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NIH Consensus Development Conference: Management of Hepatitis B
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National Institutes of Health (NIH) Consensus Development Conferences.
http:// consensus.nih.gov
Sponsored by NIDDK (Natl Kidney Institute of Diabetes and Digestive an Kidney Diseases), Office of Medical Applications (OMAR)
Cosponsors: Natl Cancer Institute, NIAID (Natl Institute of Allergy and Infectious Diseases, CDC, FDA
Draft Panel Statement (October 22, 2008)
Conclusions of the Panel's Draft Conference Statement
Agency for Healthcare Research and Quality Systematic Literature Review Webcast Archive Day 1, Day 2 and Day 3 (coming soon)
NIH Press Release
Program and Abstract Book
Sponsors, Cosponsors, and Partners
October 20-22, 2008
NIH consensus and state-of-the-science statements are prepared by independent panels of health professionals and public representatives on the basis of (1) the results of a systematic literature review prepared under contract with the Agency for Healthcare Research and Quality (AHRQ), (2) presentations by investigators working in areas relevant to the conference questions during a 2-day public session, (3) questions and statements from conference attendees during open discussion periods that are part of the public session, and (4) closed deliberations by the panel during the remainder of the second day and morning of the third. This statement is an independent report of the panel and is not a policy statement of the NIH or the Federal Government.
The statement reflects the panel's assessment of medical knowledge available at the time the statement was written. Thus, it provides a "snapshot in time" of the state of knowledge on the conference topic. When reading the statement, keep in mind that new knowledge is inevitably accumulating through medical research, and that the information provided is not a substitute for professional medical care or advice.
This panel was charged with answering the following critical questions about the management of hepatitis B:
· What is the current burden of hepatitis B?
· What is the natural history of hepatitis B?
· What are the benefits and risks of the current therapeutic options for hepatitis B?
· Which persons with hepatitis B should be treated?
· What measures are appropriate to monitor therapy and assess outcomes? · What are the greatest needs and opportunities for future research on hepatitis B?
At the conference, invited experts presented information relevant to these questions, and a systematic literature review prepared under contract with the AHRQ was summarized. The evidence report
(http://www.ahrq.gov/clinic/tp/hepbtp.htm) emphasizes RCTs with health outcomes as their endpoints. Conference attendees also provided oral and written comments in response to the conference questions, and the panel considered all evidence when preparing this consensus statement.
Conclusions of the Panel's Draft Conference Statement
The most important predictors of cirrhosis or hepatocellular carcinoma in persons who have chronic HBV are persistently elevated HBV DNA level and ALT levels in blood. Other risk factors include HBV genotype C infection, male sex, older age, family history of hepatocellular carcinoma, and co-infection with HCV and HIV.
The major goals of anti-HBV therapy are to prevent the development of progressive disease, specifically cirrhosis and liver failure, as well as hepatocellular carcinoma development and subsequent death. To date, no RCTs of anti-HBV therapies have demonstrated a beneficial impact on overall mortality, liver-specific mortality, and development of hepatocellular carcinoma.
Most published reports of hepatitis therapy use changes in short-term virologic, biochemical, and histologic parameters to infer likelihood of long-term benefit. Approved therapies are associated with improvements in intermediate biomarkers, including HBV DNA, HBeAg loss/seroconversion, decreases in ALT levels, and improvement in liver histology.
Patients for whom therapy is indicated:
* Patients who have acute liver failure
* Patients who have cirrhosis complications
* Patients who receive immunosuppressive therapy
* Infants born to HBsAg-positive women
* Patients who have reactivation of chronic HBV
Patients for whom therapy may be indicated:
* Patients in the immune active phase
Patients for whom immediate therapy is not routinely indicated:
* Patients in the immune tolerant phase
* Patients in the inactive carrier/low replicative phase
* Patients who have latent HBV infection (HBV DNA without HBsAg)
Although a variety of monitoring practices has been recommended, no clear evidence exists for an optimal approach.
The most important research needs include representative prospective cohort studies to define the natural history of the disease and large RCTs, including placebo-controlled, of mono- and combined therapies with effects on clinical health outcomes.
The panel recommends routine screening for hepatitis B for newly arrived immigrants to the United States from countries where HBV prevalence rate is greater than 2 percent. Screening will facilitate the provision of medical and public health services for infected patients and their families and provide public health data on the burden of disease in immigrant populations. The screening test would in no way be used to prohibit immigration.
NIH Press Statement
Oct 22 2008
Panel Advocates Improved Understanding of Hepatitis B and Screening of High-Risk Populations
Note to Reporters: Press conference to be held at 2:00 p.m. EST today on the NIH campus in Bethesda, Maryland. Participate online via http://videocast.nih.gov
Management of hepatitis B is a challenge for physicians and patients due to an incomplete understanding of the disease course, complex treatment indications, and the lack of large studies focusing on important health outcomes. To examine these issues, the NIH convened an independent, impartial panel this week to weigh the available evidence on the management of hepatitis B.
While more than 95 percent of U.S. children are routinely vaccinated for hepatitis B, the vaccine does not protect individuals already infected with the virus. In unprotected individuals, acute infection with the hepatitis B virus is usually resolved by the body's immune system and does not cause long-term problems. The transition from acute to chronic infection appears to occur when the immune system does not effectively destroy and clear virus-infected cells.
A number of antiviral therapies approved by the U.S. Food and Drug Administration are available for use in fighting chronic hepatitis B infection including interferons and nucleos(t)ides. "We know that these therapies have positive effects on indicators such as viral load, but further controlled trials are needed to substantiate that these agents prevent disease progression to liver failure, cancer, or death," explained panel chair Dr. Michael F. Sorrell, Professor of Medicine at the University of Nebraska Medical Center.
To address this gap in the evidence, the panel recommended several avenues for future research. Among these, they gave top priority to large andomized studies, including placebo-controlled trials, testing single drug and combination therapies' effects on liver failure, cancer, and death. The panel also proposed representative prospective cohort studies to define the natural history of the disease to optimize management across diverse patient subgroups. This would also help decide which patients are most in need of immediate therapy and which could be carefully followed without drug therapy.
The panel is encouraged by the National Institute of Diabetes and Digestive and Kidney Disorders' plans to launch the Hepatitis B Clinical Research Network to promote translational research on this challenging condition. It is anticipated that the recommendations in the consensus statement will inform the consortium's research agenda.
The panel identified elevated hepatitis B DNA blood levels and elevated levels of ALT (alanine aminotransferase, a liver enzyme) as the most important indicators for progression to cirrhosis and liver cancer (hepatocellular carcinoma). Older age, male sex, family history of liver cancer, coinfection with hepatitis C or HIV, and elevated blood levels of hepatitis B DNA were also found to be key predictors.
The panel recommends routine hepatitis B screening for newly arrived immigrants from countries where hepatitis B prevalence is greater than two percent. These practices are intended to facilitate access to care for infected individuals and their families and to provide valuable data on disease prevalence, not to exclude immigrants in any way.
The panel recommends therapy for certain patients, including those with acute liver failure and complications from cirrhosis. However, immediate therapy is not indicated for patients with inactive forms of the disease.
The panel's complete consensus statement will be available later today at http://consensus.nih.gov. The conference was sponsored by the NIH Office of Medical Applications of Research (OMAR) and the National Institute of Diabetes and Digestive and Kidney Diseases, along with other NIH and Department of Health and Human Services components. This conference was conducted under the NIH Consensus Development Program, which convenes conferences to assess the available scientific evidence and develop objective statements on controversial medical issues.
The 12-member conference panel included experts in the fields of hepatology and liver transplantation, gastroenterology, public health and epidemiology, infectious diseases, pathology, oncology, family practice, internal medicine, biostatistics, and a public representative. A complete listing of the panel members and their institutional affiliations is included in the draft conference statement. Interviews with panel members can be arranged by contacting Lisa Ahramjian at 301-496-4999 or AhramjianL@od.nih.gov.
In addition to the material presented at the conference by speakers and the input from conference participants provided during discussion periods, the panel considered pertinent research from the published literature and the results of a systematic review of the literature. The systematic review was prepared through the Agency for Healthcare Research and Quality (AHRQ) Evidence-based Practice Centers (EPC) program, by the Minnesota Evidence-based Practice Center. The EPCs develop evidence reports and technology assessments based on rigorous, comprehensive syntheses and analyses of the scientific literature, emphasizing explicit and detailed documentation of methods, rationale, and assumptions. The evidence report on management of hepatitis B is available at http://www.ahrq.gov/clinic/tp/hepbtp.htm.
The panel's statement is an independent report and is not a policy statement of the NIH or the federal government. The NIH Consensus Development Program was established in 1977 as a mechanism to judge controversial topics in medicine and public health in an unbiased, impartial manner. NIH has conducted 119 consensus development conferences, and 29 state-of-the-science (formerly "technology assessment") conferences, addressing a wide range of issues. A backgrounder on the NIH Consensus Development Program process is available at http://consensus.nih.gov/forthemedia.htm.
The Office of the Director, the central office at NIH, is responsible for setting policy for NIH, which includes 27 Institutes and Centers. This involves planning, managing, and coordinating the programs and activities of all NIH components. The Office of the Director also includes program offices which are responsible for stimulating specific areas of research throughout NIH. Additional information is available at http://www.nih.gov/icd/od.
The National Institutes of Health (NIH) - The Nation's Medical Research Agency - includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
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