BACKGROUND/AIMS: Sodium taurocholate co-transporting polypeptide (NTCP) is the receptor for the hepatitis B virus (HBV) and hepatitis D virus (HDV) entry into hepatocytes. Ezetimibe is a cholesterol-lowering drug that possesses the pharmacophore features to inhibit NTCP. This study evaluates the efficacy of ezetimibe in patients with chronic HDV infection in a nonrandomized trial. MATERIALS AND METHODS: This proof of concept phase 2 trial evaluated the efficacy and safety of ezetimibe 10 mg daily in (interferon treatment-experienced or interferon ineligible) patients with chronic hepatitis D (CHD). Forty-four patients with CHD were recruited, 38 male and 6 female patients, mean age 35.2±8.7 (range 19-64). Fifteen (34%) patients were on concomitant nucleoside therapy, and cirrhosis was present in 14 subjects. The primary therapeutic endpoint was a decline in HDV RNA at one log or more from the baseline at week 12. RESULTS: The mean HDV RNA level was 5.4±1.3 log10 IU/mL. HBeAg was non-reactive in 43 (98%). HBV DNA was undetectable in 28 (64%). One patient stopped treatment at week 4, and one patient did not follow-up. One log or more reduction in the HDV RNA levels was observed in 18/44 (41%) patients. No log reduction occurred in 16 patients, and 8 experienced a log increase. No adverse effects from the concomitant nucleoside analogue use or clinical cirrhosis were observed. The drug exhibited a positive safety profile. CONCLUSION: Treatment of CHD patients with ezetimibe resulted in a one log reduction of viral load in 43% (18/42) of the patients who completed the 12 weeks of therapy.
BACKGROUND/AIMS: Sodium taurocholate co-transporting polypeptide (NTCP) is the receptor for the hepatitis B virus (HBV) and hepatitis D virus (HDV) entry into hepatocytes. Ezetimibe is a cholesterol-lowering drug that possesses the pharmacophore features to inhibit NTCP. This study evaluates the efficacy of ezetimibe in patients with chronic HDV infection in a nonrandomized trial. MATERIALS AND METHODS: This proof of concept phase 2 trial evaluated the efficacy and safety of ezetimibe 10 mg daily in (interferon treatment-experienced or interferon ineligible) patients with chronic hepatitis D (CHD). Forty-four patients with CHD were recruited, 38 male and 6 female patients, mean age 35.2±8.7 (range 19-64). Fifteen (34%) patients were on concomitant nucleoside therapy, and cirrhosis was present in 14 subjects. The primary therapeutic endpoint was a decline in HDV RNA at one log or more from the baseline at week 12. RESULTS: The mean HDV RNA level was 5.4±1.3 log10 IU/mL. HBeAg was non-reactive in 43 (98%). HBV DNA was undetectable in 28 (64%). One patient stopped treatment at week 4, and one patient did not follow-up. One log or more reduction in the HDV RNA levels was observed in 18/44 (41%) patients. No log reduction occurred in 16 patients, and 8 experienced a log increase. No adverse effects from the concomitant nucleoside analogue use or clinical cirrhosis were observed. The drug exhibited a positive safety profile. CONCLUSION: Treatment of CHD patients with ezetimibe resulted in a one log reduction of viral load in 43% (18/42) of the patients who completed the 12 weeks of therapy.
Authors: Alexander König; Barbara Döring; Christina Mohr; Andreas Geipel; Joachim Geyer; Dieter Glebe Journal: J Hepatol Date: 2014-05-15 Impact factor: 25.083
Authors: Cihan Yurdaydin; Zaigham Abbas; Maria Buti; Markus Cornberg; Rafael Esteban; Ohad Etzion; Edward J Gane; Robert G Gish; Jeffrey S Glenn; Saeed Hamid; Theo Heller; Christopher Koh; Pietro Lampertico; Yoav Lurie; Michael Manns; Raymundo Parana; Mario Rizzetto; Stephan Urban; Heiner Wedemeyer Journal: J Hepatol Date: 2018-12-27 Impact factor: 25.083
Authors: Antje Blank; Christoph Markert; Nicolas Hohmann; Alexandra Carls; Gerd Mikus; Thorsten Lehr; Alexander Alexandrov; Mathias Haag; Matthias Schwab; Stephan Urban; Walter E Haefeli Journal: J Hepatol Date: 2016-04-27 Impact factor: 25.083
Authors: Pavel Bogomolov; Alexander Alexandrov; Natalia Voronkova; Maria Macievich; Ksenia Kokina; Maria Petrachenkova; Thorsten Lehr; Florian A Lempp; Heiner Wedemeyer; Mathias Haag; Matthias Schwab; Walter E Haefeli; Antje Blank; Stephan Urban Journal: J Hepatol Date: 2016-04-27 Impact factor: 25.083