound visualization for HCC nodules, particularly those with obesity or alcohol-related or nonalcoholic fatty liver disease cirrhosis. Ultrasound quality can change between exams, including improvement in many patients with limited visualization.
| S-EPMC8660956 | biostudies-literature
Project description:Background & aimsSurveillance of patients with cirrhosis increases early detection of hepatocellular carcinoma (HCC) and prolongs survival. However, its effectiveness is limited by underuse, particularly among racial/ethnic minorities and individuals of low socioeconomic status. We compared the effectiveness of mailed outreach strategies, with and without patient navigation, in increasing the numbers of patients with cirrhosis undergoing surveillance for HCC in a racially diverse and socioeconomically disadvantaged cohort.MethodsWe performed a prospective study of patients with documented or suspected cirrhosis at a large safety-net health system from December 2014 through March 2016. Patients were assigned randomly (1:1:1) to groups that received mailed invitations for an ultrasound screening examination (n = 600), mailed invitations for an ultrasound screening examination and patient navigation (barrier assessment and motivational education for patients who declined screening; n = 600), or usual care (visit-based screening; n = 600). Patients who did not respond to outreach invitations within 2 weeks received up to 3 reminder telephone calls. The primary outcome was completion of abdominal imaging within 6 months of randomization.ResultsBaseline characteristics were similar among groups. Cirrhosis was documented, based on International Classification of Diseases, 9th revision, codes, for 79.6% of patients, and suspected, based on noninvasive markers of fibrosis, for 20.4%. In an intent-to-treat analysis, significantly greater proportions of patients who received the mailed invitation and navigation (47.2%) or the mailed invitation alone (44.5%) underwent HCC screening than patients who received usual care (24.3%) (P < .001 for both comparisons). However, screening rates did not differ significantly between outreach the outreach groups (P = .25). The effects of the outreach program were consistent in all subgroups, including Caucasian vs non-Caucasian race, documented vs suspected cirrhosis, Child-Pugh A vs B cirrhosis, and receipt of gastroenterology care.ConclusionsIn a prospective study, we found outreach strategies to double the percentage of patients with cirrhosis who underwent ultrasound screening for HCC. However, adding patient navigation to telephone reminders provided no significant additional benefit. ClinicalTrials.gov no: NCT02312817.
| S-EPMC5285373 | biostudies-literature
Project description:ObjectivesHepatocellular carcinoma (HCC) surveillance with biannual ultrasound is currently recommended for all patients with cirrhosis. However, clinical implementation of this "one-size-fits-all" approach is challenging as evidenced by its low application rate. We aimed to evaluate the cost-effectiveness of risk-stratified HCC surveillance strategies in patients with cirrhosis.MethodsA Markov decision-analytic modeling was performed to simulate a cohort of 50-year-old subjects with compensated cirrhosis. Risk-stratified HCC surveillance strategies was implemented, in which patients were stratified into high-, intermediate-, or low-risk groups by HCC risk biomarker-based scores and assigned to surveillance modalities tailored to HCC risk (2 non-risk-stratified and 14 risk-stratified strategies) and compared with non-stratified biannual ultrasound.ResultsQuality-adjusted life expectancy gains for biannual ultrasound in all patients and risk-stratified strategies compared with no surveillance were 1.3 and 0.9-2.1 years, respectively. Compared with the current standard of biannual ultrasound in all cirrhosis patients, risk-stratified strategies applying magnetic resonance imaging (MRI) and/or ultrasound only in high- and intermediate-risk patients, without screening in low-risk patients, were cost-effective. Abbreviated MRI (AMRI) for high- and intermediate-risk patients had the lowest incremental cost-effectiveness ratio (ICER) of $2,100 per quality-adjusted life year gained. AMRI in intermediate- and high-risk patients had ICERs <$3,000 across a wide range of HCC incidences.ConclusionsRisk-stratified HCC surveillance strategies targeting high- and intermediate-risk patients with cirrhosis are cost-effective and outperform the currently recommended non-stratified biannual ultrasound in all patients with cirrhosis.
| S-EPMC5518949 | biostudies-literature
Project description:BACKGROUND & AIMS:Screening patients with cirrhosis for hepatocellular carcinoma (HCC) has been recommended. We conducted a matched case-control study within the US Veterans Affairs (VA) health care system to determine whether screening by abdominal ultrasonography (USS) and/or by measuring serum level of ?-fetoprotein (AFP) was associated with decreased cancer-related mortality in patients with cirrhosis. METHODS:We defined cases (n = 238) as patients with cirrhosis who died of HCC from January 1, 2013 through August 31, 2015 and had been in VA care with a diagnosis of cirrhosis for at least 4 years before the diagnosis of HCC. We matched each case to 1 control (n = 238), defined as a patient with cirrhosis who did not die of HCC and had been in VA care for at least 4 years before the date of the matched case's HCC diagnosis. Controls were matched to cases by year of cirrhosis diagnosis, race and ethnicity, age, sex, etiology of cirrhosis, Model for End-Stage Liver Disease score, and VA medical center. We identified all USS and serum AFP tests performed within 4 years before the date of HCC diagnosis in cases or the equivalent index date in controls and determined by chart extraction (blinded to case or control status) whether these tests were performed for screening. RESULTS:There were no significant differences between cases and controls in the proportions of patients who underwent screening USS (52.9% vs 54.2%), screening measurement of serum AFP (74.8% vs 73.5%), screening USS or measurement of serum AFP (81.1% vs 79.4%), or screening USS and measurement of serum AFP (46.6% vs 48.3%) within 4 years before the index date, with or without adjusting for potential confounders. There also was no difference in receipt of these screening tests within 1, 2, or 3 years before the index date. CONCLUSIONS:In a matched case-control study of the VA health care system, we found that screening patients with cirrhosis for HCC by USS, measurement of serum AFP, either test, or both tests was not associated with decreased HCC-related mortality. We encourage additional case-control studies to evaluate the efficacy of screening for HCC in other health care systems, in which available records are sufficiently detailed to enable identification of the indication for USS and AFP tests.
| S-EPMC6180323 | biostudies-literature
Project description:Background/aimsCirrhosis is the most important risk factor of hepatocellular carcinoma (HCC), and patients with cirrhosis are recommended to receive semiannual surveillance for early HCC detection. However, early cirrhosis is often asymptomatic and can go undiagnosed for years, leading to underuse of HCC surveillance in clinical practice. We characterized the frequency and associated factors of unrecognized cirrhosis in a national sample of patients with HCC from the United States.MethodsHCC patients aged 68 years and older, diagnosed during 2011 to 2015 were included from the SEERMedicare Linked Database. If cirrhosis was diagnosed within 6 months immediately preceding HCC diagnosis or after HCC diagnosis, cases were categorized as unrecognized cirrhosis. Factors associated with unrecognized cirrhosis were identified using logistic regression analyses. Factors associated with overall survival were evaluated using Cox regression analyses.ResultsAmong 5,098 HCC patients, 74.8% patients had cirrhosis. Among those with cirrhosis, 57.4% had unrecognized cirrhosis, with the highest proportion (76.3%) among those with NAFLD-related HCC. Male sex (aOR: 2.12, 95% CI: 1.83-2.46), non-Hispanic Black race (aOR: 1.93, 95% CI: 1.45-2.57), and NAFLD etiology (aOR: 4.46, 95% CI: 3.68-5.41) were associated with having unrecognized cirrhosis. Among NAFLD-related HCC patients, male sex (aOR: 2.32, 95% CI: 1.71-3.14) was associated with unrecognized cirrhosis. Unrecognized cirrhosis was independently associated with worse overall survival (aHR: 1.17, 95% CI: 1.08-1.27) compared to recognized cirrhosis.ConclusionUnrecognized cirrhosis is common in NAFLD-related HCC, particularly among male and Black patients, highlighting these groups as important intervention targets to improve HCC surveillance uptake and outcomes.
| S-EPMC10121289 | biostudies-literature
Project description:Exosomal microRNAs have recently been studied as potential diagnostic marker for various malignancies, including hepatocellular carcinoma (HCC). The aim of this study was to investigate serum exosomal microRNA profiles as HCC diagnostic marker. Transmission electron microscopy and western blot were used to identify serum exosomes. Deep sequencing was performed to screen differentially expressed microRNAs between HCC (n=5) and liver cirrhosis (LC, n=5) group. Three upregulated and two downregulated microRNAs were selected for qPCR analysis. The levels of selected microRNAs were normalized to Caenorhabditis elegans miR-39 microRNA mimics. Serum exosomal level of miR-122, miR-148a, and miR-1246 were further analyzed and significantly higher in HCC than LC and normal control (NC) group (P<0.001), but not different from chronic hepatitis group(p>0.05). The receiver operating characteristic curve was used to evaluate diagnostic perfromance of candidate microRNAs. Area under the curve (AUC) of miR-148a was 0.891 [95 % confidence interval (CI), 0.809-0.947] in discriminating HCC from LC, remarkably higher than alpha fetoprotein (AFP) (AUC: 0.712, 95 % CI: 0.607-0.803). Binary logistic regression was adpoted to establish the diagnostic model for discriminating HCC from LC. And the combination of miR-122, miR-148a and AFP increased the AUC to 0.931 (95% CI, 0.857-0.973), which can also be applied for distinguishing early HCC from LC. miR-122 was the best for differentiating HCC from NC (AUC: 0.990, 95% CI, 0.945-1.000). These data suggests that serum exosomal microRNAs signature or their combination with traditional biomarker may be used as a suitable peripheral screening tool for HCC.
2018-10-01 | GSE104251 | GEO
Project description:BACKGROUND:Hepatocellular carcinoma (HCC) is the most common type of liver tumour, and is closely related to liver cirrhosis. Previous studies have focussed on the pathogenesis of liver cirrhosis developing into HCC, but the molecular mechanism remains unclear. The aims of the present study were to identify key genes related to the transformation of cirrhosis into HCC, and explore the associated molecular mechanisms. METHODS:GSE89377, GSE17548, GSE63898 and GSE54236 mRNA microarray datasets from Gene Expression Omnibus (GEO) were analysed to obtain differentially expressed genes (DEGs) between HCC and liver cirrhosis tissues, and network analysis of protein-protein interactions (PPIs) was carried out. String and Cytoscape were used to analyse modules and identify hub genes, Kaplan-Meier Plotter and Oncomine databases were used to explore relationships between hub genes and disease occurrence, development and prognosis of HCC, and the molecular mechanism of the main hub gene was probed using Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis. RESULTS:In total, 58 DEGs were obtained, of which 12 and 46 were up- and down-regulated, respectively. Three hub genes (CDKN3, CYP2C9 and LCAT) were identified and associated prognostic information was obtained. CDKN3 may be correlated with the occurrence, invasion, and recurrence of HCC. Genes closely related to changes in the CDKN3 hub gene were screened, and Kyoto Encyclopedia of Genes and Genomes (KEGGs) pathway analysis identified numerous cell cycle-related genes. CONCLUSION:CDKN3 may affect the transformation of liver cirrhosis into HCC, and represents a new candidate molecular marker of the occurrence and progression of HCC.
| S-EPMC6993496 | biostudies-literature
Project description:To validate cancer screening programs, experts recommend estimating effects on case fatality rates (CFRs) and cancer-specific mortality. This study evaluates hepatocellular carcinoma (HCC) screening in patients with cirrhosis for those outcomes using a modeling approach. We designed a Markov model to assess 10-year HCC-CFR, HCC-related, and overall mortality per 100,000 screened patients with compensated cirrhosis. The model evaluates different HCC surveillance intervals (none, annual [12 months], semiannual [6 months], or quarterly [3 months]) and imaging modalities (ultrasound [US] or magnetic resonance imaging [MRI]) in various annual incidences (0.2%, 0.4%, or 1.5%). Compared to no surveillance, 6-month US reduced the 10-year HCC-CFR from 77% to 46%. With annual incidences of 0.2%, 0.4%, and 1.5%, the model predicted 281, 565, and 2059 fewer HCC-related deaths, respectively, and 187, 374, and 1356 fewer total deaths per 100,000 screened patients, respectively. Combining alpha-fetoprotein screening to 6-month US led to 32, 63, and 230 fewer HCC-related deaths per 100,000 screened patients for annual incidences of 0.2%, 0.4%, and 1.5%, respectively. Compared to 6-month US, 3-month US reduced cancer-related mortality by 14%, predicting 61, 123, and 446 fewer HCC-related deaths per 100,000 screened patients with annual incidences of 0.2%, 0.4%, and 1.5%, respectively. Compared to 6-month US, 6-month MRI (-17%) and 12-month MRI (-6%) reduced HCC-related mortality. Compared to 6-month US, overall mortality reductions ranged from -0.1% to -1.3% when using 3-month US or MRI. A US surveillance interval of 6 months improves HCC-related and overall mortality compared to no surveillance. A shorter US interval or using MRI could reduce HCC-CFR and HCC-related mortality, with a modest effect on overall mortality.
| S-EPMC9512473 | biostudies-literature
Project description:Neutrophil extracellular traps (NETs) are web-like structures consisting of DNA, histones and granule proteins, released from neutrophils in thrombus formation, inflammation, and cancer. We asked if plasma levels of the NET markers myeloperoxidase (MPO)-DNA and citrullinated histone H3 (H3Cit)-DNA, are elevated in liver cirrhosis and hepatocellular carcinoma (HCC) and if the levels correlate with clinical parameters. MPO-DNA, H3Cit-DNA, and thrombin-antithrombin (TAT) complex, as a marker of coagulation activity, were measured using ELISA in plasma from 82 patients with HCC, 95 patients with cirrhosis and 50 healthy controls. Correlations were made to clinical parameters and laboratory data and patients were followed for a median of 22.5 months regarding thrombosis development. H3Cit-DNA was significantly (p < 0.01) elevated in plasma from cirrhosis (66.4 ng/mL) and HCC (63.8 ng/mL) patients compared to healthy controls (31.8 ng/mL). TAT levels showed similar pattern (3.1, 3.7, and 0.0 µg/mL respectively, p < 0.01). MPO-DNA was significantly (p < 0.01) elevated in cirrhosis patients (0.53 O.D.) as compared to controls (0.33 O.D.). Levels of MPO-DNA and H3Cit-DNA correlated positively with Child-Pugh and MELD score. TAT was increased in all Child-Pugh and MELD groups. In multivariable logistic regression, Child B and C liver cirrhosis were independent predictors of elevated H3Cit-DNA in plasma. Levels of MPO-DNA and H3Cit-DNA were similar in patients with or without history of thrombosis, or thrombus formation during follow-up. In conclusion, plasma markers of NET formation are elevated in liver cirrhosis and correlate to the degree of liver dysfunction in patients with liver cirrhosis and/or HCC. The presence of HCC did not further increase the plasma levels of NET markers as compared to patients with cirrhosis only.
| S-EPMC8429678 | biostudies-literature