HBV Infection Group Research Articles

Prophylactic antiviral therapy in allogeneic hematopoietic stem cell transplantation in hepatitis B virus patients.

To investigate the timing, safety and efficacy of prophylactic antiviral therapy in patients with hepatitis B virus (HBV) infection undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). This prospective study recruited a total of 57 patients diagnosed with malignant hematological diseases and HBV infection at the First Affiliated Hospital of Sun Yat-sen University between 2006 and 2013. The patients were classified as hepatitis B surface antigen (HBsAg)-positive or HBsAg-negative/ antiHBc-positive. Patients were treated with chemotherapy followed by antiviral therapy with nucleoside analogues. Patients underwent allo-HSCT when serum HBV DNA was < 10(3) IU/mL. Following allo-HSCT, antiviral therapy was continued for 1 year after the discontinuation of immunosuppressive therapy. A total of 105 patients who underwent allo-HSCT and had no HBV infection were recruited as controls. The three groups were compared for incidence of graft-vs-host disease (GVHD), drug-induced liver injury, hepatic veno-occlusive disease, death and survival time. A total of 29 of the 41 subjects with chronic GVHD exhibited extensive involvement and 12 exhibited focal involvement. Ten of the 13 subjects with chronic GVHD in the HBsAg(-)/hepatitis B core antibody(+) group exhibited extensive involvement and 3 exhibited focal involvement. Five of the 10 subjects with chronic GVHD in the HBsAg(+) group exhibited extensive involvement and 5 exhibited focal involvement. The non HBV-infected group did not differ significantly from the HBsAg-negative/antiHBc-positive and the HBsAg-positive groups which were treated with nucleoside analogues in the incidence of graft-vs-host disease (acute GVHD; 37.1%, 46.9% and 40%, respectively; P = 0.614; chronic GVHD; 39%, 40.6% and 40%, respectively; P = 0.98), drug-induced liver injury (25.7%, 18.7% and 28%, respectively; P = 0.7), death (37.1%, 40.6% and 52%, respectively; P = 0.4) and survival times (P = 0.516). One patient developed HBV reactivation (HBsAg-positivity) due to early discontinuation of antiviral therapy. Suppression of HBV DNA to < 10(3) IU/mL before transplantation, continued antiviral therapy and close monitoring of immune markers and HBV DNA after transplantation may assure the safety of allo-HSCT.

Individuals having variant genotypes of cytochrome P450 2C19 are at increased risk of developing primary liver cancer in Han populations, without infection with the hepatitis virus

Recently, many researchers have reported that the genetic polymorphisms of CYP2C19 may account for the interpatient variability of the clinical course in cancers including primary liver cancer (PLC). Besides the genetic polymorphisms of CYP2C19, hepatitis viruses (HV, including HAV, HBV, HCV, HDV, HEV, especially HBV and/or HCV) also account for the interpatient variability of the clinical course in PLC. This research covered the above two factors and divided the patients with PLC into two groups (one group with HBV infection and another without any HV infection) to find out whether the genetic polymorphisms of CYP2C19 have different effects in the progressing of PLC in different groups of patients. Eight hundred sixty-four cancer-free Han people (controls, named group 1), 207 Han PLC patients with HBV infection (group 2), and 55 Han PLC patients without any HV infection (group 3) were involved in this study. A wild-type allele (CYP2C19*1) and two mutated alleles (CYP2C19*2 and CYP2C19*3) were identified. The frequencies of the mutant alleles and genotypes were then compared with each other. The frequencies of the homozygous and heterozygous variant genotypes (*2/*2, *2/*3, *3/*3) in group 3 (25.5 %) were significantly higher than those in other groups (11.9 % in group 1 and 13.5 % in group 2, P = 0.014, 95 % confidence interval (CI)). The differences were statistically significant between group 1 and group 3 (P = 0.004, 95 % CI), but they were not statistically significant between group 1 and group 2 (P = 0.527, 95 % CI). Thus, we conclude that people which were not infected with HV but with the homozygous or heterozygous variant genotypes (*2/*2, *2/*3, *3/*3) of CYP2C19 may have higher possibilities of getting PLC than people with other allelic genotypes (*1/*1, *1/*2, *1/*3) (odds ratio (OR) = 2.523, 95 % CI = 1.329 ~ 4.788). However, in patients with HBV infection, the genetic polymorphisms of CYP2C19 did not seem to be an important factor in the risk of developing PLC (OR = 1.156, 95 % CI = 0.738 ~ 1.810).

Comparisons of presentations and outcomes of cryptococcal meningitis between patients with and without hepatitis B virus infection

The clinical characteristics and outcomes in cryptococcal meningitis (CM) have been shown to vary depending on the underlying condition. The purpose of this study was to investigate these differences in patients with and without hepatitis B virus (HBV) infection. We performed a retrospective study at the Third Affiliated Hospital of Sun Yat-Sen University from January 2006 to June 2012. Thirty-two HBV-positive patients and 58 HBV-negative patients were included. Among the 90 patients with CM, 32 (35.6%) were HBV-infected. CM occurred in a younger population in the HBV-positive group, with a higher Charlson comorbidity score than the HBV-negative group. The HBV-positive group presented with lower initial complaints of visual symptoms, lower cerebrospinal fluid (CSF) white blood cell counts, lower percentages of the total protein in the CSF exceeding 0.45 g/l, higher glucose levels in the CSF, a higher percentage of positive results for Cryptococcus culture in the CSF, more extraneural involvement sites, and a higher proportion of normal brain images than the HBV-negative group. Factors for a poor prognosis in the HBV-positive group included liver cirrhosis and HBV DNA >10³ copies/ml. In the HBV-uninfected group, lower glucose in the CSF and hydrocephalus were the indicators of an unsatisfactory outcome. Certain clinical features of CM were found to be significantly different between HBV-infected and HBV-uninfected patients, including age and initial laboratory findings, as well as the indicators of an unsatisfactory outcome. Host defense defects in the HBV-infected group may lead to a lower intensity of inflammation in the pathogenesis of CM compared with the HBV-uninfected patients and may account for these divergences between the two groups.

Increased frequency of micronuclei in the lymphocytes of patients chronically infected with hepatitis B or hepatitis C virus

In this study, we analysed the frequency of micronuclei (MN), nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) and evaluated mutagen-induced sensitivity in the lymphocytes of patients chronically infected with hepatitis B virus (HBV) or hepatitis C virus (HCV). In total, 49 patients with chronic viral hepatitis (28 HBV-infected and 21 HCV-infected patients) and 33 healthy, non-infected blood donor controls were investigated. The frequencies (‰) of MN, NPBs and NBUDs in the controls were 4.41 ± 2.15, 1.15 ± 0.97 and 2.98 ± 1.31, respectively. The frequencies of MN and NPBs were significantly increased (p < 0.0001) in the patient group (7.01 ± 3.23 and 2.76 ± 2.08, respectively) compared with the control group. When considered separately, the HBV-infected patients (7.18 ± 3.57) and HCV-infected patients (3.27 ± 2.40) each had greater numbers of MN than did the controls (p < 0.0001). The HCV-infected patients displayed high numbers of NPBs (2.09 ± 1.33) and NBUDs (4.38 ± 3.28), but only the HBV-infected patients exhibited a significant difference (NPBs = 3.27 ± 2.40, p < 0.0001 and NBUDs = 4.71 ± 2.79, p = 0.03) in comparison with the controls. Similar results were obtained for males, but not for females, when all patients or the HBV-infected group was compared with the controls. The lymphocytes of the infected patients did not exhibit sensitivity to mutagen in comparison with the lymphocytes of the controls (p = 0.06). These results showed that the lymphocytes of patients who were chronically infected with HBV or HCV presented greater chromosomal instability.

Association of Human Leukocyte Antigen Class I Polymorphism with Spontaneous Clearance of Hepatitis B Surface Antigen in Qidong Han Population

Aim. To investigate whether HLA class I polymorphisms could influence the clearance of hepatitis B surface antigen (HBsAg) in Qidong Han population. Methods. We genotyped HLA-A, -B, and -C loci of 448 individuals with HBV persistent infection and 140 persons with spontaneous clearance of HBsAg by polymerase chain reaction with sequencing based typing (PCR/SBT). All the individuals were unrelated males enrolled from Qidong Han population and were followed up for 10 years. Results. The frequency of HLA-A∗33:03:01G was increased in persistent HBV infection group (P value is 0.028), while frequency of HLA-B∗13:01:01G was increased in HBsAg clearance group (P value is 0.0004). Conclusion. These findings suggested that the host HLA class I polymorphism is an important factor in determining the outcomes of HBV infection.

The role of the toll-like receptor TLR4 in hepatitis B virus-associated glomerulonephritis

Toll-like receptor 4 (TLR4) plays an important role in innate immunity. The aim of our study was to detect the expression of TLR4 in HBV-associated glomerulonephritis (HBV-GN) and explore the pathogenesis of TLR4 in inhibition of HBV replication in kidney. Immunohistochemical methods were used to detect the distribution of immunoglobulin, HBsAg, HBcAg and TLR4. Because TLR4 was mainly distributed in renal tubules and interstitial spaces, we used human proximal tubular epithelial cells (HK-2) as target cells, which were cultured with HBV-DNA-positive serum. Cells were divided into four groups: A, a normal control group; B, an HBV-induced group; C, an HBV and 10μg/ml LPS (TLR4-stimulating factor) group; and D, an HBV and 5μg/ml CLI095 (TLR4 inhibitor) group. The morphology of HK-2 cells was observed by microscopy, and the expression of α-SMA was examined by immunofluorescence before and after culturing with HBV-DNA-positive serum. MTT was used to detect HK2 proliferation. The expression of TLR4 protein was detected by immunofluorescence and western-blotting assays, HBsAg and HBeAg levels in supernatants were measured by ELISA, and the expression of HBV-DNA was measured by semi-quantitative reverse transcription-PCR (RT-PCR). The immunohistochemical staining for TLR4 in the normal control group was negative. The expression of TLR4 in HBV-GN was significantly higher than in the HBV-antigen-positive and -negative primary glomerulonephritis (PGN) groups and was mainly distributed in renal tubules and the interstitial area, where the distribution of HBsAg had similar intensity. The expression of TLR4 was significantly associated with renal tubular and interstitial lesions. In an in vitro study with prolonged infection with HBV-DNA-positive serum, more irregularly shaped cells and fewer HK-2 were observed. The expression of α-SMA in the cytoplasm of HK-2 was significantly increased after HBV infection. Immunofluorescence results showed that almost no expression of TLR4 in HK2 cells cultured with normal serum (group A), while the expression of TLR4 was increased after HBV infection (group B). With increasing LPS concentration, the rate of the proliferation of HK2 cells, the levels of HBV-DNA in the supernatant, and the expression of HBsAg and HBeAg decreased. TLR4 was mainly expressed in HBV-GN in renal tubules and interstitial spaces and was significantly associated with renal tubular and interstitial lesions. The stimulation of TLR4 not only inhibited HBV replication but also inevitably induced immune injury to cells. Therefore, we speculate that TLR4 may be involved in an immune inflammatory reaction by inhibiting HBV replication in HK2 cells, which could have an antiviral effect during HBV infection in the kidney.

Immunological and virological responses to combined antiretroviral therapy in HIV/hepatitis B virus-coinfected patients from a multicenter cohort

To evaluate the influence of hepatitis B virus (HBV) coinfection on immunological, virological and clinical responses to lamivudine (3TC)-based combined antiretroviral therapy (cART) in Chinese patients. This prospective, multicenter cohort study recruited 529 antiretroviral-naive participants (aged 18–65 years, both sexes) between 2008 and 2010.They were grouped by HBV serostatus. Virological and immunological responses were monitored at baseline and week 4, 8, 12, 24, 36 and 48. cART for all patients was nevirapine, 3TC with either zidovudine or stavudine. First, HIV/HBV coinfection rate in our cohort was 14.6%. Second, among 508 patients with complete baseline information, median CD4 level was significantly lower in the chronic HBV-infected (CHB) group and isolated core group. In the CHB group,hepatitis B e antigen positivity rather than HBV DNA level was associated with lower CD4 cell count. Third, in the isolated core group, occult infection rate was 9.5%.Fourth, at week 48, rate of HIV suppression below 40 copies/ml was 74.2%. Median increase in the CD4 cell count at week 48 was 127 cells/ml. Of note, HBV serostatus did not influence virological and immunological response to cART at each follow-up time point. Although HBV serostatus was associated with different alanine aminotransferase levels during follow-up, hepatitis and hyperbilirubinemia rates were not significantly different. Fifth, the 3TC-based regimen was efficacious against HBV replication, with median decrease in HBV DNA of 2.87 log copies/ml. However, hepatitis B e antigen positivity was associated with poorer HBV DNA suppression. In our cohort, CHB infection and isolated hepatitis B core antibody positivity were related to faster HIV progression. Despite of this, virological and immunological responses were not affected by HBV serostatus.

Genetic association between interleukin-10 promoter microsatellite polymorphisms and hepatitis B virus infection in Yi, Yao and Han ethnic populations of Guizhou province

To investigate the association between interleukin-10 (IL-10) gene promoter microsatellite polymorphisms and the susceptibility to hepatitis B virus infection in Han, Yi and Yao ethnicities in GuiZhou province. 500 volunteers were selected from Guizhou province. Allelic frequency of IL-10.G and IL-10.R loci was identified by short tandom repeat polymerase chain reaction. The relativity between allelic frequency and HBV infection was analyzed. Genotype data from H-W analysis on all the IL-10 polymorphisms indicated that it was a random distribution. Very high HBV infection rates were found in the native ethnic minorities of Guizhou province. The overall HBV infection rate among the total population was 67.00%, with the HBV infection rates of Yi nationality in Weining, Yi nationality in Qianxi, Yao nationality in Libo and Han nationality in Libo as 51.85%, 42.86%, 79.52% and 84.30%, respectively. The polymorphisms distribution of IL-10.G and IL-10.R were statistically different among the ethnic groups (P < 0.05). The polymorphisms distribution of IL-10.R had no significant difference between HBV infection group and non-infection group, as well as among HBV natural removal group and non-infected group in all the ethnic groups. The frequency of IL-10.G 459 bp (19CA) was significantly higher in non-infection group than in the infected group (P < 0.05). The frequency of IL-10.G 471 bp (25CA) was significantly higher in the non-infection group than in the HBV natural removal group (P < 0.05). The polymorphisms distribution of IL-10.G did not show significant difference between the HBV infection group and the HBV natural removal group in all the ethnic groups. We did not find any differences in allelic and genotypic frequencies of IL-10.G between infection group and non-infection group in Yi nationality in Weining, and Yao nationality in Libo (P > 0.05), as well as HBV natural removal group and non-infected group (P > 0.05). The polymorphisms distribution of IL-10.R and IL-10.G did not show significant difference in Yi, Yao and Han ethnics population living in Guizhou province. IL-10.G seemed to influence the susceptibility of HBV infection in Han, Yao and Yi ethnics population of Guizhou province.

Association of human leukocyte antigen-DRB1 alleles with chronic hepatitis B virus infection in the Han Chinese of Northeast China

Human leukocyte antigen (HLA) class II molecule is an integral component of the immune response on which the majority of host genetic studies have concentrated. Many different HLA-II alleles have been demonstrated to play roles in HBV infection. PCR-SSOP methods were applied to determine the HLA-DRB1 genotypes of 769 unrelated healthy individuals from Han Chinese of Northeast China. The frequencies of HLA-DRB1*09 in hepatitis B virus (HBV)-infected subjects were higher compared to those in the control group. Frequencies of HLA-DRB1*04 and *13 in the HBV-infected group were significantly lower compared to those in the healthy control group. Frequencies of HLA-DRB1*12 in the cirrhosis and liver cancer groups were significantly higher than those in the chronic hepatitis B (CHB) patients. The frequency of LA-DRB1*03 in the CHB patient group was significantly higher compared to that in the asymptomatic hepatitis B carrier patients. The above results suggest that the host HLA-II gene is an important factor in the determination of the outcome of HBV infection.

Rather than interleukin‐27, interleukin‐6 expresses positive correlation with liver severity in naïve hepatitis B infection patients

Effective cytokines can drive the commitment of naive T cells to regulate immune response after antigen-mediated activation. Aims are to elucidate the clinical role of serum IL-27 and IL-6 in the different stages of naïve hepatitis B virus (HBV)-infected patients. Samples with well-characterized clinical profiles were assessed from 395 HBV-infected patients including chronic hepatitis B (CHB) group in 291 patients, liver cirrhosis (LC) group in 57 patients, hepatocellular carcinoma (HCC) group in 47 patients. Another 139 non-HBV infected individuals were enrolled as control group (CG) including 104 with normal liver function (NF) and 35 with liver dysfunction (LD). The HBV-infected group and separated groups presented significantly higher IL-27 and IL-6 expression than the CG or subgroups of CG. In contrast to IL-27, IL-6 showed significant differences with deteriorating liver condition compared with LC or HCC with CHB groups. Furthermore, IL-6, rather than IL-27, showed significant statistical differences in patients with advanced liver disease compared with those of mild or moderate to severe liver disease and in patients with terminal stage HCC compared with those of early to intermediate or advanced stage HCC. The data associated with liver function, including Albumin, Bilirubin, INR, Platelet and AFP levels, were significantly correlated to IL-6 expression, but had weak correlation to IL-27 expression in HBV patients. Serum IL-27 can trigger immune response to prevent hepatic injury in different clinical-pathologic stages of HBV-infected patients earlier, but IL-6 may play an extremely important role to determine the liver progression.

The balance between intrahepatic IL-17+ T cells and Foxp3+ regulatory T cells plays an important role in HBV-related end-stage liver disease

BackgroudIL-17+ T helper cells and Foxp3+ regulatory T cells are CD4+ T helper cells with reciprocally regulated differentiation and function. Their frequency and function vary in patients with chronic hepatitis B. In this study, we investigated the balance between IL-17+ T cells and Foxp3+ regulatory T cells and illustrated their function in the aggravation of chronic hepatitis B (CHB).ResultsTwenty-six patients with chronic HBV -related liver failure (CLF), thirty-one patients with acute on chronic HBV-related liver failure (ACLF) and twelve normal controls were enrolled in our study. The expressions of IL-17, Foxp3, CD4, CD8 and perforin in liver tissue were measured by immunochemistry for the evaluation of liver-infiltrating lymphocytes. The frequency of liver IL-17+ T cells on liver inflammatory cells and their proportion in the total CD4+ T cell population increased markedly in the ACLF group, while the frquency of Foxp3+ T cells and their proportion in the total CD4+ T cell population did not show a significant difference in the two HBV infection groups. In addition, the ACLF group showed a dramatically higher IL-17+ /Foxp3+ ratio than the CLF group. CD4+ T cells increased significantly in the liver of patients with ACLF, compared with those in the liver of patients with CLF.ConclusionsOur findings suggest that intrahepatic IL-17+ T cells play an important role in the development of chronic HBV and that the imbalance between IL-17+ and Foxp3+ T cells in the liver may lead to progression of the disease but the mechanism should be further explored.

Expression and significance of human zinc finger 23 gene in hepatocellular carcinoma

Objective To detect the expression level of human zinc finger 23 (ZNF23) in hepatocellular carcinoma tissue samples and HepG2 cell lines and investigate the relationship between hZNF23 expression and clinicopathological characteristics of HCC and cell apoptosis. Methods The expression levels of hZNF23 and GAPDH mRNA in 37 cases of HCC were measured by real-time RT-PCR. The association between the expression of hZNF23 and the clinicopathological characteristics of HCC was analyzed. Cultured HepG2 cells were divided into 4 groups ( control group, 1.25 μg/ml , 2.5 μg/ml and 5 μg/ml cisplatin)or 6 groups( control group, 1.25 μg/ml, 2.5 μg/ml, 5 μg/ml, 10 μg/ml and 20 μg/ml cisplatin). MTT method was employed to evaluate cell proliferation. Annexin V-FITC assay was used to assess percentage of apoptotic HepG2 cells. The expression levels of hZNF23 and GAPDH mRNA of HepG2 cells after apoptosis induced by cisplatin with a series of concentrations were measured by real-time RT-PCR.Results The median ( quartile1, quartile 3) expression levels of hZNF23 mRNA in 37 HCC tissue samples and adjacent tissue samples were 8.84 (3.59-15.05), 22.20 ( 13.85-42.90 ), respectively. There was significant difference ( U = 259.5, P ＜ 0.01 ). The median ( quartile1, quartile 3 ) expression levels of hZNF23 mRNA in cancer tissue samples with Edmondson stage Ⅰ + Ⅱ [12.80(4.80-19.50)] was much higher than those in stage Ⅲ + Ⅳ [5.01 ( 2.88-11.68 ), U = 99.00, P ＜ 0.05] The median ( quartile1,quartile 3 ) expression levels of hZNF23 mRNA in patients with and without hepatic cirrhosis were 9.92(3.80-15.25) , 3.21 (2.78-3.60), respectively. The median ( quartile1, quartile 3 ) expression levels of hZNF23 mRNA in HBV infection and non-infection patients was 9.09(3.72-15.25 ), 2.48 (1.79-12.10),respectively. There was no significant difference between groups with and without hepatic cirrhosis and between HBV infection and non-infection groups( U = 16. 00 and 24.00, P ＞0.05 ). MTT assay indicated that cisplatin significantly inhibited HepG2 cells proliferation in a dose-dependent manner. Annexin V-FITC/PI assay showed that HepG2 cells apoptosis rates were (0.9 ± 0.2 ) %, ( 4. 2 ± 0.3 ) %, ( 9.8 ± 4. 3 ) %,(23.0 ± 6.0)%, respectively. Cisplatin significantly induced HepG2 cells apoptosis in a dose-dependent manner( F = 27.89, P ＜ 0.01 ). The expression levels of hZNF23 mRNA in cisplatin groups [( 10.39 ±3.08) × 10-5, (24.10 ± 2.09) × 10-5, (6.90 ± 2.24) × 10-4] were significantly lower than that of the controlgroup[(94.80±1.80) ×10-5, F=6.027, P＜0.01]. Conclusions The expression level hZNF23 mRNA is related to Edmondson stage of HCC. The apoptosis effect of cisplatin on HepG2 cells may be associated with the upregulation of hZNF23. Key words: Hepatocellular carcinoma; Human zinc finger; Reverse transcription-polymerase chain reaction; Annexin V-FITC/PI assay; Apoptosis

Metabolic syndrome and severity of fibrosis in patients with chronic viral hepatitis B infection or non-alcoholic fatty liver disease

To investigate the prevalence of metabolic syndrome (MS) in patients with chronic viral hepatitis B (HBV) infection or non-alcoholic fatty liver disease (NAFLD), and to determine the relationship between MS and the risk of fibrosis in those patients, 136 patients with chronic HBV infections and 110 NAFLD patients were analyzed retrospectively between January 2008 and June 2009. The results showed that the prevalence of MS in the NAFLD group was significantly higher that of the HBV infection group (49.1 and 11.8%, respectively; P < 0.01). In HBV group, severity of fibrosis was associated with increased body mass index (BMI), higher aspartate aminotransferase (AST) and gamma-glutamyl-transpeptidase (GGT), severity of necroinflammation and MS. However, in NAFLD group, MS was more prevalent in patients with non-alcoholic steatohepatitis (NASH) than that of simple fatty liver (55.4 and 40%, respectively; P < 0.01). Severity of fibrosis was associated with MS, higher alanine transarninase (ALT), AST, GGT, and severe necroinflammation. We concluded that MS might be more prevalent in NAFLD patients, and associated with the severity of fibrosis in patients with chronic HBV infection or NAFLD. Key words: Metabolic syndrome, viral hepatitis B, non-alcoholic fatty liver disease, fibrosis.

The dendritic cell subsets function and the cytokines levels in plasma change in different period in patients with HBV infection

We studied the function of dendritic cells subsets and the cytokines levels in plasma in patients with different periods of returning (immune tolerance, hepatitis active and non-replicating period) and aimed to explore the possible reasons for HBV chronic infection. Thirty HBV infected patients in different stages of infection were enrolled and divided into three groups: the immune tolerance group (10 cases), the hepatitis active group (10 cases), and the non-replicating group (10 cases). Ten healthy people were enrolled and served as controls. Blood from the patients and controls were collected and the dendritic cells subsets function (The cytokine levels in different groups) were analyzed using statistical method. The total IL-12 output and single nucleus IL-12 output of the total HBV infected patients were lower than that of the healthy control group (P value less than 0.01). The total IFNa output and single nucleus IFNa output of the total HBV infected patients had no significant difference between the total HBV infected patients and the healthy controls (P value more than 0.05). The total IL-12 output of the healthy control group was higher than that in others 3 groups of the HBV infected patients. (Z = -3.039, -2.967 ,-2.949, P value less than 0.01) and the single nucleus IL-12 output of the healthy control group was also higher than that in others 3 groups of the HBV infected patients. (Z =-3.027, -2.671 , -2.863, P value less than 0.01) . The total IFNa output and the single nucleus IFNa output of the healthy control group was higher than that in the hepatitis active group of HBV infected patients (Z = -3.016, -3.176, P value less than 0.01). While the plasma IFNa cytokine levels in the 3 HBV infection groups were higher than in the healthy control group (Z = -2.967, -2.896, -3.054, P value less than 0.01). Difference existed between the function of dendritic cells subsets and the IFNa levels in different returning periods of HBV infected patients. The function of dendritic cells subsets has no significant difference in HBV patients with different periods of returning. The flawed function of dendritic cells subsets and the abnormal IFNa level may be one of the reasons for chronic HBV infection.

E0239 N-terminal pro-brain natriuretic peptide (NT-proBNP): a potential diagnostic biomarker for predicting cardiac dysfunction in patients with liver diseases

BackgroundNT-proBNP has emerged as a powerful diagnostic and prognostic biomarker in heart disease. Studies showed that NT-proBNP is a sensitive biomarker for identifying patients with heart failure caused by hepatitis...

High Frequency of Variant Alleles of the Mannose-Binding Lectin 2 (MBL2)Gene Are Associated with Patients Infected by Hepatitis B Virus

Patients with hepatitis B virus (HBV) infection may develop severe chronic liver disease. Carriers of HBV have an increased risk of developing cirrhosis, hepatic decompensation, and hepatocellular carcinoma. Worldwide an estimated 350 million people are infected with HBV, and 15-40% will develop serious sequelae in their lifetime. In our study we investigated the association of single nucleotide polymorphisms (SNPs) in the first exon and promoter region of the mannose-binding lectin gene 2 (MBL2) situated on chromosome 10, with susceptibility to HBV infection. One-hundred and two patients infected with HBV were included in this study, and 232 uninfected individuals were used as healthy controls. Genotyping of the first exon (alleles A/O) was performed using a melting temperature assay. Genotyping of the promoter region (-550 H/L; -221 Y/X) was performed using the Taqman PCR technique. In the HBV-infected group we found a significantly increased frequency of haplotypes associated with low serum MBL. Our findings may indicate that MBL has a protective role against HBV infection in the studied population.

Sexual Behavior and HBV Infection Among Noninjecting Cocaine Users (NICUs)

The aim is to estimate HBV prevalence and the associated risks among noninjecting cocaine users (NICUs). In 2002–2003, a total of 824 NICUs from Buenos Aires (Argentina) and Montevideo (Uruguay) were interviewed using a structured questionnaire. Serologic tests were carried out for Human Immunodeficiency Virus (HIV), hepatitis B (HBV), syphilis, and others. The population was divided into two serologic groups: HBV-infected and seronegative group. Univariate and binary logistic model were developed. The results seem to indicate that, among NICUs, HBV is transmitted through sexual contact. Prevention measures, including vaccine, are needed in order to control and minimize risks. The study's limitations are noted.

The correlation of HBV infection and HCMV reactive infection after liver transplantation

Objective To study the correlation of HBV infection pretransplantation and posttrans-plantation and HCMV recurrence after liver transplantation (LT). Methods We reviewed historical patient medical records of LT patients in recent two years in our hospital. All the patients were divided into HBV in-fection group and a control group based on a peripheral blood HB antigen assay before LT. The HBV infec-tion group was divided into HBV reactive infection group and HBV non-relapse group. HCMV antigen pp~65 was detected by immunohistochemical methods. HB antigens and antibodies were detected by time-resolved fluorescence immunoassay, and liver enzyme levels were detected by conventional methods. Results Com-paring two groups of patients, pp65-positive rates of LT patients with HBV infection and control group pa-tients were 84.3% and 57.9% respectively (P=0.024). While in HBV recurrence infection group and non-recurrence infection group, the incidences of HCMV recurrence were 90.9% and 83.3% (P=0.843). The changes in the liver transaminases level in both groups have no statistical significance (P>0.05). Conclusion Pretransplantation HBV infection may increase the incidence of HCMV recurrence. Posttrans-plantation HBV reactive infection, however, may not increase the incidence of HCMV reactive infection. Meanwhile, compare with either HBV infection or HCMV infection alone, co-infection may not serious in liv-er enzymes levels. Key words: Hepatitis B virus; Liver transplantation; Cytomegalovirus; Transaminase

Negative correlation between viral load and HBsAg levels in chronic HBV-infected patients

The objective of this study is to reveal the relationship between viral load (as HBV DNA) and HBsAg levels. Ninety-two chronically HBV-infected patients were included in the study. The patients were divided in two different groups: the cirrhotic group (n = 32) and the non-cirrhotic group (n = 60). The correlation between study groups was also examined with regard to HBeAg status. Hepatitis B viral markers (HBsAg, HBeAg, Anti-HBs, anti-HBc and anti-HBe) and HBV viral load of the patients were measured. A significant negative correlation between HBV DNA and HBsAg levels was found in the non-cirrhotic group (p < 0.01). The anti-HBc level was higher in the non-cirrhotic group than in the cirrhotic group (p < 0.016). The viral load was significantly higher in HBeAg (+) patients in comparison with HBeAg (-) cases (p < 0.0001). The HBsAg level was low in HBeAg (+) patients, whereas it was higher in HBeAg (-) cases (p < 0.001). In conclusion, a significant negative correlation between viral load and HBsAg levels was detected in the non-cirrhotic chronically HBV-infected group. Therefore, concomitantly low HBsAg and HBV DNA levels may indicate a better prognosis compared to high HBsAg and low HBV DNA levels.

Cytokine expression during chronic versus occult hepatitis B virus infection in HIV co-infected individuals

Chronic hepatitis B virus infection is characterized by persistent detectable levels of hepatitis B surface antigen (HBsAg) and HBV DNA in the serum. In contrast, HBsAg is not detectable during occult HBV infection, despite the presence of HBV DNA. An altered host immune response could play a role in the development of occult HBV infection; however, potential differences in immune responses among chronic and occult HBV-infected patients have not been evaluated in vivo. In the current study, we evaluated serum levels of regulatory, apoptotic, and fibrotic/anti-fibrotic cytokines/markers as indicators of immune responses in 25 chronic and 12 occult HBV-infected patients. More than half of the patients in both chronic and occult HBV infection groups had IL-2, IL-4, IL-13, and IFN-γ levels below detectable limits. In contrast, most patients had detectable levels of IL-8, IL-10, IP-10, sFas, sFasL, and TGF-β1. Of these, only sFas was significantly different between the two groups, with lower levels observed during occult compared to chronic HBV infection ( p = 0.01). As a surrogate marker of apoptotic inhibition, decreased sFas during occult HBV infection suggests that apoptosis occurs at different rates in occult compared to chronic HBV infection and therefore, may contribute to persistence of occult HBV infection.