Clinical Model for Predicting Hepatocellular Carcinomas in Patients with Post-Sustained Virologic Responses of Chronic Hepatitis C: A Case Control Study

BACKGROUND/AIMS: No clinical model exists to predict the occurrence of hepatocellular carcinoma in sustained virologic response-achieving (HCC after SVR) patients with chronic hepatitis C (CHC). METHODS: We performed a case-control study using a clinical database to research the risk factors for HCC after SVR. A predictive model based on risk factors was established, and the area under the receiver operating characteristic curve (AUC) was calculated. RESULTS: In the multivariate model, an initial diagnosis of compensated cirrhosis and post-SVR albumin reductions of 1 g/L were associated with 21.7-fold (95% CI, 4.2 to 112.3; p0, an AUC of 0.880, a sensitivity of 0.833, a specificity of 0.896, and a negative predictive value of 0.956. CONCLUSIONS: An initial diagnosis of compensated cirrhosis combined with a post-SVR albumin value of ≤36.0 g/L predicts the occurrence of HCC after SVR in patients with CHC.

Hyperammonemia-induced hepatic injury in rats: characterization of a new animal model / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To establish an accurate new rat model of hyperammonemia-induced liver injury for use in studies of the molecular mechanisms underlying acute liver failure (ALF).</p><p><b>METHODS</b>Twenty-six Sprague-Dawley rats were administered D-galactosamine (400 mg/kg) and endotoxin (50 mug/kg) via intraperitoneal injection to induce ALF and sacrificed at 12 h post-injection (ALF-12 group, n = 10) or 24 h post-injection (ALF-24 group, n = 16). Ten rats administered physiological saline served as the control group. In addition, 20 rats were given serial oral administrations of 10% NH4Cl solution (10 ml/kg, every 8 hrs) to establish the hyperammonemia-induced liver injury model; an additional 20 rats were prepared in parallel to serve as the ALF control group (n = 10; D-galactosamine at 800 mg/kg every 6 d for 30 days) and the physiological saline control group (n = 10). Serum samples were collected from each mouse and used to detect markers of liver function, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alpha-fetal protein (AFP), and gamma-glutamyltransferase (GGT), as well as blood ammonia (BA) level and prothrombin time activity (PT-A). Affects on liver histology was assessed by hematoxylin and eosin staining of resected liver tissues, and on apoptosis by TUNEL assay and calculating the apoptotic index (AI).</p><p><b>RESULTS</b>ALF rats showed elevated levels of ALT (1202.51+/-282.00 U/L), AST (1560.14+/-298.98 U/L), and BA (165.9+/-23.6 mumol/L) as early as 6 hrs after model establishment; these levels peaked at 12 hrs after model establishment (ALT: 774.40+/-207.65 U/L; AST: 967.60+/-121.94 U/L; BA: 143.4+/-18.1 mumol/L; P less than 0.05). No significant variations were detected in the levels of AFP (except for the ALF-24 group) or GGT. Liver tissues of the ALF-12 and ALF-24 groups showed large or diffuse hemorrhagic necroses with sinusoidal congestion or spotty bleeding, as well as increased AI. Hyperammonemia-induced liver injury rats showed elevated levels of ALT and BA as early as 6 hrs after model establishment. Similar to the ALF rats, AFP and GGT were unaffected and AI increased. However, in contrast to the ALF rats, the liver tissues of the hyperammonemia-induced liver injury rats showed no signs of hepatocyte swelling, necrosis, or inflammatory cell invasion.</p><p><b>CONCLUSION</b>ALF rats and hyperammonemia-induced liver injury rats have elevated BA and marked hepatocyte necrosis. Given that reducing the level of ammonemia can improve the animal's biochemistry indexes, it is likely that hyperammonemia plays a role in acute liver injury or ALF consequent to repeated injury. The pathogenic mechanisms of repeated injury may involve promotion of hepatocyte apoptosis in conjunction with inhibition of cellular regeneration.</p>

Expression profile of altered long non-coding RNAs in patients with HBV-associated hepatocellular carcinoma / 华中科技大学学报（医学）（英德文版）

In China, hepatitis B virus (HBV) infection is the major cause of hepatocellular carcinoma (HCC), which is called HBV-related HCC (HBV-HCC), but the pathogenesis has not been clearly elucidated. Long non-coding RNAs (lncRNAs) have been paid increasing attention to, as an important regulatory molecule involved in many biological processes, as well as a variety of diseases. This study examined lncRNA that might play an important role in HBV-HCC pathogenesis by conducting lncRNA and mRNA profile comparison between HBV-HCC and normal liver tissues. The differentially expressed lncRNA and mRNA profiles between HBV-HCC and normal liver tissues were analyzed by microarrays. The potential protein-encoding gene regulated by lncRNA, and the biological function (gene ontology, pathway analysis) of the target gene were investigated. The results showed that the expression levels of lncRNA and mRNA in HBV-HCC tissues were different from those in normal liver tissues. As compared with normal liver tissue, 837 (4.30%) lncRNAs exhibited more than two-fold change (P<0.05); 325 were up-regulated, and 512 were down-regulated; 991 (5.70%) mRNAs exhibited more than 2-fold change (P<0.05); 733 were up-regulated and 258 were down-regulated in HBV-HCC tissue. Besides, there were 7 lncRNAs with above 10-fold elevation, 6 lncRNAs with above 10-fold decrease, 18 mRNAs with above 10-fold elevation and 11 mRNAs with above 10-fold decrease. 444 (53.05%) lncRNAs had their corresponding mRNAs, some of which were adjacent to lncRNAs. The biological analysis showed that the target gene of differentially expressed lncRNAs took part in the important biological regulatory function. Target gene-related pathway analysis revealed the pathways in carcinoma and mitogen-activated protein kinase (MAPK) signaling pathways significantly changed in the HBV-HCC tissues as compared with normal liver tissues (P<0.05). It was suggested that as compared with normal liver tissues, the expression of lncRNAs in HBV-HCC tissues changed significantly, and lncRNAs played a key role in the pathogenesis of HBV-HCC probably by mainly regulating the carcinoma-related signaling pathway and MAPK signaling pathways.

Expression profile of altered long non-coding RNAs in patients with HBV-associated hepatocellular carcinoma / 华中科技大学学报（医学）（英德文版）

In China, hepatitis B virus (HBV) infection is the major cause of hepatocellular carcinoma (HCC), which is called HBV-related HCC (HBV-HCC), but the pathogenesis has not been clearly elucidated. Long non-coding RNAs (lncRNAs) have been paid increasing attention to, as an important regulatory molecule involved in many biological processes, as well as a variety of diseases. This study examined lncRNA that might play an important role in HBV-HCC pathogenesis by conducting lncRNA and mRNA profile comparison between HBV-HCC and normal liver tissues. The differentially expressed lncRNA and mRNA profiles between HBV-HCC and normal liver tissues were analyzed by microarrays. The potential protein-encoding gene regulated by lncRNA, and the biological function (gene ontology, pathway analysis) of the target gene were investigated. The results showed that the expression levels of lncRNA and mRNA in HBV-HCC tissues were different from those in normal liver tissues. As compared with normal liver tissue, 837 (4.30%) lncRNAs exhibited more than two-fold change (P<0.05); 325 were up-regulated, and 512 were down-regulated; 991 (5.70%) mRNAs exhibited more than 2-fold change (P<0.05); 733 were up-regulated and 258 were down-regulated in HBV-HCC tissue. Besides, there were 7 lncRNAs with above 10-fold elevation, 6 lncRNAs with above 10-fold decrease, 18 mRNAs with above 10-fold elevation and 11 mRNAs with above 10-fold decrease. 444 (53.05%) lncRNAs had their corresponding mRNAs, some of which were adjacent to lncRNAs. The biological analysis showed that the target gene of differentially expressed lncRNAs took part in the important biological regulatory function. Target gene-related pathway analysis revealed the pathways in carcinoma and mitogen-activated protein kinase (MAPK) signaling pathways significantly changed in the HBV-HCC tissues as compared with normal liver tissues (P<0.05). It was suggested that as compared with normal liver tissues, the expression of lncRNAs in HBV-HCC tissues changed significantly, and lncRNAs played a key role in the pathogenesis of HBV-HCC probably by mainly regulating the carcinoma-related signaling pathway and MAPK signaling pathways.

Effects of cefodizime on chemokines of liver tissues in mice with immunological hepatic injury / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Chronic hepatic inflammation is characterized by the accumulation of lymphocytes as a consequence of increased recruitment from the blood and retention within the tissue at sites of infection. CXC chemokine ligand 16 (CXCL16) mRNA has been detected in both inflamed and normal liver tissues and is strongly upregulated in the injured liver tissues in a murine model. The aim of this study was to investigate the effect of cefodizime on CXCL16 mRNA of liver tissues in mice with immunological hepatic injury.</p><p><b>METHODS</b>The murine model of immunological hepatic injury was induced by Bacillus Calmette Guerin and Lipoposaccharide. The mice with immunological hepatic injury were randomly assigned to the model group, the cefodizime group and the ceftriaxone group. The three groups were continuously given agents for seven days and CXCL16 mRNA of liver tissue was determined and contrasted with the control group treated by normal saline. Reverse transcription-polymerase chain reaction was used to assay CXCL16 mRNA levels in liver tissues.</p><p><b>RESULTS</b>The expressions of CXCL16 mRNA were significantly higher in the model group and the ceftriaxone group than in the control group and the cefodizime group (P < 0.05), indicating the mice in the model group and the ceftriaxone group were immunodeficient. There was no statistical difference in the expressions of CXCL16 mRNA between the control group and the cefodizime group. Similarly, no statistical difference in the expressions of CXCL16 mRNA between the model group and the ceftriaxone group was detected (P > 0.05).</p><p><b>CONCLUSION</b>Cefodizime effectively reduces the infiltration of lymphocytes into liver tissues and alleviates the liver damage by decreasing CXCL16 mRNA in liver tissues in mice with immunological hepatic injury.</p>

A cross-sectional survey of occult hepatitis B virus infection in HIV-infected patients in acquired immune deficiency syndrome area / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To assess the prevalence of occult HBV infection in HIV-infected patients inacquired immune deficiency syndrome area.</p><p><b>METHODS</b>Serum samples were obtained from 97 HIV-infected patients who transmitted by paid blood donation. ELISA was used to detect HBV erologic markers (HBsAg, Anti-HBs, HBeAg, anti-HBe and anti-HBc) and HCV antibody. Flow Cytometry were used to detect CD4+ T cell count. Nested PCR was used to amplify surface protein region of HBV DNA.</p><p><b>RESULTS</b>Ninety two patients were HBsAg negative in the 97 HIV-infected patients (94.85%). Twenty seven patients were co-infected with occult hepatitis B virus infection in the 92 HBsAg negative patients (29.35%). Seventy three patients were co-infected with HCV in the 92 HBsAg negative patients(79.35%). CD4 cell count of subjects with occult HBV infection were significantly lower (212.11 +/- 133.1 cells/mm3 versus 318.9 +/- 172.2 cells/mm3, respectively, P < 0.01). A significantly higher prevalence of isolated anti-HBc was observed in HIV-infected subjects co-infectioned with occult HBV infection [62.96% (13 of 27) versus 18.46% (15 of 65), P < 0.01]. No statistical significant association could be established between the age, sex and whether co-infected with HCV.</p><p><b>CONCLUSION</b>It is found that occult HBV infection did occurs in HIV-infected patients. Individuals co-infected with HIV and occult HBV infection are more likely to have isolated anti-HBc than subjects with HIV alone. Co-infection with HIV and occult HBV is more likely to occue in subjects with lower CD4.</p>

Study on the association between chronic hepatitis B cirrhosis and HLA-DRB1 * 1301,1302 allele / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the association between the chronic hepatitis B cirrhosis and HLA-DRB1 * 1301,1302 gene.</p><p><b>METHODS</b>HLA-DRB1 * 1301,1302 allele in 27 patients with chronic hepatitis B cirrhosis and 30 patients with chronic hepatitis B was analyzed by using the polymerase chain reaction/sequence specific primer (PCR-SSP) technique.</p><p><b>RESULTS</b>The frenquency of HLA-DRB1 * 1301,1302 allele in the chronic hepatitis B cirrhosis group was markly higher than that in the chronic hepatitis B group.</p><p><b>CONCLUSION</b>HLA-DRB1 * 1301,1302 is closely associated with the suseptibility to chronic hepatitis cirrhosis.</p>

Study on the association between severe chronic hepatitis B and HLA-DRB1 gene polymorphism / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To study the association between HLA-DRB1 gene polymorphism and severe chronic hepatitis B.</p><p><b>METHODS</b>26 patients with severe chronic hepatitis B were investigated for HLA-DRB1 gene polymorphism by polymerase chain reaction-sequence specific primers technique. The results were compared with those from 45 normal healthy people by use of chi2-test of Microsoft SPSS 13.0.</p><p><b>RESULTS</b>The frequency of HLA-DRB1 * 1301/1302 allele in severe chronic hepatitis B group was significantly higher than the frequency in the control group, while the frequencies of HLA-DRB1 * 1201/1202, 1501/1502 allele were not significantly different.</p><p><b>CONCLUSION</b>HLA-DRB1 * 1301,1302 is closely associated with the suseptibility to severe chronic hepatitis B, While HLA-DRB1 * 1201/1202, 1501/1502 have no association with severe chronic hepatitis B.</p>

Complete human immunodeficiency virus-1 specific T lymphocyte response to Chinese human immunodeficiency virus-1 B/C chronic infectors / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To characterize the human immunodeficiency virus (HIV) -specific T lymphocyte responses and identify the immunodominant regions in Chinese HIV-1 recombinant subtype B/C chronic infectors at complete genome level.</p><p><b>METHODS</b>Twenty-five HIV-1B/C recombinant chronic infectors were screened for their specific T lymphocyte responses to a panel of peptides corresponding to the complete HIV-1 subtype B genome by gamma interferon ELISPOT assay. Kruskal-Wallis nonparametric analysis of variance was used to test significant differences across gene regions, and Tukey pairwise analysis was used to identify differences between gene regions. Spearman rank correlation was used to assess the relation between responses. Results The order of recognized frequencies of specific T lymphocyte responses to HIV proteins was Nef>Vpr>Gag>Pol>Vpu>Env>Rev>Vif>Tat. When adjusted for protein length, Nef, Vpr, Gag, and Pol were the most intensely targeted proteins and the central region of Nef, Gag p24, Pol RT, and Vpr was most frequently recognized. No significant correlation was observed between the magnitude of IFN-gamma production of HIV-l-specific T lymphocyte responses and plasma viremia, breadth of response and CD4 counts. Conclusion The central region of Nef, Gag p24, Pol RT, and Vpr is most frequently targeted in HIV-1 B/C recombinants chronic infectors. HIV-l-specific T lymphocyte responses and plasma viremia or CD4 counts play no protective role at complete genome level in these infectors.</p>

Analysis on the decline of hepatitis C virus RNA in the blood using a mathematical model / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To establish a mathematical model of hepatitis C virus (HCV) replication and develop a working theory for antiviral therapy in order to understand the dynamics of HCV replication.</p><p><b>METHODS</b>Peripheral blood cells of 4 hepatitis C patients were cultured. Quantities of the HCV were detected every 15 min by real-time PCR. The data were analyzed using SPSS software. A mathematical functional relationship between HCV RNA and the time lapse was established.</p><p><b>RESULTS</b>The quantity of HCV RNA declined and it fell into a mathematical model: Y=3E+0.8e(-0.5467x) (r=0.9547). The estimated virion half-life was 45 min on the average.</p><p><b>CONCLUSIONS</b>The decline of HCV RNA in the blood is not of a linear trend and the HCV RNA lasts a longer time although the speed of the decline is faster than that in vivo.</p>

The comparison of the effects of three kinds of anti-retroviral therapy on patients with human immunodeficiency virus infection in acquired immune deficiency syndrome area / 中华传染病杂志

0.05);however there were significant difference between D4T+DDI+NVP group and AZT+DDI+NVP group(P

Construction and expression of the recombinant human immunodeficiency virus Tat gene and analysis on its biological characteristics / 中华传染病杂志

Objective To determine the influence of protein fusion on the biological characteris- tics of hymidine kinase(TK)and human immunodeficiency virus(HIV)Tat recombinant protein. Methods By utilizing polymerase chain reaction(PCR)technique,different fragments containing two,four or six glycines(Gly)were inserted between the HIV Tat gene and TK,and cloned into PBK vector.After testified by sequencing,the vectors were transfected into E coli.After induced by iso- propyl thiogalactose(IPTG),bacilli were collected and destructed by ultrasonic,the fusion proteins were determined by monoclonal antibody against HIV protein.HepG2 cells were incubated in DMEM supplement with 10?g/mL HIV-Gly(n)-TK(n=0,2,4,6)fusion protein,TK-HIV Tat and only HIV Tat.HepG2 cells in different groups were detected by immunofluorescence assay 24 hours after transduction with HIV Tat monoclonal antibody.The rate of apoptosis after cells were incubated with gencilovir(10?g/mL)for 3 days was determined by cell flow cytometry,while survival cell ratio was recorded by trypan blue.The data were analyzed by statistics(t-test).Results The Tat-Gly(n)-TK (n= 0,2,4,6)recombinant genes were constructed and inserted into PBK vectors,which were expressed in E coli and then purified.Cells in different groups,which were incubated with Tat-Gly (n)-TK(n=0,2,4,6)fusion proteins,Tat-TK fusion protein,TK-Tat fusion proteins or only Tat proteins respectively,were detected by immunofluorescence assay.The intensities of fluorescence in different groups were almost same,but the ratios of cell survival or apoptosis were different.The highest ratio of cells apoptosis(14.77%)was in the group that cellular culture medium was mixed with Tat-Gly(4)-TK fusion protein,followed by the groups containing 6,2 glycines or no TK gene in genes(4.30%,12.69% and 1.03%,respectively).There were significant differences between each 2 groups among the all groups(t-test,P