A dynamic study of the intrafamilial spread of hepatitis B virus infection: relation with the viral replication

A total of 848 household contacts of 285 hepatitis B surface antigen (HBsAg) chronic carriers were included in a prospective study. Of the total number of contacts negative for hepatitis B virus (HBV) markers at baseline, 330 relatives of 145 HBsAg carriers were observed over a mean period of 20.1 months. Among all household contacts, 284 (33.5%) were found positive for at least one HBV marker. The prevalence of HBV markers was significantly higher among the contacts of more than one HBsAg carrier (75.9%) than among those with only one (26.0%) (P less than .001). The presence of hepatitis B e antigen (HBeAg), specific HBV-DNA polymerase (HBV-DNAp), HBV-DNA, and polymerized human serum albumin (pHSA-R) in the index case was associated with a significantly higher incidence of HBV markers among household contacts. During the follow-up, the number of household contacts initially negative for HBV markers who became infected was found to be in direct relation to the presence of HBeAg, HBV-DNAp, HBV-DNA and pHSA-R in the index case.     

Factors associated with intrafamilial transmission of hepatitis B virus infection in Korea.

Epidemiologic and serologic data on 137 household contacts of 51 chronic carriers of HBsAg and 111 household contacts of 38 controls who were negative for serologic markers of hepatitis B virus (HBV) were obtained from March 1990 to August 1991. Using this data, possible routes of intrafamilial transmission of hepatitis B virus among household contacts of chronic carriers of hepatitis B surface antigen (HBsAg) were evaluated and analyzed. The HBsAg prevalence among the household contacts of carriers was 14. 1% (95% CI 7.8-24.0) compared to 0.0% (95% CI 0.0-7.0) among those of controls (P < 0.01). The offspring of carriers showed significantly higher risk of HBV infection(relative risk; 6.6). Sharing of towels and handkerchieves, and drinking vessels was associated with an increased risk of HBV infection via intrafamilial transmission in Korea (relative risk 11.5 for towel and handkerchief, 12.1 for drinking vessels).     

Seroepidemiology of hepatitis A, B, and D viruses and human T-lymphocyte tropic viruses in Japanese drug abusers

To evaluate the prevalence of hepatitis virus markers and human T-cell lymphotropic virus infections among drug abusers in Japan, serum samples were collected from 91 male drug abusers at the Shinshu University Hospital and the rehabilitation facility in Matsumoto and from 519 healthy male blood donors as controls. Sera were tested for antibody to hepatitis A virus (anti-HAV), hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti-HBs), antibody to hepatitis B core antigen (anti-HBc), immunoglobulin M anti-HBc (IgM anti-HBc), antibody to hepatitis D virus (anti-HDV), antibody to HTLV type 1 (anti-HTLV 1), and antibody to human immunodeficiency virus (anti-HIV). The prevalence of anti-HAV was 13.2% in drug abusers and 10.8% in controls (not significant). The prevalences of HBsAg, anti-HBs, anti-HBc and exposure rate to hepatitis B virus (HBV) were 4.4%, 24.2%, 31.9%, and 35.2%, respectively, in drug abusers and 0.8%, 6.7%, 9.6%, and 9.6% in controls. The exposure rate to HBV was significantly different (P less than 0.001). IgM anti-HBc and anti-HDV were not detected in any sera. Anti-HTLV I was detected in three drug abusers (3.3%) and in one (0.2%) of the controls (P less than 0.01). All sera were negative for anti-HIV in all subjects. Infection with HBV and HTLV I is more common among drug abusers than in the general population of blood donors in Japan.     

Human herpesvirus-6 infections in infants admitted to hospital

The development of hepatocellular carcinoma (HCC) is very closely associated with chronic liver disease. In the present study, the prevalence of the hepatitis B virus (HBV) and hepatitis C virus (HCV) infection as a causative role in the development of HCC was analysed in 253 patients with HCC, who were admitted to our hospital during 1976–90. Among these patients, 68 (27%) were positive for HBsAg but negative for anti-HCV antibody (group I); in contrast, 147 (58%) were negative for HBsAg but positive for anti-HCV antibody (group II), 19 (7.5%) were both positive (group Ill), and 19 (7.5%) were both negative (group IV). To evaluate the serial changes in the prevalence of HBsAg and anti-HCV antibody, changes in the number of patients were compared between group I and group II. The number of group I patients reached a peak during 1982–84 and was thereafter followed by a decreasing trend, whereas the number of group ll patients steadlly increased and reached a plateau over 6 recent years. These results suggest that HCV infection recently seems to play a more important role in the development of HCC than chronic HBV infection, even in the Nagasaki Prefecture, where the HBV carrier rate is higher than elsewhere in Japan. © 1993 Wiley-Liss, Inc.     

Familial clustering of hepatitis B and C viruses in Korea.

In order to evaluate the familial clustering of hepatitis B virus(HBV) and hepatitis C virus(HCV) infections and to elucidate the possible routes of HCV transmission among Korean adults with chronic liver disease, 137 household contacts of 51 chronic carriers of HBsAg and 111 household contacts of 38 controls, and 181 household contacts of 96 anti-HCV positives and 102 household contacts of 76 anti-HCV negatives were tested from July 1990 to March 1994. Of 71 non-vaccinated household contacts of HBsAg carriers, 10 gave positive result for HBsAg(14.1%), but none of the household contacts of the controls were positive for HBsAg(p < 0.05). Familial clustering of HBV infection was found, when the offspring of carriers and controls were compared. A significantly higher percentage of the offspring of carriers were positive for HBV infection(54.6% vs 15.4%, p < 0.05) with OR of 6.6(95% Cl; 1.3-34.5). No evidence of familial clustering of HCV infection was found with 2.2%(4/181) anti-HCV positivity among the household contacts of index cases, similar to 1.0%(1/102) among those of controls. History of acute hepatitis(OR 3.2), transfusion(OR 3.2), and acupuncture(OR 2.5) were associated with an increased risk of HCV infection. In conclusion, HBV has strong familial clustering whereas HCV does not in Korea.     

Mutations in hepatitis B virus DNA from patients with coexisting HBsAg and anti-HBs

Background

The serological markers with coexistence of hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti-HBs) of hepatitis B virus (HBV) infection were rare pattern. The virological significance, immune response and clinical outcome of these patients remain largely unknown.

Objectives

This research explores the relationship between this serological profile and HBV genome variants.

Study design

We studied 35 patients both carrying HBsAg and anti-HBs (group I), and 70 patients with HBsAg positive but anti-HBs negative (group II, served as control). The HBV genome sequences were obtained by direct sequencing of polymerase chain reaction (PCR) products.

Results

The amino acid (aa) variation within major hydrophilic region (MHR), especially in the first loop (aa124-137) of “a” determinant in group I is significantly higher than those in group II. The aa variation of cytotoxic lymphocyte (CTL) epitope in HBsAg (aa87–aa95) in group I is also significantly higher than that in group II. Interestingly, the basal core promoter (BCP) double mutations (A1762T/G1764A) in group I is significantly higher than those in group II as well.

Conclusions

In patients with HBV infection, the coexistence of HBsAg and anti-HBs is associated with an increased aa variability in several key areas of HBV genome. The molecular characteristic of HBV in HBsAg and anti-HBs positive patients is distinct and worth further studies.     

Assessment of HBV persistent infection in an adult population in Taiwan

In order to study the prevalence of hepatitis B virus (HBV) in the adult population of Taiwan, we screened for the presence of HBV DNA in 205 blood samples from adult (20-59-year-old) volunteers. According to the serological markers of HBV, samples were divided into three groups: group I (173 subjects) was negative for both HBsAg and HBeAg; group II (14 subjects) was positive for both HBsAg and HBeAg; and group III consisted of 18 subjects who were HBsAg-positive but HBeAg-negative. Plasma HBV DNA was not detected in group I, but it was found in 85.7% and 11.8% of samples in group II and group III, respectively. A free-form HBV DNA was found in 14.3% of the leukocyte samples in group II. Furthermore, an integrated form of HBV DNA was detected in the leukocytes of two cases of group I who remained healthy based on clinical data. HBV DNA was also detected in the spermatozoa and liver cells of one of the cases.     

Immunogenicity and protective efficacy of low dose recombinant DNA hepatitis B vaccine in normal and high-risk neonates.

A low dose of recombinant DNA hepatitis B vaccine (HB-VAX II, MSD) was tested for efficacy in the prevention of perinatal hepatitis B virus (HBV) transmission in normal and high-risk neonates born from HBsAg carrier mothers. A dose of 2.5 micrograms recombinant vaccine was injected intramuscularly at 0, 1, 2 and 12 months of age to 30 newborns from HBsAg negative mother (group I), 30 from HBeAg negative/HBsAg carrier mother (group II) and 30 from HBeAg positive/HBsAg carrier mother (group III). The incidence of persistent HBsAg carrier infants at 13 months of age was 0, 0, and 30.4 percent in groups I, II and III, respectively. The protective efficacy in high risk infants in group III was 65.7 percent. The seroconversion at month 4, after the third dose of vaccination was 96.3, 95.7 and 100 percent in group I, group II and group III, respectively. After a booster dose of vaccination at 12 months of age, the seroconversion rose to 100 percent at month 13 in all three groups. The geometric mean titer (GMT) of anti-HBs antibody at 13 months of age were 2,092, 1,657 and 1,938 mIU/ml in group I, group II and group III, respectively. It is concluded that the low dose (2.5 micrograms) recombinant hepatitis B vaccine using alone is effective in prevention of perinatal HBV transmission in low risk infants (groups I and II), but it is less effective in high risk infants (group III).(ABSTRACT TRUNCATED AT 250 WORDS)     

Significance of liver histology in HBsAg‐positive,IgM anti‐HBc‐negative acute hepatitis B virus‐related hepatitis

Delladetsima I, Papatheodoridis G V, Tiniakos D G, Hatzakis A & Tassopoulos N C
(2012) Histopathology  61, 881–888 Significance of liver histology in HBsAg‐positive, IgM anti‐HBc‐negative acute hepatitis B virus‐related hepatitis Aims: The natural course of HBsAg‐positive, IgM anti‐HBc‐negative acute hepatitis B virus (HBV)‐related hepatitis is unclear. The aim of this study was to evaluate the prognostic significance of histological features and hepatic expression of HBV antigens in such patients. Methods and results: Fifty patients with HBsAg‐positive, IgM anti‐HBc‐negative acute hepatitis B who underwent liver biopsy during the acute hepatitis episode were studied [HBeAg seroconversion (n = 16), persistently positive for HBeAg (n = 9), and persistently negative for HBeAg (n = 25)]. Twenty‐six cases had features of typical acute hepatitis only (group A), and 24 cases had changes suggesting pre‐existing chronic hepatitis (group B). HBcAg and/or HBsAg immunoreactivity was detected less frequently in group A than in group B (31% versus 79%, P = 0.01). HBsAg clearance was observed in 24% of patients, almost exclusively in cases with HBeAg seroconversion. HBsAg loss was significantly more frequent in group A than in group B (52% versus 0%, P < 0.001), and in cases without rather than with immunohistochemical expression of HBV antigens (55% versus 0%, P < 0.001). In group A, HBsAg clearance was observed in 80%, 54% and 0% of patients with mild, moderate or severe acute hepatitis, respectively (P = 0.034). Conclusions: Histological information is very important for the prognosis of HBsAg‐positive, IgM anti‐HBc‐negative acute hepatitis B. HBeAg seroconversion with underlying typical acute hepatitis changes of mild to moderate severity without hepatic expression of HBV antigens strongly predicts subsequent HBsAg loss.     

Hepatitis B virus DNA in unusual serological profiles of hepatitis B surface antigen-positive sera

On the basis of a seroepidemiological survey of hepatitis B virus (HBV) infection conducted on 6208 random serum samples from four provinces of Thailand, we found 19 of 246 (7.7%) hepatitis B surface antigen (HBsAg)-positive samples with unusual serological constellations of HBV infection. Ten samples tested positive for HBsAg, anti-HBc (anti-hepatitis B core antibody), and anti-HBs (anti-hepatitis B surface antibody) markers (group I), 3 specimens were HBsAg and anti-HBs positive without detectable anti-HBc (group II), and the remaining 6 specimens showed only HBsAg (group III). In group I, 7 of 10 HBsAg-positive sera could be confirmed by HBsAg neutralization, yielding positive results for all samples. None of the group II sera were available in sufficient amounts for confirmation. In group III, five of six sera were confirmed by HBsAg neutralization, with four showing a positive reaction. HBV DNA was detected in 7 of 10 (70%) specimens in group I, in 1 of 3 (33.3%) specimens in group II, and in 3 of 6 (50%) specimens in group III. On the basis of HBsAg neutralization, HBV DNA was found in five of seven (71.4%) HBsAg-positive samples in group I and in three of four (75%) HBsAg-positive samples in group III, whereas the one confirmed HBsAg-negative sample in group III also remained negative for HBV DNA. Amino acid sequences were compared with those specifying the "a" determinant of the wild-type virus, particularly focusing on HBV-S protein variations between positions 110 and 160. Among 11 HBV DNA-positive sera, G145A was detected in 2 samples in group I, with the remaining samples identical to the wild-type virus. These unusual serological profiles may be due to the altered immune response of the host or to HBV variants.     

Hepatitis B antigen and antibody in patients with leprosy: a study of three resettlement villages in Thailand

It remains uncertain whether the cellular immune abnormalities of patients with lepromatous leprosy interfere with resolution of hepatitis B virus (HBV) infections. To investigate this question in an area coendemic for the two diseases, we determined the prevalence of hepatitis B surface antigen (HBsAg) and antibody (anti-HBs) in: 1) 204 leprosy patients living in three leprosy resettlement villages; 2) 198 contacts living in the same villages; and 3) 44 newly diagnosed leprosy patients in Thailand. Within the villages, the prevalence of HBsAg positivity was inversely related to age, tended to be more frequent in patients with tuberculoid than lepromatous leprosy, and was similar after age adjustment among persons with and without leprosy. The prevalence of HBV markers found in newly diagnosed patients was similar to that in the villagers. We conclude that extensive HBV transmission had occurred in the resettlement villages and that the natural history of HBV infection was similar in persons with, whether tuberculoid or lepromatous, and without leprosy.     

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.     

Correlation of HBV DNA and monoclonal reactivity to HBsAg in serum of patients with HBV infection

Hepatitis B virus (HBV) DNA hybridization assay, a monoclonal radioimmunoassay (M-RIA) for hepatitis B surface antigen (HBsAg) and conventional polyclonal immunoassays for HBV associated antigens were used to study sera from patients on dialysis and with acute hepatitis B. HBV DNA was detectable in hepatitis B e antigen (HBeAg) negative patients with acute hepatitis but not in HBsAg+ HBeAg- dialysis patients. In acute hepatitis, HBsAg immunoreactivity by M-RIA could still be detected even though a commercial immunoassay for HBsAg, the AUSRIA II, and the HBV DNA assay were no longer positive. Unlike in acute HBV infection, serum HBV DNA was detectable in dialysis patients who were AUSTRIA II negative but M-RIA positive. Serial determination of HBsAg by M-RIA and HBV DNA revealed episodes of HBV DNA positivity months after both the HBsAg was no longer positive by polyclonal immunoassay. Thus, the M-RIA for HBsAg and the molecular hybridization technique for HBV DNA are sensitive and specific assays for the identification of potentially infectious individuals who would not have been characterized as such based on the results of conventional polyclonal immunoassays.     

Occult hepatitis B virus infection in Korean patients with isolated anti-HBc

Serological detection of isolated anti-hepatitis B core antibody (anti-HBc) can occur in various scenarios, but the most clinically relevant situation is occult hepatitis B virus (HBV) infection (OBI). The purpose of this study was to evaluate the prevalence and clinical relevance of isolated anti-HBc and of OBI with isolated anti-HBc from an unselected hospital population. A total of 14,253 patients referred for hepatitis B surface antigen (HBsAg)/anti-HBs testing were classified into either the Health Promotion Center (HPC) group or the patient group. For patients who were negative for both HBsAg and anti-HBs, an anti-HBc test was additionally performed. An HBV DNA real-time PCR test was performed on isolated anti-HBc patients, and their demographic and clinical data were reviewed. The measured prevalence of isolated anti-HBc and OBI in isolated anti-HBc patients was 5.9 % and 4.7 %, respectively. Prevalence was higher in males, elderly people, and the patient group than in females, the younger, and the HPC group, respectively. In most cases, the levels of HBV DNA load were very low (less than 200 IU/mL), and most cases of OBI presented without liver disease or history of HBV infection. The prevalence of isolated anti-HBc and OBI are affected by the methods of detection, subject population, and constituent factors such as sex and age. Although detection of HBV DNA does not always indicate infectivity, highly sensitive standardized HBV DNA tests are needed in clinical settings to exclude the possibility of OBI, especially in the advanced age group.     

Clinical characteristics of hepatitis B virus infection in middle school students born after the universal infant vaccination program in Shanghai,China

The aim of this study was to investigate the prevalence of hepatitis B surface antigen (HBsAg) and clinical characteristics of middle school students infected with hepatitis B virus (HBV) after initiation of the HBV immunization program in China. A total of 82,156 serum samples were collected from students in 33 junior schools and 25 senior schools. HBsAg was tested by ELISA. Samples from HBsAg-positive students were collected and analyzed for HBV serum markers, alanine aminotransferase (ALT), HBV DNA levels, and HBV genotypes. The overall prevalence of HBsAg was 1.11% in middle school students in Shanghai, China. The prevalence of HBsAg in students born during the immunization program to HBsAg-positive mothers was significantly higher than that in students born during the universal vaccination program (1.47% vs 0.78%, P < 0.01). Only HBV genotypes B and C were found in these infections, and genotype C was the dominant one. Twenty-one (13.0%) of 162 HBsAg-positive students had active hepatitis B, and 18 were hepatitis B e antigen (HBeAg) positive. The universal infant vaccination program has reduced the prevalence of HBsAg significantly. HBeAg-positive hepatitis B, however, needs to be monitored among the students in whom vaccination failed.     

Prevalence of serologic markers of the hepatitis B virus in pregnant women of Bamako, Mali

A prospective study of the serological markers of hepatitis B virus (HBV) including hepatitis B virus surface antigen (HBsAg) and hepatitis B surface antibody (anti HBs) was conducted over 5 years in Bamako. The aims of this study were to assess the prevalence of HBsAg in pregnant women and to determine the risk of HBV infection for this population. The study involved 829 pregnant women for whom blood samples were collected after the first quarter of pregnancy. HBsAg and anti HBs were detected in all cases by radioimmunoassay. The prevalence of HBsAg and anti HBs in pregnant women was respectively 15.5% and 16.9%. This prevalence of HBsAg, higher than in the general population, points to the fact that pregnant women are a high risk group for hepatitis B infection. In addition, scarification and tattooing practices increase significantly the risk of infection by hepatitis B virus (OR = 2.03; 1.07 < OR < 3.82; chi 2 = 5.62; p: 1%). Thus, we can presumably conclude that infants and new borns in such conditions are largely exposed to hepatitis B virus infection, even though hepatitis B core antibody and hepatitis B e antigen were not investigated for technical reasons. In conclusion, the authors believe that infants and new borns must be systematically immunised against hepatitis B virus infection in Bamako.     

Viral replication in patients with concomitant hepatitis B and C virus infections

The aim of this study was to assess the implications of dual infection with hepatitis B virus (HBV) and hepatitis C virus (HCV). The HBV and HCV status in 100 patients with chronic hepatitis was analysed. HBV DNA was studied using liquid hybridization and the polymerase chain reaction (PCR). HCV viremia was measured using qualitative and quantitative PCR. The HCV genotype was determined by PCR. Patients were divided into three groups according to their HCV-RNA and HBsAg status: group I consisted of 40 patients with chronic hepatitis caused by HBV; group II, 40 patients with chronic hepatitis caused by HCV; and group III, 20 patients infected with both viruses. The HBV-DNA level was higher in group I than in group III (66.4 vs. 11.5 pg/ml; p<0.05). Quantification of HCV viremia revealed mean values of 36.9 copies × 10⁵/ml in group II and 5.5 copies/ml × 10⁵ in group III (p<0.05). The mean aminotransferase level and histological activity were higher in group III. HCV genotype 1b was the predominant type. The data suggest that there is reciprocal inhibition of viral replication in patients with dual HBV and HCV infection. Liver disease appears to be more severe in patients with chronic hepatitis B and C.     

Application strategies of serum HBV DNA detection in HBV infection patients: A retrospective study of 5611 specimens

The detection of hepatitis B virus (HBV) DNA plays a critical role in determining the level of viral replication in HBV-infected patients. However, how to select appropriate HBV DNA detection method, low-sensitivity (ls) and hypersensitivity (hs) remains unclear. In this study, hepatitis B surface antigen (HBsAg), hepatitis B e-antigen (HBeAg), alanine transaminase (ALT), aspartate transaminase (AST), and hs HBV DNA titers in serum of 5611 cases with suspected HBV infection were reviewed. Besides, the dynamic changes of HBV DNA and HBsAg in 85 chronic hepatitis B (CHB) patients receiving peginterferon α (PegIFNα) or entecavir (ETV) were observed. The results showed the positive rate of HBV DNA was 32.8%, of which low viral load (20 to 500 IU/mL) accounted for 51.8%. In the 5611 cases, when the HBsAg was less than 1000 IU/mL, the proportion of low viral load was 76.3%. Moreover, in patients receiving antiviral treatment, when HBsAg was less than 2000 IU/mL (PegIFNα) or HBsAg was less than 3500 IU/mL (ETV), the proportion of patients with low viral load was 79.5% or 78.0%, respectively. We developed a strategy of serum HBV DNA detection in HBV-infected patients. When HBsAg was negative, HBV DNA detection should be unnecessary. When HBsAg was 0.05 to 1000 IU/mL, hs HBV DNA should be detected in patients with abnormal level of ALT, AST, or HBeAg. While HBsAg was greater than or equal to 1000 IU/mL, ls HBV DNA was recommended. Moreover, the cutoff value of HBsAg increased during antiviral therapy of CHB patients. In conclusion, hs HBV DNA is of great value in HBV-infected patients with low viral load. HBV DNA detection methods should be selected reasonably according to the levels of HBsAg, HBeAg, ALT, and AST.     

Distribution of hepatitis B virus in the liver of chronic hepatitis C patients with occult hepatitis B virus infection

Although occult hepatitis B virus (HBV) infection (HBV-DNA in serum in the absence of hepatitis B surface antigen [HBsAg]) is common in chronic hepatitis C, its characteristics are not well known. In this work, the presence of HBV-DNA (by polymerase chain reaction; PCR) and its distribution (by in situ hybridization) in liver biopsies and peripheral blood mononuclear cells (PBMCs) from 32 patients with chronic hepatitis C and occult HBV infection and in 20 HBsAg chronic carriers were determined. The results showed that serum HBV-DNA levels were statistically lower (P = 0.001) in patients with occult HBV infection than in HBsAg chronic carriers. The HBV infection pattern in liver cells was identical between patients with occult HBV infection and those with chronic hepatitis B. However, the mean percentage of HBV-infected hepatocytes was significantly lower (P = 0.001) in patients with occult HBV infection (5 +/- 4.44%) than in HBsAg chronic carriers (17.99 +/- 11.58%). All patients with chronic hepatitis B have HBV-DNA in their PBMCs while this occurred in 50% of the cases with occult HBV infection. In conclusion, patients with occult HBV infection have a low number of HBV-infected hepatocytes and this fact could explain the lack of HBsAg detection and low viremia levels found in these cases.     

The effect of recombinant interferon-alpha on lymphocyte subpopulations and HLA-DR expression on liver tissue of HBV-positive individuals.

Interferon-alpha (IFN-alpha) has been reported to be beneficial in the treatment of chronic active hepatitis occurring as a result of hepatitis B virus (HBV) infection. Treatment with IFN-alpha has been proposed as a means of reducing the high rate of allograft infection in clinical liver transplantation in patients transplanted for HBV-related chronic active hepatitis and cirrhosis who are positive for hepatitis B surface antigen (HBsAg). We obtained resected whole livers from two groups of patients who received liver transplants. Group A consisted of 11 patients who were HBsAg+ but were not treated with IFN-alpha, and group B consisted of 10 patients who were also HBsAg+ but received IFN-alpha therapy for 29.4 +/- 5.6 days prior to orthotopic liver transplantation. No differences between the two groups existed in terms of a variety of demographic and clinical characteristics. The liver tissue was stained with monoclonal antibodies to cell surface antigens unique to different mononuclear cell populations by the avidin-biotin-immunoperoxidase technique to determine the effect of IFN-alpha on the lymphocyte subsets as well as HLA antigen expression on liver-infiltrating mononuclear cells. The number of HLA-DR+ lymphocytes in the liver was significantly increased (P less than 0.005) within the portal areas in group B compared with that found in group A (84 +/- 14 versus 33 +/- 5 per one high-power field). Moreover, the intensity of the HLA-DR antigen expression on lymphocytes in the portal areas (P less than 0.02) and in the hepatic lobule (P less than 0.05) was greater in group B than in group A. The number of natural killer (NK) cells was increased in the portal areas (P less than 0.05) of group B compared with group A. These alterations in the lymphocyte and NK cell populations present in the liver in response to IFN-alpha therapy presumably reflect an IFN-alpha-induced enhancement of the immune response to virus-infected cells.