<b>OBJECTIVEb>To investigate the prevalence of occult HBV infection in the normal population in Xiamen.

<b>METHODSb>4 437 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.

<b>RESULTSb>Among 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).

<b>CONCLUSIONb>In 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

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

<b>METHODSb>A 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.

<b>RESULTSb>A 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.

<b>CONCLUSIONb>Anti-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

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

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

<b>OBJECTIVEb>To 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.

<b>METHODSb>A 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.

<b>RESULTSb>HBV-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.

<b>CONCLUSIONSb>Anti-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

BACKGROUND/AIMS: The prevalence of occult HBV infection depends on the prevalence of HBV infection in the general population. Hemodialysis patients are at increased risk for HBV infection. The aim of this study was to determine the prevalence of occult HBV infection in hemodialysis patients. METHODS: Total of 98 patients undergoing hemodialysis in CHA Bundang Medical Center (Seongnam, Korea) were included. Liver function tests and analysis of HBsAg, anti-HBs, anti-HBc and anti-HCV were performed. HBV DNA testing was conducted by using two specific quantitative methods. RESULTS: HBsAg was detected in 4 of 98 patients (4.1%), and they were excluded. Among 94 patients with HBsAg negative and anti-HCV negative, one (1.1%) patient with the TaqMan PCR test and 3 (3.2%) patients with the COBAS Amplicor HBV test were positive for HBV DNA. One patient was positive in both methods. Two patients were positive for both anti-HBs and anti-HBc and one patient was negative for both anti-HBs and anti-HBc. CONCLUSIONS: The present study showed the prevalence of occult HBV infection in HBsAg negative and anti-HCV negative patients on hemodialysis at our center was 3.2%. Because there is possibility of HBV transmission in HBsAg negative patients on hemodialysis, more attention should be given to prevent HBV transmission.
Adult ; Aged ; Aged, 80 and over ; Antibodies/blood ; DNA, Viral/analysis ; Feces/*virology ; Female ; Hepatitis B/complications/*epidemiology/transmission ; Hepatitis B Core Antigens/immunology ; Hepatitis B virus/genetics/immunology ; Hepatitis C Antibodies/blood ; Humans ; Kidney Failure, Chronic/*complications/diagnosis ; Male ; Middle Aged ; Polymerase Chain Reaction ; Prevalence ; Renal Dialysis ; Risk Factors

Occult HBV infection is characterized by the absence of serum HBsAg with persistence of low level of intrahepatic HBV DNA. Several suggested mechanisms for the origin of occult HBV infection include strong suppression of viral replication and gene expression, mutation in the regulatory regions of HBV genome, formation of immunoglobulin-bound HBsAg, viral interference, and blockage of HBsAg secretion from infected hepatocytes. Standardized assays are not yet available, and sensitive HBV DNA amplification assay is necessary for the diagnosis of cryptic infection. Detection rate of HBV DNA is highest in IgG anti-HBc positive population. However, neither anti-HBc nor anti-HBs can be detected in a significant proportion of infected persons. Occult HBV infection occurs in a number of clinical settings and is highly prevalent in HCV-infected patients as well as in patients with cryptogenic chronic liver disease including hepatocellular carcinoma.
DNA, Viral/analysis ; Hepatitis B/*diagnosis/*epidemiology/metabolism ; Hepatitis B Antibodies/blood ; Hepatitis B Core Antigens/immunology ; Hepatitis B Surface Antigens/blood ; Humans

Several studies have reported that ABO blood group, hepatitis B virus (HBV) and hepatitis C virus (HCV) infection contribute to the development of pancreatic cancer. The aim of this study was to evaluate the association between these factors and pancreatic cancer in the Korean population. We retrospectively recruited 753 patients with pancreatic cancer and 3,012 healthy controls, matched 4 to 1 with cancer patients for age and sex, between 2001 and 2011, at the National Cancer Center, Korea. A multivariate logistic regression analysis was employed to estimate adjusted odds ratios (AORs). The AOR for pancreatic cancer in subjects with non-O blood types (A, AB, and B), compared to blood type O, was 1.29 (95% CI, 1.05-1.58; P = 0.01). Seropositivity for hepatitis B virus surface antigen was not significantly related to pancreatic cancer, either in univariate (odds ratio 1.03; 95% CI, 0.69-1.53; P = 0.91) or multivariate analysis (AOR, 1.02; 95% CI, 0.67-1.56; P = 0.93). The AOR for pancreatic cancer in subjects displaying seropositivity for anti-HCV was 2.30 (95% CI, 1.30-4.08; P < 0.01). Our results suggest that the non-O blood types and anti-HCV seropositivity, but not HBV infection, may increase the risk of developing pancreatic cancer in Korea, where HBV is endemic.
ABO Blood-Group System ; Aged ; Case-Control Studies ; Female ; Hepatitis B/complications/diagnosis ; Hepatitis B Surface Antigens/blood ; Hepatitis C/*complications/diagnosis ; Hepatitis C Antibodies/blood ; Humans ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Pancreatic Neoplasms/diagnosis/*etiology ; Republic of Korea ; Retrospective Studies ; Risk Factors

The prevalence of hepatocellular carcinoma (HCC) has increased in recent years. However, HCC remains poorly characterized in elderly patients, and comprehensive data are limited. This study aimed to investigate the clinical characteristics, prognostic features and survival outcome of elderly HCC patients. We retrospectively analyzed 992 HCC patients treated at Dongsan Hospital from January 2003 to December 2007. The patients were divided into two age groups: < 70 yr (n = 813) and > or = 70 yr (n = 179). Elderly HCC patients, compared to younger patients, had significantly higher incidence of females (31.3% vs 18.9%, P = 0.001), hepatitis C-related disease (HCV antibody positivity 26.3% vs 9.2%, P = 0.001) and comorbid condition (53.6% vs 32.1%), but lower rates of hepatitis B-related disease (HBs antigen positivity 31.3% vs 69.4%, P = 0.001). There were no significant differences in underlying liver function, stage and survival outcomes. Factors significantly influencing the prognosis of HCC were Child-Pugh grade, number of HCC, level of alpha-fetoprotein, presence of metastasis. The survival outcome of older patients with HCC was not different from that of younger patients. There were no differences between groups in independent factors influencing the prognosis of HCC. Therefore, determining the optimal management strategy for elderly HCC patients is important to improve survival and long-term outcomes.
Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; Carcinoma, Hepatocellular/etiology/*mortality/*therapy ; Chemoembolization, Therapeutic ; Female ; Hepatitis B/complications/diagnosis ; Hepatitis B Surface Antigens/blood ; Hepatitis C/complications/diagnosis ; Hepatitis C Antibodies/blood ; Humans ; Liver Neoplasms/etiology/*mortality/*therapy ; Male ; Middle Aged ; Palliative Care ; Regression Analysis ; Republic of Korea ; Retrospective Studies ; Survival Analysis ; alpha-Fetoproteins/analysis

BACKGROUND/AIMS: Many patients are diagnosed with cryptogenic hepatocellular carcinoma (HCC) without metabolic syndrome (MS). We investigated the risk factors for cryptogenic HCC in patients with a low body mass index (BMI) or without MS. METHODS: Thirty-six patients were diagnosed with cryptogenic HCC over a 10-year period at a tertiary research hospital. Data including BMI score and risk factors for MS were analyzed retrospectively. Patients with fewer than two risk factors for MS (n = 16) were compared with those with two or more risk factors (n = 20). Patients with high BMI (> or = 23 kg/m2, n = 20) were also compared with those with lower BMI (n = 16). RESULTS: Patients with fewer than two risk factors for MS were significantly more likely to smoke and be hepatitis B surface antibodies (anti-HBs)-positive vs. patients with two or more risk factors. However, only smoking was statistically significant on multivariate analysis. Peaks of BMI were observed in two regions. Lower BMI was significantly associated with the presence of anti-HBs compared with high BMI, although this association was not statistically significant on multivariate analysis. CONCLUSIONS: Smoking is a potential risk factor for cryptogenic HCC in patients without MS. Remote hepatitis B virus infection may be a risk factor for cryptogenic HCC in patients without MS or with a low BMI.
Aged ; Aged, 80 and over ; *Body Mass Index ; Carcinoma, Hepatocellular/*epidemiology ; Chi-Square Distribution ; Female ; Hepatitis B/diagnosis/epidemiology ; Hepatitis B Antibodies/blood ; Hepatitis B Surface Antigens/immunology ; Humans ; Liver Neoplasms/*epidemiology ; Logistic Models ; Male ; Metabolic Syndrome X/*epidemiology ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Republic of Korea/epidemiology ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Smoking/adverse effects/epidemiology ; Time Factors