Warnings

These warnings are taken from postings in the hepc.bull, and they have been compiled by Joan King. 

CORTICOSTEROIDS

Liver transplant recipients have a problem: They must take corticosteroids to prevent rejection, but at the same time, it was believed that corticosteroids increase the replication of the hepatitis C virus. The researchers involved with this study confirmed those beliefs, both in humans (liver transplant recipients) and in vitro (test tube). The patients were treated with corticosteroids during a rejection episode, and their virus levels were measured, and temporarily increased.Source: Magy N, et al, Int J Immunopharmacol 1999 Apr;21(4):253-61, Effects of corticosteroids on HCV infection PMID: 10408633, UI: 99335118

LIVER CANCER WITHOUT FIBROSIS

In this issue of Hepatology, two groups of doctors from different French institutions discuss the occurrence of liver cancer (HCC) in people with little or no fibrosis, basing their opinions on their own observations and those reported in a previous article by Bralet, et al. They discuss the importance of studying livers with little, as well as no, fibrosis, and the fact that some HCC seems to be caused by viruses, while others by alcohol abuse or iron deposits. Some have no known cause. A problem exists in determining whether damage found in a biopsy has been resolved or if it just starting. The first group reports that 8 to 12 of their patients are treated for HCC each year that don't have cirrhosis, and suggest that studies should be done world wide, because there may be other factors involved. Although at odds about what kind of scarring should be included in these studies, both groups agreed that there are, in fact, many cases of liver cancer with little fibrosis, occurring equally in men and women, young and old, at least a third of cases in patients with viral hepatitis, and both groups hope that studies will continue. These findings seem to indicate that we should get ultrasounds done often, even if we don't have cirrhosis.Source: Hepatology, December 2000, p. 1411-1411, Vol. 32, No. 6

 

INJECTING VACCINES

Many of hepatitis C patients have had problems responding to their hepatitis A and B vaccines. A recent article in the British Medical Journal talks about the necessity of using different size needles for different patients, and the importance of injecting into the muscle rather than into the layer of fat, which can cause vaccine failure and decay of antibody response. The authors say that the buttocks are not a good vaccination site. Subcutaneous injections can cause abscesses and granulomas. The doctor should stretch the skin flat. If the skin is pinched, a longer needle should be used. The size of the needle should depend on the patient's age, size of the muscle, and amount of vaccine to be given. In a recent study, the thickness of this fat pad was measured by ultrasound in 220 adults. A standard 16 mm needle was not long enough for 17% of men and almost 50% of the women in the study. For men weighing 59-118 kg, and women of 60-90 kg, it may be better to use a 25 mm needle. Women usually have more fat over their arm (deltoid) muscles. For women over 90 kg, a 38 mm needle should be used. A wider gauge needle is more effective.Source: BMJ 2000;321:1237-1238 ( 18 November )Editorial by Jane N Zuckerman http://bmj.com/cgi/content/full/321/7271/1237

 

TAKING RIBAVIRIN? PROTECT AGAINST SUN

A recent case shows that people with hepatitis C taking ribavirin may have to take caution with exposure to sunlight. A 65-year-old woman on her 16th week of combo therapy developed an itchy, eczema-like skin rash in body parts exposed to UV rays (sunlight). When the ribavirin was stopped, the skin lesions and itching disappeared completely, and no changes in skin color remained. People on combo therapy should be aware of their sun exposure.Source: Am J Gastroenterol 1999 Jun;94(6):1686-8,Stryjek-Kaminska D, et al, Photoallergic skin reaction to ribavirin. PMID: 10364046, UI: 99290714

 

SHOU-WU-PIAN

A case of acute hepatitis caused by the Chinese herb Shou-Wu-Pian, or Polygonum multiflorum, was reported in Australia. A lady was taking the preparation to get rid of her grey hair. A liver biopsy showed a toxic reaction. The problem resolved when the lady stopped taking the herb.Source: J of Gast and Hepat 16 (1) 115-117, Acute hepatitis induced by Shou-Wu-Pian, a herbal product derived from Polygonum multiflorum, Gordon J-H Park, et al

 

HEINZ BEANS and SOME SOUPS RECALLED

Beware of Heinz Beans in Tomato Sauce with UPC 057000007034 on the product's bright green label and an eight digit code on one end of the can, starting with 2420. There is a risk of botulism, although no one has been reported getting sick yet. Several kinds of soups made by Les Produits Freddy Inc. have also been recalled because they were underprocessed. The soups have been distributed nationally. If you have any of these products, check back with us for the UPC codes. They can be returned to the store for a full refund.Source: Web Posted Thu Nov 23 2000

 

METRONIDAZOLE

These authors reported a case metronidazole accumulation in the brain of a Hep C patient with cirrhosis. The 34 year old man was being treated for meningitis and bacteremia. This was the second case of of metronidazole-induced MRI changes in a patient with liver dysfunction.Source: Horlen CK, et al, Ann Pharmacother 2000 Nov;34(11):1273-5 Toxic metronidazole-induced MRI changes

 

ST JOHN'S WORT AFTER TX

Many drugs can interact with cyclosporin, which is given to patients after transplant to prevent rejection episodes. A 63 year old liver recipient developed sudden severe rejection 14 months after transplantation, due to a drop in cyclosporin levels. He had begun taking St John's wort 2 weeks earlier. His levels dropped to normal when he stopped taking the herb (Hypericum perforatum--2 x 900 mg/day).Source: Karliova M, et al, J Hepatol 2000 Nov;33(5):853-5, Interaction of Hypericum perforatum (St. John's wort) with cyclosporin A metabolism in a patient after liver transplantation.

 

BIOPSIES FOR ALL HEP C PATIENTS

This author, citing a study done on 35 Hep C + patients with elevated ALTs, compared to 35 Hep C+ patients with normal ALT levels, recommends liver biopsy for all Hep C patients. Although there was generally more damage in patients with elevated ALTs, 20% of the patients with normal ALTs had liver damage. When prescribing medication for patients with Hep C, doctors should consider the state of the liver in their pretreatment evaluations.Source: JP Callen , Journal Watch Dermatology 24 October 2000 Normal Liver Enzymes Do Not Exclude Important Abnormalities on Liver Biopsy in Patients with Hepatitis C

 

PREGNANCY MAY MAKE HEPC WORSE

The authors of this study found evidence that Hep C worsened after pregnancy when they compared liver biopsy results from Hep C 12 patients before and after delivery to the biopsy results of 12 non-pregant Hep C women patients. The biopsy results showed increase in inflamantion 83.3% of the women who gave birth, compared to 25% of the women who did not. Fibrosis scores were 41.6% and 8.3% in those same groups.Source: Fontaine, H et al, Lancet 2000;356:9238 Effect of pregnancy on chronic hepatitis C: a case-control study

 

LAMOTRIGINE

Lamotrigine, a drug to control epilepsy, seems to provoke serious liver damage in some patients, according to this article, which is rare, but can be deadly. One 28 year old woman developed signs of liver damage after only 2 weeks of using the medication. Her symptoms included headaches, drowsiness, low body temperature, and a rash. Her liver enzymes skyrocketed, only to return to normal six days after coming off the Lamotrigine. Two previous cases were reported. In all cases the patients were also taking valproic acid.Patients' enzyme levels should be monitored when this medication is introduced.Source: Dig Dis Sci 2000;45:1874-1877, Case Report Adds to Evidence of Possible Hepatotoxic Side Effects With Lamotrigine

 

NOT JUST NEEDLES

Australian researchers reported that in spite of the number of infections from HIV among IVDUs going down, the same is not the case with HCV, and they mentioned that HCV has probably been around longer than HIV, and that it is more easily transmitted than is HIV. The authors examined used injecting equipment for HCV among IV drug users known to be infected with HCV, and found HCV on 70% of syringes, 67% of swabs, 40% of filters, 25% of spoons, and 33% of water samples. These findings show that HCV can be transmitted through the sharing of equipment other than needles and syringes, so the message about not sharing needles may not be sufficient. They suggest that IVDUs be encouraged to use non-injectable drugs, wash their hands more, and not share any equipment used while injecting.Source: BMJ 2000;321:899, Oct 7 2000, Crofts, N, et al. Minimising harm from hepatitis C virus needs better strategies

 

THREAT FROM THE OCEAN

Hep C sufferers have an enemy in the ocean. V. vulnificus is a bacteria commonly found in the Gulf of Mexico and other warm waters, where it can infect oysters and other shellfish, and does not occur because of pollution, so the normal precaution of avoiding contaminated waters may not be enough. Eating raw or undercooked shellfish, yes, even from the ocean, can be a serious danger, and can even cause death, especially in people with liver disease. Think twice what you eat the next time you go to a sushi bar. And not only that, but V. vulnificus can infect open wounds when a person goes swimming in infected waters.Source: Superintendent of Documents, U.S. Government Printing Office (GPO), Washington, DC 20402-9371; telephone: (202) 512-1800

 

SAMe WARNING FOR MANIC-DEPRESSIVES

SAMe has been used in Europe for many disorders, such as depression, osteoarthritis, and liver disorders. Its mood-enhancing effects have been demonstrated in clinical trials. There are no known confirmed drug interactions with SAMe, but it can cause mild gastrointestinal problems. Otherwise it seems to be generally well tolerated, but agitation and manic reactions have been reported to appear soon after taking SAMe, so patients with a history of mania or bipolar disorders should avoid it. A company conducting independent analyses of supplements recently found serious differences between the amount claimed on the label and the actual amount of SAMe contained in several brand products, and almost half of the products tested did not contain thecorrect amounts. Also, SAMe may cost more than most prescription antidepressants. Efficacy, safety, long-term tolerability and relapse rates should be evaluated through large controlled trials and by formal evaluation.Source: West J Med, 2000;173:229-230, Linda Shu1 and Nancy P Lee, SAMe targets consumers via the Web

 

CAESARIANS SAFER

In a recent study of 441 HCV positive mothers and their babies in the UK and Ireland, researchers attempted to discover how many babies were infected and exactly when their babies were infected. Results showed 50% of uninfected babies were HCV-antibody negative y 8 months, and 95% by 13 months. Delivery by C-section before membrane rupture occurred resulted in less HCV transmission than vaginal or emergency C-sections. The researchers believe that HCV transmission from mother to child occurs usually around the time of delivery, and that all mothers-to-be should be tested for HCV.Source: D M Gibb, et al, Lancet 2000; 356: 904 - 907 Mother-to-child transmission of hepatitis C virus: evidence for preventable peripartum transmission

 

SELENIUM

A letter from some Danish scientists appearing in Lancet this month reviewed a collection of studies which show that "although selenium is an important trace element, it is also toxic, with a narrow therapeutic window, and some individuals are more sensitive than others." Selenium toxicity has been studied in animals for several decades, and can include liver and nervous system damage, as well as stunting of growth. The authors warn against too much selenium, especially in children, and suggest it may be cancer causing, calling for more testing. At the same time, other writers stressed the importance of selenium for the heart and immune system, especially in areas where there is not enough naturally-occurring selenium in the soil.Source: Hans Ãrskov, Allan Flyvbjerg, Lancet 2000; 356: 938 - 946 Selenium and human health

 

BEWARE OF THYMUS PRODUCTS

Although there is no evidence of any herbal product being contaminated, experts are considering the possibility that herbal supplements, such as thymus products which some Hep C patients take, may contain "raw animal parts". Theoretically, the risk of transmitting "mad cow" disease could exist. Dr. Scott A. Norton, in an interview with Reuters Health, stated, "I would advise all of my patients not to take supplements that contain central nervous system tissue from animals." The article warned readers that not all supplements list their full ingredients, or some people may not realize that the word "hypothalamus" means brain tissue, and "orchis" means bull testicles. It says that regulatory institutions have little or no power over dietary and herbal supplements.SOURCE: REUTERS HEALTH, JUL 26, 2000. "'HERBAL' SUPPLEMENTS CAN CONTAIN ANIMAL PARTS" BY AMY NORTON

 

ALENDRONATE

Alendronate is for treating people with osteoporosis. A 71-year-old woman with a possible history of primary biliary cirrhosis and normal liver function, was treated with Alendronate. Two months later, routine blood work showed high liver enzymes, which returned to normal slowly after stopping the Alendronate. The patient was negative for hepatitis A, B, C and other viruses. Biopsy showed liver damage, but no primary biliary cirrhosis. Another case of hepatitis as a result of alendronate treatment was recently reported in a 77-year-old woman. Physicians treating patients with a bisphosphonate should check for liver damage therapy.Source: NEJM 2000,343: 5, Halabe, Aaron M.D., et al., "Liver Damage Due to Alendronate:

 

SPORTS TRANSMISSION?

Researchers in France seem to have documented the first transmission of HCV to occur during a fight. This discovery should put those involved in high-impact sports, such as boxing, football, and rugby, on guard. A man tested positive for HCV, but had no usual risk factors. He then reported a fight with his nephew that took place 2 months earlier, in which both men bled, and then shared a handkerchief to clean up their blood. Upon performing PCRs on both men, the results showed they had "nearly identical strains of the virus." There had been no of razors or toothbrushes, and the men did not live together. The authors of the article suggest that single-use or disposable material be used to clean up blood during sports or fights.Source: Reuters Health Aug 09, 2000 Hepatitis C transmitted during bloody fight

 

CHINESE WEIGHT LOSS PILLS

Chinese herbal weight-loss pills containing Aristolochia fangchi has been found to cause cancer of the urinary tract.N Engl J Med 2000;342:1686-92 Urothelial Carcinoma Associated with the Use of a Chinese Herb (Aristolochia fangchi)Joelle L. Nortier, et al.

 

TROVAFLOXACIN

According to the article cited above, the US FDA has found that trovafloxacin, an antibiotic, has been associated with more than 100 cases of liver toxicity, with 14 of the patients experiencing liver failure, and 4 requiring a transplant. Five of the patients died. There have been other reports of liver toxicity with quinolones.The New England Journal of Medicine -- February 3, 2000 -- Vol. 342, No. 5 Acute Eosinophilic Hepatitis from Trovafloxacin. Henry J.L. Chen, M.D., et al, Massachusetts General Hospital

 

ALCOHOL

It is well known that chronic alcohol use impairs a person's defense mechanisms and immunity, and that nonalcoholic cirrhosis can make a person susceptible to infection, but it was not known if the infections were due to alcohol or the results of alcohol, such as cirrhosis and malnutrition. Since both alcohol abuse and cirrhosis can make people susceptible to infection, the authors assume that people who both abuse alcohol and have cirrhosis will be even more susceptible to infection. In the above cited edition of the Journal, Rosa et al., after studying 383 patients with cirrhosis, reported a more frequent bacterial infection in patients with alcoholic cirrhosis than in those with nonalcoholic cirrhosis. The group with alcoholic cirrhosis had more severe and more frequent infections (61%) than the nonalcoholic cirrhotics (39%). The data from the study clearly show that alcohol is a risk factor for infection in well compensated cirrhotics. The author of the review suggests that the cause may be leaky gut syndrome, and that patients should avoid things like NSAIDS and abstain from alcohol.From: American Journal of Gastroenterology, Editorial, May 2000, Volume 95, Number 5, Pages 1124-1125. Alcohol: "Ice-Breaker" Yes, "Gut Barrier-Breaker," Maybe

 

CHECK YOUR INGREDIENTS!

Beware! The US FDA is concerned about botanical products containing aristolochic acid. Some of these botanicals include: Aristolochia spp., Asarum spp., Bragantia spp., Stephania spp., Clematis spp., Akebia spp., Cocculus spp., Diploclisia spp., Menispernum spp., Sinomenium spp., Mu tong, Fang ji, Guang fang ji, Fang chi, Kan-Mokutsu (Japanese), and Mokutsu (Japanese). Practitioners who prescribe botanical remedies are urged to throw away any products with the above listed ingredients.. Cases of nephropathy and end-stage kidney disease associated with their use have been reported. Because of the Chinese tradition of interchanging similarly named herbs, there is a great tendency for many harmless herbs to be accidentally substituted with Aristolochia spp., not only in traditional medicines but also in dietary supplements.SOURCE: HTTP://VM.CFSAN.FDA.GOV/~DMS/DS-BOTL2.HTML LETTER TO HEALTH CARE PROFESSIONALS ON FDA CONCERNED ABOUT BOTANICAL PRODUCTS, INCLUDING DIETARY SUPPLEMENTS, CONTAINING ARISTOLOCHIC ACID

 

CHOMPERS

``Chompers,'' a dietary supplement made by Arise and Shine of Mount Shasta, is thought to be a natural colonic cleanser. Federal investigators later determined that the plantain in the herbal remedy had been contaminated with digitalis, which can be a lethal poison. FDA investigators found an untold number of people had been affected by the supplement, with resulting lawsuits. Public health officials complain that there is next to no regulation of dietary supplements, and that consumers can't be certain about the ingredients, or if they are contaminated, or even spiked with restricted drugs or even if there are any active ingredients. Australia, Japan and Taiwan, for example, set strict quality standards and manufacturing procedures.Source: Friday June 2 2000, San Francisco Chronical, Herb Remedies: Panacea or Problem? Health officials look to improve safety, labeling in $14 billion industry. Kenneth Howe, Chronicle Staff Writer

 

COLD REMEDY: Loxoprofen sodium

An ingredient used in some prescriptions to fight the common cold may cause serious liver problems, Japan's Health and Welfare Ministry warned hospitals and physicians after two patients died. Eight patients who have taken loxoprofen since 1997 have had serious liver damage. Some NSAIDS also include loxoprofen sodium.Source: Information about an anti-inflammatory analgesic drug used for the management of pain and inflammation associated with muscle skeletal and joint disorder or operative procedures, from Labkorea. Japan Issues Health Alert on Common Cold Remedies. May 29 (Reuters)

 

RISKS OF VITAMIN OVERDOSE

A US government advisory panel has warned consumers against taking large doses of antioxidants such as vitamins C and E. The panel warned that high levels of vitamin C can cause diarrhea, too much vitamin E can increase the risk of stroke, and excessive selenium can cause hair loss and brittle nails. At high levels, vitamin E acts as an anti-clotting agent.Source: US panel warns on excessive antioxidant intake, by Tim Dobbyn (1999 Reuters Limited)

 

SAM-E: THE WONDER SUPPLEMENT? By Robert Bazell NBC NEWS CORRESPONDENT

Feb. 7 - Some say SAM-e, the latest fad in dietary supplements, can treat an amazing variety of health problems - a claim that has led to its use by more than 140,000 people, mostly women, nationwide. But others argue that the evidence for its effectiveness is lacking. "This drug is supposed to cure depression, sexual dysfunction, liver disease, diabetes, nerve trouble and arthritis," said Dr. Robert Packman, a psychiatrist and neuroscientist at the University of Washington in St. Louis. Debbie Hutcherson says SAM-e changed her life. She used to take prescription medicines to treat severe depression until a friend turned her on to SAM-e. "I truthfully have to say it saved my life . I'm a totally different person today than I was a year ago," she said. But the manufacturers are careful about what they claim, saying the supplement promotes joint health and emotional well being. SAM-e is actually a laboratory-produced version of a chemical found naturally in the body - part of the process for burning energy. It's expensive, costing $75 to $200 a month depending on the dose. But Packman has extensively reviewed the studies to date and says they don't prove much. "What I think is actually happening in the case of SAM-e is that we' re really seeing a placebo response. I just find it hard to believe that that compound is doing all of these things," he said. Indeed, experts say placebo - or imagined - responses to alternative remedies are common for depression and other ailments. Apart from whether SAM-e works, there are also questions on whether people who buy it may not be getting what they think - in fact, some of these capsules may contain no SAM-e at all. The laboratory for Good Housekeeping magazine analyzed samples of eight brands. Five contained more SAM-e than the label said, two had less and one had none. "We were not able to detect SAM-e. Now, the label claim on the product is 100 milligrams per tablet," said Dr. Gerald Buonopane of the Good Housekeeping Institute. Bazell: "But there's nothing in the tablet according to your tests?" Buonopane: "That's - that's correct." Of the three companies criticized in the Good Housekeeping test: Food Science of Vermont says, "There was a discrepancy on the original label" and it has been "changed." Aspen Group will not comment until it completes its own testing. And Nature's Vision says, "Our own SAM-e has been discontinued pending our lab analysis." These types of questions about scientific proof and proper labelling are common complaints these days in the $14 billion a year dietary supplement industry.

 

ST. JOHN'S WORT WARNING

The Natural Pharmacist.com advises that, although safe while taken by itself, St. John's wort may be dangerous when taken with other medications, and may even be lethal, according to articles in the February 12, 2000 issue of Lancet. Studies began in 1998, and further causes for worry were found last spring at the Annual Congress for Clinical Pharmacology in Berlin, where it was announced that St. John's wort interferes with the heart drug digoxin and the blood-thinning drug warfarin (Coumadin). Since even slight changes in the activity of these two medicines may cause serious problems, possible interactions with St. John's wort may possibly be dangerous. Other dangerous combinations include St. John's wort with: -- protease inhibitors used for treatment of HIV infection. -- cyclosporine. -- oral contraceptives. There is at present a good system to detect possible dangerous interactions between drugs, but not between herbs and drugs. If in doubt about any natural medicines, check with The Natural Pharmacist.com (http://www.naturalpharmacist.com), an interactive Web site, directed by a team of physicians and pharmacologists.

 

HAVE YOU CHECKED YOUR TRIGLYCERIDES?

A case of hypertriglyceridemia, or high triglycerides, associated with IV interferon use for melanoma was reported in the cited article. This is important because high triglycerides provoked by interferon (IFN) can cause a potentially life-threatening case of pancreatitis. It is important to diagnose this problem early so that it may be treated. The problem of high triglycerides during IFN treatment has been reported several times during the past 10 years, and usually goes away after stopping treatment. The above mentioned case did not go away, even after almost one year. In spite of a high incidence rate (15 to 90%), the problem is not listed as an adverse reaction. Levels exceeding 1,000 mg/dL are thought to be capable of causing acute inflammation of the pancreas. As use of IFN increases, doctors should be aware of this possible complication.Drug-Induced Hypertriglyceridemia With and Without Pancreatitis, Yi-Kong Keung, MBBS, Division of Oncology/Hematology; Rafat Rizk, MD, Division of Gastroenterology; Xiao-Yan Wu, MD, Department of Internal Medicine; Everado Cobos, MD, Department of Psychiatry, Texas Tech University Health Sciences Center, Lubbock. [South Med J 92(9):912-914, 1999. © 1999 Southern Medical Association]

 

KNOWN HERB-DRUG INTERACTIONS

Although the area of herb-drug interactions is under-researched, there are some interactions we do know about.

	Feverfew: Feverfew is most commonly used for the treatment of migraines. Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin or ibuprofen (Motrin, Advil) may reduce the effectiveness of feverfew. It can also inhibit platelet activity and should not be taken together with blood thinners such as Coumadin. Feverfew contains tannin, which has the ability to inhibit iron absorption, and should not be used for longer than four months without medical supervision. The recommended dosage is 125 mg daily; each dosage unit should contain at least 0.2% parthenolide.
	Garlic: Most recent uses for garlic focus on its ability to treat high cholesterol and high blood pressure. Garlic can increase the risk of bleeding and should not be used concurrently with blood thinners. It has been reported to induce heartburn and flatulence, sweating, lightheadedness and allergic reactions. The German Commission E (Germany's equivalent to the FDA in the United States) recommends a dosage of 4 g of fresh garlic daily.
	Ginger: Ginger is often recommended for motion sickness, nausea and for loss of appetite. It has also been shown to prolong bleeding time and its use with aspirin or Coumadin should be avoided. Excessive consumption of ginger may also interfere with cardiac and anti-diabetic therapy. It is usually well tolerated but may cause stomach upset or heartburn in some people. For motion sickness it is taken one hour before traveling. The total daily dose is 2-4 g.
	Ginkgo Biloba: Ginkgo biloba is one of the most popular plant extracts in Europe and has recently received approval in Germany for the treatment of dementia. There have been reports of spontaneous bleeding in people taking ginkgo and again, it should not be used with blood thinners. People who take anti-convulsant medications, such carbamazepine and phenytoin, or phenobarbital should not take gingko without the knowledge of a physician, because it reduces the efficacy of these medications. Ginkgo is generally safe and well tolerated with the most common adverse reactions being stomach upset, headache and dizziness. German Commission E recommends a dosage of 40 mg of ginkgo three times daily with meals for at least four to six weeks. Preparations should be standardized to contain 6% terpene lactones and 24% ginkgo flavone glycosides.
	Ginseng: Ginseng is used to combat overall debility, as well as lack of energy and concentration. It has also been used as an aphrodisiac. There is tremendous variation in products labeled as ginseng; in one study, only 25% of the commercially available products actually contained ginseng. Nevertheless, ginseng enjoys widespread popularity. Siberian ginseng has been associated with falsely elevated digoxin levels (a heart drug used to treat congestive heart failure) by interfering with the test used to determine digoxin blood levels. Ginseng may also affect fasting blood glucose levels, so people who need to control their blood glucose levels should take ginseng with caution. Concomitant use with warfarin, heparin, aspirin and NSAID's should be avoided. Additionally, ginseng may cause headache, nervousness, and manic episodes in patients with manic-depressive disorders or psychosis or those on anti-depressants, particularly the monoamine oxidase inhibitors (MAOI) such as phenelzine (Nardil). Side effects include high blood pressure, restlessness, nervousness, insomnia, skin eruptions, edema and diarrhea. German Commission E recommends Asian ginseng be taken as 1-2 g of crude herb daily or as 100-300 mg of ginseng extract three times daily. Commercial products should contain at least 4%-5% ginsenosides.
	Kava Kava: Kava Kava is recommended for anxiety, sedation and relaxation. Excessive sedation may result when Kava Kava is taken with other sedatives (flurazepam, temazepam) or anti-anxiety drugs, particularly alprazolam (Xanax). The toxicity of kava is increased if taken with alcohol. Until the clinical significance of Kava's action on platelet activity is determined, its use with blood thinners should be cautioned. Long-term use is not advised and is characterized by dry, flaking, discolored skin and reddened eyes. The herb is contraindicated in patients with certain types of depression because it may increase the risk of suicide. The daily dosage is the equivalent of 60 mg to 120 mg kava pyrones.
	St. John's Wort: St. John's Wort is most widely used to treat mild to moderate depression, anxiety and seasonal affective disorder. Adverse reactions reported include stomach upset, allergic reactions, fatigue and restlessness. Photosensitivity is usually rare and is associated with higher dosages. Fair-skinned people should be particularly cautious. Concomitant use with other photosensitizers, such as piroxicam (Feldene) or tetracycline should be avoided. St. John's Wort should not be used with MAOIs (phenelzine) or selective serotonin reuptake inhibitors (SSRIs) such as Prozac, Zoloft or Celexa. St. John's Wort has been reported to prolong narcotic-induced (codeine) sleeping times as well as decreasing barbiturate-induced sleeping times and caution is advised when combining these medications. The herb also contains tannin and may interfere with iron absorption. The usual dosage is 300 mg of standardized extract three times daily or 450 mg twice daily. It may take up to four to six weeks to see desired effect.
	Valerian: German Commission E recommends valerian for use in the management of restlessness and nervous disturbances of sleep. Valerian may cause headache, hangover, excitability, insomnia, uneasiness and cardiac disturbances. Given its sedative property it would be wise to avoid barbiturates (phenobarbital), sedatives (flurazepam, temazepam) and alcohol while on valerian. Valerian is also a tannin-containing herb and may interfere with iron absorption. Persons currently taking antidepressants should take valerian only under medical supervision. The usual dosage of the extract is 2-3 g, one to several times per day.

Source: When medicine and herbs don't mix by Tammy Chernin, R.Ph. http://www3.healthgate.com

 

HERB WARNING: CELANDINE

An article in November's Gastroenterology (Nov;117(5):1234-1237) states that 10 cases of acute hepatitis in the last two years were observed which resulted from these people taking preparations of greater celandine (Chelidonium majus), which are often recommended for treatment of gastric and biliary disorders. The course of hepatitis was mild to severe. Liver failure did not occur. Other causes of liver disease were excluded, and the hepatitis disappeared after stopping the herbal treatment.

 

DRINKING, AND VITAMIN A AND YOU

Through experimenting with the metabolic effects of alcohol and vitamin A in test tubes, these doctors have come to the conclusion that many interactions occur between retinol, ethanol, and other drugs.1 Therefore, longtime use of alcohol, drugs, or both, results not only in lowered dietary intake of retinoids and carotenoids (included in vitamin A), but also speeds up the breakdown of retinol. The loss of vitamin A affects the liver, and may cause cancer cells to form. Normally, vitamin A supplements are suggested for drinkers, but vitamin A is, to some degree, toxic for the liver, and drinking alcohol increases this toxicity. On the other hand, beta carotene, a precursor of vitamin A, was considered harmless until recently. Now it is known to interact with alcohol and that stops it from converting into vitamin A. Not only that. The combination of beta carotene and alcohol is toxic for the liver. In people who smoke and drink, beta-carotene supplements can produce lung cancer and perhaps heart problems. The toxicity of beta-carotene was made worse when it was given as part of beadlets. So alcohol causes vitamin A deficiency and makes both vitamin A and beta-carotene, more toxic. This should be taken into account when trying to correct vitamin A deficiency in drinkers.1.American Journal of Clinical Nutrition, Vol. 69, No. 6, 1071-1085, June 1999 Maria A Leo and Charles S Lieber, "Alcohol, vitamin A, and ß-carotene: adverse interactions, including hepatotoxicity and carcinogenicity''

 

AMOXICILLIN/CLAVULANATE WARNING

Clinicians should be aware that amoxicillin/clavulanate is capable of causing hepatitis with eventual systemic dysfunction. Reported hepatic reactions have been mainly cholestatic, with some mixed cholestatic/hepatocellular liver function test abnormalities. Most cases of liver injury have been benign and reversible on discontinuation of the drug, and recovery is usually complete. However, signs and symptoms of jaundice and pruritus may appear up to six weeks after therapy has been stopped. In patients with rash associated with hepatic dysfunction, renal insufficiency, or other unusual symptoms, clinicians are advised to consider earlier initiation of systemic steroids or liver transplantation referral, in hopes of avoiding progressive systemic response. In one recent case, a 37-year-old white male without significant past medical history died of progressive hepatic failure, renal failure, and Stevens-Johnson Syndrome after receiving a 10-day course of amoxicillin/clavulanate for treatment of pneumonia. Thirty-two days after starting his treatment, the man developed jaundice, rash, pruritus, and increasing fatigue. The time of development of cholestatic jaundice correlated with the use of amoxicillin/clavulanate. The likelihood of toxicity from other drugs or diseases was excluded.CONTACT: D.L. Limauro, N.H. Chan-Tompkins, R.W. Carter, G.J. Brodmerkel Jr, & R.M. Agrawal, Division of Gastroenterology, Allegheny University Hospitals/Allegheny General, Pittsburgh, PA 15212, USA. From Ann Pharmacother 1999 May;33(5):560-4 PMID: 10369618, UI: 99296309

 

TROVAN WARNING

One hundred forty cases of serious liver damage have been reported among Trovan users since February 1998. While most recovered after stopping the antibiotic, five patients died and three required liver transplants. Trovan is an antibiotic made by Pfizer, Inc. The consumer advocacy group Public Citizen has petitioned the Food and Drug Administration to ban Trovan. The European Union last week warned Europeans to stop taking Trovan if they experience symptoms suggesting liver damage, such as fatigue, yellowing of the skin or eyes, stomach pain with nausea or vomiting, or dark urine. Officials call the risk rare, since Trovan has been prescribed to 2.5 million people. The FDA called the liver problems serious. The FDA often approves drugs with liver risks as long as doctors are warned to monitor patients carefully so they can stop the drug if a problem arises.From: Group Seeks Ban of Antibiotic Trovan By LAURAN NEERGAARD, AP Medical Writer, WASHINGTON (AP)

 

HERB AND DRUG INTERACTIONS

 

	Echinacea, if used for more than eight consecutive weeks, could cause liver toxicity and should not be used with drugs such as anabolic steroids, amiodarone and methotrexate which are toxic to the liver as the affect may be additive.
	Feverfew, garlic, ginger, ginseng, and ginkgo biloba all affect bleeding time and should not be taken by patients using warfarin or by patients that have decreased platelet counts.
	St. John's Wort should not be taken with monoamine oxidase inhibitors or selective serotonin reuptake inhibitors like Prozac and Paxil until more information is available.
	Licorice, plantain, hawthorn and ginseng may interfere with digoxin therapy and valerian root should not be taken when barbiturates are used because it could cause an increase in the barbituate effects.
	Evening primrose oil and borage are contraindicated in patients taking anticonvulsants (e.g., clonazepam). lmmunostimulants such as echinacea and zinc should not be given with immuno suppressants such as corticosteroids (like prednisone) and cyclosporine and are contraindicated in patients suffering from rheumatoid arthritis, systemic lupus erythematosus and autoimmune hepatitis.

Source: Hans Larsen is a health sciences researcher living in Victoria, British Columbia from Alive Magazine March 1999 with some changes by D. Morrow

 

IBUPROFEN FOLLOW-UP Darlene Morrow

I have done an exhaustive (read exhausting) search on ibuprofen and HCV. The bottom line is that there is not much evidence to support drastic action. What I have been able to find is miniscule when you look at other drugs and HCV. I was very surprised to find a lot of problems with diclofenac-induced hepatitis that looked very serious. In my article on pain management, I mentioned this anti-inflammatory. In the light of this research I think that a warning should be published. What I did find out about ibuprofen is it is very bad for the kidneys, and it also caused some visual problems. Sowe know that drugs are bad for the liver. That is a given. Some are worse than others. Certainly the case for ibuprofen should be investigated seriously. I must say that Paxil also disturbs me because it is a widely used anti-depressant that has also been associated with hepatotoxicity and death. And again, it is only isolated but ....

 

ASPIRIN? THINK TWICE!

If you have cirrhosis, you may want to think twice about popping an aspirin or other NSAID. It is universally accepted that NSAIDs can have severe gastrointestinal effects and cause peptic ulcers to bleed. They may cause oesophageal bleeds, as well. According to an article (Anti-inflammatory drugs and variceal bleeding: a case-control study) in the February 1999 issue of GUT magazine, interviews were conducted at the University Hospital in Poitiers, France, with 200 patients with cirrhosis. Of these patients, 125 had been admitted for a first bleeding episode mainly related to oesophageal varices, and 75 patients had never had a bleed. Twenty five percent of the patients who were admitted for bleeding had used NSAIDs during the week before the bleed. In contrast, only 8 of the 75 who had not had a bleed had used NSAIDS. Use of aspirin alone or combined with other NSAIDs was also more prevalent in the cases with bleeds (17%) than in the cases with no bleeds (4%). Analysis showed that NSAID and the size of the varices were the only variables independently associated with the risk of bleeding. The study concluded: "Aspirin, used alone or combined with other NSAIDs, was associated with a first variceal bleeding episode in patients with cirrhosis. Given the life threatening nature of this complication, the possible benefit of this treatment should be weighed against the risk shown here. No firm conclusions could be drawn on non-aspirin NSAIDs used alone."Source: http://www.gutjnl.com GUT 1999;44:270-273 (February)

 

MELATONIN WARNING

"Is melatonin associated with the development of autoimmune hepatitis?" Melatonin is a neurohormone produced by the human pineal gland that plays a role in the regulation of many physiologic processes and has been proposed as a therapy for everything from insomnia to metastatic carcinoma. Melatonin is available in the United States without prescription, and adverse effects appear to be uncommon. However, because melatonin appears to have immunomodulatory properties, the potential exists for the development of autoimmune-related side effects. We describe a patient in whom characteristic clinical and laboratory features of autoimmune hepatitis developed after beginning melatonin therapy for the treatment of insomnia. Liver biopsy demonstrated histologic features of autoimmune hepatitis. Rapid symptomatic and biochemical improvement resulted from the initiation of immunosuppressive therapy; however, hepatitis recurred after the withdrawal of steroid therapy. The temporal relation observed between melatonin use and the development of autoimmune hepatitis raises the possibility that the drug might be involved in the pathogenesis of this patient's autoimmune disease.Hong YG, Riegler JL Department of Gastroenterology, Wilford Hall Medical Center, Lackland Air Force Base, Texas, USA., J Clin Gastroenterol 1997 Jul;25(1):376-378, PMID: 9412927, UI: 98074407

 

DURACT: PAINKILLER LINKED TO DEATHS IS WITHDRAWN

WASHINGTON, June 22 (UPI) - The manufacturer of the painkiller Duract says it it withdrawing the drug because of reports of rare severe liver failure and deaths. Wyeth-Ayerst Laboratories, of St. Davids, Pa., says Monday it is advising doctors to discontinue prescribing and dispensing the drug, generically known as bromfenac, immediately. The drug was approved in July l997 for management of acute pain for 10 days or less. The company says the reports of deaths and injuries were associated with long-term use, beyond 10 days. In a statement, the company notes the drug was never approved as a treatment for longer term use for chronic conditions such as osteoarthritis or rheumatoid arthritis. Also, it says, no cases of serious liver injury were reported in clinical trials. But because researchers recorded a higher incidence of liver enzyme elevations in patients treated long term in clinical trials, the product was approved for use for 10 days or less. The information about the elevated liver enzymes was included in the product labeling. After Duract was marketed, the Food and Drug Administration and the company received reports of several cases of rare severe hepatitis and liver failure, some of which required transplantation, in patients taking the drug for more than 10 days. In February l998, in response to the reports of severe liver failure, and transplants, the FDA and the company strengthened the warnings in Duract's labeling with a special black box warning and Wyeth-Ayerst issued a Dear Doctor letter. The revised label re-emphasized that patients should not take the drug for more than 10 days and alerted physicians and other health care professionals to the cases of severe hepatitis and liver failure, and cases in which patients required a transplant, in patients who had taken Duract. Despite these efforts, the agency and the company continued to receive reports of severe injuries and death with long-term use of Duract. In the statement, the company says, given the availability of other therapies, the FDA and Wyeth-Ayerst concluded that it would not be practical to implement the restrictions necessary to assure the safe use limited to less than 10 days of Duract. The company and FDA agreed that it would be prudent to withdraw the drug from the market. Questions about withdrawal of Duract can be addressed to Wyeth-Ayerst's hotline at 1-(800) 281-9260. Copyright 1998 by United Press International All rights reservedSource: UPI Science News Monday June 22 2:54 PM EDT

 

WARNING FOR PEOPLE TAKING CESAMET (Nabilone)

I spoke with Dr. Anderson this morning. He was very concerned about something that he had heard. It appears that some people with HCV are taking Cesamet (nabilone) for nausea. This drug is very toxic to the liver and should NOT be used by HCV patients. Nabilone is used in the treatment of nausea associated with chemotherapy. Nabilone should be used in extreme caution in patients with severe liver dysfunction (HCV). In addition, the side effects of Nabilone include depression, loss of appetite, confusion, fatigue and headache. These side effects are already common in HCV patients especially those taking interferon. A decrease in the white blood cells is also seen with both the nabulone and interferon. If nausea is a problem, it is recommended that ginger be used. You can buy standardized, organic ginger in the health food store ($10.00 for 100-500mg capsules). Take 3 capsules as needed. If this doesn't work, Gravol would be the second choice. Darlene Morrow

 

LIST OF HAZARDOUS HERBS

Here is a list of nine herbs that the FDA says are related to serious adverse reactions or possible dangers:

	Chaparral. Can cause liver inflammation. Has been promoted as a "blood purifier,'' cancer cure and acne treatment.
	Comfrey. At least seven cases of liver complications have been reported in users. Comfrey stimulates cell growth and is used for wound healing when taken externally. Toxic to the liver when taken internally.
	Yohimbe. Produces adverse reactions when consumed with certain foods -- liver, cheese and red wine. Is valued as an aphrodisiac.
	Lobelia. High doses can suppress breathing, cause sweating, speed the heart, lower blood pressure and even lead to coma or death. The source of lobeline, an ingredient in some over-the-counter smoking deterrents.
	Germander. Linked to liver inflammation, including one death. Used as a weight-loss aid.
	Willow bark. Contains salicylates, like aspirin, which could cause stomach irritation or Reye syndrome Is promoted as an ``aspirin-free'' pain reliever, but no adverse effects have been reported.
	Jin Bu Huan. An overdose can result in severe sedation requiring medical treatment, and liver inflammation. Is marketed as a sedative and pain reliever.
	Stephania and Magnolia. Have been implicated in severe kidney injury to at least 48 women.
	Ma huang. Associated with high blood pressure, rapid heart rate, nerve damage, muscle injury, psychosis, stroke and memory loss; Used for weight control and enhanced energy and to treat asthma and hay fever. Contains pseudoephedrine, the active ingredient in decongestants such as Sudafed.

 

METHIONINE AND LIVER DISEASE - A WORD OF CAUTION BY DARLENE MORROW, BSC

Methionine or SAM has been recommended to people with HCV as a liver protectant particularly in conjunction with tylenol (500mg twice a day). While it is generally accepted that methionine is a liver protectant, the evidence is not conclusive as to the recommended dosage and possible side effects. Extreme caution is necessary in individuals with severe liver disease because drugs/substances are processed in the liver. The effects of hepatitis C and liver disease vary from individual to individual. The extent of damage and your particular condition (fibrosis, cirrhosis, etc.) will all have a bearing on your body's ability to deal with outside substances. The following excerpt demonstrates the possible dangers of self-medicating. We strongly recommend that all supplements be approved for your use by your physician. Please keep in mind when reading the following article that the suggested dosage of methionine was 2 x 500mg which is equal to 1g.

 

"SHOULD METHIONINE BE ADDED TO PARACETAMOL (TYLENOL) FORMULATIONS? - CAUTION IN PATIENTS WITH LIVER DISEASE!"

Adverse effects associated with methionine include nausea, vomiting, drowsiness and irritability. [1] Moreover, methionine should be used with caution in patients with severe liver disease as this agent may aggravate hepatic damage and this drug should not be used in patients with acidosis. [2] Although methionine (an amino acid) is an essential dietary constituent, studies have shown that methionine may cause reduced serum folate levels, leucocytosis, changes in serum pH and potassium and increased urinary calcium excretion when given at dosages of 8 to 13.9 g/day for 4 to 5 days. Moreover, functional psychoses have been seen in schizophrenic patients receiving higher dosages of 10 to 20 g/day for 2 weeks, and single doses of 8g have precipitated hepatic encephalopathy in patients with cirrhosis. [3] Although there is no evidence in humans, animal studies indicate that methionine may have adverse effects on the cardiovascular and coagulation systems. [3]References: 1.Martindale. The Extra Pharmacopoeia, 31st ed. London: Pharmaceutical Press, 1996: 683-4. 2.Jones AL, Hayes PC, Proudfoot AT, et al. "Should methionine be added to every paracetamol tablet? No: the risks are not well enough known." BMJ 1997 Aug 2; 315: 301-4 3.Krenzelok EP. "Should methionine be added to every paracetamol tablet? Yes: but perhaps only in developing countries." BMJ 1997 Aug 2; 315: 303-4(Reprinted with permission from [Drugs & Ther Perspect 10(11): 11-13, 1997. (c) 1997 Adis International Limited] source: http://www.medscape.com/

 

AFLATOXINS

Moulds are organisms capable of growing on many substances, according to varying conditions of temperature and moisture. Some moulds are useful to man. Carefully cultivated varieties enhance the flavour of Camembert, and give blue and Roquefort cheeses their marbled appearance and characteristic tang. Probably the most famous beneficial mould is a Penicillium. The discovery of its ability to kill harmful bacteria led to the development of antibiotics and a whole new era in the treatment of disease. However, many moulds are a nuisance because they spoil food, clothing and leather, and cause extensive food crop losses in the form of blights and rusts. In addition, some moulds may pose a health hazard by producing substances called mycotoxins. Mycotoxins (mycos is Greek for mould) are undesirable chemical compounds produced by some species of mould under certain temperature and moisture conditions. Mycotoxins are persistent substances and may remain in a product even after the moulds which produced them are killed. The illness, disease or condition resulting from the intake of mycotoxin- contaminated food or feed is called mycotoxicosis. In the past, scattered outbreaks of mycotoxin poisoning in man and animals were recorded. However, these incidents were isolated and were usually linked with unusual circumstances involving consumption of poorly stored grains. The view that mycotoxins did not constitute a general health hazard changed in 1960, when an outbreak of Turkey-X disease killed more than 100,000 turkey poults in England. The mysterious Turkey-X outbreak was traced to imported peanut meal contaminated by the mould Aspergillus flavus, which is capable of producing several mycotoxins called aflatoxins. Aflatoxin toxicity The discovery of aflatoxins renewed scientific interest in mycotoxicosis and led to the development of improved methodologies for detecting and isolating mycotoxins. Further studies revealed that aflatoxins were acute poisons at high concentrations, and also were potent liver carcinogens when fed to experimental animals at low levels over long periods of time. In addition, epidemiological studies in Southeast Asia and Africa have shown that liver cancer is significantly higher among certain human population groups who consume diets high in aflatoxins, although other factors such as local diseases may influence this incidence. Food susceptible to aflatoxins Certain crops grown in warm, humid climates are susceptible to mould contamination which can result in the production of aflatoxins. These crops include corn, tree nuts and peanuts. Aflatoxins are rarely found in Canadian field crops because of our climate. Reducing levels in food products Since moulds are a naturally occurring crop problem, it is not possible to eliminate traces of aflatoxin entirely from food products. However, contamination can be minimized by careful storage and handling of the crops after harvest, and by rigorous inspection of products before they are offered for sale. Of all mycotoxins, aflatoxins are the most studied and regulated. Reduction of aflatoxin levels in food products is the shared responsibility of the grower, distributor and food processor. The Health Protection Branch has an active program aimed at further reducing aflatoxin levels in foods sold in Canada. Because of the popularity of peanuts and peanut butter, the presence of aflatoxins in these vulnerable foods is of particular concern. In accordance with the Canadian Food and Drug Regulations, the maximum tolerated level of aflatoxins in nuts and nut products sold in Canada is 15 parts per billion. Aflatoxins and peanut products Peanuts consumed in Canada are primarily imported from other countries, mainly the USA. Peanuts and peanut butter are checked for aflatoxin contamination at many points during the manufacturing and marketing process. In the United States, the Department of Agriculture analyzes every lot of raw peanuts to ensure that peanuts sold for human consumption do not contain excessive amounts of aflatoxins. Each lot of peanuts imported into Canada from the United States is accompanied by a certificate of analysis. Peanuts grown in Canada are regularly monitored for aflatoxin contamination. No detectable levels have been found to date in the domestic peanut crop. The Canadian food processors are responsible for ensuring that each shipment of peanuts is of an acceptable quality before processing it. Peanuts of acceptable quality are then roasted. This has been shown to destroy approximately half of any aflatoxin in the nuts. After roasting, the nuts are sorted to remove damaged or discoloured kernels, which are likely to contain most of any aflatoxin residues present. Peanut processors also analyze samples of finished peanut butter for aflatoxin residues to ensure that they do not exceed the standard set out in the Food and Drug Regulations. Inspectors of the Health Protection Branch inspect peanut processing plants to assess manufacturing procedures for reducing aflatoxins in the finished product. The inspector will identify any specific weakness in a firm's quality control program and will advise the plant managers on any need for improvement. Inspectors obtain samples of peanut butter for analysis from every manufacturing plant in Canada. Enforcement action, including product recalls, is initiated when a batch of market-ready peanuts, peanut butter or other nut products is found to contain excessive amounts of aflatoxins. Safety tips for the consumer Throw away all food contaminated with mould. This is a good rule to follow to avoid mycotoxin intake in general. Do not eat shrivelled, discoloured, mouldy or damaged nuts of any variety. Do not allow peanut butter or other foods susceptible to mould growth to stand uncovered for long periods of time. Store in a cool dry place to avoid mould contamination.

From: Health Canada "It's Your Health" series http://www.ehso.com/ehshome/aflatoxin.php  Aflatoxins in Your Food - and their Effect on Your Health