ABSTRACT
Objective@#To investigate the efficacy of sequential therapy with telbivudine in the treatment of HBeAg-positive chronic hepatitis B (CHB) patients with partial response after a standard course of interferon therapy.@*Methods@#A retrospective cohort study was performed for 58 HBeAg-positive CHB patients with partial response at the end of interferon therapy (48-60 weeks) from January 2009 to December 2013. According to whether telbivudine was used sequentially or withdrawn at the end of the course of treatment, the patients were divided into telbivudine sequential therapy group and withdrawal group, and the two groups were compared with in terms of biochemical, virological, and serological response rates. The chi-square test, the t-test, and the non-parametric test were used based on data type.@*Results@#A total of 58 patients were enrolled in this study, with 31 in the telbivudine sequential therapy group and 27 in the withdrawal group. At 12 and 24 weeks after interferon therapy ended, the telbivudine sequential therapy group had a significantly higher HBeAg clearance rate than the withdrawal group (22.6%/29.0% vs 0%/3.7%, P < 0.05). At week 48 of follow-up, the telbivudine sequential therapy group had a significantly higher combined response rate than the withdrawal group (22.6% vs 0%, P = 0.015). Among the 31 patients in the telbivudine sequential therapy group, 11 had an increase in creatine kinase during the administration of telbivudine. No patient in either group experienced serious adverse reactions during follow-up, such as muscular soreness, myositis, peripheral neuropathy, renal dysfunction, and liver function decompensation.@*Conclusion@#In HBeAg-positive CHB patients with partial response to interferon therapy, sequential therapy with telbivudine can increase serological HBeAg clearance rate and combined response rate at week 48, and it is safe in HBeAg-positive CHB patients achieving partial response at the end of interferon therapy.
ABSTRACT
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.
ABSTRACT
The incidence rate of hepatocellular carcinoma (HCC) is increasing around the world and tends to decrease in East Asia and several regions in China;however, China still has higher incidence rate and mortality rate of HCC than most countries.Studies have shown that long-term antiviral therapy can inhibit HBV replication to a very low level or help patients with HCV infection achieve sustained virologic response, which can further reduce the incidence rate of virus-related HCC.New evidence suggests that compared with nucleos(t)ide analogues, PEG-IFNα has a better effect of secondary prevention.Studies also indicate that interferons play an important role in tertiary prevention of virus-related HCC.This article reviews the epidemiological studies on virus-related HCC in recent years and the role of antiviral therapy in second and tertiary prevention and points out that adequate and effective antiviral therapy is the basis for preventing the development and recurrence of HCC.
ABSTRACT
Objective To investigate the distribution of serum hepatitis B surface antigen (HBsAg) levels in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).Methods A total of 226 cases of HBV-related HCC were collected from June 2009 to December 2013.Demographic characteristics of patients with different barcelona clinica liver cancer (BCLC) stages,the status of cirrhosis and HBsAg levels with different virological indicators were compared.HBsAg quantification was tested by chemiluminescence.The statistical analysis was conducted by t test,x2 test,Kruskal-Wallis H rank sum test and Mann-Whitney U rank sum test.Results A total of 226 cases were included with 201male patients and 25 female patients.HBsAg levels in HBV-related HCC patients with different ages were significantly different (x2=12.30,P =0.015),but with no statistical difference in those with different gender (Z=-0.35,P＞0.05).The HBsAg levels were not significantly different between patients with or without liver cirrhosis (Z =-0.80,P =0.419).HBsAg levels in liver cirrhosis cases with different liver function stages were not significant different (x2=2.15,P=0.341).HBsAg levels in HBeAg-positive group or HBV DNA positive group were significantly higher than those in HBeAg-negative group or HBV DNA negative group,respectively (Z =-3.67 and-4.80,respectively,both P＜0.01).The HBsAg levels in patients with different BCLC stages were not significantly different (x2 8.05,P =0.09).No significant differences were found in HBsAg levels between patients with or without portal vein violation,lymph node transfer or distant transfer (Z=-0.65,-0.03 and-1.24,respectively,all P＞ 0.05).The constituent ratios of patients with different HBsAg levels in different BCLC stages were statistically different (x2 =28.17,P-0.005).Conclusions There are no significant differences of HBsAg levels in patients with different BCLC stages,indicating that HBsAg may not be a contributor for disease progression after emergence of HCC.
ABSTRACT
Esophagogastric variceal bleeding and hepatorenal syndrome are common complications in patients with decompensated liver cirrhosis and portal hypertension. Terlipressin can lead to the constriction of visceral vessels, reduce portal venous pressure, and increase renal perfusion and is the first-line drug. In recent years, it has been reported that some patients experienced hyponatremia during the treatment with terlipressin. Since patients with liver cirrhosis tend to develop hyponatremia, the application of terlipressin may have an adverse effect on the management of serum sodium level in such patients. This article summarizes the incidence rate of hyponatremia during terlipressin treatment and related risk factors and introduces the pathogenesis of hyponatremia during terlipressin treatment in patients with decompensated liver cirrhosis and the treatment principles for hyponatremia. If the occurrence of hyponatremia can be controlled, terlipressin may be an effective drug for the treatment of portal hypertension.
ABSTRACT
Objective To investigate the correlation between non-alcoholic fatty liver disease and serum and histological viral parameters in patients with chronic hepatitis B (CHB).Methods Clinical and laboratory data from patients with CHB who received liver biopsy from 2009 to 2015 were collected. Patients were divided into steatosis and non-steatosis groups based on the presence of steatosis in liver biopsies.Propensity score matching (PSM)was conducted to adjust the confounding bias including age, sex,body mass index (BMI),total cholesterol (TC)and triglyceride (TG).Correlation of liver fatty and viral parameters was compared between steatosis and non-steatosis groups.Student t test,χ2 test,rank sum test and Pearson correlation test were employed to analyze the data.Results A total of 874 patients with a mean age of (37.0±10.1)years were enrolled in the study,with 690 males and 184 females,and 270 (30.9%)patients were diagnosed with steatosis by liver biopsy.Age,gender,BMI,TC and TG were significantly different between the two groups before PSM (all P 0.05 ).Serum hepatitis B virus (HBV)DNA,hepatitis B surface antigen (HBsAg) level,proportion of hepatitis B e antigen (HBeAg )positivity,HBsAg and hepatitis B core antigen (HBcAg)immunohistological staining in liver tissue were not significantly different between steatosis and non-steatosis groups after PSM (all P >0.05).Patients in steatosis group were stratified into two groups according to the degree of steatosis confirmed by liver biopsies:mild steatosis group (F1 )and medium to severe steatosis group (F2-F4).The serum alanine aminotransferase (ALT),HBV DNA,HBsAg level, proportion of HBeAg positivity,immunohistological HBsAg and HBcAg staining in liver tissue between those two groups showed no differences (all P >0.05).The mean rank of liver inflammation and fibrosis in F1 group were 129.9 and 128.2,respectively,which were both significantly higher than those in F2-F4 group (105 .9 and 108.5 ,respectively;both P <0.05).Steatosis was negatively correlated with either inflammatory grade (r=-0.183,P =0.005)or fibrosis stage (r=-0.150,P =0.020).Conclusions There is no correlation between serum viral factors and hepatic steatosis. Hepatic steatosis is not associated with the expressions of HBsAg and HBcAg in liver tissue.The severity of steatosis is negatively correlated with both liver inflammation and fibrosis.
ABSTRACT
Objective To investigate the early diagnostic value and cost‐effectiveness analysis of common inflammatory markers , including interleukin‐6 (IL‐6 ) , procalcitonin (PCT ) and C‐reactive protein (CRP) in cirrhotic patients with infectious fever .Methods From January 2012 to January 2015 , cirrhotic patients hospitalized in liver center of First Affiliated Hospital ,Fujian Medical University who were excluded with community‐acquired infections and developed fever 48 hours after admission were selected .According to having infection or not ,they were divided into infection group and non‐infection group .White blood cell count (WBC) ,neutrophil percentage (N % ) ,IL‐6 ,PCT ,and CRP at admission (baseline) and at the time point of fever were recorded .The diagnostic threshold of WBC ,N% ,IL‐6 , PCT ,and CRP for infectious fever in cirrhotic patients were analyzed by receiver operating characteristic analysis curve (ROC) .The cost‐effectiveness (C/E) of those biomarkers were compared .Results A total of 299 cases were enrolled ,with 162 in infection group and 137 in non‐infection group .Two hundred and forty‐four were male and 55 were female .The mean age was 55 .1 ± 13 .0 years .Upon the onset of fever , WBC ,N% ,IL‐6 ,PCT ,and CRP of infection group were all significantly higher than those of non‐infection group (all P< 0 .05) .The area under the curve of IL‐6 for infectious fever was 0 .939 (95% CI 0 .910 - 0 .968) ,which was significantly higher than those of PCT and CRP (Z = 5 .718 and 9 .048 , respectively ,both P< 0 .01) .The optimal cut‐off point of IL‐6 was 184 .5 ng/L ,with the sensitivity of 85 .2% and specificity of 94 .9% .C/E value was 38 .3 for N% ,and 51 .2 for CRP . However ,both specificity and specificity of CRP and N % were low .C/E value was 389 .0 for PCT and 63 .4 for IL‐6 .IL‐6 had the highest sensitivity (85 .2% ) and specificity (94 .9% ) among all the biomarkers .Conclusions Compared to PCT and CRP ,IL‐6 has the highest sensitivity and specificity with lower cost‐effectiveness for diagnosis of infectious fever in cirrhotic patients .
ABSTRACT
Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is a major public health problem in Southeast Asia. In recent years, researchers from Hong Kong and Taiwan have reported predictive models or risk calculators for HBV-associated HCC by studying its natural history, which, to some extent, predicts the possibility of HCC development. Generally, risk factors of each model involve age, sex, HBV DNA level, and liver cirrhosis. This article discusses the evolution and clinical significance of currently used predictive models for HBV-associated HCC and assesses the advantages and limits of risk calculators. Updated REACH-B model and LSM-HCC model show better negative predictive values and have better performance in predicting the outcomes of patients with chronic hepatitis B (CHB). These models can be applied to stratified screening of HCC and, meanwhile, become an assessment tool for the management of CHB patients.
ABSTRACT
Objective T he present study aimed to optimize the established predictive models (REACH‐B scoring model) for hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC) . Methods The hepatitis B surface antigen (HBsAg) positive (> 6 months) patients who were firstly admitted in the Liver Center of First Affiliated Hospital ,Fujian Medical University between Oct 1st 2004 and May 1st 2014 were selected as the subjects and divided into two groups ,namely ,the case group (HCC group) and the control group (non‐HCC group) .Clinical data of all the subjects were retrospectively collected and analyzed .Receiver operating characteristic curves were used to evaluate the predictive values of the various models .Results To predict the development of HBV‐related HCC within 3 years ,a total of 627 patients (151 HCC cases and 476 non‐HCC controls) were enrolled .Area under curve (AUC) of HBV‐related HCC (REACH‐B) scoring model was 0 .78 (95% CI:0 .74-0 .82) ,with the sensitivity of 73 .00% and specificity of 78 .70% in predicting 3‐year risk of HCC occurrence .By combining alpha‐fetoprotein (AFP) and REACH‐B ,the R‐AFP scoring model was constructed .The AUC increased to 0 .80 (95% CI:0 .76 -0 .83 , Z= 2 .50 , P= 0 .01) ,with the sensitivity of 71 .03% and specificity of 79 .13% in predicting 3‐year HCC development .By combining AFP isoform 3 (AFP‐L3% ) and REACH‐B ,the R‐AFP‐L3% scoring model was constructed .The AUC further increased to 0 .83 (95% CI:0 .80-0 .87 ,Z=2 .45 ,P=0 .01) ,with the sensitivity of 75 .01% and specificity of 79 .32% in predicting 3‐year HCC development .To predict the development of HBV‐related HCC within 5 years ,a total of 159 (65 HCC cases and 94 non‐HCC controls) were enrolled .The AUC of REACH‐B scoring model was 0 .79 (95% CI:0 .72-0 .87) ,with the sensitivity of 73 .60% and specificity of 75 .43% .The R‐AFP scoring model had an AUC of 0 .84 (95% CI:0 .77-0 .90 ,Z=2 .70 ,P=0 .006) ,with the sensitivity of 83 .12%and specificity of 77 .89% .Conclusion Combination of AFP or AFP‐L3% may optimize the predictive values of REACH‐B scoring model in predicting 3‐year and 5‐years risks of developing HBV‐related HCC .
ABSTRACT
<p><b>OBJECTIVE</b>To use a rat model of nonalcoholic liver disease (NAFLD) to observe effects of the peroxisome proliferator-activated receptor-a (PPAR-a) agonist fenofibrate on hepatic steatosis in nonalcoholic fatty liver and to investigate the underlying mechanism.</p><p><b>METHODS</b>Sixty-six Sprague-Dawley rats were given adaptive feeding for 1 week and then randomly allocated into the following three groups: unmodeled control (group C,n =18), untreated NAFLD model (group M, n =24), and fenofibrate-treated NAFLD model (group F, n =24).Group C rats were given a normal diet, while group M and group F rats were given a high-fat diet. After model establishment, the group F rats were treated with fenofibrate (10 mg/kg/d, intraperitoneal) and the group C and group M rats were given sham-treatment with cosolvent (5 mL/kg/d, intraperitoneal). At the end of treatment weeks 4, 6 and 8, one-third of rats in each group were euthanized.Liver tissues were assessed by hematoxylin-eosin (HE) staining to determine level of steatosis and inflammaion activity, and by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling to measure changes in hepatocyte apoptosis index. Changes in expression levels of the PPAR-a receptor and apoptosis factors (bcl-2, bax and caspase-3) were assessed by reverse transcription-PCR and immunohistochemistry.</p><p><b>RESULTS</b>The NAFLD modeled rats showed appropriate induction of hepatic steatosis, hepatic inflammation, and hepatocyte apoptosis. Compared to the group M rats, the group F rats showed lower expression of PPAR-and bcl-2 and higher expression of bax and caspase-3 at both the mRNA and protein level.</p><p><b>CONCLUSION</b>Fenofibrate can ameliorate hepatic steatosis in an experimental rat model of NAFLD, and the mechanism may be associated with inhibition of hepatocyte apoptosis.</p>
Subject(s)
Animals , Rats , Apoptosis , Caspase 3 , Metabolism , Diet, High-Fat , Fenofibrate , Pharmacology , Hepatocytes , Non-alcoholic Fatty Liver Disease , Pathology , Peroxisome Proliferator-Activated Receptors , Metabolism , Proto-Oncogene Proteins c-bcl-2 , Metabolism , Rats, Sprague-Dawley , bcl-2-Associated X Protein , MetabolismABSTRACT
OBJECTIVE@#To investigate the factors that influence the curative effect in patients with HBeAgpositive chronic hepatitis B (CHB) treated with peg-interferon α-2a, and to explore whether such factors might predict the therapeutic effect.@*METHODS@#HBeAg-positive CHB patients treated with peg-interferon α-2a (180 μg once a week) were divided into a standard therapy group (48 weeks) and an extended therapy group (>48 weeks). The rates of HBsAg loss, HBeAg loss, HBeAg seroconversion, HBV DNA clearance, and ALT normalization were all evaluated in the two groups at the end of treatment and after 24 weeks follow up.@*RESULTS@#A total of 81 patients were enrolled in the study. The standard therapy group included 37 patients, and the extended therapy group included 44 cases, with durations ranging from 52 to 92 (median 72) weeks. The baseline clinical data were comparable between the two groups (P>0.05). At the end of treatment and at 24 weeks of follow-up, the HBeAg seroconversion rate of the extended therapy group was significantly higher than that of the standard therapy group (54.5% vs 29.7%, P=0.025, at 24 weeks; 76.9% vs 52.9%, P=0.008, after follow-up). In the standard therapy group, age and half-quantification of HBeAg at 24 weeks of treatment were the predictive factors for HBeAg seroconversion at 24 weeks of follow-up. Using a logistic regression model, the area under the receiver operating characteristic curve was 0.872, taking the optimum cut-off point of -1.299, with 100.0% sensitivity at 66.7% specificity. COX multi-factor analysis (of the two groups) showed that age and therapy duration were predictive factors for HBeAg seroconversion at 24 weeks of follow-up.@*CONCLUSION@#HBeAg-positive CHB patients treated with peg-interferon α-2a may have a better curative effect at a young age or with extended therapy. Age and half-quantification of HBeAg at 24 weeks of treatment may predict HBeAg seroconversion at 24 weeks of follow-up after completion of the standard therapy.
Subject(s)
Adult , Female , Humans , Male , Young Adult , Age Factors , Antiviral Agents , Therapeutic Uses , Hepatitis B Surface Antigens , Blood , Hepatitis B e Antigens , Blood , Hepatitis B, Chronic , Drug Therapy , Virology , Interferon-alpha , Therapeutic Uses , Polyethylene Glycols , Therapeutic Uses , Recombinant Proteins , Therapeutic Uses , Treatment OutcomeABSTRACT
Objective To investigate the relationship between levels of ceruloplasmin (CP) and inflammation grade,fibrosis stages in liver of patients with chronic hepatitis B (CHB),and to establish liver fibrosis non-invasive model and evaluate its diagnostic value for liver pathological stages.Methods Both liver biopsy samples and sera were collected from 148 consecutive CHB patients in Liver Center,First Affiliated Hospital,Fujian Medical University during January 2009 to June 2011.The relationships between CP and liver pathological stages were analyzed using Spearman rank correlation analysis.Receiver operator characteristic (ROC) curve was used to evaluate the diagnostic value of CP for liver pathological stages.The diagnostic values of relevant indicators were analyzed by Logistic regression.The liver pathology-predicting model was built and the diagnostic value of the model was analyzed by ROC curve.Results The mean values of CP in 148 CHB patients with liver inflammation grades of G1 to G4 were (212.5 ± 34.9),(205.5± 32.0),(201.4 ± 37.7) and (172.8 ± 20.4) mg/L,respectively,which were significantly different by ANOVA test (F=6.309,P＜0.01).Similarly,the mean values of CP in patients with liver fibrosis stages of S1 to S4 were (217.4±32.3),(206.0±37.7),(194.2±29.8) and (179.7±30.4) mg/L,respectively,which were significantly different by ANOVA test (F =8.608,P ＜ 0.01).Spearman rank correlation analysis showed that CP was negatively correlated with liver inflammation grades (r=-0.316,P＜0.01) and fibrosis stages (r=-0.404,P＜0.01).ROC curve analysis revealed that the area under the curves (AUC) were 0.71 (S≥2),0.70 (S≥3) and 0.72 (S=4).Multiple Logistic regression analysis showed that CP,α-fetoprotein,cholesterol,platelet and age were independent predictors for liver fibrosis.ROC curve analysis revealed that AUC were 0.84 in model-1 (S≥2),0.83 in model-2 (S≥3) and 0.87 in model-3 (S=4).The accuracy rates were 71.8％,80.3％ and 79.2％,respectively.Conclusions The CP levels are negatively correlated with inflammation grades and fibrosis stages in the liver of CHB patients.CP could be an important non-invasive indicator for liver fibrosis and the model including CP can be used to predict liver fibrosis in CHB.
ABSTRACT
Objective To investigate the relationship between serum HBeAg level and inflammation grade (G)/fibrosis stage (S) in the liver tissues of chronic hepatitis B (CHB) patients in the immune clearance phase (IC). Methods Both liver biopsy samples and serum samples were consecutively collected from CHB patients in Liver Center,First Affiliated Hospital,Fujian Medical University during March 2007 to June 2010.Electro-chemiluminescence and fluorogenic quantitative polymerase chain reaction (PCR) methods were used to determine HBeAg titer and hepatitis B virus (HBV) DNA level,respectively.The relationships between HBeAg titer and liver pathological stages were analyzed using Spearman rank correlation analysis.Receive operating characteristic (ROC) curve was used to evaluate the diagnostic value of HBeAg for liver pathological stages.Results Totally 249 patients with CHB were enrolled into this study.The serum HBeAg absorbances in patients with liver inflammation G1 to G4 were (2.93±2.85),(2.96±2.74),(2.69±2.67) and (2.30±2.41) lg s/co,respectively,while those in patients with liver fibrosis S1 to S4 were (2.99±2.74),(2.89±2.73),(2.58±2.55) and (2.32±2.44) lg s/co,respectively,which indicated that serum HBeAg titers were significant different in patients with different grading and staging of liver tissues (x2 =47.13,P＜0.01; x2 =74.12,P＜0.01).Spearman rank correlation analysis showed that serum HBeAg titer was negatively correlated with inflammation grades and fibrosis stages of liver tissues (r=-0.418 and-0.532,respectively; both P＜0.01).ROC curve analysis revealed that the areas under the curve (AUC) were 0.74 (G≥≥3) and 0.73 (G≥4),and the HBeAg (s/co) cut-off values were 2.95 and 2.64 lg s/co,respectively.Similarly,ROC curve analysis revealed that the AUC were 0.80 (S≥3) and 0.77 S≥4),and the HBeAg cut-off values were 2.99 and 2.82 lg s/co,respectively.Conclusions The serum HBeAg titer is negatively correlated with the inflammation grades and fibrosis stages m liver tissues of CHB patients in IC phase.The level of HBeAg may be used as an adjunctive noninvasive marker to reflect the inflammation and fibrosis status in the liver.
ABSTRACT
Objective To investigate the association between hepatitis B virus (HBV)genotype, the mutations in HBV basic core gene promoter(BCP), pre C/C gene region and treatment response to interferon (IFN)α-1b. Methods Hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients were treated with IFNα-Ib for 6 months and were followed up for 6 months after the end of treatment. Restriction Fragment Length Polymorphism (RFLP) was used for determining HBV genotype. HBV DNA was amplified by polymerase chain reaction (PCR) and analyzed for BCP and pre C/C gene region by sequencing. Measurement data were compared using t test and analysis of variance. Enumeration data were compared using chi-square test, Fisher exact probability test.Logistic regression analysis was utilized for multi-factor analysis. Results There were 39 patients who completed the treatment and follow up in this study. At the end of treatment, 16(41.0%) patients showed response to the IFNα-lb treatment. At the end of follow-up, four out of 16 patients who achieved on treatment response relapsed. Among 3a patients, 29 (74.4 %) were infected with genotype B and 10 (25. 6%) with genotype C. The treatment response rates were not significant different between the groups with different genotypes. The double mutation pattern (T1762/A1764) was found in eight (20. 5%) patients. The response rates to IFNα-lb treatment were not significant different between the group with and without double mutation pattern. A1896 mutation was detected in eight patients at baseline. Three of them became HBeAg negative at the end of treatment and returned to HBeAg positive during follow-up. The non-lyphocyte epitope mutations, L60V and I97L, were found in 15 patients (38. 5%) and 14 patients (35.9%), respectively. At the end of follow-up, the patients with 60V had a significantly lower HBeAg seroconversion rate and HBV DNA undetectable rate compared to the patients with 60L (Fisher exact probability test; P = 0.0126 and 0.0069,respectively). The HBV DNA undetectable rates in the patients with 97I were significantly lower than those in patients with 97L both at the end of treatment and the end of follow-up (Fisher exact probability test; P= 0.0484 and 0. 0024, respectively). Logistic regression analysis results showed that there was no association between the above viral mutations and the treatment response to IFNαlb. Conclusions There is no association between HBV genotype, BCP double mutation pattern and IFN-α treatment response. The non-lyphocyte epitope mutations, L60V and I97L, may have impact on IFN-α treatment response.
ABSTRACT
Objective To identify the predictive factors associated with hepatitis B surface antigen (HBsAg) loss in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients treated with pegylated interferon (PEG-IFNα-2a).Methods Seventy-two HBeAg positive CHB patients were treated with PEG-IFNa-2a 180 μg weekly for 48 weeks. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hepatitis B virus (HBV) DNA,HBeAg, and HBsAg were quantitatively detected every 3 months. The relationship between HBV DNA, HBeAg, and HBsAg levels at baseline, week 12, 24 of treatment and HBsAg loss was analyzed.The data were statistically assessed by Fisher's exact test,and receiver operating characteristic (ROC) curve. ResultsTotally 65 patients accomplished the therapy, and 7 (10.8％)patients achieved HBsAg loss. HBsAg loss at week 48 of treatment was associated with HBeAg level at week 12 of treatment (Fisher's exact test, P= 0. 023), HBeAg level at week 24 (Fisher's exact test, P=0. 004), and lower HBsAg levels (＜250 IU/mL) at week 12 and 24 of treatment (Fisher's exact test,P=0. 001 and 0.002, respectively). HBsAg loss was associated with HBV DNA negative ( ＜ 1000 copy/mL) at week 12 of treatment (Fisher's exact test, P = 0. 039), while not associated with HBV DNA negative at week 24 of treatment (Fisher's exact test, P=0. 130). ROC curve analysis revealed that the AUC was 0. 8584(P=0. 0021) of HBsAg level at week 12, 0. 9606(P=0. 001) of HBsAg level at week 24, and 0. 8350(P=0. 040) of HBeAg level at week 24. ConclusionLevels of HBsAg and HBeAg at week 24 of treatment might serve as effective factors to predict HBsAg loss in patients received PEG-IFN monotherapy.
ABSTRACT
Objective To investigate risk factors for hepatic steatosis in patients with chronic hepatitis B (CHB). Methods One hundred and eighty patients with biopsy-proven chronic hepatitis B were included in the study. Those with liver steatosis (61 from 93 cases) and those without it (61 from 87 cases)were matched on gender and age ( ± 3 years). Results Body mass index (BM I) was significantly higher in case group (24 ±3) than that in controls (22 ±3) (P ＜0.01 ). No significant difference was found in fasting plasma glucose, total cholesterol, triglycerides, urine acid, alanine aminotransferase, glutamyl transpeptidase and hepatitis B virus ( HBV ) DNA between the cases and controls ( all P ＞ 0. 05 ).Conditional logistic regression analysis with proportional hazard regression model statement by SPSS software showed that BMI was the only independent correlate to liver steatosis in patient with CHB ( OR = 1. 488, P ＜0. 01 ). Conclusions Liver steatosis in patients with CHB associates with BMI of the hosts, but does not correlate to their HBV DNA level.
ABSTRACT
Aim To purify monoclonal antibody in mouse ascites by a modified membrane affinity chromatography(MAC). Methods Human serum albumin HSA was adsorbed on the zeta-bind membrane (ZBM), a positively charged nylon membrane filter. Then the mouse aecites containing mAbs were filtrated through the ZBM to cause the mAbs bind to HSA adsorbed on ZBM. Finally,the purified mAbs were dissociated from the ZBM with guanidine hydrochloride solution. Results A sheet of ZBM(diameter 50mm) absorbed with HSA filtrated by 10 mL ascites could reach its maximum mAb binding capacity after two rounds of re-fitration. The dissociation of mAb from ZBM need only one round of filtration of dissociating solution. The purified mAb displayed a single band after PAGE. Sensitivity of detedcting HSA with purified mAbs was 20-fold higher than that with unpurified ascites in dot innunogold filtration assay(DIGFA). Conclusion The modified MAC with ZBM is a much easier, time-saving and effective method for affinity purification of antibodies in ascites.
ABSTRACT
Objective To improve the method of abdominal transplantation of hepatocytes. Methods The rat hepatic cells were embedded in collagen gel and cultured in vitro. The total protein (TP) and BUN levels in the nutrient solution were measured. The mixture of collagen nutrient solution and the hepatocytes was injected into abdominal cavity of rat recipients and then turned to gel there, so the hepatocytes were embedded in the gel. The hepatocytes in the abdominal cavity were rinsed out by the nutrient solution containing collagenase and were cultured in vitro in the nutrient solution without glucose (Glu). The Glu levels in the nutrient solution were measured. The control groups underwent the same process as the experimental groups except collagen. Results The TP, BUN and Glu levels in the experimental groups (hepatocytes embedded in collagen gel) were significantly higher than those in the control groups ( P