NIH panel issues consensus statement on HCV

With no vaccine in sight, 4 million infected in U.S.

Without effective clinical interventions, the death toll of 8,000 Americans annually from hepatitis C virus infection is expected to triple in the next 10 to 20 years, the Bethesda, MD-based National Institutes of Health recently reported.1

The NIH convened a panel of hepatitis experts and developed a consensus statement on current management strategies for HCV. Highlights and recommendations from the NIH statement — which should be viewed as state-of-the-art clinical guidance rather than formal public health recommendations — are summarized as follows:

Nearly 4 million Americans are infected with HCV. The incidence of HCV appears to be declining since its peak in 1989; however, approximately 30,000 new infections are diagnosed each year. HCV accounts for 20% of all cases of acute hepatitis and is the leading cause of liver transplantation in the United States.

The disease is transmitted primarily by parenteral means, and is not easily cleared by the host’s immunologic defenses. Thus, a persistent infection develops in perhaps as many as 85% of patients with acute HCV. There is no vaccine to prevent HCV infection. The host’s inability to clear the virus sets the stage for the development of chronic liver disease. The range of disease states following HCV infection is broad. HCV can lead to chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The course of illness may be adversely affected by various factors, especially alcohol consumption. Therefore, patients with HCV are strongly discouraged from taking more than one drink per day, and abstinence from alcohol is recommended.

Recommendations to prevent transmission

• In health care settings, adherence to universal (standard) precautions for protection of medical personnel and patients is essential.

• HCV-positive people should refrain from donating blood, organs, tissues, or semen. Strategies should be developed to identify prospective blood donors with any prior history of injection drug use. Such individuals must be deterred from donating blood. In some situations, the use of organs and tissues from HCV-positive individuals may be considered.

• To avoid transmission in people with multiple sexual partners, safe sexual practices, including the use of latex condoms, should be strongly encouraged. Transmission is of low likelihood in monogamous long-term relationships, and therefore no changes in sexual practices are recommended. In such cases, an individual’s decision to modify sexual practices should follow a discussion of the potential risks of transmission. It is recommended that sexual partners of infected patients should be tested for HCV antibodies.

• In households with an HCV-positive member, the sharing of razors and toothbrushes should be avoided. Covering of open wounds is recommended. It is not necessary to avoid close contact with family members or to avoid the sharing of meals or utensils.

• Pregnancy is not contraindicated in HCV-infected individuals. Perinatal transmission from mother to baby occurs in less than 6% of instances. Babies born to HCV-positive mothers should be tested for anti-HCV at one year. Breast-feeding is considered safe.

• Needle-exchange programs are of proven benefit in reducing parenterally transmitted diseases. Expansion of such programs should be considered in an effort to reduce the rate of transmission of HCV.

• There is no evidence to justify exclusion of HCV-positive children or adults from participation in social, educational, and employment activities.

Testing and treatment options

• The second-generation enzyme immunoassay (EIA-2) should be the initial test for the diagnosis of HCV. In low-risk populations, supplemental recombinant immunoblot assay (RIBA-2) and/or HCV RNA polymerase chain reaction (PCR) testing should be performed. In patients with clinical findings of liver disease, qualitative HCV RNA PCR can be used for confirmation.

• Liver biopsy is indicated when histologic findings will assist decision making regarding patient management. In patients who are not treated with antiviral therapy initially, liver biopsy can be repeated to assess disease progression.

• HCV genotyping may provide useful prognostic information, but at present must be considered a research tool.

• Because of assay variability, HCV RNA PCR testing must be interpreted cautiously. Rigorous proficiency testing of clinical laboratories performing this assay is recommended.

• Currently available therapy for chronic HCV is clearly indicated for patients who have persistently abnormal serum alanine aminotransferase (ALT) for more than six months, a positive HCV RNA, and liver biopsy evidence of septal fibrosis and/or moderate to severe necroinflammatory changes. Patients with milder histological disease, compensated cirrhosis, or age under 18 or over 60 should be managed on an individual basis or in the context of clinical trials. Patients with decompensated cirrhosis should not be treated with interferon but should be considered for liver transplantation. Patients with persistently normal ALT should not be treated outside of clinical trials. Treatment with interferon is contraindicated in patients with a history of major depressive illness, cytopenia, active alcohol use or illicit drug use, hyperthyroidism, renal transplantation, or autoimmune disease. Therapy should not be limited by mode of acquisition, risk group, HIV status, HCV RNA levels, or genotype.

• Because 12-month regimens with interferon are more successful in achieving sustained responses, initial therapy with interferon alpha (or its equivalent) should be 3 million units thrice weekly subcutaneously for 12 months.

• Non-responders to interferon therapy can be identified early by assessing the serum ALT level and presence of serum HCV RNA after three months of therapy. If the ALT level remains abnormal and the serum HCV RNA remains detectable, interferon therapy should be stopped, as further treatment is unlikely to produce a response. Non-responders should not receive further therapy with interferon alone, but should be considered for combination therapy or enrollment in investigational protocols.

• Patients who relapse should receive retreatment with their original therapy or combination interferon-ribavirin therapy, preferably in a clinical trial.

• Hepatitis A and B vaccination is recommended for all HCV-positive patients.

• Patient support groups should be encouraged.

Reference

1. National Institutes of Health. Consensus Development Conference Statement: Management of Hepatitis. Bethesda, MD; March 27, 1997.