High Level of Hepatitis B Core–Related Antigen Associated With Increased Risk of Hepatocellular Carcinoma in Patients With Chronic HBV Infection of Intermediate Viral Load

Abstract Background: It has been reported that polymorphisms of signal transducer and activator of transcription (STAT) 3 and STAT4 might be associated with susceptibility to hepatitis B virus (HBV) infection and risk of chronic hepatocellular carcinoma (HCC). Owing to limitation of sample size and inconclusive results, we conducted a meta-analysis to clarify the association. Methods: We identified relevant studies by a systematic search of Medline/PubMed, Embase, Web of Science and the Cochrane Library up to 20 February 2019. The strength of the association measured by odds ratios (OR) with 95% confidence intervals (CIs) was studied. All the statistical analyses were conducted based on Review Manager 5.3 software. Results: A total of 5242 cases and 2717 controls from five studies were included for the STAT3 polymorphism, 5902 cases and 7867 controls from nine studies for the STAT4 polymorphism. Our results suggested that STAT3 rs1053004 polymorphism was a significant risk factor of chronic HBV infection (C vs. T: OR = 1.17, 95% CI: 1.07–1.29, PA=0.0007; CC + CT vs. TT: OR = 1.38, 95% CI: 1.09–1.76, PA=0.008). Validation with all the genetic models revealed that rs7574865 polymorphism of STAT4 gene was closely associated with chronic HBV infection (PA<0.01) and chronic hepatitis B (CHB)-related HCC (PA<0.05). Meanwhile, the authenticity of the above meta-analysis results was confirmed by trial sequential analysis (TSA). Conclusions: The meta-analysis showed that STAT3 rs1053004 polymorphism may be the risk for developing chronic HBV infection but not associated with HCC. The present study also indicates that STAT4 rs7574865 polymorphism increased the risk of chronic HBV infection and HCC.

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Studies on Mutual Relationship between Anti-HBx and sFas, IL-10 or IL-12 in Sera of Cases with Chronic Hepatitis B Infection

Infection International ◽

10.1515/ii-2017-0075 ◽

2014 ◽

Vol 3 (2) ◽

pp. 49-53

Author(s):

Ai-kun Ding ◽

Li-wei Guo ◽

Yong-kong Wang ◽

Wei Liu ◽

Cheng Li ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Chronic Hepatitis ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Sandwich Elisa ◽

Hbv Infection ◽

Mutual Relationship ◽

Chronic Hbv Infection ◽

Chronic Hbv

Abstract Objective To study the mutual relationship between anti-HBx and IL-10, IL-12 or soluble Fas (sFas) in sera of patients with chronic HBV infection and to explore the importance of anti-HBx detection as well as its role in the development of chronic HBV infection. Methods Total of 90 cases with chronic HBV infection were randomly selected, including 10 of asymptomatic carriers (ASC), 28 of chronic hepatitis B (CHB), 26 of liver cirrhosis (LC) and 26 patients of hepatocellular carcinoma (HCC). Their clinical data and blood samples were collected, and serum was prepared and stored at -73℃. Anti-HBx was detected with an indirect ELISA established in our earlier research, and levels of IL-10, IL-12 and Fas were determined with commercial double-antibody sandwich ELISA kits. The mutual relationship between anti-HBx and IL-10, IL-12 or sFas in serum were analyzed with the software SPSS 20.0. Results All levels of IL-10, IL-12 and sFas in peripheral blood showed a rising trend with development of chronic HBV infection. The levels of IL-10 in ASC, CHB, LC and HCC groups were 13.93 ± 14.40 ng/L, 39.38 ± 20.77 ng/L, 69.06 ± 46.37 ng/L and 62.82 ± 23.42 ng/L, respectively, levels of IL-12 in the 4 groups were 15.64 ± 23.04 ng/L, 68.50 ± 23.14 ng/L, 76.83 ± 12.82 ng/L and 83.74 ± 24.88 ng/L, respectively, and levels of sFas were 58.17 ± 77.42 ng/L, 179.88 ± 104.36 ng/L, 249.22 ± 107.80 ng/L and 252.98 ± 87.65 ng/L, respectively. Twenty-seven out of 90 patients showed a positive result for anti-HBx detection, including 1 in ASC, 4 in CHB, 12 in LC and 10 in HCC group. The levels of IL-10, IL-12 and sFas were higher in anti-HBx positive group than in negative group. Statistical analysis demonstrated significant differences of IL-10 and IL-12 between the two groups (P < 0.05), but the differences of sFas had no statistical significance (P = 0.094). Conclusions Anti-HBx antibody is not protective, and is closely related to IL-10, IL-12 and sFas. It may be an important serum indicator for aggravation from chronic hepatitis B to liver cirrhosis or hepatocellular carcinoma in patients with chronic HBV infection.

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Screening for chronic hepatitis B and C in migrants from Afghanistan, Iran, Iraq, the former Soviet Republics, and Vietnam in the Arnhem region, The Netherlands

Epidemiology and Infection ◽

10.1017/s0950268813003415 ◽

2014 ◽

Vol 142 (10) ◽

pp. 2140-2146 ◽

Cited By ~ 23

Author(s):

C. RICHTER ◽

G. TER BEEST ◽

E. H. GISOLF ◽

P. VAN BENTUM ◽

C. WAEGEMAEKERS ◽

...

Keyword(s):

Liver Cirrhosis ◽

Hepatitis B ◽

Risk Groups ◽

Hbv Infection ◽

Chronic Hbv Infection ◽

Increased Risk ◽

Chronic Hbv ◽

First Generation Migrants ◽

Chronic Hcv ◽

Former Soviet Republics

SUMMARYMigrants born in hepatitis B virus (HBV) and hepatitis C virus (HCV) endemic countries are at increased risk of being infected with these viruses. The first symptoms may arise when liver damage has already occurred. The challenge is to identify these infections early, since effective treatment has become available. In 2011 we conducted a screening project in first-generation migrants (FGMs) born in Afghanistan, Iran, Iraq, the former Soviet Republics, and Vietnam and living in Arnhem and Rheden. All participants were offered free blood screening for HBV and HCV. In total 959 participants were tested, with the country of origin known for 927, equating to 28·7% of all registered FGMs from the chosen countries. Nineteen percent (n = 176) had serological signs of past or chronic HBV infection and 2·2% (n = 21) had chronic HBV infection. The highest prevalence of chronic HBV infection was found in the Vietnamese population (9·5%, n = 12). Chronic HCV was found in two persons from the former Soviet Republics and one from Vietnam. Twenty-four percent (n = 5) of the newly identified patients with chronic HBV and one of the three patients with chronic HCV received treatment. Three of the patients, two with HCV and one with HBV, already had liver cirrhosis. The highest (9·5%) HBV prevalence was found in FGMs from Vietnam, indicating a high need for focusing on that particular immigrant population in order to identify more people with silent HBV infection. The fact that three patients already had liver cirrhosis underlines the necessity of early identification of HBV and HCV infection in risk groups.

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Impact of Hepatitis B Virus (HBV) X Gene Mutations on Hepatocellular Carcinoma Development in Chronic HBV Infection

Clinical and Vaccine Immunology ◽

10.1128/cvi.00661-12 ◽

2013 ◽

Vol 20 (1) ◽

pp. 127-127 ◽

Cited By ~ 1

Author(s):

Jong-Han Lee ◽

Kwang-Hyub Han ◽

Jae Myun Lee ◽

Jeon Han Park ◽

Hyon-Suk Kim

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Gene Mutations ◽

Hbv Infection ◽

Chronic Hbv Infection ◽

B Virus ◽

Chronic Hbv ◽

X Gene

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Increased risk of developing chronic HBV infection in infants born to chronically HBV infected mothers as a result of delayed second dose of hepatitis B vaccination

Vaccine ◽

10.1016/j.vaccine.2009.08.034 ◽

2009 ◽

Vol 27 (44) ◽

pp. 6110-6115 ◽

Cited By ~ 23

Author(s):

Piyanit Tharmaphornpilas ◽

Aim-orn Rasdjarmrearnsook ◽

Saowanee Plianpanich ◽

Pattaratida Sa-nguanmoo ◽

Yong Poovorawan

Keyword(s):

Hepatitis B ◽

Hbv Infection ◽

Hepatitis B Vaccination ◽

Chronic Hbv Infection ◽

Increased Risk ◽

Chronic Hbv

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Hepatitis B Virus

10.2310/im.5483 ◽

2021 ◽

Author(s):

Ming V. Lin ◽

April Wall

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Chronic Infection ◽

Treatment Options ◽

Hbv Infection ◽

Chronic Hbv Infection ◽

Chronic Hepatitis B Virus ◽

B Virus ◽

Chronic Hbv

Chronic hepatitis B virus (HBV) infection is a major health burden worldwide, with approximately 257 million people with chronic infection. HBV is a small partially double-stranded DNA virus that replicates within the nucleus of the hepatocyte and commonly leads to chronic infection. Chronic HBV infection can cause cirrhosis, hepatocellular carcinoma, and extrahepatic manifestations such as glomerulonephritis or vasculitis. The latter is due to deposition of circulating immune complex in the different tissues. The natural history of HBV infection can be conceptualized as a spectrum encompassing different phases, including immune tolerance, immune clearance, inactive carrier, and reactivation and resolution. The diagnosis of the different phases of chronic HBV infection relies on various HBV serologies, liver enzyme levels, and histology findings. There are currently eight therapies approved for the treatment of HBV. Tenofovir alafenamide was the most recently approved therapy with a better side effect profile compared with tenofovir disoproxil fumarate. With the recent advances in the basic research in hepatitis B, new treatment options may become available in the near-future. This review contains 9 figures, 11 tables and 80 references Key words: cirrhosis, entecavir, Hepadnaviridae, hepatitis B virus, hepatocellular carcinoma, precore mutation, tenofovir

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Hepatitis B Virus

10.2310/em.5483 ◽

2021 ◽

Author(s):

Ming V. Lin ◽

April Wall

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Chronic Infection ◽

Treatment Options ◽

Hbv Infection ◽

Chronic Hbv Infection ◽

Chronic Hepatitis B Virus ◽

B Virus ◽

Chronic Hbv

Chronic hepatitis B virus (HBV) infection is a major health burden worldwide, with approximately 257 million people with chronic infection. HBV is a small partially double-stranded DNA virus that replicates within the nucleus of the hepatocyte and commonly leads to chronic infection. Chronic HBV infection can cause cirrhosis, hepatocellular carcinoma, and extrahepatic manifestations such as glomerulonephritis or vasculitis. The latter is due to deposition of circulating immune complex in the different tissues. The natural history of HBV infection can be conceptualized as a spectrum encompassing different phases, including immune tolerance, immune clearance, inactive carrier, and reactivation and resolution. The diagnosis of the different phases of chronic HBV infection relies on various HBV serologies, liver enzyme levels, and histology findings. There are currently eight therapies approved for the treatment of HBV. Tenofovir alafenamide was the most recently approved therapy with a better side effect profile compared with tenofovir disoproxil fumarate. With the recent advances in the basic research in hepatitis B, new treatment options may become available in the near-future. This review contains 9 figures, 11 tables and 80 references Key words: cirrhosis, entecavir, Hepadnaviridae, hepatitis B virus, hepatocellular carcinoma, precore mutation, tenofovir

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Enhancers and attenuators of risk associations of chronic hepatitis B virus infection with hepatocellular carcinoma in type 2 diabetes

Endocrine Related Cancer ◽

10.1530/erc-12-0290 ◽

2012 ◽

Vol 20 (2) ◽

pp. 161-171 ◽

Cited By ~ 17

Author(s):

Xilin Yang ◽

Ying Wang ◽

Andrea O Y Luk ◽

Wing Yee So ◽

Ronald C W Ma ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Type 2 Diabetes ◽

Hepatitis B ◽

Hbv Infection ◽

Promoting Effect ◽

Chronic Hbv Infection ◽

Chronic Hepatitis B Virus ◽

B Virus ◽

Chronic Hbv

Chronic hepatitis B virus (HBV) infection promotes hepatocellular carcinoma (HCC) risk. In type 2 diabetes (T2D), use of insulin and statins was associated with reduced cancer risk while co-presence of low LDL cholesterol (LDLC <2.8 mmol/l) plus low triglyceride (TG; <1.7 mmol/l) increased cancer risk. There is experimental evidence showing that insulin insufficiency might promote HCC. In this study, we examined whether this lipid subphenotype and use of insulin or statins might modify the promoting effect of chronic HBV infection (indicated by the presence of hepatitis B surface antigen) on HCC. We analyzed data of 1319 T2D patients enrolled into the Hong Kong Diabetes Registry from December 1996 to January 2005 and followed up to 2005. Additive interaction was estimated using relative excess risk due to interaction and attributable proportion due to interaction. During 5782 person-years of follow-up, 1.74% (n=23) of patients developed HCC (incidence, 3.98; 95% confidence interval, 2.36–5.60/1000 person-years). HbA1c ≥7.0% and the lipid phenotype (LDLC <2.8 mmol/l plus TG <1.7 mmol/l) increased the hazard ratios (HRs) of chronic HBV infection for HCC from 3.74 to 74.96 and from 11.01 to 89.82 respectively with significant interactions. Use of insulin or statins decreased the HRs from 37.51 to 5.87 and from 64.94 to 16.99 respectively with significant interactions (allPvalues <0.05). These findings support our hypothesis that hyperglycemia and co-presence of low LDLC plus low TG might enhance, while insulin or statin usage might attenuate the promoting effect of chronic HBV infection on HCC in T2D.

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Antiviral l-Nucleosides Specific for Hepatitis B Virus Infection

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.45.1.229-235.2001 ◽

2001 ◽

Vol 45 (1) ◽

pp. 229-235 ◽

Cited By ~ 132

Author(s):

Martin L. Bryant ◽

Edward G. Bridges ◽

Laurent Placidi ◽

Abdesslem Faraj ◽

Anna-Giulia Loi ◽

...

Keyword(s):

Viral Load ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Hepatitis Virus ◽

Hbv Infection ◽

Virus Surface ◽

Chronic Hbv Infection ◽

Hbv Replication ◽

B Virus ◽

Chronic Hbv

ABSTRACT A unique series of simple “unnatural” nucleosides has been discovered to inhibit hepatitis B virus (HBV) replication. Through structure-activity analysis it was found that the 3′-OH group of the β-l-2′-deoxyribose of the β-l-2′-deoxynucleoside confers specific antihepadnavirus activity. The unsubstituted nucleosides β-l-2′-deoxycytidine, β-l-thymidine, and β-l-2′-deoxyadenosine had the most potent, selective, and specific antiviral activity against HBV replication. Human DNA polymerases (α, β, and γ) and mitochondrial function were not affected. In the woodchuck model of chronic HBV infection, viral load was reduced by as much as 108 genome equivalents/ml of serum and there was no drug-related toxicity. In addition, the decline in woodchuck hepatitis virus surface antigen paralleled the decrease in viral load. These investigational drugs, used alone or in combination, are expected to offer new therapeutic options for patients with chronic HBV infection.

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Hepatitis B-related hepatocellular carcinoma and stress: untangling the host immune response from clinical outcomes

Hepatic Oncology ◽

10.2217/hep-2020-0028 ◽

2020 ◽

pp. HEP35

Author(s):

Peter D Block ◽

Brianna Shinn ◽

Jin Hyang Kim ◽

Hie-Won Hann

Keyword(s):

Hepatocellular Carcinoma ◽

Immune Response ◽

Chronic Hepatitis ◽

Risk Factor ◽

Hepatitis B ◽

Chronic Stress ◽

Hbv Infection ◽

Host Factors ◽

Chronic Hbv Infection ◽

Chronic Hbv

Chronic hepatitis B virus (HBV) infection is a major public health challenge on the global scale. Affecting hundreds of millions worldwide, HBV is a leading risk factor for hepatocellular carcinoma (HCC). Clinical outcomes from chronic HBV infection are varied and appear to be influenced by a complex and dysregulated host immune response. In turn, much attention has been given to the immunologic response to HBV in an effort to identify host factors that lead to the development of HCC. However, the role of nonimmunologic host factors, such as chronic stress, in HBV-related HCC is poorly defined. Indeed, a growing appreciation for the effects of stress on chronic liver diseases raises the question of its role in chronic HBV infection. In this light, the present review will untangle the roles of key host factors in HBV-related HCC with an emphasis on chronic stress as a viable contributor. First discussed is the interplay of stress, inflammation and chronic liver disease. The host immune response’s role as a driver of HBV-related HCC is then reviewed, allowing for a close exploration of the effects of stress on immune function in chronic hepatitis B and as a potential risk factor for HBV-related HCC.

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