Hepatitis: He J

Liu P, Hu YY, Liu C, Xu LM, Liu CH, Sun KW, Hu DC, Yin YK, Zhou XQ, Wan MB, Cai X, Zhang ZQ, Ye J, Zhou RX, He J, Tang BZ. · Institute of Liver Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. · World J Gastroenterol. · Pubmed #15902724 links to  free full text

Abstract: AIM: To study the efficacy and safety of Fuzhenghuayu capsule (FZHY capsule, a capsule for strengthening body resistance to remove blood stasis) against liver fibrosis due to chronic hepatitis B. METHODS: Multicenter, randomized, double blinded and parallel control experiment was conducted in patients (aged from 18 to 65 years) with liver fibrosis due to chronic hepatitis B. Hepatic histologic changes and HBV markers were examined at wk 0 and 24 during treatment. Serologic parameters (HA, LM, P-III-P, IV-C) were determined and B ultrasound examination of the spleen and liver was performed at wk 0, 12 and 24. Liver function (liver function and serologic parameters for liver fibrosis) was observed at wk 0, 6, 12, 18 and 24. Blood and urine routine test, renal function and ECG were examined before and after treatment. RESULTS: There was no significant difference between experimental group (110 cases) and control group (106 cases) in demographic features, vital signs, course of illness, history for drug anaphylaxis and previous therapy, liver function, serologic parameters for liver fibrosis, liver histologic examination (99 cases in experimental group, 96 cases in control group), HBV markers, and renal function. According to the criteria for liver fibrosis staging, mean score of fibrotic stage(s) in experimental group after treatment (1.80) decreased significantly compared to the previous treatment (2.33, P<0.05), but there was no significant difference in mean score of fibrotic stage(s) (2.11 and 2.14 respectively). There was a significant difference in reverse rate between experimental group (52%) and control group (23.3%) in liver biopsy. With marked effect on decreasing the mean value of inflammatory activity and score of inflammation (P<0.05), Fuzhenghuayu capsule had rather good effects on inhibiting inflammatory activity and was superior to that of Heluoshugan capsule. Compared to that of pretreatment, there was a significant decrease in HA, LM, P-III-P and IV-C content in experimental group after 12 and 24 wk of treatment. The difference in HA, LM, P-III-P and IV-C content between 12 and 24 wk of treatment and pretreatment in experimental group was significantly greater than that in control group (P<0.01-0.05). The effect, defined as two of four parameters lowering more than 30% of the baseline, was 72.7% in experimental group and 27.4% in control group (P<0.01). Obvious improvement in serum Alb, ALT, AST and GGT was seen in two groups. Compared to that of control group, marked improvement in GGT and Alb was seen in experimental group (P<0.05). The effective rate of improvement in serum ALT was 72.7% in experimental group and 59.4% in control group. No significant difference was seen in blood and urine routine and ECG before and after treatment. There was also no significant difference in stable rate in ALT and serologic parameters for liver fibrosis between experimental group and control group after 12 wk of withdrawal. CONCLUSION: Fuzhenghuayu capsule has good therapeutic effects on alleviating liver fibrosis due to chronic hepatitis B without any adverse effect and is superior to that of Heluoshugan capsule.

Liu P, Hu YY, Liu C, Xu LM, Liu CH, Sun KW, Hu DC, Yin YK, Zhou XQ, Wan MB, Cai X, Zhang ZQ, Ye J, Tang BZ, He J. · Research Institute of Liver Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. · Zhong Xi Yi Jie He Xue Bao. · Pubmed #15339577 links to  free full text

Abstract: OBJECTIVE: To study the efficacy and safety of Fuzheng Huayu Capsule (FZHY Capsule) against liver fibrosis with chronic hepatitis B. METHODS: Multicentric, randomized, double blinded and paralleled control led trial was conducted on patients (aged between 18 and 65) with liver fibrosis in chronic hepatitis B Indexes observed: (1) hepatic histological changes and HBV markers were observed at 0 and 24th week during the treatment; serological indexes (HA, LN, P-III-P, IV-C) were determined and B ultrasound examination of spleen and liver was taken at 0, 12th, 24th week; liver function (during the period of follow-up, liver function and serological indexes for liver fibrosis were evaluated) were observed at 0, 6th, 12th, 18th, 24th week; (2) indexes for safety: blood and urine routine tests, renal function and ECG were examined. RESULTS: (1) Enrollment and demographic data: There was no significant difference between the trial (110 cases) and control group (106 cases) in demographic feature, vital signs, course of illness, history for drug anaphylaxis, history of previous therapy, liver function, serological indexes for liver fibrosis, liver histological examination (99 cases for test group, 96 cases for control group), HBV markers, and renal function, etc. (2) Histological pathological examination: 93 cases of liver histological examination were taken, of these 50 cases for the trial group and 43 cases for control group which turned out to be at S mean value of 2.33 and 2.11 respectively pretreatment according to criteria for liver fibrosis staging. Post-treatment, the trial showed a significant decrease with S value of 1.80 compared to that of pretreatment; however, there was no significant improvement in control group before and after the treatment with S mean value of 2.14. There was significant difference in reversing rate (decrease at least 1 stage according to criteria for liver fibrosis staging) between the trial (52%) and control (23.3%) after liver biopsy. The trial had a rather good effect on improving inflammatory activity and was superior to control group with a marked decrease of mean value of inflammatory activity and score of inflammation (P<0.05). (3)Serological indexes for liver fibrosis: There was a significant decrease in HA, LN, P-III-P, IV-C content in test group after 12 and 24 weeks' treatment compared to that of pretreatment; the differences of HA, LN, P-III-P, IV-C between 12, 24 weeks' treatment and pretreatment were significantly greater than control group (P<0.01 or 0.05); the effectual was defined as 2 of 4 indexes lowered more than 30% of the baseline, according to this criteria, the trial was 72.7%, while control group 27.4% (P<0.01). (4)Liver function: Obvious improvement of serum Alb, ALT, AST, GGT was seen in 2 groups; compared with control group, marked improvement of GGT and Alb in the trial (P<0.05); the effective rate of serum ALT in the trial group was 72.7%, while control 59.4%. (5)No changes of significant difference between pre- and post-treatment in routine tests for blood and urine, renal function and ECG, etc. There was also no difference in the stable rate of ALT and serological indexes for liver fibrosis between the trial and control group 12 weeks after withdrawal (P<0.05). CONCLUSION: Fuzheng Huayu Capsule has good effect on alleviating liver fibrosis in chronic hepatitis B without any adverse effect and is superior to Heluo Shugan Capsule. Fuzheng Huayu Capsule is a safe and effective medicine for the treatment of liver fibrosis in chronic hepatitis B.

Yang L, Ren J, He J, Chen LB. · Hepatobiliary Center, Union Hospital, Huazhong University of Science and Technology, Wuhan 430022, China. · Zhonghua Gan Zang Bing Za Zhi. · Pubmed #19403031 No free full text.

Abstract: OBJECTIVE: To explore the role SMYD3 and histone methylation in the carcinogenesis of HBV-related hepatocellular carcinoma (HCC). METHODS: HBx expressing plasmid was transfected into HepG2 cell, the localization of HBx and SMYD3 was detected by immunofluorescence, SMYD3 mRNA and protein were checked by real-time reverse transcription polymerase chain reaction and western blot, cell proliferation and apoptosis were detected by flow cytometry. RESULTS: After HBx transfection, HBx and SMYD3 protein were mainly localized in nucleus. HBx protein enhanced SMYD3 mRNA and SMYD3 expressions in HepG2. After HBx transfection, apoptosis of HepG2 was decreased, and cell proliferation was increased. CONCLUSIONS: HBx may induce the expression of histone methyltransferase SMYD3, which in turn stimulates cell proliferation and blocks apoptosis.

Jiang TJ, Fan R, Xie YX, Zhao P, Zhang X, Zhao M, Zhou ZP, He J. · First Department of Infectious Diseases, PLA 302 Hospital, Beijing 100039, China. · Zhonghua Gan Zang Bing Za Zhi. · Pubmed #18423159 No free full text.

This publication has no abstract.

He J, Kuschner RA, Dewar V, Voet P, Asher LV, Vaughn DW. · Armed Forces Institute of Pathology, 1413 Research Boulevard, Rockville, MD 20850, USA. · J Biomed Sci. · Pubmed #17487571 No free full text.

Abstract: Twenty-seven monoclonal antibodies (Mabs) recognizing the open reading frame 2 structural protein of the Pakistan strain of hepatitis E virus (HEV) were generated by conventional hybridoma technique. These Mabs were characterized by ELISA, affinity-capture reverse transcriptase-polymerase chain reaction (AC/RT-PCR), immune electron microscopy (IEM), and a RT-PCR based seroneutralization assay. Twenty-seven Mabs were positive by ELISA. By AC/RT-PCR, 24 Mabs bound to Pakistan and Namibia HEV strains. Thirteen Mabs were examined by IEM. Nine Mabs, positive by ELISA and AC/RT-PCR, bound and aggregated to Mexican HEV strain. We tested five Mabs that were positive by ELISA, AC/RT/PCR, and IEM by a RT-PCR based seroneutralization assay. Only one Mab (Mab 7) showed activity that inhibited the ability of HEV to attach to Alexander hepatoma cells (PLC-PRF-5). When Mab 7 was diluted to 1: 160, its inhibition activity persisted suggesting that Mab 7 might be a potential candidate for further evaluation in primates (passive protection experiments).

He J. · Department of Virus Diseases, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Silver Spring, MD, USA. · J Viral Hepat. · Pubmed #17109684 No free full text.

Abstract: Sporadic and epidemic acute viral hepatitis E in many developing countries is caused by hepatitis E virus (HEV). The HEV genome has been classified into three major genotypes. However, extensive diversity has been noted among HEV isolates from patients with acute hepatitis in China and Taiwan. Some reports indicated that multiple genotypes of HEV could cocirculate in the same area; even distinct genotypes of HEV could exist in the same patient. Pakistan is a highly endemic area for hepatitis E. So far only two Pakistan HEV isolates Sar-55 (87-Pakistan-A) and Abb-2B (88-Pakistan-2B) have been characterized, and the nucleotide sequences of these two HEV isolates show only 90% homology. In this study, a third HEV isolate from Pakistan (87-Pakistan-B) is reported. The sequences of a 438-bp fragment from ORF-2 and a 259-bp fragment from the ORF-1-3 region of this new HEV isolate were obtained and sequenced. The sequence analysis showed that this new HEV isolate was very closely related to the Sar-55 but different from the Abb-2B HEV isolate. These results indicated that the Sar-55 (87-Pakistan-A) genotype is the main endemic HEV strain in the Sargodha area. These data will be useful for HEV epidemiological studies, diagnosis and vaccine development.

He J, Xin SJ, Shen HH, Yang JY, Zhu L, Hu Y, Hou J, Mao PY. · The No. 302 Hospital of the People's Liberation Army, Beijing 100039, China. · Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. · Pubmed #16642215 No free full text.

Abstract: BACKGROUND: To evaluate an enzyme linked immunospot (ELISPOT) method for testing the specific cellular immunity of patients with hepatitis B and preliminarily investigate into the difference of cellular immunity in patients with various types of hepatitis B. METHODS: The patients with acute hepatitis B, chronic hepatitis B liver cirrhosis, healthy persons with HBV vaccine immunization, healthy persons with past HBV infection and HBV naive persons were enrolled in this study. Their peripheral blood mononuclear cells were tested by ELISPOT to determine the number of gamma-interferon secreting cells. RESULTS: The number of gamma-interferon secreting cells was significantly different between the patients with acute hepatitis B and those with chronic hepatitis B, and between the patients with acute hepatitis B and those with liver cirrhosis (P=0.0209 and P=0.0211). CONCLUSION: The specific cellular immunity in the patients with hepatitis B could be evaluated by determining the number of gamma-interferon secreting cells with the method of testing their peripheral blood mononuclear cells by ELISPOT. The specific cellular immunity was stronger in the patients with acute hepatitis B than in those with chronic hepatitis B and liver cirrhosis.

He J, Xin SJ, Zhao JM, Wang SS, You SL, Zou ZS. · The No. 302 Hospital of The People's Liberation Army, Beijing 100039, China. · Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. · Pubmed #16261212 No free full text.

Abstract: OBJECTIVE: To investigate the relation of the viral markers in serum and those expressed by hepatocytes to pathological lesions of hepatic tissue in patients with chronic hepatitis B. METHODS: The relation of viral markers including HBsAg, HBsAb, HBeAg, HBeAb, HBcAb and HBV DNA in serum of 647 patients with chronic hepatitis B and HBsAg, HBcAg expressed by hepatocytes in 418 of these patients to pathological lesions of hepatic tissue was determined. RESULTS: Viral markers in serum and those expressed by hepatocytes in patients with chronic hepatitis B were closely correlated with pathological lesions of hepatic tissue. CONCLUSION: The degree of inflammation and fibrosis in hepatic tissue is milder in serum HBsAg, HBeAb, HBcAb positive and HBV DNA negative patients but more serious in those with negative hepatocytic expression of HBsAg and HBcAg. HBV DNA is not significantly associated with pathological lesions of hepatic tissue.

Xu J, He J, Zi XY, Yu HY, Liu HM, Li YL, Hu YP. · Department of Pathology, Changzheng Hospital, Shanghai 200003, China. · Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. · Pubmed #15766408 No free full text.

Abstract: AIM: To make immunopathological study of hepatitis B virus transgenic mice line C57-TgN (HBV adr2.0) SMMU. METHODS: Twenty transgenic C57-TgN mice of SPF grade and corresponding control mice C57BL/6 were used for the study. The expressions of CD3, CD4 and CD8 on lymphocytes in peripheral blood from transgenic and normal C57BL/6 mice were detected by flow cytometry. T lymphocyte subsets in the liver tissues from transgenic mice and hepatitis B patients were analyzed by EnVision staining. RESULTS: The expression of CD3, CD4 and CD8 on lymphocytes in peripheral blood from transgenic mice was lower than those from normal mice. The infiltrative mononuclear cells in the liver tissues of transgenic mice were mainly CD3+ CD4+ cells, and no CD8+ CD57+ cells was found. The infiltrative mononuclear cells in the liver tissues of human hepatitis B patients were mainly CD3+ CD4+ or CD3+ CD8+ cells. CONCLUSION: T cell subsets in the peripheral blood and liver tissues of transgenic mice C57-TgN (adr2.0) SMMU are different from those in human chronic hepatitis B patients.

Ge JH, Zhang LZ, Li JX, Liu H, Liu HM, He J, Yao YC, Yang YJ, Yu HY, Hu YP. · Department of Pathology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China. gerllini@ yahoo.com.cn · World J Gastroenterol. · Pubmed #15457560 links to  free full text

Abstract: AIM: To establish the transgenic mouse line harbouring complete hepatitis B virus (HBV) genome with mutant s gene (adr subtype). METHODS: Transgenic mice were generated by microinjecting HBV genome into fertilized eggs. Integration, expression, replication of HBV gene and histological changes in transgenic mice were estimated by genomic DNA PCR, serum DNA PCR, Southern blot, ELISA, HE staining, immunohistochemistry and transmission electron microscopy. Transgenic mice with HBsAg positive in serum were bred and analyzed. RESULTS: A total of 288 eggs survived from microinjections were transplanted into the oviducts of 13 pseudopregnant mice and 49 pups were produced. Twenty-six mice were identified to have the integrated HBV gene. Serum HBsAg and HBeAg were detected in 2 of 43 mice. HBsAg and HBcAg in cytoplasm or nuclei of hepatocytes were detected in 10 mice. Founders with HBsAg in serum were named lineages G145R-15 and G145R-18. Of the 16 F1 offsprings generated by G145R-15 founder, 12 were positive for HBV genome with PCR, 10 were positive for HBsAg and HBcAg with immunohistochemistry and 7 were positive for HBsAg and HBeAg with ELISA. Only 1 of 8 F1 offsprings generated by G145R-18 founder was survived and it was detected positive for HBV genome, HBsAg, HBcAg and HBeAg. Both of the two lineages had some pathological characteristics of mild chronic hepatitis B in the liver, such as swelling of hepatocytes and focal hepatocellular necrosis and parenchymal lymphomononuclear cell infiltrate. CONCLUSION: Transgenic mice harbouring HBV with mutant s gene can be generated. The HBV genes are integrated in the transgenic mice genome and can be expressed, replicated, packaged and excreted. HBV DNA can be stably transmitted in the transgenic mice.

Ge JH, Liu HM, Sun J, Zhang LZ, He J, Li YL, Liu H, Xu Y, Yu HY, Hu YP. · Department of Pathology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China. · World J Gastroenterol. · Pubmed #15457559 links to  free full text

Abstract: AIM: To investigate the change of immunological characteristics of HBsAg caused by the mutation at codon 145 of HBsAg using DNA-based immunization. METHODS: Plasmids expressing mutant and wild type envelope antigens were transfected into human hepatocellular carcinoma cells via electrotransformation. The antigenicity of HBsAg was studied with EIA and immunocytochemical staining. Then plasmids were used to immunize 5 C57BL/6 mice. Sera of mice were detected for anti-HBs and anti-preS2 with ELISA. RESULTS: The mutant HBsAg could be detected by native antibody in EIA and immunocytochemical study. But the A((450 nm)) value of the mutant HBsAg in the supernatant was apparently lower than that of the wild-type. Both mutant and native HBsAg expression plasmid could stimulate a strong humoral immune response to HBsAg and preS2 antigen in mice. Protective antibodies against HBsAg elicited by the native HBsAg occurred earlier than that elicited by the mutant HBsAg about one to two weeks. The occurrence of protective antibodies against preS2 antigen was one to two weeks earlier than that of anti-HBs. CONCLUSION: The amino acid substitution causes changes of the antigenicity and immunogenicity of HBsAg, but mutant HBsAg can still induce a protective humoral immune response in mice.

Ge JH, Liu HM, He J, Li YL, Yu HY, Ye Z, Zhang LZ, Hu YP. · Department of Pathology, Changzheng Hospital, Shanghai 200003, China. · Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. · Pubmed #15169652 No free full text.

Abstract: AIM: To construct the recombinant eukaryotic expression vector pCMV-S2. S + 145R(PR) containing mutant HBV s gene and detect the specific humoral immune response to the PR in mice. METHODS: The PR was constructed by positional cloning of restriction endonuclease, and then it was transfected into human hepatocellular carcinoma cell line Hep G2 through electrotransformation. The antigenicity of PR was examined by EIA, ELISA and immunocytochemical staining. The PR and empty vector pcDNA3.0 were then used respectively to immunize intramuscularly 5 C57BL/6 mice, dosage being 100 pg purified plasmid each mouse.The titers of serum anti-HBs and anti-HBs2 antibodies were detected by ELISA. RESULTS: In vitro experiment showed that mutant HBsAg could bind to anti-HBs antibody. The PR could induce anti-HBs and anti-HBs2 antibody production in immunized mice. But the appearance time of serum anti-HBs2 antibody one or two weeks earlier than that of serum anti-HBs antibody. CONCLUSION: The expression product of PR had a good antigenicity, which can induce specific hu-moral immune response in C57BL/6 mice.

He J, Xin S, Zhao J. · The 302nd Hospital of PLA, Beijing 100039, China. · Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. · Pubmed #11986721 No free full text.

Abstract: BACKGROUND: To study the expression of endothelial nitric oxide synthase (eNOS) and its mRNA in liver tissues of patients with chronic hepatitis B (CHB) and the relationship between its expression and pathological changes of hepatic tissues and the clinical significance. METHODS: 48 cases of specimens of liver tissues with CHB were observed and analyzed using immunohistochemical method and in situ nucleic acid hybridization. RESULTS: eNOS was expressed in hepatocytes, sinusiod endothelial cells and vessel endothelial cells, being predominantly expressed in hepatocytes. The number and distribution of eNOS mRNA positive cells were similiar to those of its protein. Increase in expression of eNOS was correlated with degrees of inflammatory activity and fibrosis (r=0.6855 [P<0.05]; r=0.4828 [P<0.05]; respectively), and with decreasing PA and ALB (F=3.4101 [P<0.05]; F=9.1714 [P<0.0]). Changes of expression of TGF-alpha-R were parallel to those of eNOS. CONCLUSIONS: eNOS may be involved in pathological lesion of CHB by affecting the expression of TGF-R in liver tissues with CHB.

Hu Y, Tan S, Shao C, Jin W, Ji Q, He J, Chen H, Yan J. · Institute of Medical Biology, Chinese Academy of Medical Sciences, Kumming 650107, China. · Chin Med J (Engl). · Pubmed #11775230 links to  free full text

Abstract: OBJECTIVE: To evaluate the safety and immunogenicity of lyophilized, live attenuated hepatitis A vaccine (H2 strain) in rhesus monkeys. METHODS: Nine adult rhesus monkeys were used as experimental animals. The rhesus monkeys without anti-HAV were divided randomly into the aqueous vaccination group (4 rhesus monkeys), the lyophilized vaccination group (3 rhesus monkeys), and the control group (2 rhesus monkeys). Monkeys were inoculated by intramuscular injection, with control monkeys being inoculated with Minimum Essential Medium Eagle (MEM). Following vaccination, the monkeys were observed for the development of diarrhoea and other adverse side-effects, such as changes in appetite, frequency of defaecation and stool consistency for seven days. At the weeks 2, 3, 4, 6, 8, 10 and 12 positnoculation, the peripheral blood was collected from all animals and assayed for anti-HAV and alanine aminotransferase (ALT) and aspartate aminotransferase (AST), at weeks 0, 4 and 8 postinocuation, needle-biopsy specimens were taken at weeks 0, 4, 8 and 12, all monkeys were sacrificed and tissue samples were taken from liver, lung, heart, kidney and brain for pathological examination at week 12. RESULTS: Animals were immunized with a dose of 7.0 logTCID50/ml which is stable after freeze-drying. During the 12-week observation, no animals showed abnormal elevations of liver enzymes (ALT and AST) and no change in appetite or activity. Two monkeys (one in the aqueous group and the other in lyophilized group) showed possible lesions at week 8. The lyophilized vaccine, in addition to eliciting an anti-HAV IgG response similar to aqueous vaccine (P > 0.05), also showed IgM anti-HAV response at week 2 which was not observed with aqueous vaccine. CONCLUSIONS: These results demonstrate that lyophilized, live hepatitis A vaccine is safe and highly immunogenic in primates, supporting its further evaluation in human clinical studies.

Isaäcson M, Frean J, He J, Seriwatana J, Innis BL. · Department of Clinical Microbiology and Infectious Diseases, South African Institute for Medical Research, Johannesburg. · Am J Trop Med Hyg. · Pubmed #11289674 links to  free full text

Abstract: In 1983 in Namibia's Kavango region, epidemic jaundice affected hundreds of people living in settlements lacking potable water and waste disposal facilities. Many were Angolan refugees. The disease, which after investigation was designated non-A non-B hepatitis, was most common in males (72%), in persons aged 15-39 years, and was usually mild except in pregnant women, who incurred 6 (86%) of the 7 fatal infections. Fifteen years later, archived outbreak-associated samples were analyzed. Hepatitis E virus (HEV) was detected by reverse transcription-polymerase chain reaction in feces from 9 of 16 patients tested. Total Ig and IgM to HEV were quantitated in serum from 24 residents of an affected settlement at the outbreak's end: 42% had IgM diagnostic of recent infection and 25% had elevated total Ig without IgM, consistent with past HEV infection. The Namibia outbreak was typical hepatitis E clinically and epidemiologically. This first report of hepatitis E confirmed by virus detection from southern Africa extends the known range of HEV and highlights its risk for refugees.

He J, Hayes CG, Binn LN, Seriwatana J, Vaughn DW, Kuschner RA, Innis BL. · Department of Virus Diseases, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Silver Spring, MD 20910, USA. · J Biomed Sci. · Pubmed #11287754 No free full text.

Abstract: Injection of an expression vector pJHEV containing hepatitis E virus (HEV) structural protein open reading frame 2 gene generates a strong antibody response in BALB/c mice that can bind to and agglutinate HEV. In this study, we tested for immunologic memory in immunized mice whose current levels of IgG to HEV were low or undetectable despite 3 doses of HEV DNA vaccine 18 months earlier. Mice previously vaccinated with vector alone were controls. All mice were administered a dose of HEV DNA vaccine to simulate an infectious challenge with HEV. The endpoint was IgG to HEV determined by ELISA. Ten days after the vaccine dose, 5 of 9 mice previously immunized with HEV DNA vaccine had a slight increase in IgG to HEV. By 40 days after the vaccine dose, the level of IgG to HEV had increased dramatically in all 9 mice (108-fold increase in geometric mean titer). In contrast, no control mice became seropositive. These results indicate that mice vaccinated with 3 doses of HEV DNA vaccine retain immunologic memory. In response to a small antigenic challenge delivered as DNA, possibly less than delivered by a human infective dose of virus, mice with memory were able to generate high levels of antibody in less time than the usual incubation period of hepatitis E. We speculate that this type of response could protect a human from overt disease.

He J, Xin S, Zhao J, Wang S. · Institute of Infectious Diseases, 302 nd Hospital of PLA, Beijing 100039, China. · Zhonghua Gan Zang Bing Za Zhi. · Pubmed #11135690 No free full text.

Abstract: OBJECTIVE: To study the expression of transforming growth factor-beta receptor I (TGF-beta RI) and its mRNA in liver tissues of chronic hepatitis B (CHB) and the relationship between its expression and the pathological injury of hepatic tissues. METHODS: Forty-eight liver specimens from patients with CHB were observed by techniques of immunohistochemistry and in situ nucleic acid hybridization. RESULTS: TGF-beta RI was expressed in the hepatocyte, sinusoid endothelial cell and bile duct epithelial cell, with predominance in the hepatocyte and distribution in small granule or cell membrane. Increased expressing of TGF-beta RI was parallel to the degree of inflammatory activity and fibrosis (r=0.7095, P<0.05; r=0.6915, P<0.05; respectively). The number and the distribution of TGF-beta RI mRNA in the positive cells were coincident to those of its protein. The expression of TGF-beta RI was closely correlated with Tbil (r= 0.3396, P<0.05), PA (r= -0.3430, P<0.05) and ALB (r= -0.4173, P<0.01). CONCLUSION: The TGF-beta RI may involve in the pathological injury of hepatic tissues of CHB.

Ng KP, He J, Saw TL, Lyles CM. · Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. · Med J Malaysia. · Pubmed #11072492 No free full text.

Abstract: Hepatitis E virus (HEV) is a RNA virus transmitted enterically. A study of anti-HEV antibodies in 145 human immunodeficiency virus type 1 (HIV-1) infected subjects found that 14.4% of them were reactive to anti-HEV antibodies. Anti-HEV IgG and anti-HEV IgM was detected in 10.3% and 4.1% of the subjects respectively. Prevalence of anti-HEV (either IgG or IgM) was similar across all adult ages (p = 0.154), between the three ethnic groups (p = 0.378), and across risk groups (p = 0.120). The results showed that HEV infection in subjects recruited in this study was most likely transmitted via faecal-route.

Ng KP, He J, Saw TL, Lyles CM. · Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. · Med J Malaysia. · Pubmed #10944903 No free full text.

Abstract: Hepatitis E virus (HEV) is a RNA virus transmitted enterically. A study of anti-HEV antibodies in 145 human immunodeficiency virus type 1 (HIV-1) infected subjects found that 14.4% of them were reactive to anti-HEV antibodies. Anti-HEV IgG and anti-HEV IgM was detected in 10.3% and 4.1% of the subjects respectively. Prevalence of anti-HEV (either IgG or IgM) was similar across all adult ages (p = 0.154), between the three ethnic groups (p = 0.378), and across risk groups (p = 0.120). The results showed that HEV infection in subjects recruited in this study was most likely transmitted via faecal-route.

He J, Binn LN, Tsarev SA, Hayes CG, Frean JA, Isaacson M, Innis BL. · Department of Virus Diseases, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Silver Spring, MD 20910, USA. · J Biomed Sci. · Pubmed #10895057 No free full text.

Abstract: Hepatitis E virus (HEV) causes sporadic and epidemic acute viral hepatitis in many developing countries. In Africa, hepatitis E has been documented by virus detection (reverse transcriptase polymerase chain reaction, RT-PCR) in Egypt, Chad, Algeria, Morocco and Tunisia. Cases of presumptive hepatitis E also have been documented by detection of antibody to HEV in the Sudan, Kenya, Ethiopia, Somalia, Djibouti and South Africa. Recently, we reported the recovery of 9 isolates of HEV from feces collected during an outbreak of jaundice in Namibia. These specimens were stored frozen for many years at the South African Institute for Medical Research awaiting new methods to determine the etiology of jaundice. HEV genomic sequences were detected by antigen-capture RT-PCR with primers that amplified 2 independent regions of the HEV genome (ORF-2 and ORF-3). To further characterize the HEV 83-Namibia isolates, we determined the nucleotide (nt) sequence of the 3' end of the capsid gene (296 of 1, 980 nt in ORF-2) and ORF-3 for 1 isolate. The capsid gene sequence shared 86% identity with the prototype Burma strain and up to 96% identity with other African strains at the (nt) level, and 99% identity with Burma or other Africa strains at the amino acid level. A 188 (nt) fragment amplified from ORF-3 was also highly homologous to other HEV but was too short for meaningful comparison. Phylogenetic analysis indicated that HEV 83-Namibia is closely related to other African isolates, and differs from Burmese, Mexican and Chinese HEV. These data link the HEV causing the 1983 Namibia outbreak to more recent HEV transmission in northern and sub-Saharan Africa, suggesting this subgenotype of HEV is firmly established throughout the continent.

He J, Binn LN, Caudill JD, Asher LV, Longer CF, Innis BL. · Department of Virus Diseases, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Washington, DC 20307-5100, USA. · Virus Res. · Pubmed #10513287 No free full text.

Abstract: Previously, we have described that injection of an expression vector containing hepatitis E virus (HEV) open reading frame 2 (HEV-ORF-2) generated a strong antibody response in mice. To characterize the reaction of this antiserum with native HEV and to evaluate its potential diagnostic application, we tested the antiserum's ability to bind HEV using immune electron microscope (IEM) and affinity-capture reverse transcription polymerase chain reaction (RT-PCR) amplification. Antiserum to ORF-2 aggregated HEV virions as seen by electron microscopy, providing direct evidence that ORF-2 encodes a structural protein. Antiserum also captured HEV for RT-PCR amplification. This antiserum bound HEV from diverse origins (Asia, Africa, Mexico) at virus concentrations found in patient fecal specimens and bile from inoculated non-human primates. The specificity of the affinity binding was demonstrated when pre-immune sera or sera collected from mice injected with control DNA vector (lacking the HEV ORF-2 gene) failed to bind HEV for RT-PCR amplification and IEM. Specific RT-PCR amplification was confirmed by restriction enzyme digestion of PCR products. The sensitivity of the binding was evaluated by RT-PCR amplification of serially diluted bile containing a genetically divergent HEV, Mexico'86. HEV was detected in a 10(-8) dilution of this bile. This is the first report that antibodies elicited by a DNA vaccine recognize native HEV. Our results indicate that ORF-2 encodes a structural protein and that antiserum to this protein enables simple, sensitive, and specific HEV detection by affinity-capture RT-PCR.

He J, Innis BL, Shrestha MP, Clayson ET, Scott RM, Linthicum KJ, Musser GG, Gigliotti SC, Binn LN, Kuschner RA, Vaughn DW. · Walter Reed Army Institute of Research, Silver Spring, Maryland, USA. · J Clin Microbiol. · Pubmed #16517936 links to  free full text

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He J, Innis BL, Shrestha MP, Clayson ET, Scott RM, Linthicum KJ, Musser GG, Gigliotti SC, Binn LN, Kuschner RA, Vaughn DW. · Walter Reed Army Institute of Research, Silver Spring, Maryland, USA. · J Clin Microbiol. · Pubmed #12454141 links to  free full text

Abstract: Hepatitis E virus (HEV) is an important cause of enterically transmitted hepatitis in developing countries. Sporadic autochthonous cases of hepatitis E have been reported recently in the United States and other industrialized countries. The source of HEV infection in these cases is unknown; zoonotic transmission has been suggested. Antibodies to HEV have been detected in many animals in areas where HEV is endemic and in domestic swine and rats in the United States. There is evidence supporting HEV transmission between swine and humans. Nevertheless, HEV has not been detected in wild rodents. We tested murid rodents and house shrews trapped in Nepal's Kathmandu Valley, where hepatitis E is hyperendemic, for HEV infection. The most commonly trapped species was Rattus rattus brunneusculus. Serum samples from 675 animals were tested for immunoglobulin G against HEV by enzyme-linked immunosorbent assay; 78 (12%) were positive, indicating acute or past infection. Antibody prevalence was higher among R. rattus brunneusculus and Bandicota bengalensis than in Suncus murinus. Forty-four specimens from 78 antibody-positive animals had sufficient residual volume for detection of HEV RNA (viremia) by reverse transcription-PCR. PCR amplification detected four animals (9%; three were R. rattus brunneusculus and one was B. bengalensis) with viremia. Phylogenetic analysis of the four genome sequences (405 bp in the capsid gene) recovered showed that they were identical, most closely related to two human isolates from Nepal (95 and 96% nucleotide homology, respectively), and distinct from HEV sequences isolated elsewhere. These data prove that certain peridomestic rodents acquire HEV in the wild and suggest that cross-species transmission occurs, with rodents serving as a virus reservoir for humans.