The role of hepatitis B virus genome variations in HBV-related HCC: effects on host signaling pathways.

Hepatocellular carcinoma (HCC) is a significant global health issue, with a high prevalence in many regions. There are variations in the etiology of HCC in different regions, but most cases are due to long-term infection with viral hepatitis. Hepatitis B virus (HBV) is responsible for more than 50% of virus-related HCC, which highlights the importance of HBV in pathogenesis of the disease. The development and progression of HBV-related HCC is a complex multistep process that can involve host, viral, and environmental factors. Several studies have suggested that some HBV genome mutations as well as HBV proteins can dysregulate cell signaling pathways involved in the development of HCC. Furthermore, it seems that the pathogenicity, progression of liver diseases, response to treatment and also viral replication are different among HBV mutants. Understanding the relationship between HBV genome variations and host signaling pathway alteration will improve our understanding of the molecular pathogenesis of HBV-related HCC. Furthermore, investigating commonly dysregulated pathways in HBV-related HCC is necessary to discover more specific therapeutic targets and develop more effective strategies for HCC treatment. The objective of this review is to address the role of HBV in the HCC progression and primarily focus on the impacts of HBV genome variations on HCC-related signaling pathways.

Identification of plasma lncRNA-ATB levels in hepatitis B virus-related cirrhosis and non-cirrhotic chronic hepatitis B patients.

Long non-coding RNA-ATB (LncRNA-ATB) which is activated by transforming growth factor-ß (TGF-ß), is a key regulator of TGF-ß signaling pathway. TGF-ß plays an important role in various pathogenic processes, from inflammation and fibrosis to cirrhosis and cancer. In this study, we evaluated the plasma levels of lncRNA-ATB in patients with hepatitis B virus (HBV)-related cirrhosis and non-cirrhotic patients with chronic hepatitis B (CHB) and investigated the clinical values. Plasma samples were collected from 44 HBV-related cirrhosis patients, 45 non-cirrhotic CHB and 75 healthy controls. Briefly, after total RNA extraction and cDNA synthesis, quantitative real-time PCR (qPCR) was performed to detect plasma lncRNA-ATB levels. Results show the plasma levels of lncRNA-ATB in HBV-related cirrhosis patients were significantly higher in comparison to healthy controls (Fold change=2.60, p value=0.04). Also, we determined plasma levels of lncRNA-ATB as a specific biomarker of HBV-related cirrhosis (AUC=0.65, p value=0.03, Sensitivity 61.36%; Specificity 70.00%). In addition to, we investigated the plasma levels of lncRNA-ATB in non-cirrhotic CHB patients were significantly lower than healthy controls (Fold change= 0.33, p value=0.01). We also indicated plasma lncRNA-ATB levels were as a sensitive biomarker for diagnosis of non-cirrhotic CHB patients compared with healthy (AUC=0.66, p value=0.00, Sensitivity 71.11%; Specificity 57.78%). According to our results, circulating lncRNA-ATB has good specificity for diagnosing hepatitis B virus (HBV)-related cirrhosis and good sensitivity for diagnosis of non-cirrhotic chronic hepatitis B (CHB) patients.

Association between Interleukin-21 and Interleukin-21 receptor gene polymorphisms with susceptibility to chronic hepatitis B virus infection and HBV spontaneous clearance in Iranian population.

Hepatitis B virus (HBV) infection is a major public health concern due to the infection often leads to chronic infection, liver cirrhosis and also liver cancer. The host immune response to HBV infection and also genetic background play significant role in outcome of infection. Single nucleotide polymorphisms (SNPs) are the most important kind of variation in genetic sequences that caused by point mutations. As cytokines have major roles in viral infections, it seems that cytokine gene polymorphisms are independently associated with response to viral infections. Interleukin 21 (IL-21) plays an influential role in both innate and adaptive immune responses. Its specific receptor, IL-21R, produced and located on the surface of T, B and natural killer (NK) cells and is critical for the proliferation and differentiation of these immune effector cells. Many studies confirmed that the IL-21 involved in response to viral infections. We aimed to investigate the association of G/T IL-21 (rs2055979) and C/T IL-21R (rs3093390) gene polymorphisms with chronic hepatitis B virus infection and HBV spontaneous clearance in Iranian population. METHODS: In this study, blood samples were gathered from 320 patients with chronic HBV and 310 healthy controls and also 120 HBV spontaneous clearance individuals. Following genomic DNA extraction, genotypes of the selected SNPs determined by PCR and restriction fragment length polymorphism (RFLP) method. The results were analyzed by SPSS software using Chi-square, Logistic Regression, ANOVA and Independent Samples t-Test. RESULTS: According to our results, in IL-21R (rs3093390 C/T) gene polymorphism, allele frequency of T is statistically different in the HBV spontaneous clearance group compared to chronic HBV cases. But there is no significant difference between G/T IL-21 (rs2055979) and C/T IL-21R (rs3093390) genotypes distribution in three groups. Also we found that higher serum aspartate transaminase (AST) level in HBV spontaneous clearance group is significantly associated with TT genotype of IL-21 (rs2055979) compared to GG genotype (P value = 0.006). DISCUSSION: Our results showed that T allele frequency in IL-21R (rs3093390 C/T) gene polymorphism could consider as a host genetic factor for HBV spontaneous clearance. Probably we can serve it as a potential prognostic genetic marker for spontaneous clearance of HBV infection.