effect of 1 month simvastatin 40mg

[stef2011]

since i am on a complex combo made of etv, gcmaf, ntz, heptech supplements, any effect on hbv, hbsag is from the combo and it cannot be determined if from sim, ntz or whatever

anyway we can say one thing for sure use of simvastatin 40mg for 1 month had no negative effects, normal alt etc, i will slowly increase to 80mg dose and see if any sides or positive effects

i am wating for hbsag quantification, hbvdna and hbvdna genes sequence, any of these tests is very useful to determine effect of the combo, especially hbvdna sequence which is able to detect extremely low hbvdna in serum (sensibility should be 1-5iu/ml).
if hbvdna resistance test is not able to detect any hbvdna, like the test i had dec 2010, we can say hbvdna suppressionin serum is very good

[stef2011]

this post is from 2011 we are in another universe today

simvastatin showed no effect as monotherapy as expected, a member, otan, used it in combo with pegintf and cleared hbsag in about 16 weeks only then kept pegintf a year to boost hbsab levels

[Seattledude]

Are you still on Sim and how is it working?

[stef2011]

by the way the back pain was gone the following day i decreased sim to 40mg, i am keeping this dose for now

i m definitely feeling very good since on sim, liver function is improved for sure and oxidative stress too

[stef2011]

no those are the most important

[nihi120]

Thanks for reply..I will test hbsag quantity & fibroscan then i get back to you.
Is any more test required?

[stef2011]

your doctor has missed the most important tests of all:

fibroscan
hbsag quantity in iu/ml, the one you did is not quantitative and the number has no meaning and no quantitative unit

check old posts where to have fibroscan and hbsag quantity by abbott architect in iu/ml in india

[nihi120]

I am male and my age is 29yrs. Last week I come across that HBV virus in my blood. I Consulate with Dr. Mahesh K Goenka in Kolkata, India. Then I went for some test , test result are
LFT-
Serum Total Protein(Biuret)        7.5g/dl                         (6.4-8.3 g/dl)
Serum Albumin (B C Purple)       4.4g/dl                       (3.5-5.1 g/dl)
Serum Globulin                          3.1g/dl                       (1.8-3.6g/dl)
Ratio                                        1.4:1:0                          (1.0-2.0:1.0)
Serum Total Bilirubin(jendrassik Grof)  0.6mg/dl           (upto 1.0mg/dl)
Serum Direct Bilirubin(Diazo Method)  0.1mg/dl           (0- 0.2mg/dl)
Serum SGOT/AST(UV Kinetic)        57U/L                        (10-42U/L)
Serum SGPT/ALT(UV Kinetic)        58U/L                       (10-40U/L)
Serum GGT(SZASZ)                          12U/L                      (07-64U/L)
Serum Alkaline Phosphatase(PNP-AMP) 99U/L              (53-128UL)


Hepatitis B Surface Antigen            Reactive
Value                                                          1211                 (0.0-1.0)


HBV DNA Viral Load
Waiting for test result

USG U/A
Ultrasound Report shows liver and kidney is normal.


P Time(Prothrombin Time)
Test         15.6secs
Control    14.4secs
INR( International Normalised Ratio)  1.09

Serum Triiodothyronine(T3)        1.1ng/ml              For Adult(0.8-2.0)
Serum Throxine(T4)        12.8ug/dl                        For Adult(5.1-14.1)
Thyriod Stimulating Hormone(TSH)        2.3ulU/mL   For Adult(0.27-4.2)

I  still don’t know how it comes in my blood.
Can  I cure?
Should I take HBV vaccination now?
What type of foods(Diet) I take or not?
How I monitor it, so that it is not increase further?
Where I have to go for best treatment?
Should I need more test?
How much time after I have go again 4 tests?

Please help me.

[stef2011]

today i got a very bad back pain, difficult to say exactly is there is correlation with sim 80mg because i have no muscles pains but just a very bad pain in the back.all bood tests are normal

since fibroguard has reservatrol which henances simvastatin potency i will lower to 40mg for a couple of days and see what happens to the back pain and then i will re-think if go to the 80mg, 60mg or 40mg dose

[stef2011]

it is all in vitro data so impossible to say we have to try on ourselves

i think artesunate is very potent, cfs patients are using it and they have many viral infections and they also suggested the use of sim to lower viral titers, so i d use a combo of the two.
always think these compounds in combo because i dont think they have the potential to clear hbv but only weaken the virus, so a combo of interferon or nucs plus sim, artesunate, vit d3, chloroquine etc have the potential to improve results

[deamer]

stef2011
thanks for your reply.
another question:
which do you think is more potential, artesunate and simvastatin?

[stef2011]

i just posted all the links just read them all

[deamer]

My hbeag is negative since I knew I was  infected with hbv

"artesunate is much more potent than chloroquine on hbv "
Are there some proof or articles about it ?

[stef2011]

simvastatin is reported to make a shift from th1 immune responses to th2 immune responses

in hbv infection:
th1=cellular immunity= interferon gamma, interleukin 2, LT ?, macrophages activation
Cell-mediated immunity is an immune response that does not involve antibodies but rather involves the activation of macrophages, natural killer cells (NK), antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen.

th2= interleukin 4 and 5
The Humoral Immune Response (HIR) is the aspect of immunity that is mediated by secreted antibodies (as opposed to cell-mediated immunity, which involves T lymphocytes) produced in the cells of the B lymphocyte lineage (B cell). B Cells (with co-stimulation) transform into plasma cells which secrete antibodies.

both th1 and th2 are needed but maybe we luck some more humoral immunity on cronic hbv?

http://www.bio.davidson.edu/people/sosarafova/Assets/Bio307/chbrough/page04.html

[stef2011]

http://www.atherosclerosis-journal.com/article/S0021-9150(06)00360-1/abstract

Pierre Cherfan, Andrea Tompa, Anders Wikby, Sture Löfgren, Lena Jonasson
Received 15 February 2006; received in revised form 7 June 2006; accepted 14 June 2006. published online 25 July 2006.

Abstract Full Text PDF Images References
Abstract
Objective
The use of statins has shown several anti-inflammatory actions, including modulatory effects on T cells in vitro. Since the effects on human T cells in vivo are less clarified, our aim was to investigate the effects of simvastatin on human T cells in vivo and ex vivo.

Methods and results
A randomized, double-blind, placebo-controlled study design was applied. Eighty volunteers with mild to moderate hypercholesterolemia received either simvastatin 40mg or placebo for 6 weeks. The serum levels of C-reactive protein (CRP) were significantly reduced by simvastatin. The proportions of CD4+ and CD8+ T cell subsets expressing early (CD25) or late (HLA-DR) activation markers, as assessed by flow cytometry, were not changed by simvastatin. However, simvastatin tended to increase the density of HLA-DR and L-selectin per CD8+ T cell. The T helper(h)1/Th2 response was evaluated by stimulatory assays followed by intra-cellular staining of interferon-γ and interleukin-4. Simvastatin treatment did not affect the Th1 response but the results indicated a potential to suppress Th2.

Conclusion
Simvastatin treatment resulted in a few discrete changes as regards peripheral T cells. However, the findings do not provide evidence that simvastatin-induced anti-inflammatory actions are related to any significant modulatory effects on human T cells in clinically healthy men with hypercholesterolemia.

[stef2011]

http://www.univie.ac.at/asem/Graz_MC_09/papers/73198.pdf

Cholesterol depletion and replenishment of hepatitis B virions
reversibly alter their ultrastructure and infectivity
M. Raunest1, C.M. Bremer2, N. Kott2, C. Bung2, W.H. Gerlich2, D. Glebe 2, F. Cemic3,
and M. Hardt4
1. Dep. KMUB, Univ. of Appl. Science Giessen-Friedberg, D-35390 Giessen, Germany
2. Institute of Medical Virology, JLU Giessen, D-35392 Giessen, Germany
3. . Institute for Biochemical Engineering and Analytics, Univ. of Appl. Science Giessen-
Friedberg, D-35390 Giessen, Germany
4. Central Biotechnology Unit, JLU Giessen, D-35392 Giessen, Germany
Martin.***@****-giessen.de
Keywords: infectiology, virus, negative stain, 3d modeling
Hepatitis B virus (HBV) infection of primary hepatocyte cultures is dependent on the
presence of viral cholesterol. Extraction of cholesterol from highly purified HBV from
plasma of HBV-infected patients with methyl-beta-cyclodextrin (MβCD) leads to a strongly
reduced level of infection but addition of exogenous cholesterol restores infectivity of HBV
[1]. We analyzed ultrastructural changes of HBV that parallel these effects in untreated HBV
(group 1), cholesterol-depleted HBV (group 2) and cholesterol-depleted HBV after
cholesterol-replenishment (group 3).
Conventional negative stain preparations were inspected in an EM912 AB (ZEISS)
TEM at 120 kV under zero loss conditions. Images were recorded using a slow scan-ccd
camera (Proscan) and the SIS software package (Olympus) at a magnification of 50.000 x
(pixel size = 0.27 nm).
In all three groups the proportion of disrupted particles was below 5%. Particles were
isomorphic regardless of previous treatment indicating that neither the MβCD-treatment nor
the cholesterol-replenishment destroyed the integrity of the virions. HBV from group 1
appeared as mainly negatively stained spherical particles with a diameter of 48.4 ± 4.2 nm.
The nucleocapsid of these virions displayed only a relatively weak positive contrast. MβCDtreated
viral particles from group 2 (which lost their infectivity) had a clearly smaller
diameter of 38.7 ± 4.9 nm and and showed an overall positive contrast. Viral particles
replenished with cholesterol (group 3) with regained infectivity appeared as negatively
stained again and nearly but not fully reached wild-type diameters ranging at 46.5 ± 4.0 nm
(compare Fig. 1).
In order to study the viral morphology in more detail 3d models from virions of all
three groups were calculated and inspected using EMAN and CHIMERA. The resolution
(FSC) of these models was rather poor (~ 35 Å), due to the limited resolution of negative
staining and to the relatively low number of particles included in the modeling (n~40 to 50
particles per model). The models reflect the size differences between the virions of the three
groups revealed by the statistical analysis of the single images. Within the capsid of all three
models it was possible to detect twofold, threefold and fivefold symmetry axes corresponding
to an icosahedral symmetry (T=4 organisation). The innermost structures however show
features pointing towards an octahedral packing of the internal DNA. The envelope of the
infectious HBV (group 1and group 3) appears to be closed with no clear symmetry whereas
in the cholesterol-depleted HBV (group 2) it appears as a very porous meshwork of structures
(compare Fig. 2).

[stef2011]

a Institut de Génétique Humaine, IGH-CNRS, 141, rue de la Cardonille, 34396 Montpellier Cedex 5, France
b Department of Medical Research and Education, Veterans General Hospital, Shih-Pai, Taipei, Taiwan
c Department of Life Science, National Yang-Ming University, Taipei, Taiwan
Received 18 October 2002; revised 28 April 2003; Accepted 6 May 2003. Available online 17 July 2003.

Abstract
Hepatitis B virus-infected patients secrete enormous quantities (50–300 μg/ml) of hepatitis B surface antigen (HBsAg) in their serum. One hypothesis for this synthetic effort is that these lipoprotein particles serve to adsorb neutralizing antisurface antibodies. We have shown that insulin suppresses the expression of HBsAg in human hepatoma cell Hep3B cells. We further studied the signaling pathway of insulin on the inhibition of HBsAg. Using a fungal metabolite, lovastatin, to block the p21Ras signaling pathway of insulin, we found that lovastatin inhibited the secretion of HBsAg into culture medium in Hep3B cells; however, the involvement of p21Ras-MAPKs was excluded in this effect. The cholesterol depletion from the membrane, leading to the destabilization of rafts, was the mechanism for the lovastatin inhibition of HBsAg secretion. However, lovastatin has no effect on the secretion of infectious viral Dane particles. Herein, we show for the first time that cholesterol is required for HBsAg secretion.

[stef2011]

Cell Microbiol. 2009 Feb;11(2):249-60. Epub 2008 Nov 5.
Hepatitis B virus infection is dependent on cholesterol in the viral envelope.
Bremer CM, Bung C, Kott N, Hardt M, Glebe D.
Source
Institute of Medical Virology, Justus Liebig University, Frankfurter Str. 107, 35392, Giessen, Germany.
Abstract
The viral and cellular determinants leading to binding and entry of hepatitis B virus (HBV) are still not fully understood. We found that HBV infection of primary hepatocyte cultures is dependent on the presence of cholesterol in the viral envelope. Extraction of cholesterol from HBV purified from plasma of HBV-infected patients with methyl-beta-cyclodextrin (MbetaCD) leads to a strongly reduced level of infection. The cholesterol-depleted virions showed higher buoyant density (1.23 versus 1.17 g ml(-1)), a smaller diameter (39 versus 48 nm), but maintained particle integrity, antigenicity and ability to bind to hepatocytes. Although addition of exogenous cholesterol and cholesterol analogues restored the physical appearance of cholesterol-depleted virions, infectivity was only regained by cholesterol add-back. Infectivity of HBV produced from cell culture in the presence of inhibitors of cholesterol-synthesis is severely impaired. Interestingly, cholesterol extraction from cellular membranes, incubation with filipin and the protein tyrosine kinase inhibitor genistein showed no effect on HBV infection, excluding a role of lipid rafts for the infection process of HBV. In summary, presence of cholesterol within the viral envelope is not important for viral binding, but indispensable for the entry process of HBV and might be important for a later step in viral uptake, e.g. fusion in a yet unknown compartment.

[stef2011]

J Virol. 2011 Oct 12. [Epub ahead of print]
Cholesterol depletion of hepatoma cells impairs Hepatitis B virus envelopment by altering the topology of the large envelope protein.
Dorobantu C, Macovei A, Lazar C, Dwek RA, Zitzmann N, Branza-Nichita N.
Source
Institute of Biochemistry of the Romanian Academy, Department of Viral Glycoproteins, Splaiul Independentei 296, Sector 6, Bucharest 77700, Romania.
Abstract
Previous reports have shown that cholesterol depletion of the membrane envelope of the Hepatitis B virus (HBV) impairs viral infection of target cells. A potential function of this lipid in later steps of the viral life cycle remained controversial, secretion of virions and subviral particles (SVP) being either inhibited or not affected, depending of the experimental approach employed to decrease the intracellular cholesterol level. This work addressed the role of host cell cholesterol on HBV replication, assembly and secretion, using an alternative method to inhibition of the enzymes involved in the biosynthesis pathway. Growing HBV-producing cells with lipoprotein depleted serum (LPDS) resulted in an important reduction of the amount of cholesterol within 24 h of treatment (about 40%). Cell exposure to chlorpromazine, an inhibitor of the clathrin-mediated pathway used by the LDL receptor for endocytosis, also impacted on cholesterol level; however, this level of inhibition was not achievable when the synthesis inhibitor, lovastatin, was used. HBV secretion was significantly inhibited in cholesterol depleted cells (by ∼80 %), while SVPs release remained unaffected. Viral DNA genome accumulated in LPDS-treated cells, in a time-dependent manner. Specific immunoprecipitation of nucleocapsids and mature virions revealed an increased amount of "naked" nucleocapsids, while synthesis of the envelope proteins occurred as normally. Following analysis of the large envelope protein conformation in purified microsomes, we concluded that cholesterol is important in maintaining the dual topology of this polypeptide, which is critical for viral envelopment.

[stef2011]

my hbvdna:2990 copys/ml

it is a good low value, also hbsag might be low, are you hbeag negative?

,quantity of hbsag is not available in my city,

without this i think we cannot determine if sim and artesunate work, hbvdna is not enough
why dont you ship to india to get it tested?we posted a lab in india willing to test for hbsag and they are not expensive at all.fedex ships biological samples like blood samples

sim has been show to lower hbvdna in vitro, red yeast rice lovastatin hbsag in vitro
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2869246/

http://www.ncbi.nlm.nih.gov/pubmed/14517078

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2951407/

artesunate/artemisin (this is active as a broad spectrum antiviral on many viruses)
http://www.ncbi.nlm.nih.gov/pubmed/16122816

chloroquine
http://www.ijpsonline.com/article.asp?issn=0250-474X;year=2006;volume=68;issue=4;spage=538;epage=540;aulast=Chandramohan

http://jem.rupress.org/content/202/6/817.abstract

there was another article from iran research on the inhibition of cell entry by hbv and hcv by chloroquine.chloroquine blocks a vescicle used by viruses to enter cells.i can find it, if i do i will post this too

[deamer]

thanks,stef2011
maybe I try artesunate or simvastatin.
I will Just think it over,but my hbvdna:2990 copys/ml,  Liver function: almost normal,quantity of hbsag is not available in my city,  can artesunate or simvastatin work effectively?

[stef2011]

if you try them please let us know what the results are on hbsag quant iu/ml and hbvdna iu/ml, this is very imprtant because we have no data on this although it is impossible that no people had malaria and hbv at the same time and took both drugs and it is also impossible taht no people is taking hbv drugs+statins.
sharing this data is very important whatever the pos or neg results

[stef2011]

Chloroquine?

it does work too, a doctor wrote me that her mother cleared hbv after malaria treatment many times ago and all malaria treatments are active on hbv especially a combo of artesunate and choloroquine.
artesunate is much more potent than chloroquine on hbv

ketoconazole pills have also strong effects on hbsag,they damage the lipid coating for fungal infections and might do the same on hbv.i dont remember percantage on inhibition, i think it was something like 80% or more

please monitor liver and kidneys function close if you do these combos, i do think they can work but needs to be done on combos and with hbvdna undetactable

inactive carriers with hbvdna undetactable and hbsag less than 1000iu/ml would be perfect for this

[stef2011]

we know simvastatin lowers the whole virions, hbvdna, but they didn t study effect on hbsag only
lovastatin from red yeast rice has been shown to reduce hbsag, but not the synthetic type of lovastatin

i think simvastatin has an effect for sure but not potent enough monotherpy, anyway nobody made the trials yet so one has to try.
iyou better start with low dose 4 weeks like 40mg and check ast/alt cpk and then go for the 80mg dose
i think only 80mg dose can work and i am sure it does because fda is trying to block the use of sim at 80mg.this makes no sense because they never made studies on generic, their action can have only 2 explanations:
1 they are afraid for the use of sim as antiviral because it s produced in india and not in US anymore and it is extremely cheap, few dollars

2 they want people to take the new US patented statins

anyway we will find out soon

[deamer]

I want to know if simvastatin can reduce hbsag.
In addition, what is your opinion about Chloroquine?
some articles about it
the link:
http://jem.rupress.org/content/202/6/817.abstract
http://www.ncbi.nlm.nih.gov/pubmed/3752892
http://www.sciencedirect.com/science/article/pii/S0168827887803902
http://www.sciencedirect.com/science/article/pii/0042682291901577