Rather than Rs1800796 Polymorphism, Expression of Interleukin-6 Is Associated with Disease Progression of Chronic HBV Infection in a Chinese Han Population

Interleukin-6 plays an important role in chronic inflammation as well as tumor growth and progression. Here, a case-control study was undertaken to investigate the association of rs1800796 polymorphism of IL-6 gene and serum levels with disease progression of chronic HBV infection. Rs1800796 polymorphism was genotyped in 641 Chinese Han patients with chronic HBV infection, including 23 IT, 25 IC, 292 CHB, 153 LC, and 148 HCC patients and 265 healthy controls. Serum IL-6 levels were measured in 23 IT, 25 IC, 47 CHB, 41 LC, and 49 HCC patients and 45 healthy controls, and the classifications of HCC were accorded to BCLC staging system. We found no significant association between rs1800796 polymorphism and disease progression of chronic HBV infection; however, serum IL-6 levels showed significant statistical differences between patients with CHB, LC, and HCC. Moreover, statistical differences can be observed in patients with terminal stage HCC compared with those of early to intermediate or advanced stage HCC. Our findings suggest that rs1800796 polymorphism unlikely contribute significantly to affect the progression of chronic HBV infection, and serum IL-6 levels can act as a useful indicator for disease progression and severity of chronic HBV infection.

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IL6 receptor358Ala variant and trans-signaling are disease modifiers in amyotrophic lateral sclerosis

Neurology Neuroimmunology & Neuroinflammation ◽

10.1212/nxi.0000000000000631 ◽

2019 ◽

Vol 6 (6) ◽

pp. e631 ◽

Cited By ~ 8

Author(s):

Marlena Wosiski-Kuhn ◽

Mac Robinson ◽

Jane Strupe ◽

Phonepasong Arounleut ◽

Matthew Martin ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Disease Progression ◽

Interleukin 6 ◽

Serum Levels ◽

Interleukin 6 Receptor ◽

The Common ◽

Paired Serum ◽

Control Study ◽

Lateral Sclerosis

ObjectiveTo test the hypothesis that patients with amyotrophic lateral sclerosis (ALS) inheriting the common interleukin 6 receptor (IL6R) coding variant (Asp358Ala, rs2228145, C allele) have associated increases in interleukin 6 (IL6) and IL6R levels in serum and CSF and faster disease progression than noncarriers.MethodsAn observational, case-control study of paired serum and CSF of 47 patients with ALS, 46 healthy, and 23 neurologic disease controls from the Northeastern ALS Consortium Biofluid Repository (cohort 1) was performed to determine serum levels of IL6, sIL6R, and soluble glycoprotein 130 and compared across groups and IL6R genotype. Clinical data regarding disease progression from a separate cohort of 35 patients with ALS from the Wake Forest ALS Center (cohort 2) were used to determine change in ALSFRS-R scores by genotype.ResultsPatients with ALS had increased CSF IL6 levels compared with healthy (p < 0.001) and neurologic (p = 0.021) controls. Patients with ALS also had increased serum IL6 compared with healthy (p = 0.040) but not neurologic controls. Additive allelic increases in serum IL6R were observed in all groups (average increase of 52% with the presence of the IL6R C allele; p < 0.001). However, only subjects with ALS had significantly increased CSF sIL6R levels compared with controls (p < 0.001). When compared across genotypes, only patients with ALS inheriting the IL6R C allele exhibit increased CSF IL6. ALSFRS-R scores decreased more in patients with ALS with the IL6R C allele than in those without (p = 0.019).ConclusionsTheses results suggest that for individuals inheriting the IL6R C allele, the cytokine exerts a disease- and location-specific role in ALS. Follow-up, prospective studies are necessary, as this subgroup of patients may be identified as ideally responsive to IL6 receptor–blocking therapies.

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

Scientific Reports ◽

10.1038/s41598-020-77332-3 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Huan Deng ◽

Xiude Fan ◽

Xiaoyun Wang ◽

Lu Zeng ◽

Kun Zhang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Chronic Hepatitis ◽

Early Stage ◽

Hbv Infection ◽

Healthy Controls ◽

Pentraxin 3 ◽

Chronic Hbv Infection ◽

Chronic Hepatitis B Virus ◽

B Virus ◽

Chronic Hbv

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.

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Distinct Bile Acid Profiles in Patients With Chronic Hepatitis B Virus Infection Reveal Metabolic Interplay Between Host, Virus and Gut Microbiome

Frontiers in Medicine ◽

10.3389/fmed.2021.708495 ◽

2021 ◽

Vol 8 ◽

Author(s):

Zeyu Sun ◽

Chenjie Huang ◽

Yixian Shi ◽

Rusha Wang ◽

Jun Fan ◽

...

Keyword(s):

Chronic Hepatitis ◽

Bile Acid ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Gut Microbiome ◽

Hbv Infection ◽

Healthy Controls ◽

Chronic Hbv Infection ◽

B Virus ◽

Chronic Hbv

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.

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Immune-Escape Mutations and Stop-Codons in HBsAg Circulates in a Relevant Proportion of Patients with Chronic HBV Infection Exposed to Anti-HBV Drugs in Europe: Implications for HBV Transmission in the Setting of Vaccination and Disease Progression

Journal of Hepatology ◽

10.1016/s0168-8278(16)00549-3 ◽

2016 ◽

Vol 64 (2) ◽

pp. S367-S368

Author(s):

L. Colagrossi ◽

L.E. Hermans ◽

R. Salpini ◽

S.D. Pas ◽

M. Alvarez ◽

...

Keyword(s):

Disease Progression ◽

Immune Escape ◽

Hbv Infection ◽

Chronic Hbv Infection ◽

Stop Codons ◽

Chronic Hbv ◽

Hbv Transmission

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Toll Like Receptor 4 D299G Associates with Disease Progression in Caucasian Patients with Chronic HBV Infection: Relationship with Gender

Journal of Clinical Immunology ◽

10.1007/s10875-012-9822-9 ◽

2012 ◽

Vol 33 (2) ◽

pp. 313-316 ◽

Cited By ~ 9

Author(s):

Annarosa Cussigh ◽

Carlo Fabris ◽

Giovanna Fattovich ◽

Edmondo Falleti ◽

Sara Cmet ◽

...

Keyword(s):

Disease Progression ◽

Hbv Infection ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Chronic Hbv Infection ◽

Caucasian Patients ◽

Chronic Hbv

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Single Nucleotide Polymorphisms rs2227284, rs2243283 and rs2243288 in the IL-4 Gene Show no Association with Susceptibility to Chronic Hepatitis B in a Chinese Han Population

Infection International ◽

10.1515/ii-2017-0068 ◽

2014 ◽

Vol 3 (1) ◽

pp. 16-21

Author(s):

Qin Zhou ◽

Yu-feng Gao ◽

Xiao-miao Zhao ◽

Fa-ming Pan ◽

Xu Li

Keyword(s):

Hepatitis B ◽

Hbv Infection ◽

Nucleotide Polymorphisms ◽

Chinese Han ◽

Single Nucleotide ◽

P Values ◽

Chronic Hbv Infection ◽

Han Population ◽

B Virus ◽

Chronic Hbv

Abstract Objective To investigate the relationship between single nucleotide polymorphisms (SNPs) of the interleukin-4 (IL-4) gene and outcome of hepatitis B virus (HBV) infection in a Chinese Han population. Methods Total of 501 patients with chronic hepatitis B virus (HBV) infection and 301 controls with selflimiting HBV infection were studied. Three tag SNPs in the IL-4 gene (rs2227284G/T, rs2243283C/G and rs2243288A/G) were genotyped by the Multiplex snapshot technique. The genotype and allele frequencies were calculated and analyzed. Results The three SNPs showed no significant genotype/allele associations with chronic HBV infection. Overall allele P values were: rs2227284, P = 0.655, odds ratio (OR) [95% confidence interval (CI)] = 1.070 (0.793-1.445); rs2243283, P = 0.849, OR (95% CI) = 0.976 (0.758-1.257); rs2243288, P = 0.659, OR (95% CI) = 1.060 (0.818-1.375). Overall genotype P values were: rs2227284, P = 0.771; rs2243283, P = 0.571; rs2243288, P = 0.902. There were no statistically significant differences between patients with chronic HBV infection and controls. Haplotypes generated by these three SNPs also had no significant differences between the two groups. Conclusions The three tag SNPs of IL-4 were not associated with the outcome of HBV infection in the Han Chinese population.

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