The role of hepatitis E virus infection in adult Americans with acute liver failure

Acute hepatitis E virus (HEV) infection is a leading cause of acute liver failure (ALF) in many developing countries, yet rarely identified in Western countries. Given that antibody testing for HEV infection is not routinely obtained, we hypothesized that HEV‐related ALF might be present and unrecog...

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Published inHepatology (Baltimore, Md.) Vol. 64; no. 6; pp. 1870 - 1880
Main Authors Fontana, Robert John, Engle, Ronald E., Scaglione, Steven, Araya, Victor, Shaikh, Obaid, Tillman, Holly, Attar, Nahid, Purcell, Robert H., Lee, William M.
Format Journal Article
LanguageEnglish
Published United States Wolters Kluwer Health, Inc 01.12.2016
Subjects
Adult
Aged
Female
Hepatitis
Hepatitis Antibodies - blood
Hepatitis B virus
Hepatitis E - blood
Hepatitis E - complications
Hepatitis E - epidemiology
Hepatitis E virus
Hepatitis E virus - immunology
Hepatology
Hepeviridae
Humans
Immunoglobulin G - blood
Immunoglobulin M - blood
Infections
Liver
Liver Failure, Acute - blood
Liver Failure, Acute - complications
Male
Prospective Studies
Seroepidemiologic Studies
United States
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Abstract Acute hepatitis E virus (HEV) infection is a leading cause of acute liver failure (ALF) in many developing countries, yet rarely identified in Western countries. Given that antibody testing for HEV infection is not routinely obtained, we hypothesized that HEV‐related ALF might be present and unrecognized in North American ALF patients. Serum samples of 681 adults enrolled in the U.S. Acute Liver Failure Study Group were tested for anti‐HEV immunoglobulin (Ig) M and anti‐HEV IgG levels. Subjects with a detectable anti‐HEV IgM also underwent testing for HEV RNA. Mean patient age was 41.8 years, 32.9% were male, and ALF etiologies included acetaminophen (APAP) hepatotoxicity (29%), indeterminate ALF (23%), idiosyncratic drug‐induced liver injury DILI (22%), acute hepatitis B virus infection (12%), autoimmune hepatitis (12%), and pregnancy‐related ALF (2%). Three men ages 36, 39, and 70 demonstrated repeatedly detectable anti‐HEV IgM, but all were HEV‐RNA negative and had other putative diagnoses. The latter 2 subjects died within 3 and 11 days of enrollment whereas the 36‐year‐old underwent emergency liver transplantation on study day 2. At admission, 294 (43.4%) of the ALF patients were anti‐HEV IgG positive with the seroprevalence being highest in those from the Midwest (50%) and lowest in those from the Southeast (28%). Anti‐HEV IgG+ subjects were significantly older, less likely to have APAP overdose, and had a lower overall 3‐week survival compared to anti‐HEV IgG‐ subjects (63% vs. 70%; P = 0.018). Conclusion: Acute HEV infection is very rare in adult Americans with ALF (i.e., 0.4%) and could not be implicated in any indeterminate, autoimmune, or pregnancy‐related ALF cases. Past exposure to HEV with detectable anti‐HEV IgG was significantly more common in the ALF patients compared to the general U.S. population. (Hepatology 2016;64:1870‐1880)
AbstractList Acute hepatitis E virus (HEV) infection is a leading cause of acute liver failure (ALF) in many developing countries, yet rarely identified in Western countries. Given that antibody testing for HEV infection is not routinely obtained, we hypothesized that HEV-related ALF might be present and unrecognized in North American ALF patients. Serum samples of 681 adults enrolled in the U.S. Acute Liver Failure Study Group were tested for anti-HEV immunoglobulin (Ig) M and anti-HEV IgG levels. Subjects with a detectable anti-HEV IgM also underwent testing for HEV RNA. Mean patient age was 41.8 years, 32.9% were male, and ALF etiologies included acetaminophen (APAP) hepatotoxicity (29%), indeterminate ALF (23%), idiosyncratic drug-induced liver injury DILI (22%), acute hepatitis B virus infection (12%), autoimmune hepatitis (12%), and pregnancy-related ALF (2%). Three men ages 36, 39, and 70 demonstrated repeatedly detectable anti-HEV IgM, but all were HEV-RNA negative and had other putative diagnoses. The latter 2 subjects died within 3 and 11 days of enrollment whereas the 36-year-old underwent emergency liver transplantation on study day 2. At admission, 294 (43.4%) of the ALF patients were anti-HEV IgG positive with the seroprevalence being highest in those from the Midwest (50%) and lowest in those from the Southeast (28%). Anti-HEV IgG+ subjects were significantly older, less likely to have APAP overdose, and had a lower overall 3-week survival compared to anti-HEV IgG- subjects (63% vs. 70%; P = 0.018). Conclusion: Acute HEV infection is very rare in adult Americans with ALF (i.e., 0.4%) and could not be implicated in any indeterminate, autoimmune, or pregnancy-related ALF cases. Past exposure to HEV with detectable anti-HEV IgG was significantly more common in the ALF patients compared to the general U.S. population. (Hepatology 2016;64:1870-1880)
Acute hepatitis E virus (HEV) infection is a leading cause of acute liver failure (ALF) in many developing countries, yet rarely identified in Western countries. Given that antibody testing for HEV infection is not routinely obtained, we hypothesized that HEV-related ALF might be present and unrecognized in North American ALF patients. Serum samples of 681 adults enrolled in the U.S. Acute Liver Failure Study Group were tested for anti-HEV immunoglobulin (Ig) M and anti-HEV IgG levels. Subjects with a detectable anti-HEV IgM also underwent testing for HEV RNA. Mean patient age was 41.8 years, 32.9% were male, and ALF etiologies included acetaminophen (APAP) hepatotoxicity (29%), indeterminate ALF (23%), idiosyncratic drug-induced liver injury DILI (22%), acute hepatitis B virus infection (12%), autoimmune hepatitis (12%), and pregnancy-related ALF (2%). Three men ages 36, 39, and 70 demonstrated repeatedly detectable anti-HEV IgM, but all were HEV-RNA negative and had other putative diagnoses. The latter 2 subjects died within 3 and 11 days of enrollment whereas the 36-year-old underwent emergency liver transplantation on study day 2. At admission, 294 (43.4%) of the ALF patients were anti-HEV IgG positive with the seroprevalence being highest in those from the Midwest (50%) and lowest in those from the Southeast (28%). Anti-HEV IgG super(+) subjects were significantly older, less likely to have APAP overdose, and had a lower overall 3-week survival compared to anti-HEV IgG super(-) subjects (63% vs. 70%; P = 0.018). Conclusion: Acute HEV infection is very rare in adult Americans with ALF (i.e., 0.4%) and could not be implicated in any indeterminate, autoimmune, or pregnancy-related ALF cases. Past exposure to HEV with detectable anti-HEV IgG was significantly more common in the ALF patients compared to the general U.S. population. (Hepatology 2016; 64:1870-1880)
Acute hepatitis E virus (HEV) infection is a leading cause of acute liver failure (ALF) in many developing countries, yet rarely identified in Western countries. Given that antibody testing for HEV infection is not routinely obtained, we hypothesized that HEV-related ALF might be present and unrecognized in North American ALF patients. Serum samples of 681 adults enrolled in the U.S. Acute Liver Failure Study Group were tested for anti-HEV immunoglobulin (Ig) M and anti-HEV IgG levels. Subjects with a detectable anti-HEV IgM also underwent testing for HEV RNA. Mean patient age was 41.8 years, 32.9% were male, and ALF etiologies included acetaminophen (APAP) hepatotoxicity (29%), indeterminate ALF (23%), idiosyncratic drug-induced liver injury DILI (22%), acute hepatitis B virus infection (12%), autoimmune hepatitis (12%), and pregnancy-related ALF (2%). Three men ages 36, 39, and 70 demonstrated repeatedly detectable anti-HEV IgM, but all were HEV-RNA negative and had other putative diagnoses. The latter 2 subjects died within 3 and 11 days of enrollment whereas the 36-year-old underwent emergency liver transplantation on study day 2. At admission, 294 (43.4%) of the ALF patients were anti-HEV IgG positive with the seroprevalence being highest in those from the Midwest (50%) and lowest in those from the Southeast (28%). Anti-HEV IgG subjects were significantly older, less likely to have APAP overdose, and had a lower overall 3-week survival compared to anti-HEV IgG subjects (63% vs. 70%; P = 0.018). Acute HEV infection is very rare in adult Americans with ALF (i.e., 0.4%) and could not be implicated in any indeterminate, autoimmune, or pregnancy-related ALF cases. Past exposure to HEV with detectable anti-HEV IgG was significantly more common in the ALF patients compared to the general U.S. (Hepatology 2016;64:1870-1880).
Acute hepatitis E virus (HEV) infection is a leading cause of acute liver failure (ALF) in many developing countries, yet rarely identified in Western countries. Given that antibody testing for HEV infection is not routinely obtained, we hypothesized that HEV‐related ALF might be present and unrecognized in North American ALF patients. Serum samples of 681 adults enrolled in the U.S. Acute Liver Failure Study Group were tested for anti‐HEV immunoglobulin (Ig) M and anti‐HEV IgG levels. Subjects with a detectable anti‐HEV IgM also underwent testing for HEV RNA. Mean patient age was 41.8 years, 32.9% were male, and ALF etiologies included acetaminophen (APAP) hepatotoxicity (29%), indeterminate ALF (23%), idiosyncratic drug‐induced liver injury DILI (22%), acute hepatitis B virus infection (12%), autoimmune hepatitis (12%), and pregnancy‐related ALF (2%). Three men ages 36, 39, and 70 demonstrated repeatedly detectable anti‐HEV IgM, but all were HEV‐RNA negative and had other putative diagnoses. The latter 2 subjects died within 3 and 11 days of enrollment whereas the 36‐year‐old underwent emergency liver transplantation on study day 2. At admission, 294 (43.4%) of the ALF patients were anti‐HEV IgG positive with the seroprevalence being highest in those from the Midwest (50%) and lowest in those from the Southeast (28%). Anti‐HEV IgG + subjects were significantly older, less likely to have APAP overdose, and had a lower overall 3‐week survival compared to anti‐HEV IgG ‐ subjects (63% vs. 70%; P = 0.018). Conclusion : Acute HEV infection is very rare in adult Americans with ALF (i.e., 0.4%) and could not be implicated in any indeterminate, autoimmune, or pregnancy‐related ALF cases. Past exposure to HEV with detectable anti‐HEV IgG was significantly more common in the ALF patients compared to the general U.S. population. (H epatology 2016;64:1870‐1880)
Acute hepatitis E virus (HEV) infection is a leading cause of acute liver failure (ALF) in many developing countries yet rarely identified in Western countries. Since antibody testing for HEV infection is not routinely obtained, we hypothesized that HEV-related ALF might be present and unrecognized in North American ALF patients. Serum samples of 681 adults enrolled in the US ALF Study Group were tested for anti-HEV IgM and anti-HEV IgG levels. Subjects with a detectable anti-HEV IgM also underwent testing for HEV-RNA. Mean patient age was 41.8 years, 32.9% male, and ALF etiologies included acetaminophen hepatotoxicity (29%), indeterminate ALF (23%), idiosyncratic DILI (22%), acute HBV infection (12%), autoimmune hepatitis (12%) and pregnancy related ALF (2%). Three men ages 36, 39, and 70 demonstrated repeatedly detectable anti-HEV IgM but all were HEV RNA negative and had other putative diagnoses. The latter two subjects died within 3 and 11 days of enrollment while the 36 year old underwent emergency liver transplantation on study day 2. At admission, 294 (43.4%) of the ALF patients were anti-HEV IgG positive with the seroprevalence being highest in those from the Midwest (50%) and lowest in those from the Southeast (28%). Anti-HEV IgG + subjects were significantly older, less likely to have APAP overdose, and had a lower overall 3 week survival compared to anti-HEV IgG − subjects (63% vs 70%, p= 0.018).
Author Purcell, Robert H.
Scaglione, Steven
Tillman, Holly
Attar, Nahid
Fontana, Robert John
Engle, Ronald E.
Araya, Victor
Shaikh, Obaid
Lee, William M.
AuthorAffiliation 4 Einstein Medical Center, Philadelphia, PA
5 University of Pittsburgh, Pittsburgh, PA
2 National Institute of Allergy and Infectious Diseases, Bethesda, MD
1 Department of Internal Medicine, University of Michigan, Ann Arbor, MI
6 Medical University of South Carolina, Dallas, TX
7 University of Texas Southwestern, Dallas, TX
3 Loyola Medical Center, Maywood, Il
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Notes Potential conflict of interest: Dr. Araya advises for and is on the speakers' bureau for Merck, AbbVie, and Gilead. He received grants from Intercept and Johnson & Johnson. Dr. Fontana received grants from Bristol‐Myers Squibb, Janssen, and Gilead. Dr. Lee consults for Lilly, Novartis, and Sanofi. He received grants from Bristol‐Myers Squibb, Merck, Gilead, and Conatus.
See Editorial on Page 1837
We gratefully acknowledge the support provided by the members of The Acute Liver Failure Study Group. This study was funded by the National Institute of Diabetes, Digestive and Kidney Diseases (DK U‐01‐58369). Additional funding provided by the Tips Fund of Northwestern Medical Foundation and the Jeanne Roberts and Rollin and Mary Ella King Funds of the Southwestern Medical Foundation. This work was supported, in part, by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases.
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Snippet Acute hepatitis E virus (HEV) infection is a leading cause of acute liver failure (ALF) in many developing countries, yet rarely identified in Western...
Acute hepatitis E virus (HEV) infection is a leading cause of acute liver failure (ALF) in many developing countries yet rarely identified in Western...
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SourceType Open Access Repository
Aggregation Database
Index Database
Enrichment Source
Publisher
StartPage 1870
SubjectTerms Adult
Aged
Female
Hepatitis
Hepatitis Antibodies - blood
Hepatitis B virus
Hepatitis E - blood
Hepatitis E - complications
Hepatitis E - epidemiology
Hepatitis E virus
Hepatitis E virus - immunology
Hepatology
Hepeviridae
Humans
Immunoglobulin G - blood
Immunoglobulin M - blood
Infections
Liver
Liver Failure, Acute - blood
Liver Failure, Acute - complications
Male
Prospective Studies
Seroepidemiologic Studies
United States
Title The role of hepatitis E virus infection in adult Americans with acute liver failure
URI https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fhep.28649
https://www.ncbi.nlm.nih.gov/pubmed/27215797
https://www.proquest.com/docview/1844952873
https://www.proquest.com/docview/1850773748
https://pubmed.ncbi.nlm.nih.gov/PMC5115940
Volume 64
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