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 .

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.

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.

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

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.

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.

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),but those were comparable after 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.

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.

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.

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.