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

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. 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). CONCLUSIONS 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. Prior exposure to HEV with detectable anti-HEV IgG was significantly more common in the ALF patients compared to the general US population.

Hepatitis E Virus Infection as a Possible Cause of Acute Liver Failure in Europe

“…Results from recent US populationbased surveys also have shown hepatitis E as a rare cause of ALF. 9 In contrast, European data have suggested 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 that some cases of severe acute liver injury can be related to hepatitis E. 11,12 Q11 Improved diagnostics and awareness of various possible causes have reduced the number of cases of cryptogenic ALF. Despite this, 18% to 20% of ALF cases in industrialized countries have an unknown etiology.…”

Hepatitis E virus in acute liver failure: An unusual suspect?

“…In this issue, Fontana et al describe the rate of acute HEV infection in ALF cases in North American patients . Serum samples from nearly 700 ALF cases of different etiologies were collected during the period 1998‐2011 and retrospectively analyzed for signs of acute HEV infection.…”

“…The initial diagnoses of the three cases before HEV testing were DILI (n = 2) and fulminant hepatitis B infection (n = 1). All three suspected HEV cases in this study were non‐Hispanic, Caucasian men …”

Hepatitis E in decompensated alcoholic cirrhosis

“…Only 3 patients obtained positive anti-HEV immunoglobulin M (IgM) tests, whereas their HEV RNA tests were negative. (1) In the setting of chronic liver disease (CLD), several studies have shown the presence of HEV infection in 3.2%-6.5% cases of decompensated CLD, mostly in patients with alcoholic CLD. (2) No differences were observed in terms of mortality between patients with and without HEV infection, but the number of HEV cases was low.…”