No abstract

Hepatitis C virus (HCV) is remarkably efficient in establishing persistent infection, possibly mediated by an impaired immune response to HCV infection. There is compelling evidence that HCV can infect immune cells, such as macrophages, B cells, and T cells. It has been previously reported that HCV core, the first protein expressed during the early phase of viral infection, contains the immunomodulatory function of suppressing host immune responses. This altered function of immune cells caused by HCV infection may explain the ineffective immune response to HCV. To further characterize the immunomodulatory role of HCV core in vivo, we generated transgenic (TG) mice by directing the expression of core protein to T lymphocytes by using the CD2 promoter. T-lymphocyte responses, including the production of gamma interferon and interleukin-2, were significantly diminished in these mice compared to their non-TG littermates. The inhibition of T-lymphocyte responsiveness may be due to the increased susceptibility of peripheral T lymphocytes to Fas-mediated apoptosis. Surprisingly, significant lymphocyte infiltration was observed in the portal tracts of livers isolated from core TG mice, associated with increasing serum alanine aminotransferase levels. Moreover, no intrahepatic lymphocytes or liver damage was found in non-TG littermates and core TG mice bred to Fas-deficient lpr mice. These results suggest that HCV core drives liver injury by increasing Fas-mediated apoptosis and liver infiltration of peripheral T cells.Hepatitis C virus (HCV) is a serious and growing worldwide threat to human health. It is the major etiologic agent of non-A, non-B hepatitis and infects an estimated 400 million people, more than 3% of the world population. One of the remarkable features of HCV infection is the high rate of viral persistence. More than 80% of HCV-infected individuals develop chronic disease, which can progress to liver cirrhosis and hepatocellular carcinoma. In addition to HCV replication in hepatocytes, immune cells, such as monocytes, B cells, and T cells, can also support viral replication (13,33,41), although studies of viral replication in the peripheral lymphocytes of HCV-infected patients have had conflicting results (8). The widespread cellular distribution of CD81 and low-density lipoprotein receptor, putative HCV receptors, is consistent with HCV binding to cells other than hepatocytes (2, 47). However, studies of HCV pathogenesis have been hampered by the lack of a small-animal model.

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De novo hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT) is commonly believed to be a relatively benign condition, in contrast to post-OLT infection recurrence, considered a very aggressive complication. We reviewed the charts of 569 non-HBV-related OLTs performed at our institution and identified 19 patients (3%) with de novo HBV infection (appearance of hepatitis B surface antigen [HBsAg] after OLT). After a median follow-up of 25 months beyond the detection of HBsAg, 12 patients (63%) had developed serious HBVrelated graft damage (cirrhosis in 6 patients, bridging chronic hepatitis in 4 patients, and fulminant hepatitis in 2 patients); 7 patients (37%) had lost their grafts; and 4 patients (21%) had died. All graft losses and deaths were related to de novo HBV infection. Similar rates of severe graft damage (62%), graft loss (38%), and death (33%) related to HBV infection were found in a concomitant series of 21 patients with recurrent HBV infection after OLT. Responses to antiviral therapy (interferon or lamivudine) were also similar in the 2 groups of patients. In 12 patients with de novo HBV infection, evidence of past HBV infection (positive serum antibody to hepatitis B core antigen and/or serum or liver tissue HBV DNA) were detected in the donor (7 patients) or recipient (5 patients). No differences were observed in the clinical course after stratification according to the attributed origin of de novo HBV infection. We conclude that de novo HBV infection after OLT is associated with high rates of morbidity and mortality, similar to those described for post-OLT HBV infection recurrence. (Liver Transpl 2001;7:106-112.)