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Hepatocellular Carcinoma in the Absence of Cirrhosis in United States Veterans is Associated With Nonalcoholic Fatty Liver Disease.

ABSTRACT: Hepatocellular carcinoma (HCC) can develop in individuals without cirrhosis. We investigated risk factors for development of HCC in the absence of cirrhosis in a U.S.We identified a national cohort of 1500 patients with verified HCC during 2005 to 2010 in the U.S. Veterans Administration (VA) and reviewed their full VA medical records for evidence of cirrhosis and risk factors for HCC. Patients without cirrhosis were assigned to categories of level 1 evidence for no cirrhosis (very high probability) or level 2 evidence for no cirrhosis (high probability), which were based on findings from histologic analyses, laboratory test results, markers of fibrosis from noninvasive tests, and imaging features.A total of 43 of the 1500 patients with HCC (2.9%) had level 1 evidence for no cirrhosis, and 151 (10.1%) had level 2 evidence for no cirrhosis; the remaining 1203 patients (80.1%) had confirmed cirrhosis. Compared with patients with HCC in presence of cirrhosis, greater proportions of patients with HCC without evidence of cirrhosis had metabolic syndrome, nonalcoholic fatty liver disease (NAFLD), or no identifiable risk factors. Patients with HCC without evidence of cirrhosis were less likely to have abused alcohol or have hepatitis C virus infection than patients with cirrhosis. Patients with HCC and NAFLD (unadjusted odds ratio, 5.4; 95% confidence interval, 3.4-8.5) or metabolic syndrome (unadjusted odds ratio, 5.0; 95% confidence interval, 3.1-7.8) had more than 5-fold risk of having HCC in the absence of cirrhosis, compared with patients with HCV-related HCC.Approximately 13% of patients with HCC in the VA system do not appear to have cirrhosis. NAFLD and metabolic syndrome are the main risk factors for HCC in the absence of cirrhosis.

SUBMITTER: Mittal S

PROVIDER: S-EPMC4690789 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Hepatocellular Carcinoma in the Absence of Cirrhosis in United States Veterans is Associated With Nonalcoholic Fatty Liver Disease.

Mittal Sahil S El-Serag Hashem B HB Sada Yvonne H YH Kanwal Fasiha F Duan Zhigang Z Temple Sarah S May Sarah B SB Kramer Jennifer R JR Richardson Peter A PA Davila Jessica A JA

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 20150718 1

<h4>Background & aims</h4>Hepatocellular carcinoma (HCC) can develop in individuals without cirrhosis. We investigated risk factors for development of HCC in the absence of cirrhosis in a U.S.<h4>Methods</h4>We identified a national cohort of 1500 patients with verified HCC during 2005 to 2010 in the U.S. Veterans Administration (VA) and reviewed their full VA medical records for evidence of cirrhosis and risk factors for HCC. Patients without cirrhosis were assigned to categories of level 1 evi ...[more]

PMID: 26196445

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Project description:BACKGROUND & AIMS:It is important to quantify medical costs associated with hepatocellular carcinoma (HCC), the incidence of which is rapidly increasing in the United States, for development of rational healthcare policies related to liver cancer surveillance and treatment of chronic liver disease. We aimed to comprehensively quantify healthcare costs for HCC among patients with cirrhosis in an integrated health system and develop a model for predicting costs that is based on clinically relevant variables. METHODS:Three years subsequent to liver cancer diagnosis, costs accrued by patients included in the Veteran's Outcome and Cost Associated with Liver disease cohort were compiled by using the Department of Veterans Affairs Corporate Data Warehouse. The cohort includes all patients with HCC diagnosed in 2008-2010 within the VA with 100% chart confirmation as well as chart abstraction of tumor and clinical characteristics. Cancer cases were matched 1:4 with non-cancer cirrhosis controls on the basis of severity of liver disease, age, and comorbidities to estimate background cirrhosis-related costs. Univariable and multivariable generalized linear models were developed and used to predict cancer-related overall cost. RESULTS:Our analysis included 3188 cases of HCC and 12,722 controls. The mean 3-year total cost of care in HCC patients was $154,688 (standard error, $150,953-$158,422) compared with $69,010 (standard error, $67,344-$70,675) in matched cirrhotic controls, yielding an incremental cost of $85,679; 64.9% of this value reflected increased inpatient costs. In univariable analyses, receipt of transplantation, Barcelona Clinic Liver Cancer (BCLC) stage, liver disease etiology, hospital academic affiliation, use of multidisciplinary tumor board, and identification through surveillance were associated with cancer-related costs. Multivariable generalized linear models incorporating transplantation status, BCLC stage, and multidisciplinary tumor board presentation accurately predicted liver cancer-related costs (Hosmer-Lemeshow goodness of fit; P value ? 1.0). CONCLUSIONS:In a model developed to comprehensively quantify healthcare costs for HCC among patients with cirrhosis in an integrated health system, we associated receipt of liver transplantation, BCLC stage, and multidisciplinary tumor board with higher costs. Models that predict total costs on the basis of receipt of liver transplantation were constructed and can be used to model cost-effectiveness of therapies focused on HCC prevention.

Project description:The US prevalence of nonalcoholic fatty liver disease (NAFLD) is 30.6% and increasing. NAFLD shares some risk factors with periodontitis and dental caries. We explored the association between NAFLD and several oral conditions among US adults, using data from the cross-sectional, nationally representative National Health and Nutrition Examination Survey (NHANES), 1988 to 1994. NAFLD was assessed with ultrasonography (USON), the screening gold standard not available in the more recent NHANES, and the noninvasive Fibrosis Score (FS), Fatty Liver Index (FLI), and US Fatty Liver Index (US-FLI) as other screening alternatives. There were 5,421 eligible dentate adults aged 21 to 74 y with complete relevant data, with transferrin levels ?50%, without hepatitis B or C, who were not heavy drinkers. Multivariable models were developed to examine the independent effects of moderate-severe periodontitis, untreated dental caries, caries experience, and tooth loss (<20 teeth) on NAFLD while controlling for clinical, biological, and sociodemographic factors. Weighted estimates for odds ratios (ORs) and 95% CIs were calculated with logistic regression. Between 17% and 24% of adults had NAFLD depending on the classification criteria. In adjusted models, as compared with those with better oral health, adults with <20 teeth were more likely to have NAFLD depending on the measure (USON: OR = 1.50, 95% CI = 1.11 to 2.02; FS: OR = 4.36, 95% CI = 3.47 to 5.49; FLI: OR = 1.99, 95% CI = 1.52 to 2.59; US-FLI: OR = 2.32, 95% CI = 1.79 to 3.01). People with moderate-severe periodontitis were more likely to have NAFLD (USON: OR = 1.54, 95% CI = 1.06 to 2.24; FS: OR = 3.10, 95% CI = 2.31 to 4.17; FLI: OR = 1.61, 95% CI = 1.13 to 2.28; US-FLI: OR = 2.21, 95% CI = 1.64 to 2.98). People with any untreated caries were more likely to have NAFLD (USON: OR = 1.51, 95% CI = 1.20 to 1.90; FLI: OR = 1.80, 95% CI = 1.33 to 2.44). NAFLD was associated with tooth loss, periodontitis, and, for some NAFLD measures, untreated dental caries but not overall caries experience after controlling for several key sociodemographic and behavioral factors. Results suggest that further evaluation is needed to better understand this health-oral health interrelationship and potential opportunities for medical-dental integration.

Project description:Population-level nonalcoholic fatty liver disease (NAFLD) death rate data are sparse. We described death rates for adults with NAFLD in the United States using mortality data from the National Vital Statistics System multiple-cause mortality data (2007-2016). Decedents who had NAFLD were identified by International Classification of Diseases (ICD) codes K75.81, K76.0, K74.0, K74.6, and K76.9. Among NAFLD decedents, cause-specific deaths (e.g., cardiovascular disease [CVD], cirrhosis, hepatocellular carcinoma [HCC], non-liver cancer, diabetes mellitus [DM]) were identified by underlying cause of death ICD-10 codes. Trends were evaluated by average annual percentage change (AAPC) in age-standardized death rate (ASDR) per 100,000 persons. Among the 25,129,960 decedents aged ≥20 years, 353,234 (1.4%) decedents had NAFLD (212,322 men; 260,765 non-Hispanic whites, 32,868 non-Hispanic blacks, 46,530 Hispanics, 5,025 non-Hispanic American Indian or Alaska Natives [AIANs], 7,023 non-Hispanic Asian or Pacific Islanders [APIs]), with a mean age at death of 64.47 ± 13.17 years. During the study period, the ASDR for NAFLD increased by 15% (12.94 to 14.90; AAPC, 1.98%; P < 0.001]), while women (AAPC, 2.99% vs. 1.16% men; P = 0.003), non-Hispanic whites (AAPC, 2.48%), non-Hispanic AIANs (AAPC, 2.31%), and Hispanics (AAPC, 0.74%) experienced the highest annual increases. Stable trends were noted for non-Hispanic blacks and non-Hispanic APIs. Among subgroups, Mexican (AAPC, 1.75%) and Asian Indians (AAPC, 6.94%) experienced annual increases. The top six underlying causes of death (155,894 cirrhosis, 38,444 CVD, 19,466 non-liver cancer, 10,867 HCC, 8,113 DM, and 5,683 lung disease) accounted for 67.5% of NAFLD-related deaths. For cause-specific deaths, ASDR increased for HCC (AAPC, 3.82%), DM (AAPC, 2.23%), non-liver cancer (AAPC, 2.14%), CVD (AAPC, 1.59%), and cirrhosis (AAPC, 0.96%). Conclusion: NAFLD-related deaths in U.S. adults are increasing. Cirrhosis is the top cause-specific death, followed by CVD. Women, non-Hispanic whites, and non-Hispanic AIANs (subgroups Mexicans and Asian Indians) experienced the highest increases in deaths. Policies addressing the societal burden of NAFLD are needed.

Dataset Information

Hepatocellular Carcinoma in the Absence of Cirrhosis in United States Veterans is Associated With Nonalcoholic Fatty Liver Disease.

Publications

Hepatocellular Carcinoma in the Absence of Cirrhosis in United States Veterans is Associated With Nonalcoholic Fatty Liver Disease.

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