Considerations for therapy
The National Institutes of Health Consensus Conference concluded that all patients with chronic HCV infection should be considered for antiviral therapy, but it was recognized that decision to treat must be individualized. Factors influencing this decision include the expected rate of disease progression in the absence of treatment, the likelihood of achieving viral eradication or other treatment benefits, the presence of relative or absolute contraindications to receipt of interferon or ribavirin, and the motivation and expected compliance of the patient.
Because only a proportion of patients with chronic hepatitis C progress to cirrhosis, and antiviral therapy is not effective in all patients, identification of those at increased risk for cirrhosis and liver-related complications may be useful in evaluating the risks vs benefits of antiviral therapy. Although certain factors have been associated with worse disease severity, they are not predictive enough to be used in individual treatment decisions. The finding of moderate inflammation and portal or bridging fibrosis on liver biopsy examination usually is indicative of increased risk for disease progression. For patients with cirrhosis, treatment is indicated if the disease is well compensated. For patients with de-compensated cirrhosis, antiviral therapy is not recommended outside of clinical trials because of poor tolerability and a risk of serious complications, especially infections.
Approximately 30% of HCV-infected individuals have persistently normal ALT levels and such patients typically have mild histologic disease. Nonetheless, some may have or progress to advanced liver disease. Treatment results in patients with persistently normal ALT levels are equivalent to those with abnormal ALT levels, and increases in ALT levels, and increased in ALT levels during or after treatment occur in the minority of patients. Therefore, patients with normal ALT levels require an individualized assessment or risk-benefit regarding liver biopsy examination and antiviral treatment. Lastly, in considering antiviral therapy, one needs to consider potential contraindications to the use of interferon (IFN) and ribavirin. Historically, active substance use or depression was considered absolute contraindications for treatment with IFN-based therapy. However, more recent trials have shown that comparable efficacy and tolerability can be achieved in these patients, especially with use of concomitant treatment for drug use and depression. Therefore, the populations being considered for antiviral therapy are expanding.