scholarly journals Is hepatocellular carcinoma surveillance in high-risk populations effective?

2020 ◽  
Vol 7 (3) ◽  
pp. HEP25
Author(s):  
Kristeen Onyirioha ◽  
Sukul Mittal ◽  
Amit G Singal

Several professional societies recommend hepatocellular carcinoma (HCC) surveillance in high-risk patients including patients with cirrhosis from any etiology and subsets of noncirrhotic chronic hepatitis B virus infection. The efficacy of HCC surveillance to increase early detection and improve survival has been demonstrated in a large randomized controlled trial among hepatitis B virus patients and several cohort studies among those with cirrhosis. However, the effectiveness on HCC surveillance, when applied in clinical practice, is lower due to low utilization of HCC surveillance among at-risk patients, poorer test performance given operator dependency and differences in patient characteristics, and downstream process failures such as treatment delays. Interventions to increase surveillance utilization and improve surveillance test performance should improve surveillance effectiveness in the future.

2012 ◽  
Vol 18 (4) ◽  
pp. 378-387 ◽  
Author(s):  
Xinghui Zhao ◽  
Zhanzhong Zhao ◽  
Junwei Guo ◽  
Peitang Huang ◽  
Xudong Zhu ◽  
...  

Chronic hepatitis B virus (HBV) infection is an independent risk factor for the development of hepatocellular carcinoma (HCC). The HBV HBx gene is frequently identified as an integrant in the chromosomal DNA of patients with HCC. HBx encodes the X protein (HBx), a putative viral oncoprotein that affects transcriptional regulation of several cellular genes. Therefore, HBx may be an ideal target to impede the progression of HBV infection–related HCC. In this study, integrated HBx was transcriptionally downregulated using an artificial transcription factor (ATF). Two three-fingered Cys2-His2 zinc finger (ZF) motifs that specifically recognized two 9-bp DNA sequences regulating HBx expression were identified from a phage-display library. The ZF domains were linked into a six-fingered protein that specified an 18-bp DNA target in the Enhancer I region upstream of HBx. This DNA-binding domain was fused with a Krüppel-associated box (KRAB) transcriptional repression domain to produce an ATF designed to downregulate HBx integrated into the Hep3B HCC cell line. The ATF significantly repressed HBx in a luciferase reporter assay. Stably expressing the ATF in Hep3B cells resulted in significant growth arrest, whereas stably expressing the ATF in an HCC cell line lacking integrated HBx (HepG2) had virtually no effect. The targeted downregulation of integrated HBx is a promising novel approach to inhibiting the progression of HBV infection–related HCC.


2017 ◽  
Author(s):  
◽  
Andrew Douglas Huber

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Chronic hepatitis B virus (HBV) infection leads to liver disease, cirrhosis, and hepatocellular carcinoma. Globally, an estimated 50% of all hepatocellular carcinoma cases are linked to chronic HBV infection. More than 240 million people are chronically infected, and there are 0.5-1 million deaths per year due to HBVrelated liver conditions. HBV treatment options rarely cure infections and are associated with adverse side effects that often outweigh the potential benefits of treatment. New treatments, therefore, are highly desired for HBV therapy. Towards this goal, we have developed novel compounds targeting two viral targets and assessed the mechanisms of action by which these compounds act. We have developed systems for the discovery and evaluation of compounds that inhibit 2 distinct steps in the HBV life cycle. Using these systems, we have developed potent inhibitors of HBV replication that have potential to become clinically used HBV drugs. Furthermore, we have used our methods to evaluate which properties of these compounds are likely to result in better viral inhibition. The work described in this thesis has led to at least 2 new compound groups for potential use as HBV antivirals and provides insight into mechanisms by which potent antivirals can be achieved.


1992 ◽  
Vol 136 (9) ◽  
pp. 1115-1121 ◽  
Author(s):  
Chung-Cheng Hsieh ◽  
Anastasia Tzonou ◽  
Xenophon Zavitsanos ◽  
Evagelia Kaklamani ◽  
Shou-Jen Lan ◽  
...  

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