"Excessive hepatic deposition of iron"
"Increases the risk of hepatocellular carcinoma development"
"None of these patients developed hepatocellular carcinoma (HCC)."
"Phlebotomy and Low Iron Diet"
Current Experimental Perspectives on the Clinical
Progression of Alcoholic Liver Disease
Alcoholism: Clinical and Experimental Research
Katja Breitkopf, Laura E. Nagy, Juliane I. Beier,
Sebastian Mueller, Honglei Weng, and Steven Dooley
From the Molecular Alcohol Research in Gastroenterology,
Department of Medicine II, University Hospital Mannheim,
University of Heidelberg, Mannheim, Germany
Correspondence to Reprint requests: Dr. K. Breitkopf,
Molecular Alcohol Research in Gastroenterology,
Department of Medicine II, University Hospital Mannheim,
University of Heidelberg, Theodor-Kutzer-Ufer 1-3,
Mannheim 68167, Germany; Fax: +49 621 3831467;
E-mail: katja.breitk...@medma.uni-heidelberg.de
Review of the corresponding symposium which took place
at the RSA/ISBRA meeting 2008.
Copyright © 2009 Research Society on Alcoholism
KEYWORDS
Steatosis • Steatohepatitis • Liver Fibrosis • HCC
ABSTRACT
Chronic alcohol abuse is an important cause of morbidity
and mortality throughout the world.
Liver damage due to chronic alcohol intoxication initially
leads to accumulation of lipids within the liver and with
ongoing exposure this condition of steatosis may first
progress to an inflammatory stage which leads the way
for fibrogenesis and finally cirrhosis of the liver.
While the earlier stages of the disease are considered
reversible, cirrhotic destruction of the liver architecture
beyond certain limits causes irreversible damage of the
organ and often represents the basis for cancer development.
This review will summarize current knowledge about the
molecular mechanisms underlying the different stages of
alcoholic liver disease (ALD).
Recent observations have led to the identification of
new molecular mechanisms and mediators of ALD.
For example, plasminogen activator inhibitor 1 was shown
to play a central role for steatosis, the anti-inflammatory
adipokine, adiponectin profoundly regulates liver macrophage
function and excessive hepatic deposition of iron is caused
by chronic ethanol intoxication and increases the risk of
hepatocellular carcinoma development.
Received for publication March 2, 2009; accepted May 7, 2009.
DIGITAL OBJECT IDENTIFIER (DOI)
10.1111/j.1530-0277.2009.01015.x About DOI
Early View (Articles online in advance of print)
Published Online: 23 Jul 2009
© 2009 Research Society on Alcoholism
-----------------
"None of these patients developed hepatocellular carcinoma (HCC)."
http://cancerres.aacrjournals.org/cg...act/61/24/8697
Clinical Investigations
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 Hospital
[T. I.], Sapporo 060-8543, Japan
Accumulation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in DNA, which may
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 formation 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 (6 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
detection. With this treatment, elevated hepatic 8-OHdG levels in
patients with chronic hepatitis C (8.3 ± 4.6/105 dG) significantly
decreased to almost normal levels (2.2 ± 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.
Who loves ya.
Tom
Jesus Was A Vegetarian!
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Man Is A Herbivore!
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DEAD PEOPLE WALKING
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