Open Access Highly Accessed Research article

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

Sang Soo Lee1, Sook-Hyang Jeong1*, Young-Sang Byoun1, Seong Min Chung1, Mun Hyuk Seong1, Hyung Rae Sohn1, Bo-young Min1, Eun Sun Jang1, Jin-Wook Kim1, Guan Jung Park2, Yoon Jin Lee2, Kyoung Ho Lee2 and Soyeon Ahn3

Author Affiliations

1 Department of Internal Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro, 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do 463-707, South Korea

2 Radiology, Seoul National University Bundang Hospital, Seongnam, South Korea

3 Medical Research Collaborating Center, Seoul National University Bundang Hospital, Seongnam, South Korea

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BMC Cancer 2013, 13:335  doi:10.1186/1471-2407-13-335

Published: 8 July 2013



Cryptogenic 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.


The 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.


Cryptogenic 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.


Cryptogenic 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.

Hepatocellular carcinoma; Non-alcoholic fatty liver disease; Alcohol; Visceral fat; Prognosis