Factors associated with persistent positive in HBV DNA level in patients with chronic Hepatitis B receiving entecavir treatment.

Introduction: The clinical significance of persistent positive in Hepatitis B Virus (HBV) DNA level in patients receiving antiviral therapy is not well known. We investigated factors associated with persistent viremia (PV) in patients with chronic hepatitis B (CHB) given 78-week entecavir. Methods: A total of 394 treatment-naïve CHB patients who had undergone liver biopsy at baseline and week 78 of treatment were analyzed in this prospective multicentre study. We identified patients with PV (above the lower limit of quantification, 20 IU/ml) after 78 weeks of entecavir therapy. Stepwise, forward, multivariate regression analyses of specified baseline parameters were apllied to identify factors associated with PV. Futhermore, we assessed the incidence of hepatocellular carcinoma (HCC) in all patients using models of the risk of HCC development. Results: Of the 394 patients, 90 (22.8%) still with PV after 78-week antiviral treatment. Factors associated significantly with PV (vs complete virological response, CVR) were HBV DNA level ≥8 log10 IU/mL (OR, 3.727; 95% CI, 1.851-7.505; P < 0.001), Anti-HBc level < 3 log10 IU/mL (OR, 2.384; 95% CI, 1.223-4.645; P=0.011), and HBeAg seropositivity (OR, 2.871; 95% CI, 1.563-5.272; P < 0.001). Patients with PV were less likely to have fibrosis progression and HCC development than those with the CVR. Of the 11 HBeAg-positive patients with HBV DNA level ≥8 log10 IU/mL and Anti-HBc level < 3 log10 IU/mL at baseline, 9 (81.8%) had persistent positivity in HBV DNA level and 0 had fibrosis progression at week 78 of treatment. Discussion: In conclusion, HBV DNA level ≥8 log10 IU/mL, Anti-HBc level < 3 log10 IU/mL and HBeAg seropositivity at baseline contribute to PV in patients with CHB receiving 78-week antiviral treatment. In addition, the rate of fibrosis progression and the risk of HCC development in patients with PV were kept low. The complete protocol for the clinical trial has been registered at clinicaltrials.gov (NCT01962155 and NCT03568578).

An-Luo-Hua-Xian Pill Improves the Regression of Liver Fibrosis in Chronic Hepatitis B Patients Treated with Entecavir.

Background and Aims: Chronic hepatitis B (CHB) can cause liver fibrosis and lead to cirrhosis and cancer. As the effectiveness of antiviral therapy to reverse liver fibrosis is limited, We aimed to evaluate the effect of An-Luo-Hua-Xian pill (ALHX) on fibrosis regression in CHB patients treated with entecavir (ETV). Methods: Treatment-naïve patients with CHB were randomly treated with ETV alone or combined with ALHX (ETV+ALHX) between October 1, 2013 and December 31, 2020. Demographic, laboratory, and liver histology data before and after 78 weeks of treatment were collected. The Ishak fibrosis score (F) was used and fibrosis regression required a decrease in F of ≥1 after treatment. Results: A total of 780 patients were enrolled, and 394 with a second liver biopsy after treatment were included in the per-protocol population, 132 in ETV group and 262 in ETV+ALHX group. After 78 weeks of treatment, the fibrosis regression rate in the ETV+ALHX group was significantly higher than that of the ETV group at baseline F≥3 patients: 124/211 (58.8%) vs. 45/98 (45.9%), p=0.035. The percentage of patients with a decreased liver stiffness measurement (LSM) was higher in the ETV+ALHX group: 156/211 (73.9%) vs. 62/98 (63.%), p=0.056. Logistic regression analysis showed that ETV combined with ALHX was associated with fibrosis regression [odds ratio (OR)=1.94, p=0.018], and a family history of hepatocellular carcinoma was on the contrary. (OR=0.41, p=0.031). Conclusions: ETV combined with ALHX increased liver fibrosis regression in CHB patients.

Quantitative serum HBV markers in predicting phases of natural history of chronic HBV infection.

BACKGROUND: Clinical importance of commercially available quantitative HBV markers has not been fully investigated. OBJECTIVE: To choice and to evaluate clinically valuable HBV markers for predicting phases of natural history with chronic HBV infection. METHODS: 472 naïve patients with chronic HBV infection were enrolled, in which 21 and 220 were confirmed as HBeAg-positive inactive and active hepatitis (EPIH and EPAH), respectively, and 106 and 125 were confirmed as HBeAg-negative inactive and active hepatitis (ENIH and ENAH), respectively. HBsAg, HBcrAg and anti- HBc were measured using chemiluminescent immunoassay, and HBV DNA was measured using PCR-fluorescence probing assay. RESULTS: There were all statistical differences in medians of HBsAg, anti-HBc, HBcrAg and HBV DNA between EPIH and EPAH and between ENIH and ENAH (all P < 0.01). According to binary logistic stepwise regressions, HBsAg and anti-HBc were preferred variables for predicting EPAH, and HBcrAg and HBV DNA were preferred variables for predicting ENAH. Based on normalization for coefficients of preferred variables entering regression equations, a handy model of MEPAH for predicting EPAH and of MENAH for predicting ENAH was constructed, respectively. Area under receiver operating characteristic curves of MEPAH and MENAH for predicting EPAH and ENAH were 0.882 and 0.931, respectively. With standard of MEPAH ≤ 5.997 and MENAH > 10.535, sensitivity or specificity of which for predicting EPAH and ENAH were about 81.0 % and 87.0 %, respectively. CONCLUSION: HBsAg and anti-HBc for predicting EPAH and HBcrAg and HBV DNA for predicting ENAH are dependable markers; MEPAH for predicting EPAH and MENAH for predicting ENAH have very good performance.

Quantitative HBcrAg and HBcAb versus HBsAg and HBV DNA in predicting liver fibrosis levels of chronic hepatitis B patients / HBcrAg y HBcAb cuantitativos versus HBsAg y ADN del VHB en la predicción de los niveles de fibrosis hepática de los pacientes con hepatitis B crónica

OBJECTIVE: To evaluate the performance of the quantitative markers of hepatitis B core-related antigen (HBcrAg) and anti-hepatitis B core antigen antibodies HbcAb versus hepatitis B surface antigen (HBsAg) and hepatitis B virus DNA (HBV DNA) in predicting liver fibrosis levels in chronic hepatitis B patients. METHODS: Two hundred and fifty hepatitis B e antigen (HBeAg)-positive and 245 HBeAg-negative patients were enrolled. With reference to the Scheuer standard, stage 2 or higher and stage 4 liver disease were defined as significant fibrosis and cirrhosis, respectively. A receiver operating characteristic (ROC) curve was used to evaluate the performance of the HBV markers investigated. RESULTS: The areas under the ROC curves (AUCs) of HBcrAg in predicting significant fibrosis and cirrhosis in HBeAg-positive patients (0.577 and 0.700) were both close to those of HBsAg (0.617 and 0.762) (both P> 0.05). In HBeAg-negative patients (0.797 and 0.837), they were both significantly greater than those of HBV DNA (0.723 and 0.738) (P=0.0090 and P=0.0079). The AUCs of HBcAb in predicting significant fibrosis and cirrhosis in HBeAg-positive patients (0.640 and 0.665) were both close to those of HBsAg. In HBeAg-negative patients (0.570 and 0.621), they were both significantly less than those of HBcrAg (P <0.0001 and P=0.0001). Specificity in predicting significant fibrosis and sensitivity in predicting cirrhosis in HBeAg-positive patients, using a single cut-off of HBsAg ≤5,000 IU/ml, were 76.5% and 72.7%, respectively. In HBeAg-negative patients, using a single cut-off of HBcrAg>80kU/ml, they were 85.9% and 81.3%, respectively. CONCLUSIONS: HBsAg has good performance in predicting liver fibrosis levels in HBeAg-positive and HBeAg-negative patients, and HBcrAg has very good performance in predicting liver fibrosis levels in HBeAg-negative patients

OBJETIVO: Evaluar el rendimiento de los marcadores cuantitativos del antígeno central de la hepatitis B (HBcrAg) y los anticuerpos contra el antígeno central de la hepatitis B (HBcAb) frente al antígeno de superficie de la hepatitis B (HBsAg) y el ADN del virus de la hepatitis B (ADN del VHB) en la predicción de los niveles de fibrosis hepática de los pacientes con hepatitis B crónica. MÉTODOS: Se inscribieron 250 pacientes con HBsAg positivo y 245 pacientes con HBeAg negativo. Con referencia al estándar de Scheuer, la etapa patológica hepática 2 o superior y la etapa 4 se definieron como fibrosis y cirrosis significativas, respectivamente. Se utilizó la curva característica de funcionamiento del receptor (ROC) para evaluar el rendimiento de los marcadores del VHB investigados. RESULTADOS: Las áreas bajo la curva ROC (AUC) del HBcrAg en la predicción de la fibrosis y cirrosis significativa de los pacientes positivos para el HBeAg (0,577 y 0,700) fueron ambas cercanas a las del HBsAg (0,617 y 0,762) (ambas p > 0,05); de los pacientes negativos para el HBeAg (0,797 y 0,837) fueron ambas significativamente mayores que las del ADN del VHB (0,723 y 0,738) (p = 0,0090 y p = 0,0079); las AUC del HBcAb en la predicción de la fibrosis y cirrosis significativa de los pacientes positivos para el HBeAg (0,640 y 0,665) fueron ambas cercanas a las del HBsAg; de los pacientes negativos para el HBeAg (0,570 y 0,621) fueron ambas significativamente menores que las del HBcrAg (p < 0,0001 y p = 0,0001). La especificidad en la predicción de la fibrosis significativa y la sensibilidad en la predicción de la cirrosis de los pacientes positivos para el HBeAg, utilizando un solo corte de HBsAg ≤ 5.000 UI/mL fueron 76,5 y 72,7%, respectivamente; de los pacientes negativos para el HBeAg utilizando un solo corte de HBcrAg > 80 kU/mL fueron 85,9 y 81,3%, respectivamente. CONCLUSIONES: El HBsAg tiene un buen rendimiento en la predicción de los niveles de fibrosis hepática de los pacientes HBeAg positivos y negativos, mientras que HBcrAg tiene un muy buen rendimiento en la predicción de los niveles de fibrosis de los pacientes HBaAg negativos

Quantitative HBcrAg and HBcAb versus HBsAg and HBV DNA in predicting liver fibrosis levels of chronic hepatitis B patients.

OBJECTIVE: To evaluate the performance of the quantitative markers of hepatitis B core-related antigen (HBcrAg) and anti-hepatitis B core antigen antibodies HbcAb versus hepatitis B surface antigen (HBsAg) and hepatitis B virus DNA (HBV DNA) in predicting liver fibrosis levels in chronic hepatitis B patients. METHODS: Two hundred and fifty hepatitis B e antigen (HBeAg)-positive and 245 HBeAg-negative patients were enrolled. With reference to the Scheuer standard, stage 2 or higher and stage 4 liver disease were defined as significant fibrosis and cirrhosis, respectively. A receiver operating characteristic (ROC) curve was used to evaluate the performance of the HBV markers investigated. RESULTS: The areas under the ROC curves (AUCs) of HBcrAg in predicting significant fibrosis and cirrhosis in HBeAg-positive patients (0.577 and 0.700) were both close to those of HBsAg (0.617 and 0.762) (both P> 0.05). In HBeAg-negative patients (0.797 and 0.837), they were both significantly greater than those of HBV DNA (0.723 and 0.738) (P=0.0090 and P=0.0079). The AUCs of HBcAb in predicting significant fibrosis and cirrhosis in HBeAg-positive patients (0.640 and 0.665) were both close to those of HBsAg. In HBeAg-negative patients (0.570 and 0.621), they were both significantly less than those of HBcrAg (P <0.0001 and P=0.0001). Specificity in predicting significant fibrosis and sensitivity in predicting cirrhosis in HBeAg-positive patients, using a single cut-off of HBsAg ≤5,000 IU/ml, were 76.5% and 72.7%, respectively. In HBeAg-negative patients, using a single cut-off of HBcrAg>80kU/ml, they were 85.9% and 81.3%, respectively. CONCLUSIONS: HBsAg has good performance in predicting liver fibrosis levels in HBeAg-positive and HBeAg-negative patients, and HBcrAg has very good performance in predicting liver fibrosis levels in HBeAg-negative patients.

Unsatisfying antiviral therapeutic effect in patients with mother-to-child transmissed chronic hepatitis B virus infection: a prospective multi-center clinical study.

BACKGROUND: Few data are available regarding the progression of liver disease and therapeutic efficacy in chronic hepatitis B virus (HBV) carriers infected by mother-to-child transmission (MTCT). This study aimed to investigate these two aspects by comparing the adult chronic HBV carriers in MTCT group with those in horizontal transmission group. METHODS: The 683 adult chronic HBV patients qualified for liver biopsy including 191 with MTCT and 492 with horizontal transmission entered the multi-center prospective study from October 2013 to May 2016. Biopsy results from 217 patients at baseline and 78 weeks post antiviral therapy were collected. RESULTS: Patients infected by MTCT were more likely to have e antigen positive (68.6% vs. 58.2%, χ = -2.491, P = 0.012) than those with horizontal transmission. However, in patients with MTCT, levels of alkaline phosphatase (ALP) (P = 0.031), Fibroscan (P = 0.013), N-terminal propeptide of Type III procollagen (PIIINP) (P = 0.014), and Laminin (LN) (P = 0.006) were high, in contrast to the patients with horizontal transmission for whom the levels of albumin (ALB) (P = 0.041), matrix metalloproteinase-3 (MMP-3) (P = 0.001) were high. The 47.2% of patients with MTCT and 36.8% of those with horizontal transmission had significant liver fibrosis (P = 0.013). Following antiviral therapy for 78 weeks, 21.2% and 38.0% patients with MTCT and horizontal transmission acquired hepatitis B e antigen (HBeAg) clearance, respectively (P = 0.043), and the virological response rates were 54.7% and 74.1% in the MTCT and horizontal groups, respectively (P = 0.005). MTCT was a risk factor for HBeAg clearance and virological response. CONCLUSION: Adult patients with MTCT were more prone to severe liver diseases, and the therapeutic efficacy was relatively poor, which underlined the importance of earlier, long-term treatment and interrupting perinatal transmission. TRIAL REGISTRATION: NCT01962155; https://clinicaltrials.gov.

Performance of Hepatitis B Core-Related Antigen Versus Hepatitis B Surface Antigen and Hepatitis B Virus DNA in Predicting HBeAg-positive and HBeAg-negative Chronic Hepatitis.

BACKGROUND: We examined changes in hepatitis B core-related antigen (HBcrAg) during the four sequential phases of chronic hepatitis B virus (HBV) infection: hepatitis B e antigen (HBeAg)-positive chronic infection (EPCI) and hepatitis (EPCH), followed by HBeAg-negative chronic infection (ENCI) and hepatitis (ENCH). We compared the performance of serum HBcrAg, hepatitis B surface antigen (HBsAg), and HBV DNA in predicting EPCH and ENCH. METHODS: We enrolled 492 consecutive patients: 49 with EPCI, 243 with EPCH, 101 with ENCI, and 99 with ENCH. HBcrAg was detected by chemiluminescent enzyme immunoassays. HBsAg and HBeAg were detected by chemiluminescent microparticle immunoassays. HBV DNA was detected by real-time PCR. Predictive performance of HBcrAg, HBsAg, and HBV DNA was evaluated using ROC curves. RESULTS: Areas under ROC curves (AUCs) of HBcrAg, HBsAg, and HBV DNA for predicting EPCH were 0.738, 0.812, and 0.717, respectively; optimal cutoffs were ≤1.43×105 kU/mL, ≤1.89×104 IU/mL, and ≤3.97×107 IU/mL, with sensitivities and specificities of 66.3% and 77.6%, 65.0% and 93.9%, and 60.5% and 79.6%, respectively. AUCs of HBcrAg, HBsAg, and HBV DNA for predicting ENCH were 0.887, 0.581, and 0.978, respectively; optimal cutoffs were >26.8 kU/mL, >2.29×10² IU/mL, and >8.75×10³ IU/mL, with sensitivities and specificities of 72.7% and 95.1%, 86.9% and 39.6%, and 89.9% and 92.1%, respectively. CONCLUSIONS: HBsAg and HBV DNA were the best predictors of EPCH and ENCH, respectively. HBcrAg is an important surrogate marker for predicting EPCH and ENCH.

Quantitative Anti-HBc in Liver Pathological States in Patients with Chronic Hepatitis B Virus Infection.

BACKGROUND: Changes of hepatitis B core antigen antibody (anti-HBc) in liver pathological involvement in patients with chronic hepatitis B virus (HBV) infection have not been investigated in detail. This study aimed to explore evolving patterns of anti-HBc following liver pathological states and to investigate validities of anti-HBc for predicting liver pathological states. METHODS: 254 HBeAg-positive and 237 HBeAg-negative patients with chronic HBV infection were enrolled. Liver pathological diagnoses referred to Scheuer standard, and anti-HBc was measured using chemiluminescence microparticle immunoassay. RESULTS: Anti-HBc was significantly positively correlated with pathological grades and stages in both HBeAg-positive (r s = 0.312, P < 0.0001, and r s = 0.268, P < 0.0001) and HBeAg-negative (r s = 0.270, P < 0.0001, and r s = 0.147, P=0.0237) patients. The medians of anti-HBc in pathological grades of G1, G2, and G3 and stages of S1, S2, S3, and S4 in HBeAg-positive patients were all significantly lower than those in HBeAg-negative patients (all P < 0.005). The areas under receiver-operating characteristic curves (95% confidence interval) of anti-HBc for predicting pathological grades ≥G2 and ≥G3, and stages ≥S2 and =S4 in HBeAg-positive patients were 0.683 (0.622-0.740) and 0.662 (0.601-0.720), and 0.627 (0.564-0.687) and 0.683 (0.622-0.740), respectively, and in HBeAg-negative patients were 0.681 (0.618-0.740) and 0.702 (0.639-0.760), and 0.569 (0.503-0.633) and 0.630 (0.565-0.691), respectively. CONCLUSION: Following hepatic aggravation of necroinflammation and progression of fibrosis, anti-HBc increases gradually in HBeAg-positive patients and continues to increase gradually in HBeAg-negative patients, which is a useful but unsatisfactory marker for monitoring pathological states.

Distinct patterns of serum hepatitis B core-related antigen during the natural history of chronic hepatitis B.

BACKGROUND: The current clinical practice on chronic hepatitis B (CHB) requires better on-treatment monitoring of viral persistence. Quantified assays for hepatitis B surface antigen (HBsAg) and core-related antigen (HBcrAg) hold promise for further optimization of therapy. Here, we aimed to characterize HBcrAg during the natural course of CHB. METHODS: Four-hundred and forty four treatment naïve CHB patients, who all underwent liver histology examination, were enrolled in this cross-sectional study. Their HBV DNA, HBsAg, HBeAg and HBcrAg titres were quantified and analyzed in the context of four distinct clinical phases. Correlation of HBcrAg and HBsAg with other markers were performed. The relationship between liver and serum antigen levels were also assessed. RESULTS: HBcrAg, like HBsAg, exhibited high degree of correlation with HBV DNA. However, a more significant linear relationship was found between HBcrAg and HBeAg titre in immune tolerant (IT) and immune clearance (IC) phases, while in HBeAg negative hepatitis (ENH) group, HBV DNA is a major determinant of HBcrAg. Significant difference was observed in liver HBcAg score and HBcrAg level in both IT and IC phases whereas barely significant positive correlations between liver HBsAg score and HBsAg titre was documented. CONCLUSION: HBcrAg titre exhibited distinct correlative profile in a phase-specific manner. In addition, its level is well-related to the intrahepatic expression of core antigen. It has a considerable utility in monitoring and refining antiviral therapy.

Phase IIb trial of in vivo electroporation mediated dual-plasmid hepatitis B virus DNA vaccine in chronic hepatitis B patients under lamivudine therapy.

AIM: To assess the efficacy and safety of in vivo electroporation (EP)-mediated dual-plasmid hepatitis B virus (HBV) DNA vaccine vs placebo for sequential combination therapy with lamivudine (LAM) in patients with chronic hepatitis B. METHODS: Two hundred and twenty-five patients were randomized to receive either LAM + vaccine (vaccine group, n = 109) or LAM + placebo (control group, n = 116). LAM treatment lasted 72 wk. Patients received the DNA vaccine or placebo by intramuscular injection mediated by EP at weeks 12 (start of treatment with vaccine or placebo, SOT), 16, 24, and 36 (end of treatment with vaccine or placebo, EOT). RESULTS: In the modified intent-to-treat population, more patients had a decrease in HBV DNA > 2 log10 IU/mL in the vaccine group at week 12 after EOT compared with the control group. A trend toward a difference in the number of patients with undetectable HBV DNA at week 28 after EOT was obtained. Adverse events were similar. In the dynamic per-protocol set, which excluded adefovir (ADV) add-on cases at each time point instantly after ADV administration due to LAM antiviral failure, more patients had a decrease in HBV DNA > 2 log10 IU/mL in the vaccine group at week 12 and 28 after EOT compared with the control group. More patients with undetectable HBV DNA at week 28 after EOT in the vaccine group were also observed. Among patients with a viral load < 1000 copies/mL at week 12, more patients achieved HBeAg seroconversion in the vaccine group than among controls at week 36 after EOT, as well as less virological breakthrough and YMDD mutations. CONCLUSION: The primary endpoint was not achieved using the HBV DNA vaccine. The HBV DNA vaccine could only be beneficial in subjects that have achieved initial virological response under LAM chemotherapy.

On-treatment quantitative hepatitis B e antigen predicted response to nucleos(t)ide analogues in chronic hepatitis B.

AIM: To investigate potential predictors for treatment response to nucleos(t)ide analogues (NAs) in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients. METHODS: Seventy-six HBeAg-positive CHB patients received 96-wk NAs optimized therapy (lamivudine and adefovir dipivoxil) were studied retrospectively. Serum hepatitis B surface antigen, HBeAg, hepatitis B core antibody, hepatitis B virus (HBV) DNA and alanine aminotransferase levels were quantitatively measured before and during the treatment at 12 and 24 wk. Stepwise logistic regression analyses were performed to identify predictors for treatment response, and areas under the receiver operating characteristic curves (AUROC) of the independent predictors were calculated. RESULTS: Forty-three CHB patients (56.6%) achieved virological response (VR: HBV DNA ≤ 300 copies/mL) and 15 patients (19.7%) developed HBeAg seroconversion (SC) after the 96-wk NAs treatment. The HBeAg level (OR = 0.45, P = 0.003) as well as its declined value (OR = 2.03, P = 0.024) at 24-wk independently predicted VR, with the AUROC of 0.788 and 0.736, respectively. The combination of HBeAg titer < 1.3 lg PEIU/mL and its decreased value > 1.6 lg PEIU/mL at 24-wk predicted VR with a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) of 85%, 100%, 100% and 83%, respectively, and the AUROC increased to 0.923. The HBeAg level (OR = 0.37, P = 0.013) as well as its declined value (OR = 2.02, P = 0.012) at 24-wk also independently predicted HBeAg SC, with the AUROC of 0.828 and 0.814, respectively. The HBeAg titer < -0.5 lg PEIU/mL combined with its declined value > 2.2 lg PEIU/mL at 24-wk predicted HBeAg SC with a sensitivity, specificity, PPV, NPV of 88%, 98%, 88% and 98%, respectively, and the AUROC reached 0.928. CONCLUSION: The combination of HBeAg level and its declined value at 24-wk may be used as a reference parameter to optimize NAs therapy.

Measurement of the hepatitis B core-related antigen is valuable for predicting the pathological status of liver tissues in chronic hepatitis B patients.

The objective of this study was to evaluate the validities of serum hepatitis B core-related antigen (HBcrAg) for predicting the pathological status of liver tissues of chronic hepatitis B (CHB). A total of 205 Chinese patients with CHB, including 121 HBeAg-positive and 84 HBeAg-negative patients, were enrolled in this study. In HBeAg-positive patients, AUCs of serum HBcrAg for predicting severe necro-inflammation and advanced fibrosis were greater than 0.70; using serum HBcrAg<=4.81×10(4)kUmL(-1) and <=2.45×10(4)kUmL(-1) as cutoffs, the sensitivities, specificities, accuracies for predicting severe necro-inflammation and advanced fbrosis were 0.697, 0.716, 0.711 and 0.818, 0.778, 0.785, respectively. In HBeAg-negative patients, the AUCs of serum HBcrAg for predicting significant necro-inflammation and significant fibrosis were greater than 0.70; using serum HBcrAg>=1.70×10(2)kUmL(-1) and >=4.02kUmL(-1) as cutoffs, the sensitivities, specificities, accuracies for predicting significant necro-inflammation and significant fibrosis were 0.929, 0.964, 0.952 and 1.000, 1.000, 1.000, respectively. These results indicated favorable performances of serum HBcrAg for predicting severe necro-inflammation and advanced fibrosis in HBeAg-positive patients and significant necro-inflammation and significant fibrosis in negative patients.

[Proteomic analysis of peripheral blood mononuclear cells to identify potential markers of fibrosis in chronic hepatitis B].

OBJECTIVE: To identify non-invasive biomarkers for diagnosis and/or prognosis of liver fibrosis in chronic hepatitis B (CHB). METHODS: Peripheral blood samples were obtained from 48 patients with CHB, including 24 with mild fibrosis (stage 1, S1) and 24 with severe fibrosis (stage 4, S4), and subjected to Ficoll density gradient centrifugation in order to obtain enriched samples of peripheral blood mononuclear cells (PBMCs).The PBMC proteomes of the two groups were assessed by first separating the total proteins by two-dimensional gel electrophoresis (2DE) and then identifying the differentially expressed proteins by liquid chromatography combined with tandem mass spectrometry (LCMS/MS). RESULTS: The enriched PBMC samples from the S1 group and the S4 group had similar amounts of platelets [(19.268+/- 6.413) * 109/L and(19.480+/- 6.538) * 109/L, respectively); however, for both, the platelet amounts were 5 to 15-fold lower than that of the normal reference (100-300 *109/L). There was no significant difference found between the platelet amounts in the S1 patients and healthy controls (P=0.930). Twelve differentially expressed proteins were identified through 2DE-LC-MS/MS, including proteins such as moesin and NADH dehydrogenase [ubiquinone] iron-sulfur protein 3 that are involved in various biological processes like cell movement, cell adhesion, kinase signaling and transcription. CONCLUSION: s The 12 proteins with differential expression in S1 and S4 patients with CHB and liver fibrosis may represent markers related to development and/or progression of liver fibrosis.

[Plasma proteome analysis of chronic hepatitis B patients with different stages of liver fibrosis].

OBJECTIVE: To identify plasma biomarkers with specific relation to the various liver fibrosis stages that can be used to assess hepatitis B virus (HBV)-infected patients for non-invasive liver fibrosis and to evaluate the prognosis of the liver fibrosis. METHODS: Plasma samples were collected from 80 HBV-positive patients at the Hepatitis Department of Shanghai Public Health Clinical Center between September 2008 and January 2011. The samples were grouped according to the patient's stage of hepatic fibrosis determined by liver biopsy: S0-1 (n = 40), S2-3 (n = 20), and S4 (n = 20). Each plasma sample was processed to remove the two most abundant proteins, albumin and immunoglobulin G (IgG), and then resolved by two-dimensional (2D) electrophoresis. ImageMaster 2D analysis software was used to identify differentially expressed proteins related to the liver fibrosis stages. After trypsin digestion, the differential proteins were identified by online reversed-phase nano-flow liquid chromatography coupled with electrospray ionization ion trap mass spectrometry (MS). RESULTS: The patients in the three groups were not significantly different in age (range: 30-50 years; P = 0.053) or sex (x² = 0.155, P = 0.926). Low-abundance proteins were efficiently enriched by the albumin/IgG depletion method. Fourteen differentially expressed proteins were detected among the S0-1, S2-3 and S4 groups, all of which were identified by tandem MS and included fibrinogen gamma chain, haptoglobin, complement C3, Ig kappa chain C region, and apolipoprotein A-I. CONCLUSION: Plasma proteomic analysis of chronic hepatitis B patients identified a panel of differentially expressed proteins related to different stages of liver fibrosis. These proteins may represent diagnostic and prognostic biomarkers of HBV-related hepatic fibrosis.