Chronic hepatitis B serum promotes apoptotic damage in human renal tubular cells

AIM： To investigate the effect of the serum of patients with chronic hepatitis B （CHB） on apoptosis of renal tubular epithelial cells in vitro and to study the role of hepatitis B virus （HBV） and transforming growth factor-β1 （TGF-β1） in the pathogenesis of hepatitis B virus associated glomerulonephritis （HBV-GN）. METHODS： The levels of serum TGF-β1 were measured by specific enzyme linked immunosorbent assay （ELISA） and HBV DNA was tested by polymerase chain reaction （PCR） in 44 patients with CHB ,and 20 healthy persons as the control. The normal human kidney proximal tubular cell （HK-2） was cultured together with the sera of healthy persons, CHB patients with HBV-DNA negative（20 cases） and HBV-DNA positive （24 cases） for up to 72 h. Apoptosis and Fas expression of the HK-2 were detected by flow cytometer. RESULTS： The apoptosis rate and Fas expression of HK-2 cells were significantly higher in HBV DNA positive serum group 19.01±5.85% and 17.58±8.35%, HBV DNA negative serum group 8.12±2.80% and 6.96 ± 2.76% than those in control group 4.25±0.65% and 2.33 ± 1.09%, respectively （P 〈 0.01）. The apoptosis rate and Fas expression of HK-2 in HBV DNA positive serum group was significantly higher than those in HBV DNA negative serum （P 〈 0.01）. Apoptosis rate of HK-2 cells in HBV DNA positive serum group was positively correlated with the level of HBV-DNA （r = 0.657）. The level of serum TGF-β1 in CHB group was 163.05 ± 91.35 μg/L, signifi- cantly higher as compared with 81.40 ± 40.75 μg/L in the control group （P 〈 0.01）.CONCLUSION： The serum of patients with chronic hepatitis B promotes apoptotic damage in human renal tubular cells by triggering a pathway of Fas up-regulation. HBV and TGF-β1 may play important roles in the mechanism of hepatitis B virus associated glomerulonephritis.

Analyses of prognostic indices of chronic liver failure caused by hepatitis virus

AIM: To analyze the related indices about the prognoses of chronic liver failure caused by hepatitis virus. METHODS: Retrospectively reviewed 320 cases of chronic liver failure caused by hepatitis viruses. An improved group and an ineffective group (IG) were made to compare and analyze their clinical manifestations, laboratory examination indices and complications. Logistic regression was also carried out. RESULTS: There were significant differences (P<0.05) between the improved group and the IG upon such indices as age, bilirubin, prothrombin time, albumin, alpha fetoprotein, the size of liver and complications (P<0.05). The regression formula was as follows: P=1/(1+e^(-y)) (y=1.7262-0.0948X_1+2.9846X_2+0.6992X_3+1.6019X_4+2.0398X_5). (Note: X_1-Prothrombin activity; X_2-digestive tract hemorrhage; X_3-hepatic encephalopathy; A_4-hepatorenal syndrome; X_5-pulmonary infection.). CONCLUSION: Laboratory examination such as bilirubin, prothrombin time and alpha fetoprotein can be regarded as indices of the prognoses of chronic liver failure caused by hepatitis. Moreover, the regression equation can evaluate prognoses more comprehensively and direct our treatments.

Programmed death-1 expression is associated with the disease status in hepatitis B virus infection

AIM： TO define the potential role of programmed death-i/programmed death-ligand （PD-1/PD-L） pathway in different hepatitis B virus （HBV） infection disease status; we examined the expression of PD-1 on antigen specific CD8＋T cells in peripheral blood of patients with chronic hepatitis B （CriB） and acute exacerbation of hepatitis B （AEHB） infection. METHODS： The PD-1 level on CD8＋ T lymphocytes and the number of HBV specific CD8＋ T lymphocytes in patients and healthy controls （HCs） were analyzed by staining with pentameric peptide-human leukocyte antigen2 （HLA2） complexes combined with flow cytometry. Real-time quantitative polymerase chain reaction （PCR） was used to measure the serum HBV- DNA levels. RESULTS： The level of PD-1 expression on total CD8＋ T cells in CHB patients （13.86% ± 3.38%） was significantly higher than that in AEHB patients （6.80%± 2.19%, P 〈 0.01） and healthy individuals （4.63% ± 1.23%, P 〈 0.01）. Compared to AEHB patients （0.81% ± 0.73%）, lower frequency of HBV-specific CD8＋ T cells was detected in chronic hepatitis B patients （0.37% ± 0.43%, P 〈 0.05）. There was an inverse correlation between the strength of HBV-specific CD8＋ T-cell response and the level of PD-1 expression. Besides, there was a significant positive correlation between HBV viral load and the percentage of PD-1 expression on CD8＋ T cells in CriB and AEHB subjects （R = 0.541, P 〈 0.01）. However, PD-1 expression was not associated with disease flare-ups as indicated by alanine aminotransferase （ALT） levels （R = 0.066, P 〉 0.05）. CONCLUSION： Our results confirm previous reports that HBV specific CD8＋T-cell response in the peripheral blood is more intense in patients with AEHB than in chronic hepatitis B wlth persistent viral infection. Moreover, there is a negative correlation between the level of PD-1 and the intensity of virus specific CD8＋ T cell response.

Effects of six months losartan administration on liver fibrosis in chronic hepatitis C patients: A pilot study

AIM： TO evaluate the safety and efficacy of chronic administration of Iosartan on hepatic fibrosis in chronic hepatitis C patients.METHODS： Fourteen patients with chronic hepatitis C non-responders （n = 10）, with contraindications （n = 2） or lack of compliance （n = 2） to interferon plus ribavirin therapy and liver fibrosis were enrolled. Liver and renal function test, clinical evaluation, and liver biopsies were performed at baseline and after Iosartan administration at a dose of 50 mg/d during the 6 mo. The control group composed of nine patients with the same inclusion criteria and paired liver biopsies （interval 6-14 mo）. Histological activity index （HAI） with fibrosis stage was assessed under blind conditions by means of Ishak＇s score. Subendothelial fibrosis was evaluated by digital image analyses.RESULTS： The changes in the fibrosis stage were significantly different between Iosartan group （decrease of 0.5±1.3） and controls （increase of 0.89±1.27; P〈0.03）. In the treated patients, a decrease in fibrosis stage was observed in 7/14 patients vs 1/9 control patients （P〈0.04）. A decrease in sub-endothelial fibrosis was observed in the Iosartan group. No differences were found in HAI after Iosartan administration. Acute and chronic decreases in systolic arterial pressures （P〈0.05） were observed after the Iosartan administration, without changes in mean arterial pressure or renal function.CONCLUSION： Chronic AT-Ⅱ type 1 receptor （AT1R） blockade may reduce liver fibrosis in patients with chronic hepatitis C.

Occult hepatitis B virus infection and cryptogenic chronic hepatitis in an area with intermediate prevalence of HBV infection

AIM： To assess the possible role of occult HBV infection in the pathogenesis of chronic hepatitis in Iranian patients. METHODS： After exclusion of autoimmune, metabolic and viral etiologies, 104 consecutive adult patients with histologic and biochemical features of chronic hepatitis and negative HBsAg were enrolled in the study. Qualitative PCR with a sensitivity of 150 × 10^3 copies/L, using two primers for Pre-S and core regions was applied to measure presence of HBV DNA in serum of the patients. RESULTS： All 104 patients completed the study Qualitative HBV DNA was positive in two patients （1.9%） CONCLUSION： Occult HBV infection has negligible role in the pathogenesis of cryptogenic chronic hepatitis in Iranian patients.

Snapshot of HIV pathogenesis in China

Several reviews have focused on the nature of HIV infection and its spread in various geographical regions of China. In contrast, this review provides a comprehensive update on the prevalence of multiple HIV- 1 subtypes, consequent emergence of recombinant and novel forms of HIV- 1 in China, and the implications this may have on HIV diversity and the development of effective vaccines. In addition it also examines the dissemination of primary drug resistance in therapy naive patients, as well as co-infections with two other important viruses-hepatitis B and C. The main purpose of this review is to provide a current snapshot of HIV-1 pathogenesis in China and possibly shed some light on the future of HIV evolution, and potential challenges for future vaccine and anti-retroviral therapeutics against HIV strains in this area.

AIDS and associated malignancies

AIDS associated malignancies （ARL） is a major complication associated with AIDS patients upon irnmunosuppression. Chronically immunocompromised patients have a markedly increased risk of developing lymphoproliferative disease. In the era of potent antiretrovirals therapy （ARV）, the malignant complications due to HIV-1 infection have decreased in developed nations where ARV is administered, but still poses a major problem in developing countries where HIV-1 incidence is high and ARV is still not yet widely available. Even in ARV treated individuals there is a concern that the prolonged survival of many HIV-1 carriers is likely to eventually result in an increased number of malignancies diagnosed. Malignancies that were found to have high incidence in HIV-infected individuals are Kaposi＇s sarcoma （KS）, Hodgkin＇s disease （HD） and non-Hodgkin＇s lymphoma （NHL）. The incidence of NHL has increased nearly 200 fold in HIV-positive patients, and accounts for a greater percentage of AIDS defining illness in the US and Europe since the advent of HAART therapy. These AIDS related lymphomas are distinct from their counterparts seen in HIV- 1 seronegative patients. For example nearly haft of all cases of ARL are associated with the presence of a gamma herpesvirus, Epstein Barr virus （EBV） or human herpesvirus-8 （HHV-8）/Kaposi＇s sarcoma associated herpesvirus （KSHV）. The pathogenesis of ARLs is complex. B-cell proliferation driven by chronic antigenemia resulting in the induction of polyclonal and ultimately monoclonal lymphoproliferation may occur in the setting of severe immunosuppression.

New animal models for hepatitis C viral infection and pathogenesis studies

Hepatitis C virus （HCV） is a major cause of chronic liver disease, cirrhosis and hepatocellular carcinoma （HCC）. In man, the pathobiological changes associated with HCV infection have been attributed to both the immune system and direct viral cytopathic effects. Until now, the lack of simple culture systems to infect and propagate the virus has hampered progress in understanding the viral life cycle and pathogenesis of HCV infection, including the molecular mechanisms implicated in HCV-induced HCC. This clearly demonstrates the need to develop small animal models for the study of HCV-associated pathogenesis. This review describes and discusses the development of new HCV animal models to study viral infection and investigate the direct effects of viral protein expression on liver disease.

Adeno-associated virus mediated interferon-gamma inhibits the progression of hepatic fibrosis in vitro and in vivo

AIM:To investigate the effects of adeno-associated virus (AAV) mediated expression of human interferon-γ for gene therapy in experimental hepatic fibrosis in vitro and in vivo. METHODS: We constructed the recombinant AAV encoding human INF-γ (rAAV- INF-γ) and took the primary rat hepatic stellate cells and carbon tetrachloride induced rats as the experimental hepatic fibrosis model in vitro and in vivo. Immunocytochemistry analysis was used to reveal the expression of α-SMA, the marker protein expressed in hepatic stellate cells. The mRNA expression of TGF-β, TIMP-1, and MMP-13 were analyzed by RT-PCR method. In vivo study, the hydroxyproline content in liver and serum AST, ALT were also detected. RESULTS: In vitro study, AAV vector could mediated efficient expression of human INF-γ, which inhibit the activation of hepatic stellate cells, decrease the expression of α-SMA and mRNA of TIMP-1, TGF-β, with the MMP-13 unchanged. In vivo study, the histological examination revealed that rAAV- INF-γ could inhibit the progression of the hepatic fibrosis. In the rAAV-INF-γ induced group, the hydroxyproline content and serum AST, ALT level were decreased to 177±28 μg/g wet liver, 668.5±140.0, 458.4±123.5 U/L, compare with the fibrosis control group 236±31 μg/g wet liver, 1 019.1±276.3, 770.5±154.3 U/L, respectively (P<0.01). mRNA expression of TIMP-1 in the rAAV-INF-γ induced rat liver was decreased while no significant change was observed in TGF-β and MMP-13. CONCLUSION: All these results indicated that rAAV-INF-γ has potential effects for gene therapy of hepatic fibrosis, which could inhibit the progression of hepatic fibrosis.

Animal models for studying hepatitis C and alcohol effects on liver

Chronic consumption of ethanol has a dramatic effect on the clinical outcome of patients with hepatitis C virus (HCV) infection, but the mechanism linking these two pathologies is unknown. Presently, in vitro systems are limited in their ability to study the interaction between a productive wild-type HCV infection and chronic ethanol exposure. Mouse models are potentially very useful in dissecting elements of the HCV-ethanol relationship. Experiments in mice that transgenically express HCV proteins are outlined, as are experiments for the generation of mice with chimeric human livers. The latter models appear to have the most promise for accurately modeling the effects of chronic ethanol intake in HCV-infected human livers.

Different outcomes of nosocomial infection with hepatitis C virus from the same origin

The outcome of infection with hepatitis C virus （HCV） varies substantially from self-limiting infection to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma among the individuals. The mechanisms that determine the clearance or the persistence of HCV have not yet been clarified. Here, we experienced two cases of hospital-related infection with HCV from the same origin but with quite different outcomes. One case resolved after an episode of acute hepatitis, while the other case developed a chronic hepatitis although they were infected with HCV of the same origin. Although infected with the virus of the same origin, the clinical and virological courses were completely different. This suggests that host factors play a major role in conditioning the outcome of acute HCV infection.

Remission of bronchial asthma after viral clearance in chronic hepatitis C

A 53-year-old man with a history of blood transfusion at the age of 20 was admitted to our hospital because of liver dysfunction. He had bronchial asthma when he was 18 years old, which naturally resolved within 2 years. However, his bronchial asthma recurred at the age of 45 and was treated with oral theophylline. He was diagnosed as having chronic hepatitis C based on the histological and clinical findings, and then interferon (IFN) therapy was administered. The frequency of bronchial asthma attack was gradually decreasing after IFN therapy with marked improvement of hypereosinophilia. He achieved sustained viral response (SVR) and his bronchial asthma did not worsen even after the cessation of IFN. Hepatitis C virus (HCV) infection and IFN therapy were considered in the remission of asthma in this case. HCV infection could be the cause of bronchial asthma, especially in patients with late appearance of asthma.

Three Cases of Reinfection Syphilis

These three cases of reinfection syphilis all had complete medical histories, clinical symptoms, and laboratory records of prior primary or secondarysy philis infection. The author held that the main reason for reinfection was failure of diagnosis and treatment of sex partners.

中国大陆乙脑病原学研究的历史与现状

乙脑病毒为黄病毒科病毒,通过蚊虫叮咬而感染人畜动物,引起巨大公共卫生负担。我国自20世纪40年代即分离到乙脑病毒,此后在病毒分离、传播媒介、疫苗研发等方面开展大量研究,取得极大进展。本文在回顾我国乙脑病毒研究历史和研究现状基础上提出我国乙脑病毒研究存在的问题以及今后的研究内容等,以推动我国乙脑病毒研究进一步发展。