Hepatitis - Hepatitis C

Other agents under investigation include vaccines, genetic therapies known as antisense oligonucleotides or monoclonal antibodies, and drugs that will help prevent or reduce progression of liver scarring or progression to liver cancer. Even if successful, none of these agents would be available for some years.

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Of interest are studies using phlebotomy (which is simply drawing blood) to reduce iron levels. In one study, maintenance therapy with this procedure reduced liver inflammation and possible slowed progression of cirrhosis.

Liver Transplantation for Hepatitis C. If the disease progresses to the point where it becomes life-threatening, liver transplantation may be an option. In fact, nearly 40% of liver transplant patients are infected with hepatitis C. In any case, liver transplantation is not a cure for hepatitis C. The virus nearly always returns. One study of patients with hepatitis C reported five-year risks for viral recurrence of 80% and for cirrhosis of 10%. A 2004 study found that the hepatitis C virus recurs with more severity with liver donations from living donors than livers taken from cadavers. Retreatment with antiviral agents is being investigated.

Description of Interferons

Interferons are natural proteins that activate certain immune functions in the body and have anti-viral properties. The natural interferons being used for chronic hepatitis B, C or both are called type I interferons. They are given by injection, need to be taken three times a week, and include the following:

Interferon alpha 2b (Intron A). Used for both hepatitis B and C.
Interferon alpha 2a (Roferon-A). Mostly used for hepatitis C.
Interferon alfa-n1 (Wellferon). Approved but mostly used in Canada for hepatitis C.

Newer synthetic interferons have been developed that are showing some advantages over the natural forms:

Pegylated interferon (PegINF). Pegylated interferons employ a small molecule called polythelene glycol (PEG), which attaches to a protein and extends the activity of the interferon. This action allows the drug to be taken only once a week. Agents available include pegylated interferon alfa-2b (Peg-Intron) and alfa-2a (Pegasys).
Interferon alfacon-1 (Infergen). This agent is referred to as a consensus interferon (CIFN) because it was genetically developed using the most commonly occurring amino acid sequences from each of the natural type 1 alpha interferons. It is five to 10 times more biologically active than natural type 1 interferons. CIFN is usually given three times a week when used as initial treatment.

Interferon Candidates

The best candidates for interferon treatments are those at greatest risk for cirrhosis. Factors suggesting a higher risk for cirrhosis include the following:

Detectable virus levels as determined by an assay test.
High levels of aminotransferase enzyme for more than six months. (Those with normal liver enzyme levels appear to have almost no risk for liver damage, even if the virus is evident. In the latter case, however, the disease may progress in some patients. Whether to treat these patients is still under debate.)
Indication of liver scarring on biopsy.

Patients who are not good candidates for interferon and are usually ineligible are the following:

Women who are pregnant or planning to become pregnant soon.
Patients with advanced cirrhosis. (It is unclear if the drug improves survival in patients with advanced cirrhosis and, in any case, it may be dangerous for them.)
Patients with fluid in the abdomen.
Patients with anemia or risk factors for anemia should not take the combination treatments, although they may be candidates for interferon alone.

The response of children to interferon may be better than those in adults, although large studies are needed to confirm this and to uncover any possible long-term complications of the drugs. At this time, children are given interferons only as part of clinical trials.

A number of patients are currently ineligible for treatment because of the high risk for noncompliance and because of the severe psychiatric effects of the drugs. They include patients with psychiatric and medical problems and substance abusers. Some experts suggest that many of these individuals may be eligible and there should be greater efforts to determine more candidates. For example, many alcohol and drug users have been successfully treated even if they have not consistently abstained or if they were on methadone at the time. It is unclear whether treatment is useful in active drug users, although this should be considered on a case-by-case basis. Even moderate alcohol use can compromise treatment and accelerate disease progression.

Disease Recurrence

In both hepatitis B and C, the disease often persists or returns despite treatment. The virus continually generates many ?mutant viruses? that differ just slightly from the parent virus. These mutated viruses may be resistant to interferons and so, over time, the drugs become ineffective.

Side Effects and Complications

Common side effects of any interferon are flu-like symptoms (fever, chills, muscle aches) that usually occur within six hours and gradually decline over a week or two. (Pegylated interferon may pose a higher risk for these symptoms than the natural interferons.)

Chronic or more serious effects include the following:

Emotional and mental changes. Depression can be very severe and cases of suicidal thoughts have been reported. Other mental and emotional symptoms include anxiety, amnesia, confusion, irritability, impaired concentration, decreased alertness, memory problems, and mental slowing.
Changes in sensation.
Weight loss.
Skin rashes.
Hair loss.
Gastrointestinal problems, including nausea, vomiting, and diarrhea, and, in severe cases intestinal bleeding and ulcers.
Fatigue and general weakness.
Back pain.
Complications in the lungs, including exacerbation of asthma. In severe cases, interferon can cause shortness of breath, inflammation in the lungs, and pneumonia.
Possible negative effects on cholesterol and lipid levels.
Heart rhythm disturbances, which, in rare cases, can be serious.
Mild anemia.
Interferon often causes a drop in platelet and white blood cell counts, increasing susceptibility to bacterial infections. Growth factors are being investigated to reduce this effect.
May trigger an autoimmune response, possibly causing anemia, diabetes, lupus-like symptoms, hypothyroidism, or even autoimmune hepatitis.
Complications in the eye, including bleeding that, in some cases, may lead to loss of vision if not detected promptly.
Rare reports of acute pancreatitis.
In children, interferon therapy temporarily disrupts growth.

Patients have a difficult time with prolonged therapy. Over 20% drop out if treatment lasts longer than two years. Depression is the most common reason for withdrawal.

A number of different methods for delivering interferons are under investigation to help reduce some of the problems with injections. They include oral compounds and the use of pumps, controlled release implants, encapsulation in tiny fatty or synthetic spheres, and other methods.

Warnings on Alternative and So-Called Natural Remedies

Many patients with serious or chronic diseases are now investigating alternative medications. Among the natural substances being investigated for hepatitis are ginseng, glycyrrhizin (a compound in licorice), catechin (found in green tea), and silymarin (found in milk thistle). A 2001 review analyzed studies on ten herbal remedies for hepatitis C. None showed significant benefits except silymarin, which improves liver enzyme levels. Other studies are also reporting benefits on the liver from silymarin.

Alternative or natural remedies are not regulated and their quality is not publicly controlled. In addition, any substance that can affect the body's chemistry can, like any drug, produce side effects that may be harmful. Even if studies report positive benefits from herbal remedies, the compounds used in such studies are, in most cases, not what are being marketed to the public.

There have been a number of reported cases of serious and even lethal side effects from herbal products. In addition, some so-called natural remedies were found to contain standard prescription medication. The following warnings are of particular importance for people with hepatitis:

Kava (an herb used for anxiety and tension) can be toxic to the liver and cause severe hepatitis and even liver failure if taken excessively.
Black licorice (not the red candy) can increase blood pressure and may be harmful in people with hypertension.

Consumer Lab (www.consumerlab.com ) is building a database of natural remedy brands that it tests and rates. Not all are available yet. The Food and Drug Administration has a program called MEDWATCH for people to report adverse reactions to untested substances, such as herbal remedies and vitamins. Call 800-332-1088.