In view of the limited efficacy of lamivudine monotherapy for chronic hepatitis B (HBV) infection, combination with other drugs seems logical. Intravenous neutralization of circulating HBsAg by specific hepatitis B immunoglobulin (HBIg) has been shown to protect hepatocytes against (re-)infection with HBV in the setting of liver transplantation and postexposure prophylaxis. Large controlled vaccination trials have revealed that HBV can be prevented by HBIg therapy in the majority of newborns after perinatal infection. A benefit of anti-HBs in HBV patients has so far only been investigated in three small studies. In this pilot study we investigated the effects of polyclonal i.v. HBIg (HepatectR, Biotest) administration in HBV-infected patients. Six liver biopsy-proven HBV-infected patients, all on lamivudine treatment and HBV DNA negative by PCR, were investigated. Pre-treatment HBsAg levels varied between 120 and 9760 ng/mL. On day 1, 10.000 IU HBIg was given, followed by 10.000 IU once, twice or three times on day 29. Long-term follow-up lasted at least 4 months. HBsAg and anti-HBs were measured quantitatively by standard MEIA and also by an experimental EIA. In vitro neutralization of HBsAg by Hepatect was mimicked in an `inhibition in solution assay'.
Complete neutralization of HBsAg by HBIg in vitro was possible, 50% inhibition concentrations varied between 100 and 250 IU/L HBIg with HBsAg levels of 68 and 120 ng/mL. No HBIg-related side-effects were observed. In two patients with low pretreatment HBsAg levels HBsAg reached levels below the detection limit of the assay, which persisted a maximum of 31 and 7.5 h, respectively. Peak anti-HBs concentrations were 5100 and 4648 IU/L. In the other four patients, with higher pretreatment HBsAg levels, HBsAg concentrations in serum hardly changed. For the whole population, the drop in HBsAg did not reach statistical significance. However, in four of the six patients a further decrease in HBsAg [18%–66%] was observed.
In conclusion, HBIg was well tolerated; however, efficacy was limited due to high HBsAg levels in spite of maximum inhibition of virion production. `Neutralization' was achieved only in two patients with low HBsAg levels. Passive immunization in HBV-DNA negative patients is not a feasible option. This strategy seems only feasible if agents inhibiting both the production of viral proteins and Dane particles more selectively, become available.