Palmer: Thank you.  Many of my colleagues have given the book to their physician extenders- i.e. nurse practitioners, physician assistants, nurses, and medical assistants to assist them in the care of patients with hepatitis and other liver diseases.  The feedback that I have received is that my book is extremely helpful, especially when dealing with the side effect management of interferon.  I have devoted an entire chapter to this specific issue. Other doctors have either given the book or suggested the purchase of the book to their patients to use as a reference guide.  For example, if a patient is suffering from hair loss on interferon therapy – they may use the index to look up “hair loss interferon induced” and then refer to the chapter for management.

MASJ:   The chapters ‘Herbs and Other Alternative Therapies’ and “Diet, Nutrition and Exercise’ provide an important professional assessment of adjunct therapies that are often not well integrated into some medical practices.  As you point out, recent surveys indicate that more people are visiting alternative medicine professionals than those who practice conventional medicine. What are the obstacles to physicians discussing and possibly monitoring these alternate therapies with patients who may choose to supplement traditional medicine with some of these alternatives?

Palmer:  While the amount of information and research concerning herbs is increasing, there are still two important matters that have not been clearly defined as to herbs. First, due to the lack of controlled research on herbal remedies, the exact extent of drug-herb interaction is not entirely known. Thus, an herb that a person may be taking in an attempt to prevent liver damage may have a negative interaction with the medication that he or she is taking to control high blood pressure. For example, licorice—proclaimed to be beneficial in the treatment of viral hepatitis—might cause fluid retention and worsen high blood pressure. Furthermore, licorice may cause a decrease of libido in men, which is a potential side effect of interferon therapy, in addition to being a side effect of many antidepressants which are often used during interferon therapy for hepatitis C. Many herbs may increase or decrease the action of conventional medicines. For example, the herb cannabis sativa (marijuana) has been demonstrated to diminish the effectiveness of interferon and to suppress the immune system. Though potential adverse drug-herb interactions can be looked up in the PDR for Herbal Medicines, this list may be incomplete. An example of such an interaction includes the death of women who was taking St. Johns Wort at the time she underwent anesthesia with the drug Demerol.  Due to an adverse drug-herb interaction, this patient experienced fatal cardiac arrest.  This also resulted in the filing of a large lawsuit against the herb manufacturer.

Furthermore, the noted side effects of an herb, in general, may be incomplete. This is due to the fact that it can be very difficult to trace side effects to a particular herb. It may take weeks, months, or even years for problems to show up. By that point, people don’t always remember that they have taken an herbal remedy or they have become so accustomed to a particular side effect that they dismiss it. Complicating matters even further, many natural remedies contain dozens of active ingredients depending on exactly how they were prepared by the manufacturer. The composition of these ingredients may vary greatly (even among bottles of the same type of herb). Finally, there are no regulatory laws mandating that the manufacturer or distributor of an herbal preparation report possible adverse reactions of the herb to the FDA or other government agency. So, in all likelihood, all the possible drug-herb interactions and other side effects associated with a given herb are not listed in the PDR for Herbal Medicine.  This is made clear by reports which appear on a regular basis alerting the public to the danger of an herb that was once thought to be safe.  Usually the herb –in-question has caused some unsuspecting consumer to suffer severe, or even fatal, side effects including cancer, kidney failure and liver failure, thereby necessitating the removal of the herb from the market or at least stronger warning labels on the bottle.  Examples of such herbs include kava and ephredra respectively.

Second, there is a lack of standardization among herbal products. It is important to be aware that not all parts of the herb contain the active ingredient proclaimed to produce the beneficial effect. For example, one study compared ten different brands of the herb ginseng and found that the active ingredient ginsenoside varied drastically among different brands, although all were essentially similar in their descriptions of ingredients contained in the bottle. In fact, some pills or capsules contained almost none of the active ingredient. A different study found that up to one-quarter of the products on health food store shelves did not contain any of the listed ingredients.

Due to the absence of regulation, it is possible that a totally different herb can be substituted for the one on the label. Furthermore, there have been reports that some herbs have been spiked with steroids, painkillers, tranquilizers, thyroid extracts or other substances to improve their effectiveness. Toxic metals, including lead and arsenic and even powerful heart stimulants (such as digitalis), the blood thinner warfarin, and the diabetic medication glyburide have been discovered mixed in with herbal preparations. And, some herbs have been found to contain dangerous microorganisms, such as staphylococcus aureus, escherichia coli (E. coli), salmonella, and shigella, each of which can make a person quite ill.  Of course, the product labels, did not mention the addition of any of these adulterants, and all labels claimed to contain only “natural” ingredients.    

MASJ:     The chapter ‘Pregnancy, Sex, Medications, and Prevention” includes a comprehensive discussion of drug-induced liver disease that appears to be alarmingly high in my age category - with 40 percent of hepatitis cases in people over fifty years old. Would you comment on the factors contributing to this high incidence and what actions physicians and patients can take to reduce the incidence of drug-induced hepatitis in general and especially in this age group?

Palmer:   Since all medications are processed through the liver at least to some degree, people with liver disease must become aware of which medications can cause liver damage, which medications can worsen preexisting liver disease, and which medications are safe to take. It is the liver’s job to detoxify any substances that are potentially harmful to the body. An already damaged and weakened liver must work much harder than a healthy liver in order to accomplish this task. When a person with liver disease ingests a potentially hepatotoxic drug, this puts an additional strain on the liver and can result in further liver injury or possibly even liver failure. Even people with a healthy liver can develop liver disease as a consequence of ingesting a toxic medication or drug.

In general, people with liver disease should avoid medications known to be hepatotoxic. People who must be treated with a medication that is potentially hepatotoxic should have their LFTs closely monitored by their doctors. If a person’s LFTs become greater than three times baseline values, the medication causing these elevations should be discontinued. Also, it is essential that people with liver disease inform their liver specialists of every medication or drug that they are taking—including herbs, over-the-counter drugs and/or recreational drugs. There is no reason for the patient to expect the doctor to be judgmental. Her goal is the same as the patient’s. Therefore, complete information should be provided to the doctor concerning prescription medications, over-the-counter medications, and herbal and alternative therapies. Remember, a doctor’s objective is to help her patient get better and to help protect her patient from unintentional additional liver damage. 

People with cirrhosis must be particularly aware of which drugs are hepatotoxic, as they are typically more sensitive to drugs side effects due to the inability of the liver to clear the drug from the body (excretion rate).  Even drugs that are not known to be hepatotoxic may have a prolonged excretion rate.  This means that the drug and its metabolites will stay in the body longer.  Therefore, usual dosages of these drugs should not be taken - the dosage of these drugs should be decreased.  Examples of such drugs that require a decrease in the dosage when used for a prolonged period of time in people with cirrhosis include Benadryl (diphenhydramine), morphine, Demerol  (meperidine) and methadone.

A person’s susceptibility to a potentially hepatotoxic drug is enhanced by many factors. Some of these factors may be within the person’s control, such as cigarette smoking , excessive alcohol intake, and obesity.  So, it is important for all individuals with liver disease, especially older people to discontinue cigarette smoking, alcohol use and to loose weight when required. 

MASJ:    With IV drug use accounting for 70 percent of new HCV infections, could you comment on the options for and obstacles to accessing appropriate treatment for HCV in this population?

Palmer:  Recent studies have demonstrated that people with HCV who actively use intravenous drugs - a condition previously considered to be a contraindication to treatment with interferon, may be successfully treated with interferon.  Since intravenous drug use is currently the most common mode of transmission of new HCV infections, treatment of these individuals is important as it may potentially reduce the spread of HCV.  Ideally, these individuals should be enrolled in a methadone maintenance drug treatment program.  The use of methadone is not a contraindication to interferon treatment.  Furthermore, the decision of the NIH Consensus Statement of 2002 concluded that active intravenous drug use should not be considered a contraindication to treatment with interferon.