Phlebotomy Improves Hepatitis C

Bloodletting in hepatitis ..
Whoda .. thunk.

Dig Dis Sci. 2008 Mar;53(3):815-22. Epub 2007 Sep 12.
Phlebotomy improves therapeutic response to interferon in patients
with chronic hepatitis C: a meta-analysis of six prospective
randomized controlled trials.
Desai TK, Jamil LH, Balasubramaniam M, Koff R, Bonkovsky HL.
William Beaumont Hospital, Royal Oak, MI, USA. tusarde...@aol.com

Prospective randomized controlled trials (RCTs) comparing phlebotomy
and interferon (IFN) treatment to IFN alone in
patients with chronic hepatitis C (CHC) have suggested a
benefit for the phlebotomy group.
However, statistical significance was achieved in only one of these
trials.
We performed a meta-analysis of RCTs comparing phlebotomy and IFN to
IFN alone for the treatment of CHC.
The MEDLINE database and Cochrane registry of controlled trials were
searched using the key words "phlebotomy" and "treatment of hepatitis
C."
Reference lists of review articles discussing the interaction between
iron and CHC, and prospective RCTs comparing phlebotomy plus IFN
therapy to IFN alone were searched to identify additional RCTs that
compared phlebotomy
plus IFN to IFN alone.
Peto odds ratios with their 95% confidence intervals and Forrest plots
were generated for each variable to assess the relationships among the
studies that had provided that information.
Statistical analysis was performed using Comprehensive
META-Analysis version 2.0.
Six prospective RCTs were identified: all used sustained viral
response (SVR) as an endpoint.
The three largest RCTs excluded patients with cirrhosis.
Two RCTs specifically included only patients with either high ferritin
or high hepatic iron content.
IFN treatment regimes varied.
Length of treatment varied between 6 and 12 months.
The phlebotomy plus IFN group and the IFN group did not
differ with respect to the percentage of patients with cirrhosis or
genotype 1.
SVR was attained in 50/182 (27%) patients in the phlebotomy plus IFN
group, compared to 22/185 (12%) patients in the
IFN group.
Peto odds ratio for SVR in phlebotomy plus IFN group was
2.7; 95% CI 1.6-4.5, P < 0.0001.
All five RCTs published in manuscript form showed a trend towards a
benefit from the phlebotomy plus IFN in attaining SVR, and the results
of the meta-analysis were not dependent on any single RCT, since
excluding any single RCT did not change the
results.
Phlebotomy improves the SVR in response to IFN treatment in
patients with CHC.
Confirmation of this will require RCT with detailed pre-treatment iron
studies and appropriately powered to demonstrate a
statistically significant benefit.


PMID: 17846887 [PubMed - in process]


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Tom


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DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk

ironjustice@aol.com used his keyboard to write :
> Bloodletting in hepatitis ..
> Whoda .. thunk.
>
> Dig Dis Sci. 2008 Mar;53(3):815-22. Epub 2007 Sep 12.
> Phlebotomy improves therapeutic response to interferon in patients
> with chronic hepatitis C: a meta-analysis of six prospective
> randomized controlled trials.
> Desai TK, Jamil LH, Balasubramaniam M, Koff R, Bonkovsky HL.
> William Beaumont Hospital, Royal Oak, MI, USA. tusarde...@aol.com
>
> Prospective randomized controlled trials (RCTs) comparing phlebotomy
> and interferon (IFN) treatment to IFN alone in
> patients with chronic hepatitis C (CHC) have suggested a
> benefit for the phlebotomy group.
> However, statistical significance was achieved in only one of these
> trials.
>...

People need to be very careful about this. Might help people who have
iron overload (primarily men) reduce their iron, which would make sense
since iron overload has been shown to reduce SVR and make liver disease
worse.

Not so clear if someone is iron deficient (particularly common in
women), since phlebotomy (removing blood) would make that worse, then
anemia is worse, and that would make the side effects from riba worse
(requiring a drop in riba dose).

Since higher doses of riba are needed for best SVR chances, phlebotomy
might be a really bad idea in people who are borderline or low on iron.

-- Fee Fi

On Apr 18, 10:36 am, "ironjust...@aol.com" <ironjust...@aol.com>
wrote:

<<snip>>
None of these patients developed hepatocellular carcinoma (HCC).
<<snip>>

http://cancerres.aacrjournals.org/cgi/content/abstract/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!
http://tinyurl.com/2r2nkh


Man Is A Herbivore!
http://tinyurl.com/a3cc3


DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk




> Bloodletting in hepatitis ..
> Whoda .. thunk.
>
> Dig Dis Sci. 2008 Mar;53(3):815-22. Epub 2007 Sep 12.
> Phlebotomy improves therapeutic response to interferon in patients
> with chronic hepatitis C: a meta-analysis of six prospective
> randomized controlled trials.
> Desai TK, Jamil LH, Balasubramaniam M, Koff R, Bonkovsky HL.
> William Beaumont Hospital, Royal Oak, MI, USA. tusarde...@aol.com
>
> Prospective randomized controlled trials (RCTs) comparing phlebotomy
> and interferon (IFN) treatment to IFN alone in
> patients with chronic hepatitis C (CHC) have suggested a
> benefit for the phlebotomy group.
> However, statistical significance was achieved in only one of these
> trials.
> We performed a meta-analysis of RCTs comparing phlebotomy and IFN to
> IFN alone for the treatment of CHC.
> The MEDLINE database and Cochrane registry of controlled trials were
> searched using the key words "phlebotomy" and "treatment of hepatitis
> C."
> Reference lists of review articles discussing the interaction between
> iron and CHC, and prospective RCTs comparing phlebotomy plus IFN
> therapy to IFN alone were searched to identify additional RCTs that
> compared phlebotomy
> plus IFN to IFN alone.
> Peto odds ratios with their 95% confidence intervals and Forrest plots
> were generated for each variable to assess the relationships among the
> studies that had provided that information.
> Statistical analysis was performed using Comprehensive
> META-Analysis version 2.0.
> Six prospective RCTs were identified: all used sustained viral
> response (SVR) as an endpoint.
> The three largest RCTs excluded patients with cirrhosis.
> Two RCTs specifically included only patients with either high ferritin
> or high hepatic iron content.
> IFN treatment regimes varied.
> Length of treatment varied between 6 and 12 months.
> The phlebotomy plus IFN group and the IFN group did not
> differ with respect to the percentage of patients with cirrhosis or
> genotype 1.
> SVR was attained in 50/182 (27%) patients in the phlebotomy plus IFN
> group, compared to 22/185 (12%) patients in the
> IFN group.
> Peto odds ratio for SVR in phlebotomy plus IFN group was
> 2.7; 95% CI 1.6-4.5, P < 0.0001.
> All five RCTs published in manuscript form showed a trend towards a
> benefit from the phlebotomy plus IFN in attaining SVR, and the results
> of the meta-analysis were not dependent on any single RCT, since
> excluding any single RCT did not change the
> results.
> Phlebotomy improves the SVR in response to IFN treatment in
> patients with CHC.
> Confirmation of this will require RCT with detailed pre-treatment iron
> studies and appropriately powered to demonstrate a
> statistically significant benefit.
>
> PMID: 17846887 [PubMed - in process]
>
> Who loves ya.
> Tom
>
> Jesus Was A Vegetarian!http://tinyurl.com/2r2nkh
>
> Man Is A Herbivore!http://tinyurl.com/a3cc3
>
> DEAD PEOPLE WALKINGhttp://tinyurl.com/zk9fk

On Apr 18, 10:36 am, "ironjust...@aol.com" <ironjust...@aol.com>
wrote: Bloodletting in hepatitis <<

<<snip>>
direct hepatocarcinogenic effect of free iron is mediated by the
generation of oxygen reactive species and oxidative damage that are
mutagenic and carcinogenic
<<snip>>

1: Toxicology. 2005 Dec 5; [Epub ahead of print] Links


Hepatocellular carcinoma caused by iron overload: A possible
mechanism
of direct hepatocarcinogenicity.


Asare GA, Mossanda KS, Kew MC, Paterson AC, Kahler-Venter CP, Siziba
K.


MRC/University Molecular Hepatology Research Unit, Department of
Medicine, University of the Witwatersrand, 7 York Road, Parktown
2193,
Johannesburg, South Africa.


BACKGROUND/AIMS:
Excess hepatic iron may be both directly and
indirectly carcinogenic. The aim of this study was to determine if
generation of reactive oxygen species and the resulting oxidative
damage induced by free hepatic iron is directly hepatocarcinogenic.
METHODS: Sixty male Wistar albino rats were iron-loaded by ferrocene
supplementation of their diet. Biochemical parameters of oxidative
damage and lipid peroxidation, DNA unwinding and strand breaks, and
the
Ames Mutagenesis Test were measured at 4 monthly intervals and
correlated with the degree of hepatic iron overload, the presence of
iron-free preneoplastic foci in the liver, and the development of
hepatocellular carcinoma in comparison with 60 control rats.
RESULTS:
Levels of lipid hydroperoxides, malonaldehyde, 8-isoprostane and
8-hydroxy-2'-deoxyguanosine increased, reaching peak concentrations
at
20-24 months, and correlating with an increase in the rate of DNA
unwinding, strand breaks, and positive Ames Tests. Iron-free
neoplastic
foci became evident at 16 months and thereafter increased in number.
Preneoplastic foci were present in five of eight rats remaining at 32
months and HCC had developed in one of the five.
CONCLUSIONS:
Our findings are compatible with the hypothesis that the direct
hepatocarcinogenic effect of free iron is mediated by the generation
of
oxygen reactive species and oxidative damage that are mutagenic and
carcinogenic.


PMID: 16337327 [PubMed - as supplied by publisher]


---------------------------------------------------------------------------=
-----


Who loves ya.
Tom


Jesus Was A Vegetarian!
http://tinyurl.com/2r2nkh


Man Is A Herbivore!
http://tinyurl.com/a3cc3


DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk




> Bloodletting in hepatitis ..
> Whoda .. thunk.
>
> Dig Dis Sci. 2008 Mar;53(3):815-22. Epub 2007 Sep 12.
> Phlebotomy improves therapeutic response to interferon in patients
> with chronic hepatitis C: a meta-analysis of six prospective
> randomized controlled trials.
> Desai TK, Jamil LH, Balasubramaniam M, Koff R, Bonkovsky HL.
> William Beaumont Hospital, Royal Oak, MI, USA. tusarde...@aol.com
>
> Prospective randomized controlled trials (RCTs) comparing phlebotomy
> and interferon (IFN) treatment to IFN alone in
> patients with chronic hepatitis C (CHC) have suggested a
> benefit for the phlebotomy group.
> However, statistical significance was achieved in only one of these
> trials.
> We performed a meta-analysis of RCTs comparing phlebotomy and IFN to
> IFN alone for the treatment of CHC.
> The MEDLINE database and Cochrane registry of controlled trials were
> searched using the key words "phlebotomy" and "treatment of hepatitis
> C."
> Reference lists of review articles discussing the interaction between
> iron and CHC, and prospective RCTs comparing phlebotomy plus IFN
> therapy to IFN alone were searched to identify additional RCTs that
> compared phlebotomy
> plus IFN to IFN alone.
> Peto odds ratios with their 95% confidence intervals and Forrest plots
> were generated for each variable to assess the relationships among the
> studies that had provided that information.
> Statistical analysis was performed using Comprehensive
> META-Analysis version 2.0.
> Six prospective RCTs were identified: all used sustained viral
> response (SVR) as an endpoint.
> The three largest RCTs excluded patients with cirrhosis.
> Two RCTs specifically included only patients with either high ferritin
> or high hepatic iron content.
> IFN treatment regimes varied.
> Length of treatment varied between 6 and 12 months.
> The phlebotomy plus IFN group and the IFN group did not
> differ with respect to the percentage of patients with cirrhosis or
> genotype 1.
> SVR was attained in 50/182 (27%) patients in the phlebotomy plus IFN
> group, compared to 22/185 (12%) patients in the
> IFN group.
> Peto odds ratio for SVR in phlebotomy plus IFN group was
> 2.7; 95% CI 1.6-4.5, P < 0.0001.
> All five RCTs published in manuscript form showed a trend towards a
> benefit from the phlebotomy plus IFN in attaining SVR, and the results
> of the meta-analysis were not dependent on any single RCT, since
> excluding any single RCT did not change the
> results.
> Phlebotomy improves the SVR in response to IFN treatment in
> patients with CHC.
> Confirmation of this will require RCT with detailed pre-treatment iron
> studies and appropriately powered to demonstrate a
> statistically significant benefit.
>
> PMID: 17846887 [PubMed - in process]
>
> Who loves ya.
> Tom
>
> Jesus Was A Vegetarian!http://tinyurl.com/2r2nkh
>
> Man Is A Herbivore!http://tinyurl.com/a3cc3
>
> DEAD PEOPLE WALKINGhttp://tinyurl.com/zk9fk

On Apr 20, 5:14 am, "ironjust...@aol.com" <ironjust...@aol.com> wrote:
Bloodletting in hepatitis <<

Effects of Dietary Iron Reduction Versus Phlebotomy in Patients with
Chronic Hepatitis C: Results from a Randomized, Controlled
Trial on 40 Japanese Patients.
Intern Med. 2007;46(10):637-642. Epub 2007 May 24.
Sumida Y, Kanemasa K, Fukumoto K, Yoshida N, Sakai K.
Department of Gastroenterology and Hepatology, Nara City Hospital.

Background and Aim
Iron may play an important role in the pathogenesis
of hepatitis C.
We conducted this randomized, controlled trial
comparing phlebotomy with dietary iron reduction.
Methods
Forty patients with chronic hepatitis C showing serum
ferritin levels of over 150 ng/ml wererandomized to
either group A (low-iron diet for six months) or group B
(phlebotomy biweekly).
Phlebotomy was continued until serum ferritin had reached
20 ng/ml or less.
Results
At enrollment the clinical characteristics of patients
in the two groups were similar.
Serum ALT levels were significantly reduced
in both groups, but the percent change in alanine
aminotransferase (ALT) was larger in group B
(median, -47.1[range, -69.1 to -16.7] %) than in
group A (-24.2 [-72.6 to 15.9] %, p<0.001).
In group A subjects, no correlation wasdetected
between percent change in ALT and clinical
parameters.
In group B subjects, the baseline ALT activity was
significantly correlated with percent change in ALT (p<0.05),
but iron- related parameters were not correlated.
Conclusion
The efficacy of phlebotomy is superior to that of dietary iron
reduction in chronic hepatitis C.
Serum levels of transaminase activities were a better indicator
for phlebotomy thanconventional indices of iron overload.

PMID: 17527035 [PubMed - as supplied by publisher]


Who loves ya.
Tom


Jesus Was A Vegetarian!
http://tinyurl.com/2r2nkh


Man Is A Herbivore!
http://tinyurl.com/a3cc3


DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk





> On Apr 18, 10:36 am, "ironjust...@aol.com" <ironjust...@aol.com>
> wrote: Bloodletting in hepatitis <<
>
> <<snip>>
> direct hepatocarcinogenic effect of free iron is mediated by the
> generation of oxygen reactive species and oxidative damage that are
> mutagenic and carcinogenic
> <<snip>>
>
> 1: Toxicology. 2005 Dec 5; [Epub ahead of print] Links
>
> Hepatocellular carcinoma caused by iron overload: A possible
> mechanism
> of direct hepatocarcinogenicity.
>
> Asare GA, Mossanda KS, Kew MC, Paterson AC, Kahler-Venter CP, Siziba
> K.
>
> MRC/University Molecular Hepatology Research Unit, Department of
> Medicine, University of the Witwatersrand, 7 York Road, Parktown
> 2193,
> Johannesburg, South Africa.
>
> BACKGROUND/AIMS:
> Excess hepatic iron may be both directly and
> indirectly carcinogenic. The aim of this study was to determine if
> generation of reactive oxygen species and the resulting oxidative
> damage induced by free hepatic iron is directly hepatocarcinogenic.
> METHODS: Sixty male Wistar albino rats were iron-loaded by ferrocene
> supplementation of their diet. Biochemical parameters of oxidative
> damage and lipid peroxidation, DNA unwinding and strand breaks, and
> the
> Ames Mutagenesis Test were measured at 4 monthly intervals and
> correlated with the degree of hepatic iron overload, the presence of
> iron-free preneoplastic foci in the liver, and the development of
> hepatocellular carcinoma in comparison with 60 control rats.
> RESULTS:
> Levels of lipid hydroperoxides, malonaldehyde, 8-isoprostane and
> 8-hydroxy-2'-deoxyguanosine increased, reaching peak concentrations
> at
> 20-24 months, and correlating with an increase in the rate of DNA
> unwinding, strand breaks, and positive Ames Tests. Iron-free
> neoplastic
> foci became evident at 16 months and thereafter increased in number.
> Preneoplastic foci were present in five of eight rats remaining at 32
> months and HCC had developed in one of the five.
> CONCLUSIONS:
> Our findings are compatible with the hypothesis that the direct
> hepatocarcinogenic effect of free iron is mediated by the generation
> of
> oxygen reactive species and oxidative damage that are mutagenic and
> carcinogenic.
>
> PMID: 16337327 [PubMed - as supplied by publisher]
>
> --------------------------------------------------------------------------=
------
>
> Who loves ya.
> Tom
>
> Jesus Was A Vegetarian!http://tinyurl.com/2r2nkh
>
> Man Is A Herbivore!http://tinyurl.com/a3cc3
>
> DEAD PEOPLE WALKINGhttp://tinyurl.com/zk9fk
>
>
>
> > Bloodletting in hepatitis ..
> > Whoda .. thunk.
>
> > Dig Dis Sci. 2008 Mar;53(3):815-22. Epub 2007 Sep 12.
> > Phlebotomy improves therapeutic response to interferon in patients
> > with chronic hepatitis C: a meta-analysis of six prospective
> > randomized controlled trials.
> > Desai TK, Jamil LH, Balasubramaniam M, Koff R, Bonkovsky HL.
> > William Beaumont Hospital, Royal Oak, MI, USA. tusarde...@aol.com
>
> > Prospective randomized controlled trials (RCTs) comparing phlebotomy
> > and interferon (IFN) treatment to IFN alone in
> > patients with chronic hepatitis C (CHC) have suggested a
> > benefit for the phlebotomy group.
> > However, statistical significance was achieved in only one of these
> > trials.
> > We performed a meta-analysis of RCTs comparing phlebotomy and IFN to
> > IFN alone for the treatment of CHC.
> > The MEDLINE database and Cochrane registry of controlled trials were
> > searched using the key words "phlebotomy" and "treatment of hepatitis
> > C."
> > Reference lists of review articles discussing the interaction between
> > iron and CHC, and prospective RCTs comparing phlebotomy plus IFN
> > therapy to IFN alone were searched to identify additional RCTs that
> > compared phlebotomy
> > plus IFN to IFN alone.
> > Peto odds ratios with their 95% confidence intervals and Forrest plots
> > were generated for each variable to assess the relationships among the
> > studies that had provided that information.
> > Statistical analysis was performed using Comprehensive
> > META-Analysis version 2.0.
> > Six prospective RCTs were identified: all used sustained viral
> > response (SVR) as an endpoint.
> > The three largest RCTs excluded patients with cirrhosis.
> > Two RCTs specifically included only patients with either high ferritin
> > or high hepatic iron content.
> > IFN treatment regimes varied.
> > Length of treatment varied between 6 and 12 months.
> > The phlebotomy plus IFN group and the IFN group did not
> > differ with respect to the percentage of patients with cirrhosis or
> > genotype 1.
> > SVR was attained in 50/182 (27%) patients in the phlebotomy plus IFN
> > group, compared to 22/185 (12%) patients in the
> > IFN group.
> > Peto odds ratio for SVR in phlebotomy plus IFN group was
> > 2.7; 95% CI 1.6-4.5, P < 0.0001.
> > All five RCTs published in manuscript form showed a trend towards a
> > benefit from the phlebotomy plus IFN in attaining SVR, and the results
> > of the meta-analysis were not dependent on any single RCT, since
> > excluding any single RCT did not change the
> > results.
> > Phlebotomy improves the SVR in response to IFN treatment in
> > patients with CHC.
> > Confirmation of this will require RCT with detailed pre-treatment iron
> > studies and appropriately powered to demonstrate a
> > statistically significant benefit.
>
> > PMID: 17846887 [PubMed - in process]
>
> > Who loves ya.
> > Tom
>
> > Jesus Was A Vegetarian!http://tinyurl.com/2r2nkh
>
> > Man Is A Herbivore!http://tinyurl.com/a3cc3
>
> > DEAD PEOPLE WALKINGhttp://tinyurl.com/zk9fk- Hide quoted text -
>
> - Show quoted text -