Hepatitis C virus in pregnancy

Abstract

Despite recent advances in the pathogenesis, treatment, and public health response to hepatitis C virus (HCV), HCV as it specifically relates to pregnancy has been a neglected condition. HCV-monoinfected pregnant women have a 2-8% risk of viral transmission to their infant, but the mechanism and timing of mother to child transmission (MTCT) are not fully understood, nor is the natural history of the illness in pregnant women and their offspring. Recognition of HCV-infected pregnant women is relevant because of the long-term health implications for the mother, potential adverse effects of infection on pregnancy outcomes, and the possibility of transmission to their infants. Certain risk factors for MTCT of HCV appear similar to those for human immunodeficiency virus (HIV); however, unlike HIV, effective methods for prevention of HCV vertical transmission have not been developed. It is possible that a better understanding of HCV MTCT and pathogenesis in pregnancy will guide development of useful prevention strategies, particularly as we enter an era where interferon-free drug cocktails may emerge as viable treatment options for HCV.

Figure 1

Patterns of viremia and cellular immunity in acute resolving infection, acute persisting infection, and a model of chronic HCV infection during pregnancy. (Upper left) Following a prolonged incubation period, viremia declines when HCV-specific CD8+ and CD4+ T-cells appear in the blood. Concurrent spikes in alanine aminotransferase (ALT) levels likely reflect immune-mediated hepatocyte injury. Successful T-cell responses do not fully contract into memory populations until after viremia is resolved. (Bottom left) In persisting infections viremia may be temporarily contained but eventually rebounds as HCV-specific CD4+ T-cell responses are lost and CD8+ T-cell responses become ineffective. (Bottom right) In some women, viral levels rise during pregnancy and then decline significantly in the postpartum period, together with inverse changes in ALT. In this model we hypothesize that these viral load and ALT fluctuations reflect further suppression of the already dysfunctional HCV-specific T-cell responses during pregnancy followed by a sharp and unusual rebound in T-cell function after delivery.