scholarly journals Serum pentraxin 3 as a biomarker of hepatocellular carcinoma in chronic hepatitis B virus infection

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Huan Deng ◽  
Xiude Fan ◽  
Xiaoyun Wang ◽  
Lu Zeng ◽  
Kun Zhang ◽  
...  

AbstractBiomarkers for early diagnosis of hepatocellular carcinoma (HCC) are needed in chronic hepatitis B virus (HBV) infection, a leading cause of HCC. We evaluated whether measurement of serum pentraxin 3 (PTX3) could improve diagnosis of HCC in chronic HBV infection. Data from patients with HBV-related chronic hepatitis (n = 159), cirrhosis (n = 99) and HCC (n = 107), and healthy controls (n = 151) were analyzed. Serum PTX3 concentration was measured by immunoassay. Area under the receiver operating characteristic curve (AUC) was applied to assess diagnostic accuracy. PTX3 levels were significantly higher in HBV patients than in healthy controls (P < 0.001) and in HCC than in chronic hepatitis (P < 0.001) or cirrhosis patients (P < 0.001). PTX3 was an independent risk factor of HCC [odds ratio (OR) 1.617, P < 0.001] and could distinguish HCC in chronic HBV infection [cutoff 9.231 ng/mL, AUC 0.929 with 95% confidence interval (CI) of 0.898–0.953], including α-fetoprotein (AFP) negative [cutoff 8.985 ng/mL, AUC (95%CI) 0.947 (0.908–0.973)] and early-stage HCC [cutoff 9.359 ng/mL, AUC (95%CI) 0.920 (0.885–0.947)]. Combination of PTX3 with AFP improved the discrimination of early HCC from chronic HBV infection [AUC (95%CI) 0.948 (0.918–0.970)]. In short, PTX3 measurement could identify HCC, including AFP-negative and early-stage HCC, in chronic HBV infection.

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.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Steffen B. Wiegand ◽  
Bastian Beggel ◽  
Anika Wranke ◽  
Elmira Aliabadi ◽  
Jerzy Jaroszewicz ◽  
...  

Abstract Chronic hepatitis B virus (HBV) infection may follow four different consecutive phases, which are defined by virology as well as biochemical markers and differ in terms of prognosis and need for antiviral treatment. Currently, host responses reflected by immune markers are not considered in this definition. We aimed to study soluble immune markers and their distribution in different phases of chronic HBV infection. In this cross-sectional retrospective study, we investigated a panel of 14 soluble immune markers (SIM) including CXCL10 in 333 patients with chronic HBV infection. In a small cohort of HBeAg positive patients we analyzed SIM before and after HBeAg seroconversion and compared seroconverters to patients with unknown outcome. Significant differences were documented in the levels of several SIM between the four phases of chronic HBV infection. The most pronounced difference among all investigated SIM was observed for CXCL10 concentrations with highest levels in patients with hepatitis. TGF-β and IL-17 revealed different levels between HBeAg negative patients. HBeAg positive patients with HBeAg seroconversion presented higher amounts of IL-12 before seroconversion compared to HBeAg positive patients with unknown follow up. SIM such as CXCL10 but also IL-12, TGF-β and IL-17 may be useful markers to further characterize the phase of chronic HBV infection.


BMJ Open ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. e027696 ◽  
Author(s):  
Jiahui Si ◽  
Canqing Yu ◽  
Yu Guo ◽  
Zheng Bian ◽  
Ruogu Meng ◽  
...  

ObjectivesChronic hepatitis B virus (HBV) infection is associated with a higher risk of liver diseases. Substantial uncertainty remains, however, about the associations of HBV infection with mortality from extrahepatic causes, especially from subtypes of cardiovascular diseases. We prospectively examined the association of chronic HBV infection with total and cause-specific mortality.DesignPopulation-based prospective cohort study.SettingChina Kadoorie Biobank in which participants from 10 geographically diverse areas across China were enrolled between 2004 and 2008.Participants475 801 participants 30–79 years of age without reporting major chronic diseases at baseline were enrolled. Hepatitis B surface antigen (HBsAg) was tested using an on-site rapid test strip at baseline.Primary and secondary outcome measuresTotal and cause-specific mortality.ResultsA total of 35 822 deaths were recorded during ~10 years of follow-up. In multivariable-adjusted analyses, compared with HBsAg-negative participants, HBsAg-positive participants had an increased risk of total mortality (HR=2.01, 95% CI: 1.91 to 2.12), which was higher in men (HR=2.16, 95% CI: 2.01 to 2.31) than in women (HR=1.74, 95% CI: 1.60 to 1.90). Presence of HBsAg was associated with increased mortality from liver cancer (1339 deaths, HR=13.95, 95% CI: 12.46 to 15.62), infections (410 deaths, HR=10.30, 95% CI: 8.21 to 12.94), digestive diseases (688 deaths, HR=6.83, 95% CI: 5.49 to 8.50), intracerebral haemorrhage (4077 deaths, HR=1.38, 95% CI: 1.14 to 1.68) and ischaemic heart diseases (4624 deaths, HR=1.31, 95% CI: 1.09 to 1.58). The positive association between HBsAg status and risk of death was stronger in participants younger than 50 years, smokers, physically active or non-hypertensive participants.ConclusionsAmong Chinese adults, chronic HBV infection was associated with increased mortality from a range of hepatic and extrahepatic diseases.


2021 ◽  
Vol 8 ◽  
Author(s):  
Zeyu Sun ◽  
Chenjie Huang ◽  
Yixian Shi ◽  
Rusha Wang ◽  
Jun Fan ◽  
...  

Hepatitis B virus (HBV) can hijack the host bile acids (BAs) metabolic pathway during infection in cell and animal models. Additionally, microbiome was known to play critical role in the enterohepatic cycle of BAs. However, the impact of HBV infection and associated gut microbiota on the BA metabolism in chronic hepatitis B (CHB) patients is unknown. This study aimed to unveil the distinct BA profiles in chronic HBV infection (CHB) patients with no or mild hepatic injury, and to explore the relationship between HBV, microbiome and BA metabolism with clinical implications.Methods: Serum BA profiles were compared between CHB patients with normal ALT (CHB-NALT, n = 92), with abnormal ALT (CHB-AALT, n = 34) and healthy controls (HCs, n = 28) using UPLC-MS measurement. Hepatic gene expression in CHB patients were explored using previously published transcriptomic data. Fecal microbiome was compared between 30 CHB-NALT and 30 HCs using 16S rRNA sequencing, and key microbial function was predicted by PICRUSt analysis.Results: Significant higher percentage of conjugated BAs and primary BAs was found in CHB patients even without apparent liver injury. Combinatory BA features can discriminate CHB patients and HCs with high accuracy (AUC = 0.838). Up-regulation of BA importer Na+ taurocholate co-transporting peptide (NTCP) and down-regulation of bile salt export pump (BSEP) was found in CHB-NALT patients. The microbial diversity and abundance of Lactobacillus, Clostridium, Bifidobacterium were lower in CHB-NALT patients compared to healthy controls. Suppressed microbial bile salt hydrolases (BSH), 7-alpha-hydroxysteroid dehydrogenase (hdhA) and 3-dehydro-bile acid Delta 4, 6-reductase (BaiN) activity were found in CHB-NALT patients.Conclusion: This study provides new insight into the BA metabolism influenced both by HBV infection and associated gut microbiome modulations, and may lead to novel strategy for clinical management for chronic HBV infection.


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.


2021 ◽  
Author(s):  
Ming V. Lin ◽  
April Wall

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


2021 ◽  
Author(s):  
Ming V. Lin ◽  
April Wall

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


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.


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.


2016 ◽  
Vol 10 (08) ◽  
pp. 851-856 ◽  
Author(s):  
Xue-ren Gao ◽  
Cui-min Wang ◽  
Wen-jun Wang ◽  
Guo-rong Han ◽  
Jian-qiong Zhang

Introduction: Maternal 25-hydroxyvitamin D [25(OH)D] deficiency has a negative influence on the health of the mother and the developing fetus. The aim of this study was to assess serum 25(OH)D status and its relationship to virologic and biochemical parameters in pregnant women with chronic hepatitis B virus (HBV) infection. Methodology: Serum 25(OH)D levels among 142 pregnant women with chronic HBV infection and 251 healthy pregnant women were measured using enzyme-linked immunosorbent assay. Results: The mean ± SD values for serum 25(OH)D levels were 13.63 ± 5.5 ng/mL in healthy pregnant women and 12.05 ± 3.3 ng/mL in pregnant women with chronic HBV infection (p < 0.01). Serum 25(OH)D levels were associated with seasonal variation in healthy pregnant women (p = 0.01); however, similar results were not observed in pregnant women with chronic HBV infection (p = 0.10). Furthermore, multivariate analysis indicated that only ALT level was independently associated with severe vitamin D deficiency (p = 0.01). A significant positive correlation was found between serum 25(OH)D level and ALT level in pregnant women with chronic HBV infection (r = 0.32; p < 0.001). Conclusions: Vitamin D levels were lower in pregnant women with chronic HBV infection compared with healthy pregnant women. Vitamin D supplementation can be routinely recommended for pregnant women in China.


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