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OBJECTIVES:The race of patients infected with hepatitis C virus (HCV) in the United States may be associated with the risk for cirrhosis and hepatocellular carcinoma (HCC). However, previous studies are too small to provide convincing data regarding the effect of race on cirrhosis and HCC risk after accounting for demographic, clinical, and virological factors.METHODS:We used the Veterans Administration (VA) HCV Clinical Case Registry to identify patients with confirmed viremia between 2000 and 2009 and with at least 1 year of follow-up in the VA. We identified cirrhosis and HCC cases through early 2010. Cox proportional hazard regression models were performed to examine the effect of race on the risk for cirrhosis and HCC while adjusting for patients' age, gender, period of service (World War I/II, Vietnam era, post-Vietnam era), HIV coinfection, HBV coinfection, alcohol abuse, diabetes, body mass index, and antiviral treatment receipt and response.RESULTS:There were 149,407 patients with active HCV viremia. Of them, 56.3% were non-Hispanic White (NHW), 36.1% were African American (AA), 6.0% were Hispanic, and 1.6% belonged to other racial groups. After an average follow-up of 5.2 years, 13,099 patients were seen to have a recorded diagnosis of cirrhosis and 3,551 had HCC. Hispanics had the highest annual incidence rates of cirrhosis and HCC (28.8 and 7.8%, respectively), whereas AAs had the lowest rates (13.3% and 3.9%, respectively) compared with NHWs (21.6 and 4.7%, respectively). There were differences among NHW, AA, and Hispanic patients in the rates of HIV infection (2.1, 2.5, and 6.0%, respectively), HCV genotype 1 (50.0, 50.6, and 64.2%, respectively), obesity (28.0, 25.4, and 30.9%, respectively), diabetes (8.7, 16.1, and 16.1%, respectively), and absence of antiviral treatment (81.1, 89.6, and 82.1%, respectively). However, adjusting for differences in demographic and clinical factors did not change the magnitude or direction of the race effect. Compared with NHWs, Hispanic patients had a higher risk of having cirrhosis recorded (adjusted hazard ratio (HR)=1.28, 95% confidence interval (CI)=1.21-1.37) and HCC (1.61, 95% CI=1.44-1.80). In contrast, AAs had a lower risk of cirrhosis (HR=0.58, 95% CI=0.55-0.60) and HCC (0.77, 95% CI=0.71-0.83) compared with NHWs.CONCLUSIONS:Hispanics with HCV are at a significantly higher risk, whereas AAs are at a considerably lower risk of developing cirrhosis and HCC than are NHWs. These associations persisted even after adjusting for a range of factors including HCV genotype, HCV treatment, diabetes, and body mass index. [ABSTRACT FROM AUTHOR]

Background & Aims: Little information is available about what factors determine serum levels of alpha fetoprotein (AFP) (eg, demographic, virologic, or clinical features) among individuals who do not develop hepatocellular carcinoma (HCC). This information might improve AFP-based algorithms for HCC detection. Methods: We examined data from patients in the national Veterans'' Affairs Hepatitis C Virus (HCV) Clinical Case Registry who received at least 1 AFP test (258,275 AFP tests in 76,357 patients; 1.9% developed HCC). We constructed hierarchical multivariate models of AFP levels. Potential predictors of AFP values included patients'' sex, race, cirrhosis status, Model for End-Stage Liver Disease (MELD) score, HCV genotype, level of alanine aminotransferase (ALT) within 30 days before the AFP test, time to diagnosis of HCC, and time elapsed from the HCV index date. Results: Significant determinants for increased levels of AFP included presence of cirrhosis, higher MELD scores, and increased levels of ALT. AFP levels were also affected by the interaction between ALT levels and the presence and time to development of HCC. Among patients who did not have HCC, the AFP level increased with the level of ALT; the AFP values in the presence of ALT 37–56 U/L, ALT 57–92 U/L, or ALT >92 U/L were 16%, 35%, and 68% higher, respectively, than AFP values at ALT 0–36 U/L. However, patients who developed HCC within 30 days of receiving the AFP test had a lower rate of increase in AFP with each higher category of ALT level, with increases of 31%, 39%, and 37% for the same respective ALT categories. Conclusions: In patients with chronic HCV infection, AFP and ALT values correlate; however, among patients with HCC, levels of AFP increase disproportionately to or unaccompanied by increases in levels of ALT. The prognostic and diagnostic value of AFP levels might be increased by adjusting for ALT values. [Copyright &y& Elsevier]

Background & Aims: Hepatocellular carcinoma (HCC) can result from hepatitis C virus (HCV)-related liver disease and is the fastest-growing cause of cancer-related death in the United States. α-fetoprotein (AFP) has been used as a prognostic factor for HCC, but the value of AFP as a prognostic factor for HCV-related HCC in the United States is unknown. We investigated whether higher levels of AFP at the time of diagnosis are associated with increased mortality of patients with HCV-related HCC. Methods: In a retrospective study, we collected data from a cohort of HCV-infected veterans, identifying incident HCC cases from October 1, 1998, to January 1, 2007 (n = 1480 patients). The mean serum levels of AFP, obtained within 60 days before to 30 days after HCC diagnosis, were determined for 1064 patients and categorized as less than 10 ng/mL (18%), 10 to less than 100 ng/mL (30%), 100 to less than 1000 ng/mL (22%), or 1000 ng/mL or more (29%). Cox proportional hazard models were used to associate serum levels of AFP with mortality, adjusting for demographic features, clinical factors, and treatment. Results: The median survival times were significantly lower among patients with higher levels of AFP: 709 days for patients with less than 10 ng/mL, 422 days for patients with 10 to less than 100 ng/mL, 208 days for patients with 100 to less than 1000 ng/mL, and 68 days for patients with 1000 ng/mL or more. In the multivariate analysis, increased levels of AFP (10 to <100, 100 to <1000, and ≥1000) were associated significantly with increased mortality, compared with a serum AFP level of less than 10; hazard ratios were 1.50, 2.23, and 4.35, respectively. Conclusions: Serum AFP level at the time of diagnosis with HCV-related HCC is an independent predictor of mortality. [Copyright &y& Elsevier]

Background & Aims 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. population. Methods 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. Results 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. Conclusions 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. [ABSTRACT FROM AUTHOR]

Background & Aims Nonalcoholic fatty liver disease (NAFLD) is a risk factor for hepatocellular carcinoma (HCC). However, no systemic studies from the United States have examined temporal trends, HCC surveillance practices, and outcomes of NAFLD-related HCC. Methods We identified a national cohort of 1500 patients who developed HCC from 2005 through 2010 from Veterans Administration (VA) hospitals. We reviewed patients’ full VA medical records; NAFLD was diagnosed based on histologic evidence for, or the presence of, the metabolic syndrome in the absence of hepatitis C virus (HCV) infection, hepatitis B, or alcoholic liver disease. We compared annual prevalence values for the main risk factors (NAFLD, alcohol abuse, and HCV), as well a HCC surveillance and outcomes, among HCC patients. Results NAFLD was the underlying risk factor for HCC in 120 patients (8.0%); the annual proportion of NAFLD-related HCC remained relatively stable (7.5%–12.0%). In contrast, the proportion of HCC cases associated with HCV increased from 61.0% in 2005 (95% confidence interval, 53.1%–68.9%) to 74.9% in 2010 (95% confidence interval, 69.0%–80.7%). The proportion of HCC cases associated with only alcohol abuse decreased from 21.9% in 2005 to 15.7% in 2010, and the annual proportion of HCC cases associated with hepatitis B remained relatively stable (1.4%–3.5%). A significantly lower proportion of patients with NAFLD-related HCC had cirrhosis (58.3%) compared with patients with alcohol- or HCV-related HCC (72.4% and 85.6%, respectively; P < .05). A significantly higher percentage of patients with NAFLD-related HCC did not receive HCC surveillance in the 3 years before their HCC diagnosis, compared with patients with alcohol- or HCV-associated HCC. A lower proportion of patients with NAFLD-related HCC received HCC-specific treatment (61.5%) than patients with HCV-related HCC (77.5%; P < .01). However, the 1-year survival rate did not differ among patients with HCC related to different risk factors. Conclusions NAFLD is the third most common risk factor for HCC in the VA population. The proportion of NAFLD-related HCC was relatively stable from 2005 through 2010. Although patients with NAFLD-related HCC received less HCC surveillance and treatment, a similar proportion survive for 1 year, compared with patients with alcohol-related or HCV-related HCC. [ABSTRACT FROM AUTHOR]

Background Transarterial chemoembolization (TACE) is the most common procedure for the treatment of hepatocellular carcinoma (HCC). However, HCC is generally considered chemoresistant and data demonstrating the superiority of TACE over bland embolization (TAE) are lacking. Materials and methods A nationwide, retrospective cohort study of HCC patients treated with first-line TACE or TAE within the Veterans Affairs health care system (2005–2012) was performed. The primary outcome was overall survival. Risk of death by treatment type (TACE or TAE) was evaluated using multivariate (adjusted for age, presence of cirrhosis, Barcelona Clinic Liver Cancer stage, and Charlson comorbidity score) and propensity score-adjusted Cox regression. Results The cohort included 405 patients treated with first-line transarterial embolization. Among these patients, 32 (7.9%) underwent TAE. Most of the patients (76.8%) had intermediate or advanced stage at presentation. Similar proportions of patients (TACE 53.3% versus TAE 43.7%; P = 0.30) received more than one embolization procedure. There was no difference in median survival (20.1 versus 23.1 mo, respectively; log-rank P = 0.84). Compared to TACE, there was no difference in risk of death associated with TAE after multivariate (hazard ratio [HR] 0.92; 95% CI, 0.61–1.37) and propensity score adjustment (HR = 0.86; 95% CI = 0.58–1.29). Conclusions There is no clear benefit associated with chemotherapy infusion over bland embolization for HCC treatment. Given the rising incidence of HCC in the United States and considering the added costs associated with TACE compared to TAE, future work comparing these competing management strategies is needed. [ABSTRACT FROM AUTHOR]