Hepatitis C Virus: The Silent Epidemic, Part Three

From June 10-12, 2002, the NIH Consensus Development Conference - Management of Hepatitis C: 2002 was held at the NIH campus in Bethesda, Maryland. The two-and-a-half-day conference was an important development for all who are infected and/or affected by hepatitis C. Since 1997, when the last Consensus Development Conference on hepatitis C was held, there has been a vast increase in hepatitis C virus (HCV) diagnosis within the U.S. population, and marked improvements in Western pharmaceutical therapies for hepatitis C.

The conference examined the current state of knowledge regarding management of HCV and identified future research directions. A final statement from the conference was released on August 26, 2002.

For one-and-a-half days, experts presented the latest hepatitis C research findings to a nonadvocate, nonfederal panel.¹ After weighing all of the scientific evidence, the panel drafted a statement and addressed the following questions:

1. What is the natural history of hepatitis C?
2. What is the most appropriate approach to diagnose and monitor patients?
3. What is the most effective therapy for hepatitis C?
4. Which patients with hepatitis C should be treated?
5. What recommendations can be made to patients to prevent transmission of hepatitis C?
6. What are the most important areas for future research?²

On the last day, the panel chair read the draft statement to the conference audience. Advocates, physicians and people with HCV then had an opportunity to make comments and suggestions for the panel's consideration.

The NIH Consensus Statement was a powerful message for people with hepatitis C, and gave good guidelines for Western diagnosis and treatment and, most importantly for NIH, questions for future research. Many of the HCV activists, progressive-thinking physicians and caregivers were happy at how well thought out the preliminary draft consensus statement was.

Panel Conclusions

• The incidence of new hepatitis C infections has diminished in the U.S. This is largely due to a decrease among injection drug users (IDUs) and to testing of blood donors for HCV.
• Transmission now occurs primarily through injection drug use; sex with an infected partner or multiple partners; and occupational exposure. Most infections become chronic, and the prevalence of HCV infections is high, with about 3 million Americans chronically infected.
• HCV is a leading cause of cirrhosis, a common cause of hepatocellular carcinoma (HCC) and the leading cause of liver transplantation in the U.S.
• Chronic hepatitis C infection often is diagnosed first on the basis of abnormalities in alanine aminotransferase (ALT) levels; is established by an HCV antibody test; and is confirmed by a viral load test. Although there is little correlation between viral level and disease manifestation, the viral load assays are useful in identifying patients more likely to benefit from treatment and, particularly, in demonstrating successful response to treatment as defined by a sustained viral response (SVR).
• Liver biopsy is useful in defining baseline abnormalities of liver disease and in enabling patients and health care providers to reach a decision regarding antiviral therapy. Noninvasive tests do not currently provide this information.
• Information on the genotype of the virus is important to guide treatment decisions. Genotype 1, most commonly found in the U.S., is less amenable to treatment than genotypes 2 or 3. Clinical trials of antiviral therapies should require genotyping information for appropriate stratification of subjects.
• Trials using pegylated interferons have yielded improved SVR rates. Results continue to show that the SVR rate is less common in patients with genotype 1 infections, higher HCV RNA levels, or more advanced stages of fibrosis.
• Ongoing trials are exploring the usefulness of combination drug therapy in various populations. Preliminary experience in IDUs; HIV co-infected individuals; children; and other special groups suggests similar responses are achievable in these populations. Patients with acute hepatitis C may be treated, but specific recommendations cannot yet be determined.
• Preventive measures include prompt identification of infected individuals; awareness of the potential for perinatal transmission; implementation of safe injection practices; linkage of drug users to drug treatment programs; and implementation of community-based education and support programs to modify risk behavior. Some of these measures have been successfully implemented in the control of HIV infections, and would be valuable for reducing HCV transmission.
• Future advances in the diagnosis and management of hepatitis C require continued vigilance concerning the transmission of this infection, extending treatment to populations not previously evaluated in treatment trials and the introduction of more effective therapies.

Panel Recommendations

• Educate the American public on the transmission of HCV to better identify affected individuals and institute preventive measures.
• Develop reliable, reproducible and efficient culture systems for propagating HCV, and expand basic research in the pathogenic mechanisms underlying hepatic fibrosis.
• Promote the standardization and wide availability of diagnostic tests for HCV infection and its complications, which will lead to early diagnosis and the implementation of appropriate treatment practices.
• Promote the establishment of screening tests for all groups at high risk of HCV infection, including IDUs and incarcerated individuals.
• Expand the delineation of disease manifestations, noninvasive tests and the role of the liver biopsy, so that the application of current treatment practices may be refined.
• Establish a hepatitis clinical research network for the purpose of conducting research related to the natural history, prevention and treatment of hepatitis C.
• Organize randomized, controlled trials to extend treatment to special populations not represented in current clinical trials and to determine the applicability of accepted antiviral drug combinations to populations such as children, adolescents and patients with acute hepatitis. Effective approaches are needed for drug users receiving drug treatment; alcohol abusers; prisoners; patients with stabilized depression; those co-infected with HIV; patients with decompensated cirrhosis; and HCV-infected transplant recipients. Such efforts should lead to decreased morbidity and mortality from the disease, and a decrease in the reservoir of disease.
• Institute measures to reduce transmission of HCV among IDUs, including providing access to sterile syringes through needle exchange, physician prescription and pharmacy sales; and expanding the nation's capacity to provide treatment for substance abuse. Physicians and pharmacists should be educated to recognize that providing IDUs with access to sterile syringes and education in safe injection practices may save lives.
• Evaluate strategies to prevent mother-infant transmission of HCV.
• Compare new therapies to current treatments in nonresponders, to include not just antiviral agents, but also combinations of antifibrotic drugs, immunomodulatory agents and alternative therapies.
• Encourage a comprehensive approach to promote collaboration among health professionals concerned with management of addiction, primary care physicians and specialists involved in various aspects of HCV to deal with the complex societal, medical and psychiatric issues of IDUs afflicted by the disease.
• Seek appropriate support from government agencies and the private sector to address urgent research questions concerning the epidemiology and treatment of this disease.³

Chinese Medicine, Alternative Therapies and the NIH Consensus Statement

During the conference, there was little mention of complementary and alternative therapies for hepatitis C, including Chinese traditional medicine. This was primarily due to the lack of reliable documented evidence associated with these therapies in hepatitis C. Although a number of small studies have been conducted using the Western herb (standardized) milk thistle in the form of silymarin, as a group the studies are inconclusive as to the long-term effects of milk thistle. Also, many anecdotal reports in the United States and studies from China have reported on the efficacy of Chinese herbal medicine in the treatment of HCV and other forms of hepatitis. There have never been controlled human clinical trials conducted within the U.S. on the quality necessary for conclusive evidence-based treatment protocols. However, the NIH consensus statement did conclude that "alternative therapies" needed to be researched more fully.

The final statement may be read and downloaded at the NIH's website at http://consensus.nih.gov/cons/116/Hepc091202.pdf

References

1. NIH Consensus Development Program Consensus Statement Overview: Management of Hepatitis C: 2002. Available at http://consensus.nih.gov/cons/116/116cdc_intro.htm.
2. NIH Consensus Development Conference: Management of Hepatitis C: 2002. Handout.
3. NIH Consensus Development Program Consensus Statement Overview: Management of Hepatitis C: 2002.