The goals of this Program are to work cooperatively in developing critical areas of medical science in an effort to improve the treatment and control of viral hepatitis in both nations as well as in other countries of the Pacific Rim. The 20th Joint Hepatitis Panel Meeting was held in Maihama, Urayasu, Chiba, Japan. The 65 participants attending the meeting included representatives from academia, industry, and the government agencies of 10 different countries. The meeting focused on advances in the treatment and prevention of disease caused by hepatitis B virus (HBV) and hepatitis C virus (HCV). A special session focused on 2 emerging infectious agents, TT virus (TTV) and hepatitis E virus (HEV), while another special session reviewed the current status of chronic hepatitis and hepatocellular carcinoma in the Pacific Rim nations. As is always the case with this meeting, the contrasting perspectives of Asian and American investigators working in this field were of particular interest.
EMERGING AND RE-EMERGING INFECTIONS
The opening session dealt with the molecular virology and potential clinical importance of TTV, a recently recognized virus that was first identified in Japanese patients with non-A to G posttransfusion hepatitis. Hiroaki Okamoto (Jichi Medical School) and Isa Mushahwar (Abbott Laboratories) reviewed what is now known of this small, nonenveloped DNA virus. The TTV genome is 3,852 bases in length, singlestranded, and apparently negative sense. Evidence presented by Dr. Mushahwar indicates that the genome is circular, and that it contains multiple inverted repeats as well as 3 open reading frames potentially encoding proteins of about 765, 150, and 57 amino acids each. It shares a number of molecular features with members of the virus family Circoviridae, but has no significant nucleotide homology with the latter viruses. Masashi Mizokami (Nagoya City University), Minako Hijikata (Toshiba General Hospital), and Dr. Mushahwar each reported the existence of considerable genetic heterogeneity among different strains of TTV. Depending on the approach to classification, there are between 3 to 15 major genotypes, some of which share as little as 50% nucleotide homology with each other. Also surprising is the very high prevalence of this infection, which appears to be worldwide in its distribution. With optimal selection of primers for polymerase chain reaction (PCR) amplification of TTV sequences, the virus can be found in the blood of up to 90% of healthy Japanese blood donors and at least 10% of healthy American blood donors. The virus frequently establishes a persistent infection, but reports from Kendo Kiyosawa (Shinshu University) and Hitoshi Taijiri (Osaka University) indicate that this is not associated with either chronic hepatitis or hepatocellular carcinoma despite previous reports that the virus may be hepatotropic. For example, Dr. Taijiri reported the presence of the virus in 69% of children with otherwise unexplained chronic hepatitis, but he and his coworkers also found the virus in 66% of normal children.
The concept that TTV, like GB virus C (also known as ''hepatitis G virus''), might represent ''normal virus flora'' was further buttressed by the description of experimental TTV infections of chimpanzees that were performed by the Abbott Laboratories group. Dr. Mushahwar reported that infection was confirmed in 2 animals inoculated with human material, but that it was not associated with increases in serum alanine transaminase (ALT) activities, nor with changes in liver histology. He also described the presence of PCR-detectable TTV-like sequences in 20% to 30% of domestic animals, including pigs, cows, sheep, and even chickens.
Thus, the data presented at this meeting are consistent with the view that TTV is widely distributed in human populations and represents a new class of human viruses. Although there are few data that support an association between TTV infection and diseases of the liver in humans, concern is warranted because data from several of the studies show that TTV may be transmitted by blood transfusion. In Dr. Okamoto' s study, posttransfusion hepatitis occurred in 4 of 18 patients infected with TTV, compared with none of 19 patients who were not infected. In contrast, although Harvey Alter (National Institutes of Health) and colleagues documented new TTV infections in as many as 26% of transfused patients (compared with only 5% in nontransfused controls), they found no association between TTV infection and non-A