lactoferrin and Hepatitis--Chronic

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

We found that bovine lactoferrin (bLF), a milk protein belonging to the iron transporter family, effectively prevented hepatitis C virus (HCV) infection in cultured human hepatocytes (PH5CH8), a cell line susceptible to HCV infection and supportive of HCV replication. Because preincubation of HCV with bLF was required to prevent the infection of HCV to the cells, and preincubation of bLF with the cells showed no inhibitory effect on HCV infection, we demonstrated that the anti-HCV activity of bLF was due to the interaction of bLF with HCV, but not due to the interaction of bLF with the cells. We further found that human lactoferrin also had anti-HCV activity, but bovine transferrin, the other member of the iron transporter family, did not have anti-HCV activity. Our findings suggest that lactoferrin is one of candidates for an anti-HCV reagent that will be well-tolerated and effective in the treatment of patients with chronic hepatitis.

Topics: Animals; Antiviral Agents; Cattle; Cell Line; Hepacivirus; Hepatitis, Chronic; Humans; Lactoferrin; Liver; Milk Proteins; RNA, Viral