Clinicopathological characteristics of non-B non-C hepatocellular carcinoma without past hepatitis B virus infection.
OBJECTIVE
Past hepatitis B virus (HBV) infection is considered a risk factor for hepatocarcinogenesis, but the clinicopathological characteristics of non-B non-C hepatocellular carcinoma (NBNC-HCC) excluding past HBV infection have not been investigated. This study aimed to clarify the clinicopathological features of strictly defined NBNC-HCC.


METHODS
Among HCC patients who underwent surgical resection at our affiliated hospitals in Nagano prefecture, Japan, between 1996 and 2012, 77 were negative for serum anti-HBV core/surface antibodies in addition to HBV surface antigen and anti-hepatitis C virus antibody without signs of autoimmune liver disease, Wilson disease, or hemochromatosis. These patients were divided into the alcohol intake-positive group (ethanol intake >20 g/day, n = 31), non-alcoholic fatty liver group (steatosis >5% and ethanol intake <20 g/day, n = 30), and cryptogenic group (no ethanol intake or steatosis, n = 16). Preoperative clinical parameters, tumor and background liver pathology, and prognosis were analyzed.


RESULTS
Advanced fibrosis and steatosis were detected in 64% and 60% of all patients, respectively. Approximately 85% of the alcohol intake-positive patients had advanced fibrosis. Non-alcoholic fatty liver HCC subjects had the highest body mass index and prevalence of diabetes, but 30-40% had none to mild fibrosis. The cryptogenic group of HCC patients had the lowest incidence of accompanying hepatic inflammation/fibrosis but the largest tumor size. Recurrence/survival rates were comparable among the groups.


CONCLUSIONS
Liver fibrosis and steatosis are risk factors of HCC regardless of past HBV infection and ethanol consumption. The present results also indicate the possibility of hepatocarcinogenesis independent of hepatic steatosis, inflammation and fibrosis, ethanol intake, and past HBV infection.
Department of Internal Medicine, Division of Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan.|Department of Gastroenterology, Nagano Red Cross Hospital, Nagano, Japan.
Takefumi
T
Kimura
Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan.
Akira
A
Kobayashi
Department of Metabolic Regulation, Shinshu University Graduate School of Medicine, Matsumoto, Japan.
Naoki
http://orcid.org/0000-0002-3212-3836
N
Tanaka
Department of Laboratory Medicine, Shinshu University Hospital, Matsumoto, Japan.
Kenji
K
Sano
Department of Internal Medicine, Division of Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan.
Michiharu
M
Komatsu
Department of Internal Medicine, Division of Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan.
Naoyuki
N
Fujimori
Department of Internal Medicine, Division of Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan.
Tomoo
T
Yamazaki
Department of Internal Medicine, Division of Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan.
Soichiro
S
Shibata
Department of Internal Medicine, Division of Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan.
Yuki
Y
Ichikawa
Department of Internal Medicine, Division of Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan.
Satoru
S
Joshita
Department of Internal Medicine, Division of Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan.
Takeji
T
Umemura
Department of Internal Medicine, Division of Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan.
Akihiro
A
Matsumoto
Digestive Disease Center, Showa Inan General Hospital, Komagane, Japan.
Akira
A
Horiuchi
Department of Gastroenterology, Nagano Red Cross Hospital, Nagano, Japan.
Hiromitsu
H
Mori
Department of Gastroenterology, Nagano Red Cross Hospital, Nagano, Japan.
Shuichi
S
Wada
Department of Internal Medicine, Shironishi Hospital, Matsumoto, Japan.
Kendo
K
Kiyosawa
Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan.
Shin-Ichi
SI
Miyagawa
Department of Internal Medicine, Division of Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan.
Eiji
E
Tanaka
diabetes; liver fibrosis; non-B non-B hepatocellular carcinoma; normal liver; obesity; past HBV infection