Renal manifestations of hepatitis C virus infection

Abstract

The existence of viral hepatitis has been known for centuries. In the 5th century B.C. Hippocrates noted epidemics of a jaundice-like illness. These were particularly common during various military campaigns, and likely represents one of the earliest reports of “infectious hepatitis” due to hepatitis A virus, an illness passed by fecal-oral route as a consequence of poor sanitation. The observation in the late 1800's that hepatitis could develop after smallpox vaccination with human lymph [1] and in the 1940's that hepatitis could be passed by transfusion to volunteers [2] led to the realization that there was a second type of hepatitis (that is, “serum” hepatitis) spread by contaminated blood products. Following the discovery of the “Australia” antigen (hepatitis B surface antigen, HBsAg) by Blumberg, Alter and Visnich in 1964 [3], it was recognized that many of the cases of “serum” hepatitis were due to infection with hepatitis B virus (HBV) [4], and that HBV was also an important cause of chronic active hepatitis and cirrhosis [reviewed in 5]. Unfortunately, by the late 1970s it was apparent that HBV was not the only cause of “serum” hepatitis, and that other “non-A-non-B” hepatitis viruses existed [6], which could be transmitted by blood products to humans and chimpanzees [7]. Using molecular biologic methods, Houghton and colleagues cloned and expressed portions of a RNA virus from the plasma of an infected chimpanzee in 1989 [8, 9]. This virus, designated hepatitis C virus (HCV), is now known to be a major cause of both transfusion-associated and sporadic non-A-non-B hepatitis [10, 11]. Infection with this virus is often persistent, and may result in chronic active hepatitis, cirrhosis or hepatocellular carcinoma [10–12, and reviewed in 13].The persistent and indolent nature of HCV infection often results in prolonged viremia in spite of a strong humoral immune response [reviewed in 13, 14]. It is perhaps not surprising, then, that chronic immune complex diseases may occur in this setting. The relationship between immune complex disease of the kidney and hepatitis B infection, a long appreciated connection, has been recently reviewed [15]. In this paper, we will discuss some of the more recently recognized extrahepatic manifestations of HCV infection, with particular emphasis on its association with glomerular disease