Risk Of Developing Liver Cancer After HCV Treatment

Saturday, October 2, 2010

Milk Thistle/The Study 2010




Effects of Milk Thistle Extract on the Hepatitis C Virus Lifecycle
A laboratory study suggests that silymarin—an extract from the milk thistle plant—has multiple effects against the lifecycle of the hepatitis C virus. Hepatitis C is a chronic (long lasting) disease that primarily affects the liver and is often difficult to cure. The laboratory study examined the antiviral properties and mechanisms of silymarin on cultured (grown in a lab) human liver cells infected with the virus.

The study, funded in part by NCCAM, was published in the journal Hepatology.
.The researchers grew human liver cells and infected them in vitro with the hepatitis C virus. The cells were then exposed to either standard hepatitis C drug treatment or to a diluted dose of silymarin. By analyzing the interactions between silymarin and the virus, the researchers observed that silymarin prevented the entry and fusion of the hepatitis C virus into the target liver cells.
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They also found that silymarin inhibited the ability of the virus to produce RNA (a chemical that plays an important role in protein synthesis and other chemical activities of the cell), interfering with a portion of the virus's lifecycle. When measured against untreated cells, silymarin also significantly decreased viral load (the amount of virus in the cells), although to a lesser degree than treatment with interferon did. The researchers also found that silymarin prevented the cell-to-cell spread of the virus.

These findings build on previous research of silymarin's antiviral and anti-inflammatory properties and provide more information about the potential mechanisms involved in silymarin's antiviral actions. Further research, particularly in clinical trials, is needed to determine if silymarin could be a safe and effective supplement for treating hepatitis C in humans.
ReferenceWagoner J, Negash A, Kane OJ, et al.
Hepatology. 2010;51(6):1912–1921.
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The Study
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Hepatology. 2010 Jun;51(6):1912-21.
Multiple effects of silymarin on the hepatitis C virus lifecycle.
Wagoner J, Negash A, Kane OJ, Martinez LE, Nahmias Y, Bourne N, Owen DM, Grove J, Brimacombe C, McKeating JA, Pécheur EI, Graf TN, Oberlies NH, Lohmann V, Cao F, Tavis JE, Polyak SJ.
Department of Laboratory Medicine, University of Washington, Seattle, WA 98104-2499, USA.
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Abstract
Silymarin, an extract from milk thistle (Silybum marianum), and its purified flavonolignans have been recently shown to inhibit hepatitis C virus (HCV) infection, both in vitro and in vivo. In the current study, we further characterized silymarin's antiviral actions.
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Silymarin had antiviral effects against hepatitis C virus cell culture (HCVcc) infection that included inhibition of virus entry, RNA and protein expression, and infectious virus production.
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Silymarin did not block HCVcc binding to cells but inhibited the entry of several viral pseudoparticles (pp), and fusion of HCVpp with liposomes. Silymarin but not silibinin inhibited genotype 2a NS5B RNA-dependent RNA polymerase (RdRp) activity at concentrations 5 to 10 times higher than required for anti-HCVcc effects.
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Furthermore, silymarin had inefficient activity on the genotype 1b BK and four 1b RDRPs derived from HCV-infected patients.
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Moreover, silymarin did not inhibit HCV replication in five independent genotype 1a, 1b, and 2a replicon cell lines that did not produce infectious virus.
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Silymarin inhibited microsomal triglyceride transfer protein activity, apolipoprotein B secretion, and infectious virion production into culture supernatants. Silymarin also blocked cell-to-cell spread of virus.
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CONCLUSION:
Although inhibition of in vitro NS5B polymerase activity is demonstrable, the mechanisms of silymarin's antiviral action appear to include blocking of virus entry and transmission, possibly by targeting the host cell. Publication Types
PMID: 20512985 [PubMed - indexed for MEDLINE]
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Cases in CAM: Milk Thistle for the Liver -- Any Evidence?Désirée Lie, MD, MSEd
Posted: 03/02/2010

A Warning about Milk Thistle and Drug Interactions
lThe seeds of the milk thistle plant are commonly used to protect the liver from
damage caused by hepatitis viruses as well as alcohol and other substances. Compounds found in milk thistle - sylibin, sylimarin - act as antioxidants and also stimulate the repair of the liver. But now it appears that these and possibly other compounds in milk thistle can have other effects.Researchers at the University of Pittsburgh have suspected that milk thistle can slow down or reduce the activity of enzymes in the liver.
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What does this have to do with HIV? you might ask.
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Well, enzymes in the liver break down many of the substances that we eat and drink, including medications. If the activity of these enzymes are reduced, then drugs remain in the blood longer than they otherwise might. This could lead to having higher-than-expected levels of drugs in the body, causing side effects or intensifying already-existing side effects. Indeed, in recent experiments using milk thistle and human liver cells, the researchers found that relatively small concentrations of milk thistle did significantly slow down the activity of the liver enzyme CYP3A4 by 50% to 100%.

lMany medications taken by people with HIV/AIDS (PHAs) - such as protease inhibitors and non-nukes - are processed by this liver enzyme. If milk thistle is taken by someone using protease inhibitors or non-nukes, it has the potential to raise levels of these drugs, causing unpleasant or even dangerous side effects.
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Below is a short list of some other medications that are processed through the CYP3A4 enzyme. Levels of these medications may increase if taken by people who are also using milk thistle.
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This list is not exhaustive:
lmethadoneheart drugs - Tambocor (flecainide), Rythmol (propafenone)antibiotics - erythromycin, rifampinanti-seizure drugs - carbamazepine (Tegretol)antidepressants - St. John's wort, Zyban/Wellbutrin (bupropion), Paxil (paroxetine), Prozac (fluoxetine), Luvox (fluvoxetine) Serzone (nefazodone), Zoloft (sertraline), Effexor (venlafaxine)antihistamines - Hismanal (astemizole), Seldane (terfenadine)antifungals - itraconazole (Sporanox), Ketoconazole (Nizoral)gastrointestinal motility agents - Prepulsid (Cisapride)ergot drugs - Ergonovine, Ergomar (ergotamine)anti-psychotics - Clozaril (clozapine), Orap (pimozide)sedatives/sleeping pills - Ambien (zolpidem), Halcion (triazolam), Versed (midazolam)lipid-lowering drugs (statins) - Lescol (fluvastatin), Mevacor (lovastatin), Pravachol (pravastatin) and Zocor (simvastatin), Baycol (cerivastatin)transplant drugs - cyclosporine (Neoral, Sandimmune), ProGraf (tacrolimus)Milk thistle also has the potential to lower levels of the following drugs:anti-parasite drugs - Mepron (atovaquone)sedatives/sleeping pills -

Ativan (lorazepam)hormones - estrogen
lThe research by the scientists in Pittsburgh should emphasize to readers that simply because a product is "natural" it does not mean it is safe when taken with other substances. This research also shows the need to conduct further research on herb-drug interactions on liver cells as well as in people. Such studies may find combinations of herbs and drugs that can be safely used together.

The Pittsburgh researchers noted that "patients and health care professionals must be encouraged to discuss the use of herbs and be educated about the potential interactions between herbs and drugs." This cannot be stressed enough.

REFERENCE Venkataramanan R, Ramachandran V, Komoroski BJ, et al. Milk thistle, a herbal supplement, decreases the activity of CYP3A4 and uridine diphosphoglucuronosyl transferase in human hepatocyte cultures. Drug Metabolism and Disposition 2000;28(11):1270-1273.This information was provided by the Community AIDS Treatment Information Exchange

(CATIE). For more information, contact CATIE at 1-800-263-1638.For more information chekc out our Herbal Glossary , and also check out our CAM information

Other Studies
Other studies have produced some interesting findings, including a small 2009 study led by Columbia University scientists that found that milk thistle reduced liver toxicity in children undergoing chemotherapy

(Complementary and Alternative Medicine) on our FactSheet page

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