Asymptomatic Hepatitis B Surface Antigen Carriers Research Articles

HBV Vaccines: Advances and Development.

Hepatitis B virus (HBV) infection is a global public health problem that is closely related to liver cirrhosis and hepatocellular carcinoma (HCC). The prevalence of acute and chronic HBV infection, liver cirrhosis, and HCC has significantly decreased as a result of the introduction of universal HBV vaccination programs. The first hepatitis B vaccine approved was developed by purifying the hepatitis B surface antigen (HBsAg) from the plasma of asymptomatic HBsAg carriers. Subsequently, recombinant DNA technology led to the development of the recombinant hepatitis B vaccine. Although there are already several licensed vaccines available for HBV infection, continuous research is essential to develop even more effective vaccines. Prophylactic hepatitis B vaccination has been important in the prevention of hepatitis B because it has effectively produced protective immunity against hepatitis B viral infection. Prophylactic vaccines only need to provoke neutralizing antibodies directed against the HBV envelop proteins, whereas therapeutic vaccines are most likely needed to induce a comprehensive T cell response and thus, should include other HBV antigens, such as HBV core and polymerase. The existing vaccines have proven to be highly effective in preventing HBV infection, but ongoing research aims to improve their efficacy, duration of protection, and accessibility. The routine administration of the HBV vaccine is safe and well-tolerated worldwide. The purpose of this type of immunization is to trigger an immunological response in the host, which will halt HBV replication. The clinical efficacy and safety of the HBV vaccine are affected by a number of immunological and clinical factors. However, this success is now in jeopardy due to the breakthrough infections caused by HBV variants with mutations in the S gene, high viral loads, and virus-induced immunosuppression. In this review, we describe various types of available HBV vaccines, along with the recent progress in the ongoing battle to develop new vaccines against HBV.

Polymorphisms of RIG-I-like receptor influence HBV clearance in Chinese Han population.

Retinoic acid-inducible gene I-like receptors (RLRs) play an essential role in human innate immune, which may influence the spontaneous clearance of hepatitis B virus (HBV) infection. We aimed to investigate whether the SNPs in RLR family were associated with HBV spontaneous clearance. The current study included 82 participants with spontaneous clearance, 601 asymptomatic hepatitis B surface antigen (HBsAg) carriers, and 168 participants with chronic hepatitis B (CHB). Six SNPs (DDX58 rs3824456, rs3205166, DHX58 rs2074160, rs2074158, IFIH1 rs2111485, rs3747517) were genotyped to explore their association with HBV spontaneous clearance. Patients carrying the mutant allele C at rs3824456 or A at rs2074160 were more likely to achieve spontaneous clearance compared with asymptomatic HBsAg carriers (additive model: odds ratio [OR] = 0.69, 95% confidence interval [CI] = 0.49-0.97; dominant model: OR = 0.54, 95% CI = 0.31-0.95, respectively). In addition, patients carrying the mutant allele G at rs2111485 were more likely to achieve spontaneous clearance compared with CHB (dominant model: OR = 0.47, 95% CI = 0.25-0.87). The mutations were protective factors for HBV spontaneous clearance. These results suggest the DDX58 rs3824456, DHX58 s2074160, IFIH1 rs2111485 were associated with spontaneous clearance of HBV, which may be predictive markers in the Chinese Han population of HBV.

Asymptomatic hepatitis B carriers who were vaccinated at birth.

The long-term persistence of immunity following universal infant immunization against hepatitis B virus (HBV) and the need for a subsequent booster dose in adolescence remain under debate. With data derived from Long'an County, Guangxi, China, we reported previously that the prevalence of hepatitis B surface antigen (HBsAg) among adults born from 1987 to 1993 increases with age, although these individuals had received a first dose of the vaccine within 24 hours of birth. Here, we sought the source of transmission by comparison of genotypes among their family members using phylogenetic analysis of complete HBV S gene sequences. For comparison, we screened 2199 vaccinated individuals aged 5 to 17 in Cang Wu County and 1592 vaccinated individuals aged 3 to 7 in Ling Shan County in Guangxi for HBsAg carriers and investigate their family members. In total, 50 asymptomatic HBsAg carriers who were vaccinated at birth and 152 family members were analyzed. The results showed that 25% (95% CI: 6.0-44.0) of the HBsAg-positive children had not acquired their HBV infection from their mothers. This phenomenon showed a trend that increases with age. Antibody escape mutations were detected in 22.9% (95% CI: 11.0-34.8) of the isolates. In conclusion, a booster dose may be necessary for adolescence who were vaccinated at birth in highly endemic countries.

Hepatitis B virus infection in undocumented immigrants and refugees in Southern Italy: demographic, virological, and clinical features

BackgroundThe data on hepatitis b virus (HBV) infection in immigrants population are scanty. The porpoise of this study was to define the demographic, virological, and clinical characteristics of subjects infected with HBV chronic infection in a cohort of immigrants living in Naples, Italy.MethodsA screening for HBV infection was offered to 1,331 immigrants, of whom 1,212 (91%) (831 undocumented immigrants and 381 refugees) accepted and were screened for hepatitis B surface antigen (HBsAg) and anti-hepatitis B core antibody (HBc). Those found to be HBsAg positive were further investigated at third-level infectious disease units.ResultsOf the 1,212 immigrants screened, 116 (9.6%) were HBsAg positive, 490 (40.4%) were HBsAg negative/anti-HBc positive, and 606 (50%) were seronegative for both. Moreover, 21 (1.7%) were anti-human immunodeficiency virus positive and 45 (3.7%) were anti-hepatitis C virus positive. The logistic regression analysis showed that male sex (OR: 1.79; 95%CI: 1.28–2.51), Sub-Saharan African origin (OR: 6.18; 95%CI: 3.37–11.36), low level of schooling (OR: 0.96; 95%CI: 0.94–0.99), and minor parenteral risks for acquiring HBV infection (acupuncture, tattoo, piercing, or tribal practices, OR: 1.54; 95%CI: 1.1–2.16) were independently associated with ongoing or past HBV infection. Of the 116 HBsAg-positive immigrants, 90 (77.6%) completed their diagnostic itinerary at a third-level infectious disease unit: 29 (32.2%) were asymptomatic non-viremic HBsAg carriers, 43 (47.8%) were asymptomatic viremic carriers, 14 (15.6%) had chronic hepatitis, and four (4.4%) had liver cirrhosis, with superimposed hepatocellular carcinoma in two.ConclusionsThe data illustrate the demographic, clinical and virological characteristics of HBV infection in immigrants in Italy and indicate the need for Italian healthcare authorities to enhance their support for providing screening, HBV vaccination, treatment, and educational programs for this populations.

A novel hepatitis B virus subgenotype, D7, in Tunisian blood donors

Tunisia is a medium-level epidemic country for hepatitis B virus (HBV). This study characterizes, for the first time, full genome HBV strains from Tunisia. Viral load quantification and phylogenetic analyses of full genome or pre-S/S sequences were performed on 196 hepatitis B surface antigen (HBsAg)-positive plasma samples from Tunisian blood donors. The median viral load was 64.65 IU ml(-1) (range<5-7.7x10(8) IU ml(-1)) and 89% of samples had viral loads below 10,000 IU ml(-1). Fifty-nine strains formed a novel subgenotype D7, 41 strains clustered in subgenotype D1, seven strains in subgenotype A2 and one strain in genotype C. The novel subgenotype D7 was defined by maximum Bayesian posterior probability, a genetic divergence from other HBV/D subgenotypes by >4% and a stronger HBV/E signal in the X to core genes than subgenotype D1. In conclusion, HBV/D is dominant in asymptomatic Tunisian HBsAg carriers and a novel subgenotype, D7, was the most common subgenotype found in this population.

Genotype, phylogenetic analysis, and transmission pattern of occult hepatitis B virus (HBV) infection in families of asymptomatic HBsAg carriers

Occult hepatitis B is defined by the presence of hepatitis B virus (HBV) DNA in the serum in absence of hepatitis B surface antigen (HBsAg). Studies were conducted to screen for occult HBV infection among family members of HBV carriers, incidentally detected positive for HBV infection with a view to assess the pattern of virus transmission among them. Nested PCR assay, employing independent sets of primers to surface and core genes, was used for detection of HBV DNA in serum samples from 28 index cases with asymptomatic HBV infection, and in serum samples from 72 HBsAg negative/anti-HBc positive family members. HBV DNA was detected in 15 HBsAg negative family members of 10 HBsAg positive index patients and was studied in detail. Direct sequencing of S gene region of 25 isolates (10 index cases and 15 contacts) and phylogenetic analysis with data base sequences revealed that genotypes A, C, and D and subtype adw2, adr, and ayw3 were present among them. Evidence of transmission from outside family sources was found in addition to intrafamilial transmission among individuals with occult infection. Mutations in the major hydrophilic loop (MHL) of the S gene region were also detected, including the 'vaccine escape' mutation G145R in three cases. Although majority of the occult infection was associated with low viral load, 3/15 (20%) cases were with higher viral load and potential infectivity. These cases are especially notable in diagnostic, blood banking, and transplantation services.

Effects of Indomethacin on Viral Replication Markers in Asymptomatic Carriers of Hepatitis B: A Randomized, Placebo-Controlled Trial

Previous studies have suggested some benefits of nonsteroidal antiinflammatory drugs (NSAIDs) use in patients with chronic viral hepatitis. We evaluated potential effects of indomethacin in asymptomatic carriers of hepatitis B surface antigen (HBsAg). Randomized, placebo-controlled, double-masked clinical trial. One hundred and twelve patients who were confirmed to be HBsAg carriers for at least 6 months and had normal liver function tests, normal abdominal sonography, and no sign of cirrhosis were randomly assigned into two groups. One group (56 participants, mean age (+/-SD) 31.7 (+/-9.6) yr, 29 male, mean serum alanine aminotransferase (ALT) (+/-SD) 24.9 (+/-9.2)) received indomethacin capsules (25 mg) three times daily and the other group (56 participants, mean age (+/-SD) 33.8 (+/-10.2) yr, 33 male, mean serum ALT (+/-SD) 24.5 (+/-8.7)) took placebo capsules with identical package and appearance. All participants were under treatment for 6 months and were followed 3 months thereafter. Statistical analyses were performed both by intention-to-treat and on-treatment methods. Nine participants in the indomethacin group (16%) and 8 in the placebo group (14%) did not complete the trial. HBsAg seroconversion did not differ by treatment group (2 subjects in each group became seronegative). Hepatitis B virus DNA (HBV-DNA) became negative in sera of 7 participants in the indomethacin group but only in 1 in the placebo group (intention-to-treat p= 0.06; on-treatment p= 0.03). Seroconversion of HBeAg to anti-HBe occurred only in 5 participants in the indomethacin group (intention-to-treat p= 0.06; on-treatment p= 0.03). Adverse events included one case of hepatotoxicity and two cases of gastritis in the indomethacin group and one suspected gastritis in the placebo group. We suggest use of indomethacin only in the subgroup of asymptomatic HBsAg carriers who have detectable HBV-DNA or HBeAg in their sera.

Increased risk for hepatitis B-related liver cirrhosis in relatives of patients with hepatocellular carcinoma in northern Taiwan.

There is a tendency for familial aggregation of hepatocellular carcinoma (HCC). The aims of this study were to assess the degree to which familial aggregation of hepatitis B surface antigen (HBsAg) carriers accounts for familiality of HCC in families of hepatitis B-related HCC patients, and whether HCC shares a familial predisposition with liver cirrhosis among HBsAg carriers. A total of 671 first-degree relatives of HBsAg-positive HCC cases were recruited using abdominal ultrasonography and tests for HBsAg and serum aminotransferases. They were from 165 simplex families defined as having only one HCC case and 72 multiplex families with more than one case. In analyses of family history of HCC and cirrhosis, the data set consisted of 4,471 unrelated asymptomatic HBsAg carriers recruited in a prospective study. There was no significant difference in the HBsAg-positive rate among relatives between multiplex (55.7%) and simplex (48.1%) families. Sonographic evidence of liver cirrhosis was present in 14.4% of HBsAg-positive relatives from multiplex families but in only 7.8% of HBsAg-positive relatives from simplex families (multiplex versus simplex families: adjusted odds ratio [OR] = 2.29; 95% CI: 1.10-4.77). Among unrelated asymptomatic HBsAg carriers, the adjusted OR of liver cirrhosis associated with a first-degree family history of HCC was 2.80 (95% CI: 1.68-4.66). This association was stronger in HBsAg carriers <50 years. No association was seen between family history of HCC and hepatitis activity based on elevated levels of aminotransferases. Familial aggregation of HCC in HBsAg carriers is associated with familial clustering of liver cirrhosis.

The hepatologist in the haematologists' camp.

The hepatologist in the haematologists' camp.

Replication of hepatitis B virus in first-degree relatives of patients with hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) may occur in family clusters. No genetic mechanism has been identified as responsible for this familial tendency. We suspected that a longer hepatitis B virus (HBV) replication phase might be the reason for a higher risk of HCC in families with this disease. We performed liver biochemical tests, test for viral hepatitis markers and hepatitis B e antigen (HBeAg), and liver ultrasonography in relatives of patients with HCC. A total of 1,885 first-degree relatives from 688 families participated in this study. Seven hundred fifty-two relatives were found to be carriers of hepatitis B surface antigen (HBsAg) and 675 of them were tested for HBeAg. The prevalence of HBeAg was 27.4% in relatives of those with HCC and 20% in asymptomatic HBsAg carriers. The HBeAg prevalence rate was higher in relatives of those with HCC > or = 40 years old than in asymptomatic HBsAg carriers. Moreover, HBeAg was more likely to persist in men than in women > or = 40 years old. We conclude that families with HCC showed a prolonged HBV replication phase that may be one of the cofactors for a familial tendency for HCC.

Seroepidemiological study of hepatitis delta virus infection in Okinawa, Japan

A seroepidemiological study on hepatitis delta virus (HDV) infection was conducted in the Okinawan islands, the area of Japan where hepatitis B virus infection is most prevalent. The subjects of this study included 116 asymptomatic hepatitis B surface antigen (HBsAg) carriers, 48 patients with chronic hepatitis (CH), 19 with liver cirrhosis (LC), and 11 with hepatocellular carcinoma (HCC). Among the 194 serum samples examined, a total of 10 (5.2%) were anti-HDV seropositive. Anti-HDV was detected in 2 (1.7%) of the 116 asymptomatic HBsAg carriers, in 3 (6.3%) of the 48 patients with CH, and in 5 (26.3%) of the 19 with LC. However, none of the patients with HCC had detectable anti-HDV. Eight of the 10 were born in the Miyako island group and the remaining 2 on the main island of Okinawa. Since the subjects included 34 individuals who were living and/or born in the Miyako islands, the positive rate of anti-HDV in the islands was 23.5%. This study demonstrates the existence of an endemic area of HDV infection in Japan.

The frequency of hepatitis B virus infection in Greek patients with various types of glomerulonephritis

The frequency of hepatitis B surface antigen (HBsAg) was studied in the sera of 622 patients with glomerulonephritis (GN). The prevalence of HBs-antigenemia was 2.8% (18/622; eleven adults and seven children); the difference from 2.6% in the general population of Central and Southern Greece was not statistically significant (chi 2 = 0.01; p > 0.50). Two of the 11 HBsAg-seropositive adult patients with GN suffered from IgA nephropathy, one from IgA and membranous glomerulonephritis (MGN), four from diffuse proliferative GN, two from membranous GN and one each from crescentic GN and focal segmental glomerulosclerosis. Five children out of 12 with membranous glomerulonephritis, one out of 24 with IgA nephropathy and one out of 16 with focal segmental glomerulosclerosis had HBs-antigenemia. The frequency of HBs-antigenemia in children with MGN was 41.7%, which is significantly higher than in children with other types of GN (0.9%). All seropositive patients were asymptomatic HBsAg carriers, while one seropositive HBsAg child with MGN suffered from chronic persistent hepatitis. HBsAg was detected by the immunoperoxidase-antiperoxidase (PAP) method in the glomeruli of only 3 children with MGN and HBs antigenemia, while HBcAg was not detected in any case. Our study suggests that in the Greek population there is no increased prevalence of HBs-antigenemia in patients with glomerulonephritis. Moreover, HBsAg was not found to contribute in the pathogenesis of GN in adults but it may be associated with the pathogenesis of membranous GN in children.

Splenomegaly in asymptomatic chronic carriers of hepatitis B and D viruses

To investigate whether splenomegaly, a common and striking feature of hepatitis D virus (HDV)-related cirrhosis, is manifested in both the late cirrhotic phase and the early and asymptomatic stages of chronic HDV infection. A blind ultrasonographic study of HDV-positive and -negative hepatitis B surface antigen (HBsAg) carriers in the Community of Archangelos of Rhodes Island, Greece, where HDV infection is endemic. The ultrasonographic findings were compared with clinical, biochemical and demographic data by uni- and multivariate analysis. The study population comprised 47 HDV-positive and 78 HDV-negative asymptomatic HBsAg carriers. A maximal longitudinal diameter of the spleen of >12cm and >15cm was detected in 13 of 47 (27.7%) and three of 47 (6.4%) of the HDV-positive and in 13 of 78 (16.7%) and three of 78 (3.8%) of the HDV-negative group, respectively (P>0.1). Splenomegaly (>12cm) was associated with significant dilation of the portal vein and enlargement of the left hepatic lobe. Multivariate analysis demonstrated that in both the HDV-positive and -negative HBsAg carriers, factors associated with chronic hepatic injury and/or biochemical markers of liver necro-inflammation correlated significantly with splenomegaly and could explain most of the variability in splenic size, particularly in the HDV-positive group. Although splenomegaly is more frequent and pronounced in chronic liver disease due to HDV than in HBV disease alone, it does not appear to be a feature specific to chronic HDV infection. The main determinants of splenic enlargement in the present field study of HBsAg carriers were found to be liver necro-inflammation and ultrasonographic indices of portal hypertension, regardless of the presence or absence of HDV infection.

Clinicopathologic Course of Hepatitis B Infection in Surface Antigen Carriers Following Living-Related Renal Transplantation

We present the clinical course, serology, and histopathology of 17 living-related renal allograft recipients who were hepatitis B surface antigen (HBsAg) positive at the time of transplantation. Although 14 patients were hepatitis B e antigen (HBeAg) positive, none had clinical hepatitis at the time of transplantation. All patients were receiving moderate doses of prednisolone and azathioprine only. At the mean short-term follow-up of 70 months (range, 6 to 132 months), none of the patients had seroconversion to antibody to HBsAg. Four patients died due to extrahepatic complications between 16 and 50 months following transplantation. Of these, three had normal liver function at the time of death and one had portal tract infiltration by chronic inflammatory cells. One patient died due to fulminant hepatitis at 6 months after transplantation. Of the remaining 12 patients, although 11 were HBeAg positive, only two developed chronic active hepatitis. Our short-term follow-up data suggest that chronic liver disease is not a frequent complication following living-related renal transplantation in HBsAg carriers. In addition, the presence of HBeAg at the time of transplantation does not predict a bad prognosis. Thus, in a living-related renal transplant program, asymptomatic carriers of HBsAg with positive HBeAg are not a contraindication for renal transplantation.

Presence of hepatitis B surface antigen (HBsAg)-specific cytotoxic T cells in asymptomatic HBsAg carriers.

To investigate whether there is any evidence of an immune stimulation against hepatitis B virus surface antigen (HBsAg) in asymptomatic HBsAg carriers, proliferative and cytotoxic responses to HBsAg were measured in their peripheral blood lymphocytes. Although the majority of asymptomatic carriers had no proliferative response to HBsAg, 3 (25%) of 12 carriers showed significant T cell proliferation against HBsAg. In addition, using HBsAg-expressing autologous lymphoblastoid cell line (LCL) as target cells, HBsAg-specific cytotoxic activity was found in 2 of 3 asymptomatic HBsAg carriers who had a proliferative response against HBsAg. Furthermore, 6 cytotoxic T lymphocyte (CTL) clones were isolated from 1 asymptomatic carrier. The epitope recognized by 2 CTL clones was mapped to the major HBsAg residues 158-172. These CTL clones were able to produce interferon-gamma, tumor necrosis factor-alpha, or granulocyte-macrophage colony-stimulating factor. These findings demonstrate the presence of HBsAg-specific, major histocompatibility complex class I-restricted CTL in asymptomatic HBsAg carriers.

New assays for quantitative determination of viral markers in management of chronic hepatitis B virus infection.

We performed a quantitative study of serum hepatitis B virus (HBV) markers, including new parameters such as pre-S1 antigen (Ag), pre-S2 Ag, and anti-HBx, in 88 chronic hepatitis B surface antigen (HBsAg) carriers. New IMx assays for HBsAg and immunoglobulin M (IgM) anti-HBc detection were also used. The population studied was composed of 65 chronic hepatitis cases (40 positive for hepatitis B antigen [HBeAg] and 25 positive for anti-HBe) and 23 anti-HBe-positive, asymptomatic HBsAg carriers. Serum HBsAg levels detected by IMx were higher in HBeAg-positive than in anti-HBe-positive HBsAg carriers (all patient subgroups included) and correlated with the serum HBV DNA level (P = 0.0001). Both pre-S1 and pre-S2 Ags were detected by enzyme immunoassays in almost all HBsAg carriers. Both pre-S1 and pre-S2 Ag titers correlated positively with the serum HBsAg concentration (P = 0.0001), but only the pre-S1 Ag titer correlated with the level of serum HBV DNA (P = 0.02). The detection of low levels of IgM anti-hepatitis B core (anti-HBc) antibodies by IMx was associated with the presence of liver disease (P = 0.05) but not with the level of viral replication. The prevalence of anti-HBx antibodies detected by the enzyme immunoassay was slightly, although not significantly, higher in patients with high levels of HBV DNA (greater than 100 pg/ml) than in patients without detectable HBV DNA (P = 0.16). In anti-HBe-positive chronic HBsAg carriers, the quantitative detection of serum HBV DNA, pre-S Ag titers, and IgM anti HBc allowed us to predict which patients suffered from chronic liver disease and/or supported viral replication (P < 0.05). In a follow-up study of eight patients undergoing antiviral therapy, the clearance of both pre-S1 Ag and HBV DNA was associated with a subsequent clearance of HBV. Therefore, the quantitative determination of HBV DNA, pre-S Ags, IgM anti-HBc may prove useful for the decision to use and the monitoring of antiviral therapy, especially in anti-HBe-positive HBsAg carriers.

Role of hepatitis C virus infection in spontaneous hepatitis B surface antigen clearance during chronic hepatitis B virus infection.

To examine the role of hepatitis C virus (HCV) infection in spontaneous hepatitis B surface antigen (HBsAg) clearance during the course of chronic hepatitis B virus (HBV) infection, serum specimens from 32 asymptomatic HBsAg carriers and 22 patients with chronic hepatitis type B who underwent spontaneous HBsAg clearance were studied for antibody to HCV (anti-HCV) using commercial EIAs. The results were compared with those of control groups matched for age, sex, hepatitis B e antigen, antibody to hepatitis delta virus, and cirrhosis. Eight (25%) of the asymptomatic carriers and 9 (41%) of the patients with chronic hepatitis were seropositive for anti-HCV in contrast to 1.6% and 9.1% of their respective control groups (P less than .01). Serum alanine aminotransferase level was persistently abnormal after HBsAg clearance in one asymptomatic carrier and in four patients with chronic hepatitis. These patients were seropositive for anti-HCV and at least one of them was negative for HBV-DNA by polymerase chain reaction. The data suggest that HCV superinfection may not only suppress HBV or terminate the HBsAg carrier state but may also assume the role of HBV as the cause of persistent hepatitis or transaminase elevation.

Infection due to hepatitis delta virus in Africa: report from Senegal and review.

A review of the literature shows strong variations in the prevalence of hepatitis delta virus (HDV) among Africans seropositive for hepatitis B surface antigen (HBsAg). In Senegal, West Africa, prevalence of antibodies to HDV among asymptomatic HBsAg carriers appears to be linked to regional and/or socioeconomic factors. Antibodies to HDV were found in 22 (47%) of 47 HBsAg-seropositive patients with liver disease who were hospitalized in the main hospital of Dakar and in 4% to 44% of asymptomatic HBsAg carriers. Eight (36%) of 22 patients with liver disease were seropositive for IgM antibodies to HDV, whereas none of 18 asymptomatic subjects were seropositive (P less than .01). According to studies conducted in Europe and the United States, the presence of this marker may constitute support for the argument that HDV plays a role in the development of HBsAg-associated liver diseases in Senegal and, presumably, within the African continent.

Natural seroconversion from hepatitis be antigen to antibody among hepatitis B virus carriers in Okinawa islands

In the Okinawa Islands, the great majority of hepatitis B surface antigen (HBsAg) carriers have already acquired antibody to hepatitis Be antigen (anti-HBe) by the age of 30 years (preliminary cross-sectional data). To elucidate natural seroconversion from hepatitis Be antigen (HBeAg) to anti-HBe among HBsAg carriers found in the islands of Okinawa Prefecture, 34 HBeAg-positive HBsAg carriers were followed for 1-6 years with serial measurements of aminotransferase levels, HBeAg, and anti-HBe. The 34 subjects included 24 patients with chronic hepatitis (group 1) and ten asymptomatic HBsAg carriers (group 2). During the follow-up period, HBeAg disappeared from 14 subjects in group 1 with the cumulative clearance rate of HBeAg of 56.3% within the first 2 years and with 10 of the 14 subsequently developing anti-HBe. Moreover, the aminotransferases in 12 of the 14 spontaneously seroconverted fell into the normal range. The annual clearance rates of HBeAg among group 1 and group 2 were 25.6% and 9.3%, respectively. The tendency for early disappearance of HBeAg during a carrier's life time or in the course of chronic hepatitis may lead to the low death rate from hepatocellular carcinoma (HCC) particularly HCC associated with hepatitis B virus infection in this area.

Why most patients with hepatitis delta virus infection are seronegative for hepatitis B e antigen: A prospective controlled study

A prospective age/sex matched control and follow-up study was conducted to explore the reason(s) for the association of hepatitis delta virus (HDV) infection with hepatitis B e antigen (HBeAg) negative hepatitis B surface antigen (HBsAg) carrier state. Over a 3-year period, a total of 110 patients (104 males and six females) with acute HDV superinfection were documented in our unit. Twenty-four (21.8%) of them were HBeAg positive at the onset of acute HDV infection. In the control study, 110 age- and sex-matched asymptomatic HBsAg carriers with normal serum transaminase, as well as 110 age- and sex-matched patients with chronic type B hepatitis were randomly selected from the computer files of the same 3-year period of entry. The prevalence of serum HBeAg in patients with HDV infection was similar to that of asymptomatic HBsAg carriers (20.9%), but significantly lower than that of the patients with chronic type B hepatitis (72.7%). In a follow-up study of 16 HBeAg-positive patients with HDV infection, eight (50%) cleared HBeAg and three (18.8%) seroconverted to anti-HBe within 3 months. The HBeAg clearance rate was significantly higher than for chronic type B hepatitis and asymptomatic carriers ( p < 0.01). The results suggest that the low prevalence of serum HBeAg in HDV infection simply reflects the HBeAg/anti-HBe status of the asymptomatic HBsAg carriers in the population under study. Also in some patients HDV superinfection may itself suppress HBV and thus clear HBeAg.