Serum hepatitis B virus RNA is a predictor of HBeAg seroconversion and virological response with entecavir treatment in chronic hepatitis B patients

BACKGROUND Characteristics of alterations of serum hepatitis B virus(HBV) RNA in different chronic hepatitis B(CHB) patients still cannot be fully explained. Whether HBV RNA can predict HBeAg seroconversion is still controversial.AIM To investigate whether HBV RNA can predict virological response or HBeAg seroconversion during entecavir(ETV) treatment when HBV DNA is undetectable.METHODS The present study evaluated 61 individuals who were diagnosed and treated with long-term ETV monotherapy at the Department of Infectious Diseases of Peking University First Hospital(China) from September 2006 to December 2007.Finally, 30 treatment-naive individuals were included. Serum HBV RNA were extracted from 140 μL serum samples at two time points. Then they were reverse transcribed to cDNA with the HBV-specific primer. The product was quantified by real-time quantitative PCR(RT-PCR) using TAMARA probes. Statistical analyses were performed with IBM SPSS 20.0.RESULTS Level of serum HBV RNA at baseline was 4.15 ± 0.90 log10 copies/mL. HBV RNA levels showed no significant difference between the virological response(VR)and partial VR(PVR) groups at baseline(P = 0.940). Serum HBV RNA significantly decreased among patients who achieved a VR during ETV therapy(P < 0.001). The levels of HBV RNA in both HBeAg-positive patients with seroconversion group and those with no seroconversion increased after 24 wk of treatment. Overall, HBV RNA significantly but mildly correlated to HBsAg(r =0.265, P = 0.041), and HBV RNA was not correlated to HBV DNA(r = 0.242, P =0.062). Furthermore, serum HBV RNA was an independent indicator for predicting HBeAg seroconversion and virological response. HBeAg seroconversion was more likely in CHB patients with HBV RNA levels below4.12 log10 copies/mL before treatment.CONLUSION The level of serum HBV RNA could predict HBeAg seroconversion and PVR during treatment. In the PVR group, the level of serum HBV RNA tends to be increasing.

Efficacy and safety of combined directly acting antivirals for treatment of Chinese chronic hepatitis C patients in a real-world setting

AIM To assess the efficacy and safety of combined directly acting antivirals(DAAs) for the treatment of Chinese chronic hepatitis C(CHC) patients in a real-world setting.METHODS Hospitalized CHC patients who were treated with DAAs at Peking University First Hospital between January 2015 and December 2016 were enrolled. Samples and clinical data were collected at 0 wk, 2 wk, 4 wk, 8 wk, 12 wk, or 24 wk during DAAs treatment and at 4 wk, 12 wk, and 24 wk after the end of treatment. RESULTS Fifty-four patients who underwent DAAs treatment were included in our study, of whom 83.3%(45/54) achieved rapid virological response at 2 wk after treatment initiation(RVR 2) and 94.4%(51/54)achieved sustained virological response at 24 wk after the end of treatment(SVR 24). Serum creatinine and uric acid levels at the end of treatment were significantly increased compared with baseline levels(83.6 ± 17.9 vs 88.8 ± 19.4, P 01 < 0.001; 320.8 ± 76.3 vs 354.5 ± 87.6, P 01 < 0.001), and no significant improvements were observed at 24 w after the end of treatment(83.6 ± 17.9 vs 86.8 ± 19.1, P 02 = 0.039; 320.8 ± 76.3 vs 345.9 ± 89.4, P 02 = 0.001). The total frequency of adverse events(AEs) during treatment was 33.3%(18/54), with major AEs being fatigue(16.7%), headache(7.4%), anorexia(7.4%), and insomnia(5.6%). CONCLUSION Though based in a small cohort of patients, the abnormal changes in renal function indices and relative high frequency of AEs during combined DAAs treatment should be taken as a note of caution.

Thyroid dysfunction in Chinese hepatitis C patients: Prevalence and correlation with TPOAb and CXCL10

AIM: To investigate the relationship among pretreatment serum CXC chemokine ligand 10(CXCL10),thyroid peroxidase antibody(TPOAb) levels and thyroid dysfunction(TD) in Chinese hepatitis C patients.METHODS: One hundred and thirty-nine treatmentnaive genotype 1 chronic hepatitis C patients with no history of TD or treatment with thyroid hormones were enrolled in this study.Patients underwent peginterferon alfa-2a/ribavirin(Peg IFNα-2a/RBV) treatment for 48 wk,followed by detection of clinical factors at each follow-up point.Hepatitis C virus(HCV) antibodies were analyzed using microsomal chemiluminescence,and serum HCV RNA was measured by real-time PCR assay at 0,4,12,24 and 48 wk after the initiation of therapy and 24 wk after the end of therapy.To assess thyroid function,serum thyroid stimulating hormone(TSH),free thyroxine(FT4),free triodothyronine(FT3) and TPOAb/thyroglobulin antibody(TGAb) levels were determined using chemiluminescent immunoassays every 3 mo.Serum CXCL10 levels were determined at baseline.RESULTS: The prevalence of TD was 18.0%.Twentyone(84.0%) out of twenty-five patients exhibited normal thyroid function at week 24 after therapy.The rate of sustained virological response to Peg IFNα-2a/RBV in our study was 59.0%(82/139),independent of thyroid function.Pretreatment serum CXCL10 levels were significantly increased in patients with euthyroidstatus compared with patients with TD(495.2 ± 244.2 pg/m L vs 310.0 ± 163.4 pg/m L,P = 0.012).Patients with TD were more frequently TPOAb-positive than non-TD(NTD) patients(24.2% vs 12.3%,P = 0.047) at baseline.Three of the one hundred and fifteen patients without TPOAb at baseline developed TD at the end of treatment(37.5% vs 2.6%,P = 0.000).Female patients exhibited an increased risk for developing TD compared with male patients(P = 0.014).CONCLUSION: Lower pretreatment serum CXCL10 levels are associated with TD,and TD prevalence increases in female patients and patients who are positive for TPOAb at baseline.

Soluble programmed death-1 is predictive of hepatitis B surface antigen loss in chronic hepatitis B patients after antiviral treatment

BACKGROUND Hepatitis B surface antigen(HBsAg)loss,a functional cure in patients with chronic hepatitis B(CHB)undergoing antiviral therapy,might be an ideal endpoint of antiviral treatment in clinical practice.The factors that contribute to the functional cure remain unclear,and the predictors of functional cure are worth exploring.The concentration and kinetics of soluble programmed death-1(sPD-1)in patients with CHB may play an important role in elucidating the immune response associated with functional cure after nucleos(t)ide analogs therapy.AIM To investigate the factors associated with HBsAg loss and explore the influence of sPD-1 Levels.METHODS This study analyzed the data and samples from patients with CHB who underwent antiviral treatment in a non-interventional observational study conducted at Peking University First Hospital in Beijing(between 2007 and 2019).All patients were followed up:Serum samples were collected every 3 mo during the first year of antiviral treatment and every 6 mo thereafter.Patients with positive hepatitis B e antigen levels at baseline and with available sequential samples who achieved HBsAg loss during antiviral treatment served as the case group.This case group(n=11)was further matched to 44 positive hepatitis B e anti patients without HBsAg loss as controls.The Spearman’s rank correlation test and receiver operating characteristic curves analysis were performed.RESULTS The sPD-1 Levels were higher in patients with HBsAg loss than in those without HBsAg loss from baseline to month 96,and the differences were significant between the groups at baseline(P=0.0136),months 6(P=0.0003),12(P<0.0001),24(P=0.0007),48(P<0.0001),and 96(P=0.0142).After 6 mo of antiviral treatment,the sPD-1 levels were positively correlated with alanine transaminase(ALT)levels(r=0.5103,P=0.0017),and the sPD-1 levels showed apparent correlation with ALT(r=0.6883,P=0.0192)and HBV DNA(r=0.5601,P=0.0703)levels in patients with HBsAg loss.After 12 mo of antiviral treatment,the sPD-1 levels also showed apparent correlation with ALT(r=0.8134,P=0.0042)and HBV DNA(r=0.6832,P=0.0205)levels in patients with HBsAg loss.The sPD-1 levels were negatively correlated with HBsAg levels in all patients after 12 mo of antiviral treatment,especially at 24(r=-0.356,P=0.0497)and 48(r=-0.4783,P=0.0037)mo.After 6 mo of antiviral treatment,the AUC of sPD-1 for HBsAg loss was 0.898(P=0.000),whereas that of HBsAg was 0.617(P=0.419).The cut-off value of sPD-1 was set at 2.34 log pg/mL;the sensitivity and specificity were 100%and 66.7%,respectively.CONCLUSION The sPD-1 levels at 6 mo can predict HBsAg loss after 144 mo of antiviral treatment.

Dynamic Characteristics of Serum Hepatitis B Surface Antigen in Chinese Chronic Hepatitis B Patients Receiving 7 Years of Entecavir Therapy

Background：The ultimate goal of hepatitis B treatment is hepatitis B surface antigen （HBsAg） seroclearance.Several factors have been suggested to be associated with the rate of HBsAg reduction in antiviral-naive or lamivudine therapy cohorts.However,there are few studies evaluating the factors during long-term entecavir （ETV） therapy.In the present study,we aimed to evaluate the factors to predict the outcome of ETV therapy for 7 years.Methods：A total of 47 chronic hepatitis B （CHB） patients treated with ETV monotherapy were included in this study.Liver biochemistry,hepatitis B virus （HBV） serological markers,serum HBV DNA,and HBsAg titers were tested at baseline,3 months,6 months,and yearly from 1 to 7.The associations between factors and HBsAg reduction were assessed using multivariate tests with repeated measure analysis of variance.Results：At baseline,serum HBsAg levels showed a positive correlation with baseline HBV DNA levels （r =0.625,P 〈 0.001）.The mean HBsAg titers after ETV treatment were significantly lower than the baseline titers （P ranges from 0.025 to 0.000,000,6）.The HBsAg reduction rate during the 1st year was greater compared to after 1 year of treatment （P 〈 0.05）.Multivariate test showed that hepatitis B e antigen （HBeAg） seroclearance and/or HBsAg reduction ≥0.5 log10 IU/ml at 6 months had a high negative predictive value （96.77%） for HBsAg seroclearance （P =0.002,P =0.012,respectively）.Conclusions：The HBsAg reduction rate during the 1st year was greater than that after 1 year of treatment.Further,HBeAg status and HBsAg levels at month 6 are the optimal factors for the early prediction of HBsAg seroclearance after long-term ETV therapy in CHB patients.