European Association for the Study of the Liver (EASL) Publishes First Guidelines for Management of Chronic Hepatitis B

By Liz Highleyman

The European Association for the Study of the Liver (EASL) has published its first clinical practice guidelines for the management of patients with chronic hepatitis B virus (HBV) infection, appearing in the February 2009 Journal of Hepatology.

The new document begins with an overview of the epidemiology of chronic hepatitis B, as well as the natural history of disease progression. It is estimated that about one-third of the world's population has evidence of past or present HBV infection, while some 350 million people are believed to be chronically infected.

The new guidelines cover pre-treatment assessment of liver disease using both biochemical markers and liver biopsy, goals and endpoints of therapy, definitions of treatment response, and a summary of data from studies of anti-HBV therapies.

"The goal of therapy for hepatitis B is to improve quality of life and survival by preventing progression of the disease to cirrhosis, decompensated cirrhosis, end-stage liver disease, HCC [hepatocellular carcinoma] and death," the EASL panel wrote. "This goal can be achieved if HBV replication can be suppressed in a sustained manner, the accompanying reduction in histological activity of chronic hepatitis lessening the risk of cirrhosis and decreasing the risk of HCC in non-cirrhotic patients and probably also, but to a lesser extent, in cirrhotic patients. However, HBV infection cannot be completely eradicated due to the persistence of covalently closed circular DNA (cccDNA) in the nucleus of infected hepatocytes."

Several new antiviral agents have been evaluated and licensed since the previous EASL consensus conference in 2002. Currently 7 hepatitis B therapies are approved in Europe: conventional interferon alpha, pegylated interferon alpha, lamivudine (Epivir-HBV), telbivudine (Tyzeka or Sebivo), entecavir (Baraclude), adefovir (Hepsera), and tenofovir (Viread).

Low baseline HBV DNA and elevated ALT predict good response to interferon or nucleoside/nucleotide drugs, but HBV genotype only seems to make a difference with regard to interferon response, with genotypes A and B being associated with better response than C and D.

Development of drug resistance is a major barrier to long-term treatment success, and the guidelines include a discussion of treatment strategies, including combination versus sequential therapy and short-term versus continuous treatment.

The document includes guidance for management of patients with compensated and decompensated cirrhosis, as well as liver transplant recipients. Management of children and pregnant women with hepatitis B is also discussed.

There are also sections on dealing with patients with HIV-HBV coinfection and HBV-HCV coinfection. Indications for treatment are the same in HIV positive and HIV negative individuals, based on HBV DNA level, serum ALT, and extent of liver damage. In agreement with current HIV treatment guidelines, the EASL panel recommended that coinfected patients should be simultaneously treated for both HIV and HBV using the dually active agents tenofovir and emtricitabine (Emtriva) plus a third agent active against HIV. For the small number of patients who must be treated for HBV before HIV, adefovir and telbivudine -- which are not proven to be active against HIV -- should be preferred. In contrast, lamivudine, entecavir, and tenofovir are contraindicated as single agents for hepatitis B in coinfected patients.

Finally, the guidelines conclude with a section on unresolved questions and unmet needs that could be addressed in future research, including improved knowledge of the natural history of chronic hepatitis B, indirect markers of liver disease severity, the role of HBV genotype in determining disease prognosis, optimal duration of treatment, efficacy of various combination regimens, and development of new agents for multidrug-resistant HBV.

"Several difficulties remain in formulating treatments for chronic hepatitis B, thus areas of uncertainty exist," the EASL panel wrote. "At the present time clinicians, patients and public health authorities must continue to make choices on the basis of evidence that is not fully matured."

The EASL Clinical Practice Guidelines: Management of Chronic Hepatitis B are available online at: www.easl.ch/easl_cpg.asp.

For more information on EASL or the guidelines, please contact:

Margaret Walker
Policy & Communications Manager
margaret.walker@easloffice.eu
www.easl.eu

2/03/09

Reference
European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines: Management of chronic hepatitis B. Journal of Hepatology 50(2): 227-242. February 2009.

Other source
European Association for the Study of the Liver. First EASL Clinical Practice Guidelines on Management of Chronic Hepatitis B issued by the European Association for the Study of the Liver (EASL). Press release (http://www.easl.ch/mailshots/press3.htm).