What about Vitamin D and HCV ?

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Good Afternoon Readers,

It appears that the subject of Vitamin D has been a topic of interest lately among the medical community researching HCV. In the middle of 2010 it was found that supplementing pegylated interferon and Ribavirin with a daily dose of vitamin D might increase virologic response rates according to a study presented at the 45th Annual Meeting of the European Association for the Study of the Liver (EASL 2010) back in May.

They found that a low vitamin D level was associated with a poor treatment response and more severe liver fibrosis. Earlier data found that vitamin D may also improve insulin sensitivity and possibly inhibit the virus from replicating. This data from researchers confirms the fact that not only living with chronic Hepatitis C and liver disease is accompanied by a vitamin D deficiency it also shows that by supplementing vitamin D during HCV therapy can improve response rates.
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Below Abstracts Will Be Presented At This Years Liver Meeting:
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The Liver Meeting®61st Annual Meeting of the American Association for the Study of Liver Diseases
October 29 – November 2, 2010
Boston, MA Hynes Convention CenterASSLD Meeting
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Low Vitamin D Serum Level Is Related to Rapid, Early and Sustained Virological Response to IFN-based Therapy in Genotype 1 Chronic Hepatitis
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C S. Petta1; D. Ferraro2; C. Scazzone3; D. Cabibi4; C. Cammà1; V. Di Marco1; R. Di Stefano2; A. Mazzola1; A. Bono3; A. Craxì1 1. Cattedra ed U.O.C. di Gastroenterologia ed Epatologia, Palermo, Italy. 2. Cattedra di Virologia, Dipartimento di Scienze per la Promozione della Salute 'G. D'Alessandro', University of Palermo, Palermo, Italy. 3. Dipartimento di Biotecnologie Mediche e Medicina Legale Sezione di Chimica e Biochimica Medica,Università degli Studi di Palermo, Palermo, Italy. 4. Cattedra di Anatomia Patologica, University of Palermo, Palermo, Italy.
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Background/Aims:
Different large scale studies showed that genotype 1 chronic hepatitis C (G1CHC) patients achieving a rapid virological response(RVR) during PEG-IFN plus ribavirin therapy, had very higher chances for a sustained virological response(SVR). High viral load, severity of fibrosis and insulin resistance (IR) represent the known factor affecting RVR achievement.
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A recent study showed that lower 25-hydroxyvitamin D (25(OH)D) serum levels are independently associated with a lower likelihood to achieve sustained virological response after PEG-IFN plus ribavirin therapy in this setting of patients.
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We aimed to assess if 25(OH)D serum levels are independently associated with RVR in G1CHC patients.
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Methods:
155 consecutive patients with Genotype 1 CHC were evaluated by liver biopsy and anthropometric and metabolic measurements, including IR by HOMA. 25(OH)D serum levels were measured by HPLC. All biopsies were scored by one pathologist for staging and grading (Scheuer), and graded for steatosis.
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All patients underwent antiviral therapy with PEG-IFN plus ribavirin. HCVRNA was detected at baseline, week 4, week 12, at the end of therapy, and after six months of follow-up.
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Results:
Seventy-eight patients were males, 49(31.6%) had fibrosis F3-F4, 64(41.3%) had steatosis≥10%, and mean 25(OH)D serum levels were 17.8±10.0mcg/L (range 8.2-58.0). Overall RVR was achieved in 44 patients(28.3%), EVR in 98(63.2%), and SVR in 81(52.2%). Forty out of 44 patients(90.9%) with RVR had a SVR, compared to 34/111(30.6%) without RVR. By contrast, seventy-two out of 98 patients(73.4%) with EVR achieved SVR, compared only 2/57(3.5%) without EVR. By multivariate analysis, hepatic steatosis (OR0.961;95%CI 0.926-0.998;p=0.03), lower cholesterol (OR1.014;95% CI 1.003-1.024;p=0.01) and lower 25(OH)D levels (OR1.047;95%CI 1.007-1.089;p=0.02), were independently associated with no RVR.
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Similarly lack of both EVR and SVR were independently linked to lower cholesterol (OR1.010;95% CI 1.001-1.020;p=0.04) and lower 25(OH)D levels (OR1.036;95%CI 1.001-1.075;p=0.04), and to lower cholesterol (OR1.016;95% CI 1.004-1.027;p=0.006), lower 25(OH)D levels (OR1.042;95%CI 1.003-1.082;p=0.03), and hepatic steatosis (OR0.962;95%CI 0.932-0.992;p=0.001), respectively.
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Thirty-eight percent(28/73) of patients with vitamin D levels more then 24.5(AUC 0.634;Sens. 63%;Spec. 61%) had RVR, compared to 19.5%(16/82) of those with vitamin D levels less then 24.5.
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Higher vitamin D levels more then 24.5 had SVR, compared to 42.6%(35/82) of those with vitamin D levels less then 24.5
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Conclusions:
In G1CHC patients 25(OH)D serum levels are directly associated with the likelihood to achieve RVR, EVR and SVR.

Vitamin D Metabolites Inhibit Replication of the Hepatitis C Virus
J. A. Gutierrez1; K. A. Jones1; R. L. Fitzgerald2; J. Allina3; A. D. Branch3; D. L. Trump4; R. T. Schooley1; D. L. Wyles1 1. Medicine, University of California, San Diego, La Jolla, CA, United States. 2. Pathology, University of California, San Diego, La Jolla, CA, United States. 3. Medicine, Mount Sinai School of Medicine, NY, NY, United States. 4. Roswell Park Cancer Institute, Buffalo, NY, United States.
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Introduction:
Vitamin D is a potent activator of the innate immune system and modulator of the cell cycle, while persistence of hepatitis C (HCV) infection may be due to derangement of these same systems. Furthermore, preliminary data suggest that vitamin D supplementation to a serum level of 32 ng/mL is associated with an improvement in virologic response to pegylated interferon plus ribavirin therapy. In this study, we tested the ability of vitamin D and its metabolites to inhibit the replication of HCV replicons and infectious HCV in cell culture.
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Methods:
Cell lines stably expressing luciferase reporter BM4-5 (gt 1b replicon), SGR-JFH-1 (gt 2a replicon), or J6/JFH (infectious gt 2a) were generated. Supernatants from cells replicating J6/JFH were used to infect naïve cells at an MOI of 0.01 (HCVcc). HCV expressing cells were incubated in the presence of D2, D3 or 1,25(OH)2 D3 at concentrations from 0.5 µM to 25 µM for 120 hours. HCV expression was measured by relative light unit reporter assays after 120 hours and analyzed for EC50s using GraphPad Prism 4.03. HPLC was performed on supernatant to determine 25(OH) D3 after 24 hours of exposure to vitamin D3. Expression of vitamin D receptor (VDR) and core protein was examined by immunoblot in lysate from cells infected with J6/JFH.Results: In the genotype 1b replicon, the EC50 of vitamin D2, D3 and 1,25(OH)2 D3 were 14 µM, 3.8 µM and 1.1 µM, respectively.
The EC50s in genotype 2a replicon cells were similar (13 µM, 8.4 µM and 4.7 µM). The EC50 in HCVcc for vitamin D3 was 2.1 µM. The mean CC50 at 120 hours of D2, D3 and 1,25(OH)2 D3 was 42 µM, 55 µM, and 23 µM.
Conversion of 1 µM, 5 µM and 25 µM vitamin D3 to 25(OH) D3 was found to be 2 ng/mL, 24 ng/mL, and 191 ng/mL. In J6/JFH infected cells, we found that D3 and 1,25(OH)2 D3 increased protein expression of the VDR receptor after 24 hours of exposure, but was similar to controls at 72 and 120 hours. Conversely, HCV core production in treated cells was similar to controls at 24 hours, and then decreased at 72 and 120 hours.
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Conclusions:
This study shows the ability of vitamin D to inhibit HCV replication in model systems. Conversion of vitamin D3 to 25(OH) D3 was about 1% at 24 hours, and the EC50s of vitamin D3 generally had 25(OH) D3 levels that are comparable to those found in serum (25-50ng/mL).
Intriguingly, vitamin D3 increased VDR protein expression and inhibited HCV expression. This suggests that Huh-7.5.1cells generate metabolites of vitamin D3 that activate the VDR leading to anti-HCV effects. Our future studies will be aimed at understanding the mechanism of how vitamin D affects hepatocytes and HCV.
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Note :(see below Is There A Test To Check For Vitamin D Deficiency ?)
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Optimal 25-hydroxy-vitamin D values are: 45-50 ng/ml or 115-128 nmol/l
Normal 25-hydroxy-vitamin D lab values are: 20-56 ng/ml 50-140 nmol/l
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Living With HCV
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Liver Disease and Vitamin D Deficieny
With research connecting vitamin D deficiency with chronic HCV it is tempting to assume that taking vitamin D supplements is the answer. However even if this analogy can be beneficial there are warnings and concerns about vitamin D toxicity that should be discussed with your physician.
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The Liver And Vitamin D ,
The products of digestion are absorbed by the intestine and processed by the liver to produce Vitamin D. The vitamin is also obtained from exposure to ultraviolet rays of sunlight. Because the liver plays a vital role in the metabolism and successful functioning of vitamin D it's not surprising to discover that several diseases which affect the liver also affect vitamin D metabolism. Diseases such as liver cirrhosis caused by hepatitis B or C, alcoholic cirrhosis and primary biliary cirrhosis have all been shown to decrease hydroxylated vitamin D in the blood.
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How Much Vitamin D ?
The recommended daily allowance is 200 IU per day until the age of 50, and 400 IU daily for ages 50 to 70, and 600 IU for people over 70. Toxicity reports are associated with dosages above these levels. However, too much vitamin D is especially toxic and dangerous for anyone with liver disease.

The Dangers Of Vitamin D Toxicity From Supplements
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Vitamin D toxicity, also called hypervitaminosis D, is a potentially serious but treatable medical condition that occurs when you get too much vitamin D.
Vitamin D toxicity usually results from taking an excessive amount of vitamin D supplements — not from your diet or too much sun exposure. That's because your body produces only a limited amount of vitamin D from sun exposure, and even fortified foods don't contain large amounts of vitamin D.
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Although vitamin D toxicity is rare even among people who take supplements, you may be at greater risk if you have health problems, such as liver or kidney conditions, or if you take thiazide-type diuretics.
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The main consequence of vitamin D toxicity is a buildup of calcium in your blood
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(hypercalcemia), causing symptoms such as:
Nausea
Vomiting
Poor appetite
Constipation
Weakness
Confusion
Heart rhythm abnormalities
Kidney stones
Treatment of vitamin D toxicity may include:
Stopping vitamin D supplements
Restricting calcium intake
Medications
Hydration with fluids
Hospitalization in severe cases

What Is A natural Way to Get Vitamin D ?
The are some misconceptions about “vitamin” D , most people do not realize that " vitamin" D is actually a hormone. Like other hormones, your body can manufacture D, but again only with a little help from the sun.
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As mentioned above a good source of vitamin D is from sunlight, if we only take the safe amount of sun nature intended. However for people on HCV therapy there are important warnings; Photosensitivity is a side effect of pegylated interferon, and also with the newer drug "Telaprevir" which showed in clinical studies to have a mild to moderate rash or photosensitivity reactions.

If you are not on HCV therapy the suggested time in the sun to reek the benefits of vitamin D in the "fair skinned" population is approximately 20 minutes. At this point the skin is saturated and cannot produce more vitamin D. According to Reinhold Vieth, a University of Toronto researcher who studies vitamin D ; this amount in the sun, 10 minutes laying on your back, and ten minutes laying on your front can equate to the amount of vitamin D found in 100 glasses of milk. For the darker skinned population the skin color makes it harder to make vitamin D, and more time is needed the sun. As we age, natural degenerative changes that occur in skin make it harder for UV-B rays to convert cholesterol to vitamin D. Elderly people typically need to rely more on food sources than sunlight for their vitamin D needs.

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What is the safest Way To Get Vitamin D From The Sun ?
The best way to accomplish this is by spreading out the time you spend in the sun.

How much sun is enough ?
This comes from an article written by Edward L. Schneider, M.D.;
Weekly sun exposure should be without sunscreen, with face and arms exposed.
Keep in mind that the sun isn’t strong enough to trigger vitamin D production during the winter at high latitudes.
Under 65: 3-5 minutes, 2-3 times a week.
65 and above: 5-15 minutes, 2-3 times a week.

The take home message is that you can't overdose on the vitamin D from the sun, however you can get too much vitamin D from supplements .
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Food A Natural Source Of Vitamin D

Aside from the body's natural production of vitamin D, food sources provide another important supply of this essential nutrient.

One cup of vitamin D fortified milk supplies about one-fourth of the estimated daily need for this vitamin for adults. Although milk is fortified with vitamin D, dairy products made from milk such as cheese, yogurt, and ice cream are generally not fortified with vitamin D. Only a few foods naturally contain significant amounts of vitamin D, including fatty fish and fish oils. (see the chart below)

When taking supplements for vitamin D there can be a risk for toxicity, but food is a safe source of vitamin D, toxicity from food intake is extremely unlikely. Less than one-third of all persons in the U.S. meet the Dietary Reference Intake level for vitamin D, and are far from consuming anything close to potentially toxic levels. h

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A Note For People With Cirrhosis

Low-protein diets were recommended routinely in the past for patients with cirrhosis. High levels of aromatic amino acids contained in animal proteins were believed to lead to increased blood levels of the false neurotransmitters tyramine and octopamine, with resulting worsening of encephalopathy symptoms. In this author's experience, the vast majority of patients can tolerate a protein-rich diet (more then 1.2 g/kg/d) including well-cooked chicken, fish, vegetable protein, and, if needed, protein supplements.
Protein restriction is rarely necessary in patients with chronic encephalopathy symptoms. Many patients with cirrhosis have protein-calorie malnutrition at baseline. The routine restriction of dietary protein intake increases their risk for worsening malnutrition.
In the author's opinion, protein restriction is infrequently valuable in patients with an acute flare of hepatic encephalopathy symptoms. One study randomized hospitalized patients with hepatic encephalopathy to receive either a normal-protein diet or a low-protein diet, in addition to standard treatment measures. There was no difference in hepatic encephalopathy outcome in the two treatment groups
Full Article

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Is There A Test To Check For Vitamin D Deficiency ?,

It is imperative to have a simple blood test that a General Practitioner can request, to check your current levels of vitamin D before considering any supplementation. This is because over supplementing with vitamin D could have serious consequences, such as bone resorption (breaking down of the calcium) and soft tissue calcification (hardening). It is very important to know this before considering taking any cod liver oil or other vitamin D supplements. It is very wise to have your vitamin D levels checked 3-4 months after initial supplementation to see if a deficiency is still present.

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The name of the test is the 25-hydroxy-vitamin D test

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Also known as: Vitamin D2; Vitamin D3; Calcidiol (25-hydroxy-vitamin D); Calcifidiol (25-hydroxy-vitamin D); Calcitriol (1,25 dihydroxy-vitamin D)
Formal name: 25-hydroxy-vitamin D; 1,25 dihydroxy-vitamin D; 25-hydroxycholecalciferol
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Related tests: Calcium; Phosphorus; Parathyroid hormone (PTH); Magnesium

The 25-hydroxy-vitamin D test will give a more complete picture of your values. The values stated as normal are actually not optimal, according to Vitamin D researchers. The low value of the normal is too low and the high value of the normal is just a little too high.

Optimal 25-hydroxy-vitamin D values are: 45-50 ng/ml or 115-128 nmol/l

Normal 25-hydroxy-vitamin D lab values are: 20-56 ng/ml 50-140 nmol/l

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Links To More Information:

Please remember that these articles are not written with liver disease at the forefront, always consult your physician for information before you begin any vitamin regimen.

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Great Article From The Huffington Post

By Dr. Frank Lipman

Vitamin D Health: Why You Shouldn't Shun the Sun

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kA Special Note For Support:

The success of this blog is because of the; digest of information gathered and made accessible in one place. This same success was also established in a prior website called "Janis and Friends Hepatitis C Website", that website created by myself is evolving into a new site called Hepatitis C New Drug Research and is currently being developed.

However looking for one on one support can be found at a great source in the way of a chat room and message boards under the name of "Janis and Friends Hepatitis C Support".

This site can be found here, and is ran by caring devoted people living with Hepatitis C, I suggest you visit these boards and begin to connect with other people deciding on treatment and finding their way through the medical maze of treating this disease. The site continues on with the support Janis Morrow; "who sadly passed away from HCV in July 23, 2001" began back in April of 2000 by offering support to the newly diagnosed. I personally have made many friends through this site, and would love to name each person by name, but if I forget one name , I'd feel horrible, please know that all those members and staff remain in my heart. I have an attachment to this site that will stay with me forever .
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More Information On Their Chat Room and Message Boards.
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Sources
HIV and Hepatitis

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