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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 Vol. 34 No. 4 (2025): December
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.
Kesintasan Hidup Satu Tahun Pasien Sirosis Hati yang Dirawat di Rumah Sakit Cipto Mangunkusumo pada Periode COVID-19 Aprilicia, Gita; Baihaki, Ichwan; Banjarnahor, Riri Oktavani; Kalista, Kemal Fariz; Gani, Rino Alvani
Jurnal Penyakit Dalam Indonesia
Publisher : UI Scholars Hub

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Abstract

Introduction. Liver cirrhosis represents the terminal stage of chronic liver disease and is characterized by a markedly reduced survival rate. Understanding the characteristics and laboratory parameters of patients with liver cirrhosis can provide valuable insights into their prognosis and potential interventions. This study was conducted during the COVID-19 pandemic period, which may have influenced patient outcomes due to potential impact of COVID-19 infection on patients with chronic liver disease. This study aimed to evaluate the one-year survival rate of hospitalized liver cirrhosis patients at Cipto Mangunkusumo Hospital during the COVID-19 and to identify clinical and laboratory factors associated with patient survival. Methods. This retrospective study analyzed data from 73 in-hospital liver cirrhosis patients during January to December 2020. Demographic characteristics, comorbidities, diagnosis upon admission, and laboratory parameters were collected. Patients were categorized into two groups: those who survived and those who died within one year of hospitalization. Survival analysis was performed using the Kaplan–Meier method to estimate 1 year survival probability of cirrhosis patients. Results. The analysis revealed significant differences in several characteristics and laboratory parameters between the survival and death groups during COVID-19 period. The etiology of liver cirrhosis was predominantly related to HBV (41.1%) and HCV (23.3%), which constituted the most common causes. Diagnosis upon admission showed a significant association with survival, with bleeding esophageal varices (53.4%) being the most prevalent. Laboratory parameters such as SGOT, SGPT, albumin, bilirubin, prothrombin time, INR, and Child Pugh score demonstrated significant differences between the two groups. The 1-year survival rate for the Child Pugh class A, B and C was approximately 100%, 61.2% (CI 95% 42.2 - 80.2%) and 0%, respectively. The overall 1-year survival rate of in-hospital liver cirrhosis patients was 52.6% (CI 95% 38.7 - 66.5%). Conclusions. This study found the overall survival of in-hospital liver cirrhosis patients during COVID-19 period was low. It’s essential to develop a comprehensive and personalized treatment plan for optimal patient outcomes.
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 Baihaki, Ichwan Bambang Sutopo Banjarnahor, Riri Oktavani 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