Changes in circulating Foxp3^+ regulatory T cells and interleukin-17-producing T helper cells during HBV-related acute-on-chronic liver failure

AIM: To longitudinally investigate cytokine gene expression and protein levels in Th17 and Treg cells, to observe T-cell phenotypes during hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACHBLF) and to analyze changes in Th17 and Treg phenotypes during disease progression.

Viral infection parameters not nucleoside analogue itself correlates with host immunity in nucleoside analogue therapy for chronic hepatitis B

AIM: To determine the relationship between host immunity and the characteristics of viral infection or nucleoside analogues (NAs) themselves in patients with chronic hepatitis B (CHB) receiving NA therapy.

Progression and status of antiviral monitoring in patients with chronic hepatitis B:From HBsAg to HBV RNA

As alternative indexes of hepatitis B virus(HBV),co-valently closed circular DNA(cccDNA) transcriptional activity,hepatitis B surface antigen(HBsAg),hepatitis B core-related antigen(HBcrAg),and peripheral blood RNA known as pgRNA,have been advocated as novel serum markers for prediction of prognosis and treatment response in chronic hepatitis B(CHB). Since the availability of commercial quantitative assays of HBsAg in 2011,HBsAg has been widely used for predicting treatment response of patients with CHB. Patients who received interferon therapy have shown a sharper reduction of HBsAg level than those who received nucleoside drug(NAs) therapy. Upon peginterferon treatment,sustained responders have presented a larger reduction of HBsAg level than the non-responders. An absence of HBsAg decline,together with < 2 log reduction in HBV DNA at week 12,can serve as a stopping rule in HBsAg-negative patients infected with genotype D HBV. A sharp reduction of HBs Ag titer in the NAs therapy is a predictor of HBsAg clearance in long-term treatment. HBcrAg,which consists of three species of related proteins sharing an identical 149 amino acid sequence,including HbcAg,hepatitis B e antigen(HBeAg),and a truncated 22-kDa precore protein,is still detectable in situations where serum HBV DNA levels become undetectable or HBsAg loss is achieved. Therefore,HBcrAg remains a measurable serum marker to correlate with cccDNA in this situation. The decline in HBcrAg has been observed with NAs therapy and the pattern of decline might provide prognostic information on the risk of HBV posttreatment reactivation. Peripheral blood RNA,which is known as pgRNA,directly derives from cccDNA and reflects intrahepatic cccDNA level. Quantitative pgRNA has been suggested to be helpful in CHB management. However,commercial quantitative assays are lacking. Additionally,the use of simultaneous and continuous clearance of HBV RNA and HBV DNA in serum has been suggested to be a safe stopping rule of NAs therapy for patients with CHB. However,clinical studies of large sample sizes are needed to prove the feasibility andsignificance of using serum HBV RNA as the assessment standard of antiviral therapy in CHB and the safety of the stopping rule in clinics.