My laboratory is run jointly with Tomasz Laskus, M.D., Ph.D. Our focus is on molecular aspects of viral hepatitis.

We have demonstrated that hepatitis C virus also replicates extrahepatically; we have found evidence of replication in macrophages and lymphocytes as well as in pancreas and thyroid. This was initially described in patients with co- infection, HCV and HIV. We are currently studying extrahepatic HCV replication in patients who are only infected with HCV. We have also observed that replication of HCV in cells apart from liver cells is associated with unique 5'UTR changes. We are currently conducting studies in vitro to determine whether the latter represent specific viral adaptations to different cells. These observations have important clinical implications since HCV has been epidemiologically associated with diabetes mellitus and thyroidal dysfunction. These pathologic associations may be reflecting direct injury on these organs by HCV.

We have also found that in liver transplant HCV positive recipients who receive an organ from an HCV positive recipient, only one strain predominates. Subtype 1b or genotype tend to predominate over a non-1 HCV genotype or subtype. Our laboratory is studying the molecular mechanisms which determine this subtype/genotype predominance utilizing plasmid constructs in transfection experiments. HCV infection is the leading cause of end-stage liver disease among liver allograft recipients. The prevalence of HCV infection has increased from 30% to over 60%.

There is universal recurrence after transplantation. These patients tend to reproduce the clinical course of HCV that leads to transplantation. We are embarked in clinical trials designed to prevent and treat recurrent HCV infection among liver allograft recipients.

Our laboratory provides support for HCV infection studies. There are conflicting observations on the role of HCV quasispecies in determining a bland, slowly progressive clinical course or on the other hand, a rapid progressive course to hepatic failure. We are currently studying HCV quasispecies behavior after liver transplantation among patients transplanted at MCS and MCR and define whether we could predict those patients who are more likely to have an aggressive clinical course.

Our group was one of the first to report that anti-HBc positive donors lead to de novo HBV infection among liver allograft recipients. These organs are given preferentially to HbsAg positive recipients. There have been several instances of HBV infection among recipients and we are currently embarked in a collaborative effort with MCR to define whether the donor or recipient strain predominates.