Treating chronic Hepatitis D infection with bulevirtide, a bile-acid transporter inhibitor
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Reviewed by Dat Tien Nguyen, B.A, ScM.
Translated by An Duc Thien Le |
Posted on August 2nd, 2023
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To enter and infect hepatocytes, Hepatitis D viruses (HDV) must use the Hepatitis B surface antigen (HBsAg). Thus, a person can be infected with both Hepatitis B (HBV) and Hepatitis D viruses. This co-infection increases the risk of cirrhosis and carcinoma. It is possible to suppress HBV proliferation, but there is currently no approved treatment for HDV. Besides HBsAg, HDV can use the sodium taurocholate cotransporting polypeptide (NTCP) to enter liver cells. Thus, Bulevirtide, an inhibitor of NTCP, was tested for its potential clinical benefit in treating Hepatitis D infection.
The phase 3 clinical trial included 150 patients who were diagnosed with chronic hepatitis D infection for at least 6 months before enrolling in the trial. Diagnosis was made based on either the anti-HDV antibody test or a PCR test for HDV RNA. These patients were randomly assigned to receive placebo or 2 different dose schedules of bulevirtide. One group received a daily subcutaneous injection of 2 mg of bulevirtide, and the other one received 10 mg every day. After 48 weeks of treatment, both doses of bulevirtide normalized the level of alanine transaminase and significantly reduced the level of HDV RNA in approximately half of the patients; on the other hand, only 2% of the control group reached the same clinical outcome. There was little difference between the rate of adverse reactions between the 2 doses of bulevirtide. However, those who received bulevirtide reported more cases of headache, fatigue, upper-abdominal pain and arthralgia than those in the control group. Since NTCP helps with bile acid transportation, the usage of bulevirtide affects bile acid level following a dose-dependent level.
The phase 3 clinical trial included 150 patients who were diagnosed with chronic hepatitis D infection for at least 6 months before enrolling in the trial. Diagnosis was made based on either the anti-HDV antibody test or a PCR test for HDV RNA. These patients were randomly assigned to receive placebo or 2 different dose schedules of bulevirtide. One group received a daily subcutaneous injection of 2 mg of bulevirtide, and the other one received 10 mg every day. After 48 weeks of treatment, both doses of bulevirtide normalized the level of alanine transaminase and significantly reduced the level of HDV RNA in approximately half of the patients; on the other hand, only 2% of the control group reached the same clinical outcome. There was little difference between the rate of adverse reactions between the 2 doses of bulevirtide. However, those who received bulevirtide reported more cases of headache, fatigue, upper-abdominal pain and arthralgia than those in the control group. Since NTCP helps with bile acid transportation, the usage of bulevirtide affects bile acid level following a dose-dependent level.