Hepatitis C

Overview

Most people with an acute hepatitis C infection aren't treated. Often, they don't even realize they're sick until the disease has become chronic, and even when they do, treatment may not be advised. When liver disease is mild, the medications' side effects (and the fact that the drugs are not always effective) often tip the balance toward a wait-and-see approach. But recent studies indicate that early treatment with pegylated interferon (a long-acting form of interferon alpha) and ribavirin improves the clearance of virus from the bloodstream.

With chronic hepatitis C, the goal of treatment is to use medication to eliminate the virus. Eliminating the virus makes it possible to decrease the progression of fibrosis of the liver and the risk of developing liver cancer. In certain cases in which the viral load is decreased but not eliminated, it is thought that long-term "suppressive" therapy may be of benefit to thwart disease progression and prevent the development of liver cancer. Clinical trials are underway to test this hypothesis. In patients with manifestations of disease beyond the liver, there is an additional goal of relieving symptoms.

This section discusses

Drug therapy

Controversies about treatment

Liver transplantation

Drug Therapy

The decision to initiate treatment should occur only after a thorough medical evaluation and extensive discussion between the clinician and patient to review risks and benefits of medical therapy. People who are infected but show no signs of liver damage may not be appropriate candidates for drug treatment.

Hepatitis C is usually treated with a long-acting form of interferon alpha called pegylated interferon, combined with the antiviral drug ribavirin. Interferon alpha is a protein that cells secrete naturally in response to viruses; it results in a stronger immune response and interferes with the virus's ability to replicate. The pegylated interferon is injected once a week; ribavirin is taken by mouth twice daily.

Depending on the type or "genotype" of hepatitis C virus a person has contracted, treatment may be necessary for six months to a full year; even then, not all treated patients can achieve a "sustained response," meaning no virus can be detected in their bloodstream. Treatment success is achieved when no virus is detectable in the blood 24 weeks after the end of treatment; depending on the genotype of the virus, therapy is successful in 40 percent to 80 percent of cases. This represents a significant improvement over the track record of past therapy.

Interferon and ribavirin, however, cause numerous adverse side effects. The impact of these adverse effects on a given individual can be unpredictable. Certain medical conditions generally preclude treatment with interferon and ribavirin. These include, but are not limited to, severe heart disease, kidney disease, poorly controlled psychiatric disease, ongoing infection, autoimmune disease, pregnancy or planned pregnancy, and blood disorders such as a low red blood cell count, low white cell count, or low platelets. Treatment, even in otherwise very healthy patients, requires close monitoring to ensure safety. This includes frequent blood work and office visits.

Among the factors associated with higher likelihood of elimination of the virus are a low amount of virus in the blood at diagnosis, body weight of less than 165 pounds, non-African American race, minimal fibrosis or hardening of the liver on biopsy, the ability to tolerate full-dose medicine for the length of treatment, and infection with a type of hepatitis C known as "non-1 genotype." A small number of patients may experience a recurrence months or years after treatment has succeeded. It is uncertain if this represents reinfection or reactivation of disease.

Liver Transplantation

Liver transplantation is reserved for patients with advanced and irreversible liver disease. Patients with complications related to chronic hepatitis or cirrhosis should be referred to medical centers specializing in liver transplantation for evaluation. This should be done before the onset of terminal liver disease. Transplantation can dramatically prolong and improve quality of life for patients in advanced stages of this disease, which would otherwise be untreatable. Hepatitis C is the leading indication for liver transplantation in the United States. If possible, treatment with interferon and ribavirin to reduce or eliminate the virus prior to transplantation is optimal. Although transplantation cures the cirrhosis, the hepatitis C infection persists, and reinfection of the new liver is universal.

Patients who are deemed to be good candidates for a transplant are placed on a waiting list and scored by severity of disease. The donated liver may come either from a living person, who provides a piece of his own liver (in both parties, the divided liver grows to normal size again within a short time), or from a cadaver. The operation itself may take as long as 12 hours and requires antirejection drugs afterward to prevent the patient's immune system from attacking the unfamiliar tissue.

Controversies Over Treatment

Clinicians, even those who are expert at treating liver disease and hepatitis C, may disagree about the best course of treatment. In some patients, medical conditions may increase the risk of treatment somewhat but not entirely eliminate the possibility. These "relative" contraindications may change over time as new research becomes available and clinicians gain experience with interferon and ribavirin. Cirrhosis is an example. Until recently, clinicians avoided treating patients with cirrhosis because of concern that the side effects would be intolerable and the liver disease would worsen. Now, however, many clinicians believe that patients with early cirrhosis can tolerate treatment.

Likewise, some patients previously treated with interferon alone may be considered for retreatment with the combination protocol, or doctors may want to try a different pegylated interferon product. However, there is no general agreement as to whether retreatment is effective or cost-effective.

For people with normal liver enzymes, there is disagreement over whether treatment is called for. Some doctors believe that patients with persistently normal liver enzymes have a relatively benign prognosis and that the side effects of the drugs are not worth any minimal benefit. Others, however, note that patients can develop scarring and even cirrhosis in the presence of normal liver enzymes and believe that everyone should be treated.