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All Journal Medical Journal of Indonesia The Indonesian Journal of Gastroenterology, Hepatology and Digestive Endoscopy Jurnal Penyakit Dalam Indonesia Occupational and Environmental Medicine Journal of Indonesia
Rino Alvani Gani
Division of Hepatobiliary, Department of Internal Medicine, Faculty of Medicine University of Indonesia/Dr. Cipto Mangunkusumo Hospital, Jakarta
Environmental Science Health Professions Medicine & Pharmacology Nursing Public Health

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Effect of matrix metalloproteinase-9 inhibitors in hepatitis B virus replication Kalista, Kemal Fariz; Harimurti, Kuntjoro; Immanuel, Suzanna; Iskandriati, Diah; Lesmana, Cosmas Rinaldi Adithya; Ibrahim, Fera; Gani, Rino Alvani
Medical Journal of Indonesia Online First
Publisher : Faculty of Medicine Universitas Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.13181/mji.oa.257895

Abstract

BACKGROUND Hepatitis B virus (HBV) remains difficult to eradicate due to the persistence of covalently closed circular DNA (cccDNA). Matrix metalloproteinase-9 (MMP-9) enhances HBV replication, but the effects of its inhibition remain unexplored. This study aimed to investigate the effects of MMP-9 inhibitors on HBV replication markers. METHODS Primary hepatocyte cultures were obtained from the livers of 6 Tupaia javanica. Cultures were infected with HBV from human sera and divided into control and intervention groups. The intervention group received MMP-9 inhibitors at 1, 3, and 7 nM. The control group received phosphate-buffered saline. Levels of hepatitis B surface antigen (HBsAg), HBV DNA, cccDNA, MMP-9, interferon alpha and beta receptor subunit 1 (IFNAR1), and interferon beta (IFN-β) were measured in both groups before and 72 hours post-intervention. RESULTS MMP-9 inhibitor administration at 1, 3, and 7 nM consistently reduced HBsAg, HBV DNA, cccDNA, and MMP-9 levels, though not statistically significant. Median HBV DNA levels at 1, 3, and 7 nM were 7.05, 5.29, and 5.98 ×103 copies/ml, respectively. Mean cccDNA levels at 1, 3, and 7 nM were 14.15, 11.04, and 13.94 ×103 copies/ml, respectively. The 3 nM dose increased IFNAR1 levels, while the 7 nM dose increased IFN-β, but neither change was significant. Among the tested doses, 3 nM showed the most favorable effects despite the lack of significance. CONCLUSIONS MMP-9 inhibitor suppressed HBsAg, HBV DNA, cccDNA, and MMP-9 while increasing IFNAR1 and IFN-β in vitro.
Co-Authors -, Arles - -, Suhendro - -, Suhendro - A.A. Ketut Agung Cahyawan W Abdul Aziz Rani Adityo Susilo, Adityo Agus Sudiro Waspodo Ahimsa, Titos Ahimsa, Titos Ali Sulaiman Anandhara Indriani Khumaedi, Anandhara Indriani Anandita, Faizal Ablansah ANDI UTAMA Andri Sanityoso Andri Sanityoso Sulaiman Aprilicia, Gita Ari Fahrial Syam Bambang Sutopo Bhanu S Kumar C Rinaldi A Lesmana Chudahman Manan Chyntia Olivia Maurine Chyntia Olivia Maurine Jasirwan, Chyntia Olivia Maurine Cleopas Martin Rumende Devy Serevina DIAH ISKANDRIATI Dyah Ratna Budiani E. Mudjaddid A. Siswanto Deddy N.W.Achadiono Hamzah Shatri Edy Rizal Wahyudi Ening Krisnuhoni Epistel Pangujian Simatupang Evy Yunihastuti Fera Ibrahim FX Pridady Griscalia Christine Hanif, Muhammad Yusuf Hardigaloeh, Amanda Trixie Ihsanil Husna Ika Prasetya Wijaya Ikhwan Rinaldi Imelda Maria Loho, Imelda Maria Indra Marki Indra, Suwito Irsan Hasan Isman Firdaus Jacobus Albertus Jasirwan, Chyntia Olivia M Joyce Bratanata, Joyce Juferdy Kurniawan Kaka Renaldi Kemal Fariz Kalista, Kemal Fariz Kuntjoro Harimurti Kusumaningrum, Profitasari Laurentius A Lesmana, Laurentius A Laurentius Lesmana Lianda Siregar Lies Luthariana Loli J Simanjuntak Lutfie Lutfie, Lutfie Marcellus Simadibrata Marcellus Simandibrata Mesanti, Oska Muchtaruddin Mansyur Murdani Abdullah Nababan, Saut Horas H. Nanang Sukmana Nurul Akbar Pratiwi, Amalia Nur Ralph Girson Gunarsa Ratu Ratih Kusumayanti Retno Asti Werdhani Sabarinah Prasetyo Sabarudin, Adang Sjaifoellah Noer Soemarno Soemarno Suhendro Suhendro Sulaeman, Andri Sanityoso Susan Tai Suzanna Immanuel Teguh Haryono Karjadi, Teguh Haryono Teressa, Maria Unggul Budihusodo Vera Yuwono Yustar Mulyadi