NIH Consensus Statement on Management of Hepatitis C: 2002.

OBJECTIVE

To provide health care providers, patients, and the general public with a responsible assessment of currently available data regarding the management and treatment of hepatitis C.

PARTICIPANTS

A non-Federal, nonadvocate, 12-member panel representing the fields of infectious diseases, gastroenterology, medical oncology, molecular genetics, geriatrics, internal medicine, and the public. In addition, experts in these same fields presented data to the panel and to a conference audience of approximately 300.

EVIDENCE

Presentations by experts; a systematic review of the medical literature provided by the Agency for Healthcare Research and Quality; and an extensive bibliography of hepatitis C research papers, prepared by the National Library of Medicine. Scientific evidence was given precedence over clinical anecdotal experience.

CONFERENCE PROCESS

Answering predefined questions, the panel drafted a statement based on the scientific evidence presented in open forum and the scientific literature. The draft statement was read in its entirety on the final day of the conference and circulated to the experts and the audience for comment. The panel then met in executive session to consider these comments and released a revised statement at the end of the conference. The statement was made available on the World Wide Web at http://consensus.nih.gov immediately after the conference. This statement is an independent report of the panel and is not a policy statement of the NIH or the Federal Government.

CONCLUSIONS

The incidence of newly acquired hepatitis C infection has diminished in the United States. This decline is largely due to a decrease in cases among IDUs for reasons that are unclear and, to a lesser extent, to testing of blood donors for HCV. The virus is transmitted by blood and such transmission now occurs primarily through injection drug use, sex with an infected partner or multiple partners, and occupational exposure. The majority of infections become chronic, and therefore the prevalence of HCV infections is high, with about 3 million Americans now estimated to be chronically infected. HCV is a leading cause of cirrhosis, a common cause of HCC and the leading cause of liver transplantation in the United States. The disease spectrum associated with HCV infection varies greatly. Various studies have suggested that 3 to 20 percent of chronically infected patients will develop cirrhosis over a 20-year period, and these patients are at risk for HCC. Persons who are older at the time of infection, patients with continuous exposure to alcohol, and those co-infected with HIV or HBV demonstrate accelerated progression to more advanced liver disease. Conversely, individuals infected at a younger age have little or no disease progression over several decades. The diagnosis of chronic hepatitis C infection is often suggested by abnormalities in ALT levels and is established by EIA followed by confirmatory determination of HCV RNA. Several sensitive and specific assays are now partly automated for the purposes of detecting HCV RNA and quantifying the viral level. Although there is little correlation between viral level and disease manifestations, these assays have proven useful in identifying those patients who are more likely to benefit from treatment and, particularly, in demonstrating successful response to treatment as defined by an SVR. Liver biopsy is useful in defining baseline abnormalities of liver disease and in enabling patients and healthcare providers to reach a decision regarding antiviral therapy. Noninvasive tests do not currently provide the information that can be obtained through liver biopsy. Information on the genotype of the virus is important to guide treatment decisions. Genotype 1, most commonly found in the United States, is less amenable to treatment than genotypes 2 or 3. Therefore, clinical trials of antiviral therapies require genotyping information for appropriate stratification of subjects. Recent therapeutic trials in defined, selected populations have clearly shown that combinations of interferons and ribavirin are more effective than monotherapy. Moreover, trials using pegylated interferons have yielded improved SVR rates with similar toxicity profiles. However, 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. Genotype 1 infections require therapy for 48 weeks, whereas shorter treatment is feasible in genotype 2 and 3 infections. In genotype 1, the lack of an early virologic response (< 2 log decrease in HCV RNA) is associated with failure to achieve an SVR. The SVR is lower in patients with advanced liver disease than in patients without cirrhosis. Ongoing trials are exploring the usefulness of combination therapy in various populations. Preliminary experience in IDUs, individuals co-infected with HIV, children, and other special groups suggests similar responses are achievable in these populations. Patients with acute hepatitis C may be treated, but specific recommendations for antiviral treatment must await further evaluation of the rate of spontaneous clearance of the virus and determination of the optimal time to initiate treatment. Preventive measures beyond blood-banking practices 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 it stands to reason that they 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.