ACTIVE HEPATITIS-C VIRUS-INFECTION IN BONE-MARROW AND PERIPHERAL-BLOOD MONONUCLEAR-CELLS FROM PATIENTS WITH MIXED CRYOGLOBULINEMIA

The presence of hepatitis C virus (HCV) genomic sequences was checked in plasma, liver, peripheral blood mononuclear cells (PBMC) and bone m arrow cells from 11 patients with mixed cryoglobulinaemia positive for anti-HCV antibodies, and from 11 patients with chronic HCV hepatitis without serological evidence of cryoglobulinaemia. HCV RNA sequences w ere demonstrated by reverse transcription polymerase chain reaction in seven plasma samples, in six PBMC samples, and in seven bone marrow c ell samples from the 11 cryoglobulinaemic subjects; otherwise, viral s pecific nucleic acids were detected in 10 plasma samples, in one PBMC sample, and in two bone marrow cell samples from the 11 patients with chronic hepatitis. The HCV replicative intermediate was evidenced in f our of the six PBMC and in five of the seven bone marrow aspirate HCV RNA-positive samples. Analysis of subpopulations isolated from bone ma rrow and peripheral blood samples showed HCV RNA sequences in mononucl ear cells belonging either to the CD2(+) subset or to the CD19(+) subp opulation or to the adherent cells. Finally, we compared the nucleotid e sequences of a large portion (-270 to -59) of the HCV 5'-untranslate d region from five patients with mixed cryoglobulinaemia and from seve n patients with chronic hepatitis without cryoglobulinaemia; the degre e of heterogeneity, compared with the prototype HCV sequence, was simi lar in both groups. These findings from two groups of HCV-infected pat ients indicate that transient or permanent active HCV infection of bon e marrow and PBMC is frequent in anti-HCV-positive patients with mixed cryoglobulinaemia, and suggest that extra-hepatic infection may play a major role in influencing the pathophysiology of this infection as w ell as the viral persistence.