Antiviral Therapy in Hepatitis B Virus-Associated Liver Cirrhosis

2015 ◽  
Vol 33 (4) ◽  
pp. 608-612 ◽  
Author(s):  
Tobias Boettler ◽  
Robert Thimme

Background: Chronic hepatitis B virus (HBV) infection is a major risk factor for the development of liver cirrhosis and hepatocellular carcinoma (HCC). Key Messages: In patients with advanced liver fibrosis or liver cirrhosis, antiviral therapy is mandatory to slow down, halt or reverse disease progression and possibly reduce the risk of HCC development. As in patients without advanced fibrosis, PEG-interferon and nucleoside/nucleotide analogues (NUCs) are available for antiviral therapy. NUC therapy should be performed indefinitely as the rates of HBs-Ag loss are low. Entecavir or tenofovir should be preferred due to their strong antiviral potency and their high barrier to resistance. PEG-interferon therapy can be administered to patients with compensated liver disease but should not be offered to patients with signs of hepatic decompensation. Conclusions: Antiviral therapy in chronic HBV infection can reduce liver fibrosis and even revert overt cirrhosis. Whether it also reduces the risk of HCC development in cirrhotic patients remains elusive and might vary in different countries and ethnicities.

2013 ◽  
Vol 62 (8) ◽  
pp. 1235-1238 ◽  
Author(s):  
Inmaculada Castillo ◽  
Javier Bartolomé ◽  
Juan Antonio Quiroga ◽  
Vicente Carreño

Hepatitis C virus (HCV) infection in the absence of detectable antibodies against HCV and of viral RNA in serum is called occult HCV infection. Its prevalence and clinical significance in chronic hepatitis B virus (HBV) infection is unknown. HCV RNA was tested for in the liver samples of 52 patients with chronic HBV infection and 21 (40 %) of them were positive for viral RNA (occult HCV infection). Liver fibrosis was found more frequently and the fibrosis score was significantly higher in patients with occult HCV than in negative ones, suggesting that occult HCV infection may have an impact on the clinical course of HBV infection.


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.


2021 ◽  
Author(s):  
Shuisen Zheng ◽  
Huale Zhang ◽  
Rongxin Chen ◽  
Jianying Yan ◽  
Qing Han

Abstract Background: We aimed to investigate whether maternal chronic hepatitis B virus (HBV) infection affects preterm birth(PTB) in pregnant women. Methods: We retrospectively analyzed HBV-infected and non-infected pregnant women attending antenatal care at Fujian Provincial Maternity and Child Health Hospital, Fuzhou, China between January 1, 2016 to December 31, 2018. Participants were divided into HBV infection (n = 1302) and control (n = 12813) groups. We compared baseline data, pregnancy and perinatal complications, and preterm delivery outcomes between groups and performed subgroup comparisons and multiple logistics regression analysis to adjust for confounding factors. Results: The incidence of PTBs before 37 weeks was similar between the groups. PTBs before 34 weeks were significantly more among the HBV infection group than among the controls (1.6% VS. 0.8% ; P = 0.003) After adjusting for confounding factors through logistics regression, HBV infection was found to be an independent PTB risk factor before 34 weeks gestation (adjusted odds ratio 1.796; 95% confidence interval[1.071, 3.012]). According to the subgroup analysis based on whether hepatitis B e-antigen (HBeAg) was positive and whether alanine aminotransferase (ALT) levels were normal during the second trimester, PTB was more frequent in HBeAg negative HBV infection before 34 weeks than among controls(1.8% VS. 0.8%). The PTB rate for pregnant women with normal ALT and HBV infection before 34 weeks was higher than that of the controls (1.6% VS. 0.8%) Conclusion HBV infection is an independent risk factor for PTB before 34 weeks. Comprehensive programs focusing on pregnant women with HBV infection would reduce the incidence of adverse outcomes.


Author(s):  
Jonathan S. Mellen ◽  
Victor W. Xia ◽  
Mehrtash Hashemzadeh ◽  
David Imagawa ◽  
Mazen Jamal ◽  
...  

2019 ◽  
Vol 5 (3) ◽  
pp. 207-211
Author(s):  
Muayad A Merza ◽  
Sagvan Kareem Taha ◽  
Sara Muhsin Ibrahim ◽  
Ahmed Tayar Sadeeq ◽  
Mahabad R Abdulrahman

Thrombocytopenia is a relatively uncommon extra-hepatic manifestation of uncomplicated chronic hepatitis B virus (HBV) infection. This study has two aims: to assess the prevalence of thrombocytopenia in non-cirrhotic patients with chronic hepatitis B (CHB); and to determine the association of certain variables with thrombocytopenia in Duhok province. It is a case control study conducted in Azadi Teaching Hospital during June 2016 - May 2019. Chronic active hepatitis B was defined according to the following parameters: the presence of detectable hepatitis B surface antigen (HBsAg) in the blood longer than six months, positive or negative HBeAg, HBV-DNA level >2000 IU/ml, elevated ALT, and/or at least moderate histopathological fibrosis. Thrombocytopenia was defined as platelet counts below 150,000/μl. The obtained results were analyzed by entering data into Microsoft Excel 2010. A total of 379 CHB patients and 200 cases as control were enrolled in this study. Their mean ages were 33.62 ± 14.48 and 40.72 ± 18.56 for HBV and control cases, respectively. There were 236 (62.27%) males in the HBV patients and 109 (54.50%) males in the control group. Comparing both groups, significant association was found between HBV and younger age, cigarette smoking, and alcohol consumption. Chronic active hepatitis B without liver cirrhosis was strongly associated with an increased rate of thrombocytopenia. This finding is paramount as it is statistically significant (P = 0.042). Significant association with younger age and Syrian nationality was found more in CHB patients with thrombocytopenia compared to non-thrombocytopenic. In conclusion, chronic active hepatitis B is strongly associated with thrombocytopenia. As hypersplenism resulting from liver cirrhosis was excluded in our patients, the cause of thrombocytopenia is due to other mechanisms. Therefore, it is important to consider CHB in the differential diagnosis of patients presenting with isolated thrombocytopenia. Older age and Syrian nationality were predictors for developing thrombocytopenia in chronic active HBV infection. Asian J. Med. Biol. Res. June 2019, 5(3): 207-211


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