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Objective:To explore the early predictors for clinical cure by sequential combined interferon therapy in nucleos(t)ide analogues (NAs) experienced patients with chronic hepatitis B(CHB).Methods:CHB patients received NAs treatment≥one year with hepatitis B surface antigen (HBsAg) ≤1 500 IU/mL, hepatitis B e antigen (HBeAg) negative and hepatitis B virus (HBV) DNA <100 IU/mL in the Third Affiliated Hospital of Sun Yat-sen University from June 2016 to September 2019 were included. According to the different treatment regimens, the patients were divided into interferon alone for 48 weeks group (group A), interferon combined with NAs for 12 weeks and continued NAs treatment for 48 weeks group (group B), interferon combined with NAs for 48 weeks group (group C). Basic data such as age and gender of patients were collected. HBsAg, hepatitis B surface antibody (anti-HBs) and alanine aminotransferase (ALT) were monitored at week 4, 8, 12, 24, 36 and 48. The decline of HBsAg from baseline, and the rates of clinical cure at 48 weeks were analyzed. The independent sample t test, chi-square test and rank sum test were used for statistical analysis. Logistic regression analysis was used to achieve the early prediction index of clinical cure at week 48. Results:A total of 1 020 CHB patients were followed up regularly for at least five time points. The rates of clinical cure at week 48 in group A, B and C were 34.6%(157/454), 32.7%(69/211) and 33.5%(119/355), respectively, with no statistical significance ( χ2=0.25, P=0.883). Patients were divided into the cured group (345 cases) and the uncured group (675 cases) according to the clinical outcomes at week 48. The age ((38±13) years old vs (43±12) years old), baseline HBsAg (131.00(359.80) IU/mL vs 437.60(531.50) IU/mL) and the proportion of male patients (81.7%(282/345) vs 89.5%(604/675)) of patients in the cured group were all lower than those of patients in the uncured group. The differences were all statistically significant ( t=6.32, Z=12.67, χ2=11.99, respectively, all P<0.050). There were 212 patients in the cured group who achieved clinical cure within 24 weeks of treatment. The rate of clinical cure at 48 weeks in patients whose HBsAg at week 4 decreased from baseline was higher than that in patients with increased HBsAg (41.6%(149/358) vs 28.2%(108/383)). The difference was statistically significant ( χ2=14.13, P<0.001). The rate of clinical cure at week 48 in patients with HBsAg at week 12 decreased ≤34.03% of baseline was only 6.9%(13/188). Multivariate logistic regression analysis showed that age (odds ratio ( OR)=0.962, 95% confidence interval ( CI) 0.936 to 0.989, P=0.006), HBsAg level at week 24 ( OR=0.950, 95% CI 0.934 to 0.966, P<0.001) and anti-HBs level at week 24 ( OR=1.012, 95% CI 1.005 to 1.019, P=0.001) were early predictors for clinical cure at week 48 of treatment in NAs experienced CHB patients. Conclusions:Clinical cure of NAs experienced CHB patients received sequential combined interferon therapy mostly occurs in the early stage (within 24 weeks). Age, HBsAg level at week 24, and anti-HBs level at week 24 are early predictors for clinical cure of 48-week sequential combined interferon treatment.
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Hepatitis B virus (HBV) infection is closely associated with the adverse events such as liver cirrhosis, liver cancer, and liver failure and remains a serious threat to human health. Pegylated interferon is an indispensable drug for the treatment of chronic hepatitis B (CHB), and interferon-stimulated genes are associated with a variety of viruses, but few studies have mentioned their association with hepatitis B and their predictive effect after the treatment of hepatitis B with interferon. This article introduces the predictive factors for interferon treatment of CHB and summarizes the association of interferon-stimulated genes with hepatitis B and their predictive effect, so as to provide a reference for clinical work and basic research.
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Nucleos(t)ide analogues (NAs), which are widely used as the first-line anti-hepatitis B virus (HBV) drugs in clinical practice, can effectively inhibit the replication of HBV DNA, significantly slow down disease progression in chronic hepatitis B (CHB) patients, and reduce the development of end-stage liver diseases such as liver failure and liver cancer. However, for some CHB patients receiving first-line NAs for 48 weeks or longer, serum HBV DNA is still persistently or intermittently higher than the lower detection of limit of sensitive nucleic acid detection reagents. After discussion by the authors, low-level viremia (LLV) is defined as follows: persistent LLV refers to the condition in which CHB patients, who receive entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide fumarate for ≥48 weeks, test positive for HBV DNA by two consecutive detections with sensitive quantitative PCR, with an interval of 3-6 months, but have an HBV DNA level of ＜2000 IU/ml; intermittent LLV refers to the condition in which patients test positive for HBV DNA intermittently by at least three consecutive detections with sensitive quantitative PCR, with an interval of 3-6 months, but have an HBV DNA level of ＜2000 IU/ml. For the diagnosis of LLV, the issues of poor compliance and drug-resistant mutations should be excluded. LLV might be associated with the increased risk of progression to liver fibrosis or hepatocellular carcinoma in patients with liver cirrhosis under NA treatment, but there are still controversies over whether the original treatment regimen with NAs should be changed after the onset of LLV. This article summarizes the incidence rate of LLV under NA treatment and the influence of LLV on prognosis and analyzes the possible mechanisms of the osnet of LLV, so as to provide a reference for the management of LLV in patients treated with NAs.
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Objective:To analyze the value of serum ceruloplasmin (CP) levels in predicting the outcome of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).Methods:The clinical data of 1 751 patients with HBV-ACLF treated in the Third Affiliated Hospital of Sun Yat-sen University from January 2010 to March 2018 were retrospectively analyzed. According to 30-day outcomes, 1 220 survival patients were classified into group A; 465 fatal patients and 46 patients receiving liver transplantation were classified into group B (total 531 cases). Risk factors associated with 30-day survival were estimated using Cox proportional hazards regression. ROC curve analysis was performed to evaluate the predictive value of CP on the 30-day outcome of patients with HBV-ACLF.Results:Multivariate analysis indicated that CP, albumin and alpha fetoprotein were independent protective factors for 30-day survival of HBV-ACLF patients ( P<0.05 or <0.01), while age, white blood cell count, AST, total bilirubin, INR, serum creatinine, HBV DNA, hepatorenal syndrome and hepatic encephalopathy were independent risk factors ( P<0.01). The area under the ROC curve (AUC) of CP was 0.570 (95% CI 0.540-0.599, P<0.01); while AUC of MELD score was 0.783 (95% CI 0.759-0.807, P<0.01) and MELD-Na score was 0.774 (95% CI 0.750-0.798, P<0.01). Compared with MELD score and MELD-Na score, the value of CP in predicting the 30-day prognosis of HBV-ACLF patients was lower ( P<0.01). The cut-off value of CP for predicting 30-day outcome of HBV-ACLF patients was 0.173 g/L, with the sensitivity of 69.4%, and the specificity of 41.6%. According to the cut-off value, the patients were divided into low CP level group (level of CP<0.173 g/L) and high CP level group (level of CP≥0.173 g/L); the 30-day cumulative survival rate of low CP level group was lower than that of high CP level group ( χ2=17.75, P<0.01). Conclusions:Serum CP level can predict the 30-day outcome of HBV-ACLF patients to a certain extent.
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Objective@#Hepatitis B surface antigen (HBsAg) loss is seldom achieved with nucleos(t)ide analog (NA) therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon (Peg-IFN) alfa-2a. We assessed HBsAg loss with 48- and 96-week Peg-IFN alfa-2a in chronic hepatitis B patients with partial response to a previous NA.@*Methods@#Hepatitis B e antigen (HBeAg)-positive patients who achieved HBeAg loss and hepatitis B virus DNA < 200 IU/mL with previous adefovir, lamivudine or entecavir treatment were randomized 1:1 to receive Peg-IFN alfa-2a for 48 (n = 153) or 96 weeks (n = 150). The primary endpoint of this study was HBsAg loss at end of treatment. The ClinicalTrials.gov identifier is NCT01464281.@*Results@#At the end of 48 and 96 weeks' treatment, 14.4% (22/153) and 20.7% (31/150) of patients, respectively, who switched from NA to Peg-IFN alfa-2a cleared HBsAg. Rates were similar irrespective of prior NA or baseline HBeAg seroconversion. Among those who cleared HBsAg by the end of 48 and 96 weeks' treatment, 77.8% (14/18) and 71.4% (20/28), respectively, sustained HBsAg loss for a further 48 weeks. Baseline HBsAg < 1 500 IU/mL and week 24 HBsAg < 200 IU/mL were associated with the highest rates of HBsAg loss at the end of both 48- and 96-week treatment (51.4% and 58.7%, respectively). Importantly, extending treatment from 48 to 96 weeks enabled 48.3% (14/29) more patients to achieve HBsAg loss.@*Conclusion@#Patients on long-term NA who are unlikely to meet therapeutic goals can achieve high rates of HBsAg loss by switching to Peg-IFN alfa-2a. HBsAg loss rates may be improved for some patients by extending treatment from 48 to 96 weeks, although the differences in our study cohort were not statistically significant. Baseline and on-treatment HBsAg may predict HBsAg loss with Peg-IFN alfa-2a.
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Objective@#To evaluate the safety and efficacy of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) 25/150/100 mg once daily combined with dasabuvir 250mg, twice daily in non-cirrhotic Chinese adult patients with newly diagnosed and treated chronic HCV genotype 1b infection. @*Methods@#A randomized, double-blind, placebo-controlled, multicenter phase 3 clinical trial was conducted in mainland China, Korea, and Taiwan.Safety and efficacy of OBV/PTV/r plus DSV administered for 12 weeks were evaluated in a newly diagnosed and treated (interferon alpha /pegylated interferon alpha) and ribavirin non-cirrhotic adults with chronic HCVgenotype 1b infection. Patients randomly received OBV/PTV/r plus DSV for 12 weeks (Group A), or placebo for 12 weeks (Group B) followed by an open-label phase of OBV/PTV/r plus DSV for 12 weeks. Sustained response (SVR12) rate obtained at 12 weeks and (SVR24) 24 weeks after discontinuation of treatment, and the incidence of adverse events and laboratory abnormalities after double-blind and open-label phase treatment were assessed. @*Results@#A total of 410 cases of Chinese patients were included and randomly assigned to group A and B (with 205 cases in each group) in a 1:1 ratio. The rates of SVR12 and SVR24 were 99% (95% CI: 94.8% - 99.8%) in the newly diagnosed patients in group A (205 patients) and the rates of SVR12 and SVR24 were 100% in treated patients (95% CI: 96.3% - 100%). Different baseline characteristics had no effect on SVR12 and SVR24 rates. Most of the adverse events occurred were mild, asymptomatic, and≥ 3 laboratory abnormalities during treatment were rare, including elevation of alanine aminotransferase (2 cases in double-blind stage A group), aspartate aminotransferase (Double-blind stage A (3 cases) and total bilirubin (1 case in open-label phase B group); however, those mild adverse events could be recovered after drug withdrawal or discontinuation. only1 person discontinued drugs due to adverse events (Group B, open-label phase). @*Conclusion@#The 12 weeks treatment course of OBV/PTV/r combined with DSV produced 99% ~ 100% rates of SVR12 and SVR24 in non-cirrhotic Asian adult patients with newly diagnosed and treated chronic HCV genotype 1b infection, and the tolerance and safety were good.
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Objective@#To evaluate the efficacy and safety of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) 25/150/100 mg once daily and dasabuvir (DSV) 250 mg twice daily combined with ribavirin in adult patients of Mainland China with chronic HCV genotype 1b infection and compensated cirrhosis. @*Methods@#An open-label, multicenter, phase 3 clinical trial study was conducted in mainland China, Taiwan, and South Korea. Adult patients with compensated cirrhosis (Metavir score =F4) who were newly diagnosed and treated for hepatitis C virus genotype 1b infection with ombitasvir/paritaprevir/ritonavir and dasabuvir combined with ribavirin for 12 weeks were included. Assessed SVR rate of patients obtained at 12 and 24 weeks after drug withdrawal. Efficacy and safety were evaluated in patients who received at least one time study drugs. @*Results@#A total of 63 patients from mainland China were enrolled, 62 of whom (98.4%) had a baseline Child-Pugh score of 5 points. The overall rate of SVR12 and SVR24 in patients was 100% (95% CI: 94.3% to 100.0%). Most of the adverse events that occurred were mild. The incidence of common (≥10%) adverse events and laboratory abnormalities included elevated total bilirubin (36.5%), weakness (19.0%), elevated unconjugated bilirubin (19.0%) and conjugated bilirubin (17.5%), and anemia (14.3%). Three cases (4.8%) of patients experienced Grade ≥ 3 adverse events that were considered by the investigators to be unrelated to the study drug. None patients had adverse events leading to premature drug withdrawal. @*Conclusion@#Mainland Chinese patients with chronic HCV genotype 1b infection and compensated cirrhosis who were treated with OBV/PTV/r plus DSV combined with RBV for 12 weeks achieved 100 % SVR at 12 and 24 weeks after drug withdrawal. Tolerability and safety were good, and majority of adverse events were mild.
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Objective To evaluate the prevalence and risk factors of metabolic syndrome among hepatitis C patients in Chinese Han population .Methods This was a multicenter ,cross-sectional study . A total of 997 Chinese Han patients with hepatitis C virus (HCV) infection were enrolled .Demographic data ,anthropometric data and clinical parameters related to metabolic syndrome were collected .Statistical analysis was performed by t-test (normal distribution) or Mann-Whitney U two-sample test (non-normal distribution) and χ test .Binary logistic regression analyses were used to determine the parameters significantly related to metabolic syndrome .Results Among the 997 patients ,170 (17 .1%) patients were diagnosed with metabolic syndrome .Binary logistic regression showed that genotype 2 (OR＝1 .594 ;95% CI :1 .045－2 .431 , P＝ 0 .030) ,older age (OR＝ 1 .040 ;95% CI :1 .022 －1 .058 , P＜ 0 .01) , overweight (OR＝3 .876 ;95% CI :2 .593－5 .792 ,P＜0 .01) ,fatty liver history (OR＝2 .106 ;95% CI : 1 .384－3 .204 ,P＝0 .001) ,homeostasis model assessment insulin (HOMA-IR) (OR＝1 .263 ;95% CI :1 .118－1 .427 , P＜0 .01) ,fasting insulin (OR＝0 .949 ;95% CI :0 .915 －0 .985 , P＝0 .006) ,lower serum albumin level (OR＝0 .957 ;95% CI :0 .915 －1 .000 , P＝0 .049) and higher γ-GT level (OR＝1 .004 ;95% CI :1 .000 －1 .008 , P＝ 0 .0041 ) were all significantly associated with the presence of metabolic syndrome .Conclusions Hepatitis C patients with genotype 2 ,older age ,overweight ,fatty liver history ,higher HOMA-IR ,lower fasting insulin level ,lower serum albumin level or higher γ-GT level should be screened for metabolic syndrome .
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Liver failure caused by hepatitis B virus (HBV) infection is common in China, among which acute-on-chronic liver failure (ACLF) is the main type.Because the pathogenesis is complex and the diagnosis and treatment is difficult,HBV related ACLF has high mortality.In recent years, some progress has achieved in diagnosis and therapy of ACLF.This article reviews the new strategies and advances about HBV related ACLF on basis of researches at home and abroad,including the definition, mechanisms, management and prognosis assessment of ACLF.
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[Objective]To evaluate the two-dimensional shear wave elastography(2D SWE)in predicting the prognosis of the patients with acute-on-chronic hepatitis B liver failure(ACLF-HBV).[Methods]312 patients diagnosed with ACLF-HBV at the De-partment of Infectious Diseases in the Third Affiliated Hospital of Sun Yat-sen University from October 1st 2013 to December 31th 2015 were recruited. The baseline data of all patients,including 2D SWE,laboratory data,ultrasonographic data,Model for End-stage Liver Disease score(MELD),Child-Turcotte-Pugh score(CTP),and King′s College Hospital score(KCH),were collected when enrolled. All patients were followed up for at least 90 days and their clinical outcomes(recovering or worsening)were recorded. 2D SWE values of all patients were dynamically collected every 2~4 weeks during the follow-up until death,liver transplantation, or discharging from hospital.[Results]The worsening patients showed higher 2D SWE values than the recovering ones[(44.0 ± 7.5) kPa vs(36.8 ± 10.3)kPa,t=-6.5,P=0.000],2D SWE value less than 39.2 kPa could be a prediction of the patient′s recovery in 90 days.The predictive value of 2D SWE(AUROC=0.73)was higher than that of KCH(AUROC:0.65,z=2.1,P=0.033). Among all the dynamically measured patients,2D SWE rose from(42.1 ± 8.0)kPa to(47.5 ± 9.3)kPa in the worsening group during the 90-day follow-up,while nearly stable in the recovery group.[Conclusion]Noninvasive liver stiffness measurement by 2D SWE is a use-ful method in evaluating the prognosis of ACLF-HBV patients. Taking a cutoff of 39.2 kPa,patients with higher 2D SWE values could have worse clinical outcomes ,otherwise better. It seems that dynamically measuring 2D SWE values could also be helpful ,but more research in the future should be needed.
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Objective@#To investigate the efficacy and safety of the new investigational drug pegylated interferon α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 µg/week) combined with ribavirin in the treatment of patients with genotype 1/6 chronic hepatitis C (CHC), with standard-dose Peg-IFN-α-2a combined with ribavirin as a positive control.@*Methods@#A multicenter, randomized, open-label, and positive-controlled phase III clinical trial was performed. Eligible patients with genotype 1/6 CHC were screened out and randomly divided into Peg-IFN-α-2b(Y shape, 40kD) group and Peg-IFN-α-2a group at a ratio of 2:1. The patients in both groups were given oral ribavirin for 48 weeks in addition and then followed up for 24 weeks after drug withdrawal. Abbott Real Time HCV Genotype II was used to determine HCV genotype, and Cobas TaqMan quantitative real-time PCR was used to measure HCV RNA level at 0, 4, 12, 24, 48, and 72 weeks. Adverse events were recorded in detail. The primary efficacy endpoint was sustained virological response (SVR), and a non-inferiority test was also performed.@*Results@#A total of 561 patients with genotype 1/6 CHC were enrolled, among whom 529 received treatment; 90.9% of these patients had genotype 1 CHC. The data of the full analysis set showed that SVR rate was 69.80% (95% CI 65.00%-74.60%) in the trial group and 74.16% (95% CI 67.73%-80.59%) in the control group (P = 0.297 0). The data of the per protocol set (PPS) showed that SVR rate was 80.63% (95% CI 76.04%-85.23%) in the trial group and 81.33% (95% CI 75.10%-87.57%) in the control group (P = 0.849 8), and the 95% CI of rate difference conformed to the non-inferiority standard. The analysis of the PPS population showed that of all subjects, 47.9% achieved rapid virologic response, with a positive predictive value of 93.8%. The incidence rate of adverse events was 96.30% in the trial group and 94.94% in the control group, and the incidence rate of serious adverse events was 5.13% in the trail group and 5.06% in the control group.@*Conclusion@#In the regimen of Peg-IFN-α combined with ribavirin for the treatment of genotype 1/6 CHC, the new investigational drug Peg-IFN-α-2b(Y shape, 40 kD) has comparable clinical effect and safety to the control drug Peg-IFN-α-2a.
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Liver failure has various clinical types, a complex pathogenesis, and rapid disease progression, as well as a high mortality rate. Liver failure caused by hepatitis B virus infection is the most common type in China with severe conditions, various complications, and a mortality rate as high as 40%-90%. Invasive fungal disease secondary to acute-on-chronic liver failure can affect patients’ prognosis and increase mortality rate. This article introduces the research advances in hepatitis B-related liver failure, artificial liver, and invasive fungal disease secondary to acute-on-chronic liver failure in 2016.
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Objective To evaluate the efficacy and long-term safety of autologous bone marrow stem cells(ABMSC)transplantation in patients with hepatitis B virus(HBV)-associated decompensated liver cirrhosis.Methods This was an open-label,prospective matched case-control study.Thirty patients with HBV-associated decompensated liver cirrhosis hospitalized at the Third Affiliated Hospital of Sun Yat-Sen University from January 2005 to June 2010 were collected and infused with stem cells(stem cell group). Another thirty patients in control group were matched according to baseline characteristics and treated with standard medicine therapy.The patients in stem cell group were treated with stem cells infusion by hepatic artery or portal vein based on standard medicine therapy.All the patients were followed up for 5 to 10 years after surgery. Biochemical indicators were evaluated within the first 48 weeks after transplantation.The complications of cirrhosis and the cumulative incidence rate of hepatocellular carcinoma(HCC)were observed.Measurement data with normal distribution were analyzed by t test. Measurement data with non-normal distribution were compared by Mann-Whitney test.Count data were compared by χ2 test.The cumulative incidence rate of HCC development was compared by Kaplan-Meier analysis.Results The bone marrow aspiration and transplantation surgery were well tolerated in all patients in stem cell group.No complication related to stem cell transplantation therapy was observed. The levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBil) and prothrombin time(PT)decreased,albumin level increased,while model for end-stage liver disease (MELD)scores decreased in both groups after treatment.Serum albumin level in stem cell group increased and ALT level decreased markedly at week 4,compared with that in control group at week 4(Z=2.188,P=0.029,Z=3.296,P=0.001,respectively).In stem cell group,21 patients received stem cells transplantation by hepatic artery and 9 patients by portal vein.Biochemical indicators were improved in all patients compared to baseline.However,there was no statistically significant differences between hepatic artery group and portal vein group.The median follow-up time was 6 years.Two patients in stem cell group and 1 patient in control group died(χ2=0.351,P=0.554).Six patients in stem cell group (20.0%)and 11 patients(36.7%)in control group developed HCC.There was no significant differences in the cumulative incidence rate of HCC between two groups(χ2= 0.148,P= 0.701).Hepatorenal syndrome did not development in either group.There were no statistically significant differences in the rates of complications including spontaneous peritonitis,hepatic encephalopathy and gastrointestinal hemorrhage between two groups after 5 to 10 years of follow-up(χ2=0.162,P=0.688,χ2=1.071,P=0.301,χ2=1.071,P=0.301,respectively).Conclusion ABMSC transplantation in patients with HBV-associated decompensated liver cirrhosis improves liver function transiently and has long-term safety.
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Hepatitis B virus (HBV)-related liver failure has an extremely high mortality rate and a complex pathogenesis,and since related mechanisms are not fully understood,it has been very difficult to diagnose and treat this disease in clinical practice.Apart from liver transplantation,there is still a lack of specific and effective drugs and therapies for the medical treatment of HBV-related liver failure.This article summarizes our experience and research achievements in the diagnosis and treatment of HBV-related liver failure,explores the association between host's genetic background and development and aggravation of chronic hepatitis B,and elaborates on the phenomenon of three attacks and the concept of four time phases.In the aspect of treatment,this article focuses on the clinical application of antiviral therapy,anti-infective therapy,glucocorticoids,and stem cell transplantation;for the evaluation of patients' condition,this article establishes a suitable system for evaluating the prognosis of HBV-related liver failure.
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<p><b>OBJECTIVE</b>To perform a prospective,multicenter,open,randomized study to determine a treatment regimen for treatment-naive patients with refractory chronic hepatitis C (RHC) using the predictive value (PV) of early virological response (EVR).</p><p><b>METHODS</b>A total of 438 patients from 18 hospitals were recruited between December 2008 and December 2010 and administered peg-interferon/ribavirin treatment for 12 weeks. Patients who achieved complete EVR (cEVR) were assigned to group A for a 48-week course of treatment, while patients without cEVR were randomly allocated to either group B 1 for a 72-week course of treatment or to group B2 for a 96-week course of treatment. Serum hepatitis C virus RNA levels at baseline,treatment weeks 4, 12 and 24, end of treatment, and post-treatment week 24 were measured and used to evaluate the efficiency of therapy.</p><p><b>RESULTS</b>The overall sustained virological response (SVR) rate was 85.1%. In all, 91.0% of patients achieved cEVR and were assigned to group A, which had an SVR rate of 90.8%. There was no statistically significant difference in the SVR rates of groups B1 and B2 (29.4% vs. 25.0%, P more than 0.05). The positive PV of rapid virological response (RVR), cEVR and delayed virological response (DVR) for SVR was 93.4%, 90.8% and 77.8% respectively, and the negative PV of RVR, EVR and DVR for SVR was 28.0%, 93.3% and 100% respectively. Overall, 66.9% of the patients experienced adverse events (AEs), but only 1.9% of patients experienced sevcre AEs.</p><p><b>CONCLUSION</b>The majority of Chinese RHC treatmentna(i)ve patients (91.0%) can achieve cEVR and a high SVR rate with a low rate of severe AEs using the cEVR guided personal treatment regimen.</p>
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Humains , Antiviraux , Asiatiques , Association de médicaments , Hépatite C chronique , RibavirineRésumé
Objective To evaluate the efficacy of pegylated interferon ( PegIFN ) α-2a plus ribavirin ( RBV) therapy for chronic hepatitis C ( CHC) in non-responders, and to investigate the related influencing factors.Methods A prospective, open, multicenter and randomized study was conducted.A total of 81 CHC non-responders were recruited from 10 clinical centers during February 2009 to November 2011.Patients were randomly assigned into two groups:group A (n=37) was given PegIFNα-2a plus RBV treatment for 72 weeks and group B (n=44) was given PegIFNα-2a plus RBV treatment for 96 weeks.Both groups were followed up for 24 weeks after treatment.Virological responses in two groups were observed, and treatment efficacies among patients with different genotypes, and among those with different previous treatment were compared.SAS software was used for statistical analysis.Results Fifty-two patients ( 28 from group A and 24 from group B) completed the study in total.The rates of rapid virological response ( RVR) , complete early virological response ( cEVR ) , end of treatment viral response ( ETVR ) and sustained virological response (SVR) in group A were 25.0% (7/28), 60.7% (17/28), 67.9%(19/28) and 60.7%(17/28), respectively; while those in the group B were 41.7% (10/24), 70.8%(17/24), 70.8%(17/24) and 70.8% (17/24), respectively; and there were no significant differences between two groups (P>0.05).SVR was observed in 82.9%(29/35) of patients with CC genotype of IL-28B, which was higher than that in patients with other genotypes ( 3/13 ) , and the difference was of statistical significance (P0.05).The rates of RVR, cEVR, ETVR and SVR in patients who were previously treated with IFN were 36.4%(12/33), 81.8%(27/33), 81.8%(27/33) and 75.8%(25/33), and the rates of cEVR, ETVR and SVR were higher than those in patients who were previously treated with PegIFN (P0.05).Adverse events occurred in 38 patients (46.9%), but no severe ones were observed. Conclusion The efficacy of PegIFNα-2a plus RBV therapy for CHC in non-responders is satisfactory, which may influenced by IL-28B genotypes and previous treatment.
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<p><b>OBJECTIVE</b>To investigate the dynamic changes in serum levels of hepatitis B surface antigen (HBsAg) and their relation to hepatic parenchyma cell volume (hepatic cell quantity) at different grades of liver inflammation and stages of hepatic fibrosis in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B.</p><p><b>METHODS</b>Serum HBsAg levels were detected by electrochemilumineseence. Serum HBsAg levels were apportioned according to the hepatic parenchyma cell volume and compared among liver histological inflammation grade (1, 2, 3 and 4) and hepatic fibrosis stage ( I, II, III and IV), respectively.</p><p><b>RESULTS</b>The levels of serum HBsAg among the four liver histological inflammation grades were:1:6,036.4+/-2,729.4 COI/ml; 2:6,704.6+/-2,457.5 COI/ml; 3:6,332.2+/-2,409.0 COI/ml; 4:6,226.2+/-2,716.0 COI/ml. There were no differences among the groups before apportion (Fbefore apportion=0.564, P=0.640).Serum HBsAg levels apportioned by the hepatic parenchyma cell volume among liver histological inflammation grades were:1:9,174.8+/-4,142.0 COI/ml; 2:10,743.1+/-3,950.3 COI/ml; 3:11,078.0+/-4 230.0COI/ml; 4:11,540.5+/-5,058.8 COI/ml. There were significant differences among the groups after apportion (Fafter apportion =27.354, P<0.001). Serum HBsAg levels among hepatic fibrosis stages were: I: 6,222.1+/-2,665.4 COI/mL; II: 6,706.8+/-2,623.8 COI/ml; III:6 004.5+/-2,625.5 COI/ml; IV:6,455.6+/-2,344.4 COI/ml. There were no differences among groups before apportion (Fbefore apportion=0.768, P=0.513).Serum HBsAg levels apportioned by the hepatic parenchyma cell volume (hepatic cell quantity) among hepatic fibrosis stages were: I :9 417.5+/-4,034.2 COI/ml; II :10,093.3+/-4,183.4 COI/ml; III:10,177.1+/-4,445.0 COI/ml; IV:12,166.6+/-4,418.5 COI/ml. There were significant differences among the groups after apportion (Fafter apportion=57.077, P<0.001).</p><p><b>CONCLUSION</b>Serum HBsAg levels apportioned by the same hepatic parenchyma cell volume (hepatic cell quantity), rather than serum HBsAg levels, increased with hepatic pathological progress.</p>
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Humains , Hépatite B , Antigènes de surface du virus de l'hépatite B , Antigènes e du virus de l'hépatite virale B , Virus de l'hépatite B , Hépatocytes , Inflammation , Cirrhose du foieRésumé
Objective To investigate the correlation between the frequency of myeloid-derived suppressor cells (MDSC) and the frequency of regulatory T cells (Treg) in the peripheral blood in patients with chronic hepatitis B (CHB) and its clinical significance.Methods A total of 45 CHB patients including 23 mild-to-moderate CHB patients,22 severe CHB patients,and 15 healthy controls were enrolled.The frequencies of MDSC and Treg in the peripheral blood were studied using flow cytometry and its correlation with clinical data was analyzed by Sepearman correlation analysis.Results The median frequency of MDSC in CHB patients was 0.414％,which was significantly higher than that in healthy controls 0.226％ (Z=-2.356,P=0.018 9).The frequency of MDSC in CHB patients was negatively correlated with the level of alanine transaminase (ALT) and aspartate transaminase (AST) (r=-0.480,-0.478; both P＜0.01),but had no relations with hepatitis B virus (HBV) viral load (r=-0.049,P=0.75).An increase frequency of MDSC was observed in CHB patients with an ALT of 5 × upper limits of normal (ULN) or less or AST of 3 × ULN or less.The frequency of MDSC in CHB patients was positively correlated with that of Treg (r =0.345,P =0.02).Conclusions The activation and proliferation of MDSC may facilitate and maintain HBV persistent infection.The change of the frequency of MDSC is in line with that of Treg,indicating that immunosuppressive functions of MDSC may be related with the development of Treg in CHB.
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Objective To assess the application of a new scoring system for severity evaluation of acute-on-chronic liver failure induced by hepatitis B.Methods A total of 399 patients (203 survivals and 196 deaths) with acute-on-chronic liver failure induced by hepatitis B were collected from the Third Affiliated Hospital of Sun Yat-sen University during January 2003 and June 2008.All patients were graded with the new scoring system and model for end-stage liver disease (MELD) at critical stage (survivals) or terminal stage (deaths).The survival rates and fatality rates of patients who were graded by two scoring systems were analyzed and compared.Results With MELD system,the fatality rate was 11.89％ (17/143) in patients with scores of 15-26,64.68％ (141/218) with scores of 27-48,and 100％ (38/38) with scores of 49-69.No score range with fatality rate of 0 was found.While with the new scoring system,the survival rate was 99.2％ (126/127) when the severity scores were between 2 to 8,and patients with scores 2,3,4,5,6 and 8 were all survived; the fatality rates were gradually raised from 4.2％ (1/24) with scores of 9-17 to 100％ (82/82) with scores of 18 and above.Conclusion The new scoring system is more objective,simple and sensitive than MELD system,which can be used for severity evaluation of acute-onchronic liver failure induced by hepatitis B.
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Objective To study programmed death-1 (PD-1) and T-cell immunoglobulin mucin3 (Tim-3) co-expression on peripheral blood mononuclear cells (PBMC) and hepatitis B virus (HBV)-specific CD8+ T cells in patients with chronic HBV infection and its correlation with liver inflammatory activities.Methods One hundred and sixty subjects with chronic HBV infection who visited the outpatient and inpatient Department of Infectious Diseases in the Third Affiliated Hospital of Sun Yatsen University were enrolled,including 63 cases of mild or moderate CHB (MCHB),31 of severe CHB (SCHB),55 of acute-on-chronic liver failure (ACLF) and 11 inactive HBsAg carriers.Twenty healthy subjects were enrolled as controls.Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect HBV DNA,enzyme-linked immunosorbent assay (ELISA) to measure HBV serological markers,and flow cytometry to detect human leukocyte antigen (HLA)-A2 and determine the expression of PD-1 and Tim-3 on PBMC and HBV-specific CD8+ T cells.Cell counts of Tim-3+,PD-1+,and Tim-3+/PD1+ PBMC and HBV-specific CD8+ T cells were compared among different groups,and their correlation with commonly used inflammatory activity indicators were studied.Analysis of variance and Kruskal-Wallis test were used for measurement data with gaussian distribution and skewed distribution,respectively.Spearman correlation analysis was used to assess the association between Tim-3/PD-1 expression and inflammatory activity indicators.Results The frequency of Tim-3+/PD-1+ PBMC was 0.25 ％ in ACLF group (P=0.0049),0.24 ％ in SCHB group (P-0.0025) and 0.13％ in MCHB group (P=0.0006),which were significantly higher than that in control group (0.03％),and the frequency of Tim-3 /PD-1-PBMC in the three groups were significantly lower than that in control group (P =0.0000),but the differences between HBsAg carriers (0.10％) and controls (0.03％) were not statistically significant (P=0.28).Among 160 subjects,78 were HLA-A2 positive.The frequency of Tim-3+/PD-1+ HBV-specific CD8+ T cells was 68.72％±17.21％ in ACLF group,and 59.66％± 19.25％ in SCHB group,which were significantly higher than that in HBsAg carrier group (33.93％ ± 10.80％,P=0.0000,P=0.0054).The frequency of Tim-3 /PD-1-HBV-specific CD8+ T cells in ACLF group was 2.80％,which was significantly lower than that in HBsAg carrier group (27.24％,P=0.0004).The frequency of Tim3+/PD-1+ HBV-specific CD8+ T cells was positively correlated with alanine aminotransferase (r=0.26,P=0.022),aspartate aminotransferase (r=0.28,P=0.012) and total bilirubin levels (r=0.36,P=0.001); and inversely correlated with albumin level (r=-0.35,P=0.002) in serum.Furthermore,it was positively correlated with international normalized ratio (INR,r=0.34,P =0.045) and model for end-stage liver disease score (r=0.43,P=0.027) in ACLF group.Conclusions Co-expressions of Tim-3 and PD-1 on PBMC and HBV-specific CD8+ T cells are significantly upregulated in patients with CHB,and correlated with liver inflammatory activities.These findings indicate that Tim-3 and PD-1 co-expression may involve in disease activity and liver failure in CHB.