Chronic hepatitis B: a new, more powerful antiviral gets its European marketing authorization

Current therapies for treating chronic hepatitis B have shown their limits in terms of tolerance and emergence of resistance, new therapeutic approaches have emerged with the arrival of an antiviral oral entecavir (Baraclude * laboratory BMS), which recently received its marketing authorization (permission marketing) European.
This new molecule research-based Bristol-Myers Squibb has been the subject of a presentation to the press during a debate organized in Paris by the laboratory in the presence of two Parisian specialists, Drs Thierry Poynard and Stanislas Pol.

Chronic hepatitis B should be considered as a serious illness in the absence of treatment, it leads to fatal complications in a quarter of cases, such as liver failure and gastrointestinal bleeding in portal hypertension secondary to both cirrhosis, or liver cancer.

However, to date, "only 4% of diagnosed patients are treated. Moreover, there are problems for this disease resistance to treatment. Similarly, when a low response rate is obtained, the risk of reactivation of hepatitis upon discontinuation of treatment becomes important, "warns Professor Thierry Poynard (hepato-gastroenterology service Pitié-Salpêtrière, Paris).

Chronic hepatitis B never heals and viral reactivation may return at any time. "The therapeutic goal is the viral suppression that must be considered in the long term, with treatments lasting up to three years, interspersed with therapeutic windows and with monitoring for life," says Prof. Stanislas Pol (Hepatology Service, Necker Hospital, Paris).

Entecavir, a new molecule is the only antiviral having a specific action on hepatitis B, blocking three levels of action of the enzyme involved in the replication, with an exclusive property of inhibiting initiation of viral DNA by this enzyme (not observed with the other two existing antivirals), "it is emboitant on the surface of the DNA, according to a mechanism similar to a zipper" illustrates Professor Poynard questioned by Reuters Health. Outside this enzymatic mechanism primer, the other two targets of action are located at the reverse transcription and the synthesis of DNA.

"This product therefore appears more powerful than the other two antivirals (lamivudine antiviral reference and adefovir) currently available. After a year of treatment, 70% of treatment-naïve patients (that is to say, n ' who never received treatment), placed in entecavir get complete control of the viral replication (40% versus lamivudine), "said Dr. Pol. According to him, the better the efficiency, the lower the risk of resistance to treatment.

These are multiple targets that provide the new drug's ability to cause a significant decrease in viral load. "In fact, two years of treatment (96 weeks), no virologic breakthrough due to resistance was observed with entecavir," he says. Thus, 94% of naive patients have an undetectable viral load, versus 77% of patients on lamivudine.

Among those previously treated with lamivudine and become resistant to this drug, only 10% had virological rebound during the second year of treatment with entecavir (cross-resistance to lamivudine). However, entecavir in a majority of cases, is effective in patients resistant to the antiviral reference, as well as those with a more difficult to treat viral form (HBeAg-linked to a mutant virus).

In addition to its effect on viremia, this product has a positive effect on the liver by increasing the destructive phenomena such as inflammatory necrosis and fibrosis, reports the hepatologist.

Finally, the safety profile is good, with results similar to those identified in lamivudine (to type headaches, digestive disorders and ENT infections) side effects. Entecavir is also suitable for patients with renal insufficiency, with a specific dosage form, oral solution, which allows titration.

As for any standardized regimen, guiding the choice to one or another antiviral or interferon (the latter being used only in 5% of patients), it does not exist. "It must first assess the patient, in terms of viral load and liver damage, determine the natural history and the age of the disease, previous treatment, any co-infections .. ., is to integrate all parameters that will lead to individualized treatment, although recommendations exist, "said Dr. Pol, told Reuters Health.

However, he informed the decision of a start of antiviral therapy is essential when viral replication is high (due to a high risk of developing cirrhosis and / or liver cancer).

With more than 2 billion people exposed to hepatitis B in the world and about 350 million chronic carriers of the virus, including 300,000 in France, chronic hepatitis B has become a public health issue.

"Keep in mind that this virus can remain active outside the body for seven days and appears 100 times more infectious than the AIDS virus (HIV). Hence the importance of the track in especially for anyone at risk, as more than half of infected individuals do not know his HIV status, "recalls Professor Poynard.