Influence of human immunodeficiency virus infection on chronic hepatitis B in homosexual men

The aim of this study was to assess the influence of human immunodeficiency virus (HIV) infection on chronic hepatitis B. In a series of 132 (65 anti-HIV positive) homosexual non-drug addicted men with chronic hepatitis B, the liver function was assessed with biochemical tests; the degree of hepatitis B virus (HBV) replication was assessed with serum HBV DNA level and with immunoperoxidase staining of hepatitis B core (HBc) antigen on liver specimens; and the severity of liver lesions was assessed with an histology activity index. Anti-HIV-positive and anti-HIV-negative patients were not different for serum aspartate transaminase activity, bilirubin, prothrombin, and histology activity index. Anti-HIV-positive patients had lower serum alanine transaminase activity levels (P =.0001), lower serum albumin levels (P =.0009), and higher serum HBV DNA levels (P =.01). There was a higher prevalence of cirrhosis in anti-HIV-positive patients (P =.04). In homosexual men with chronic hepatitis B, HIV infection is associated with a higher level of HBV replication and a higher risk for cirrhosis without increased liver necrotico-inflammatory process.     

Prospective trial of recombinant leucocyte interferon in chronic hepatitis B: a 10-month follow-up study

Twenty-one adult patients with chronic hepatitis B and active viral replication as indicated by the presence of hepatitis Be antigen (HBeAg), increased DNA polymerase (DNAp) and positive hepatitis B virus DNA (HBV-DNA) for more than 6 months, were entered into a prospective trial of recombinant human interferon therapy. Ten patients had chronic persistent or chronic lobular hepatitis, 8 chronic active hepatitis and 3 postnecrotic cirrhosis. All cases were treated with 5 x 10(6) units of recombinant interferon alfa-2B given subcutaneously every other day for 12 weeks. During treatment, 18 patients (86%) showed a significant reduction of DNAp levels, which reached normal values in 10 patients (48%). Viral replication was controlled over a 10-month follow-up period in 7 out of 21 patients (33%). Of these 7, five patients became HBeAg negative and HBeAb positive. HBsAg disappeared in one patient. The only serious adverse effect was thrombocytopenia in one patient in whom rapid recovery occurred when interferon was withdrawn. Treatment was also terminated in a second patient because of local reactions at the injection sites occurring after 10 weeks of therapy. Our data indicate that relatively small doses of recombinant alfa-2B interferon given during a 12-week period induce a significant reduction in viral replication and might approximately triple the spontaneous seroconversion rate observed in patients with chronic hepatitis B.     

The effect of concurrent human immunodeficiency virus infection on chronic hepatitis B: a study of 150 homosexual men

To determine the influence of concurrent human immunodeficiency virus (HIV) infection on chronic hepatitis B virus (HBV) infection, 150 male homosexual chronic hepatitis B surface antigen (HBsAg) carriers were studied. Of these, 82 subjects (55%) tested positive for antibodies to HIV. They were more likely to express hepatitis B "e" antigen (HBeAg) (P less than .001) and HBV-DNA (P less than .0005) in serum than were HIV-seronegative individuals. However, the degree of immune suppression did not influence HBeAg-HBV-DNA expression. In HBeAg-seropositive subjects, concurrent HIV infection was associated with lower serum alanine transferase levels (P less than .001). This effect increased with the degree of immune suppression as determined by CD4+ lymphocyte counts. Conversely, in patients negative for HBeAg, there was a weak trend towards higher alanine transferase levels with concurrent HIV. This study suggests that chronic hepatitis B may be less severe when accompanied by HIV infection; however, greater viral replication may make it more contagious and resistant to antiviral therapy. These data support an immune-mediated pathogenesis for hepatitis B and have implications for its control.     

Antibody to the hepatitis B virus receptor for polymerized albumin in acute infection and in hepatitis B vaccine recipients

A receptor for polymerized human serum albumin is encoded by the pre-S region of the hepatitis B virus genome and may mediate attachment of the virion to hepatocytes. To investigate antibody response to the virus receptor we studied sera and their IgG fractions for inhibitory activity on hemagglutination of polyalbumin-coated red cells by virus particles containing the pre-S polypeptide. By this method antibody to the receptor was detected in serum in a goat immunized with pre-S containing particles, with no relation to levels of antibody to hepatitis B surface antigen, and in the sera of 33% and 83%, respectively, of acute hepatitis B patients studied during the early phase of illness and during convalescence. In contrast, antibody to the receptor was not detected in serum in any of the 47 subjects immunized with a commercial, plasma-derived, hepatitis B vaccine. These results demonstrate that natural acute infection with hepatitis B virus leads to production of antibody to the virus receptor for polyalbumin, while such antibody response is absent after immunization with currently licensed hepatitis B vaccines.     

Study design for a hepatitis B vaccine trial.

A short-time trial of small sample size for an evaluation of the hepatitis B vaccine is proposed and designed. The vaccine is based on the premise that antibody to the surface antigen of the hepatitis B virus is protective against viral infection. This premise is verified by using the presence of the surface antigen as the marker of infection and comparing infection rates in renal dialysis patients who had naturally acquired antibody to patients without antibody. Patients with antibody have an extremely low risk of infection. The probability of remaining uninfected decreases at an exponential rate for patients without antibody, implying a constant risk of infection at any point in time. The study design described makes use of this time independence and the observed infection rates to formulate a clinical trial which can be accomplished with a relatively small number of patients. This design might be useful if, in preliminary studies, it is shown that the vaccine produces antibody in the patients and that protection against hepatitis B virus would be beneficial to the patients.     

Anti-Idiotypic antibody production in hepatitis B vaccine recipients

Antibodies against hepatitis B surface antigen and against anti-hepatitis B surface antigen idiotype were assayed after immunization with hepatitis B vaccine both in sera, by enzyme-linked immunosorbent assay (ELISA), and in peripheral blood mononuclear cells, by enzyme-linked immunospot (ELISPOT) assay. After vaccination of 19 subjects, antibody to the idiotype of anti-hepatitis B surface antigen was detected in none of the sera tested with ELISA, but antiidiotypic antibody-secreting cells were detected by ELISPOT assay in 4 (36.4%) of the 11 vaccine recipients who were positive for anti-hepatitis B surface antigen with ELISPOT assay. On the other hand, these cells were detected in none of those who remained seronegative for anti-hepatitis B surface antigen, or in the 7 normal subjects or the 2 chronic hepatitis type C patients. These results suggest that anti-idiotypic antibody production is more sensitively detected by ELISPOT assay than by ELISA, and anti-idiotypic antibodies to anti-hepatitis B surface antigen may be present in those with anti-hepatitis B surface antigen.     

Ten-year serological follow up of hepatitis B vaccine recipients.

AIM: To determine long-term persistence of antibodies to hepatitis B surface antigen (anti-HBs) after vaccination against hepatitis B. METHODS: Thirty-four laboratory workers received hepatitis B vaccine in 1989 in a 0-1-6 month vaccination schedule. Group A (n = 16) received a booster at 3 years after vaccination whereas Group B (n = 18) did not. Anti-HBs was quantitated at 1 month and 1, 2, 3, 5, 6 and 8 years post-vaccination. RESULTS: At eight-year follow up, 10 of 15 subjects in Group A and 3 of 16 in Group B had protective levels of anti-HBs; in addition, two and four subjects, respectively, had detectable anti-HBs though below protective levels. At ten years, 9/15 and 3/16 were anti-HBs positive in Groups A and B, respectively. One subject in each group had rise in anti-HBs titer at 6-year follow up but both of them tested negative for IgG antibodies to hepatitis B core antigen (anti-HBc). A booster dose at 10 years to anti-HBs negative subjects led to an anamestic response in 3/4 and 8/10 persons in Groups A and B, respectively. CONCLUSION: Immunological memory after vaccination against hepatitis B is maintained for at least 10 years.     

Long-term follow-up of a randomized trial of interferon therapy for chronic hepatitis B in a predominantly homosexual male population

BACKGROUND/AIMS: Extended follow-up of a previously published therapeutic trial with interferon alfa is now available to further clarify the long-term outcome of HIV-negative and HIV-positive subjects with chronic hepatitis B virus infection after interferon alfa therapy. METHODS: Forty-five subjects with compensated liver disease and chronic hepatitis B infection with evidence of active hepatitis B replication were studied. These subjects were enrolled between 1986 and 1991 and had been randomized, stratified by HIV status, to either receive interferon therapy (10 MU/m2 of lymphoblastoid interferon alfa 3 times per week for 12 weeks) or no treatment. Hepatitis B serology, serum hepatitis B viral DNA and alanine aminotransferase were measured on an annual to biannual basis. CD4-positive T lymphocyte counts and HIV RNA concentration were also obtained. RESULTS: From 9 months post-interferon alfa treatment to the end of the extended follow-up (4 to 9 years), the relative risk of seroconverting to anti-HBe positive for subjects who had received interferon alfa therapy compared to those who did not was not significant in either HIV-negative (p = 0.80) or HIV-positive (p = 0.62) subjects. CONCLUSIONS: Unlike the first 9 months following interferon alfa therapy, the rate of elimination of markers of hepatitis B virus replication, regardless of HIV status, was not increased above the natural rate beyond 9 months following interferon alfa therapy.     

急性乙型肝炎与慢性乙型肝炎急性发作的临床特征比较

目的探讨鉴别急性乙型肝炎(AHB)和慢性乙型肝炎(CHB)急性发作的临床特征。方法回顾性分析2014年6月~(-1)2月在复旦大学附属公共卫生临床中心就诊的96例AHB和124例CHB急性发作患者的临床资料。计量资料组间比较采用MannWhitney U检验,计数资料组间比较采用χ~2检验。结果 AHB和CHB急性发作在发病年龄和性别方面差异无统计学意义,男性发病率高于女性。AHB以性接触和医源性传播为主,而CHB急性发作以母婴垂直传播为主。基线ALT水平≥1072 U/L诊断AHB的敏感性和特异性分别为78.6%和79.2%;抗-HBc-Ig M滴度≥13.6 S/CO诊断AHB的敏感性和特异性分别为94.5%和89.3%。入院2周时AHB组HBs Ag、HBe Ag和HBV DNA较基线的下降值均显著高于CHB急性发作组且差异有统计学意义(P值均0.05)。入院第8周时AHB患者HBs Ag阴转率、抗-HBs阳转率、HBe Ag阴转率、抗-HBe阳转率和HBV DNA阴转率均显著高于CHB急性发作患者(P值均0.05)。结论明确传播途径、基线高ALT水平和抗-HBc-Ig M水平、快速HBV DNA阴转和HBV血清学标志物转换均有助于AHB和CHB急性发作的鉴别诊断。     

α-2b干扰素治疗慢性乙型肝炎的前瞻性研究

目的:前瞻性评价国产α-2b干扰素治疗CHB的疗效.方法:32例CHB患者,每次α-2b干扰素6 MU、皮下注射、3次/wk,疗程为3 mo,停药后随访6 mo.16例患者于治疗前后进行了肝活检.结果:治疗结束时,完全应答1例(3.1%),部分应答12例(37.5%),无应答19例(59.4%),总应答率为40.6%(13/32).随访结束时,总应答率为50.0%(16/32).结论:α-干扰素具有后续抗HBV作用.部分抗病毒无效的患者仍可从α-干扰素的治疗中获益.     

The effect of recombinant hepatitis B vaccine therapy in chronic hepatitis B infection.

BACKGROUND/AIMS: Immune-modulator and antiviral treatments for carriers of hepatitis B virus are known to have poor efficacy with a high cost and frequent side effects, which has led to investigation of new treatment modalities. The aim of this study was to determine the efficacy of recombinant hepatitis B vaccine in the treatment of patients with chronic hepatitis B (HBV DNA >5 pg/ml, ALT>60) infection diagnosed histopathologically and asymptomatic carriers (HBV DNA<5 pg/ml, ALT <40, Anti Hbe positive) of the virus. METHODS: The vaccine (Gen Hevac B Pasteur) was administered at baseline and at months one and six to patients with chronic hepatitis and asymptomatic carriers. Ten cases with chronic hepatitis B infection were assigned to a control group to whom no treatment was given. Biochemical and microbiological investigations were performed at baseline and at months three, six and twelve in all cases. Seroconversion of Hbe Ag, loss of HBV DNA and normalization of ALT were considered as a positive response. RESULTS: Patients with chronic hepatitis B who were given the vaccine were found to have significantly low levels of HBV DNA at 12 months (63.2+/-20pg/ml) compared to baseline values (174.4+/-36.9pg/ml), while controls were found to have high levels of HBV DNA at 12 months (223.1+/-33pg/ml) compared to baseline values (165.2+/-33.2pg/ml) (p<0.05). At 12 months, HBV DNA had become negative in seven of 19 patients given the vaccine (36.8%) Four patients with chronic hepatitis (36.35%) were observed to have HBeAg seroconversion and one patient (5.2%) HBsAg seroconversion at the end of 12 months and there were four (21.05%) patients who responded positively to vaccine therapy in this group. Asymptomatic carriers and controls did not have seroconversion of HBs Ag. Also, HBV DNA did not become negative in controls. CONCLUSION: It may be concluded that recombinant hepatitis B vaccine is effective in the treatment of chronic hepatitis B.     

Correlation between peripheral lymphocyte subsets and antibody to hepatitis B surface antigen response in hepatitis B vaccine recipients

Peripheral lymphocyte subsets of 14 heterosexual recipients of hepatitis B vaccine were measured by indirect immunofluorescence using specific monoclonal antibodies. 12/14 vaccine recipients developed antibody to hepatitis B surface antigen after the second injection of vaccine; however, 2 recipients remained seronegative. Prior to the vaccination, these two vaccine non-responders had been found to have a significantly reduced ratio of peripheral helper-inducer T cells to suppressor/cytotoxic T cells (1.15 +/- 0.02 vs. 1.79 +/- 0.12), and an increase in the proportion of natural killer/killer cells (25.6 +/- 1.5% vs. 13.8 +/- 1.6%) as compared to the 12 responders. Enumeration of peripheral lymphocyte subsets prior to vaccination may be useful in predicting the immune response of hepatitis B vaccine recipients.     

Vitamin E treatment for children with chronic hepatitis B：A randomized placebo controlled trial

AIM：To evaluate the safety and efficacy of vitamin E in children with chronic hepatitis B.METHODS：We randomly assigned patients with chronic hepatitis B,positive for hepatitis B e antigen（HBeAg）,to receive either vitamin E or placebo once daily for 6 mo in a 3：1 ratio and double-blind manner.The primary end point was HBeAg seroconversion,defined as the loss of HBeAg,undetectable levels of serum hepatitis B virus DNA,and the appearance of antibodies against HBeAg 12 mo after therapy.RESULTS：At baseline visit,49 patients had normal and 43 had increased serum aminotransferase levels.Twenty-nine patients did not respond to previous treatment with interferon-α or lamivudine.Seventy-six children completed the study;16 were non-compliant（n = 7）,lost to follow-up（n = 7）,or started another antiviral treatment（n = 3）.Intention-to-treat analysis showed HBeAg seroconversion in 16 children（23.2%） treated with vitamin E and two（8.7%） in the placebo group（P = 0.13）.Vitamin E was well tolerated.CONCLUSION：There is only a tendency that vitamin E may promote HBeAg seroconversion.Therefore larger studies are needed to clarify the role of antioxidants in the therapy of chronic hepatitis B.