Interferon: 
Are the Side-Effects Worth It ?
         Since interferon was first introduced as a therapy for chronic non-A, non-B hepatitis in 1986, almost all patients using interferon and its combinations (i.e. ribavirin) have experienced side effects, some life threatening. Many have had to stop treatment altogether since these side effects were too overwhelming and too debilitating for them to continue treatment. Because of the low success rate in clearing the body of the hepatitis c virus in most people (especially in those with genotype 1A, and 1B commonly found in the United States and in Europe), it is now apparent that interferon cannot be considered a cure in most persons. Rather, for those who respond to this therapy (only 15-20%), interferon must be considered a method of viral suppression, not eradication or cure.

        For those individuals who absolutely cannot live with the thought of a virus lurking inside them and, therefore, are considering the use of interferon and interferon + ribavirin, we would like to present the following information on the side effects of these drugs. We do not present this information as a technique to scare you, but rather to inform you. We believe that in today's world, individuals should be armed with as much information about their health and bodies as possible. In that way, they can better make an informed decision regarding the treatments they wish to undergo for their ailments.

        All "drugs" have side effects. Since the genetic make-up of each individual is different, people will react in different ways to the same administered drugs and their combinations. The literature on interferon therapy lists the following side-effects of interferon: flu-like symptoms (fever, chills, muscle and joint pain, headache), hair loss, tiredness, low blood count, trouble with concentration and thinking, moodiness and depression. For some people, the effects are even more life threatening. They include: blood infection, thyroid disease, suicidal thoughts, seizures, acute heart, kidney, eye and lung problems, and in some instances, deaths due to liver failure or blood infections.

        A most important side effect of interferon therapy is the actual worsening of the liver disease it is designed to treat. In approximately 40 out of 100 persons treated with interferon, the dosage has had to be reduced because of the severity of side effects, and treatment stopped completely in about 15 out of 100 persons.

        These side effects are experienced with only using monotherapy, or interferon by itself. Now, add to this the combination of interferon and ribavirin and the side effects multiply. In addition to the side effects due to interferon alone, ribavirin can cause: severe anemia (low red blood cell count) and can result in kidney failure. Anemia can be life threatening for people with certain types of heart or blood vessel disease. Ribavirin has also been known to cause serious birth defects in pregnant women.       
        The following article: "Side Effects of Interferon Alpha in Viral Hepatitis" by Geoffrey Dusheiko, M.D. appeared as part of the National Institute of Health Conference on Hepatitis C, held from March 24-26, 1997 Volume 15, Number 3. The complete conference can be found at the following website address:

http://consensus.nih.gov/cons/105/105_intro.htm

        This article can be located on pages 82 thru 88 of the "Related Conference Material Program and Abstracts" section of the above web address.

Side Effects of Interferon Alpha in Viral Hepatitis
Geoffrey Dusheiko, M.D., F.R.C.P.

        Interferon alphas have been widely used to treat chronic hepatitis C virus infection. These include recombinant interferons, or purified natural leucocyte or Lymphoblastoid interferon. Interferon alpha is usually administered by subcutaneous or intramuscular injection. The terminal half-life of interferon alpha is 4-5 hours. Renal excretion is the predominant route of elimination.

        A wide array of side effects have been encountered in several large trials of treatment of hepatitis C. Side effects are common; they are usually minor but are problematic for a significant proportion of patients. Major adverse events can occur, but life-threatening adverse events have been rare in large surveys. (1) Tolerance in elderly patients and children is usually similar. (2-4)

        Early flu-like side effects are predictable and are encountered in the majority of patients. These tend to occur within 6-8 hours after starting treatment and are worst with the first injections. These side effects include fever, malaise, tachycardia, chills, headache, arthralgias, and myalgias. However, they are usually acceptable at doses of 3-6 million units (MU) of interferon alpha, and tachyphylaxis generally develops after the first few injections. These side effects are ameliorated by paracetamol (acetaminophen).

        Later side effects develop after some days. These include fatigue, malaise, apathy, and cognitive changes. Between 10 and 15 percent of patients find the chronic side effects intolerable and discontinue treatment. Higher doses (above 5-6 MU three times weekly) tend to give higher rates of adverse events. (5-7)

Neuropsychiatric Side Effects:

        Neuropsychiatric side effects can be the most troublesome and unpredictable , but their mechanisms are poorly understood. Interferon is not thought to readily cross the blood-brain barrier. These effects include fatigue, asthenia, drowsiness, lack of initiative, irritability, confusion, and apathy; behavioral, mood, and cognitive changes are a relatively frequent dose-limiting toxicity. Severe depression may occur and suicidal ideation is well described. This can be more marked in patients with a history of depression, but suicide has been reported in patients without a previous psychiatric history. (8)

        Administration at night may reduce the frequency of these side effects. They usually regress after discontinuing therapy, albeit after some weeks. Severe depression is a medical emergency. The overall incidence of neurotoxicity is 25-33 percent. Seizures have been recorded in 1.3 percent of patients. (9) There are isolated reports of extrapyramidal syndromes with ataxia and akathisia. Paraesthesias have been recorded. table 1 lists common adverse events associated with interferon alpha in a recent trial, and table 2 lists a range of laboratory variables.

table 1. Most Common Adverse Events in a Recent Large Trial of Patients Treated With Consensus Interferon (CIFN) or Interferon Alfa 2b (3 MU=15 ug) (percentage)
[Source: Amgen Inc. Phase 3: (9210). With acknowledgment].


Immune Disorders:

        Interferon has important immunomodulatory properties. Non-organ-specific antibody titers may increase, and indeed may be associated with autoimmune thyroiditis, hypothyroidism, and hyperthyroidism. (10-15) Other autoimmune endocrine diseases have been induced, but thyroid disease is particularly important. (16) Thyroid disorders have been reported in 2.5-20 percent of patients. This may not be reversible after stopping therapy, unless therapy is stopped early, and long-term thyroid replacement may be required. (17-19) It is possible that underlying thyroid disease is more common in chronic hepatitis C infection.

        An aggravation of the chronic hepatitis may occur. Patients may be genetically predisposed to this complication and can be recognized by prior autoantibody measurement and HLA haplotyping. An exacerbation of psoriasis may be part of this syndrome. Discontinuation may be required, particularly for hyperthyroidism, unless transient hyperthyroidism followed by hypothyroidism is recognizable. Autoimmune hepatitis usually necessitates discontinuation of therapy. Interferon may promote the development of systemic lupus erythematosus.

Cardiovascular Side Effects:

        Both benign and severe cardiac manifestations have been reported. Cardiac arrhythmias, including supraventricular tachycardia but also sudden death and ventricular arrhythmias, have been reported. There are single case reports of dilated cardiomyopathy. Hypotension has been reported in large trials.

Renal Side Effects:

        Proteinuria is relatively common, but is usually benign and not nephrotic. lnterstitial nephritis and acute renal failure have been reported. Interferon alpha is, however, reasonably tolerated in hemodialyzed patients. (20) Renal impairment occurs in kidney transplant patients. (21)

Hepatic Side Effects:

        Serum aminotransferases may increase during interferon alpha treatment. These are generally mild and resolve with continued treatment in responsive patients. Exacerbations occur in hepatitis B infection; these severe cytolytic episodes may presage a response, but are poorly tolerated in patients with cirrhosis. Hepatic decompensation may occur in patients with cirrhosis, and these patients are more susceptible to infections. (22,23) Autoimmune hepatitis should not be misdiagnosed as hepatitis C infection, as severe exacerbation of the disease with cholestasis and severe liver injury can occur. Patients with documented hepatitis C infection may deteriorate after interferon alpha treatment if an underlying autoimmune diasthesis is present. This has been observed in LKM antibody-positive individuals. These patients require careful monitoring if interferon is considered the first line of treatment. (24) Rejection may occur if interferon is used after liver transplantation. (25)

Gastrointestinal Side Effects:

        Nausea, vomiting, dyspepsia, diarrhea, and abdominal pain are relatively frequent.

Dermatologic Side Effects:

        A variety of rashes including erythema multiforme have been noted. Pruritus can be troublesome. Mild hair loss is relatively common but is reversible. Local erythema is common. Psoriasis can develop de novo, or be aggravated, and is usually difficult to treat. Vitiligo has been reported. (26)

Myelosuppression:

        Granulocytes, thrombocytes, and red blood cell counts are commonly decreased during treatment. These are usually mild if normal counts are present initially, but can be dose limiting in the presence of low counts, for example in patients with hypersplenism. Patients may be predisposed to infections. The mechanism of granulocytopenia is unknown, but inhibition of cell release from the bone marrow has been suggested.

Hormonal and Metabolic Side Effects:

        A sustained increase in serum triglyceride levels has been reported. Diabetes mellitus may worsen or develop.

Rare Adverse Events:

        Ocular: Retinopathy has been reported in Japanese patients. (27) Lung: interstitial fibrosis of the lung and hearing impairment have been found. (7) The cases of pneumonitis may also be due to the use of Sho-Saiko and interferon. (28)

Conclusion:

        This array of side effects indicates the importance of selecting patients for therapy and optimizing response. Careful assessment is required before treatment, and monitoring is required during treatment. Relatively little is known about the mechanisms of many of the side effects of interferon alpha. (29)

       Combination antiviral therapy, particularly ribavirin and interferon, is likely to be given to many patients with chronic hepatitis C. Interactive pharmacokinetic studies examining the distribution and metabolism of these two drugs are in progress.

         And if you are still not convinced of the dangers of interferon, we enclose a recent article written by Dr. Russell Blaylock, MD, a board-certified neurosurgeon and author of the highly recommended books: “Health and Nutrition Secrets That Can Save Your Life”,  and “Natural Strategies for Cancer Patients”,  who contributed this article about the harmful brain effects of interferon.  Anyone who contemplates taking interferon should read this article to see if the benefits outweigh the risks.
By Russell L. Blaylock, M.D.
http://www.russellblaylockmd.com/

Interferons are used in clinical medicine for a number of medical conditions including:
A wide range of cancers
Chronic hepatitis
Multiple sclerosis
Chronic granulomatous disease
AIDS-related disorders

Rarely considered are the effects of large doses of this immune cytokine on brain function. For example, the conventional treatment of chronic hepatitis is interferon-alpha-2b. Despite poor results in controlling the disease and the existence of safer, more effective natural treatments, physicians continue to use this toxic treatment. Of major concern are the neurologic effects of the treatment.

Acute Problems

It is known that interferons have two patterns of injury to the brain. One is acute and occurs within hours of treatment, often lasting for the first one to three weeks of the treatment. This usually includes fever, chills, headache and fatigue.

Chronic Problems

This is followed by a chronic phase in which more serious injuries to the nervous system result. Chronic symptoms can include malaise, lethargy, somnolence, headaches, low-grade fevers, anorexia (loss of appetite) and more serious symptoms such as psychomotor symptoms, cognitive problems, psychiatric behaviors and even delirium and coma.

Brain Toxicity

The severity of symptoms depends on the dose of the interferon and manner of administering the medication. Continuous infusion of high-dose interferons is associated with more severe neurologic problems. It is known that chronic brain toxicities occur at all doses but more so after doses higher than 18 million to 20 million units a day.Most common is severe fatigue.

Even lower doses have been associated with a lack of drive and disinterest in participating in normal activities, a process called psychomotor retardation. This occurs in anywhere from 47 percent to 80 percent of patients. Changes in the ability to think clearly (cognitive changes) are frequently seen in patients treated with as little as 9 million units of interferon per week. The difficulty with thinking reaches a peak at one to three months. This can include a decreased attention span, difficulty concentrating, defective short-term memory and mental clouding.

Studies have described frequent periods of silence and vacant staring, occurring even in mid-sentence. Objective testing for recall and cognitive function have shown an incidence of 17 percent to 50 percent in patients receiving standard doses of interferons. Most of these cognitive difficulties do improve, yet there are reports of persistent impairments lasting up to two years following cessation of treatment.

In some patients the effect is so severe on the brain that patients sleep up to 20 hours a day and during waking periods experience disorientation and confusion. Speech difficulties (expressive dysphasia) and problems with balance have also been reported. On rare instances, these neurological effects have progressed to a demented state. Hallucinations have also been reported.

It is important to appreciate that the patients in the first two categories to be described had no previous psychiatric history. Renault and co-workers, who examined many of these patients, divided the neurobehavioral effects into three syndromes: organic personality syndrome, organic affective syndrome and delirium effects. Patients with organic personality syndrome frequently experience uncontrollable overreaction to minor frustrations, are very irritable and have a short temper.

Depression Common

Those with the organic affective syndrome often describe feelings of depression and hopelessness. They cry easily and have difficulty interacting socially with others. Patients experiencing delirium have a clouding of their thinking, have short-term memory problems and have frequent mood changes. Many become severely agitated, abusive, withdrawn and may exhibit suicidal thoughts, delusions of being persecuted and phobias. Patients having delirium symptoms often had co-existing liver disease, history of psychiatric disorder or previous brain injury.

Severe Reactions in Cancer Treatment

The most severe effects have been seen in patients treated for cancers. In these patients death due to encephalopathy (widespread brain injury) and associated seizures have been described. This may be a result of combined toxicities of radiation, chemotherapy and interferon.

Interferon-gamma is less toxic than the alpha or beta-interferons. With higher doses one can see chronic neurotoxicities, which can include dizziness, slowed thinking, confusion, crying spells, and even symptoms resembling Parkinson's disease.

How Interferon Ruins Your Brain

The mechanism of this injury to the brain appears to involve the brain's special immune cell called the microglia. Normally, these cells remain dormant in the brain. That is, they are sleeping. Microglia cells can be activated by numerous factors, including mercury, aluminum, iron, overvaccination, and brain trauma, strokes, infections (viruses, bacteria, rickettsia) and cytokines such as interferons.

Once activated, microglia can move about the brain secreting very toxic compounds, which include two excitotoxins (glutamate and quinolinic acid). These excitotoxins dramatically increase free radical generation in the brain as well as oxidation of lipids (called lipid peroxidation). These radicals damage synaptic connections, interfere with neurotransmitters and can even kill neurons. In addition, these activated microglia generate other toxic compounds such as prostaglandins (PGE2), which increase brain inflammation.

If the microglia activation is short lived, the damage to the brain is minimal and recovery takes place. Yet, should the activation continue, which would occur with high-dose and long-term use of interferons, the damage could be substantial and irreversible. Protecting the brain with high-dose and varied antioxidants as well as certain metabolic stimulants can substantially reduce this damage. Certain nutrients, such as malate, pyruvate, DHA, ascorbate, magnesium and methylcobalamin inhibit excitotoxicity.

Physicians Frequently Miss Side Effects

Physicians often ignore patient complaints of neurological difficulties during interferon treatments, assuming they are benign and reversible. As stated in the beginning, natural alternatives have been shown to be much more effective and dramatically safer than interferon treatments.

References

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