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.

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 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.

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.

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.

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 .

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.

Objective: To observe and study the influence of external drainage of lateral ventricle for continuous ventricular infusion and lumbar cistern drainage for the serum and cerebrospinal fluid on inflammatory mediators of patients with intracranial infection, in order to understand the clinical application value of the treatment methods. Methods: From June 2016 to May 2018, 56 patients with intracranial infection in the People's Hospital of Lianshui County were selected in the study and randomly divided into two groups according to the random allocation principle, with 28 cases in each group.The control group was treated with repeated lumbar intrathecal drug therapy, the observation group was treated with external drainage of lateral ventricle for continuous ventricular infusion and lumbar cistern drainage.The serum and cerebrospinal fluid inflammatory mediators of two groups before treatment and at the first and second week after treatment were compared. Results: The serum and cerebrospinal fluid inflammatory mediators of the two groups before treatment had no statistically significant differences(all P>0.05). The serum levels of IL-1β, IL-6 and IL-8 of the observation group at the first and second week after treatment were (2.27±0.28)μg/L, (9.25±0.89)μg/L, (11.15±1.35)μg/L and (1.65±0.20)μg/L, (7.04±0.81)μg/L, (8.42±0.79)μg/L, respectively, which were significantly lower than those of the control group [(4.63±0.38)μg/L, (11.92±1.35)μg/L, (14.28±1.75)μg/L and (3.20±0.29)μg/L, (9.41±1.02)μg/L, (11.32±1.47)μg/L] (t=26.456, 8.737, 7.493, 23.282, 9.628, 9.195, all P<0.01). Two weeks after treatment, the levels of IL-1, IL-6 and IL-8 in CSF of the observation group were (1.51±0.15)μg/L, (5.14±0.45)μg/L and (5.96±0.59)μg/L, respectively, which were significantly lower than those of the control group(t=12.876, 12.810, 14.272, all P<0.01). The levels of leukotriene B4(LTB4), substance P(SP) and nitric oxide(NO) in serum and cerebrospinal fluid of the two groups continued to decrease after treatment for one week and two weeks, and those in the observation group were lower than the control group(all P<0.05). Conclusion External drainage of lateral ventricle for continuous ventricular infusion and lumbar cistern drainage can significantly decrease the serum and cerebrospinal fluid inflammatory mediators of patients with intracranial infection, so the treatment method has high clinical application significance.

OBJECTIVETo 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.

METHODSSixty-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.

RESULTSThe 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.

CONCLUSIONFenofibrate can ameliorate hepatic steatosis in an experimental rat model of NAFLD, and the mechanism may be associated with inhibition of hepatocyte apoptosis.

Animals ; Apoptosis ; Caspase 3 ; metabolism ; Diet, High-Fat ; Fenofibrate ; pharmacology ; Hepatocytes ; drug effects ; Non-alcoholic Fatty Liver Disease ; pathology ; Peroxisome Proliferator-Activated Receptors ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Rats, Sprague-Dawley ; bcl-2-Associated X Protein ; metabolism