Efficacy of Peginterferon alfa-2b in Nucleoside Analogue Experienced Patients with Negative HBeAg and Low HBsAg: A Non-Randomized Clinical Trial.

INTRODUCTION: Hepatitis B surface antigen (HBsAg) clearance is the treatment goal for hepatitis B e antigen (HBeAg)-negative patients with chronic hepatitis B (CHB). However, its rate is extremely low with nucleoside (acid) analogues (NAs) monotherapy. Peginterferon could enhance HBsAg clearance. This study aimed to evaluate the efficacy of peginterferon alfa-2b (PegIFNα-2b) in NAs-experienced patients with CHB with negative HBeAg and low HBsAg level. METHODS: HBeAg-negative patients with CHB who had received NAs therapy over 24 weeks with HBsAg < 1500 IU/mL and HBV DNA < 100 IU/mL were enrolled. Patients received either PegIFNα-2b add-on therapy (n = 108) or continuous NAs monotherapy (n = 75). The primary endpoint was HBsAg clearance rate at week 48. RESULTS: At week 48, serum HBV DNA was undetectable among all PegIFNα-2b add-on therapy patients. Almost all patients maintained HBV DNA suppression in the PegIFNα-2b add-on group (100%, 108/108) and NAs monotherapy group (97.33%, 73/75). Only patients with PegIFNα-2b add-on therapy achieved HBsAg clearance (50.93%, 55/108) and HBsAg seroconversion (48.15%, 52/108) at week 48. Patients with baseline HBsAg < 100 IU/mL achieved the highest HBsAg clearance rate and HBsAg seroconversion rate at week 48 (60.87%, 28/46 and 58.70%, 27/46 respectively). HBsAg clearance and HBsAg seroconversion at week 72 had no significant difference with continuing or discontinuing PegIFNα-2b therapy after 48 weeks of treatment. PegIFNα-2b add-on therapy was well tolerated. CONCLUSIONS: PegIFNα-2b add-on therapy increases HBsAg clearance rate and seroconversion rate for HBeAg-negative patients with CHB, particularly for those with lower HBsAg level. It would be unnecessary to prolong PegIFNα-2b duration after 48 weeks of PegIFNα-2b treatment.

Early Diagnostic Biomarkers of Sepsis for Patients with Acute-on-Chronic Liver Failure: A Multicenter Study.

INTRODUCTION: Sepsis is a complication in acute-on-chronic liver failure (ACLF) patients associated with high rates of mortality and morbidity. Early diagnosis of sepsis in ACLF patients can improve prognosis. This study aimed to explore potential effective biomarkers for the early diagnosis of sepsis in ACLF patients. METHODS: Ninety-four ACLF patients with sepsis were enrolled from 10 hospitals across China from January 2015 to June 2016 as well as 49 ACLF patients without infection from Xiangya Hospital. The first-day admission data and SOFA score and CLIF-SOFA score were collected. The differences of indicators between groups were compared with Kruskal-Wallis test. The receiver-operating characteristic (ROC) curve was analyzed to evaluate the diagnostic efficiency of the selected factors. RESULTS: Soluble triggering receptor expressed on myeloid cell-1 (sTREM-1) and presepsin were significantly higher in ACLF-sepsis patients compared with ACLF patients with no infection (P < 0.001). sTREM-1 and presepsin presented higher diagnostic value in sepsis for ACLF patients compared with other biomarkers [white blood cells (WBC), procalcitonin (PCT) and C-reactive protein (CRP)]. Combining sTREM-1 or presepsin with the CLIF-SOFA score increased the diagnostic efficiency (AUC = 0.876 or AUC = 0.913, respectively). CONCLUSIONS: sTREM-1 and presepsin are potential biomarkers for the early diagnosis of sepsis in ACLF patients. The combination of presepsin and the CLIF-SOFA score is a promising method for diagnosing sepsis in ACLF patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02457637.

Potential predictors for prognosis and postpartum recovery time of acute fatty liver of pregnancy.

BACKGROUND: Acute fatty liver of pregnancy (AFLP) is a potentially lethal condition of pregnant women with a high mortality rate. Potential predictors related to postpartum recovery time and prognostic factors of AFLP are still unclear. This study aimed to evaluate potential predictors for prognosis and postpartum recovery time of AFLP. METHODS: We retrospectively analyzed the clinical data of 76 AFLP patients in our hospital from 2002 to 2017 and investigated potential predictors using univariate analysis and multivariate logistic regression analysis. RESULTS: Hepatic encephalopathy (HE) was found to be associated with prognosis in AFLP patients (P = 0.005, OR = 26.844). The postpartum recovery time analysis showed that AFLP patients with a age < 25 had the shortest recovery time, but no significant difference (P = 0.134, OR = 5.952). The postpartum recovery time of patients with liver failure (LF) was significantly prolonged compared to those without LF (P = 0.036, OR = 10.052). Cryoprecipitate, and plasma infusion showed no significant effect on prognosis or recovery time. Artificial liver support therapy (ALST) had no effect on prognosis, but it might affect postpartum recovery time with no statistical significance (P = 0.128, OR = 5.470). CONCLUSION: HE is a potential predictor for prognosis of AFLP. LF is a potential predictor for postpartum recovery time.

LncRNA TP73-AS1/miR-539/MMP-8 axis modulates M2 macrophage polarization in hepatocellular carcinoma via TGF-ß1 signaling.

PURPOSE: Our study aimed to study the role of lncRNA TP73-AS1/miR-539/MMP-8 axis in modulating M2 macrophage polarization in hepatocellular carcinoma (HCC). METHODS: The gene expression levels of TP73-AS1, miR-539 and MMP-8 were modified by transfection with the overexpression or knockdown vectors. The patient survival rate was analyzed using Kaplan-Meier method. The levels of TP73-AS1, miR-539, MMP-8 and M1/2 macrophage polarization markers were analyzed by qRT-PCR, western blot, and flow cytometry. The release of TGF-ß1 in the supernatant was determined by ELISA assay. The interaction between TP73-AS1, miR-539 and MMP-8 was analyzed by bioinformatics analysis and dual-luciferase reporter assays. Mouse xenograft model was further established to examine the therapeutic effects of the TP73-AS1 knockdown and miR-539 overexpression in vivo. RESULTS: We found TP73-AS1 and MMP-8 upregulation, and miR-539 downregulation in HCC tissues and cell lines. Lower TP73-AS1 and MMP-8 expressions and higher miR-539 expression were associated with higher survival rate of patients. M2-macrophage markers CD206, Arg-1 and CD163 were significantly upregulated in the tumor tissues. TP73-AS1 negatively and directly regulated miR-539 and knockdown of TP73-AS1 inhibited MMP-8 expression and M2 macrophage polarization. Also, overexpression of miR-539 suppressed M2 macrophage polarization by negatively regulating MMP-8. Furthermore, knockdown of MMP-8 also restrained M2 macrophage polarization via inhibiting TGF-ß1 signaling. We also found knockdown of TP73-AS1 or overexpression of miR-539 inhibited HCC tumor growth and M2 macrophage infiltration in vivo. CONCLUSION: Our study demonstrated lncRNA TP73-AS1 negatively regulated miR-539 to promote MMP-8 expression, which activated TGF-ß1 signaling to induce M2 macrophage polarization in HCC.