Autochthonous hepatitis E virus (HEV) is an emerging pathogen in developed countries, and several cases of acute HEV infection have been reported in South Korea. However, there have been no reports on HEV-associated Guillain-Barré syndrome (GBS) in Korea. We recently experienced the case of a 58-year-old Korean male with acute HEV infection after ingesting raw deer meat. Persistent cholestasis was resolved by the administration of prednisolone. At 2.5 months after the clinical presentation of HEV infection, the patient developed weakness of the lower limbs, and was diagnosed with GBS associated with acute hepatitis E. To our knowledge, this is the second report on supportive steroid therapy for persistent cholestasis due to hepatitis E, and the first report of GBS in a Korean patient with acute HEV infection.
Acute Disease ; Alanine Transaminase/blood ; Antibodies, Viral/blood ; Aspartate Aminotransferases/blood ; Bilirubin/analysis ; Cholestasis/*drug therapy ; Guillain-Barre Syndrome/complications/*diagnosis ; Hepatitis E/*diagnosis/etiology ; Hepatitis E virus/immunology ; Humans ; Immunoglobulin M/blood ; Liver/pathology ; Male ; Middle Aged ; Prednisolone/therapeutic use ; Republic of Korea ; Steroids/*therapeutic use

A 25-year-old woman presented with jaundice, palpitation, and weight loss of 5 kg during a period of 2 weeks. Laboratory tests showed elevated levels of liver enzymes (AST 1,282 IU/L, ALT 1,119 IU/L) and total bilirubin (6.4 mg/dL); negative for hepatitis virus infection; elevated serum levels of triiodothyronine (T3, 3.60 ng/dL), free thyroxine (fT4, 3.82 ng/dL), and lowered serum level of thyroid stimulating hormone (TSH, <0.025 microIU/mL); and positive for thyroid stimulating antibody and anti-mitochondrial antibody (AMA). The liver biopsy findings were consistent with autoimmune hepatitis (AIH). Accordingly, oral steroid therapy was started with 60 mg of prednisolone under the impression of AIH associated with Graves' disease. After a week of steroid therapy, the clinical manifestation showed significant improvement, with normalization of both liver and thyroid functions. Diagnosis of the liver condition of patients who present with hyperthyroidism and liver dysfunction is important, so that appropriate therapy can be promptly initiated.
Adult ; Alanine Transaminase/analysis ; Antibodies, Antinuclear/blood ; Aspartate Aminotransferases/analysis ; Bilirubin/blood ; Female ; Graves Disease/complications/*diagnosis/drug therapy ; Hepatitis, Autoimmune/complications/*diagnosis/drug therapy ; Humans ; Immunoglobulins, Thyroid-Stimulating/blood ; Liver/enzymology/metabolism/pathology ; Prednisolone/therapeutic use ; Steroids/therapeutic use ; Thyrotropin/blood

No abstract available.
Aged ; Antibodies, Antinuclear/analysis/*immunology ; Antiviral Agents/therapeutic use ; Fluorescent Antibody Technique ; Hepatitis C/*diagnosis/drug therapy ; Humans ; Liver Failure/diagnosis/immunology ; Male

OBJECTIVETo investigate the prevalence of occult HBV infection in the normal population in Xiamen.

METHODS4 437 registered permanent residents, aged 1-59 years old, were selected in Xiamen using stratified random sampling method from September to October in 2006. Serum samples were obtained, the basic characteristics, inoculation of HBV vaccine, and liver disease were surveyed. The serum samples were tested five HBV seroimmunological markers. The HBsAg-negative specimens were subjected to HBV-DNA detection by nested PCR targeting for multiple gene segments. The amplified products were sequenced and the sequence was used for determination of HBV genotype and mutation analysis of amino acids located in HBsAg "a" epitope. Subjects with serum detectable HBV-DNA and negative result of HBsAg were considered as occult HBV infection.

RESULTSAmong the 4 437 subjects, 482 individuals were observed HBsAg positive and 3 944 were observed negative. Of the 3 955 HBsAg- negative specimens, 27 occult HBV infections were determined with the positive rate of 0.68% (27/3 955). There were 16 samples with genotype B and 11 with genotype C. 3 types of amino acid (AA) mutation (M133T, T140I, G145R) that influence "a" epitope conformation were observed in 9 subjects with occult HBV infection. S region was successfully sequenced in 312 of the 482 HBsAg positive samples. In subjects with occult HBV infection, the infection rate of genotype C HBV (40.74%, 11/27), inoculation rate of HBV vaccine (62.96%, 17/27), positive rate of HBsAb (51.85%, 14/27), and mutation rate of critical amino acid of "a" epitope (33.33%, 9/27) were higher than HBsAg positive individuals (22.76% (71/312), 13.78% (43/312),0.32% (1/312),0.99% (31/312), respectively), and all the difference were significant (χ(2) = 4.29, 41.26, 156.00, 13.07, respectively, and P value = 0.038, <0.001, <0.001, <0.001, respectively). While the average age in subjects with occult HBV infection (18.3 ± 16.2) were lower than that in HBsAg positive infection (34.4 ± 11.6), and the difference was significant (t = 6.67, P < 0.001). The reactive rate of HBeAb (11.11%, 3/27) and HBcAb (62.96%, 17/27) in subjects with occult HBV infection were lower than that in HBsAg positive infection (74.36% (232/312), 98.40% (307/312)), and the difference were significant (χ(2) = 46.74, 73.78, respectively, and P value <0.001, <0.001, respectively).

CONCLUSIONIn normal population in Xiamen, the infection rate of genotype C, the positive rate of HBsAb, the HBV vaccination rate, and the key AA mutation rate in "a" epitope are significantly higher in occult HBV infection than in HBsAg positive infection, and the age, the positive rate of HBeAb and HBcAb are significantly lower.

Adolescent ; Adult ; Child ; Child, Preschool ; DNA Mutational Analysis ; Genotype ; Hepatitis B ; diagnosis ; Hepatitis B Antibodies ; Hepatitis B Surface Antigens ; Hepatitis B Vaccines ; Hepatitis B virus ; Humans ; Infant ; Middle Aged ; Mutation ; Prevalence ; Vaccination

OBJECTIVETo access the antibody persistence 24-month after revaccination with 3-dose of hepatitis B vaccine (HepB) among non-response adults.

METHODSA total of 24 237 healthy adults who had no histories of hepatitis B infection and hepatitis B vaccination, resided in the local area for more than six months and were aged 18-49 years were selected from 79 villages of Zhangqiu county, Shandong province, China in 2009. Blood samples were obtained and hepatitis B surface antigen (HBsAg), antibody against hepatitis B surface antigen (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were detected using ELISA method. A total of 11 590 persons who were negative for all of these indicators were divided into four groups by cluster sampling methods. Each group was vaccinated with one of the following four types of HepB at 0-, 1-, 6-months schedule: 20 µg HepB derived in Saccharomyces Cerevisiae (HepB-SC), 20 µg HepB derived in Chinese hamster ovary cell (HepB-CHO), 10 µg HepB-SC and 10 µg HepB derived in Hansenula Polymorpha (HepB-HP). Blood samples were collected one month after the third dose of primary immunization and tested for anti-HBs using chemiluminescence microparticle immunoassay (CMIA). The non-responders were revaccinated with three doses of HepB at 0-, 1-, 6-months schedule and the type of HepB was the same as which was used for primary immunization. Blood samples were collected one month (T1) and two years (T24) after revaccination and anti-HBs, antibody against hepatitis B core antigen (anti-HBc) and hepatitis B surface angtigen (HBsAg) (if anti-HBs < 10 mU/ml) were detected by CMIA. χ(2) test was used to compared age, gender and body mass index (BMI) between different groups and the anti-HBs positive rate at T1 and T24; analysis of variance (ANOVA) was used to compare the geometric mean concentration (GMC) of anti-HBs between difference groups. The risk factors associated with positive rate of anti-HBs and GMC of anti-HBs were identified by multiple logistic regression analysis and multifactor linear regression model analysis respectively.

RESULTSA total of 900 non-responders were identified and 71.7% (645/900) of them completed three-dose revaccination and blood collection after revaccination. 467 (72.4%) non-responsive adults were followed up at T24. The anti-HBs positive rate decreased from 85.65% (95% CI: 82.14%-88.71%) at T1 to 60.60% (95% CI: 56.01%-65.06%) at T24 and the corresponding GMC decreased from 175.62 (95% CI: 139.03-221.84) mU/ml to 21.43 (95% CI: 17.62-26.06) mU/ml. Multivariate analysis showed that positive rate of anti-HBs at T24 was associated with gender, HepB type for revaccination and anti-HBs level at T1, but only anti-HBs level at T1 was associated with the anti-HBs titer at T24. No subject showed HBsAg seroconversion and anti-HBc conversion rate was 3.64% (17/467) at T24.

CONCLUSIONAnti-HBs titer decreases rapidly two years after HepB revaccination among non-responsive adults, but more than half non-responderd still kept anti-HBs above protective level. The immunity durability after revaccination was associated with gender, HepB type for revaccination and anti-HBs titer one month after revaccination.

Adolescent ; Adult ; Animals ; Body Mass Index ; CHO Cells ; China ; Cricetinae ; Cricetulus ; Enzyme-Linked Immunosorbent Assay ; Female ; Follow-Up Studies ; Hepatitis B ; prevention & control ; Hepatitis B Antibodies ; blood ; Hepatitis B Core Antigens ; immunology ; Hepatitis B Surface Antigens ; immunology ; Hepatitis B Vaccines ; administration & dosage ; classification ; Humans ; Immunization, Secondary ; Male ; Middle Aged ; Multivariate Analysis ; Pichia ; Risk Factors ; Saccharomyces cerevisiae ; Seroconversion ; Vaccination ; Young Adult

The lack of effective in vitro infection model for hepatitis E virus (HEV) has greatly hindered the quantitative analysis of neutralizing titers of anti-HEV antibodies and human sera, thus impeding further studies of HEV-stimulated antibody responses and the immunological mechanisms. In order to improve this situation, the infection of HepG2 cells that are inefficient for HEV replication was continuously monitored until the viral load reached the limit of detection on day 13, the results of which confirmed the feasibility of using this cell line to establish the infection model. Then, neutralization assays of five anti-HEV murine monoclonal antibodies and serum samples collected from four HEV vaccine recipients (collected before and after vaccination) were performed by 96 multi-channel parallel infections, nucleic acid extraction, and qPCR. The results showed that the cell model can be applied for quantitative evaluation of the neutralizing capacity of different antibodies and antiserum samples from HEV vaccine recipients. In this study, we have successfully established a high-throughput in vitro HEV replication model, which will prove to be useful for the evaluation of HEV vaccines and studies of HEV epitopes.
Animals ; Antibodies, Viral ; analysis ; immunology ; Hepatitis Antibodies ; analysis ; immunology ; Hepatitis E ; immunology ; virology ; Hepatitis E virus ; chemistry ; immunology ; physiology ; High-Throughput Screening Assays ; methods ; Humans ; Mice ; Mice, Inbred BALB C ; Neutralization Tests ; methods ; Virus Replication

BACKGROUND/AIMS: Hepatitis-B-related acute-on-chronic liver failure has a poor prognosis. However, the advent of potent oral antiviral agents means that some patients can now recover with medical treatment. We aimed to identify the prognostic factors for hepatitis-B-related acute-on-chronic liver failure including the initial as well as the dynamically changing clinical parameters during admission. METHODS: Sixty-seven patients were retrospectively enrolled from 2003 to 2012 at Samsung Medical Center. The patients were classified into three categories: Recovery group (n=23), Liver transplantation group (n=28), and Death group (n=16). The Liver transplantation and Death groups were combined into an Unfavorable prognosis group. We analyzed the prognostic factors including the Model for End-Stage Liver Disease (MELD) scores determined at 3-day intervals. RESULTS: A multivariable analysis showed that the unfavorable prognostic factors were a high initial MELD score (> or =28) (odds ratio [OR] =6.64, p=0.015), moderate-to-severe ascites at admission (OR=6.71, P=0.012), and the aggravation of hepatic encephalopathy during hospitalization (> or =grade III) (OR=15.41, P=0.013). Compared with the baseline level, significant reductions in the MELD scores were observed on the 7th day after admission in the Recovery group (P=0.016). CONCLUSIONS: Dynamic changes in clinical parameters during admission are useful prognostic factors for hepatitis-B-related acute-on-chronic liver failure.
Acute-On-Chronic Liver Failure/*diagnosis/drug therapy/etiology ; Adult ; Aged ; Antibodies, Monoclonal, Murine-Derived/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Antiviral Agents/therapeutic use ; Cyclophosphamide/therapeutic use ; DNA, Viral/analysis ; Doxorubicin/therapeutic use ; Female ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/complications/*diagnosis/drug therapy ; Hospitalization ; Humans ; Liver Transplantation ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Prednisone/therapeutic use ; Prognosis ; Retrospective Studies ; Severity of Illness Index ; Vincristine/therapeutic use ; Young Adult

OBJECTIVES: The seroprevalence of hepatitis E virus (HEV) among high-risk groups overseas is high, but studies in these groups are rare in South Korea. We conducted the present study from April to November 2012 to obtain data on the seroprevalence and associated risk factors for HEV among slaughterhouse workers in South Korea. METHODS: Slaughterhouse workers from 80 workplaces nationwide were surveyed in South Korea in 2012. The subjects comprised 1848 cases: 1434 slaughter workers and 414 residual products handlers. By visiting 80 slaughterhouses, which were mixed with 75 of which also performed residual products handling, we conducted a questionnaire survey for risk factors and obtained blood samples in order to determine the seropositivity and seroprevalence of HEV. Anti-HEV IgG and IgM were measured using HEV IgG and IgM enzyme-linked immunospecific assay kits and HEV antigen was measured by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The seropositivity of anti-HEV IgG was 33.5% (slaughter workers 32.8% and residual products handlers 36.2%), and among the seropositive individuals the seroprevalence of anti-HEV IgM was 0.5% (slaughter workers 0.5%, residual products handlers 0.7%). The response rate of HEV-antigen as measured by RT-PCR was 0.2%. Risk factors significantly related to anti-HEV IgG seropositivity were age, sex , and working duration (slaughter workers only). CONCLUSIONS: There were significant risk factors (sex, age, and working duration) for HEV identified in our study. All three positive cases for HEV-antigen by RT-PCR were related to pig slaughter but without statistical significance. To prevent HEV, an educational program and working guidelines may be needed for high risk groups.
Abattoirs ; Adult ; Aged ; Enzyme-Linked Immunosorbent Assay ; Female ; Hepatitis Antibodies/blood ; Hepatitis E/*diagnosis/epidemiology/virology ; Hepatitis E virus/genetics/*immunology/metabolism ; Humans ; Immunoglobulin G/blood ; Immunoglobulin M/blood ; Male ; Middle Aged ; Multivariate Analysis ; Prevalence ; Republic of Korea/epidemiology ; Reverse Transcriptase Polymerase Chain Reaction ; Risk Factors ; Workplace

BACKGROUND/AIMS: The aims of the present study were to determine the outcomes of inactive hepatitis B virus (HBV) surface antigen (HBsAg) carriers over a 10-year study period and to elucidate the HBV serological profile of their family members. METHODS: We retrospectively analyzed the medical files of inactive HBsAg carriers followed up at the Department of Infectious Diseases of Kocatepe University Medical Faculty Hospital between March 2001 and January 2011. RESULTS: In total, 438 inactive HBsAg carriers were enrolled in this trial. The follow-up period was 33.7+/-22.5 months (mean+/-SD). Anti-hepatitis-B surface antibody seroconversion occurred in 0.7% of cases, while chronic hepatitis B was found in 0.5%. The anti-hepatitis-D virus (HDV) status was evaluated in 400 patients and anti-hepatitis C virus (HCV) in 430. It was found that 1% and 0.2% were positive for anti-HDV and anti-HCV, respectively. HBV serology was investigated in at least 1 family member of 334/438 (76.3%) patients. The HBsAg positivity rate was 34.6% in 625 family members of 334 patients. A comparison of the HBsAg positivity rates in terms of HBV DNA levels in index cases revealed that HBsAg seropositivity rates were higher in family members of HBV DNA-negative patients than in family members of HBV DNA-positive cases (P=0.0001). CONCLUSIONS: The HBsAg positivity rate was higher in family members of inactive HBsAg carriers than in the general population; these family members therefore have a higher risk of HBV transmission. Furthermore, despite negative HBV DNA levels, transmission risk was not reduced in these patients, and horizontal transmission seems to be independent of the HBV DNA value.
Adult ; Antibodies/blood ; Carrier State ; DNA, Viral/analysis ; Family Health ; Female ; Follow-Up Studies ; Hepatitis B Antibodies/blood ; Hepatitis B Surface Antigens/*blood ; Hepatitis B virus/genetics/immunology ; Hepatitis B, Chronic/*diagnosis/transmission/virology ; Hepatitis Delta Virus/immunology ; Humans ; Male ; Middle Aged ; Retrospective Studies

OBJECTIVETo observe the change in the number of antibodies of preneoplastic hepatocellular carcinoma (HCC) using early treatment by Compound Phyllanthus Urinaria L. (CPUL) on patients with preneoplastic hepatitis B virus (HBV)-associated HCC.

METHODSA total of 102 cirrhosis patients with regenerative or dysplastic nodules whose sera were tested positive for at least one of these six proteins (five up-regulated genes URG4, URG7, URG11, URG12 and URG19, and one down-regulated gene DRG2) were assigned randomly to two groups using continual random codes by SPSS software. Fifty-two patients were in the treatment group and 50 patients were in the control group. CPUL was used in the treatment group for 3 years, while the control group did not receive any treatment. The changes in HBV-DNA level, number of antibodies, and hepatocarcinogenesis occurred were observed. Patients who did not develop HCC were followed up for another 2 years.

RESULTSHBV-DNA levels decreased ⩾2log in 22.2% (10/45) of patients in the treatment group in contrast to only 5.0% (2/40) of patients in the control group (P=0.0228). The number of antibodies that were tested positive in the treatment group (1.08±1.01) was significantly lower compared with the control group (2.11±1.12) after 24 months of drug treatment (P<0.01). Both the positive rates of anti-URG11 (33/52) and anti-URG19 (31/52) were over 60% at baseline in the two groups, and were decreased to 48.1% (25/52) and 46.2% (24/52) respectively at 36 months of drug treatment, while the rates increased to 68.0% (34/50) and 66.0% (33/50) respectively (P=0.0417, P=0.0436) in the control group. The positive rate of anti-DRG2 was increased to 55.8% (29/52) at 36 months of drug treatment, while in the control group was decreased to 36.0% (18/50, P=0.0452). Among the 102 patients who developed HCC, 2 were in the treatment group and 9 were in the control group, meaning that a significant difference between the two groups (P=0.0212). In 11 patients who developed HCC, anti-URG11 and anti-URG19 were always positive, while anti-DRG2 was negative. Patients newly developing HCC were 6 (20.0%) in the control group, and only one (2.5%) in the treatment group (P=0.0441) during 2-year follow-up after the end of the treatment.

CONCLUSIONSAnti-URG11, anti-URG19 and anti-DRG2 could be used as early markers in the prediction of the therapeutic efficacy of CPUL in treating preneoplastic HCC. CPUL is useful in preventing or delaying the development of HBV-associated cirrhosis to HCC.

Antibodies, Viral ; blood ; Carcinoma, Hepatocellular ; therapy ; virology ; DNA, Viral ; analysis ; Hep G2 Cells ; Hepatitis B virus ; genetics ; immunology ; pathogenicity ; Humans ; Liver Neoplasms ; therapy ; virology ; Phyllanthus ; chemistry ; Plant Extracts ; therapeutic use ; Precancerous Conditions ; virology