Hepatitis: Chen J

Orsini J, Nadkarni A, Chen J, Cohen N. · Division of Critical Care Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY 10467-2490, USA. · Am J Health Syst Pharm. · Pubmed #19420309 No free full text.

Abstract: PURPOSE: A case of propofol infusion syndrome in a patient with respiratory failure and sepsis is reported. SUMMARY: A 36-year-old Hispanic woman was admitted to the medical intensive care unit for treatment of respiratory failure and sepsis, likely secondary to pneumonia. Her medical history included human immunodeficiency virus infection and chronic hepatitis C virus infection. She was intubated and placed on mechanical ventilation. Empirical i.v. antimicrobial therapy was initiated with vancomycin, moxifloxacin, piperacillin-tazobactam, trimethoprim-sulfamethoxazole, and micafungin, along with corticosteroids and vasopressors. Propofol 1.5 mg/kg per hour i.v. and midazolam i.v. were initiated for sedation, but the dosages of both propofol and midazolam needed to be increased due to persistent agitation. On hospital day 7, the patient developed a morbilliform rash on her neck, shoulders, and chest and multiple abnormal laboratory test values, including elevated levels of alanine transaminase, aspartate transaminase, amylase, lipase, creatine kinase, and triglycerides. Serial electrocardiograms revealed sinus tachycardia. Computed tomography of the abdomen showed hepatomegaly with fatty infiltration of the liver, no gallstones, and a normal pancreas. I.V. phenobarbital was added for sedation, and propofol was tapered and discontinued on the same day. The patient responded adequately to phenobarbital maintenance therapy and was eventually weaned off all other sedatives. The patient's laboratory test values returned to normal within 72 hours after discontinuation of the propofol infusion, and the rash and tachycardia resolved. CONCLUSION: Propofol infusion syndrome developed in a patient with respiratory failure and sepsis after a prolonged infusion of high-dose propofol.

Wang RX, Guo Y, Yang CH, Song Y, Chen J, Pang FS, Lei SP, Jia XM, Wen JY, Shi CY. · Shenyang Center for Disease Control and Prevention, Shenyang 110031, China. · World J Gastroenterol. · Pubmed #14716846 links to  free full text

Abstract: AIM: To evaluate if HB vaccination can yield a booster effect on the anti-HBs level of those naturally acquired HBV positive markers. METHODS: Sera were collected from 1399 newly enrolled university students aged between 18-20 years at the entrance medical examination in 2001. Forty-four students (28 males and 16 females) with positive serum anti-HBs and anti-HBc markers served as an observation group and another 44 students (24 males and 20 females) without any HBV markers as the control. HB vaccination was given to all the students without positive serum HBsAg according to 0, 1, 6 month regimen and the peripheral venous blood was sampled from those of both observation and control groups for anti-HBs detection one month after the second and third doses. Anti-HBs levels were measured by ELISA. RESULTS: The seroconversion rate of anti-HBs in the control group was 100% after the second dose, but the geometric mean titers (GMTs) were low. The tendency of serum anti-HBs changes after the 3rd dose was completely different between the two groups. Although more than half of those with positive anti-HBs and anti-HBc showed a mild increase of anti-HBs levels after the 2nd boosting dose (mean anti-HBs level was 320:198 mIU), but the increase of serum anti-HBs titer was much smaller than that in the control group. The averages of their initial serum anti-HBs levels and the levels after the 2nd and 3rd doses were 198, 320 and 275 mIU respectively. All the subjects from the control group had an obvious increase in their serum anti-HBs levels which was nearly 4 times the baseline level (302:78 mIU). CONCLUSION: HB vaccination can not enhance anti-HBs levels in those with positive serum anti-HBs and anti-HBc markers.

Wang RX, Boland G, Guo Y, Lei SP, Yang CH, Chen J, Tian J, Wen JY, Du KH, van Hattum J, de Gast GC. · Shenyang Center for Disease Control and Prevention, Shenyang 110031, Liaoning Province, China. · World J Gastroenterol. · Pubmed #14562411 links to  free full text

Abstract: AIM: To determine whether or not a low dose of HB vaccine can be effectively used in the rapid vaccination. METHODS: Rapid vaccination (0, 1, 2 months) with low dose (5 microg) or routine dose (10 microg) HB vaccine was studied in 250 subjects (130 school children and 120 university students). Serum from all the participants was tested for HBsAg, anti-HBs and anti-HBc at 1, 3 and 7 months after the first dose of vaccination and all subjects were serum HBV marks negative before the vaccination. Non-responders to a complete initial vaccination from university students were given an additional vaccination with 10 microg of HB vaccine and their serum anti-HBs was tested again one month later. RESULTS: One month after the third dose of vaccination (third month) sero-conversion rates and geometric mean titer (GMTs) were significantly (P<0.01) higher in the routine dose (resp. 89% and 106.8) than in the low dose group (resp. 72% and 59.5). Sero-conversion rates and GMTs were maintained stable for another 4 months in both groups. After an additional vaccination to non-responders with 10 microg HB vaccine, 17/23 subjects (13/15 from those vaccinated with 5 microg vaccine and 4/8 from those vaccinated with 10 microg vaccine) became anti-HBs positive, yielding similar sero-conversion rates for both dose groups. CONCLUSION: Higher sero-conversion rates and GMTs were reached in those vaccinated with 10 microg HB vaccine than in those vaccinated with 5 microg HB vaccine after a complete vaccination with a 0, 1, 2 month scheme. But the subjects vaccinated with 5 microg vaccine can also reach the similar sero-conversion rate after an additional vaccination.

Liu H, Ma J, Meng Z, Zhang Y, Han C, Zhang Y, Zhao H, Liu Y, Xing Z, Chen J, Jia Z, Xia G, Cao H, Liu C, Li Z. · Hebei Provincial Sanitation and Anti-epidemic Station, Baoding, 071000, China. · Zhonghua Yi Xue Za Zhi. · Pubmed #11953126 No free full text.

Abstract: OBJECTIVE: To understand the protective efficacy of China-made recombinant hepatitis B vaccine expressed by transgenic Chinese hamster ovary cell line among newborns. METHODS: 2 969 newborns in seven townships in Zhengding County, Hebei Province, were vaccinated with 10 microgram x 3 doses of China-made recombinant hepatitis B vaccine expressed by transgenic Chinese hamster ovary cell line according to the 0 - 1 - 6 month schedule from 1 January 1997 to 31 August 1999. The newborns were to be vaccinated with the first dose within 24 hours after they were born. 1906 serum samples were selected in April 2000 to detect the hepatitis B infection markers, including HBsAg, HBsAb and HbcAb by RIA kits. RESULTS: 2 783 of the 2 969 newborns (93.74%) were vaccinated with three doses, 2 833 of them (95.42%) were vaccinated with the first dose within 24 hours after they were born. The anti-HBs positive rate was 98.25% (S/N >/= 2.1) or 94.26% (S/N >/= 10.0), and the geometric mean titer (GMT) value of antibody was 77.64 within the first year after the whole course vaccination. Then the antibody level decreased gradually with the lapse of time. The HBsAb positive rate was 92.31% (S/N >/= 2.1) or 68.96% (S/N >/= 10.0), and GMT value was 22.86 within the third year after vaccination. The HBsAg positive rates remained less than 1%, the HBcAb positive rates and HBV infection rates remained 1% approximately 3% within 3 years after vaccination. CONCLUSION: The protective efficacy of China-made recombinant hepatitis B vaccine is satisfactory.

Wang X, Ma J, Zhang Y, Zhang Y, Han C, Xing Z, Chen J, Zhang Y, Zhao S, Gu H, Xu Z. · Shanghai Medical University, Shanghai 200032, China. · Zhonghua Liu Xing Bing Xue Za Zhi. · Pubmed #11860772 No free full text.

Abstract: OBJECTIVE: To study the immunologic effect of live attenuated hepatitis A vaccine (H(2) Strain, 10(7.0)TCID(50)) after booster and to compare with the results of 1 dose live attenuated hepatitis A vaccine (H(2) Strain, 10(7.0)TCID(50)). METHODS: 42 susceptibles with negative anti - HAV were selected in Zhengding, Hebei province. Each subject received 3 doses live attenuated hepatitis A vaccine at 0, 2, 6 months and was bled at 1, 2, 6, 7, 9, 12 months after vaccination. RESULTS: The seroconversion rate at 1 month after the first dose was 81.4% and reached 100% after the second dose. GMT arrived the peak 2,739 mIU/ml at one month after the third dose, before stared declining. The seroconversion rate kept 100% at 12 months after the first dose, but GMT decreased to 979 mIU/ml. CONCLUSION: The first dose worked as the base of boostering. A booster dose of live attenuated hepatitis A vaccine could induce secondary immune response well. The immunologic effect after booster dose could match the effect with inactivated vaccine and was better than the results of 1 dose live attenuated hepatitis A vaccine. The program seemed to be useful to the protective effect and the immuno - persistence.

Yin P, Wan D, Zhao C, Chen J, Zhao X, Wang W, Lu X, Yang S, Gu J, Xu G. · CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China. · Mol Biosyst. · Pubmed #19603122 No free full text.

Abstract: Liver cirrhosis and hepatocellular carcinoma (HCC) are fatal sequelaes of chronic hepatitis B in China. The sera from HCC and cirrhosis were profiled by rapid resolution liquid chromatography coupled with quadrupole time-of-flight (Q-TOF) mass spectrometry. Reversed-phased (RP) liquid chromatography and hydrophilic interaction chromatography (HILIC) were used for the data acquisition. The normalized and combined data were handled by chemometric analysis, and the combination proved to be effective and reliable for the orthogonal projection to latent structures (OPLS) analysis. Metabonomic profiles and the potential biomarkers were found based on the OPLS models. Shared and unique structure (SUS) plots were used for the evaluation of the potential biomarkers. Glycocholic acid, glycochenodeoxycholic acid, taurocholic acid and taurochenodesoxycholic acid were found to be potential biomarkers related to liver cirrhosis, while dihydrosphingosine and phytosphingosine were potential diagnostic biomarkers of HCC. The other identified metabolites were considered as common potential biomarkers for the two liver diseases. Correlation networks based on these metabolites were also built for the systemic understanding of these diseases and the possible biological implications are discussed. This metabonomic approach may provide insight into discovery and identification of new diagnostic biomarkers for liver cancer and associated diseases.

Chen J, Han JH, Liu C, Yu RH, Li FZ, Li QF, Gong GZ. · Liver Diseases Center, Second Xiangya Hospital, Central South University, Changsha, China. · Hepatobiliary Pancreat Dis Int. · Pubmed #19502165 links to  free full text

Abstract: BACKGROUND: Chronic severe hepatitis B patients often have limited survival. This investigation aimed to evaluate the short-term effects of nucleoside analog therapy on chronic severe hepatitis B. METHODS: We retrospectively, randomly collected the data of 129 chronic severe hepatitis B patients: 55 were treated with entecavir, and the remaining 74 were not treated with nucleoside analogues. RESULTS: No significant difference in short-term survival rate was found between the group treated with entecavir and that treated without nucleoside analogues. Although entecavir greatly reduced HBV replication in different periods of therapy (P<0.001), the model for end-stage liver disease (MELD) score and liver function (alanine aminotransferase, albumin, bilirubin, prothrombin time) showed no significant change. No significant differences were found in MELD scores and liver function in patients with different HBV DNA levels (< or =10(4) copies/ml, >10(4) to <10(6) copies/ml, > or =10(6) copies/ml). Nor correlation was observed between HBV DNA levels and MELD scores in different periods of therapy (P>0.05). The HBV DNA levels of patients who survived for over 3 months or less than 3 months were not significantly different either. However, the MELD score and parameters of liver function (albumin, bilirubin, prothrombin time) were different between the two groups (P<0.05). CONCLUSION: These results suggest that short-term suppression of HBV replication may not slow down the progression of liver failure in patients with chronic severe hepatitis B.

Li X, Tian J, Wu J, He Q, Li H, Han F, Li Q, Chen Y, Ni Q, Chen J. · Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of China. · Clin Ther. · Pubmed #19446147 No free full text.

Abstract: BACKGROUND: When receiving immunosuppressive therapy, patients with idiopathic nephrotic syndrome who are also carriers of hepatitis B virus (HBV) surface antigen (HBsAg) are at risk for reactivation of HBV. OBJECTIVE: This study compared the effectiveness and tolerability of a standard-dose prednisone regimen with those of the combination of mycophenolate mofetil (MMF) and a lower prednisone dose for the treatment of idiopathic nephrotic syndrome characterized by minimal-change nephropathy or slight mesangial proliferative glomerulonephritis in Chinese adults who were also carriers of HBsAg, a combination here termed MSNS-HBV. METHODS: This was a prospective, open-label cohort study in Chinese adults with MSNS-HBV. Patients were self-assigned to 1 of 2 treatment groups: the standard prednisone regimen of 1 mg/kg daily or oral MMF 0.5 to 1.0 g BID combined with the lower prednisone dose of 0.5 mg/kg daily. The planned duration of treatment was 36 weeks, with an additional 60 weeks of follow-up. The primary outcome measures were rates of complete remission of idiopathic nephrotic syndrome (a decrease in daily proteinuria to within the normal range [<0.3 g]) and rates of HBV reactivation (detectable serum HBV DNA). Secondary outcome measures included relapse rates (>1+ albuminuria on dipstick urinalysis on 3 consecutive days), alanine aminotransferase (ALT) elevations (>50 U/L), use of lamivudine 100 mg/d (added if HBV DNA titers reached >or=10(5) copies/mL), and adverse effects. RESULTS: The intent-to-treat population included 41 patients (22 prednisone, 19 MMF). In patients who completed the study, rates of complete remission after 24 weeks of treatment were 78.9% (15/19) in the prednisone group and 76.5% (13/17) in the MMF group; 2 and 3 patients in the respective groups had a partial remission, and 2 and 1 patient had no response. HBV reactivation occurred in 63.6% (14/22) and 36.8% (7/19) of patients (P = 0.047). The only significant difference in the study was in the probability of HBV reactivation between groups (P = 0.043, log-rank test). During follow-up, at least 1 relapse occurred in 46.7% (7/15) and 30.8% (4/13) of patients. Elevations in ALT were observed in 36.4% (8/22) and 26.3% (5/19) of patients, and the addition of lamivudine was required in 40.9% (9/22) and 21.1% (4/19) of patients. The most frequent adverse effects in both groups were infections (27.3% and 26.3%), followed by gastrointestinal symptoms (13.6% and 21.1%). Two MMF patients developed leukopenia. One patient in the prednisone group discontinued treatment because of severe hepatitis, and 1 patient in the MMF group discontinued because of severe pulmonary infection. CONCLUSIONS: Among the adult Chinese patients with MSNS-HBV who completed this study, there were no significant differences in remission rates of idiopathic nephrotic syndrome between the standard prednisone regimen and the combination of MMF and a reduced prednisone dose. Rates of HBV reactivation, however, were significantly lower in the combination-therapy group.

Li Y, Hao B, Kuai X, Xing G, Yang J, Chen J, Tang L, Zhang L, He F. · State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China. · Mol Cell Biochem. · Pubmed #19234677 No free full text.

Abstract: Hepatitis C virus (HCV) is a major cause of liver disease. However, the detailed mechanism underlying hepatocyte infection with HCV is not yet completely understood. We previously identified a novel C-type lectin--LSECtin predominantly expressed on liver sinusoidal endothelial cells. Here we demonstrate that LSECtin can interact with two HCV receptors, DC-SIGNR and CD81, through its central ectodomain. Furthermore, cells expressing LSECtin specifically can be attached by the naturally occurring HCV in the sera of infected individuals. This binding was found to be mediated by the HCV E2 glycoprotein and could be efficiently inhibited by EGTA but not by mannan treatment. The present study suggests that LSECtin interaction with DC-SIGNR might contribute to HCV binding to liver sinusoidal endothelial cells.

Dong L, Zuo L, Xia S, Gao S, Zhang C, Chen J, Zhang J. · State Key Laboratory of Pharmaceutical Biotechnology, Department of Biochemistry, Nanjing University, Nanjing, China. · J Gene Med. · Pubmed #19189285 No free full text.

Abstract: BACKGROUND: Fulminant liver failure can cause extreme mortality due to the lack of effective and targeting therapeutics for the disease. Novel therapeutics using antisense technology require an efficient and safe delivery system with Kupffer cell targeting ability. METHODS: We explored the capacity of galactosylated low molecular weight chitosan (GLC) to efficiently mediate the antisense oligonucleotide (ASO) TJU-2755 into Kupffer cells, enhance the effect of the oligonucleotides on the suppression of tumor necrosis factor (TNF)-alpha and prolong the active time of the antisense drug in vivo. The protective and therapeutic effect of ASO/GLC in the animal model of D-galactosamine/lipopolysaccharide-induced fulminant hepatitis was tested. RESULTS: ASOs delivered by GLC were concentrated in Kupffer cells and more potent in reducing the expression of TNF-alpha mRNA, as well as reducing serum TNF-alpha levels. Furthermore, the ASO/GLC complex successfully rescued animals from fulminant hepatitis and mortality. Compared to naked ASO, the complex notably reduced the dose administrated in animals and prolonged its effectiveness. A single dose of 5 mg ASO per kg body weight achieved a satisfactory effect after 5 days, and 20 mg ASO per kg body weight preserved 70% of the effect after more than 2 weeks. Its efficacy was affirmed through both pretreatment and therapeutic use after liver damage had begun. CONCLUSIONS: Inhibiting TNF-alpha expression in the liver by this strategy represents a novel therapeutic approach that may be valuable for the treatment of some inflammation-related liver diseases.

Tang XH, Gao J, Chen J, Xu LZ, Tang YH, Zhao XN, Michael L. · Jiangsu Provincial Key Laboratory of Coastal Wetland Bioresources and Environmental Protection, Yancheng Teachers' College, 50 Kaifang Road, Yancheng 224002, PR China. · J Ethnopharmacol. · Pubmed #18948181 No free full text.

Abstract: AIM OF THE STUDY: Limonium sinense (Girard) Ktze is a Chinese folk medicine used to treat fever, hemorrhage, hepatitis, and other disorders. The present research focused on the protective effects of L. sinense extracts (LSE) against liver damage. MATERIALS AND METHODS: In this study the extract from the root of Limonium sinense was used. Aminotransferase activity detection, electron microscopy, mitochondrial function evaluation, RT-PCR and western blot were used to evaluate the hepatoprotection of LSE in LPS/d-GalN-intoxicated mice. RESULTS: Pretreatment with 100, 200 or 400mg/kg LSE significantly blocked the increase in both serum aspartate aminotransferase (sAST) and serum alanine aminotransferase (sALT) levels induced by treatment with LPS plus d-GalN (LPS/d-GalN). Ultrastructural observation by electron microscopy showed reduced hepatocyte nuclear condensation and less lipid deposition. The decrease in both the mitochondrial membrane potential (14.6%) and sensitivity to mitochondrial swelling induced by Ca(2+) (45.9%) observed in the liver of LPS/d-GalN-treated mice were prevented by pretreatment with LSE. In addition, different doses of LSE increased both the transcription and the translation of voltage-dependent anion channels (VDAC), which was down-regulated by LPS/d-GalN treatment. CONCLUSIONS: In summary, LSE protects livers against LPS/d-GalN-induced damage, possibly by mitochondrial mechanisms related to increased expression of VDAC.

Chen J, Wang Z, Guo Y, Peng J, Sun J, Ahmed CS, Zhou Y, Hou J. · Hepatology Unit and Department of Infectious Diseases, Nanfang Hospital, Nanfang Medical University, Guangzhou 510515, China. · Antiviral Res. · Pubmed #18948141 No free full text.

Abstract: Hepatitis B surface antigen (HBsAg) loss under antiviral therapy is rare in chronic hepatitis B patients and the dynamics of serum HBsAg in these patients are not available. The changes in serum HBsAg following treatment with adefovir (n=31) or peg-interferon-alpha-2a (n=23) were studied in hepatitis B e-antigen (HBeAg) positive chronic hepatitis B patients. Abbott Architect HBsAg assay was used to quantify serum HBsAg. HBsAg levels were significantly decreased during the first 12 weeks of treatment with median change of -397.0 IU/ml and -555.4 IU/ml, respectively for adefovir and peg-interferon-alpha-2a (p=0.005 and 0.001, respectively). Beyond 12 weeks, no further significant HBsAg reductions were found even in patients with sustained viral replication inhibition in either group. Three distinct patterns of HBsAg changes were observed in most patients in both treatment groups: biphasic pattern (rapid HBsAg reduction from baseline to week 12); assurgent pattern (higher HBsAg level at week 12 than at baseline); and wavy pattern (HBsAg reduction from baseline to week 12, followed by relapse at week 24 or week 28). These results might offer insights into the possible mechanism(s) underlying the unusual occurrences of HBsAg loss under antiviral therapy.

Majeed TA, Wai CT, Rajekar H, Lee KH, Wong SY, Leong SO, Singh R, Tay KH, Chen J, Tan KC. · Asian Center for Liver Diseases and Transplantation, Singapore. · Transplant Proc. · Pubmed #18929781 No free full text.

Abstract: Living-donor liver transplantation (LDLT) is an effective treatment for patients with unresectable hepatocellular carcinoma (HCC). However, it remains controversial whether expanded listing criteria can be used for LDLT. We aimed to review results of LDLT for patients with HCC at our center. Patients with HCC were accepted for LDLT if there was no extrahepatic spread on computed tomography (CT) and positron emission tomography CT scan. Transarterial chemoembolization was performed before LDLT to control the tumors. Sirolimus or everolimus was used as part of the immunosuppressive protocol for all patients. Over the last 6 years, 35 of the 102 (34%) LDLT were performed at our center for HCC. Age (mean +/- SEM) was 55.3 +/- 1.3 years; 28 patients (80%) were men. Eight (23%) had LDLT performed in 2002 or 2003 (period 1), and 27 (77%) in 2004 to 2007 (period 2). Eleven (31%) were within and 23 (69%) were outside the Milan criteria. After 583 +/- 76 days follow-up, nine (25%) died, three of recurrent HCC. Three-year survival was significantly better in period 2 than in period 1 (90% vs 13%; P < .001). Although the 3-year survival for those within Milan criteria was better than those outside Milan criteria, the difference did not reach statistical significance (86% vs 57%; P = .26). Six (17%) had HCC recurrence, of whom five died. We concluded that reasonable medium-term survival can be obtained for patients with HCC. The experience level of the transplant team seemed to be the most important predictor of patient outcome.

Brodsky SV, Facciuto ME, Heydt D, Chen J, Islam HK, Kajstura M, Ramaswamy G, Aguero-Rosenfeld M. · Department of Pathology, Renal and Transplant Pathology Laboratory, Ohio State University, Columbus, OH 43210, USA. · J Gastrointestin Liver Dis. · Pubmed #18836617 links to  free full text

Abstract: BACKGROUND & AIMS. Microparticles are small membrane vesicles released from the cell plasma membrane, particularly in cell stress, apoptosis and altered cellular viability. Hepatocellular carcinoma (HCC) is a hypervascular neoplasm with high levels of apoptosis and necrosis. We investigated the levels of circulating microparticles of both tumor and endothelial origins in liver transplant patients with hepatitis C (HepC) cirrhosis with and without HCC and compared them with healthy people and patients with partial hepatectomy. METHODS. Using immunolabeling of microparticles of different origin and flow cytometry-based enumeration of microparticles, the levels of circulating microparticles were studied in 8 patients with HepC and 8 patients with both HepC and HCC before and within two weeks after the transplant. RESULTS. The initial levels of circulating microparticles were increased in patients with HepC and HCC as compared to patients with HepC alone. They were also increased in liver transplant patients as compared to patients with partial hepatectomy or healthy people. Levels of circulating microparticles were dynamically changing after the transplant, showing an initial increase with a subsequent decrease by the end of the second week after surgery. In some patients with a complicated clinical outcome, the levels of microparticles were continuously increasing after the surgery. CONCLUSION. The levels of circulating microparticles of endothelial and hepatic origin in liver transplant patients dynamically change after surgery and correlate with the clinical outcome. Perspectively, the levels of circulating microparticles may be used in clinical practice as a marker of the functional status of the transplanted liver.

Tang H, Huang Y, Chen J, Yu C, Huang AL. · Key Laboratory of Molecular Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing, China. · Intervirology. · Pubmed #18753794 No free full text.

Abstract: OBJECTIVE: To identify T-cell intracellular antigen 1 (TIA-1) interacting with the posttranscriptional regulatory element (PRE) of hepatitis B virus (HBV), and reveal TIA-1 function on HBV gene expression. METHODS: In order to demonstrate TIA-1 binding to PRE, electrophoretic mobility shift and RNA and protein pull-down assays were used. The pDM138-PRE reporter system, HepG2.2.15 cell line and HBs-PRE transient expression cells were adopted to identify TIA-1 function in the HBV life cycle. RESULTS: TIA-1 could directly bind to PRE RNA. The functional binding region of TIA-1 was identified. Functional analysis indicated that TIA-1 could dose-dependently inhibit PRE function in pDM138-PRE system. Down-expression of HBs antigen induced by TIA-1 was detected both in the HepG2.2.15 cell line and in HBs-PRE transient expression cells. CONCLUSION: These data demonstrated that TIA-1 inhibits HBs expression by interacting with PRE.

Chen J, Ahmad J. · Department of Internal Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA. · J Gen Intern Med. · Pubmed #18752027 No free full text.

Abstract: Drug-induced hepatotoxicity is well recognized but can cause some diagnostic problems, particularly if not previously reported. The present case involves a 22-year-old male who presented with jaundice and elevated liver enzymes after a course of cefdinir (Omnicef) for streptococcal pharyngitis. A diagnosis of drug-induced liver injury was suspected but a liver biopsy was required after his jaundice worsened despite cessation of the presumed offending agent. A short course of steroids was initiated and eventually the jaundice resolved. This case highlights the need to suspect medication-induced liver injury in cases of jaundice, even if not previously reported. In addition, it illustrates the potential for adverse outcomes in situations where antibiotics are used inappropriately or where first line antibiotics are not used for routine infections. We report a case of a young male who developed jaundice associated with cefdinir use with pathological confirmation of moderate cholestasis with portal and lobular mixed inflammation and focal bile duct injury consistent with drug-induced liver injury.

Yu Z, Wang Z, Chen J, Li H, Lin Z, Zhang F, Zhou Y, Hou J. · Department of Infectious Diseases, Nanfang Hospital, Nanfang Medical University, Guangzhou, China. · Arch Virol. · Pubmed #18668195 No free full text.

Abstract: Multiple studies have established that GTPase activity is critical for MxA to act against RNA viruses. Recently, it was shown that MxA can also restrict the replication of hepatitis B virus (HBV), a DNA virus, but the requirements for GTPase activity in inhibition of HBV by MxA remain unknown. Here, we report that GTPase-defective mutants (K83A, T103A, and L612K) can downregulate extracellular HBsAg and HBeAg and reduce the expression of extra- and intracellular HBV DNA in HepG2 cells to levels similar to that achieved by wild-type MxA. Furthermore, TMxA and T103, two nuclear forms of wild-type MxA and a GTPase-defective mutant (T103A) could only slightly decrease the expression of extra- and intracellular HBV DNA in HepG2 cells. In conclusion, GTPase activity is not essential for MxA protein to inhibit HBV replication, and MxA may have only a minimal effect on the replicative cycle of HBV in the nucleus.

Jin HW, Chen J, He H, Williams GJ, Kelman C, O'Keefe CM. · Commonwealth Scientific and Industrial Research Organization (CSIRO), Mathematical and Information Sciences, Canberra, A.C.T. 2601, Australia. · IEEE Trans Inf Technol Biomed. · Pubmed #18632329 No free full text.

Abstract: In various real-world applications, it is very useful mining unanticipated episodes where certain event patterns unexpectedly lead to outcomes, e.g., taking two medicines together sometimes causing an adverse reaction. These unanticipated episodes are usually unexpected and infrequent, which makes existing data mining techniques, mainly designed to find frequent patterns, ineffective. In this paper, we propose unexpected temporal association rules (UTARs) to describe them. To handle the unexpectedness, we introduce a new interestingness measure, residual-leverage, and develop a novel case-based exclusion technique for its calculation. Combining it with an event-oriented data preparation technique to handle the infrequency, we develop a new algorithm MUTARC to find pairwise UTARs. The MUTARC is applied to generate adverse drug reaction (ADR) signals from real-world healthcare administrative databases. It reliably shortlists not only six known ADRs, but also another ADR, flucloxacillin possibly causing hepatitis, which our algorithm designers and experiment runners have not known before the experiments. The MUTARC performs much more effectively than existing techniques. This paper clearly illustrates the great potential along the new direction of ADR signal generation from healthcare administrative databases.

Liu G, Wang F, Ni Z, Yun T, Yu B, Huang J, Chen J. · Institute of Virology and Biotechnology, Zhejiang Academy of Agricultural Sciences, Hangzhou, People's Republic of China. · Virus Res. · Pubmed #18585813 No free full text.

Abstract: The complete sequence of an isolate (ZJ-V) of Duck hepatitis virus I (DHV-I), originally taken from the field in southeast China was determined. It was 7691 nucleotides long and had 5'- and 3'-terminal non-coding regions of 626 and 315 nucleotides, respectively. The poly(A) tail contained at least 22 residues and the single open reading frame encoded a polypeptide of 2249 amino acids. The VP1 gene was also sequenced from nine southeast China field isolates and three attenuated DHV-I vaccine strains. In phylogenetic analysis of the isolates and other published sequences, attenuated and tissue-adapted isolates (including ZJ-V) clustered as genotypes significantly different from the field isolates that had not been passaged in chicken/duck embryos. There were two consistent amino acid substitutions (E(129)-->V(129) and A(142)-->S(142)) between all the field isolates and all the tissue-adapted ones. The carboxyl terminal region was generally the most variable and here the four attenuated Chinese isolates showed six consistent differences from the field isolates (S(181)-->L(181), H(183)K(184)-->R(183)G(1841), N(193)-->D(193), E(205)-->K(205), R(217)-->K(217), N(235)-->D(235)). It seems likely that at least some of these differences result from mutations leading to isolate attenuation.

Kamijima M, Wang H, Huang H, Li L, Shibata E, Lin B, Sakai K, Liu H, Tsuchiyama F, Chen J, Okamura A, Huang X, Hisanaga N, Huang Z, Ito Y, Takeuchi Y, Nakajima T. · Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Japan. · J Occup Health. · Pubmed #18540116 links to  free full text

Abstract: Idiosyncratic generalized skin disorders complicated by hepatitis, which resemble severe drug hypersensitivities, occur sporadically in workers exposed to trichloroethylene (TCE) in China. However, it has been a matter of controversy whether the solvent itself, not its impurities or stabilizers, can cause hypersensitivity reactions or not. This study aimed to characterize the exposure of hospitalized patients and their healthy colleagues. TCE metabolites were measured in urine of 19 hospitalized patients suffering from the disorders. To assess the exposure of patients' healthy colleagues, on-site surveys were conducted in 6 factories where the disorders occurred and in 2 control factories without such occurrences despite TCE use. Urinalysis of the patients detected trichloroacetic acid (TCA) in all of them. Its average concentration in the end-of-shift urine was estimated to be 206 mg/l. On-site survey of healthy exposed workers revealed that the maximum urinary TCA concentrations and the maximum time-weighted average concentrations of personal TCE exposure were 318-1,617 mg/l and 164-2,330 mg/m(3), respectively. There was no common impurity in TCE used in the factories. These results suggested that TCE itself caused the skin hypersensitivity disorders, and that the disorders occurred in factories where TCE metabolites could be extensively accumulated, possibly due to long working hours. Since the lowest TCA concentration in the end-of-shift urine of the patients was estimated to be 72-80 mg/l, it is recommended to control TCE exposure to keep the urinary TCA concentration below 50 mg/l to reduce the disease risk.

Matsukura M, Chu FF, Au M, Lu H, Chen J, Rietkerk S, Barrios R, Farley JD, Montaner JS, Montessori VC, Walker DC, Côté HC. · Department of Pathology and Laboratory Medicine, University of British Columbia, Canada. · AIDS. · Pubmed #18525271 No free full text.

Abstract: Liver mitochondrial toxicity is a concern, particularly in HIV/hepatitis C virus (HCV) coinfection. Liver biopsies from HIV/HCV co-infected patients, 14 ON-highly active antiretroviral therapy (HAART) and nine OFF-HAART, were assessed by electron microscopy quantitative morphometric analyses. Hepatocytes tended to be larger ON-HAART than OFF-HAART (P = 0.05), but mitochondrial volume, cristae density, lipid volume, mitochondrial DNA and RNA levels were similar. We found no evidence of increased mitochondrial toxicity in individuals currently on HAART, suggesting that concomitant HAART should not delay HCV therapy.

Garten RJ, Lai SH, Zhang JB, Liu W, Chen J, Yu XF. · Department of Molecular Microbiology and Immunology, The Johns Hopkins University Bloomberg School of Public Health, Room E5148, 615 N. Wolfe St, Baltimore, MD 21205, United States. · World J Gastroenterol. · Pubmed #18350626 links to  free full text

Abstract: AIM: To study the virological and host factors influencing hepatitis C infection outcomes in heroin users in southern China. METHODS: HCV RNA and associated factors were analyzed among 347 heroin users from Guangxi Zhuang Autonomous Region, southern China who were hepatitis C virus (HCV) EIA positive for two or more consecutive visits. RESULTS: Using the COBAS AMPLICOR HCV TEST, a remarkably low HCV RNA negative rate of 8.6% was detected. After multivariate logistic regression analysis, HCV RNA clearance was significantly associated with the presence of HBsAg (OR = 8.436, P < 0.0001), the lack of HIV-1 infection (OR = 0.256, P = 0.038) and age younger than 25 (OR = 0.400, P = 0.029). CONCLUSION: Our study suggests HCV infection among Chinese heroin users results in high levels of viral persistence even amidst factors previously found to enhance viral clearance. Prospective studies of a possible genetic component within the Chinese population and the pathogenicity of non-genotype 1 HCV infections are needed.

Chen W, Zhang Z, Chen J, Zhang J, Zhang J, Wu Y, Huang Y, Cai X, Huang A. · The Institute for Viral Hepatitis, Key Laboratory of Molecular Biology on Infectious Diseases of the Ministry of Education, Chongqing Medical University, Chongqing, 400016, China. · Virus Res. · Pubmed #18325616 No free full text.

Abstract: RNA silencing is a form of nucleic acid-based immunity against viruses in plants and invertebrate animals. Successful viral infection requires evasion or suppression of gene silencing. Here, we report that the core protein of Hepatitis C virus (HCV) acts as a potent suppressor of RNA silencing (SRS). We have found that the HCV core protein inhibits RNA silencing induced by short hairpin RNAs (shRNAs) but not by synthetic small interfering RNAs (siRNAs) in various mammalian cells. We have further demonstrated that HCV core protein directly interacts with Dicer, an RNase enzyme that generates siRNA in host cells. The HCV core protein has been shown to inhibit the function of Dicer to process double-stranded RNAs (dsRNAs) into siRNAs. Through deletion analysis, we have found that the N-terminal domain is required for core protein to antagonize RNA silencing activity of Dicer enzyme. Thus, our results suggest that HCV core protein may abrogate host cell RNA silencing defense by suppressing the ability of Dicer to process precursor dsRNAs into siRNAs. This anti-Dicer ability of core protein may contribute to the persistent viral infection and pathogenesis of HCV.

Yin J, Zhang H, Li C, Gao C, He Y, Zhai Y, Zhang P, Xu L, Tan X, Chen J, Cheng S, Schaefer S, Cao G. · Department of Epidemiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, People's Republic of China. · Carcinogenesis. · Pubmed #18192693 No free full text.

Abstract: The role of genotype mixture and subgenotypes remains controversial in determining the clinical outcome of chronic hepatitis B virus (HBV) infection. We aimed to determine their role on the development and the recurrence of hepatocellular carcinoma (HCC). HBV genotypes, serum viral load and hepatitis B e antigen (HBeAg) seroconversion were determined in 462 HCC patients, 234 chronic hepatitis patients and 425 asymptomatic carriers born in Eastern China. In the 462 HCC patients, 62 (13.4%), 337 (72.9%) and 49 (10.6%) had HBV subgenotype B2, C2 and genotype mixture, respectively. Genotype mixture in HCC patients and hepatitis patients was associated with higher viral load than HBV C2 (P = 0.012, P = 0.000) and more frequent than asymptomatic carriers (P = 0.005, P = 0.000). HBV C2 was more prevalent in HCC patients compared with controls. Proportion of HBV B2 in HCC patients decreased consecutively from <30 to 50-59 years group (P = 0.024). Age-related changes of HBeAg seroconversion were not consistent with serum viral load in HCC patients with HBV B2 and genotype mixture, quite in contrast to hepatitis patients. By multivariate regression analysis, age >or=40 years and serum viral load (>or=10 000 copies/ml) were independently associated with hepatocarcinogenesis, whereas age <or=50 years and HBV B2 were independently associated with HCC recurrence after surgical resection. In conclusion, HBV coinfections with two or three genotypes were associated with higher viral load and more severe course of the disease. HBV B2 infection was related to HCC recurrence. HBV C2 predominance in HCC patients was related to the high prevalence in Eastern China.

Liao G, Wang Y, Chang J, Bian T, Tan W, Sun M, Li W, Yang H, Chen J, Zhang X, Bi S, Omata M, Jiang S. · Department of Viral Immunology, Institute of Medical Biology, Chinese Academy of Medical Science and Peking Union Medical College, Yunnan Province, People's Republic of China. · Hepatology. · Pubmed #18074356 No free full text.

Abstract: DNA immunization has been used to induce either humoral or cellular immune responses against many antigens, including hepatitis C virus (HCV). In addition, DNA immunizations can be enhanced or modulated at the nucleotide level. Genetic immunizations were examined in BALB/c mice through the use of plasmids and chimeric DNA constructs encoding HCV core proteins and hepatitis B virus (HBV) precore (preC) regions. Plasmids encoding the truncated HCV core induced potent humoral and cellular responses to HCV; pcDNA3.0A-C154 produced a stronger antibody response than pcDNA3.0A-C191 (P < 0.01) and pcDNA3.0A-C69 (P < 0.05). HBV preC enhanced the humoral and cellular immune responses of BALB/c mice to HCV; however, pcDNA3.0A-C69preC resulted in a weak cytotoxic T lymphocyte (CTL) response. In addition, the humoral and cellular immune responses to HCV of groups immunized with pcDNA3.0A-C154preC and pcDNA3.0A-C191preC plasmids were higher than those of groups immunized with pcDNA3.0A-C154 and pcDNA3.0A-C191. In vivo CTL responses verified that mice immunized with preC core fused DNAs showed significantly high specific lysis compared with mice immunized with HCV cores only (P < 0.01). In our study, pcDNA3.0A-C154preC led to the highest immune response among all DNA constructs. Conclusion: DNA that encodes truncated HCV core proteins may lead to increased immune responses in vivo, and these responses may be enhanced by HBV preC.