[Abstract efficacy of combined vaccine for the prevention of HBV transmission in highly viremic HBeAg+ mothers and the HBV markers' dynamic change of babies in follow-up].

OBJECTIVE: To evaluate the efficacy of combined vaccination with 200IU dose of HBIG and 20 µg of anti-HBV vaccine for the prevention of HBV vertical transmission in babies delivered by HBeAg + and highly viremic mothers and the HBV markers' dynamic changes in babies during follow-up. METHODS: HBeAg + mothers with HBV DNA ≥ to 1.0 × 6 log(10) copies/ml were enrolled and their babies were followed up until 12 months old. The infants received HBIG 200 IU IM in 24 hrs and on day 15, and 20 µg recombinant anti-HBV vaccine at 0, 1 and 6 months. The HBV markers and HBV DNA were tested at birth day, and 1, 7, 12 months after birth respectively. The vertical transmission rate at birth and intrauterine infection rate, the HBsAb positive rate and the HBV markers' dynamic changes during follow up were evaluated. RESULTS: (1) 29 out of 127 infants with HBsAg (+) at birth, 11 of which were HBV DNA (+), HBV perinatal transmission rate was 22.83%. 2 infants' HBsAg were positive at month 1 and became negative at month 7 and 10 infants were still HBsAg (+) and HBV DNA (+). HBV intrauterine infection rate was 7.87%. (2) The positive rate of HBeAg and HBcAb in uninfected infants were 96.58% and 98.29% respectively, which declined gradually to undetectable level after immunization. No infants were HBeAb (+). (3) Infants uninfected produced effective HBsAb after vaccination. The level of HBsAb elevated gradually, and the level of HBeAg decreased quickly even to undetectable. CONCLUSION: The combination vaccination of 200 IU HBIG with 20 µg recombinant anti-HBV vaccine in the Infants delivered by HBeAg (+) and highly viremic mothers reduced obviously the rate of perinatal transmission of HBV, enhanced largely the production of antibody against HBV surface antigen and dropped the maternal HBeAg and HBcAb in infants or even to negative.

The role of entecavir in preventing hepatitis B recurrence after liver transplantation.

OBJECTIVE: Although hepatitis B recurrence after liver transplantation has been reduced to 0%-10% since the application of the combination therapy of hepatitis B immunoglobulin (HBIG) and lamivudine, the viral mutation resistance of lamivudine is still an obstacle to the outcome of liver transplantation. Here we evaluate the role of entecavir in preventing hepatitis B recurrence after liver transplantation. METHODS: Patients who received a liver transplantation for hepatitis B virus (HBV)-related end-stage liver disease in our center from March 2006 to December 2008 were enrolled in this study. All patients received entecavir (0.5 mg orally, daily) or lamivudine (100 mg orally, daily) together with a long-term low dosage of HBIG to prevent hepatitis B recurrence after transplantation. Serum viral markers (HBsAg, anti-HBs, HBeAg, anti-HBc and anti-HBe) and HBV-DNA level were determined. RESULTS: Thirty patients receiving entecavir and 90 patients receiving lamivudine were matched with the same age and sex in both groups. No reinfection of hepatitis B was detected in the entecavir group. The hepatitis B surface antigen of patients in the entecavir group became negative within one week and no patient had any adverse effect relating to entecavir. There was no difference in the cumulative survival rate between the entecavir group and the lamivudine group (P > 0.05). CONCLUSION: This study shows that entecavir combined with low dosages of HBIG is effective and safe in preventing hepatitis B recurrence after liver transplantation, but its long-term effect is still under investigation and a large-sample study will be carried out in the future.

Factors associated with incomplete vaccination of babies at risk of perinatal hepatitis B transmission: a London study in 2006.

We measured the hepatitis B (HB) vaccination uptake in 249 London babies born in 2004 to HBsAg positive mothers. Two thirds (69%) received three vaccinations and half (49%, 95% CI 43-56) received a complete course (four doses). Complete immunization was associated with sector of delivery (p<0.001), recording of the GP details in case notes, having booked for antenatal care, having a good command of English, and receipt of written information on HB. A third of the babies (33%) had a post-vaccination test; when the mother had other children, 39% of the oldest children were vaccinated; information on partner's vaccination was available for 12%. This study highlights that appropriate counseling and information should be provided to the mothers, and the importance in London of arrangements for integrated care across acute and primary care services.

Retransplantation of patients with severe posttransplant hepatitis B in the first allograft.

BACKGROUND: The outcome of orthotopic liver transplantation (OLTX) in patients retransplanted for severe hepatitis B virus (HBV) in the first allograft has been poor due to high rates of HBV reinfection and even more aggressive disease in the second graft. Recent data suggest that hepatitis B immunoglobulin (HBIg) given after transplantation can be successful in delaying or preventing HBV reinfection in patients transplanted for chronic hepatitis B cirrhosis. We report the successful retransplantation of patients who developed recurrent or de novo hepatitis B after OLTXY. METHODS: Using similar HBIg regimens, two centers retransplanted seven patients after they developed recurrent or de novo hepatitis B in the first allograft. At retransplantation all seven patients were HBs antigen (Ag) positive; four patients were positive for HBeAg and HBV DNA by immunoblot assay, two patients were negative for HBeAg and HBV DNA, and one patient was positive for HBV DNA and negative for HBeAg. All patients were either HDV Ag or anti-HDV negative. One patient was anti-HCV positive. All patients received HBIg infusions after retransplantation to maintain serum anti-HBs levels >500 IU/L indefinitely. RESULTS: After retransplantation, six of seven patients are alive (86%): all are without evidence of HBV recurrence with serum negative for HBsAg, HBeAg, and HBV DNA by immunoblot assay. Liver biopsies are normal on routine studies with immunohistochemical stains for HBcAg and HBsAg also being negative. Mean follow-up of these six patients is 40.1 months (range 21-63 months). One patient (14%) developed HBV reinfection 7 months after his second transplant, in spite of maintaining target anti-HBs levels. He maintained stable liver function with minimal evidence of clinical hepatitis B, but died 8 months later from an unrelated stroke. CONCLUSIONS: We conclude that patients with recurrent or de novo hepatitis B after OLTX can be successfully retransplanted using aggressive immunoprophylaxis to prevent HBV reinfection. The failure of HBIg therapy in one patient underscores the need for other effective adjunctive anti-HBV modalities.

Passive transfer of hepatitis antibodies during intravenous administration of immune globulin.

We studied the effect of intravenous immune globulin (IVIG) infusion on the levels of hepatitis B and C antibodies in 10 premature babies. All four tested lots of a commercially purchased IVIG preparation were found to contain substantial amounts of hepatitis B core and hepatitis C antibodies. Our results show that passive transfer of hepatitis B and C virus antibodies occurred after IVIG infusion, and that the levels were dependent on the quantity of IVIG given. When assessing neonates for hepatitis, the factor of receipt of blood products, including IVIG, needs to be considered to interpret laboratory results.

Characterization of the immune response of volunteers vaccinated with a killed vaccine against hepatitis A.

To characterize the immune response elicited by the hepatitis A virus (HAV) vaccine, the sera of 79 subjects who received two vaccine doses at an interval of 1 month and a booster dose 6 months after the first dose, were analysed by ELISA, radioimmunofocus inhibition test (RIFIT) and by a competition monoclonal antibody assay using two neutralizing mAbs (K3-4C8 and B5-B3), which recognize different epitopes. The data show that 93.6% of the volunteers responded after one dose, as detected by ELISA. After the second dose, 100% seroconversion (total Ig) was achieved and most of the vaccines had neutralizing antibodies. Furthermore, these antibodies are able to inhibit the binding of mAbs K3-4C8 and B5-B3 to the HAV virus, indicating that they recognize two major neutralizing epitopes identified on infectious virions. Using a standard commercial radioimmunoassay test, 100% of the subjects were found positive after the third dose. These different methods of titration were also performed on sera of convalescents and immune serum globulin (ISG) recipients. Although the level of antibodies in convalescents is significantly higher than in vaccinees or in ISG recipients, the relative amount of neutralizing antibodies quantified by the competition monoclonal antibody assay is equivalent for the groups tested.

Passive immunization against hepatitis A.

Administration of human serum immune globulin (Ig) is an effective means of protecting individuals against hepatitis A virus (HAV) infection and disease. Several large field studies have demonstrated that if given before exposure, Ig will prevent infection with HAV. Furthermore, if Ig is given during the incubation period of hepatitis A, the severity of infection may be reduced and potentially clinical infections may be converted into subclinical ones. Although uncommon, infection which occurs in the presence of circulating antibody may occasionally lead to passive-active immunity. Unfortunately, the duration of Ig protection is dose dependent, and high dose administration provides less than six months protection. Ig preparations contain HAV antibodies at levels detectable by commercial immunoassays; however, recipients of Ig do not have detectable levels of HAV antibodies when tested by the same method. Using more sensitive immunoassays and neutralization assays, low titres of HAV antibody can be detected in Ig recipients. Since Ig provides approximately 90% efficacy in preventing hepatitis A, it would appear that very low levels of HAV antibody are needed to prevent infection. Consequently, measurement of HAV antibodies elicited by HAV vaccines should provide a reasonable method to evaluate their immunogenicity and predict their efficacy.

Localization of hepatitis C virus (HCV) antigen by immunohistochemistry on fixed-embedded liver tissue.

An immunohistochemical method of staining HCV-related antigens in fixed-embedded liver biopsies is described. Two primary antisera were used: 1) a high titre anti-HCV human IgG separated from an anti-HCV positive serum; and 2) rabbit anti-HCV antibodies. In our experience this method proves to be reproducible and shows a good correlation with serologic results.

[Development of an infection in monkeys as a result of their sequential natural and experimental exposure to the hepatitis A virus]. / Razvitie infektsii u obez'ian v rezul'tate posledovatel'nogo estestvennogo i éksperimental'nogo zarazheniia ikh virusom gepatita A.

The development of spontaneous outbreak of hepatitis A (HA) among African green monkeys kept under strict isolation conditions was studied. It was shown that in the case of introduction of HAV the infection involved all the susceptible monkeys, running a course with and without any increase in the level of activity of serum alanine aminotransferase (ALT) After inoculation of commercial gamma-globulin only the infection without the ALT activity increase developed and some monkeys had no signs of HA at all. Experimental reinfection with HAV was produced in monkeys having anti-HAV titres of less than or equal to 1:3500.