RESUMEN
BACKGROUND: Hepatitis B virus (HBV)-associated acute-on-chronic liver failure (HBV-ACLF) is a life-threatening condition and its exact pathophysiology and progression remain unclear. The present study aimed to assess the role of serum miRNAs 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 to 30 chronic asymptomatic HBV carriers as controls. The miRNAs expressions were measured by real-time quantitative PCR (q-PCR). Statistical analyses were conducted to assess the ability of differentially expressed miRNAs and other prognostic factors in identifying ACLF prognosis and to develop a new predictive model. RESULTS: Real-time q-PCR indicated that serum miR-146a-5p, miR-122-3p and miR-328-3p 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 miR-122-3p 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: Yâ¯=â¯0.402â¯×â¯Na+â¯-â¯1.72â¯×â¯INRâ¯-â¯4.963â¯×â¯gastrointestinal bleeding (Yesâ¯=â¯0; Noâ¯=â¯1)-0.278â¯×â¯(miR-122-3p)â¯+â¯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 miRNAs (miR-146a-5p, miR-122-3p and miR-328-3p) positively correlate with the severity of liver inflammation in patients with ACLF and may be useful to predict HBV-ACLF severity.
Asunto(s)
Insuficiencia Hepática Crónica Agudizada/sangre , MicroARN Circulante/sangre , Hepatitis B Crónica/sangre , Insuficiencia Hepática Crónica Agudizada/diagnóstico , Insuficiencia Hepática Crónica Agudizada/genética , Insuficiencia Hepática Crónica Agudizada/virología , Adulto , Área Bajo la Curva , Estudios de Casos y Controles , MicroARN Circulante/genética , Femenino , Hemorragia Gastrointestinal/sangre , Hemorragia Gastrointestinal/genética , Hemorragia Gastrointestinal/virología , Marcadores Genéticos , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/genética , Hepatitis B Crónica/virología , Humanos , Relación Normalizada Internacional , Modelos Logísticos , Masculino , MicroARNs , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , Pronóstico , Curva ROC , Reacción en Cadena en Tiempo Real de la Polimerasa , Índice de Severidad de la Enfermedad , Sodio/sangre , Regulación hacia Arriba , Adulto JovenRESUMEN
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 3730xl 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/mL), P=0.001]. The baseline ALT levels were significantly higher in the HBeAg clearance group (204.72+/-88.65 vs 162.80+/-85.81 IU/L, P<0.05) and HBeAg 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/m2, P<0.05) were prone to acquired biochemical response (BR). PC-W28STOP (ntG1896A) 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 (ntA1726C) and BCP-L134L (ntA1775C/G/T) influenced VR independently. PC-G182C (ntG2357T), PC-S64A/T (ntT2003G/A) and BMI were independent influence factors for HBeAg clearance, HBeAg 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 (ntC2288A), BCP-N118T (ntA1726C), BCP-L134L (ntA1775C/G/T), PC-G182C (ntG2357T) and PC-S64A/T (ntT2003G/A) were novel identified mutations that impacted IFN therapeutic efficacy. These novel mutations could serve as important predictors before conventional IFN treatment.