Hepatitis C virus (HCV) infection, which is common in the United States, is a major cause of end-stage liver disease and death. Current treatment is eradication of HCV infection using interferon-based treatment regimens. Long-term viral response using either interferon-a plus ribavirin or pegylated interferon is estimated to be 30 to 40 percent. Most study subjects are strictly selected and do not adequately represent subgroups of the population with a high incidence of HCV infection. Underrepresented groups include patients with alcohol or substance abuse, children, homeless or incarcerated patients, elderly patients, and persons with autoimmune or psychiatric disorders. Positive HCV responses seen in treatment studies cannot be generalized to these populations. Falck-Ytter and associates studied the treatment rate for HCV infection among patients at a metropolitan liver clinic.
Treatment criteria included a positive test for HCV RNA and two elevated alanine aminotransferase or aspartate aminotransferase levels during the previous six months. Patients were excluded if they had decompensated cirrhosis, other types of liver disease, or active alcohol or drug use; if they missed more than two visits during the period before study enrollment; and if they had poorly controlled psychiatric or seizure disorders, auto-immune disease, symptomatic cardiac disease, low neutrophil or platelet counts, retinopathy, or cancer.
Of the 293 eligible patients, 72 percent could not be treated because of the high incidence of nonadherence to visits, medical contraindications, substance abuse, normal ala-nine aminotransferase levels, and patient choice. Only 83 of the patients (28 percent) were treated with an interferon-based regimen. Eleven patients had sustained viral response (undetectable HCV RNA levels six months after treatment completion). Therefore, the viral response rate for the study population was only 4 percent. Fifteen patients stopped treatment because of side effects, and five were lost to follow-up.
The authors conclude that interferon-based therapies may be less useful in a large proportion of patients with HCV infection because of the high rate of exclusion criteria among this group. Other approaches to management of HCV infection include (1) better tolerated medications, (2) more targeted screening programs, and (3) educational efforts to improve treatment adherence and decrease detrimental comorbid conditions.
editor's note: New treatments are increasingly successful in diminishing the hepatic destruction caused by chronic hepatitis B infection. Interferon and ribavirin combination therapy, substitution of amantadine for ribavirin, and the use of pegylated interferon have provided good results with combination therapies, offering a greater sustained virologic response than single-drug treatment. Combinations have been safe and well tolerated, but patients must be monitored for hemolytic side effects, depression, and weight and lipid profiles. Appropriate selection of patients for treatment can be difficult because of drug toxicities and the importance of regular dosing compliance for a long time.
Backmund and associates described a program in which opiate-dependent injection drug users with chronic HCV infection were successfully treated with interferon or interferon plus ribavirin during detoxification. Patients were supervised by a hepatologist and a physician specializing in addiction medicine. The sustained virologic response was similar to that obtained in a non-drug-using population and did not differ in patients who relapsed. The authors concluded that drug addicts infected with HCV can be successfully treated if the proper medical supervision and support are available. This implies that some treatment exclusion criteria can be overcome by proper treatment design, making the treatment of HCV available to a larger group of patients.—r.s.