VIRAL DYNAMICS OF HEPATITIS-C EARLY AFTER ORTHOTOPIC LIVER-TRANSPLANTATION - EVIDENCE FOR RAPID TURNOVER OF SERUM VIRIONS

The pathogenesis of hepatitis C virus (HCV) infection is Likely to be associated with viral replication in vivo but little is known concerni ng the dynamics of HCV turnover. We performed serial measurements of s erum HCV-RNA levels following orthotopic liver transplantation (OLT) i n nine patients with HCV-positive cirrhosis. Serum HCV-RNA levels were determined by quantitative polymerase chain reaction before, immediat ely after, and for up to 1 month after OLT, There was a rapid decline in HCV-RNA levels from 3.1 +/- 1.3 x 10(5) copies/mL (mean +/- SEM) pr eoperatively to 0.15 +/- 0.6 x 10(5) copies/mL on the first and 0.16 /- 0.6 x 10(5) copies/mL on the second postoperative day (mean viral h alf-life, 4.0 +/- 0.5 h), Thereafter, HCV-RNA levels increased in all but one patient, and by postoperative day 8 reached 3.6 +/- 1.3 x 10(5 ) copies/mL, exceeding the preoperative levels irrespective of the use or not of rescue immunosuppressive therapy including steroid bolus ad ministration, In most patients, serum virions continued to increase av eraging 11.6 +/- 2.8 x 10(5) copies/mL on the 30th postoperative day. These findings indicate that the half-life of HCV is quite short, and that extrahepatic viral replication contributes little to the total vi rus pool in serum, Furthermore, the marked HCV replication beginning a s early as the third postoperative day strongly suggests that the Live r graft is rapidly reinfected by HCV after OLT.