Positive Rate of Different Hepatitis B Virus Serological Markers in Peking Union Medical College Hospital,a General Tertiary Hospital in Beijing

Objectives To investigate the positive rate of different hepatitis B virus （HBV） serological markers, and the demographic factors related to HBV infection. Methods We enrolled all patients tested for HBV serological markers, such as HBV surface antigen （HBsAg）, HBV surface antibody （HBsAb）, hepatitis B e antigen （HBeAg）, hepatitis B e antibody （HBeAb）, HBV core antibody （HBcAb）, and HBV-DNA from July 2008 to July 2009 in Peking Union Medical College Hospital. The positive rate of each HBV serological marker was calculated according to gender, age, and department, respectively. The positive rates of HBV-DNA among patients with positive HBsAg were also analyzed. Results Among 27 409 samples included, 2681 （9.8%） were HBsAg positive. When patients were divided into 9 age groups, the age-specific positive rate of HBsAg was 1.2%, 9.6%, 12.3%, 10.9%, 10.3%, 9.7%, 8.0%, 5.8%, and 4.3%, respectively. The positive rate of HBsAg in non-surgical department, surgical department, and health examination center was 16.2%, 5.8%, and 4.7%, respectively. The positive rate of HBsAg of males （13.3%） was higher than that of females （7.3%, P=0.000）. Among the 2681 HBsAg （＋） patients, 1230 （45.9%） had HBV-DNA test, of whom 564 （45.9%） were positive. Patients with HBsAg （＋）, HBeAg （＋）, and HBcAg （＋） result usually had high positive rate of HBV-DNA results （71.8%, P=0.000）. Conclusions Among this group of patients in our hospital, the positive rate of HBsAg was relatively high. Age group of 20-29, males, and patients in non-surgical departments were factors associated with high positive rate of HBsAg.

Elevated soluble 4-1BB is associated with serum markers of hepatitis B virus in patients with chronic hepatitis B

BACKGROUND Previous studies have suggested that the costimulatory molecule 4-1BB plays pivotal roles in regulating immunity during chronic viral infection.However,up to now,there are few studies about 4-1BB in chronic hepatitis B(CHB).AIM To clarify this issue,we report our comprehensive study results on the expression levels of 4-1BB in patients with CHB.METHODS From September 2018 to June 2019,a total of 64 patients with CHB were recruited from the Department of Hepatology,The First Hospital of Jilin University.Peripheral blood samples were collected from 52 treatment-naïve and 12 entecavir-treated patients with CHB as well as 37 healthy donors(including 24 healthy adults and 13 healthy children).The levels of soluble 4-1BB(s4-1BB)in plasma were measured by ELISA.4-1BB mRNA expression in peripheral blood mononuclear cells was detected by real-time quantitative PCR.RESULTS The s4-1BB levels in the plasma of patients with CHB were significantly higher than those in healthy adults(94.390±7.393 ng/mL vs 8.875±0.914 ng/mL,P<0.001).In addition,the s4-1BB level in plasma was significantly increased in patients with a higher viral load and a disease flare up.However,there were no significant differences between treatment-naïve and entecavir-treated patients.Interestingly,among treatment-naïve patients with CHB,the levels of s4-1BB in plasma had a significant positive correlation with hepatitis B surface antigen,hepatitis B virus DNA,hepatitis B e antigen,and triglyceride levels(r=0.748,P<0.001;r=0.406,P=0.004;r=0.356,P=0.019 and r=-0.469,P=0.007,respectively).The 4-1BB mRNA expression was higher in the peripheral blood mononuclear cells of patients with CHB than in the peripheral blood mononuclear cells of healthy adults,but the difference was not statistically significant.CONCLUSION These results suggest that the levels of s4-1BB may be associated with pathogenesis of hepatitis B virus and therefore may be a promising biomarker for disease progression.

sFRP-4, a potential novel serum marker for chronic hepatitis B-related hepatocellular carcinoma

BACKGROUND：The current methods used for diagnosing hepatocellular carcinoma（HCC）are unsatisfactory.Here,we assessed the serum levels of secreted frizzled related protein 4（s FRP-4）for diagnosing HCC in patients infected with chronic hepatitis B（CHB）.METHODS：In 272 patients with CHB enrolled,142 were pa tients with HCC.Thirty-three healthy subjects were recruited as healthy controls.The CHB patients were assigned to a test group or a validation group based on the time of enrollment. Human antibody arrays were used to screen 15 patients （8 CHB-related HCC patients, 7 CHB patients） for serum mark- ers. Four markers and one candidate marker were assessed in the test group and validation group, respectively. RESULTS： Human antibody assays indicated that the serum levels of sFRP-4 in HCC patients were significantly higher than those in CHB patients （P〈0,05）. Additionally, serum sFRP-4 levels were significantly higher in the HCC patients than those in the non-HCC patients in both test group （79.7 vs 41.3 ng/mL; P〈0.001） and validation group （89.0 vs 39.0 ng/mL; P〈0.001）. Areas under the Receiver Operating Charac- teristic curves （AUCs） for alpha-fetoprotein （AFP） and sFRP-4 were similar in both test group and validation group. In the test group, the combination of sFRP-4 （a sensitivity of 94.4%, a specificity of 60.5% at 46.4 ng/mL） and AFP （a sensitivity of 75.0%, a specificity of 87.2% at 11.3 ng/mL） showed better performance for diagnosing HCC （a sensitivity of 79.2% and a specificity of 95.3%）. The AUC for combined sFRP-4 and AFP increased to 0.941 （95% CI： 0.908-0.975）, and similar results were seen in the validation group. CONCLUSION： sFRP-4 is a candidate serum marker for diagnosing HCC in CHB patients, and the combination of sFRP-4 with AFP may improve the diagnostic accuracy of HCC.

Safety and efficacy of oral HD-03/ES given for six months in patients with chronic hepatitis B virus infection

AIM： To investigate the safety and efficacy of the formulation HD-03/ES capsules in the management of patients with chronic hepatitis B infection.METHODS： A total of 25 patients were recruited to the study and were given HD-03/ES, two capsules twice daily for six months. Clinical assessment of symptoms and signs were done using the ＂clinical observation table＂ once a month before and after the treatment. Biochemical investigations of total bilirubin, ALT, AST, serum protein for liver function tests were done every month after initiating treatment. Serum was analyzed for HBV markers for HBsAg, HBeAg and HBV DNA at baseline, 4 and 6 mo alter therapy using ELISA kits from Roche.RESULTS： After 6 mo of therapy with HD-03/ES, a significant reduction of ALT values from 66.5 ± 11.1 to 39.1 ± 5.2 （P 〈 0.01） and a significant HBsAg loss （52%, P 〈 0.001）, HBeAg loss （60%, P 〈 0.05） and HBV DNA loss （60%, P 〈 0.05） was observed. Adverse effects were mild and never warranted withdrawal of the drug.CONCLUSION： The results of this pilot study indicate that HD-03/ES might be a safe and effective treatment for chronic hepatitis B infection and a long-term multicentric comparator trial is warranted and under way.

Voacanga grandifolia(Miq.)Rolfe protects against alcohol-induced liver toxicity in rats

Objective:To evaluate the ethanol extract of Voacanga grandifolia for hepatoprotective and antioxidant potential against ethanol-induced liver toxicity in rats.Methods:Sprague-Dawley rats were administered ethanol(7 g/kg)and then treated with 100 and 200 mg/kg of Voacanga grandifolia extract.The phytochemical constituents and antioxidant potential of Voacanga grandifolia extract were evaluated by GC-MS and in vitro antioxidant assays.Biochemical indicators for liver damage and pro-apoptotic and antiapoptotic gene expression were determined using biochemical kits,ELISA,and qRT-PCR,respectively.Additionally,histopathological study of the liver was performed.Results:GC-MS identified propanoic acid,meso-erythritol,D-pinitol,myo-inositol,and hexadecanoic acid in Voacanga grandifolia extract.Voacanga grandifolia extract(100 and 200 mg/kg)increased the concentration of enzymatic antioxidants while diminishing the levels of inflammatory cytokines and biochemical indicators.qRT-PCR assay showed that Voacanga grandifolia extracts upregulated antiapoptotic gene expression while downregulating pro-apoptotic gene expression.Furthermore,the plant extract improved the hepatic architecture of ethanol-intoxicated rats.Conclusions:Voacanga grandifolia extract demonstrates hepatoprotective activity against alcohol-induced liver injury in rats and could be a potential hepatoprotective agent.

Prognostic significance of combining high mobility group Box-1 and OV-6 expression in hepatocellular carcinoma

The inflammatory environment and existence of cancer stem cells are critical for progression and intrahepatic recurrence of hepatocellular carcinoma （HCC） after curative resections. Here, we investigated the prognostic significance of combining high mobility group box 1 （HMGB1） expression and hepatic progenitor marker OV6 in hepatocellular carcinoma. Expression of HMGB 1 and OV6 was evaluated using immunohistochemistry profiling in tissue microarrays containing samples from 208 HCC patients. Invasive clinical or pathological factors were found in patients with high expression of HMGB 1 or OV6. Higher HMGB1 was associated with poorer clinical outcomes, and independently related to elevated 5-year recurrence incidence （85.5% vs. 62.4%, P〈0.001）. We also found that more OV6 positive staining was correlated with poor prognosis of HCC patients （P〈0.001）. Notably, expression of HMGB 1 was positively correlated with OV6 in density （R2=0.032, P〈0.001） and reversely related to HCC outcomes. Abnormal expression of HMGBI in combination with positive staining of OV6 displayed poorer prognostic performance than single biomarker alone （area under curve （AUC） survival=0.696）. Therefore, HMGB 1 and OV6 positive staining are promising prognostic parameters for HCC, and we propose that HMGB1 and OV6 may cooperate with each other and predict poor prognosis of HCC.