What factors determine the severity of hepatitis A-related acute liver failure?
V Ajmera, G Xia, G Vaughan, J C Forbi, L M Ganova-Raeva, Y Khudyakov, C K Opio, R Taylor, R Restrepo, S Munoz, R J Fontana, W M Lee, Acute Liver Failure Study Group, William M Lee, Julie Polson, Carla Pezzia, Ezmina Lalani, Linda S Hynan, Joan S Reisch, Anne M Larson, Hao Do, Jeffrey S Crippin, Laura Gerstle, Timothy J Davern, Sukru Emre, Timothy M McCashland, Tamara Bernard, J Eileen Hay, Cindy Groettum, Natalie Murray, Sonnya Coultrup, A Obaid Shakil, Diane Morton, Andres T Blei, Jeanne Gottstein, Atif Zaman, Jonathan Schwartz, Ken Ingram, Steven Han, Val Peacock, Robert J Fontana, Suzanne Welch, Brendan McGuire, Linda Avant, Raymond Chung, Robert Brown Jr, Deborah Casson, Michael Schilsky, Laren Senkbeil, M Edwyn Harrison, Rebecca Rush, Adrian Reuben, Nancy Huntley, Santiago Munoz, Chandra Misra, Todd Stravitz, Jennifer Salvatori, Lorenzo Rossaro, Colette Prosser, Raj Satyanarayana, Wendy Taylor, Raj Reddy, Mical Campbell, Tarek Hassanein, Fatma Barakat, Alistair Smith, V Ajmera, G Xia, G Vaughan, J C Forbi, L M Ganova-Raeva, Y Khudyakov, C K Opio, R Taylor, R Restrepo, S Munoz, R J Fontana, W M Lee, Acute Liver Failure Study Group, William M Lee, Julie Polson, Carla Pezzia, Ezmina Lalani, Linda S Hynan, Joan S Reisch, Anne M Larson, Hao Do, Jeffrey S Crippin, Laura Gerstle, Timothy J Davern, Sukru Emre, Timothy M McCashland, Tamara Bernard, J Eileen Hay, Cindy Groettum, Natalie Murray, Sonnya Coultrup, A Obaid Shakil, Diane Morton, Andres T Blei, Jeanne Gottstein, Atif Zaman, Jonathan Schwartz, Ken Ingram, Steven Han, Val Peacock, Robert J Fontana, Suzanne Welch, Brendan McGuire, Linda Avant, Raymond Chung, Robert Brown Jr, Deborah Casson, Michael Schilsky, Laren Senkbeil, M Edwyn Harrison, Rebecca Rush, Adrian Reuben, Nancy Huntley, Santiago Munoz, Chandra Misra, Todd Stravitz, Jennifer Salvatori, Lorenzo Rossaro, Colette Prosser, Raj Satyanarayana, Wendy Taylor, Raj Reddy, Mical Campbell, Tarek Hassanein, Fatma Barakat, Alistair Smith
Abstract
The reason(s) that hepatitis A virus (HAV) infection may progress infrequently to acute liver failure are poorly understood. We examined host and viral factors in 29 consecutive adult patients with HAV-associated acute liver failure enrolled at 10 sites participating in the US ALF Study Group. Eighteen of twenty-four acute liver failure sera were PCR positive while six had no detectable virus. HAV genotype was determined using phylogenetic analysis and the full-length genome sequences of the HAV from a cute liver failure sera were compared to those from self-limited acute HAV cases selected from the CDC database. We found that rates of nucleotide substitution did not vary significantly between the liver failure and non-liver failure cases and there was no significant variation in amino acid sequences between the two groups. Four of 18 HAV isolates were sub-genotype IB, acquired from the same study site over a 3.5-year period. Sub-genotype IB was found more frequently among acute liver failure cases compared to the non-liver failure cases (chi-square test, P < 0.01). At another centre, a mother and her son presented with HAV and liver failure within 1 month of each other. Predictors of spontaneous survival included detectable serum HAV RNA, while age, gender, HAV genotype and nucleotide substitutions were not associated with outcome. The more frequent appearance of rapid viral clearance and its association with poor outcomes in acute liver failure as well as the finding of familial cases imply a possible host genetic predisposition that contributes to a fulminant course. Recurrent cases of the rare sub-genotype IB over several years at a single centre imply a community reservoir of infection and possible increased pathogenicity of certain infrequent viral genotypes.
© 2010 Blackwell Publishing Ltd.
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Source: PubMed