scholarly journals Clinical relevance of the in situ assay for HBV DNA: a cross-sectional study in patients with chronic hepatitis B

2020 ◽  
Vol 73 (12) ◽  
pp. 813-818
Author(s):  
Danping Liu ◽  
Tong Xu ◽  
Bisheng Shi ◽  
Wei Lu ◽  
Ye Zheng ◽  
...  

AimsThe visualisation of HBV DNA in liver sections of patients with chronic hepatitis B (CHB) in our previous report uncovered a mosaic distribution of viral antigens and nucleic acids. Here we aim to further explore the clinical utility of the in situ hybridisation (ISH) assay for HBV DNA.MethodISH of HBV DNA along with immunohistochemistry (IHC) of HBsAg, HBcAg and routine histopathology analysis was performed in 313 treatment-naive patients with CHB. Serum HBcrAg and HBcAb titre were also measured in addition to basic biochemical and virological parameters.ResultsThe ISH of HBV DNA, HBsAg and HBcAg showed 95.2%, 97.1% and 42.8% positive rate, respectively. The staining pattern of HBV DNA differs significantly with that of HBsAg. Intrahepatic HBV DNA exhibited high-level of correlations with viral load, HBcrAg and HBsAg titre. In HBeAg-negative patients, higher intrahepatic HBV DNA is associated with histological evidence of liver inflammation and fibrosis, whereas no such trend was observed in HBeAg-positive patients. Finally, a triple staining protocol that combined the detection of HBV DNA, HBsAg and collagen fibre was developed to enable better evaluation of viral replication and antigen expression in the context of disease progression.ConclusionsThe ISH assay for HBV DNA reflects the vigour of intrahepatic viral replication. It is complementary to the routine IHC assay for viral antigens and also related to the histopathological progression of liver diseases. The application of the HBV DNA ISH assay may help a better evaluation of virological and pathological condition of patients with CHB.

Gut ◽  
2020 ◽  
pp. gutjnl-2020-323300
Author(s):  
Valentina Svicher ◽  
Romina Salpini ◽  
Lorenzo Piermatteo ◽  
Luca Carioti ◽  
Arianna Battisti ◽  
...  

ObjectiveThe involvement of HBV DNA integration in promoting hepatocarcinogenesis and the extent to which the intrahepatic HBV reservoir modulates liver disease progression remains poorly understood. We examined the intrahepatic HBV reservoir, the occurrence of HBV DNA integration and its impact on the hepatocyte transcriptome in hepatitis B ‘e’ antigen (HBeAg)-negative chronic hepatitis B (CHB).DesignLiver tissue from 84 HBeAg-negative patients with CHB with low (n=12), moderate (n=25) and high (n=47) serum HBV DNA was analysed. Covalently closed circular DNA (cccDNA), pregenomic RNA (pgRNA) were evaluated by quantitative PCR, whole exome and transcriptome sequencing was performed by Illumina, and the burden of HBV DNA integrations was evaluated by digital droplet PCR.ResultsPatients with low and moderate serum HBV DNA displayed comparable intrahepatic cccDNA and pgRNA, significantly lower than in patients with high HBV DNA, while hepatitis B core-related antigen correlated strongly with the intrahepatic HBV reservoir, reflecting cccDNA quantity. Whole exome integration was detected in a significant number of patients (55.6%, 14.3% and 25% in high, moderate and low viraemic patients, respectively), at a frequency ranging from 0.5 to 157 integrations/1000 hepatocytes. Hepatitis B surface antigen >5000 IU/mL predicted integration within the exome and these integrations localised in genes involved in hepatocarcinogenesis, regulation of lipid/drug metabolism and antiviral/inflammatory responses. Transcript levels of specific genes, including the proto-oncogene hRAS, were higher in patients with HBV DNA integration, supporting an underlying oncogenic risk in patients with low-level to moderate-level viraemia.ConclusionsHBV DNA integration occurs across all HBeAg-negative patients with CHB, including those with a limited HBV reservoir; localising in genes involved in carcinogenesis and altering the hepatocyte transcriptome.


2007 ◽  
Vol 13 (20) ◽  
pp. 2878 ◽  
Author(s):  
Hai-Ying Lu ◽  
Li-Wei Zhuang ◽  
Yan-Yan Yu ◽  
Hadad Ivan ◽  
Chong-Wen Si ◽  
...  

2021 ◽  
Author(s):  
Yang Wang ◽  
Hao Liao ◽  
Zhongping Deng ◽  
Yanna liu ◽  
Dandan bian ◽  
...  

Abstract Background: To evaluate the predictive value of serum HBV DNA, HBV RNA, HBcrAg, HBsAg, intrahepatic HBV DNA, and cccDNA for HBeAg clearance and seroconversion during long-term treatment of nucleos(t)ide analogues (NAs) in patients with chronic hepatitis B (CHB).Method: A single center, prospective cohort of CHB patients enrolled between June 2007 and July 2008 was used for this study. Serum HBV RNA levels were retrospectively measured at baseline, 6, 12, 24, 36, 48, 60, 72, and 84 months post-NAs treatment. Serum HBsAg and HBcrAg levels were quantified at baseline, month 6, 60, and 72. Histological sample from liver biopsy at baseline and month 60 were analyzed for intrahepatic HBV DNA and cccDNA.Results: Eighty-three HBeAg patients were enrolled with an median follow-up time of 108 months (range 18-138 months). Of them, 53 (63.86%) patients achieved HBeAg clearance, and 37 (44.58%) achieved HBeAg seroconversion. Only baseline HBV RNA was independently associated with HBeAg clearance (OR=0.50, 95%CI 0.309-0.809, P=0.005) and seroconversion (OR=0.689, 95% CI 0.513-0.925, P=0.013). The independent negative association with HBeAg clearance and seroconversion remained for HBV RNA levels at month 6 (OR=0.42, 95%CI 0.248-0.714, P=0.001; OR=0.44, 95%CI 0.260-0.744, P=0.002) and month 12 (OR=0.39, 95%CI 0.253-0.592, P<0.001; OR=0.58, 95%CI 0.427-0.798, P=0.001). The AUC of baseline HBV RNA for predicting the HBeAg clearance and seroconversion were 0.81 (95%CI: 0.70-0.89) and 0.68 (95%CI: 0.56-0.78), respectively, higher than that of HBV DNA, HBsAg and HBcrAg.Conclusion: Lower serum HBV RNA at baseline, month 6 and 12 post NAs treatment could predict HBeAg clearance and seroconversion during long-term NAs treatment.


2011 ◽  
pp. 25-29
Author(s):  

Aims: To measure the prevalence of HBV genotypes in chronic hepatitis B patients and their relation to HBeAg and HBV DNA level. Methods: 81 patients were enrolled in this study from January 2009 to December 2010. Clinical, laboratory data were collected during the patient’s hospitalization. Sera were quantitatively tested for HBeAg and HBV DNA. HBV genotyping was made by real-time PCR. Results: Among the 81 patients, 60.5% had genotype B, 26.7% had genotype C and 8.6% had mixed genotype B-C. Prevalence of symptoms (fatigue, anorexia, insomnia...) was higher in genotype C than in genotype B. Genotype C patients had positivity higher HBeAg than genotype B patients (56% vs. 38,8%, p <0.05). The rate of HBV DNA > 107 copies/mL was higher in genotype C group than in genotype B group (36% vs. 28,6%, p > 0.05). Conclusions: Most of the patients had genotypes B or C. Patients with genotype C had positive HBeAg and may be related to higher serological HBV DNA level than in genotype B.


Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 77
Author(s):  
Jing-Hua Wang ◽  
Sung-Bae Lee ◽  
Dong-Soo Lee ◽  
Chang-Gue Son

Oxidative stress plays a pivotal role in the progression of chronic hepatitis B; however, it is unclear whether the status of blood oxidative stress and antioxidant components differs depending on the degree of hepatic fibrosis. To explore the relationship between oxidative stress/antioxidant capacity and the extent of hepatic fibrosis, fifty-four subjects with liver fibrosis (5.5 ≤ liver stiffness measurement (LSM) score ≤ 16.0 kPa) by chronic hepatitis B virus (HBV) were analyzed. From the analysis of eight kinds of serum oxidative stress/antioxidant profiles and liver fibrosis degrees, the level of total antioxidant capacity (TAC) reflected a negative correlation with the severity of hepatic fibrosis (Pearson correlation, r = −0.35, p = 0.01). Moreover, TAC showed higher sensitivity (73.91%) than the aspartate transaminase (AST) to platelet ratio index (APRI, 56.52%) in the receiver operating characteristic (ROC) curves. Interestingly, the TAC level finely reflected the fibrosis degree in inactive carriers (HBV DNA < 2000 IU/mL), while the APRI did in active carriers (HBV DNA > 2000 IU/mL). In conclusion, TAC is a promising biomarker for evaluating the progression of liver fibrosis in patients with HBV, and this finding may indicate the involvement of TAC-composing factors in the pathogenesis of hepatic fibrosis in chronic HBV carriers.


Cytokine ◽  
2021 ◽  
pp. 155525
Author(s):  
Walid Ben Selma ◽  
Ahmed Baligh Laribi ◽  
Sana Alibi ◽  
Jalel Boukadida

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