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BMC Cancer

, 13:335

Clinical oncology


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.

KeywordsHepatocellular carcinoma Non-alcoholic fatty liver disease Alcohol Visceral fat Prognosis AbbreviationsHCCHepatocellular carcinoma

HBVHepatitis B virus

HCVHepatitis C virus

NAFLDNon-alcoholic fatty liver disease

NASHNon-alcoholic steatohepatitis

VFAVisceral fat area

CTcomputed tomography

HBV-HCCHepatitis B virus -associated hepatocellular carcinoma

HCV-HCCHepatitis C virus -associated hepatocellular carcinoma

ALC-HCCAlcohol-associated hepatocellular carcinoma

MRIMagnetic resonance imaging

BMIBody mass index


LDLLow-density lipoprotein

HDLHigh-density lipoprotein cholesterol

ALTAlanine aminotransferase

ASTAspartate aminotransferase

ALPAlkaline phosphatase


MELDModel for end-stage liver disease

BCLCBarcelona Clinic Liver Cancer

TACETransarterial chemoembolization

RFARadiofrequency ablation

PEIPercutaneous ethanol injection

HUHounsfield units

ROIRegions of interest

NAFLD-HCCNon-alcoholic fatty liver disease -associated hepatocellular carcinoma.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-13-335 contains supplementary material, which is available to authorized users.

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Autor: Sang Soo Lee - Sook-Hyang Jeong - Young-Sang Byoun - Seong Min Chung - Mun Hyuk Seong - Hyung Rae Sohn - Bo-young Min -


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