Clinical features and outcome of cryptogenic hepatocellular carcinoma compared to those of viral and alcoholic hepatocellular carcinoma

Abstract

BackgroundCryptogenic hepatocellular carcinoma (HCC) is thought to arise due to non-alcoholic fatty liver disease (NAFLD). This study investigated the prevalence, clinical features, and outcomes of cryptogenic HCC and compared them with those of HCC related to hepatitis B virus infection (HBV-HCC), hepatitis C virus infection (HCV-HCC), and alcohol (ALC-HCC) in Korea.MethodsThe clinical features, treatment modalities, and survival data for 480 patients with HCC consecutively enrolled from January 2003 to June 2012 were analyzed. Computed tomography images were used to measure the visceral fat area (VFA) and liver-spleen density ratio.ResultsCryptogenic HCC accounted for 6.8% of all HCC cases, whereas HBV-HCC, HCV-HCC, and ALC-HCC accounted for 62.7%, 13.5%, and 10.7% of HCC cases, respectively. The cryptogenic HCC group was characterized by older age, a low proportion of male patients, a high proportion of patients with metabolic syndrome or single nodular presentation, and a low proportion of patients with portal vein invasion compared to the viral-HCC and ALC-HCC groups. However, Child Pugh classes, tumor stages, and overall survival rates of cryptogenic HCC patients were similar to those of patients with HCC of other etiologies. VFA in cryptogenic HCC patients was significantly higher than that in viral-HCC patients, but similar to that in ALC-HCC patients. The liver-spleen density ratio did not vary according to HCC etiology.ConclusionsCryptogenic HCC accounts for approximately 7% of HCC cases in Korea, associated with an older age at diagnosis, more frequent occurrence of metabolic syndrome, and less aggressive tumor characteristics, but similar survival compared to viral-HCC or ALC-HCC. Based on VFA and the liver-to-spleen density ratio, cryptogenic HCC may be burnt-out NAFLD in which visceral fat remains but liver fat is depleted.

Clinical Characteristics of Patients with Cryptogenic Hepatocellular Carcinoma in a Hepatitis B Virus-Endemic Area

“…There are a few reports on the characteristics of cirrhosis according to cause [18][19][20]; however, such comparative studies of HCC are rare [4,21]. In South Korea, the incidence of cryptogenic, or NBNCNA, HCC has reportedly increased from 2.3% to 12.2% [21][22][23][24].…”

Lipid Metabolism in Liver Cancer

“…The relative risk of NAFLD/NASH alone in the absence of cirrhosis for HCC mortality was found to be as weak as 0-3% for a follow-up period up to 20 years [37]. The cumulative incidence for NAFLD with cirrhosis increased to a range between 2.4 and 11.3%, which was yet comparatively lower than that of hepatitis C with cirrhosis (17-30% for a 5-year cumulative incidence) [34,35,38]. By contrast, the relative risks for HBV and HCV to develop HCC are 15-20 folds, according to large case-control and cross-sectional studies [3,39,40].…”

“…The relationship between NAFLD and cryptogenic HCC could only be verified through medical history taking. Cryptogenic HCC may account for more advanced stage HCC through a complicated process from initial NAFLD/NASH-based hepatosteatosis to subsequent extensive lipid catabolism [32][33][34], so that the original steatosis was not observable at diagnosis. Although cirrhosis usually precedes HCC, increasing studies showed that NAFLD might induce HCC independent of cirrhosis [34][35][36].…”

“…Cryptogenic HCC may account for more advanced stage HCC through a complicated process from initial NAFLD/NASH-based hepatosteatosis to subsequent extensive lipid catabolism [32][33][34], so that the original steatosis was not observable at diagnosis. Although cirrhosis usually precedes HCC, increasing studies showed that NAFLD might induce HCC independent of cirrhosis [34][35][36]. It has been reported that NAFLD may account for 59% of non-cirrhotic HCC, compared to diabetes (36%) and chronic hepatitis C (22%), according to a recent study based on US healthcare claims database [17].…”

New players in non-alcoholic fatty liver disease induced carcinogenesis: lipid dysregulation impairs liver immune surveillance

“…Although chronic viral infections [i.e., hepatitis B or C virus (HBV, HCV)], and chronic exposition to hepatotoxic factors such as toxins and alcohol are a major cause of HCC (2), in western countries and especially in the USA, obesity and dysregulated lipid metabolism are emerging as important non-viral factors associated with HCC (3,4). In particular, non-alcoholic fatty liver disease (NAFLD), a manifestation of the metabolic syndrome, is strongly associated with obesity and dyslipidemia (5,6).…”