Serum levels of mi RNA in patients with hepatitis B virus-associated acute-on-chronic liver failure

Background: Hepatitis B virus(HBV)-associated acute-on-chronic liver failure(HBV-ACLF) is a lifethreatening condition and its exact pathophysiology and progression remain unclear. The present study aimed to assess the role of serum mi RNAs in the evaluation of HBV-ACLF and to develop a model to predict the outcomes for ACLF.Methods: Serum was collected from 41 chronic hepatitis B and 55 HBV-ACLF patients in addition to30 chronic asymptomatic HBV carriers as controls. The mi RNAs expressions were measured by real-time quantitative PCR(q-PCR). Statistical analyses were conducted to assess the ability of differentially expressed mi RNAs and other prognostic factors in identifying ACLF prognosis and to develop a new predictive model.Results: Real-time q-PCR indicated that serum miR-146 a-5 p, mi R-122-3 p and mi R-328-3 p levels were significantly upregulated in ACLF patients compared to chronic hepatitis B and chronic asymptomatic HBV carriers patients. In addition, multivariate regression analyses indicated that Na+, INR, gastrointestinal bleeding and mi R-122-3 p are all independent factors that are reliable and sensitive to the prognosis of HBV-ACLF. Therefore, we developed a new model for the prediction of HBV-ACLF disease state: Y = 0.402 × Na+-1.72 × INR-4.963 × gastrointestinal bleeding(Yes = 0; No = 1)-0.278 ×(mi R-122-3 p) + 50.449. The predictive accuracy of the model was 95.3% and the area under the receiver operating characteristic curve(AUROC) was 0.847.Conclusions: Expression levels of these mi RNAs(miR-146 a-5 p, mi R-122-3 p and mi R-328-3 p) positively correlate with the severity of liver inflammation in patients with ACLF and may be useful to predict HBV-ACLF severity.

Novel HBV mutations and their value in predicting efficacy of conventional interferon

BACKGROUND： Accumulating studies assessing the impacts of hot spot mutations on conventional interferon（IFN） efficacy come to discrepant conclusions; studies regarding the mutations in S and RT regions are also unclear. The present study aimed to evaluate the impacts of HBV mutations on the efficacy of conventional IFN. METHODS： A total of 126 patients who received conventional IFN treatment for 48 weeks were enrolled. Biochemical and serological parameters were routinely tested. The sequences of HBV from 78 serum samples were amplified by nested-PCR; mutations were identified with sequence scanner V1.0 after ABI 3730 xl direct sequencing, HBV genotypes were determined according to RT gene sequences utilizing NCBI Genotyping Tool which was based on phylogenetic analysis.RESULTS： The baseline DNA levels of virological response（VR） group were significantly lower than those of no VR group [7.13±0.76 vs 7.69±0.56 lg（copies/m L）, P=0.001]. The baseline ALT levels were significantly higher in the HBe Ag clearance group（204.72±88.65 vs 162.80±85.81 IU/L, P〈0.05） andHBe Ag seroconversion group（204.89 ±95.68 vs 166.75±84.43 IU/L, P〈0.05）. Females and lower BMI levels（20.01±2.33 vs 21.65±3.66 kg/m^2, P〈0.05） were prone to acquired biochemical response（BR）. PC-W28STOP（ntG 1896A） was significantly higher in the combined response（CR） group than that in the no CR group（91.7% vs 39.7%, P=0.001）. Multivariate logistic regression analysis showed that baseline DNA, PC-P159T（ntC2288A）, BCP-N118T（ntA 1726C） and BCP-L134L（ntA 1775C/G/T） influenced VR independently. PC-G182C（nt G2357T）, PC-S64A/T（nt T2003G/A） and BMI were independent influence factors for HBe Ag clearance, HBe Ag seroconversion and BR, respectively. The new predicting model concluded that baseline DNA and new mutations for VR were established successfully, and ROC analysis showed that AUC was 0.842（P〈0.001） with a sensitivity of 0.652 and a specificity of 0.933.CONCLUSIONS： PC-P159T（ntC 2288A）, BCP-N118T（ntA 1726C）, BCP-L134L（nt A1775C/G/T）, PC-G182C（nt G2357T） and PCS64A/T（nt T2003G/A） were novel identified mutations that impacted IFN therapeutic efficacy. These novel mutations could serve as important predictors before conventional IFN treatment.