General Epidemiological Parameters of Viral Hepatitis A,B, C,and E in Six Regions of China: A Cross-Sectional Study in 2007

Background

Viral hepatitis is a serious health burden worldwide. To date, few reports have addressed the prevalence of hepatitis A, B, C, and E in China. Therefore, the general epidemiological parameters of viral hepatitis remain unknown.

Principal Findings

In this cross-sectional study, we performed a serological prevalence analysis of viral hepatitis A, B, C, and E in 8,762 randomly selected Chinese subjects, which represented six areas of China. The overall prevalence of anti-Hepatitis C virus antibody (anti-HCV) was 0.58%, which was much lower than was estimated by WHO. The prevalences of Hepatitis B virus surface antigen (HBsAg), anti-Hepatitis B virus surface protein antibody (HBsAb), and anti-Hepatitis B virus core protein antibody (HBcAb) were 5.84%, 41.31%, and 35.92%, respectively, whereas in the group of subjects less than 5 years old, these prevalences were 1.16%, 46.77%, and 8.69% respectively, which suggests that the Hepatitis B virus (HBV)-carrier population is decreasing, and the nationwide HBV vaccine program has contributed to the lowered HBV prevalence in the younger generation in China. Meanwhile, a large deficit remains in coverage provided by the national HBV immune program. In addition, our data suggested the possibility that HBsAb may not last long enough to protect people from HBV infection throughout life. The overall prevalence of anti-Hepatitis A virus antibody (anti-HAV) and anti-Hepatitis E virus antibody (anti-HEV) were as high as 72.87% and 17.66%, respectively. The indices increased with age, which suggests that a large proportion of Chinese adults are protected by latent infection. Furthermore, the pattern of HEV infection was significantly different among ethnic groups in China.

Conclusions

Our study provided much important information concerning hepatitis A, B, C, and E prevalence in China and will contribute to worldwide oversight of viral hepatitis.     

A seroepidemiologic study of hepatitis B virus infection among barbers in Huangshi City, Hubei, China

Between March and August 1986 in Huangshi City, serum samples were collected from 316 apparently healthy barbers as a study group, as well as from 361 healthy employees of department stores as a control group. They were tested for hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti-HBs) and antibody to hepatitis B core antigen (anti-HBc) by enzyme-linked immunoadsorbent assays. Barbers showed a prevalence higher than that in controls for HBsAg (16.8 vs. 9.2%, P less than 0.01), anti-HBs (67.1 vs. 45.9%, P less than 0.001), and anti-HBc (39.2 vs. 21.2%, P less than 0.001). The prevalence of at least one marker of hepatitis B virus (HBV) infection was significantly higher in barbers than in controls (86.1 vs. 61.7%, P less than 0.001). Although the socioeconomic status and education level did not correlate with the frequency of HBV markers, the prevalence of HBsAg increased in parallel with the duration of practice. Because of their high risk for HBV infection, barbers need to be screened for markers of HBV infection on a routine basis, and are prime candidates for immunoprophylaxis with hepatitis B vaccine.     

Genotype and subtype analyses of hepatitis B virus (HBV) and possible co-infection of HBV and hepatitis C virus (HCV) or hepatitis D virus (HDV) in blood donors, patients with chronic liver disease and patients on hemodialysis in Surabaya, Indonesia

Four subtypes (adw, adr, ayw, and ayr ) and eight genotypes (A to H) of the hepatitis B virus (HBV) have been identified. They appear to be associated with particular geographic distribution, ethnicity, and possibly clinical outcomes. In this study, hepatitis B surface antigen (HBsAg) subtyping and HBV genotyping were carried out on sera obtained from HBsAg-positive HBV carriers, including healthy blood donors; patients with acute hepatitis, chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma; and patients on hemodialysis all located in Surabaya, Indonesia. We report here that all HBV isolates tested in Surabaya belonged to genotype B, with more than 90% of them being classified into subtype adw. Our results also revealed that prevalence of hepatitis C virus (HCV) co-infection among HBV carriers in Surabaya was approximately 10% for healthy blood donors and patients with chronic liver disease, and approximately 60% for patients on maintenance hemodialysis. Interestingly, HBsAg titers were lower in HBV carriers with HCV co-infection than in those without HCV co-infection. We also found that prevalence of hepatitis D virus (HDV) co-infection was < 0.5% among HBV carriers in Surabaya.     

High prevalence of human parvovirus 4 infection in HBV and HCV infected individuals in shanghai

Human parvovirus 4 (PARV4) has been detected in blood and diverse tissues samples from HIV/AIDS patients who are injecting drug users. Although B19 virus, the best characterized human parvovirus, has been shown to co-infect patients with hepatitis B or hepatitis C virus (HBV, HCV) infection, the association of PARV4 with HBV or HCV infections is still unknown.The aim of this study was to characterise the association of viruses belonging to PARV4 genotype 1 and 2 with chronic HBV and HCV infection in Shanghai.Serum samples of healthy controls, HCV infected subjects and HBV infected subjects were retrieved from Shanghai Center for Disease Control and Prevention (SCDC) Sample Bank. Parvovirus-specific nested-PCR was performed and results confirmed by sequencing. Sequences were compared with reference sequences obtained from Genbank to derive phylogeny trees.The frequency of parvovirus molecular detection was 16-22%, 33% and 41% in healthy controls, HCV infected and HBV infected subjects respectively, with PARV4 being the only parvovirus detected. HCV infected and HBV infected subjects had a significantly higher PARV4 prevalence than the healthy population. No statistical difference was found in PARV4 prevalence between HBV or HCV infected subjects. PARV4 sequence divergence within study groups was similar in healthy subjects, HBV or HCV infected subjects.Our data clearly demonstrate that PARV4 infection is strongly associated with HCV and HBV infection in Shanghai but may not cause increased disease severity.     

Prevalence of hepatitis B virus infection among atomic bomb survivors

The aim of this study was to determine whether the prevalence of hepatitis B virus (HBV) carriers increased with atomic bomb radiation dose, and whether radiation decreased the ability to clear HBV among the atomic bomb survivors. The study subjects were 6,121 participants in the Adult Health Study of atomic bomb survivors in Hiroshima and Nagasaki. After adjustment for age, sex, city and potential confounders, the rates of seropositivity for hepatitis B surface antigen (HBsAg), indicating current HBV infections, and anti-hepatitis B core antibody, indicating either cured or current infections, increased with radiation dose. However, no relationship was observed between radiation and anti-hepatitis B surface antibody (indicating cured infection). The proportion of persons who were unable to clear the virus, as the proportion of HBsAg-positive persons among those ever infected by HBV (positive for HBsAg or surface or core hepatitis B antibody), increased significantly with radiation dose among those receiving blood transfusions. This proportion was not related to dose among those who reported no such transfusions. The findings may suggest a lower likelihood of clearance after HBV infection among those who were more likely to have been infected with HBV as adults after atomic bomb irradiation rather than as infants or adults prior to irradiation.     

Hepatitis B infection among patients attending a sexually transmitted diseases clinic in Rio de Janeiro, Brazil

Hepatitis B virus (HBV) has a low endemicity in Rio de Janeiro, Brazil. Sexual transmission must play an important role in this virus, but the prevalence and risk factors have never been properly investigated. The aim of this paper is to determine the prevalence and risk factors for HBV infection in patients attending a Sexually Transmitted Diseases Clinic of the Universidade Federal Fluminense, from the State of Rio de Janeiro, Brazil. In a retrospective study, HBV seroprevalence was investigated in 440 patients. Serum of each patient was assayed for antibodies against hepatitis B core antigen (anti-HBc), hepatitis B surface antigen (HBsAg) and antibodies against hepatitis B surface antigen (anti-HBs). Demographic and risk factor data were extracted from clinic notes. The overall seroprevalence of exposure markers for HBV (anti-HBc, HBsAg and anti-HBs) were 13%, 3.4% and 8.5% respectively. Homo/bisexual behaviour, anal intercourse, HIV infection, positive serology for syphilis and blood transfusion were predictors of the HBV exposure. Among demographic data, age and place of birth were associated with the anti-HBc seropositivity.     

Delta Hepatitis in Denver

The prevalence of hepatitis D virus (HDV) infection in patients with hepatitis B virus (HBV) infection in the mid-United States is not well defined. We tested 65 patients seen between 1983 and 1986 with HBV infection in Denver for evidence of coexisting HDV infection. Five patients had anti-delta (δ) antibody. The prevalence of HDV infection was higher in patients with chronic hepatitis B (4/37) than in patients with acute hepatitis B (1/28). The prevalence of HDV infection in male homosexuals (3/32) was similar to reported figures, but the incidence of δ-infection in intravenous drug users in Denver was usually low (1/16). In comparison to Los Angeles, New York, southern Italy, and Sweden, Denver appears to have a low incidence of HDV infection, which probably reflects its low prevalence in the drug-using population.     

Shifting seroepidemiology of hepatitis A in Japan, 1973-2003

BACKGROUND: Hepatitis A infection is caused by hepatitis A virus (HAV) contracted through fecal-oral transmission. Life-long immunity is conferred after infection. Improved sanitary conditions have generally resulted in a significant decline in the incidence of hepatitis A. However, a low incidence of infection results in increased HAV susceptibility. The present study investigates the prevalence of anti-HAV antibody and clarifies the current HAV status and HAV susceptibility in Japan at 2003. METHODS: A total of 2,430 serum specimens collected during 2003 from Japanese individuals ranging in age from 0-92 years, were tested for anti-HAV antibody using an inhibition enzyme linked immunosorbent assay. All specimens were obtained from the WHO and the National Serum Reference Bank/National Institute of Infectious Diseases, Tokyo, Japan. RESULTS: The overall seroprevalence was 12.2%. Anti-HAV antibodies were rarely detected in individuals between 0-44 years of age. Starting from the age of 45-49 years, seropositivity gradually increased through age 65 years and above. Seroprevalence was not affected by gender, and geographic distribution did not affect age-specific seroprevalence until the age of 60 years. CONCLUSIONS: HAV susceptibility in Japan is increasing annually. Particularly, the prevalence of anti-HAV antibody in individuals older than 50 years in 2003 was 50.3%, which is significantly lower than that of corresponding studies in 1994 (74.3%), 1984 (96.9%) and 1973 (96.9%). The growing susceptible population of advanced age results in more frequent HAV infection among them. The surveillance of anti-HAV antibody prevalence is useful for implementing preventive measures and for controlling the spread of HAV.     

Declining prevalence of hepatitis A virus antibodies among children from low socioeconomic groups reinforces the need for the implementation of hepatitis A vaccination in Brazil

Age-related seroprevalence studies that have been conducted in Brazil have indicated a transition from a high to a medium endemicity of hepatitis A virus (HAV) infection in the population. However, most of these studies have focused on urban populations that experience lower incidence rates of HAV infection. In the current study, the prevalence of anti-HAV antibodies was investigated in children with a low socioeconomic status (SES) that live on the periphery of three capital cities in Brazil. A total of 1,162 dried blood spot samples were collected from individuals whose ages ranged from one-18 years and tested for anti-HAV antibodies. A large number of children under five years old (74.1-90%) were identified to be susceptible to HAV infection. The anti-HAV antibody prevalence reached ≥ 50% among those that were 10-14 years of age or older. The anti-HAV prevalence rates observed were characteristics of regions with intermediate level of hepatitis A endemicity. These data indicated that a large proportion of children with a low SES that live at the periphery of urban cities might be at risk of contracting an HAV infection. The hepatitis A vaccine that is currently offered in Brazil is only available for high-risk groups or at private clinics and is unaffordable for individuals with a lower SES. The results from this study suggest that the hepatitis A vaccine should be included in the Brazilian National Program for Immunisation.     

Seroprevalence of specific viral infections in confiscated orangutans (Pongo pygmaeus)

A serological survey of confiscated orangutans was conducted to determine the prevalence of specific viral infections cross reacting with human viruses. Antibodies specific for human hepatitis A (HAV) and B (HBV) viruses, herpes simplex viruses (HSV), and human T-lymphotropic virus (HTLV types I and II), as well as for the simian type D retroviruses (SRV types 1 to 3) and simian immunodeficiency virus (SIV) were tested in samples from 143 orangutans. Results revealed a high prevalence of potential pathogens. The most prevalent viral infection found was HBV (59.4% prevalence) of which 89.4% of infected individuals seroconverted to the non-infectious state and 10.6% remained as chronic carriers. Antibodies to HAV, HSV, HTLV-1, and SRV were also detected but at a lower prevalence. There was no evidence of lentiviral infections in this group of animals. The results confirm the importance of quarantine and the need for diagnostic differentiation of virus infections to determine if they are of human origin or unique orangutan viruses.     

Differential Effect of Viral Hepatitis Infection on Mortality among Korean Maintenance Dialysis Patients: A Prospective Multicenter Cohort Study

The role of infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) in terms of survival among dialysis patients remains incompletely understood. In the present multicenter prospective cohort study, we investigated the prevalences of HBV and HCV infection among 3,321 patients receiving maintenance dialysis in Korea, and assessed the impacts of these infections on survival. All included patients underwent hepatitis B antigen (HBsAg) and HCV antibody (Ab) testing, which revealed that 236 patients (7.1%) were HBsAg-positive, and 123 patients (3.7%) were HCV Ab-positive. HBsAg-positive and HCV Ab-positive patients were matched to hepatitis virus-negative patients using a propensity score at a ratio of 1:2. The prevalences of HBV and HCV infection did not significantly differ according to dialysis modality. Linear-by-linear association analysis revealed that hepatitis B prevalence significantly increased with increasing dialysis vintage (p = 0.001), and hepatitis C prevalence tended to be higher with increasing dialysis vintage (p = 0.074). We compared the survival of HBsAg-positive and HCV Ab-positive patients to that of hepatitis virus-negative patients. After propensity score matching, cumulative survival did not differ between HBsAg-positive and HBsAg-negative patients (p = 0.37), while HCV Ab-positive patients showed significantly lower survival than HCV Ab-negative patients (p = 0.03). The main conclusions of the present study are that HBV infection prevalence increased with longer dialysis vintage, and that both HBV and HCV infections were most prevalent among patients with the longest dialysis vintage. Additionally, HCV infection among maintenance dialysis patients is associated with an increased risk of mortality.     

Seroepidemiology of hepatitis A virus in Japan

A seroepidemiologic study to detect class-specific antibody against hepatitis A virus (HAV) was made with 831 randomly collected sera (415 in 1973 and 416 in 1984) from healthy Japanese. Competitive-inhibition, IgG, IgA, and IgM anti-HAV enzyme-linked immunosorbent assays (ELISA) were used. Both collections showed a low prevalence of IgG anti-HAV in young age groups and it increased rapidly at middle age and plateued at greater than or equal to 94% prevalence in the older age groups. However, two age groups spanning ages 25-34 demonstrated statistically lower IgG anti-HAV age prevalences in 1984 vs 1973 (P less than 0.001), with an average 10-year prevalence shift. These data suggest that there has been no significant level of HAV infection to alter antibody prevalences in Japan from 1973 to 1984. The markedly decreased incidence of HAV infection in Japan has created a presently large and growing population of HAV susceptibles.     

Hepatitis B virus infection profile in hemodialysis patients in Central Brazil: prevalence, risk factors, and genotypes

Hemodialysis patients are at high risk for hepatitis B virus (HBV) infection. A survey was conducted in the hemodialysis population of the state of Goiás, Central Brazil, aiming to assess the prevalence of HBV infection, to analyse associated risk factors, and also to investigate HBV genotypes distribution. A total of 1095 patients were interviewed in 15 dialysis units. Serum samples were screened for HBV serological markers by enzyme-linked immunosorbent assay. Hepatitis B surface antigen (HBsAg) positive samples were tested for HBV DNA by polymerase chain reaction and genotyped by restriction fragment length polymorphism. Global HBV infection prevalence was 29.8% (95% CI: 27.1-32.5). Multivariate analysis of risk factors showed that male gender, length of time on hemodialysis, and blood transfusion before 1993 were associated with HBV positivity. HBV DNA was detected in 65.4% (17/26) of the HBsAg-positive samples. Thirteen of 17 HBV DNA positive samples were genotyped. Genotype D (61.5%) was predominant, followed by A (30.8%), while genotype F was detected in only one (7.7%) sample.     

Duration of viral RNA circulation in blood of patients with hepatitis A

Duration of hepatitis A virus (HAV) RNA circulation in blood of patients with HA was assessed and compared with intensity of cytolytic syndrome. Detection of viral RNA was performed by RT-PCR method with specific primers to VP1/P2A region of HAV genome. 54 blood serum samples from 40 patients were prospectively studied on the presence of HAV RNA. The latterwas detected in 53.7% of serum samples. The greatest number of positive results of HAV RNA detection in blood of the patients with HA was obtained from 8th to 21st day of illness (77.4%). Prolonged viremia (42+/-9 days) was observed in more than 20% of the patients. The maximal time of HAV RNA daetection in blood serum amounted 74 days (period of follow-up). HAV RNA was present in almost all patients with AIAT activity higher than 500 U/l regardless of duration of illness.     

Prevalence of hepatitis B and C virus infection among leprosy patients in a leprosy-endemic region of central Brazil

Leprosy and hepatitis B virus (HBV) are highly endemic in some regions of the state of Mato Grosso, in central Brazil. The association of leprosy with HBV and hepatitis C virus (HCV) was assessed using a seroprevalence study and 191 leprosy outpatients were included. Demographic data and the clinical classification of leprosy were recorded. Evidence of previous HBV infection was present in 53 patients (27.7%, 95% confidence interval: 21.9-34.5) and two (1%) were HBsAg positive. Five (2.6%) had antibodies to HCV. The prevalence of previous exposure to HBV was higher than expected for an adult population in central Brazil. In contrast, the prevalence of anti-HCV antibodies was not much higher regarding the age range of participants. HBV markers were associated with a higher number of sex partners and the use of injections without proper sterilisation of the syringes. The number of HBV carriers was small, suggesting that there was no increased likelihood of chronification among these patients.     

病毒性肝炎HAV，HBV，HCV，HDV和HEV重叠感染的研究

采用ＥＬＩＳＡ法检测了１０８例乙型肝炎病毒（ＨＢＶ）感染者血清中的五种肝炎病毒──甲型（ＨＡＶ）、乙型（ＨＢＶ）、丙型（ＨＣＶ）、丁型（ＨＤＶ）和成型（ＨＥＶ）肝炎病毒的标志物,并采用ＰＣＲ技术检测了患者血清ＨＢＶＤＮＡ、ＨＣＶＲＮＡ及ＨＤＶＲＮＡ。结果五种肝炎病毒重叠感染者３５例（３２．４％）,单纯ＨＢＶ感染者７３例（６７．６％）。ＨＢＶ、ＨＡＶＭ重感染率为４．６％,ＨＢＶ、ＨＣＶ二重感染率为９．２％,ＨＢＶ、ＨＤＶＭ重感染率为１４．８％,ＨＢＶ、ＨＥＶ二重感染率为１．９％,ＨＢＶ、ＨＣＶ和ＨＤＶ三重感     

Hepatitis B virus screening in contacts of blood donors with antibodies against core protein (anti-HBC), but without surface antigen (HBsAg)

To increase blood safety Brazil introduced screening for anti-HBc among blood donors in 1993. There was a decrease in the hepatitis B virus (HB V) transmission, but this measure identified a great number ofHBsAg-negative, anti-HBc-positive donors. Surveillance policy determines that contacts of HBV carriers should be screened to HBV markers, but there is no recommendation about how to guide contacts of HBsAg-negative, anti-HBc-positive donors. Aiming to evaluate whether the contacts of this group are at greater risk for HB V infection, a cross-sectional study was performed to compare prevalence of HBV infection between contacts of HBsAg-positive blood donors (group I) and contacts of HBsAg-negative, anti-HBc-positive donors (group II). Contacts were submitted to a questionnaire and blood tests for HBV markers. In group I (n = 143), 53 (37.1%) were anti-HBc-positive and 11 (7.7%) were HBsAg-positive. In group II (n = 111), there were 9 and 0.9%, respectively. HB V exposure was associated with group I, sexual activity, blood transfusion, being one of the donor's parents, and living for more than ten years with the donor. Regarding the families as sample units, it was more common to find at least one member with HBV markers (p < 0.05) among the families of group I compared to group II. Contacts of HBsAg-negative, anti-HBc-positive individuals presented a much lower risk of having already been exposed to HBV and there is no need to screen them for HBV in low to moderate prevalence populations.     

The first large-scale nucleic acid amplification testing (NAT) of donated blood using multiplex reagent for simultaneous detection of HBV, HCV, and HIV-1 and significance of NAT for HBV.

The first nationwide nucleic acid amplification testing (NAT) for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus type 1 (HIV-1) of voluntarily donated blood after serological pre-screening and before release of cellular components and plasma for fractionation was implemented by the Japanese Red Cross Blood Transfusion Services. From February 1, 2000 to April 30, 2001, specimens from 6,805,010 units of serologically negative donation were screened in minipools of 50 samples within 24 hr after blood donation by NAT using multiplex HBV/HCV/HIV-1 reagent for blood transfusion including short shelf-life platelets. Among them, 112 HBV DNA-positives, 25 HCV RNA positives and 4 HIV-1 RNA positives were screened out and we could prevent transfusion of these NAT positive units. Subtypes/genotypes of HBV DNA, adr/C, adw/A, adw/B, adw/C, ayr/C and ayw/D were found and adr/C was predominant. A total of 61.6 % of them (69/112) were negative by overnight EIA. Sixth three of HBV NAT-positive samples carried virus loads less than 10(4) copies/mL and 92.1 % of them (58/63) were negative by overnight EIA. The virus growth curves of HBV in 6 cases obtained by retrospective and prospective follow-up study showed exponential straight lines in the early stage of serological window periods and the log times of HBV growth (10 fold increase) in serological window period were between 4.6 and 7.6 days. NAT screening with highly sensitive reagents in pool of specimens is useful to exclude blood units with low level of HBV and HBV mutants from blood transfusion.     

Hepatitis C and hepatitis B virus infection in different hemodialysis units in Belo Horizonte,Minas Gerais,Brazil

The prevalence, virological and epidemiological aspects of the hepatitis C virus (HCV) and the hepatitis B virus (HBV) infections vary among hemodialysis patients in different countries. Aiming at analyzing these aspects of HCV and HBV infections in hemodialysis patients in Belo Horizonte, MG, Brazil, we studied three hemodialysis units including 434 patients. Serology was used to detect anti-HCV and HBsAg. Reverse trancriptase nested polymerase chain reaction (RT-nested-PCR) of the 5'-noncoding region was used to detect circulating HCV RNA and restriction fragment length polymorphism analysis for genotyping. Seroprevalence varied from 26.5% to 11.1% for hepatitis C and from 5.9% to 0% for hepatitis B. Risk factors observed for HBV and/or HCV infections were the number of patients per dialysis unit, duration of treatment, number of clinics attended, number of blood units transfused, and lower level scholarity. Alanine aminotransferase levels were altered with a higher frequency in HBV or HCV seropositive patients. Half of ten patients, negative for anti-HCV, had detectable viremia by RT-nested-PCR, indicating that this technique should be used to confirm infections in this group of patients. The HCV genotype 1 was the most frequently observed, followed by the genotype 2, but no correlation was detected between genotype and clinical or epidemiological data.     

Prevalence of anti-hepatitis C virus antibody and chronic liver disease among atomic bomb survivors

To investigate whether exposure to atomic bomb radiation altered the prevalence of hepatitis C virus (HCV) infection or accelerated the progress toward chronic hepatitis after HCV infection, the seropositivity of antibody to hepatitis C virus (anti-HCV) was determined for 6,121 participants in the Adult Health Study of atomic bomb survivors in Hiroshima and Nagasaki. The seropositivity of anti-HCV antibody was 2.5 times higher among those with a history of blood transfusion and 1.2 times higher among those with a family history of liver disease, whereas acupuncture showed no association with anti-HCV. Although the prevalence of anti-HCV was lower for survivors with positive dose estimates than for those with 0 dose (relative prevalence 0.84, P = 0.022), there was no evidence of a smooth dose-response relationship. However, these data suggested that the radiation dose response for chronic liver disease among HCV antibody-positive survivors may be greater than that among HCV antibody-negative survivors (slope ratio 20). In conclusion, no dose-response relationship was found between anti-HCV positivity and radiation dose; a possible increase in the radiation dose response of chronic liver disease among anti-HCV-positive individuals was found. Thus radiation exposure may accelerate the progress of chronic liver disease associated with hepatitis C virus infection.