Dataset Information

Factors associated with unrecognized cirrhosis in patients with hepatocellular carcinoma.

ABSTRACT:

Background/aims

Cirrhosis 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.

Methods

HCC 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.

Results

Among 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.

Conclusion

Unrecognized 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.

SUBMITTER: Lee YT

PROVIDER: S-EPMC10121289 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Publications

Factors associated with unrecognized cirrhosis in patients with hepatocellular carcinoma.

Lee Yi-Te YT Karim Mohammad A MA Kum Hye Chung HC Park Sulki S Rich Nicole E NE Noureddin Mazen M Singal Amit G AG Yang Ju Dong JD

Clinical and molecular hepatology 20230201 2

<h4>Background/aims</h4>Cirrhosis 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.<h4>M ...[more]

PMID: 36726052

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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.

Project description:Over 20% of patients with cirrhosis are nonadherent with hepatocellular carcinoma (HCC) surveillance recommendations; however, few studies have evaluated the impact of patient-level factors on surveillance receipt. We characterized the association between HCC surveillance receipt and patient knowledge, attitudes, and perceived barriers in a racially diverse and socioeconomically disadvantaged cohort of patients with cirrhosis. Patients with cirrhosis followed at a large urban hospital were invited to complete a survey about HCC surveillance between August 2014 and December 2015. Multivariable logistic regression was performed to identify factors associated with HCC surveillance receipt during the 12-month period preceding and 6-month period after survey administration. We achieved a response rate of 71.8% (n = 541 of 753). Patients demonstrated high levels of HCC-related knowledge (summary score, 77.7%); however, 48.6% believed that eating a healthy diet precluded the need for HCC surveillance, and 34.0% believed that HCC surveillance was not necessary if they had a normal physical exam and/or lacked clinical symptoms. Patients expressed worry about developing and dying from HCC, but nearly half (49.9%) of patients reported barriers to receiving HCC surveillance, including difficulty with the scheduling process (30.5%), costs of surveillance testing (25.3%), and transportation difficulties (17.3%). HCC surveillance receipt was significantly higher in patients who knew cirrhosis is a risk factor for developing HCC (odds ratio [OR], 3.09; 95% confidence interval [CI], 1.25-7.62) and significantly lower in those reporting barriers to surveillance (OR, 0.42; 95% CI, 0.25-0.70).Patients with cirrhosis are knowledgeable and interested in HCC surveillance; however, patient-reported barriers are associated with lower surveillance rates in clinical practice and represent potential intervention targets to improve HCC surveillance effectiveness. (Hepatology 2017;65:875-884).

Project description:Background & aimsWorldwide, hepatocellular carcinoma (HCC) is a common malignancy. We aimed to prospectively determine the incidence and risk factors of HCC in a U.S.CohortMethodsThe multicenter Hepatocellular Carcinoma Early Detection Strategy study of the National Institutes of Health prospectively enrolled patients with cirrhosis who underwent standard surveillance for HCC. Demographics, medical and family history, etiology of liver disease, and clinical features were evaluated for associations with HCC.ResultsBetween April 10, 2013 and December 31, 2021, 1723 patients were enrolled and confirmed eligible. During median follow-up of 2.2 years (range, 0-8.7 years), there were 109 incident cases of HCC for an incidence rate of 2.4 per 100 person-years: 88 (81%) patients with very early/early Barcelona Clinic Liver Cancer stage (0, A), 20 (18%) intermediate stage (B), and 1 (1%) unknown stage. Risk factor analyses were restricted to 1325 patients, including 95 incident HCC, with at least 6 months of follow-up. The majority were men (53.2%), obese or severely obese (median body mass index, 30.2 kg/m2), and white (86.3%); 42.0% had history of hepatitis C virus infection, 20.7% had alcoholic liver disease, and 24.9% had nonalcoholic fatty liver disease. Fourteen risk factors for HCC were significant (P < .05) in univariate analyses, and a multivariate subset was selected using stepwise logistic regression. The multivariate subset contained gender (P < .001; male; odds ratio [OR], 2.47; 95% confidence interval [CI], 1.54-4.07), years with cirrhosis (P = .004; OR, 1.06; 95% CI, 1.02-1.1), family history of liver cancer (P = .02; yes; OR, 2.69; 95% CI, 1.11-5.86), age (per 5 years; P = .02; OR, 1.17; 95% CI, 1.03-1.33), obesity (P = .02; yes; OR, 1.7; 95% CI, 1.08-2.73), aspartate aminotransferase (log(1+AST); P = .06; OR, 1.54; 95% CI, 0.97-2.42), alpha-fetoprotein (log(1+AFP); P = .07; OR, 1.32; 95% CI, 0.97-1.77), and albumin (P = .10; OR, 0.7; 95% CI, 0.46-1.07).ConclusionsThus far, this is the largest prospective and geographically diverse study of a U.S. cohort of patients with cirrhosis that validates known risk factors for HCC (gender, age, obesity, years with cirrhosis, family history of liver cancer, baseline AFP, albumin, and AST). The incidence of HCC was 2.4% per 100 person-years.

Project description:The host genetic background for hepatocellular carcinoma (HCC) is incompletely understood. We aimed to determine if four germline genetic polymorphisms, rs429358 in apolipoprotein E (APOE), rs2642438 in mitochondrial amidoxime reducing component 1 (MARC1), rs2792751 in glycerol-3-phosphate acyltransferase (GPAM), and rs187429064 in transmembrane 6 superfamily member 2 (TM6SF2), previously associated with progressive alcohol-related and nonalcoholic fatty liver disease, are also associated with HCC. Four HCC case-control data sets were constructed, including two mixed etiology data sets (UK Biobank and FinnGen); one hepatitis C virus (HCV) cohort (STOP-HCV), and one alcohol-related HCC cohort (Dresden HCC). The frequency of each variant was compared between HCC cases and cirrhosis controls (i.e., patients with cirrhosis without HCC). Population controls were also considered. Odds ratios (ORs) associations were calculated using logistic regression, adjusting for age, sex, and principal components of genetic ancestry. Fixed-effect meta-analysis was used to determine the pooled effect size across all data sets. Across four case-control data sets, 2,070 HCC cases, 4,121 cirrhosis controls, and 525,779 population controls were included. The rs429358:C allele (APOE) was significantly less frequent in HCC cases versus cirrhosis controls (OR, 0.71; 95% confidence interval [CI], 0.61-0.84; P = 2.9 × 10-5 ). Rs187429064:G (TM6SF2) was significantly more common in HCC cases versus cirrhosis controls and exhibited the strongest effect size (OR, 2.03; 95% CI, 1.45-2.86; P = 3.1 × 10-6 ). In contrast, rs2792751:T (GPAM) was not associated with HCC (OR, 1.01; 95% CI, 0.90-1.13; P = 0.89), whereas rs2642438:A (MARC1) narrowly missed statistical significance (OR, 0.91; 95% CI, 0.84-1.00; P = 0.043). Conclusion: This study associates carriage of rs429358:C (APOE) with a reduced risk of HCC in patients with cirrhosis. Conversely, carriage of rs187429064:G in TM6SF2 is associated with an increased risk of HCC in patients with cirrhosis.

Dataset Information

Factors associated with unrecognized cirrhosis in patients with hepatocellular carcinoma.

Background/aims

Methods

Results

Conclusion

Publications

Factors associated with unrecognized cirrhosis in patients with hepatocellular carcinoma.

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