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Objective:To evaluate the accuracy and practicability of hepatocellular carcinoma prediction score (PAGE-B) and modified hepatocellular carcinoma prediction score (mPAGE-B) in predicting the development of hepatocellular carcinoma in patients with hepatitis B virus (HBV)-associated liver cirrhosis and received nucleos(t)ide analogue (NA) treatment.Methods:From June 2009 to December 2014, at Department of Hepatology, the First Affiliated Hospital of Fujian Medical University, the clinical data of 707 patients with HBV-associated liver cirrhosis and received NA treatment were retrospectively collected, and the patients were followed up. The risk factors of development of hepatocellular carcinoma were analyzed. PAGE-B (including platelet count, age, gender), mPAGE-B (including platelet count, age, gender and albumin), Child-Turcotte-Pugh (CTP) score and aspartate aminotransferase to platelet ratio index (APRI) were compared in area under receiver operator characteristic curve (AUROC) for predicting the occurrence of hepatocellular carcinoma within 5 years. Risk stratification analysis was carried out for mPAGE-B and PAGE-B. Multivariate Cox regression analysis, receiver operator characteristic curve, Mann-Whitney U test and Kaplan-Meier method were used for statistical analysis. Results:The age of 707 patients was (46.7±12.2) years old, including 567 males (80.2%) and 140 females (19.8%). The positive rate of hepatitis B e antigen was 56.4% (399/707). The scores of PAGE-B, mPAGE-B, CTP and APRI were 15.90±4.24, 12.39±3.58, 6.88±2.15 and 1.80 (0.85, 3.79), respectively. The overall follow up time was (38.14±20.97) months and the incidence of hepatocellular carcinoma was 8.1% (57/707). The results of multivariate Cox regression analysis showed that advanced age, low platelet count and quantitative reduction of HBV DNA were independent risk factors of development of hepatocellular carcinoma (Wald=20.44, 5.64 and 9.25; HR(95% confidence interval (95% CI) 1.056(1.031 to 1.081), 0.994(0.989 to 0.999) and 0.769(0.649 to 0.911); P<0.001, =0.018 and 0.002). The AUROCs (95% CI) of PAGE-B, mPAGE-B, CTP score and APRI for predicting the occurrence of hepatocellular carcinoma within 5 years were 0.708 (0.639 to 0.778), 0.724 (0.657 to 0.778), 0.576 (0.500 to 0.652) and 0.516 (0.443 to 0.589), respectively. There were no statistically significant differences in AUROCs for predicting the occurrence of hepatocellular carcinoma within 5 years between mPAGE-B and PAGE-B, between APRI and CTP score (both P>0.05). The AUROC for predicting the occurrence of hepatocellular carcinoma within 5 years of CTP score was less than those of PAGE-B and mPAGE-B, and the differences were statistically significant ( Z=3.00 and 3.79; P=0.003, <0.001). The AUROC for predicting the occurrence of hepatocellular carcinoma within 5 years of APRI was less than those of PAGE-B and mPAGE-B, and the differences were statistically significant ( Z=4.75 and 5.46, both P<0.001). There were 51 cases (7.2%), 394 cases (55.7%) and 262 cases (37.1%) in the low-risk (<10) group, medium-risk (10 to 17) group and high-risk (>17) group as assessed by PAGE-B. The incidence of hepatocellular carcinoma was 0(0/51), 4.8% (19/394) and 14.5% (38/262), respectively the annual average incidence of hepatocellular carcinoma was 0, 1.6% and 5.5%, respectively, the 5-year cumulative incidence of hepatocellular carcinoma was 0, 7.3% and 31.3%, respectively. The 5-year cumulative incidence of hepatocellular carcinoma of high-risk group was higher than those of medium-risk group and low-risk group (log-rank test=19.27, P<0.001). There were 97 cases (13.7%), 246 cases (34.8%) and 364 cases (51.5%) in the low-risk group (<9), medium-risk group (9 to 12) and high-risk group (>12) as assessed by mPAGE-B. The incidence of hepatocellular carcinoma was 2.1% (2/97), 3.7% (9/246) and 12.6%(46/364), the annual average incidence of hepatocellular carcinoma was 0.6%, 1.1% and 4.7%, respectively, the 5-year cumulative incidence of hepatocellular carcinoma was 2.4%, 5.1% and 26.7%, respectively. The 5-year cumulative incidence of hepatocellular carcinoma of high-risk group was higher than those of medium-risk group and low-risk group (log-rank test value=18.64, P<0.001). Conclusions:Both PAGE-B and mPAGE-B can predict the occurrence of hepatocellular carcinoma within 5 years in patients with HBV-associated liver cirrhosis treated with antiviral therapy, identify liver cirrhotic patients at high risk of development of hepatocellular carcinoma and guide clinicans to use more efficient screening strategies.
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A case of Gilbert syndrome (GS) with a heterozygous mutation in the gene is reported. The patient had no symptoms except for recurrent sclera icterus since childhood. Laboratory examinations revealed an elevated unconjugated bilirubin. Biliary obstruction, hemolysis and other diseases that might cause jaundice were excluded. *28 and c.211G>A heterozygous mutations in gene were found, which may be another type of mutation causing GS in Chinese population.
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Humans , Asian People , Bilirubin , Gilbert Disease , Genetics , Glucuronosyltransferase , Genetics , Heterozygote , MutationABSTRACT
Objective@#To investigate the correlation between interleukin-6 (IL-6) single nucleotide polymorphism (SNP) and the occurrence and prognosis of hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF).@*Methods@#Patients with chronic hepatic diseases diagnosed as HBV infection in the Hepatology Center of the First Affiliated Hospital of Fujian Medical University from July 2012 to March 2018 were divided into HBV-ACLF and non-ACLF group. SNP genotyping of eight loci in IL-6 gene (rs1524107, rs1800795, rs1800797, rs2069827, rs2069830, rs2069837, rs2069840 and rs2069845) was determined by the improved multi-temperature ligase detection reaction (imLDRTM) technique. Simultaneously, case data were reviewed with the 3-months followed up survival condition of the ACLF group. Normally distributed data were expressed as arithmetic means and SDs, and t-test was adopted. Data with skewed distribution were expressed as medians with interquartile range, and were measured by non-parametric test. Multivariate logistic regression analysis was used to analyze the relative risk of genetic polymorphism and HBV-ACLF as well as the relationship between IL-6 SNPs with the occurrence and prognosis of HBV-ACLF.@*Results@#Four hundred patients were included in the study, with 122 (30.5%) in the HBV-ACLF and 278 (69.5%) in the non-ACLF group. There were significant differences in total bilirubin, albumin, and white blood cell count, percentage of neutrophils, platelet count, alanine aminotransferase, aspartate aminotransferase, prothrombin time and international standardized ratio, creatinine and the model for end-stage liver disease score between the two groups (P < 0.001). The genotype of IL-6 genes (rs1800795, rs1800797, rs2069827, and rs2069830) of all subjects showed no mutation or the mutation rate under 1%. There was no significant difference in the genotype of IL-6 (rs1524107, rs2069837, rs2069840 and rs2069845) between the two groups (P > 0.05). Multivariate logistic regression analysis showed that the SNPs in the above four loci of IL-6 gene was not associated with HBV-ACLF risk, nor had significant correlation with the 3-months prognosis.@*Conclusion@#The SNP genotyping of eight loci in IL-6 gene (rs1524107, rs1800795, rs1800797, rs2069827, rs2069830, rs2069837, rs2069840 and rs2069845) is unrelated to the occurrence and short-term prognosis of HBV-ACLF.
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Objective To investigate the relationship between Toxoplasma gondii (T.gondii) infection and metabolic syndrome (MS).Methods A total of 20 577 patients who received serum test of anti-T.gondii IgG antibody in the National Health and Nutrition Examination Survey ( NHANES) of the United States from 2009 to 2014 were collected to analyze the clinical features of anti-T.gondii IgG antibody positive patients , and to compare metabolic related indicators in the antibody IgG positive and negative groups .The independent sample t-test, chi-square test, and logistic regression analysis were used to explore the risk factors of MS . Results A total of 2 746 participants were positive for the T.gondii antibody (13.34%), with a higher prevalence of male (14.44%vs 12.27%, χ2 ＝15.99, P＜0.01).Meanwhile, the prevalence of T.gondii increased with age and body mass index (BMI) (χ2 ＝979.98 and 50.85,respectively, both P＜0.01).Among the 2 191 patients with MS, 449 (20.49%) patients were positive for T.gondii.While 2 297 (12.49%) patients were anti-T.gondii positive in 18 386 non-MS patients.The difference was statistically significant (χ2 ＝78.504, P＜0.01).Age (t＝-37.37), BMI (t＝-4.28), glycosylated hemoglobin (t＝-11.81), fasting blood glucose (t＝-9.38), triacylglycerol (t＝-6.32), cholesterol (t＝-7.16), serum uric acid (t＝-5.25) and serum creatinine (t＝-7.69) in the seropositive group were all higher than those in the seronegative group (all P＜0.01).After adjusting for age and gender , the prevalence of T.gondii was an independent risk factor for MS (odds ratio [OR]＝1.147,P＝0.023).Conclusions BMI, blood lipids, blood uric acid and blood glucose are significantly increased in patients with T.gondii infection.T.gondii infection is an independent risk factor for MS.
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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.
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Objective To investigate the relationship between hepatic steatosis and virological markers in patients with chronic hepatitis B (CHB ) during immune clearance (IC ) phase.Methods Pathology proven CHB patients in IC phase were collected from the Liver Center of the First Affiliated Hospital of Fujian Medical University from January 2009 to October 2016 .Patients were divided into non-to mild fatty liver (F0 －F1) group and moderate to severe fatty liver (F2 －F4) group according to the liver steatosis degree .The relationship between liver steatosis and virological markers in serum was compared .The measurement data were analyzed using independent sample t test ,and the count data were analyzed by chi-square test .Results A total of 298 patients were included ,including 237 males (79 .5%) and 61(20 .5%) females ,and the average age was (32 .4 ± 10 .3) years old .The 23 .5%(70／298) of these patients had liver steatosis .A total of 273 (91 .6%) cases were in F0－F1 group ,and the remaining 25 (8 .4%) cases were in F2 －F4 group.The patients in F2 － F4 group had higher body mass index ([25.90 ± 2.70] vs [21 .68 ± 2.90] kg／m2) ,serum triglyceride ([1.52 ± 0.77] vs [1.11 ± 0.55] mmol／L) and cholesterol ([4 .88 ± 1 .15] vs [4 .33 ± 0 .92] mmol／L) than F0－F1 group ,and the differences were all statistically significant (t＝ －7 .007 ,－2 .667 ,and －2 .751 ,respectively ,all P＜0 .05).In addition , the serum levels of HBsAg and HBV DNA in F2 －F4 group were also significantly higher than F0 －F1 group (t＝ －3 .291 and －2 .831 ,respectivelt ,both P＜0 .01).According to the grading of inflammation and fibrosis ,the differences of HBsAg and HBV DNA levels between F0 －F1 group and F2 －F4 group were statistically significant only in patients with more severe inflammation (t＝ －2 .738 and －2 .135 , respectively ,both P＜0 .05) or less severe fibrosis (t＝ －2 .258 and －2 .333 ,respectively ,both P＜0 .05).Conclusion Among CHB patients experiencing immune clearance ,serum HBsAg and HBV DNA levels are positively correlated with the severity of hepatic steatosis ,and this phenomenon is closely related to the degree of liver inflammation.
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Objective To explore the dynamic expressions and clinical significance of toll-like receptor 4 (TLR4)/microRNA (miRNA)-181a in the pathogenesis of hepatic fibrosis (HF) in patients with chronic hepatitis B (CHB) .Methods CHB patients underwent liver biopsy for fibrosis staging HF (S) .Real-time polymerase chain reaction (PCR) was used to detect the expressions of miRNA-181a in both serum and liver tissue and the expression of TLR4 mRNA in liver tissue .Western blot was used to detect the expression of TLR4 protein in liver tissue . The fibrosis-4 (FIB-4 ) index and aspartate aminotransferase-to-platelet ratio index (APRI ) were calculated for noninvasive evaluation of fibrosis staging .One-way ANOVA ,Mann-Whitney U test ,spearman correlation analysis and receiver operating characteristic (ROC) curve were used for statistical analysis .Results Forty CHB patients were includedin this study ,including 7 with S0 ,6 with S1 ,14 with S2 ,7 with S3 and 6 with S4 .Serum levesl of miRNA-181a (2-ΔΔCt ) in paitents with S0-4 were 1 .00 ± 0 .00 ,0 .68 ± 0 .08 ,1 .60 ± 0 .43 ,2 .32 ± 0 .40 , and 1 .81 ± 0 .22 ,respectively ,showing an overall upward trend (F=207 .242 ,P< 0 .01) and a positive correlation with the severity of HF (r= 0 .754 , P< 0 .01) .The expressions of miRNA-181a ,TLR4 mRNA and TLR4 protein in liver tissues showed an overall increasing trend from S 0 to S4 (F=207 .242 , 110 .390 and 57 .030 ,respectively ,all P<0 .01) .The expression of miRNA-181a in liver tissue showed a positive correlation with both the expression of TLR4 protein in liver tissue and the severity of HF (r=0 .673 and 0 .911 ,respectively ,both P< 0 .01) .There was no significant difference of APRI scores between the severe (S3-4) and non-severe (S0-2) HF groups (Z= -1 .401 ,P>0 .05) .The serum level of miRNA-181a was superior to FIB-4 index for evaluation of the severe HF (S3-4) ,with areas under the ROC curve (AUROC ) of 0 .887 and 0 .695 , respectively , and accuracy of 85 .0％ and 60 .0％ , respectively .Conclusions miRNA-181a may be involved in the regulation of TLR4 signaling pathway so that to affect the progression of HF in CHB patients ,which may be a potential new target for the prevention and early treatment of HF and a non-invasive serum marker for evaluation of HF .
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Objective To investigate the association between interleukin-22 (IL-22) single nucleotide polymorphisms (SNPs) and the prognosis of hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF).Methods The patients with HBV-ACLF from the First Affiliated Hospital of Fujian Medical University were retrospectively studied.Seven SNP genotypes of IL-22 gene,including rs2227478,rs2227491,rs1179251,rs1179249,rs2227473,rs2227484,and rs11611206,were detected using imLDRTM multiple SNP typing kit and the distribution features of SNP genotypes were described.The relationship between the distribution of SNP genotypes and alleles and the prognosis of ACLF was analyzed.Comparison of genotypes and allele frequencies between groups were performed by chi-square test of R × C table or Fisher's exact tests.Binary logistic regression analysis was used to analyze whether IL-22 gene polymorphisms was an independent prognostic factor for patients with ACLF.Results A total of 122 patients with HBV-ACLF were included in this study.Ninety-two (75.1％) were male and 30 (24.59 ％) were female.Patients were stratified as survival group (90 cases) and non-survival group (32cases) according to the Results of three months follow-up.The genotype distribution of rs2227484 of IL-22 gene was significantly different between the two groups (x2=6.128,P=0.033).The A allele frequency in the non-survival group (15.6％) was significantly higher than that in the survival group (5.6％) with statistically significance (OR=0.318,95％ CI=0.126-0.804,P=0.012).There was no significant difference in the other six SNP genotypes of IL-22 gene between the two groups (all P＞0.05).However,binary logistic regression showed that rs2227484 of IL-22 gene was not an independent risk factor for the short-term mortality in HBV-ACLF patients (adjusted OR=3.102,95％ CI:0.939-10.250,P=0.063).Conclusions The A allele and AA genotype of rs2227484 of IL-22 gene may be associated with a short-term prognosis in patients with HBV-ACLF.
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Radiofrequency ablation (RFA) is one of the most important methods for the treatment of liver cancer and has the advantages of small trauma,simple operation,and repeatability.However,for tumors in high-risk locations within 5 mm of the first and second branches of the hepatic portal vein,near the hepatic vein,the inferior vena cava,or the gallbladder,within 5 mm of the intestinal tract,under the Glisson's capsule,and in the diaphragm,RFA has the issues of a low complete ablation rate,a high local recurrence rate,and serious complications.This article introduces the complications of RFA for liver cancer in high-risk locations and their prevention and points out that with the promotion of individualized and standardized RFA,liver cancer in these high-risk locations is no longer a contradiction for RFA.
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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.
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ObjectiveTo evaluate liver reserve function in patients with hepatitis B cirrhosis using indocyanine green (ICG) clearance test, and to investigate the correlation of ICG clearance test with Child-Turcotte-Pugh (CTP) class and the Model for End-Stage Liver Disease (MELD) score in evaluating liver function. MethodsA total of 127 patients with hepatitis B cirrhosis who were hospitalized in The First Affiliated Hospital of Fujian Medical University from January 2012 to January 2015 were enrolled. ICG clearance test was performed for all the patients, and the ICG plasma clearance (K value), effective liver blood flow (EHBF), and ICG retention at 15 minutes (ICG R15) were calculated. CTP class and MELD score were also determined. An analysis of variance was used for comparison between groups, the least significant difference t-test was used for comparison between any two groups, Spearman rank correlation was performed for correlation analysis, and the area under the receiver operating characteristic (ROC) curve was used to compare liver reserve function. ResultsAmong all the patients with hepatitis B cirrhosis, 63 had CTP class A, 45 had CTP class B, and 19 had CTP class C hepatitis B cirrhosis. With the increasing CTP class, ICG R15 gradually increased, while EHBF and K value gradually decreased (F=14696，9126 and 4094，P=0001,0003 and 0005). In the evaluation of liver function, ICG R15 was positively correlated with MELD score and CTP class (r=0.525 and 0.838, both P＜0.01) and was negatively correlated with EHBF and K value (r=-0.703 and -0.901, both P＜0.01). The area under the ROC curve was 0.85 for ICG R15 and 065 for MELD score. ConclusionICG test can accurately and dynamically reflect liver reserve function, and ICG R15 can evaluate liver reserve function better than CTP class and MELD score.
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<p><b>OBJECTIVE</b>To validate two previously published models (REACH-B score and CU-HCC score) for predicting the risk of developing hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>In-patients of the Liver Center of First Affiliated Hospital Fujian Medical University who tested positive for hepatitis B surface antigen (HBsAg;more than 6 months) and were admitted for treatment between October 1,2004 and May 1,2014 were enrolled for study. The 627 study participants were grouped according to presence of HCC (151 in the HCC case group, and 476 in the non-HCC control group). Relevant clinical data from 3 and 5 years prior to the current hospital admission were collected retrospectively and assessed using the REACH-B and CU-HCC scoring systems. A subset of the study participants (65 HCC cases, and 94 non-HCC controls) was used for the verification analysis of prediction for 5-year risk of HBV-related HCC.T-test, rank sum test, chisquare test and the receiver operating characteristic curve were used for statistical analyses.</p><p><b>RESULTS</b>For the REACH-B score,prediction of 3-year risk of developing HCC had an area under the curve (AUC) of 0.78,a sensitivity of 73.00% and a specificity of 78.70%.In male patients with alanine aminotransferase (ALT) more than or equal to 45 U/L, the REACH-B score prediction of 3-year risk of developing HCC had an AUC of 0.89, a sensitivity of 87.09% and a specificity of 83.86%. The REACH-B score prediction of 5-year risk of HCC had an AUC of 0.79,a sensitivity of 73.60% and a specificity of 75.53%; the CU-HCC score prediction of 5-year risk of HCC had an AUC of 0.76, a sensitivity of 78.40% and a specificity of 77.40%.</p><p><b>CONCLUSION</b>Both the REACH-B and CUHCC scoring systems can be used for HCC prediction among patients at the First Affiliated Hospital Fujian Medical University. For male patients with ALT more than or equal to 45 U/L,the REACH-B score may be a more sensitive predictor for 3-year risk of developing HBV-related HCC.</p>
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Humans , Male , Alanine Transaminase , Area Under Curve , Carcinoma, Hepatocellular , Hepatitis B , Hepatitis B Surface Antigens , Hepatitis B virus , Hepatitis B, Chronic , Liver Neoplasms , ROC Curve , Retrospective StudiesABSTRACT
<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 The aim of this prospective observational study was to analyze the prevalence and the predictive factors of hemorrhagic events after abdominal paracentesis in patients with acute-on-chronic liver failure (ACLF).Methods ACLF patients who received at least one episode of abdominal paracentesis were prospectively enrolled between January 2010 to December 2013. Prevalences of intraperitoneal and abdomen hemorrhage complications were examined. t test was performed for continuous variables and chi-square test was performed for categorical variables.Binary Logistic regression was used to analyze the risk factors of hemorrhage.Results A total of 525 abdominal paracenteses were carried out on 185 ACLF patients within a 4-year period,with 289 (55 .0%)for diagnostic purpose and 236 (45 .0%)for therapeutic purpose.A total of 16 (3.0%)hemorrhagic complications were identified, with 4 cases of abdominal wall hematomas and 12 cases of intraperitoneal hemorrhage.Patients were divided into hemorrhage group and non-hemorrhage group according to this complication.Age,gender, Child-Pugh score,volume of ascitic fluid removed,underlying cirrhosis,platelet count and thrombin time were not significantly different between two groups (all P > 0.05 ).Patients with bleeding events had lower fibrinogen levels and higher prothrombin time,international normalized ratio,activated partial thromboplastin time and model for end-stage liver disease score (all P <0.05).After adjustment of other factors,multivariate regression analysis indicated that low fibrinogen level was the only independent predictor of hemorrhagic complication (OR=0.105,95%CI :0.018-0.608,P =0.012).Conclusion Low fibrinogen level is the independent predictor of severe hemorrhagic complications following paracenteses in patients with ACLF.
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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.
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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.
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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.
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Objective To investigate the co-transfection of p53 and angiostatin gene in the inhibition of SG7901. Methods Transfected the pVITRO2-hp53-hAS into SG7901 with lipofectamine.After transfection, RT-PCR were used to know whether the aimed gene had been transfected and expressed or not. Cell clones trial, MTT growth curve, cell cycle measuring were used to analyze the differences. Results The cells were suppressed by the two genes and inhibition of the combined genes is more powerful than single one. Conclusion The effection of combined genes pVITRO2-hp53-hAS on SG7901 is stronger than either single one. Combined-gene-therapy is a useful anti-carcinoma method.
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Objective To investigate the association between tumor necrosis factor ? (TNF ?) gene polymorphism and ankylosing spondylitis (AS).Methods Genomic DNA from 98 Chinese AS patients and 70 ethnically matched controls were typed for TNF(308) polymorphism by allele specific polymerase chain reaction (AS PCR).Results The TNF genotypes in AS patients were respectively TNF1 homozygote 37%,TNF2 homozygote 10% and TNF1 and TNF2 heterozygote 53%.While TNF genotypes in controls group were respectively TNF1 homozygote 67%,TNF2 homozygote 3% and TNF1 and TNF2 heterozygote 30%.Significant difference was found in the distribution of TNF 308 genotype between both groups ( ? 2=15 73, P
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Objective To investigate the relationship between tumor necrosis factor-?(TNF-?) gene polymorphism and rheumatoid arthritis (RA). Methods Genomic DNA from 34 RA patients and 35 ethnically matched controls were typed for TNF-?(308) gene polymorphism by allele-specific polymerase chain reaction(AS-PCR). The concentration of their serum TNF-? was measured by ELISA. Results The TNF genotypes in RA patients were respectively TNF 1 homozygote 14 7%, TNF 2 homozygote 52 9%, and TNF 1 and TNF 2 heterozygote 32 4%. TNF genotypes in controls were respectively TNF 1 homozygote 68 6%, TNF 2 homozygote 2 8%, and TNF 1 and TNF 2 heterozygote 28 6%. The significant difference was found in the distribution of TNF-?(308) genotype between the two groups (? 2=27 71,P