lactoferrin and Hepatitis-B

Despite the presence of hepatitis B virus (HBV) in the human breastmilk of mothers infected with HBV, it has been shown that breastfeeding does not increase the risk of mother-to-child transmission (MTCT) of HBV. We tested the hypothesis that human breastmilk may contain active components that bind to HBV and inhibit the infectivity of HBV. The results show that human whey significantly inhibited the binding of the hepatitis B surface antigen (HBsAg) to its antibodies in competitive inhibition immunoassays. The far-western blotting showed that HBsAg bound to a protein of 80 kD in human whey, which was identified as lactoferrin by mass spectrometry. Competitive inhibition immunoassays further demonstrated that both human lactoferrin and bovine lactoferrin bound to HBsAg. Human whey, human lactoferrin, and bovine lactoferrin each significantly inhibited the infectivity of HBV in vitro. Our results indicate that human breastmilk can bind to HBsAg and inhibit the infectivity of HBV, and the active component is lactoferrin. The findings may explain the reason that breastfeeding has no additional risk for MTCT of HBV, although human breastmilk contains HBV. Our study provides experimental evidence that HBV-infected mothers should be encouraged to breastfeed their infants.

Topics: Female; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B virus; Humans; Infant; Infectious Disease Transmission, Vertical; Lactoferrin; Milk, Human; Pregnancy; Pregnancy Complications, Infectious

Lactoferrin (Lf) expression has been immunohistochemically investigated in 117 formalin-fixed paraffin-embedded liver bioptic samples obtained from an equal number of patients affected by chronic hepatitis (HCV = 76; HBV = 17; HBV + HDV = 14; cryptogenetic = 10); in addition, 10 autoptic specimens of normal liver were studied as control. The Lf immunoreactivity was evaluated by an intensity-distribution (ID) score. The Lf immunoexpression was observed in 88 out of 117 (75%) cases of chronic hepatitis; interestingly, all liver specimens from HBV hepatitis showed a constant Lf reactivity with the highest ID-score, whereas the evidence of Lf was encountered in 54/76 (71.1%) HCV as well as in 11/14 (78.6%) HDV chronic hepatitis, thus documenting a variable degree of Lf immunostaining in relation to different viruses. Moreover, in 6/10 (60%) cases of cryptogenetic hepatitis Lf immunoexpression was documented, whereas all normal liver controls were unreactive. In HCV specimens, the Lf nuclear immunoreactivity appeared to increase with the progression of the disease, with a greater expression in genotype 1. In contrast, no relationship among Lf ID-scores and different stages or grades of HBV, HDV or cryptogenetic hepatitis was encountered. This fact may suggest a role for Lf as an unspecific defensive agent in chronic inflammatory liver diseases, similarly to that elsewhere reported in other inflammatory tissue injuries.

Topics: Adult; Aged; Cell Nucleus; Coloring Agents; Cytoplasm; Female; Hepatitis; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis C; Hepatitis, Chronic; Hepatitis, Viral, Human; Hepatocytes; Humans; Immunohistochemistry; Lactoferrin; Liver; Male; Middle Aged

In healthy subjects normal plasmalactoferrin (PLf) concentrations were found to be 0.206 +/- 0.06 mg/l in 49 men and 0.148 +/- 0.06 mg/l in 62 women. A highly significant correlation of PLf with the number of circulating neutrophils (PMN) and a PLf/PMN relationship suggesting proportionality was demonstrated. Among 73 patients absolute PLf concentrations were significantly increased in septicemia, cirrhosis of the liver and tumors with liver metastases, decreased in localized infection, tumors without liver involvement, iron deficiency and acute hepatitis B, and normal in acute myocardial infarction. The PLf/PMN ratio, on the other hand, was normal in liver cirrhosis, hepatitis B and in a part of the patients with septicemia and tumor disease with liver involvement. The ratio was increased in a part of the septicemic patients, and decreased in the remaining disease types. Positive PLf/PMN correlations were found in myocardial infarction, septicemia and liver cirrhosis, whereas a very close, negative correlation existed in acute hepatitis B. These findings are discussed on the basis of existing knowledge on lactoferrin physiology, the intravascular fate of PMN and the RES function.

Topics: Anemia, Hypochromic; Female; Hepatitis B; Humans; Lactoferrin; Lactoglobulins; Leukocyte Count; Liver Cirrhosis; Liver Neoplasms; Male; Myocardial Infarction; Neutrophils; Reference Values; Sepsis; Sex Factors