"Different degree of iron deposition"

Gender differences in the livers of patients with hepatocellular
carcinoma and chronic hepatitis C infection.
Nishida N, Arizumi T, Hayaishi S, Takita M, Kitai S, Yada N, Hagiwara
S, Inoue T, Minami Y, Ueshima K, Sakurai T, Ikai I, Kudo M.
Dig Dis. 2012;30(6):547-53.
Department of Gastroenterology and Hepatology, Faculty of Medicine,
Kinki University, Osaka, Japan.

A unique causative aspect of hepatocellular carcinoma (HCC) is a
gender difference in its incidence.
To determine the specific factors that contribute to a male
predominance, we analyzed the clinicopathological factors, and genetic
and epigenetic alterations of HCCs in male and female patients.
We retrospectively analyzed three cohorts of patients: the first
cohort consisted of 547 patients identified with the first event of
HCC, the second cohort included 176 HCC patients, and the third 127
patients with chronic hepatitis C (CHC).
Male patients were found to have HCC more frequently than female
patients in cases of non-cirrhotic liver (p = 0.0030 by the П‡(2)
test), especially in hepatitis C-positive cases.
However, there were no gender-specific differences in the genetic and
epigenetic alterations of cancer-related genes.
Deposition of iron was more severe in male CHC patients than in female
Male patients with CHC develop HCC more frequently when they have a
non-cirrhotic liver than do female patients.
This gender difference could be, at least partially, attributed to a
different degree of iron deposition, which contributes to the
development of HCC in the absence of liver cirrhosis in men with CHC.

Copyright В© 2012 S. Karger AG, Basel.



"None of these patients developed hepatocellular carcinoma (HCC)."


Normalization of Elevated Hepatic 8-Hydroxy-2'-Deoxyguanosine Levels
in Chronic Hepatitis C Patients by Phlebotomy and Low Iron Diet1
Junji Kato, Masayoshi Kobune, Tokiko Nakamura, Ganji Kuroiwa, Kohichi
Takada, Rishu Takimoto, Yasuhiro Sato, Koshi Fujikawa, Minoru
Takahashi, Tetsuji Takayama, Tatsuru Ikeda and Yoshiro Niitsu2
Fourth Department of Internal Medicine [J. K., T. N., G. K., K. T.,
R. T., Y. S., K. F., M. T., T. T., Y. N.] and
Department of Molecular Medicine [M. K.],
Sapporo Medical University School of Medicine,
and Department of Clinical Pathology, Sapporo Medical University
[T. I.], Sapporo 060-8543, Japan

Accumulation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in DNA, which
result from the continuous reactive oxygen species (ROS) generation
associated with chronic inflammation, has been reported in various
human preneoplastic lesions and in cancerous tissues.
However, no direct causative relationship between the 8-OHdG
and carcinogenesis has been thus far demonstrated in humans.
Directly proving the causality requires showing that depletion of 8-
OHdG levels in tissue by interfering with ROS generation results in a
reduction in cancer.
Chronic hepatitis C virus (HCV) infection is associated with a
high risk of hepatocellular carcinoma (HCC).
Several studies on patients with chronic HCV have shown that hepatic
iron overload is attributable to liver injury and that iron depletion
improved serum aminotransferase levels.
Excess iron is known to generate ROS within cells, which causes
mutagenic lesions, such as 8-OHdG.
In this study, therefore, we have evaluated whether therapeutic iron
reduction (phlebotomy and low iron diet) with a long-term follow-up
years) would decrease the hepatic 8-OHdG levels and the risk of HCC
development in patients with chronic HCV.
Patients (34) enrolled were those who had undergone standard IFN
therapy but had no sustained response.
Quantitative immunohistochemistry using the KS-400 image
analyzing system and electrochemical detection was used for 8-OHdG
With this treatment, elevated hepatic 8-OHdG levels in
patients with chronic hepatitis C (8.3 В± 4.6/105 dG) significantly
decreased to almost normal levels (2.2 В± 0.9/105 dG; P < 0.001) with
concomitant improvement of hepatitis severity, including fibrosis,
whereas HCV titers were unaffected.
None of these patients developed HCC.
Thus, long-term iron reduction therapy in patients with chronic
hepatitis C may potentially lower the risk of progression to HCC.


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