The clinical use of measuring hepatic hepatitis C virus (HCV) RNA before and after therapy in patients with chronic hepatitis C has been assessed in a number of small clinical trials. Viral clearance from the liver may be a better marker of long-term response than eradication of serum HCV RNA. The aim of this study was to evaluate quantitative hepatic HCV-RNA measurements before and after antiviral therapy. Two thousand eighty-nine chronic hepatitis C patients were enrolled in 3 published clinical trials evaluating interferon alfa-2b alone or with ribavirin either as initial therapy or for interferon relapse. Hepatic HCV-RNA quantitation was performed with a modified reverse-transcription polymerase chain reaction (RT-PCR) before and 24 weeks after therapy in 951 and 1,316 patients, respectively. Pretherapy hepatic HCV-RNA concentrations correlated best with serum HCV-RNA concentrations (R ‫؍‬ .236, P ‫؍‬ .0001) and negatively correlated with alanine transaminase (ALT) values (؊0.178, P ‫؍‬ .0001), duration of infection (؊0.09, P ‫؍‬ .02), parenchymal injury (؊0.135, P ‫؍‬ .0001), histologic activity index (HAI) inflammatory score (؊0.085, P ‫؍‬ .01), Knodell fibrosis score (؊0.072, P ‫؍‬ .03), and body weight (؊0.078, P ‫؍‬ .02). In paired liver biopsy specimens (n ‫؍‬ 534), change in hepatic HCV RNA correlated with the change in the HAI (R ‫؍‬ .346, P ‫؍‬ .0001). Of 400 sustained virologic responders (SVR), 393 (98%) had undetectable hepatic HCV RNA, whereas 7 (2%) had detectable hepatic HCV RNA; 5 have been followed and 2 have had reappearance of serum HCV RNA 12 months after therapy. In conclusion, measurement of hepatic HCV RNA before or after therapy reflects changes observed in serum HCV RNA, and correlates inversely with hepatic inflammation and fibrosis, but otherwise has minimal clinical use. (HEPATOLOGY 2002;35:688-693.)

The tolerance and pharmacokinetic behaviour of a new injectable streptogramin antibiotic, RP 59500 were evaluated on 26 healthy male volunteers in a double-blind, placebo-controlled, phase I study. The doses used were 1.4, 2.8, 4.6, 7.0, 9.8, 12.6, 16.8, 22.4 and 29.4 mg/kg; each dose was administered as a 1 h infusion to eight subjects, two of them receiving placebo. Blood levels of RP 59500 were measured by both microbiological and HPLC assays. At the end of the infusion, Cmax for RP 59500 ranged from 0.95 +/- 0.22 to 24.20 +/- 8.82 mg/L. The apparent elimination half-life of the compound ranged from 1.27 to 1.53 h. RP 59500 did not significantly affect any of the laboratory or clinical assessments (blood pressure, pulse rate, ECG, peak expiratory flow rate). Reported adverse effects were of mild intensity; the most frequent event was mild pain or burning at the infusion site with doses of 7 mg/kg or higher. These results support further studies of RP 59500 in phase II clinical trials.

This article represents the proceedings of a workshop at the 2000 ISBRA Meeting in Yokohama, Japan. The chair was Manuela G. Neuman. The presentations were (1) New aspects of hepatic fibrosis, by D. A. Brenner; (2) Cellular immune response in hepatitis C models, by B. Rehermann; (3) The role of interleukin-10 in acute alcoholic hepatitis, by J. Taieb, S. Chollet-Martin, M. Cohard, J. J. Garaud, and T. Poynard; (4) Cytokine-mediated apoptosis in vitro, by M. G. Neuman; (5) Signaling for apoptosis and repair in vitro, by G. G. Katz, R. G. Cameron, N. H. Shear, and M. G. Neuman; (6) Interferons activate the P42/44 mitogen-activated protein kinase and Janus Kinase signal transducers and activation of transcription (JAK-STAT) signaling pathways in hepatocytes: Differential regulation by acute ethanol via a protein kinase C-dependent mechanism, by B. Gao; (7) Genetic polymorphisms of interleukin-1 in association with the development of Japanese alcoholic liver disease, by M. Takamatsu, M. Yamauchi, M. Ohata, S. Saito, S. Maeyama, T. Uchikoshi, and G. Toda; and (8) Increased levels of macrophage migration inhibitory factor in sera from patients with alcoholic liver diseases, by T. Kumagi, S. M. F. Akbar, M. Abe, K. Michitaka, N. Horiike, and M. Onji.