Treatment and Vitamin D
Relationship between vitamin D and IL-23, IL-17 and macrophage chemoattractant
protein-1 as markers of fibrosis in hepatitis C virus Egyptians
The liver plays a central role in vitamin D metabolism.
Vitamin D inadequacy is common in non-cholestatic chronic liver diseases and
correlates with disease severity. The current study showed a significant
reduction of vitamin D and its active metabolites in HCV genotype
4-infected patients compared to healthy controls. This reduction was more
prevalent and severe in cirrhotic vs non-cirrhotic patients.
This is consistent with previous studies done on patients with genotype 1,
which showed that vitamin D deficiency is universal (92%) among patients
with chronic liver disease, and at least one-third of the patients have severe
vitamin D deficiency
Full Text available at WJH World Journal Of Hepatology
Vitamin D for Your Patients with Chronic Hepatitis C?
Reference: JHEPAT 4348
To appear in: Journal of Hepatology
Vitamin D is increasingly becoming recognized as an important physiological
regulator with pleiotropic functions outside of its classical role in skeletal homeostasis.
A growing body of clinical evidence highlights the prevalence and risks of vitamin D deficiency
in patients suffering from chronic hepatitis C infection, and vitamin D supplementation has
been proposed as an adjunct to current standards of care. This review considers
the experimental evidence for the anti-inflammatory, anti-fibrotic and
anti-viral effects of vitamin D, and discusses the therapeutic potential of
vitamin D supplementation to protect against liver disease progression and
improve responses to treatment.
Advances in hepatitis C virus (HCV) pharmaceutical development are being made at a
blistering pace; however, highly effective, non-toxic therapies remain a hope
for the future. This leaves an immediate need for interventions that can
minimize disease progression and/or improve sustained virological response (SVR)
rates in the short term.
The aging of the HCV-positive population is creating an epidemic of end stage liver disease.
Many patients cannot wait for second and third generation direct acting antiviral drugs to
reach the clinic.
As an interim measure, vitamin D supplements have been proposed as an adjunct to
pegylated-interferon and ribavirin. This review integrates the known biological
effects of the vitamin D system with recent clinical findings and discusses the
therapeutic potential of vitamin D supplementation in HCV-positive patients.
Download PDF here..........
PloS ONE- Vitamin D Metabolism in the Response to Interferon-Alfa-Based Therapy of Chronic Hepatitis C
Serum Vitamin D Levels Are Not Predictive of the Progression of Chronic Liver Disease in Hepatitis C Patients with Advanced Fibrosis
Front Biosci (Elite Ed). 2012 Jan 1;4:1276-86.
Diagnostic and therapeutical role of vitamin D in chronic hepatitis C virus infection.
Cacopardo B, Camma C, Petta S, Pinzone MR, Cappellani A, Zanghi A, Nicolosi A, Nunnari G.
Source University of Catania, Department of Medicine and Medical Specialties, Division of Infectious Diseases, Via Palermo 636, Catania, Italy.
Although initially identified as a calcium homeostatic hormone, vitamin D is now known to have pleiotropic functions, dealing with both innate and adaptative immunity. Calcitriol mediates its biological effects by binding to the vitamin D receptor (VDR), which is expressed not only by intestine, bone and kidney but also on cell membranes of T lymphocytes, B lymphocytes, dendritic cells and macrophages.
Vitamin D plays a role on the degree of liver damage in patients with chronic hepatitis C (CHC): low vitamin D levels have been associated with high hepatic necroinflammatory activity and progression of liver fibrosis. Vitamin D, in CHC patients, could also affect the response to antiviral therapy: in fact, recent studies have shown a relationship between low responsiveness to IFN-based therapy and low vitamin D serum levels.
Further studies are required to better assess if vitamin D could work as a reliable noninvasive marker of liver fibrosis and whether vitamin D supplementation could be given to all CHC patients together with standard antiviral treatment, in order to improve the rate of sustained virological response (SVR).
PMID: 22201953 [PubMed - in process]
Source HCV Advocate
Article: Vitamin D: An Innate Antiviral Agent Suppressing Hepatitis C Virus in Human Hepatocyte –
Gal-Tanamy M, Bachmetov L, Ravid A, Koren R, Erman A, Tur-Kaspa1R, Zemel R. Source: Hepatology; Volume 54, Issue 5, pages 1570–1579, November 2011.
This study (see abstract below) looked at the connection between vitamin D3 supplementation and improved response rates to treatment for chronic hepatitis C virus (HCV) infection. The research showed the various pathways that vitamin D3 uses, showing the antiviral properties of vitamin D3 particularly during interferon treatment. Researchers noted that vitamin D3 combined with interferon alfa has a synergistic relationship (the drug interactions are magnified, in this case in a beneficial way). Also noted was that vitamin D3 combined with interferon alfa decreases viral production more than interferon alfa without vitamin D3.
The Bottom Line:
Vitamin D3 may have a significant impact on HCV and treatment for it.
To find current guidelines on dosing and other pertinent information, visit www.mayoclinic.com/health/vitamin-d/NS_patient-vitamind
Hepatology. 2011 Nov;54(5):1570-9. doi: 10.1002/hep.24575.
Vitamin D: an innate antiviral agent suppressing hepatitis C virus in human hepatocytes.
Gal-Tanamy M, Bachmetov L, Ravid A, Koren R, Erman A, Tur-Kaspa R, Zemel R.
Source Molecular Hepatology Research Laboratory, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Vitamin D supplementation was reported to improve the probability of achieving a sustained virological response when combined with antiviral treatment against hepatitis C virus (HCV).
Our aim was to determine the in vitro potential of vitamin D to inhibit HCV infectious virus production and explore the mechanism(s) of inhibition. Here we show that vitamin D(3) remarkably inhibits HCV production in Huh7.5 hepatoma cells. These cells express CYP27B1, the gene encoding for the enzyme responsible for the synthesis of the vitamin D hormonally active metabolite, calcitriol. Treatment with vitamin D(3) resulted in calcitriol production and induction of calcitriol target gene CYP24A1, indicating that these cells contain the full machinery for vitamin D metabolism and activity. Notably, treatment with calcitriol resulted in HCV inhibition. Collectively, these findings suggest that vitamin D(3) has an antiviral activity which is mediated by its active metabolite. This antiviral activity involves the induction of the interferon signaling pathway, resulting in expression of interferon-β and the interferon-stimulated gene, MxA. Intriguingly, HCV infection increased calcitriol production by inhibiting CYP24A1 induction, the enzyme responsible for the first step in calcitriol catabolism. Importantly, the combination of vitamin D(3) or calcitriol and interferon-α synergistically inhibited viral production.
CONCLUSION: This study demonstrates for the first time a direct antiviral effect of vitamin D in an in vitro infectious virus production system. It proposes an interplay between the hepatic vitamin D endocrine system and HCV, suggesting that vitamin D has a role as a natural antiviral mediator. Importantly, our study implies that vitamin D might have an interferon-sparing effect, thus improving antiviral treatment of HCV-infected patients.
Copyright © 2011 American Association for the Study of Liver Diseases.
J Hepatol. 2011 May;54(5):887-93. Epub 2011 Jan 20.
Vitamin D deficiency and a CYP27B1-1260 promoter polymorphism are associated with chronic hepatitis C and poor response to interferon-alfa based therapy.
Lange CM, Bojunga J, Ramos-Lopez E, von Wagner M, Hassler A, Vermehren J, Herrmann E, Badenhoop K, Zeuzem S, Sarrazin C. Source Klinikum der J.W. Goethe-Universität Frankfurt am Main, Medizinische Klinik 1, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
AIMS: Vitamin D is an important immune modulator and preliminary data indicated an association between vitamin D deficiency and sustained virologic response (SVR) rates in hepatitis C virus (HCV) genotype 1 patients. We, therefore, performed a comprehensive analysis on the impact of vitamin D serum levels and of genetic polymorphisms with functional relevance within the vitamin D cascade on chronic hepatitis C and its treatment.
METHODS: Vitamin D serum levels, genetic polymorphisms within the vitamin D receptor and 1α-hydroxylase were determined in a cohort of 468 HCV genotype 1, 2, and 3 infected patients who were treated with interferon-alfa based regimens.
RESULTS: Chronic hepatitis C was associated with a high incidence of severe vitamin D deficiency compared to controls (25(OH)D(3)<10 ng/ml in 25% versus 12%, p<0.00001). 25(OH)D(3) deficiency correlated with SVR in HCV genotype 2 and 3 patients (50% and 81% SVR for patients with and without severe vitamin D deficiency, respectively, p<0.0001). In addition, the CYP27B1-1260 promoter polymorphism rs10877012 had substantial impact on 1,25-dihydroxyvitamin D serum levels (72, 61, and 60 pmol/ml for rs10877012 AA, AC, and CC, respectively, p=0.04) and on SVR rates in HCV genotype 1, 2, and 3 infected patients (77% and 65% versus 42% for rs10877012 AA, AC, and CC, respectively, p=0.02).
CONCLUSIONS: Chronic hepatitis C virus infection is associated with vitamin D deficiency. Reduced 25-hydroxyvitamin D levels and CYP27B1-1260 promoter polymorphism leading to reduced 1,25-dihydroxyvitamin D levels are associated with failure to achieve SVR in HCV genotype 1, 2, and 3 infected patients.
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. k
A Study That Will Be Presented At This Years Liver Meeting: k
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 k
From The AASLD k
Low Vitamin D Serum Level Is Related to Rapid, Early and Sustained Virological Response to IFN-based Therapy in Genotype 1 Chronic Hepatitis k
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.
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. k 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. k We aimed to assess if 25(OH)D serum levels are independently associated with RVR in G1CHC patients. k
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. j 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. j
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. k 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. l 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. n 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 j
In G1CHC patients 25(OH)D serum levels are directly associated with the likelihood to achieve RVR, EVR and SVR. . Note :(see below Is There A Test To Check For Vitamin D Deficiency ?) .
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 k mk
Living With HCV m
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. , 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.
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
From The Mayo Clinic ;
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. ; 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. ; The main consequence of vitamin D toxicity is a buildup of calcium in your blood l (hypercalcemia), causing symptoms such as:
Heart rhythm abnormalities
Treatment of vitamin D toxicity may include:
Stopping vitamin D supplements
Restricting calcium intake
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.
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. b
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
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
Click Chart To Enlarge
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
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.k
The name of the test is the 25-hydroxy-vitamin D testk
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
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
kFor More Information On Testing
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.
Great Article From The Huffington Post
By Dr. Frank Lipman
Vitamin D Health: Why You Shouldn't Shun the Sun