Could a Patient in Iowa Have Hepatitis E?

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Could a Patient in Iowa Have Hepatitis E?

Question

A renal transplantation patient from Iowa has developed persistent unexplained hepatitis. Could this be caused by hepatitis E virus (HEV)?

Response from F. Balistreri, MD Dorothy M. M. Kersten Professor of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio; Medical Director, Liver Transplantation Program, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio

Yes, hepatitis E virus (HEV) -- an established cause of outbreaks of waterborne acute hepatitis in tropical and subtropical countries -- is rarely considered to be associated with outbreaks or sporadic cases of viral hepatitis in industrialized countries. However, emerging data suggest that HEV clearly causes acute (and perhaps even chronic) hepatitis worldwide. More than 140 articles related to HEV were published in 2009.

What Is HEV?

HEV is a small, nonenveloped particle that consists of a polyadenylated single-strand RNA molecule; it is the sole member of the genus Hepevirus in the family Hepeviridae. HEV is transmitted predominantly by the fecal-oral route and typically causes self-limited acute hepatitis.[1] Infection can be severe -- death rates among young adults and pregnant women are 0.5%-3% and 15%-20%, respectively. Identification and characterization of swine HEV in many countries and the close relationship of swine HEV to locally characterized human HEV suggest that HEV is a zoonotic virus and that there are domestic swine and wild deer reservoirs of HEV in nature.[1,2]

Does HEV Occur in the United States?

The epidemiology of HEV in the United States was recently reported by Kuniholm and associates[3] who used an enzyme immunoassay to measure anti-HEV immunoglobulin (Ig) G antibodies in 18,695 serum samples collected for the Third National Health and Nutrition Examination Survey. The calculated estimate of HEV seroprevalence in the civilian noninstitutionalized US population who reported no travel history was 21% (95% confidence interval, 19%-23%). Among US-born individuals, men, non-Hispanic whites, and persons residing in the Midwest and/or in metropolitan areas had the highest seroprevalence estimates. Having a pet in the home and consuming liver or other organ meats more than once per month were significantly associated with increased odds of HEV seropositivity. Thus, although exposure to HEV is common in the United States, hepatitis E is rarely reported.

Other recent outbreaks. Among the many outbreaks and sporadic cases described in the recent literature, several are of special interest because they reflect the epidemiology and significance of HEV. A recent outbreak of hepatitis E occurred among cruise ship passengers.[4] After receiving reports of cases of acute hepatitis E among returning cruise ship passengers, the UK Health Protection Agency surveyed passengers who had traveled for any part of the same 3-month cruise in 2008. Among 789 passengers, 4% were anti-HEV IgM- and IgG-positive, suggesting recent acute infection, and 21% were IgG-positive only, indicating past infection. HEV RNA sequences were identical, suggesting a common source. Of the 33 passengers who had serologic evidence of recent HEV infection, 11 had symptomatic hepatitis. In a multivariate analysis, factors associated with HEV infection included

being male, drinking alcohol, and eating shellfish. The investigators concluded that the most likely source was food eaten on board the ship.

During 2 multiyear outbreaks of acute viral hepatitis identified in Uzbekistan, HEV was associated with high mortality in pregnant women and in children younger than 3 years of age.[5] Increased severity has also been noted in patients coinfected with HEV and other hepatotropic viruses (including HIV). Zaki and colleagues[6] studied 162 children who had sporadic acute hepatitis and detected anti-HEV in 57% of children with HBV, 52% of HCV-infected patients, 34% of children with HAV infection, and 7% of patients who had "non- A,B,C hepatitis." The prevalence of anti-HEV IgG and IgM correlated with the levels of aspartate and alanine transaminase and outcomes compared with patients who had acute hepatitis as a result of A and C viruses alone.

HEV and Chronic Hepatitis in Organ-Transplant Recipients

Although HEV infection induces self-limiting liver disease in immunocompetent persons, chronic hepatitis E has recently been identified in immune- suppressed organ transplant recipients. Kamar and associates[7] identified 14 cases of acute HEV infection in patients who received organ transplants. HEV RNA was detected in the serum of each of these patients. Chronic hepatitis developed in 8 of the patients. Gerolami and colleagues[8] reported a case in which chronic HEV infection induced rapid and severe cirrhosis. Several subsequent reports[9-11] suggest that organ recipients who have enigmatic hepatitis be tested for HEV.

HEV Vaccine

A cell culture system for the propagation of the virus has been described, and a very successful phase 2 vaccine trial has been completed. Shrestha and associates[12] evaluated the safety and efficacy of an HEV recombinant protein vaccine in a phase 2, randomized, double-blind, placebo-controlled trial in Nepal. The vaccine efficacy was 95.5% (95% confidence interval, 85.6-98.6). Thus, in a high-risk population, HEV vaccine may be an effective method to prevent hepatitis E.

Bottom Line

HEV does, indeed, infect patients worldwide and can be associated with significant disease, especially in immune-compromised individuals. Increased surveillance and screening is recommended, even in Iowa.

http://www.medscape.com/viewarticle/714379?src=rss