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Abstract Background Epidemiological investigations, detections and vaccines of hepatitis E (HE) have been paid a focus of attention in prior studies, while studies on clinical features and risk factors with a large number of sporadic HE patients are scarce. Results Sporadic HE can occur throughout the year, with the highest incidence rate in the first quarter of a year, in central of China. Of the 210 patients, 85.2% were male, and the most common clinical symptoms were jaundice (85.7%), fatigue (70.5%) and anorexia (64.8%). Total bilirubin (TBil), blood urea nitrogen (BUN), and international normalized ratio (INR) were found as major risk factors for death of HE patients. There was an overall mortality of 10%, and the mortality in the cirrhotic and non-cirrhotic group was 25% and 6.47%, respectively. Moreover, hepatitis E virus (HEV) infected patients with liver cirrhosis had a higher mortality and incidence of complications. Conclusions TBil, BUN, and INR are major risk factors of mortality for HE. Liver cirrhosis can aggravate HE, and lead to a higher mortality. HEV infection can cause decompensation in patients with cirrhosis, as evidenced by a worsening Child-Pugh score.

Schistosomiasis is a dangerous infectious disease, and advanced schistosomiasis is a serious harm to people's lives and health. Anthelmintic treatment alone cannot effectively prevent the development and progression of advanced schistosomiasis, especially liver fibrosis. This article introduces the pathogenesis, clinical manifestations, and integrated traditional Chinese and Western medicine therapy for advanced schistosomiasis. It is pointed out that integrated traditional Chinese and Western medicine therapy is an effective approach to the control of disease progression in patients with liver fibrosis. [ABSTRACT FROM AUTHOR]

To construct and identify the specific interference vector for second mitochondria - derived activator of caspase (SMAC) gene in mice and perform lentiviral packaging. Methods According to the SMAC gene sequences in mice, three small interfering RNAs (siRNAs) ( siRNA1, siRNA2, and siRNA3 ) and one negative control sequence (siRNAn) were designed and synthesized, and mouse hepatocytes were transfected with the above siRNAs using Lipofectamine 2000. The inhibitory effects of these siRNAs on SMAC mR-NA expression were evaluated by real - time PCR, and the optimal siRNA was screened out accordingly. Oligo DNA was synthesized based on the optimal siRNA and then connected to GV115 vector to obtain recombinant interference plasmid. The candidate clones were identified by PCR and sequenced. The recombinant interference plasmid, as well as pHelper 1. 0 and pHelper 2. 0, was used to transfect 293T cells for lentivirus packaging. Then, cell supernatants were collected and concentrated, and the lentiviral titer was determined by gradient dilution. Comparison between groups was made by analysis of variance, and multiple comparisons were made by SNK - q test. Results The three siRNAs had different inhibitory effects on SMAC mRNA expression in hepatocytes; siRNA1 showed the strongest inhibitory effect, with an inhibition efficiency of 70. 3%. Based on siRNA1, the oligo DNA was successfully synthesized and correctly connected to the lentiviral vec-tor, as proved by sequencing. The lentiviral titer was 6 X 10 TU/ml, as determined by gradient dilution. Conclusion The recombinant lentivirus that inhibits SMAC expression in mice has been constructed successfully, laying the foundation for further studies on the role of SMAC gene in liver failure. [ABSTRACT FROM AUTHOR]

Background: Mammalian target of rapamycin (mTOR) inhibitors, temsirolimus and everolimus, are currently approved for the treatment of several malignancies. Hematological toxicities have been reported with these drugs, but overall incidence and relative risk remains undefined. We perform an up-to-date meta-analysis to determine the incidence and risk of hematologic toxicities associated with mTOR inhibitors. Methods: Several databases were searched, including PubMed, Embase and Cochrane databases. Eligible studies included prospective phase II and III trials of temsirolimus and everolimus with adequate safety data profile reporting anemia, leucopenia, neutropenia or thrombocytopenia. Overall incidence rates, relative risk (RR), and 95% confidence intervals (CI) were calculated by using either random effects or fixed effects models according to the heterogeneity of included studies. Results: A total of 5436 patients with a variety of solid tumors from 26 clinical trials were included for the metaanalysis. The overall incidences of mTOR inhibitor associated all-grade and high-grade hematologic toxicities were, respectively: anemia – 38.8% and 7.5%; leucopenia – 19.6% and 1.8%; neutropenia – 14.9% and 5.6%; thrombocytopenia – 33.1% and 3.6%. Compared to placebo/control arms, mTOR inhibitors were associated with a significantly increased risk of all-grade (RR 2.05, 95% CI: 1.52–2.77; p50.001) and high-grade anemia (RR 1.57, 95% CI: 1.20–2.05; p=0.001), all-grade (RR 6.03, 95% CI: 2.76–13.14; p50.001) and high-grade thrombocytopenia (RR 2.73, 95% CI: 1.87–3.99; p50.001). Additionally, a non-significantly increased risk of all-grade leucopenia (RR 1.46, 95% CI: 0.66–3.23; p=0.34) and neutropenia (RR 1.77, 95% CI: 0.80–3.93; p=0.16) was observed in the mTOR inhibitor group, while the risk of high-grade leucopenia (RR 0.53, 95% CI: 0.31–0.90, p=0.019) and neutropenia (RR 0.96, 95% CI: 0.62–1.51; p=0.87) did not increase. Similar results were also observed in sub-group analysis according to mTOR inhibitor based regimens. Conclusions: The use of mTOR inhibitors is associated with a significant increase in the risk of developing all-grade and high-grade anemia and thrombocytopenia compared with placebo/control arms. [ABSTRACT FROM AUTHOR]

Anti-HEV IgM is a diagnostic for recent or ongoing HEV infection. However, some patients with acute hepatitis E (AHE) negative for anti-HEV IgM in acute period were often observed in clinical practice. In this study, we constructed the anti-HEV IgA indirect ELISA assay to evaluate the significance of anti-HEV IgA. The specificity of anti-HEV IgA was 99.6%. Among 245 AHE patients, 84 samples from 84 patients were positive for HEV RNA. The positive rate of anti-HEV IgA, anti-HEV IgM and anti-HEV IgG in 84 samples positive for HEV RNA was 96.3, 97.6, and 88.1%, respectively, and no sample was negative for anti-HEV IgA and anti-HEV IgM simultaneously. Among 245 AHE patients, we found nine samples collected from nine patients in acute period were negative for anti-HEV IgM but positive for anti-HEV IgA and two samples were positive for HEV RNA. Detection of anti-HEV IgA can be a useful supplement for diagnosis of acute HEV infection especially in patients negative for anti-HEV IgM. [ABSTRACT FROM AUTHOR]

In order to determine the replication sites of hepatitis C virus, the in situ hybridization and immunohistochemical technique using digoxin-labeled 531bp plus-strand and minus-strand HCVRNA probes were employed to detect HCVRNA in the liver tissues, bone marrow mononuclear ceils and peripheral blood mononuclear cells (PBMCs) from the patients with chronic hepatitis C, and in HCV transfected COS cells. The results showed that both plus-strand and minusstrand HCVRNA were detected in 80% of liver tissues (4/5). Plus-strand HCVRNA could be detected in 90% of PBMCs and bone marrow mononuclear cells (18/20), minus-strand HCVRNA in 25% of PBMCs. In HCV transfected COS cells, plus-strand HCVRNA distributed evenly in 20% cellular nuclei and cytoplasms. No minus-strand HCVRNA was detected in the bone marrow mononuclear cells and HCV transfeeted COS cells. The positive signal appeared in more cells when the liver tissues, PBMCs and marrow mononuclear cells were hybridized by plus-strand probes than when hybridized by minus-strand probes. Our results suggested that the hepatocytic cytoplasms and PBMC cytoplasms were the replication sites of HCV, but the marrow mononuclear cells were not the replication sites of HCV although they were infected by HCV. HCV infection might be accounted for'the pathogenesis of chronic hepatitis and relapse of hepatitis C after liver transplantation. [ABSTRACT FROM AUTHOR]

The pathogenesis of acute liver failure has not been fully elucidated. The present study investigated the effects of the serum from patients with hepatitis E virus (HEV)-related acute liver failure on human liver cell survival and apoptosis, and evaluated the protective effects of anti-lipopolysaccharide(LPS) antibody recognizing core polysaccharide against acute liver failure serum-induced apoptosis. Serum was collected from patients with HEV-related acute liver failure. The levels of endotoxin (LPS) in the serum were measured using a quantitative tachypleus amebocyte lysate endotoxin detection kit with a chromogenic endpoint. Serum with a mean concentration of LPS was incubated with L02 human liver cells and the rate of apoptosis was detected by flow cytometry. The apoptotic rate was also evaluated in liver cells incubated with antibody and the HEV-related acute liver failure serum. The results indicated that the concentration of LPS in the serum of patients with HEV-related acute liver failure was 0.26±0.02 EU/ml, which was significantly higher than that of the control group (P<0.05). The rate of apoptosis in the human liver cells induced by acute liver failure serum was 5.83±0.42%, which was significantly increased compared with that in the cells treated with the serum of healthy individuals (P<0.05). The apoptotic rate of the cells incubated with antibody and the acute liver failure serum was 5.53±0.51%, which was lower than that of the cells incubated with acute liver failure serum alone (P>0.05). These results indicate that the serum of patients with HEV-related acute liver failure induces the apoptosis of human liver cells. LPS may be directly involved in the apoptosis of human liver cells. Moreover, the presence of the antibody did not significantly reduce the level of apoptosis of liver cells exposed to HEV-related acute liver failure serum.

Objective: To study the relationship between the gene polymorphism of HLA-DRB(1) and tumor necrosis factor (TNF)alpha with the genetic susceptibility to cirrhosis., Methods: The gene polymorphism of DRB(1) and TNF alpha of 106 cases of cirrhosis due to HBV and 108 controls were detected by means of polymerase chain reaction-sequence specific primer and RFLP techniques., Results: The frequency of DRB(1) * 120X and TNF2/1 was increased in the patients as compared with the controls (35.9% vs 11.1%, P < 0.001, 19.8% vs 10.2%, P < 0.05 respectively), The frequency of DRB(1) * 150X allele was reduced in the patients as compared with the controls (13.2% vs 30.6%, P < 0.05). It is suggested that the gene polymorphism of HLA-DRB(1) and TNF alpha to be associated with genetic susceptibility to cirrhosis. Cross analysis showed that DRB(1) * 120X allele was more strongly associated with genetic susceptibility to cirrhosis than TNF2 allele., Conclusions: The genetic susceptibility to cirrhosis is associated with DRB(1) * 120X and TNF2 allele, persons with DRB(1) * 120X and TNF2 allele have an increased risk for the liver cirrhosis occurrence; DRB(1) * 120X allele may be a susceptibility gene to liver cirrhosis and DRB(1) * 150X allele may be a protective gene from liver cirrhosis.