Table of Content

15 November 2017, Volume 22 Issue 11

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Original Articles

Study on the expression of serum sST2 and its relationship with disease severity in patients with chronic hepatitis B

LIN Lan-yi, JIANG Shao-wen, MO Rui-dong, XIANG Xiao-gang, LAI Rong-tao, WANG Hui, ZHAO Gang-de, CAI Wei, GUO Qing, XU Bei, XIE Qing.

2017, 22(11):  987-990. 

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Objective To investigate the role of interleukin-33/ST2 expression in the progression of liver fibrosis, and its relationship with disease severity in patients with chronic hepatitis B (CHB).Methods A total of 105 patients from January 2013 to December 2016 in Ruijin hospital were enrolled, containing 46 patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (HBV-ACLF) and 59 patients with CHB. Patients in CHB group all underwent liver biopsy, and were divided into F0-2 (non or mild fibrosis) subgroup (n=12), F3-4 (moderate fibrosis) subgroup (n=12), F5 (advanced fibrosis) subgroup (n=12) and F6 (liver cirrhosis) subgroup (n=23) according to Ishak scoring system. Twenty healthy volunteers were enrolled as controls. Serum levels of IL-33 and sST2 of all participants were detected using enzyme linked immunosorbent assay (ELISA), and the relationship between progression of liver fibrosis and disease severity was analyzed.Results Serum sST2 level in F6 subgroup (21.3±4.7 ng/mL) were significantly higher than that in F5, F3-4, F0-2 and control group (5.1±0.8 ng/mL, 5.6±0.8 ng/mL, 3.8±0.4 ng/mL and 6.9±0.7 ng/mL, all P<0.05 ), respectively, but was notably lower than that in HBV-ACLF group (63.5±3.9, P<0.001). In all patients, serum levels of sST2 were positively correlated with aspartate aminotransferase (AST) and total bilirubin (TBil) (both P<0.05), but negatively correlated with albumin level and platelet counts (both P<0.001). However, there was no correlation between serum sST2 and ALT levels. The serum levels of IL-33 were 4.7±1.0 pg/mL, 4.2±0.7 pg/mL, 4.1±1.1 pg/mL, 5.4±2.0 pg/mL, 5.5±0.9 pg/mL and 5.4±0.5 pg/mL in F6, F5, F3-4, F0-2, HC and HBV-ACLF group, respectively, with no statistical significance among these groups.Conclusion Serum sST2, other than serum IL-33, was associated with the progression of liver fibrosis and disease severity in CHB patients.

The diagnostic value of cell death markers M65 and M30 for liver inflammation in chronic hepatitis B

WEI Xin-huan, MA Li-xia, FAN Zuo-peng, LIANG Shan, QIU Li-xia, LIN Wei, LIU Yi-fong, HU Zhong-jie, WEI Hong-shan, ZHANG Jing.

2017, 22(11):  991-993. 

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Objective To investigate the diagnostic value of cell death marker M65 and M30 for liver inflammation in patients with chronic hepatitis B (CHB).Methods A total of 186 CHB patients with liver biopsy were enrolled in the study, and the blood samples were collected within one week before and after the liver biopsy. Histopathological inflammation was graded from G1 to G4 and fibrosis was staged from S1 to S4. Eighteen health volunteers matched by sex and age were set as controls with measuring serum levels of M65 and M30.Results Serum levels of M65 and M30 increased significantly in parallel with grades of liver inflammation. The median M65 level in G2 and cG3 groups were 208.3 U/L and 238.8 U/L, and the median M30 level in G2 and cG3 groups were 251.8 U/L and 282.9 U/L, respectively, which were both significantly higher than that in control group (M65: 144.5 U/L, M30: 208.8 U/L) and G1 group (M65: 199.6 U/L, M30: 241.9 U/L). Multivariate analysis revealed that M65 was one of the independent predictors for severe liver inflammation (≥ G2). Compared with G1S1 group, G2S1 group showed higher median M65 (206.0 U/L vs 190.5 U/L ) and M30 levels (280.7 U/L vs 241.9 U/L), respectively.Conclusion Serum M65 level was positively correlated with liver inflammation grades in CHB patients, which was better than M30 in clinical application.

Correlations between subsets of peripheral lymphocytes and the liver dysfunction in 50 liver cancer patients

ZHANG He, ZOU Han-bing, LIU Zhe, TU Meng-yun, XU Dan-hua, XIA Qiang

2017, 22(11):  994-997. 

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Objective To investigate the correlations between subsets of peripheral lymphocytes and impaired liver function in liver cancer patients by assaying CD3⁺T cells, CD4⁺T cells, CD8⁺T cells and NK cells in vivo.Methods Fifty liver cancer patients in Shanghai Renji Hospital were enrolled in the retrospective analysis, containing 10 patients with primary liver cancer, 30 with secondary liver cancer and 10 with other liver diseases. CD3⁺T cells, CD4⁺T cells, CD8⁺T cells and NK cells in these patients were assayed using flow cytometry. Ten patients with other liver diseases were recruited as disease control group, and 40 healthy blood donors were recruited as normal control group. .Results Subsets of peripheral lymphocytes in primary liver cancer patients showed no differences with that in disease control group or normal control group. In secondary liver cancer patients, the proportion of CD4⁺T cells in peripheral blood was much lower than that in normal control group (29.18±2.11% vs 35.68±0.56%, P<0.05), while the proportion of NK cells was much higher (21.45±1.69% vs 15.78±0.72%, P<0.01). However, there was no difference in lymphocyte subsets between secondary liver cancer patients and disease control group. Proportion of CD4⁺T cells in primary liver cancer patients with hepatocellular injury was higher than that in patients without hepatocellular injury (45.90±5.96% vs 30.93±1.76%, P<0.05), which showed a positive correlation with alanine aminotransferase (ALT) (r=0.941, P<0.01) and aspartate aminotransferase (AST) (r=0.903, P<0.01). Proportion of CD8⁺T cells in primary liver cancer patients with damage of liver metabolic function was lower than that in patients with no damage (27.00±4.63% vs 34.01±7.98%, P<0.05), which had negative correlations with serum total bilirubin (STB) ( r=-0,596, P<0.05) and prothrombin time (PT) (r=-0.577, P<0.05). Secondary liver cancer patients with hepatocellular injury had a lower proportion of CD4⁺T cells (23.22±3.28% vs 33.24±2.29%, P<0.05), while a higher proportion of CD8⁺T cells (34.70±4.26% vs 25.84±1.99%, P<0.05) than those without hepatocellular injury. Ratio of CD4⁺/CD8⁺T cells had negative correlations with ALT (r=-0.470, P<0.05) and AST(r=-0.424, P<0.05). Secondary liver cancer patients with damage of liver metabolic function had a higher proportion of CD4⁺T cells than the patients with no damage group (35.64±2.84% vs 25.56±2.57%, P<0.05), and the ratio of CD4⁺/CD8⁺T cells was positively correlated with STB (r=0.400, P<0.05 ) and PT(r=0.481, P<0.05).Conclusion The subsets proportion of peripheral lymphocytes in liver cancer patients is closely related to the damage of liver function. The immune balance is of great importance to protect liver function for patients with liver cancer.

Serum HBsAg quantitation using Easy CutaMiNi TRFIA and Architect I2000 CMIA and the consistency analysis in predicting liver histopathology in chronic hepatitis B patients

ZHANG Zheng-hua, JIN Hong-di, LU Wei, TIAN Hai-bing, TANG Wei-min, ZHANG Zhan-qing. Infectology Department of Guhua Hospital, Fengxian, Shanghai 201499; Division Two of hepatology Department, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China

2017, 22(11):  998-1004. 

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Objective To investigate quantitative serum hepatitis B surface antigen (HBsAg) detection using Easy CutaMiNi TRFIA (HBsAg-TRFIA) and Architect I2000 CMIA (HBsAg-CMIA), and to analyze their consistency in predicting liver histopathology in chronic hepatitis B (CHB) patients.Methods One hundred and sixty-four HBeAg-positive and 132 HBeAg-negative CHB patients with liver biopsy were enrolled in the study. Scheuer scoring system was applied in liver histopathological diagnosis.Results HBsAg-TRFIA was significantly positively linearly correlated with HBsAg-CMIA in HBeAg positive(r=0.939, F=2973.419, P<0.0001) and negative patients (r=0.952, F=1246.786, P<0.0001), respectively. Moreover, in HBeAg-positive patients, the areas under the receiver operating characteristic curve (AUROC) of HBsAg-TRFIA and HBsAg-CMIA for predicting ≥ G2 and ≥ G3 were 0.624 (95% CI: 0.539~0.710), 0.671 (95% CI: 0.578~0.764) and 0.644 (95% CI: 0.559~0.728), 0.672 (95% CI: 0.577~0.768), respectively. The AUROC of HBsAg-TRFIA and HBsAg-CMIA for predicting ≥ S2, ≥ S3 and ≥ S4 were 0.652 (95% CI: 0.566~0.738), 0.715 (95% CI: 0.631~0.799), 0.775 (95% CI: 0.692~0.857) and 0.665 (95% CI: 0.580~0.750), 0.724 (95% CI: 0.642~0.807), 0.781 (95% CI: 0.695~0.866), respectively. In HBeAg-negative patients, the AUROC curves of HBsAg-TRFIA and HBsAg-CMIA for predicting ≥ G2 and ≥ G3 were 0.555 (95% CI: 0.452~0.657), 0.581 (95% CI: 0.454~0.707) and 0.549 (95% CI: 0.444~0.654), 0.567 (95% CI: 0.433~0.701), respectively. The AUROC of HBsAg-TRFIA and HBsAg-CMIA for predicting ≥ S2, ≥ S3 and ≥ S4 were 0.525 (95% CI: 0.424~0.626), 0.582 (95% CI: 0.481~0.683), 0.566 (95% CI: 0.440~0.692) and 0.536 (95% CI: 0.436~0.636), 0.598 (95% CI: 0.495~0.700), 0.553 (95% CI: 0.420~0.686), respectively. In both HBeAg positive and negative patients, there were no significant differences between HBsAg-TRFIA and HBsAg-CMIA for predicting the pathological grade ≥ G2, ≥ G3 and stage ≥ S2, ≥ S3, ≥ S4.Conclusion There was highly consistency between HBsAg-TRFIA and HBsAg-CMIA in accuracy for measurement of HBsAg, as well as prediction of liver histopathology in CHB patients.

Preliminary study on salting-out and frozen-thaw method for exracting cryoprecipitate from plasma in hepatitis patients

XU Bing, HUANG Su-qin, WU Lin-lan, YANG Xiao-mei, WU Kai-mu.

2017, 22(11):  1005-1007. 

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Objective To investigate the efficiency of salting-out and frozen-thaw method for extracting cryoprecipitate from plasma in hepatitis patients for retransfusion therapy.Methods A total of 200 mL plasma from patients with severe hepatitis were diluted with equal volume of half-saturated sterile NaCl solution. Then the diluted plasma was frozen at -30 ℃ for at least 48 h or at -80 ℃ for 6 h. At -4 ℃, the frozen plasma was thawed and centrifugated at 500 g for 10 min. Removing the supernatant, the sediment was dissolved with acid citrate dextrose (ACD) solution to 20 mL cryoprecipitate (CP) solution. The values of Na⁺, Cl^－, fibrinogen (FIG), fibronectin (Fn), factor Ⅷ, prothrombin time (PT) and activated partial thromboplastin time (APTT) of the plasma and CP solution were measured, respectively. .Results Compared with plasma, CP solution showed 2~3 times higher levels of Na⁺ and Cl^－, 7 times higher levels of FIG and Fn, and nearly 9 times higher level of factor Ⅷ. However, CP solution showed lower levels of PT and ATPP than the plasma, with no significant difference (P>0.05 ).Conclusion The salting-out and frozen-thaw method could be used to extract CP from plasma, and the extracted CP should be diluted properly for further retransfusion.

The protective effects of helix B surface peptide on concanavalin A-induced acute liver injury in mice model

WU Sheng-di, YANG Cheng, SHEN Xi-zhong

2017, 22(11):  1008-1012. 

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Objective To investigate the protective effects of helix B surface peptide (HBSP) on concanavalin A (Con A)-induced acute liver injury (ALI) in mice.Methods ALI mice was induced with Con A administration. Two hours later, intravenous injection of HBSP was carried out every 6 h with the dose of 8 nmol·kg^-1. Serum and liver tissue samples were collected at 6 h, 12 h, and 24 h after Con A administration for evaluating liver function and histopathology. Inflammatory cell infiltration and cytokines were examined at 12 h, and hepatocytes apoptosis was measured using TUNEL analysis and immunohistochemistry (cleaved caspase-3). .Results Compared with Con A administration without HBSP treatment mice, HBSP treatment group showed significantly decreased levels of alanine aminotransferase and aspartate aminotransferase in serum and pro-inflammatory cytokines in liver tissues, as well as less hepatocyte apoptosis. Furthermore, HBSP improved the survival among those mice with ALI induced by Con A. Immunohistochemical staining indicated that HBSP relieved hepatocyte necrosis with the significantly decreased expression of cleaved caspase-3 in liver tissues, which was confirmed in TUNEL analysis.Conclusion HBSP is a potential therapeutic agent against Con A induced ALI, which might be associated with the inhibition of liver inflammation and hepatocyte apoptosis.