Correlation Between Relative Number of Circulating Low-Density Hepatitis C Virus Particles and Disease Activity in Patients with Chronic Hepatitis C KEISUKE HINO, MD, KAORI FUJII, MD, MASAAKI KORENAGA, MD, CHISA MURAKAMI, MD, MUNEKO OKAZAKI, MD, MICHIARI OKUDA, MD, and KIWAMU OKITA, MD Hepatitis C virus (HCV) circulates as particles having differing buoyant densities. Change s in the relative proportions of virus particle s of different densities were examine d in 19 patients with chronic hepatitis C: 6 without (group A) and 13 with (group B) abnormal serum alanine aminotransfe rase (ALT) levels. High- and low-density virus particles were separated by differential ¯otation centrifugation. The numbers of high-de nsity particles consistently ex- ceeded that of low-de nsity particle s in all patie nts in group A, whereas the titers of both types of particle s were the same at least once in 7 of 10 patie nts sampled at two time points in group B. The ALT level signi®cantly increased ,2 months later ( P , 0.05) when the titers of both types of particles were the same in patients in group B. Thus, we found a correlation between the relative numbers of circulating low-density HCV particles and disease activity in chronic hepatitis C patients. KEY WORDS: hepatitis C virus; chronic hepatitis C; buoyant density. Hepatitis C virus (HCV) circulates in infected hosts as particles with different buoyant densities on equi- librium density-gradie nt centrifugation (1± 6). Parti- cles of low density are thought to be highly infectious and to contain intact virions (1, 2) that are associated nonspeci®cally with plasma components such as low- density lipoprote ins (1); thus, low-density HCV par- ticles are immunoprecipitated by antibodie s to low- density lipoprotein (7). Immunopre cipitation of circulating HCV particles of higher density with an- tibodies either to the HCV core or to human immu- noglobulin indicates that these particles contain ei- ther nucleocapsids or virus±antibody complexes, respectively (5). Neutralizing antibodie s to HCV pre- vent initiation of the replication cycle in susceptible cells in vitro and are also associate d with the emer- gence of escape-mutant viruses resistant to neutral- ization (8). Therefore, the formation of virus± antibody complexes may both slow the pace of infection as well as provide a mechanism for the emergence of escape mutants. Such a scenario may underlie the alternating periods of biochemical qui- escence and activity in individuals infected with HCV. Thus, the clinical signi®cance of HCV particles of different buoyant densities is gradually becoming clear. We have now attempted to clarify this issue further by examining changes in the relative propor- tions of HCV particles of different buoyant densities Manuscript received February 27, 1997; accepted July 23, 1997. From the First Department of Internal Medicine, Yamaguchi University, School of Medicine, 1144 Kogushi, Ube, Yamaguchi 755, Japan. Uehara Memorial Foundation provided grant support. Address for reprint requests: Dr. Keisuke Hino, First Depart- ment of Internal Medicine, Yamaguchi University, School of Med- icine, 1144 Kogushi, Ube, Yamaguchi 755, Japan. Digestive Diseases and Sciences, Vol. 42, No. 12 (December 1997), pp. 2476 ±2481 2476 Digestive Diseases and Sciences, Vol. 42, No. 12 (December 1997) 0163-2116/97/1200-2476$12.50/0 Ñ 1997 Plenum Publishing Corporation