scholarly journals The Potential of Serum IFN-γ for Determining the Progression of Chronic Hepatitis B

Author(s):  
Tri Nugraha Susilawati ◽  
Winda Rahayuningtyas ◽  
Triyanta Yuli Pramana

Background: A persistent infection of hepatitis B virus (HBV) can cause liver cirrhosis and hepatocarcinoma even though the virus itself is non-cytopathic and does not cause cell injury. It has been asserted that liver injury in chronic HBV infection is attributed to the host immune system responding to HBV infection. Cytokines have a critical role in mediating immune responses to viral infection. This study aimed to determine the correlation between the levels of serum IFN-γ, IL-2, IL-17, and TNF- α with the progress of chronic HBV infection that was determined through provisional diagnosis, patient’s age, and the levels of serum transaminases.Method: Blood samples were collected from patients with chronic hepatitis B and the levels of serum IFN-γ, IL-2, IL-17, and TNF-α were measured by using ELISA. The correlation between each cytokine levels and the provisional diagnosis, patient’s age, and serum transaminases were analyzed by using the Spearman correlation test with a p value of 0.05 is considered as statistically significant.Results: A total of 47 samples were collected from patients with chronic hepatitis B (n=38), chronic hepatitis B with liver cirrhosis (n = 6), and chronic hepatitis B with hepatocellular carcinoma (nc = 3). A significant correlation was found between the levels of serum IFN-γ and aspartate aminotransferase (AST) (p = 0.04).Conclusion: The increase of serum IFN-γ and AST levels may highlight the importance of these particular cytokine and liver transaminase in the immune response to chronic HBV infection since IFN-γ is capable to induce apoptotic cell death which promotes AST release and facilitates liver injury.

2014 ◽  
Vol 3 (2) ◽  
pp. 49-53
Author(s):  
Ai-kun Ding ◽  
Li-wei Guo ◽  
Yong-kong Wang ◽  
Wei Liu ◽  
Cheng Li ◽  
...  

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.


2020 ◽  
Vol 18 (4) ◽  
pp. 149-152
Author(s):  
M.A. Abdukadyrova ◽  
◽  
S.M. Sharapov ◽  
A.S. Khikmatullaeva ◽  
◽  
...  

We have conducted a pilot study to identify the association between the HBsAg level and activity of the pathological process in the liver, as well as possibility of quantitative assessment of HBsAg for monitoring chronic liver diseases caused by hepatitis B virus (HBV) and hepatitis D virus (HDV). Objective. To assess the possibility of using HBsAg levels as a predictor of disease activity and prognosis in patients with chronic HBV infection with delta-agent. Patients and methods. We analyzed serum specimens from 30 patients with HDV and HBV co-infection. Among 15 patients with chronic hepatitis B with delta-agent, there were 5 HBV DNA positive and 10 HBV DNA negative. Among patients with liver cirrhosis, HBV DNA was detected in 11 individuals, while 4 individuals had undetectable HBV DNA levels. Results. We found that mean HBsAg level in patients with chronic HBV infection and negative HBV DNA was 1.9 ± 0.56 IU/mL. Mean HBsAg level in patients with chronic HBV infection with delta-agent and positive HBV DNA was 4.3 ± 0.62 IU/mL (p < 0.05). High HBsAg levels correlated with elevated ALT in patients with chronic hepatitis B and delta-agent. Patients with liver cirrhosis caused by HDV had normal ALT levels, but elevated bilirubin concentrations regardless of HBV DNA presence and HBsAg level. Conclusion. High levels of HBsAg can be considered as a predictor of active disease in patients with chronic HBV infection with delta-agent and also a marker of transformation of chronic hepatitis B with delta-agent into liver cirrhosis. Key words: chronic hepatitis B with delta agent, liver cirrhosis, enzyme-linked immunosorbent assay, HBsAg levels, polymerase chain reaction


2019 ◽  
Vol 39 (6) ◽  
Author(s):  
Han Shi ◽  
Hongyan He ◽  
Suvash Chandra Ojha ◽  
Changfeng Sun ◽  
Juan Fu ◽  
...  

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.


Viruses ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 97 ◽  
Author(s):  
Fu-Hsiung Su ◽  
Thi Nga Le ◽  
Chih-Hsin Muo ◽  
Sister Arlene Te ◽  
Fung-Chang Sung ◽  
...  

Chronic hepatitis B virus (HBV) infections and colorectal cancer (CRC) are prevalent in Taiwan. We carried out a population-based case-control study to assess the association between HBV infection and CRC risk. Using the National Health Insurance Research Database of Taiwan, we identified 69,478 newly diagnosed patients with CRC from 2005 to 2011. We further randomly selected 69,478 age- and gender-matched controls without CRC from the same database. Odds ratios (ORs) were calculated to evaluate the association between chronic HBV infection and CRC using a logistic regression analysis. HBV infection was found to be associated with the risk of CRC (OR = 1.27, 95% confidence interval (CI) = 1.20–1.33). This relationship was similar in men and women. Age-specific analysis revealed that the CRC risk associated with HBV decreased with age. The adjusted ORs for patients aged <55, 55–64, and 65–74 years were 1.63 (95% CI = 1.48–1.79), 1.24 (95% CI = 1.13–1.37), and 1.02 (95% = 0.92–1.13), respectively. In conclusion, this study suggests that chronic HBV infection is significantly associated with an increased risk of CRC. Monitoring the risk of CRC development in young patients with HBV infection is crucial.


2010 ◽  
Vol 28 (19) ◽  
pp. 3199-3202 ◽  
Author(s):  
Andrew S. Artz ◽  
Mark R. Somerfield ◽  
Jordan J. Feld ◽  
Andrew F. Giusti ◽  
Barnett S. Kramer ◽  
...  

Purpose An American Society of Clinical Oncology (ASCO) provisional clinical opinion (PCO) offers timely clinical direction to ASCO's membership following publication or presentation of potentially practice-changing information. This PCO addresses recommendations for chronic hepatitis B virus (HBV) infection screening in patients receiving cytotoxic or immunosuppressive chemotherapy for treatment of malignant diseases. Clinical Context The Centers for Disease Control and Prevention (CDC) issued Recommendations for Identification and Public Health Management of Persons with Chronic Hepatitis B Virus Infection, recommending screening for hepatitis B infection (hepatitis B surface antigen [HBsAg], antihepatitis B core antigen [anti-HBc], and antibodies to HBsAg [anti-HBs]) for “persons receiving cytotoxic or immunosuppressive therapy (eg, chemotherapy for malignant diseases…).” Provisional Clinical Opinion The evidence is insufficient to determine the net benefits and harms of routine screening for chronic HBV infection in individuals with cancer who are about to receive cytotoxic or immunosuppressive therapy or who are already receiving therapy. Individuals with cancer who undergo certain cytotoxic or immunosuppressive therapies and have HBV infection or prior exposure to HBV may be at elevated risk of liver failure from HBV reactivation. As such, HBV screening requires clinical judgment. Physicians may consider screening patients belonging to groups at heightened risk for chronic HBV infection or if highly immunosuppressive therapy is planned. Highly immunosuppressive treatments include, but are not limited to, hematopoietic cell transplantation and regimens including rituximab. Screening based on a high risk of prior HBV exposure or risk of reactivation due to planned therapeutic regimens should include testing for HBsAg as a serologic marker for HBV infection. In some populations, testing for anti-HBc should also be considered. There is no evidence to support serologic testing for anti-HBs in this context. When evidence for chronic HBV infection is found, antiviral therapy before and throughout the course of chemotherapy may be considered to reduce the risk of HBV reactivation, although evidence from controlled trials of this approach is limited. Screening and/or treating HBV infection should not delay the initiation of chemotherapy. NOTE. ASCO's provisional clinical opinions (PCOs) reflect expert consensus based on clinical evidence and literature available at the time they are written, and are intended to assist physicians in clinical decision-making and identify questions and settings for further research. Due to the rapid flow of scientific information in oncology, new evidence may have emerged since the time a PCO was submitted for publication. PCOs are not continually updated and may not reflect the most recent evidence. PCOs address only the topics specifically identified in the PCO and are not applicable to interventions, diseases or stages of disease not specifically identified. PCOs cannot account for individual variation among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It is the responsibility of the treating physician or other health care provider, relying on independent experience and knowledge of the patient, to determine the best course of treatment for the patient. Accordingly, adherence to any PCO is voluntary, with the ultimate determination regarding its application to be made by the physician in light of each patient's individual circumstances. ASCO PCOs describe the use of procedures and therapies in clinical practice and cannot be assumed to apply to the use of these interventions in the context of clinical trials. ASCO assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of ASCO's PCOs, or for any errors or omissions.


2019 ◽  
Vol 221 (9) ◽  
pp. 1448-1461
Author(s):  
Eva Loffredo-Verde ◽  
Sonakshi Bhattacharjee ◽  
Antje Malo ◽  
Julia Festag ◽  
Anna D Kosinska ◽  
...  

Abstract Background Chronic hepatitis B develops more frequently in countries with high prevalence of helminth infections. The crosstalk between these 2 major liver-residing pathogens, Schistosoma mansoni and hepatitis B virus (HBV), is barely understood. Methods We used state-of-the-art models for both acute and chronic HBV infection to study the pathogen-crosstalk during the different immune phases of schistosome infection. Results Although liver pathology caused by schistosome infection was not affected by either acute or chronic HBV infection, S mansoni infection influenced HBV infection outcomes in a phase-dependent manner. Interferon (IFN)-γ secreting, HBV- and schistosome-specific CD8 T cells acted in synergy to reduce HBV-induced pathology during the TH1 phase and chronic phase of schistosomiasis. Consequently, HBV was completely rescued in IFN-γ-deficient or in TH2 phase coinfected mice demonstrating the key role of this cytokine. It is interesting to note that secondary helminth infection on the basis of persistent (chronic) HBV infection increased HBV-specific T-cell frequency and resulted in suppression of virus replication but failed to fully restore T-cell function and eliminate HBV. Conclusions Thus, schistosome-induced IFN-γ had a prominent antiviral effect that outcompeted immunosuppressive effects of TH2 cytokines, whereas HBV coinfection did not alter schistosome pathogenicity.


2020 ◽  
Vol 10 (1) ◽  
pp. 55-59
Author(s):  
Amal A. Mohamed ◽  
Sherief Abd-Elsalam ◽  
Mariam Zaghloul ◽  
Mohamed Attala ◽  
Rania A. Khattab ◽  
...  

Background & Aims: Several studies, in different populations, have focused on the role of HLA-DQ gene polymorphism in the pathogenesis of HBV infection. However, these findings are still controversial. This study aimed to determine HLA-DQ polymorphism in Chronic HBV patients and its impact on the response to antiviral therapy. Methods: This study was carried out on a total number of 188 participants, they were subdivided as follows: Group I (patients’ group): included 97 patients with chronic hepatitis B viral infection that was further subdivided according to response to treatment into responder and non-responder subgroups, Group II (Control group): included 91 normal healthy subjects who were matched to the patient group by sex and age. PCR (Polymerase Chain Reaction) testing, for HBV-DNA, was done for all participants enrolled in the study to measure the viral virus load before and after treatment. HLA- DQ polymorphism allelic discrimination assay was assayed using the Real-time equipment. Results: In a general analysis for the SNP rs7453920, the overall genotypes frequencies were 37% for A/A, 60.6% for A/G, and 37% for G/G. The G alleles of HLA-DQ rs7453920 were significantly increased in chronic HBV infection patients. A total of 77 (79.4%) patients were responders. Among this group, 72.7% were male, and the average age was 38.59 ±9.15 years. On evaluation of the association between polymorphisms in HLA-DQ gene and treatment response, the results indicated that response to treatment declined when patients were carrying the more unfavorable rs 7453920 GG with a response rate of 64%. Patients carrying the mutant allele AG, or the wild type allele AA were more likely to achieve a higher rate of response (84.8% and 83.3%, respectively). Conclusion: The presence of HLA-DQB2 rs 7453920-G serves as a risk factor for chronic HBV infection and treatment failure in the Egyptian population.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jinglan Jin ◽  
Yuwei Liu ◽  
Xiaotong Xu ◽  
Zhongfeng Wang ◽  
Junqi Niu

Abstract Background Fc gamma receptor IIb (FcγRIIb) is an important inhibitory receptor that plays vital roles in regulating various immune response processes and the pathogenesis of many infectious diseases. The purpose of our research was to evaluate FcγRIIb expression in serum and liver biopsy specimens from hepatitis B virus (HBV)-infected patients and to explore the association of FcγRIIb with chronic HBV infection. Methods Enzyme-linked immunosorbent assay (ELISA) was adopted to measure the serum FcγRIIb levels in 119 HBV-infected patients and 24 healthy controls. An immunohistochemical method was then employed to identify FcγRIIb expression in biopsy specimens from patients with chronic hepatitis B (CHB). The integrated optical density (IOD) value was measured to represent FcγRIIb expression levels. Results Serum FcγRIIb levels were decreased in CHB patients compared to controls (P < 0.001). The FcγRIIb levels in the CHB patient group were remarkably lower than those in the HBV carrier group (P < 0.001). In addition, FcγRIIb levels were negatively associated with AST and ALT (r = −0.3936, P = 0.0063; r = −0.3459, P = 0.0097, respectively). The IOD values of FcγRIIb expression in the moderate and severe CHB groups were significantly lower than those in the control group (P = 0.006 and P < 0.001, respectively). The FcγRIIb level tended to be lower with pathological changes related to hepatitis. Furthermore, correlation analysis revealed that FcγRIIb had negative correlations with AST and ALT (r = −0.688, P = 0.0016; r = −0.686, P = 0.0017, respectively) but a positive association with the platelet count (r = 0.6464, P = 0.0038). Conclusions FcγRIIb levels are significantly related to chronic HBV infection and the progression of CHB. Changes in FcγRIIb may affect the progression of liver inflammation and fibrosis in CHB patients.


2021 ◽  
Vol 5 (4) ◽  
pp. 15-20
Author(s):  
Nicholas Noverati ◽  
Daniel Garrido ◽  
Dina Halegoua-DeMarzio ◽  
Hie-Won Hann

Introduction: Chronic hepatitis B virus (HBV) infection is prevalent worldwide and up to 40% is known to progress to serious complications including cirrhosis and hepatocellular carcinoma (HCC). The outcome of the remaining infected individuals is not well documented. Our case series describes a longer cohort of chronic HBV infections that have remained asymptomatic with no progression of liver disease. Case Series: Thirty-three patients (ages 31-84) with chronic HBV infection were identified. All patients had no significant elevations in transaminase levels and were followed over 32 years, collectively. 18/33 had a fluctuating greater magnitude of HBV viral load with no elevations in tumor marker or significant radiographic changes to their liver. Discussion/Conclusion: Chronic HBV infection can lead to serious complications over time, the mechanism of which are not well understood. The variation in patients that do and do not develop these complications stresses the importance of the individual response to the virus and may highlight host immune response differences.


Author(s):  
Terence T. Lao

Antenatal screening for hepatitis B surface antigen seropositivity is widely adopted to identify pregnant women with chronic hepatitis B virus (HBV) infection in order to target their newborn infants for combined passive-active neonatal immunization to prevent the maternal-to-child transmission of HBV. It is less certain whether the presence of chronic HBV infection in these largely asymptomatic women could impact their pregnancy outcome. There is now gathering information in the literature, though sometimes conflicting, on the obstetric implications of chronic HBV infection. The conflicting data is most probably related to confounding factors such as the immunological phase of chronic HBV infection, viral genotype and activity, presence of hepatic inflammation and other co-existing liver disorders such as non-alcoholic fatty liver disease, and coinfection with other virus such as hepatitis C virus and micro-organisms, which are usually not examined, but which could have made significant influence on the occurrence of many of the pregnancy complications and adverse fetal and neonatal outcome. For pregnancy complications, the evidence suggests association with increased gestational diabetes mellitus, preterm birth, intrahepatic cholestasis of pregnancy, caesarean delivery, and postpartum haemorrhage, probably increased placental abruption and prelabour rupture of the membranes, and no effect or a reduction in the hypertensive disorders of pregnancy, especially preeclampsia. For perinatal outcome, there may be increased miscarriage and fetal malformations, and increase in both low birthweight and large-for-gestational age/macrosomic infants, as well as increased intrauterine fetal demise/stillbirth and fetal distress. However, most studies have not elaborated on the mechanisms or explanations of many of the adverse outcomes. Taken together, maternal chronic HBV infection increases the risk of adverse obstetric outcome overall, but further prospective studies are warranted to elucidate the reasons and mechanisms of, and with a view to mitigate, these adverse obstetric outcomes.


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