Medical Edge Newspaper Column

Hepatitis C Treatment: An Ordeal Worth Enduring

March 12, 2007
Dear Mayo Clinic:
I am a 55-year-old male diagnosed with hepatitis C virus (genotype 1) in 1994. Liver biopsies in 1996 and 1999 showed mild inflammation. Now, a biopsy shows progression to grade-2 chronic hepatitis with stage-2 fibrosis, and I am deeply concerned about this. I have heard about interferon treatment with ribavirin, but am concerned about side effects. What other options may be available in the near future, and will any have fewer side effects? -- Tucson, Arizona

Answer:
Of the six known hepatitis viruses, hepatitis B and C are responsible for the great majority of persistent infections that result in inflammation and scarring of the liver, thereby compromising its function. Over time, usually decades, hepatitis C virus (HCV) infection can lead to cirrhosis (widespread scarring of liver tissue), liver failure or liver cancer. The virus is primarily transmitted by means of contaminated blood -- through blood transfusions, for example, or needles shared by drug users.

People with HCV may experience symptoms such as fatigue, nausea, low-grade fever and persistent or recurring yellowing of the skin and eyes (jaundice). Many patients with HCV infection, however, report few or no symptoms. This virus tends to do its nasty work in silence; it can damage the liver, sometimes extensively, even in the absence of symptoms.

If routine tests show only slight liver abnormalities, some doctors may decide against medical treatment at that point because the patient's long-term risk of developing a serious disease is slight. But given the details you provide in your question, now is a good time for you to consider treatment. Grade 2 and stage 2 respectively indicate significant, though moderate, amounts of liver-tissue inflammation and fibrosis (scar formation), both of which are measured on a scale of 0 to 4. Progression is no longer mild enough to ignore, and the benefits of treatment outweigh the risks -- it could reduce or prevent any further damage.

The standard of care for hepatitis C treatment is indeed interferon combined with ribavirin (Rebetol). Interferon (brand name: Peg-Intron or Pegasys) is a protein that stimulates the immune system to attack invaders such as HCV. Although ribavirin doesn't appear to have antiviral properties against hepatitis C when used alone, in combination with interferon it acts to prevent the HCV infection from returning once it has been cleared by the interferon.

Most patients have reasonably good prospects with this combination therapy, and in many cases it causes the virus to disappear altogether. HCV has six main "genotypes," or variants. Among genotype 1 patients, therapy will eliminate the virus some 40 percent to 50 percent of the time, and even more often -- 75 percent to 80 percent -- in genotype 2 or 3 patients.

But as you note, there is a price to pay. Interferon side effects almost always include flu symptoms (which occur because the immune system has been stimulated) and may also include diarrhea, weight loss, reduced white blood cell and platelet counts, irritability, depression, insomnia, and problems with concentration and memory. Ribavirin can cause a low red blood cell count and gout. Both drugs can lead to skin irritation and extreme fatigue. Moreover, genotype 1 patients usually require higher drug doses and a longer course than do "non-1" patients.

Although side effects can be quite unpleasant in some cases, other patients hardly notice any. Either way, there are medications and strategies for substantially reducing virtually all of these effects. Only about 7 percent of HCV patients undergoing combination therapy need to stop it.

Other medications are in the pipeline. Two classes in particular -- protease inhibitors and polymerase inhibitors -- show particular clinical promise. One drug in each class is currently in Phase III trials (with human patients) and, if successful, could be approved by the FDA in about two years. Both of these drugs, as well as others under development, will likely be used in combination with interferon too, though possibly at lower doses and for shorter duration.

-- Michael R. Charlton, M.D., Gastroenterology, Mayo Clinic, Rochester, Minn.