New Strategies to Manage Patients with Viral Hepatitis

PARIS -- The world's leading hepatitis experts, along with more than 850 physicians, will be meeting in Paris on September 10 and 11 for the first International Conference on the Management of Patients with Viral Hepatitis. The conference will review the most current information about viral hepatitis B and C, among the most frequent viral infections in the world, which have seen major advances in their treatment in recent years.

"Today, hepatitis B can be brought under control and hepatitis C can actually be cured. Therefore, these results should be applied in day-to-day clinical practice without further delay," says Professor Patrick Marcellin of the Liver Unit, hôpital Beaujon in Clichy, France.

Over the past few years, medical research has made it possible to develop effective treatments for viral hepatitis at a rapid pace, and clinicians are not always able to apply the latest findings to their clinical practice. "The objective of this international meeting," says Professor Marcellin, "is to give leading international specialists an opportunity to explain today's level of clinical knowledge in clear terms that physicians can apply directly to their practice and therefore benefit patients."

Hepatitis C: current knowledge and new developments

Worldwide prevalence of hepatitis C varies between 0.1 and five percent, depending on the country. Some 170 million people are infected by the hepatitis C virus across the globe, including 4 million in the United States and 5 million in Western Europe. In France, it is estimated that between 400,000 and 500,000 persons are infected, which represents 1.1 to 1.2 percent of the adult population. This figure reaches 60 percent for intravenous drug users, 25 percent for prisoners, and 25 percent for patients living with HIV. Hepatitis C is the cause of 60 percent of primary liver cancers and 30 percent of liver transplants. As a result, hepatitis C is the number one cause of liver transplants in the world.

"Management of patients with hepatitis C is probably the area where the most significant strides have been made. Today, doctors have more effective and better adapted treatments for patients. The virus was identified in 1989, and every year new studies make it possible to improve therapy and increase efficacy for both patients who were never treated and for patients who did not previously respond to treatment," says Professor Christian Trépo of the Hôpital Hôtel-Dieu in Lyon, France.

A combination of pegylated interferon and ribavirin has been shown to have the greatest efficacy and is currently the standard of care. Clinical studies conducted in the last few years have demonstrated a sustained virological response in more than 80 percent of patients with genotype two and three, and more than 50 percent of patients with the more difficult-to-treat genotype one[1]. Studies have also been conducted using different treatment durations (six months versus one year) and lower doses of ribavirin, according to the infecting genotype[2]. The ability to predict the patient's response after 12 weeks of treatment is a decisive factor in the management of treatment and encourages better patient adherence, which is essential for a cure. New evidence has paved the way to treat patients with either the most benign form of the disease (chronic hepatitis C with 'normal' transaminase levels[3]) or with the most severe form of the disease (cirrhosis). Among cirrhosis patients who clear the virus, a regression of hepatic lesions appears to also be possible[4],[5].

A number of studies of individuals co-infected with both hepatitis C virus (HCV) and HIV have made it possible to better define treatment for these patients. The recent publication in the New England Journal of Medicine (July 29, 2004)[6] of the results of the APRICOT study (AIDS PEGASYS(R) Ribavirin International CO-infection Trial) should lead to far-reaching changes in the treatment of HIV/HCV co-infection. This international study has shown that the combination of pegylated interferon alfa-2a and ribavirin achieved a sustained virological response in 40 percent of patients--the highest rate ever reported in a clinical trial of co-infected patients.

"Even though significant progress has been made, nearly half of patients still do not respond to the treatments that are currently available. These treatments often have side effects and can be poorly tolerated. It is important to continue research," says Professor Levrero of Policlinico Umberto I in Rome. "Research is being pursued in several directions. The most promising paths are enzyme inhibitors such as protease inhibitors, which are currently in early clinical trials[7]."

Hepatitis B: current knowledge and new developments

"Hepatitis B is the 'poor relation' among the different types of hepatitis, even though one third of the world's population is infected and 350 million people are chronic carriers of the hepatitis B virus and can potentially transmit it," explains Professor Patrick Marcellin. The hepatitis B virus is mainly prevalent in developing countries, and especially so in Southeast Asia and sub-Saharan Africa, where more than eight percent of the population are chronic carriers of the hepatitis B surface antigen. In recent years there has been an increase in the prevalence of hepatitis B in the West due to immigration from Africa and Asia. This viral disease is the cause of more than one million deaths worldwide each year.

Acute hepatitis B is often asymptomatic, but nearly one in 10 of those infected develops a chronic infection with a risk of spreading it to others. Due to the asymptomatic nature of the disease and a lack of routine screening among high-risk populations, diagnosis often comes too late. Safe, effective vaccines have been developed for hepatitis B and immunization programs make it possible to control the spread of the disease and have resulted in clear benefits for the prevention of cirrhosis and cancer.

With further research, it may be possible to develop new therapies that do not bring the disadvantages of current treatments, such as poor tolerance and diminished long-term efficacy due to viral resistance. Three drugs are currently available for the treatment of chronic hepatitis B. Conventional non-pegylated interferon-alpha induces a sustained response in only 10 to 30 percent of patients. Nucleoside (lamivudine) and nucleotide (adefovir dipivoxil) analogues are well tolerated, but their efficacy is impaired by viral resistance (especially high for lamivudine). Treatment with nucleoside or nucleotide analogues need to be indefinitely administered in the majority of patients which increases the risk of occurrence of viral resistance.

Recent studies have revealed markedly improved efficacy with pegylated interferon compared with conventional non-pegylated interferon[8], providing inhibition of viral replication in nearly 50 percent of patients[9]. Combination therapies using various drugs are currently under evaluation, although the optimal therapeutic approach remains to be determined. A number of nucleoside analogues currently under development are likely to play an important role in treatment. For the future, it appears likely that therapeutic combinations will be needed to reduce the risk of resistance.

The international hepatitis community is aware of the need to share the latest information about the progress made in the field of both hepatitis B and C. This will improve the management of all affected patients who will benefit from the optimal currently available treatments.

This conference was organized by Professor Patrick Marcellin and runs September 10th and 11th 2004 at the Palais des Congrès, Paris, France.

References

[1] Fried MW et al, N Engl J Med. 2002 ; Sep 26 ; 347(13) : 975-85

[2] Hadziyannis et al, Ann Intern Med. 2004 ; Mar 2 ; 140(5) : 346-55

[3] Marcellin et al, Gastroenterol Clin Biol. 2004 ; 28:A18.

[4] Pol et al, Hum Pathol. 2004 Jan;35(1):107-12.

[5] Marcellin, Ann Intern Med. 1997 Ann Intern Med. 1997 Nov 15;127(10):875-81.

[6] Torriani FJ et al, N Engl J Med. 2004 Jul 29 ; 351(5 ): 438-50.

[7] Lamarre D et al, Nature. 2003 Nov 13;426(6963):186-9

[8] Cooksley WG, J Viral Hepat. 2003 Jul ; 10(4) : 298-305.

[9] Marcellin et al, Gastroenterol Clin Biol. 2004 ; 28:A60.

Source: Dr. Patrick Marcellin, Beaujon Hospital