Investigational Antiviral Drugs
M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson in Kucers’ The Use of Antibiotics, 2017
This chapter covers over 50 investigational drugs most of which are in phase II or phase III clinical trials, with some emphasis on whether they are likely to be approved for clinical use, and drugs with a niche clinical focus. At present there are no drugs to treat respiratory syncytial virus infection, a cause of serious morbidity and mortality in neonates. For that reason, we have included three investigational drugs, even though some are in relatively early stages of development. We have included several drugs with activity against hepatitis B virus (HBV) that are in various stages of development, from preclinical to phase III, although most suppress HBV replication but do not cure the disease (analogous to antiretroviral drugs for HIV-1) (Brahmania et al., 2016). Of the drugs in clinical trials that inhibit HBV replication, it is hard to see them being more effective and/or less toxic than the existing the drugs, lamivudine, emtricitabine, entecavir, and tenofovir (including tenofovir disoproxil fumarate [TDF] and tenofovir alafenamide [TAF]) (see Table 269.1, Table 269.2, Table 269.3, and Table 269.4).
Liver Diseases
George Feuer, Felix A. de la Iglesia in Molecular Biochemistry of Human Disease, 2020
Epidemiologic studies have shown a strong correlation between hepatitis B virus infection and the development of hepatocellular carcinoma.14,29,30–32,364,446,461 A relationship has also been found with related viruses.451 Infection with hepatitis B virus may have several consequences. Transient infection can cause subclinical disease, anicteric hepatitis, acute icteric hepatitis, or fulminant hepatitis. Persistent infections may lead to chronic conditions, such as chronic persistent hepatitis, chronic active hepatitis, or postnecrotic cirrhosis. Any of these conditions may lead to liver neoplasia. There is, however, a long incubation period lasting from 20 to 40 years between the onset of persistent hepatitis B virus infection and the development of primary hepatocellular carcinoma.356,365
Cancer
Jahangir Moini, Matthew Adams, Anthony LoGalbo in Complications of Diabetes Mellitus, 2022
The cause of hepatocellular carcinoma is primarily cirrhosis of the liver. However, the presence of the hepatitis B virus increases risks by 100 times in people who carry HBV. The risk factors include alcoholic cirrhosis, hemochromatosis, and chronic HCV infection. In some areas of the world, hepatocellular carcinoma is of higher incidence because of ingesting foods that are contaminated with fungal aflatoxins. Liver cancer in diabetic patients may be related to medications being taken to control blood glucose. People with type 2 diabetes may develop fatty liver, which is a trigger for cirrhosis, fibrosis, and cancer. Fatty liver disease is the most common cause of hepatocellular carcinoma. However, people with type 1 diabetes do not have an increased risk of liver cancer.
CpG DNA-triggered upregulation of TLR9 expression affects apoptosis and immune responses in human plasmacytoid dendritic cells isolated from chronic hepatitis B patients
Published in Archives of Physiology and Biochemistry, 2023
Bin Zhu, Tianbao Wang, Xiaoxia Wei, Yancai Zhou, Jiansheng Li
Human peripheral blood was obtained from three healthy donors aged 45.6 ± 5.23 (two males and one female) and three chronic hepatitis B patients aged 47.2 ± 3.68 (two males and one female) in The First Affiliated Hospital of Xinxiang Medical University with the approval of Health Ethic Committee (No.2016–09-11). Inclusion criteria: patients with chronic hepatitis B had different degrees of systemic fatigue, fatigue, loss of appetite and jaundice, and were diagnosed with chronic hepatitis B by liver function, histological diagnosis, hepatitis B virus markers and hepatitis B virus deoxyribonucleic acid (HBV-DNA). The diagnosis of patients with chronic hepatitis B was consistent with the “relevant diagnostic criteria of chronic hepatitis” in the Guidelines for Prevention and Treatment of Chronic Hepatitis B. Exclusion criteria: patients who were positive for HBeAg and anti-Hbe; patients co-infected with hepatitis C virus, hepatitis D virus, or human immunodeficiency virus, hepatic decomposition; patients who had other liver diseases (alcohol liver disease, fatty liver, autoimmune liver disease, metabolic liver disease, or liver cancer), or fibrosis and cirrhosis of the liver which was determined by transient elastography. This study conformed to the ethical guidelines of the 1975 Declaration of Helsinki. All patients provided written informed consent before the participation into the study.
A ‘sandwich’ strategy promises functional cure of chronic hepatitis B
Published in Expert Review of Precision Medicine and Drug Development, 2019
Cheng Lei, Yanling Wu, Tianlei Ying
As the challenge to completely eliminate HBV in chronic hepatitis B (CHB) patients prevails, ‘functional cure’ for the CHB patients is widely accepted as the attainable goal in the near future. Functional cure refers to sustained, undetectable HBsAg and HBV DNA in serum, and cessation of a finite course of treatment does not lead to spontaneous relapse [4]. Direct and indirect approaches to achieve functional cure of HB are several, including inhibitors of viral transcription and translation, cccDNA targeting, nucleocapsid assembly and inhibitors packaging, and using viral polymerase inhibitors, therapeutic vaccines, innate immunity modulators, checkpoint modulators, entry inhibitors, interferons, nucleic acid polymers, and antibodies [5]. These comprehensive approaches remark the success of thorough studies toward HBV [5]. Still, only two treatments of CHB were licensed, namely anti-HBV nucleosides (nucleotides) drugs and interferon-α (IFN-α) [1]. Although relatively rapid responses of antiviral therapy, long-term treatment is still required for persistent viral infections, bringing problems associated with drug resistant, safety and high cost of antiviral drugs.
Long-term durability of immunogenicity induced by standard and triple-dose hepatitis B vaccine in patients receiving methadone maintenance treatment
Published in Expert Review of Vaccines, 2020
Tian Yao, Yuanting Wu, Shuang Dong, Linying Gao, Shan Shi, Zhihong Shao, Lina Wu, Dan Feng, Jing Shi, Yawei Zhang, Yongliang Feng, Xiaofeng Liang, Suping Wang
Hepatitis B virus (HBV) infection is a major global health problem, with an estimated global prevalence of 3.5%. Worldwide, approximately 257 million people live with chronic HBV infection [1], a major contributing factor to liver cirrhosis and hepatocellular carcinoma (HCC) [2,3]. Use of the hepatitis B vaccine is an effective measure to prevent HBV infection [4]. China introduced the hepatitis B vaccine into routine immunization management as a comprehensive strategy in 1992. In response, the HBV prevalence rate in adults dropped from 9.8% in 1992 to 6.1% in 2016 [5,6]. However, the rate of HBV infection remains high in specific population groups, particularly in patients receiving methadone maintenance treatment (MMT) [7–11], a widely used alternative treatment for opioid dependence in drug users [12,13].
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