Temporal Trends of Nonalcoholic Fatty Liver Disease–Related Hepatocellular Carcinoma in the Veteran Affairs Population

Abstract

Background & Aims Non-alcoholic 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, 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, HCV), as well 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 to 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 to patients with alcohol- or HCV-associated HCC. A lower proportion of patients with NAFLD-related HCC received HCC-specific treatment (61.5%) than of patients with HCV-related HCC (77.5%; P<.01). However, 1-year survival 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. The proportion of NAFLD-related HCC was relatively stable from 2005 through 2010. Although patients with NAFLD-related HCC receive less HCC surveillance and treatment, a similar proportion survive for 1 year, compared to patients with alcohol- or HCV-related HCC.

Incidence of Hepatocellular Carcinoma in All 50 United States, From 2000 Through 2012

“…Our findings are consistent with earlier research suggesting that Hispanics in the United States continue to have the fastest sustained increase in HCC age-adjusted incidence rates, 14 with rates higher in US-born Hispanics than foreign-born Hispanics. The reasons have not been examined directly, but likely are related to higher rates of HCV (particularly in Mexican Americans), 15,16 alcoholic liver disease, NAFLD, 17,18 and the metabolic syndrome including diabetes, 19 which increases the risk of developing HCC either independently or through potentiating the effect of viral hepatitis and alcoholic liver disease. Furthermore, Hispanics with chronic HCV in the United States also have a risk of progression to cirrhosis and HCC, higher than any other ethnic or racial group.…”

“…20 The high HCC rates in states with high proportions of Hispanic residents further highlight this point and the potential importance of the metabolic syndrome and nonalcoholic steatohepatitis in HCC. 19,21 …”

Hepatocellular Carcinoma From Epidemiology to Prevention: Translating Knowledge into Practice

“…The proportion of HCC cases associated with alcohol abuse alone 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%). 42 Given that HBV and HCV appear to make the greatest contribution to HCC burden, the highest quality data for primary prevention support HBV vaccination and/or anti-viral treatment programs. However, some data support evaluation of chemoprevention agents for patients with non-viral liver disease.…”

Utilization of animal models to investigate nonalcoholic steatohepatitis-associated hepatocellular carcinoma

“…Clinical and laboratory research of NASH-associated HCC is in its infancy, and faces tremendous challenges, such as multifactorial features, difficulty in establishing causative-effect links in population studies, and lack of reliable animal models for NASH and NASH-HCC. This phenomenon is especially common in regions with a higher HBV or HCV infection rate, where it is believed that the incident of HCC derived from NAFLD/NASH is very low because when an individual is HBV or HCV-positive, HCC is attributed to be the consequence of viral infection whether NAFLD/NASH is present or not [76]. …”