Search

In a prospective, non-randomized, pilot study, we evaluated the efficacy of hepatitis B virus (HBV) vaccination in inhibiting HBV replication of chronic hepatitis B. Fourteen consecutive chronic HBs antigen carriers received standard vaccination with three injections of the GenHevac B vaccine, one month apart. All the patients had active HBV replication with chronic hepatitis but not cirrhosis. They were compared to a historical group of 34 patients who fulfilled the same inclusion criteria. Over the 6-month follow-up period after the first injection, serum HBV DNA became undetectable in 3 patients (21.4%). Four additional patients (28.6%) showed a significant decrease in HBV replication. In 4 cases, the disappearance of or decrease in HBV DNA was preceded by an increase in transaminase activities, which was also observed in one patient who did not modify his viral replication. Vaccination was otherwise uneventful. By contrast, during a mean follow-up of 40 months, only 3 (9%) of the 34 unvaccinated patients who served as controls lost serum HBV DNA, giving a 6-month HBV DNA disappearance rate of 1%. In sum, vaccination appeared able to reduce or stop HBV replication in half of the chronic HBsAg carriers with chronic hepatitis. This additional therapeutic tool may enhance the rate of response to interferon-alpha therapy, which is dependent on the level of HBV replication. Thus, immunotherapy should be considered of potential importance for the treatment of HBV infection.

The role of HBV and HCV in the course of primary liver cancer in patients who are negative for HBsAg has been debated. Using a combination of serological and polymerase chain reaction assays, we investigated the association between HCV and HBV infections and primary liver cancer in 24 HBsAg-negative patients living in France. The presence of HCV RNA and HBV DNA sequences was tested for in serum and in tumorous and nontumorous liver samples. Twelve patients had anti-HCV, and 11 patients had anti-HBs and/or anti-HBc. HCV RNA sequences were found in the serum samples of all anti-HCV-positive patients and none of the patients who were negative. Patients with HCV viremia had HCV RNA genomic sequences and presumed replicative intermediates in both tumorous and nontumorous specimens. Sequence analysis of a hypervariable region in the E2/NS1 gene of HCV showed significant variations between the viral molecules isolated from the nontumorous, tumorous and serum samples. This eliminated the hypothesis of the contamination of the tumor by nontumorous cells and serum particles and assessed that liver tumor cells did contain HCV RNA genomes. Eleven of 22 patients tested had HBV DNA in the serum; 5 patients were anti-HBc positive and anti-HBs positive. Patients with HBV viremia had HBV DNA sequences in both tumorous and nontumorous liver specimens. Selective loss of part of the HBV genome in the tumorous tissue of two of these patients suggested HBV DNA persistence in clonally expanded malignant cells. Only 4 of the 22 patients were negative for both viruses. Our results show that HBsAg-negative hepatocellular cancer in France is associated with chronic HBV or HCV infection and, in some cases, both; these findings are consistent with an etiological role for HBV and HCV in HCC that develops in cirrhotic patients living in areas of low prevalence.

The sera of 36 French patients with post-transfusional and sporadic non-A, non-B chronic hepatitis were investigated, for HBV and HCV infections using a combination of serological and polymerase chain reaction (PCR) assays. Anti-HCV was detected in 75% (27/36) of the patients by ELISA1 and/or RIBA2 tests. HCV-RNA sequences were found in 75% (27/36) of the sera by a single step PCR, using a set of primers located in the 5' non-coding region. Altogether, 89% (32/36) of the patients were found positive with serological and/or molecular tests. Among the positive patients, 68% (22/32) were found positive for both anti-HCV and HCV-RNA, 16% (5/32) and 16% (5/32) were found positive for either anti-HCV or HCV-RNA, respectively. HBV-DNA sequences were detected in two patients associated to the HCV viraemia. This study confirms the extremely high prevalence of HCV infection in NANB chronic hepatitis in France. It also shows possible co-infection by HCV and HBV in hepatitis.

The significance of isolated anti-HBs antibodies in subjects not vaccinated against the hepatitis B virus (HBV) was investigated in 13 healthy blood donors. All were European and none had any risk factor for hepatitis B infection. Serological assays included HBV-DNA and anti-preS 2 antibody determinations which were all negative. After injection with hepatitis B vaccine (Hevac B), only one out of the 13 subjects exhibited an anamnestic response in favor of secondary immunization. Neutralization tests for serum anti-HBs antibody were positive in only 6 subjects. Our data suggest that in most cases isolated anti-HBs positivity does not correspond to true antibody; booster injection of HBV vaccine seems to be the best way of verifying that antibodies are really protective.

The polymerase chain reaction (PCR) was used to identify and characterise serum HBV DNA sequences in 3 patients negative for all HBV serological markers. HBsAg determinants were detected in 1 individual by monoclonal anti-HBsAg immunoradiometric assay. By use of sets of primers on the S and pre-S parts of the HBV genome the presence of HBV DNA was demonstrated in the serum of all 3 patients. Inoculation of human sera to 2 chimpanzees induced acute hepatitis in both animals; 1 became positive for HBsAg and anti-HBcAg and the other only for anti-HBsAg. Cloning of DNA sequences from viral isolates from 1 chimpanzee and 1 patient was accomplished after amplification of the 3' region of the S gene. Comparison of the partial nucleotide sequence with that of known HBV subtypes showed 0 and 1 point mutation, respectively, in the highly conserved 3' end of the S gene. Therefore the results show that PCR with HBV primers may unambigously identify HBV infectious particles among non-A, non-B viruses and is a potentially useful diagnostic test for detection of HBV DNA sequences in serum.

Hepatitis B virus infection is responsible for both morbidity and mortality in kidney transplant recipients. Adenine arabinoside 5'-monophosphate (ARA-AMP), a synthetic punne nucleotide with anti-viral activity, leads to a sustained interruption of HBV replication in approximately 40% of immunocompetent patients. We report the results of a pilot study using ARA-AMP to treat HBV-related chronic active hepat itis in kidney transplant recipients. Ten patients (2 females and 8 males, mean age 44 years, mean time post-transplantation 163 months) received a 28-day course of ARA-AMP intramuscu larly: 5 mg/kg twice daily for the first 5 days during hospitalization and subsequently 5 mg/kg once daily at home for the remaining 23 days. Mean follow-up was 18 months, ranging from 7 to 28 months. All patients but one had biopsy-proven chronic hepatitis, including five cases of cirrhosis. All patients had been chronic HBs Ag carriers for more than 1 year and had active replication as assessed by the presence of serum HBV DNA (mean titre, 270 pg/ml, ranging from 12 to 997 pg/mi, Genostics method). HBe Ag was present in 7 of the 10 patients. Pretreatment creatinine was normal. In four of the 10 patients, HBV DNA became undetectable respectively 1, 1, 5, and 11 months after beginning ARA-AMP. In five patients, HBV DNA decreased during ARA-AMP therapy but subsequently increased although no change was noted during the follow-up period. In two partial responders, a second 4-week course of ARA-AMP was given 8 and 9 months after the first course, and resulted in a sustained HBV DNA loss 1 and 4 months later: HBV DNA reappeared 3 months later in the former. Two of the responders relapsed with reappearance of HBV replication 2 and 22 months after treatment: HBV DNA disappeared 1 year later in the former. ARA-AMP was well tolerated in nine patients, without side-effects in five and mild muscular pain in four, although one patient com plained of severe but reversible peripheral neuropathy Renal function remained stable in all patients during follow-up. Our results suggest that a 4-week course of ARA AMP interrupts HBV replication in 40% of kidney recipients with chronic active hepatitis. Repetition of the treatment may enhance the efficacy of ARA-AMP in partial responders. Efficacy and tolerance seem therefore to be at least comparable to what has been previously reported in immunocompetent patients. [ABSTRACT FROM PUBLISHER]