• 1.

    Khuroo MS, Khuroo MS, Khuroo NS, 2016. Hepatitis E: discovery, global impact, control and cure. World J Gastroenterol 22: 70307045.

  • 2.

    Kamar N, Izopet J, Pavio N, Aggrawal R, Labrique A, Wedemeyer H, Dalton HR, 2017. Hepatitis E virus infection. Nat Rev Dis Primers 3: 17086.

  • 3.

    Ali G, Kumar M, Bali S, Wadhwa W, 2001. Hepatitis E associated immune thrombocytopaenia and membranous glomerulonephritis. Indian J Nephrol 11: 7072.

    • Search Google Scholar
    • Export Citation
  • 4.

    Pischke S, Hartl J, Pas SD, Lohse AW, Jacobs BC, Van der Eijk AA, 2017. Hepatitis E virus: infection beyond the liver? J Hepatol 66: 10821095.

  • 5.

    Dahl V, Wallenstein A, 2017. Self-reported infectious during international travel and notifiable infections among returning international travellers, Sweden, 2009–2013. PLoS One 12: e0181625.

    • Search Google Scholar
    • Export Citation
  • 6.

    Patel I, Ching Companioni R, Bansal R, Vyas N, Catalano C, Aron J, Walfish A, 2016. Acute hepatitis E presenting with clinical feature of autoimmune hepatitis. J Community Hosp Intern Med Perspect 6: 33342.

    • Search Google Scholar
    • Export Citation
  • 7.

    Sebode M, Pischke S, Lütgehetmann M, Polywka S, Quaas A, Lohse AW, Wege H, 2014. New foe treated with old guns—supportive role of steroids in the treatment of acute severe hepatitis E. BMC Gastroenterol 14: 191.

    • Search Google Scholar
    • Export Citation
  • 8.

    Ebbeson RL, Schruiber RA, 2004. Diagnosing autoimmune hepatitis in children: is the international autoimmune hepatitis group scoring system useful? Clin Gastroenterol Hepatol 2: 935940.

    • Search Google Scholar
    • Export Citation
  • 9.

    Alvarez F 1999. International autoimmune hepatitis group: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol 31: 929938.

    • Search Google Scholar
    • Export Citation
  • 10.

    Hiejima E, Komatsu H, Sogo T, Inui A, Fujisawa T, 2011. Utility of simplified criteria for the diagnosis of autoimmune hepatitis in children. J Pediatr Gastroenterol Nutr 52: 470473.

    • Search Google Scholar
    • Export Citation
  • 11.

    Sugitani M 2009. Detection of hepatitis E virus RNA and genotype in Bangladesh. J Gastroenterol Hepatol 24: 599604.

  • 12.

    Zuckerman JN, 2003. Hepatitis E and the traveller. Travel Med Infect Dis 1: 7376.

  • 13.

    Leder K 2013. GeoSentinel surveillance of illness in returned travelers, 2007–2011. Ann Intern Med 158: 456468.

  • 14.

    Heywood AE 2016. The contribution of travellers visiting friends and relatives to notified infectious diseases in Australia: state-based enhanced surveillance. Epidemiol Infect 144: 35543563.

    • Search Google Scholar
    • Export Citation
  • 15.

    Bradanini L, Youkee D, Fabris P, Roman L, Brunetti E, Giordani MT, 2017. Acute hepatitis E virus infection in a migrant population in north east Italy: a retrospective analysis. Travel Med Infect Dis 20: 3742.

    • Search Google Scholar
    • Export Citation
  • 16.

    Azman AS 2017. High hepatitis E seroprevalence among displaced persons in South Sudan. Am J Trop Med Hyg 96: 12961301.

  • 17.

    Sadarangani SP, Lim PL, Vasoo S, 2017. Infectious diseases and migrant worker health in Singapore: a receiving country’s perspective. J Travel Med 24: tax014.

    • Search Google Scholar
    • Export Citation
  • 18.

    Eick A 2010. Hepatitis E seroprevalence and seroconversion among US military service members deployed to Afghanistan. J Infect Dis 202: 13021308.

    • Search Google Scholar
    • Export Citation
  • 19.

    Teshale EH, 2017. Hepatitis E. Brunette GW, Kozarsky PE, eds. CDC Health Information for International Travel 2018. New York, NY: Oxford University Press.

    • Search Google Scholar
    • Export Citation
  • 20.

    Mieli-Vergani G 2009. Autoimmune hepatitis. J Pediatr Gastroenterol Nutr 49: 158164.

  • 21.

    Arcos-Machancoses JV, Molera Busoms C, Julio Tatis E, Victoria Bovo M, Quintero Bernabeu J, Juamperez Goni J, Crujeiras Martinez V, Martin de Carpi J, 2018. Accuracy of the 2008 simplified criteria for the diagnosis of autoimmune hepatitis in children. Pediatr Gastroenterol Hepatol Nutr 21: 118126.

    • Search Google Scholar
    • Export Citation
  • 22.

    Vergani D, Choudhuri K, Bogdanos DP, Mieli-Vergani G, 2002. Pathogenesis of autoimmune hepatitis. Clin Liver Dis 6: 727737.

  • 23.

    Pischke S 2014. Increased HEV seroprevalence in patients with autoimmune hepatitis. PLoS One 9: e85330.

  • 24.

    Van Gerven NM, van der Eijk AA, Pas SD, Zaaijer HL, de Boer YS, Witte BI, van Nieuwkerk CM, Mulder CJ, Bouma G, de Man RA, 2016. Seroprevalence of hepatitis E virus in autoimmune hepatitis patients in The Netherlands. J Gastrointestin Liver Dis 25: 913.

    • Search Google Scholar
    • Export Citation
  • 25.

    Vieira CL, Baldaia C, Fatela N, Ramalho F, Cardoso C, 2013. Case of acute hepatitis E with concomitant signs of autoimmunity. World J Hepatol 5: 152155.

    • Search Google Scholar
    • Export Citation
  • 26.

    Le Cann P, Tong MJ, Werneke J, Coursaget P, 1997. Detection of antibodies to hepatitis E virus in patients with autoimmune chronic active hepatitis and primary biliary cirrhosis. Scand J Gastroenterol 32: 387389.

    • Search Google Scholar
    • Export Citation
  • 27.

    Cook GC, Mulligan R, Sherlock S, 1971. Controlled prospective trial of corticosteroid therapy in active chronic hepatitis. Q J Med 40: 159185.

    • Search Google Scholar
    • Export Citation
  • 28.

    Wedemeyer H, Rybczynska J, Pischke S, Krawczynski K, 2013. Immunopathogenesis of hepatitis E virus infection. Semin Liver Dis 33: 7178.

  • 29.

    Nagasaki F, Ueno Y, Mano Y, Igarashi T, Yahagi K, Niitsuma H, Okamoto H, Shimosegawa T, 2005. A patient with clinical features of acute hepatitis E viral infection and autoimmune hepatitis. Tohoku J Exp Med 206: 173179.

    • Search Google Scholar
    • Export Citation
  • 30.

    Verghese VP, Robinson JL, 2014. A systematic review of hepatitis E virus infection in children. Clin Infect Dis 59: 689697.

  • 31.

    Ramachandran J, Ramakrishna B, Eapen CE, Abraham P, Zachariah UG, Jayram A, Mathews M, Kurian G, Mukopadhya A, Chandy G, 2008. Subacute hepatic failure due to hepatitis E. J Gastroenterol Hepatol 23: 879882.

    • Search Google Scholar
    • Export Citation

 

 

 

 

Case Report: Acute Hepatitis E in a Pediatric Traveler Presenting with Features of Autoimmune Hepatitis: A Diagnostic and Therapeutic Challenge

View More View Less
  • 1 Department of Pediatrics, Steven and Alexandra Cohen Children’s Medical Center, Northwell Health, New Hyde Park, New York;
  • 2 Division of Pediatric Gastroenterology, Steven and Alexandra Cohen Children’s Medical Center, Northwell Health, New Hyde Park, New York;
  • 3 Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York;
  • 4 Department of Pathology, Steven and Alexandra Cohen Children’s Medical Center, Northwell Health, New Hyde Park, New York;
  • 5 Division of Pediatric Infectious Diseases, Steven and Alexandra Cohen Children’s Medical Center, Northwell Health, New Hyde Park, New York

Hepatitis E virus (HEV) is globally the most common cause of acute viral hepatitis. In industrialized countries, HEV infection can be seen in travelers returning from hyperendemic countries or in individuals at risk for autochthonous infection due to zoonotic exposure. Hepatitis E virus infection is often unrecognized and at times misdiagnosed because of nonspecific findings that can overlap with other causes of hepatitis, including autoimmune hepatitis (AIH). Although most cases of acute HEV infection resolve spontaneously and do not require treatment, life-threatening acute liver failure may occur in some cases. We discuss the case of an 8-year-old boy returning from Bangladesh with progressive acute liver injury and a clinical profile suggestive of AIH, who showed a favorable response to corticosteroid treatment before the diagnosis of an acute HEV infection could be established.

Introduction

Hepatitis E virus (HEV), the leading cause of acute viral hepatitis worldwide, is a single-stranded RNA virus with four human-pathogenic genotypes. Genotypes 1 and 2 are transmitted fecal-orally via contaminated water supplies in developing countries, whereas zoonotic foodborne transmission of genotypes 3 and 4 account for disease in developed countries.1 Most infections are asymptomatic or mild, yet severe disease including fulminant hepatitis, can result in death, especially in pregnant women. Extrahepatic manifestations also occur, and chronic HEV infection has been observed among patients on immunosuppressant therapy for solid organ transplants with genotype 3 and 4 infections.14 Travel-associated HEV infection has been described in travelers returning from HEV-hyperendemic countries, mostly in Asia.5

The clinical diagnosis of acute HEV infection can be difficult to establish while awaiting the results of the HEV-specific diagnostic assays. Moreover, clinical and liver biopsy findings can be suggestive of autoimmune hepatitis (AIH).6 Of note, it has been suggested that patients with significant liver injury may benefit from treatment with corticosteroids during this period of diagnostic uncertainty.7 We present a case of acute hepatitis suggestive of AIH in a returning pediatric traveler who showed a favorable response to treatment with corticosteroids before the etiologic diagnosis of HEV infection was established.

Case

An 8-year-old boy presented with 6 days of malaise, 2 days of fever, diffuse abdominal pain, and 1 day of generalized jaundice. He was born in the United States but had frequently traveled between his parents’ country of origin in Bangladesh and the United States. He had returned from his most recent trip to Bangladesh 1 month before becoming ill. There was no significant past medical history, and the family history was not contributory. On examination, he was febrile to 39.5°C and in mild distress due to abdominal pain. He had diffuse jaundice, and his abdomen was tender in the right upper and lower quadrants. His liver was palpable 2 cm below the costal margin. Findings of the remainder of the physical examination were unremarkable. Laboratory studies at admission were notable for aspartate aminotransferase of 1,033 u/L (< 40), alanine aminotransferase of 1,154 u/L (< 41), gamma glutamyl transferase of 183 u/L (8–61), total bilirubin of 10.1 mg/dL (0.2–1.2), direct bilirubin of 8.3 mg/dL (0.1–0.2), total immunoglobulin G (IgG) level of 1,552 (620–1,474), international normalized ratio of 1.25 (0.88–1.17), and prothrombin time of 14.3 seconds (9.8–13.1 seconds). His antinuclear antibody and anti-smooth muscle antibody (SMA) titers were elevated at 1:160 and 1:80, respectively. The anti-liver kidney microsomal (LKM) antibody 1 titer was negative. Other laboratory studies including serologic tests for hepatitis A, B, C, and human herpes virus 6 infection, a malaria screen, tuberculosis interferon–gamma release assay, ceruloplasmin level, alpha-1-anti-trypsin phenotype, stool cultures, and stool for ova and parasite were all negative. Specific HEV tests (anti-HEV IgG/immunoglobulin M [IgM] and HEV RNA polymerase chain reaction [PCR] assays) were submitted and pending while the patient’s liver enzymes continued to rise (Table 1). A hepatobiliary iminodiacetic acid scan showed significant hepatocellular dysfunction, while an abdominal ultrasound examination revealed an enlarged liver but no ascites and a normal portal and hepatic vein flow pattern. A liver biopsy on day 5 of hospitalization revealed active interface hepatitis with predominantly lymphocytes and plasma cells, as well as active lobular hepatitis with scattered collections of predominantly lymphocytes and plasma cells. A probable diagnosis of AIH according to the modified international autoimmune hepatitis group scoring system (IAHGSS) was considered (Table 2).8,9 Likewise, a simplified scoring system based on the presence of anti-SMA, hypergammaglobulinemia, and compatible liver histology indicated a probable diagnosis of AIH.10 Treatment for AIH with corticosteroids was initiated on day 6 of hospitalization with subsequent improvement in his clinical status and liver function tests (Table 1). The patient was released on day 8 of hospitalization with a plan to taper corticosteroids gradually in parallel to declining transaminase levels. The use of azathioprine had been considered but then dismissed as the patient’s HEV studies (HEV IgM and HEV RNA positive) became available 1 week after hospital discharge. Hepatitis E virus genotype 1 infection was assumed, given the patient’s recent travel to Bangladesh, where genotype 1 is the most commonly distributed.11 The patient has remained asymptomatic with normal laboratory studies for a follow-up period of 6 months.

Table 1

Liver function test values during hospitalization

Day of hospitalizationAST (u/L)LT (u/L)TB (mg/dL)DB (mg/dL)Albumin (g/dL)AP (u/L)INR
11,0331,15410.18.33.43751.25
21,1151,25412.410.33.43931.15
31,17993010.88.93.13581.34
41,5871,43012.09.63.23671.21
52,2361,79710.83.23451.14
6*1,5781,57610.27.93.13221.03
7*6841,2549.86.93.7345
8*2127846.14.03.73131.01

Name of laboratory test and respective range of normal values: albumin, 3.3–5.0 g/dL; ALT = alanine aminotransferase, 4–41 u/L; AP = alkalin phosphatase, 150–440 u/L; AST = aspartate aminotransferase, 4–40 u/L; DB = direct bilirubin, 0.1–0.2 mg/dL; INR = international normalized ratio, 0.88–1.17; TB = total bilirubin, 0.2–1.2 mg/dL.

* Treatment with corticosteroids (intravenous methylprednisolone 1.25 mg per kg daily, then transitioned to oral prednisone 60 mg daily) provided on these days.

Table 2

Presented case pretreatment modified IAHGSS score9

Modified IAHGSSCase
ParameterResultAssociated scoreResultScore
GenderFemale+2Male0
AP to AST ratio (relative to the upper limit of normal)< 1.5+20.15+2
1.5–3.00
> 3.0−2
Serum IgG (relative to the upper limit of normal)> 2.0+31.05+1
1.5–2.0+2
1.0–1.5+1
< 1.00
ANA, anti-SMA, or anti-LKM antibody titers> 1:80+3Anti-SMA 1:80+2
1:80+2
1:40+1
< 1:400
AMA titerPositive−4Not tested0
Hepatitis viral markers (for hepatitis A, B, and C)*Positive−3Negative (hepatitis E testing was pending at this time)0
Negative+3
Drug historyPositive−4Negative+1
Negative+1
Average alcohol intake< 25 g/day+2< 25 g/day+2
> 60 g/day−2
Liver histologyInterface hepatitis+3Interface hepatitis with predominantly lymphoplasmacytic infiltrate+4
Predominantly lymphoplasmacytic infiltrate+1
Rosetting of liver cells+1
None of the above−5
Biliary changes−3
Other changes−3
Other autoimmune diseases (personal or family history)Yes+2No0
Optional additional parameters:0
Seropositivity for other defined antibodiesSeropositive+2Not seropositive for defined antibodies
HLA DR3 or DR4HLA positive+1HLA not tested
Total15 = definite AIH12 = probable AIH
10–14 = probable AIH

AIH = autoimmune hepatitis; AMA = anti-mitochondrial antibody; ANA = anti-nuclear antibody; AP = alkaline phosphatase; AST = aspartate aminotransferase; IAHGSS = International Autoimmune Hepatitis Group Scoring System; IgG = immunoglobulin G; HLA = human leukocyte antigen; LKM = liver kidney microsomal antibody; SMA = smooth muscle antibody. Interpretation of aggregate pretreatment score: 10–15 = probable AIH; 15 = definite AIH.

* Markers of hepatitis A, B, and C viruses include the presence of IgM anti-hepatitis A virus, hepatitis B surface antigen, IgM anti-hepatitis B core, anti-HCV, or HCV-RNA). If a viral etiology is suspected despite seronegativity for these markers, test for other potentially hepatotropic viruses such as cytomegalovirus, Epstein-Barr virus, or hepatitis E may be relevant.

Discussion

Pediatric travelers returning ill with fever and gastrointestinal symptoms from HEV hyperendemic regions need to be assessed for infections with hepatotropic viruses, including HEV. This case illustrates that clinical, laboratory, and histopathologic features of such patients are not specific for HEV and can mimic AIH, thereby creating a diagnostic dilemma. Special testing for HEV is rarely available on-site in most health centers and relevant assays must be sent out to a commercial laboratory that may run such assays only once or twice per week. This temporary diagnostic uncertainty can further lead to a therapeutic dilemma, when hepatic inflammation advances despite supportive measures. In this case corticosteroid administration was followed by improved hepatic inflammation despite the underlying viral etiology.

Hepatitis E virus infection has been recognized as a travel-associated infectious disease.12 In a 5-year review of the GeoSentinel surveillance network analyzing data from 53 specialized international travel clinics, only 45 cases were noted among 42,000 ill traveler records reported, suggesting that HEV infection may not be a high-burden infectious disease among travelers.13 On the contrary, a recent 1-year study of reportable diseases in only one region in Australia noted 24 cases of HEV infection. Moreover, the enhanced surveillance portion of the study revealed a demographic profile of affected patients that is similar to our case: most cases were travel-associated (93%), visiting friends and relatives (VFRs) was the most commonly reported reason for travel (77%), and the majority visited a destination in Asia (77%). Of note, 21% of the travel-associated cases in that study were children.14 Imported HEV infection has not only been documented in returning travelers, but also in immigrants, refugees, migrant workers, and military personnel.1518 As there is no hepatitis E vaccine commercially available outside of China, HEV infection prevention efforts focus on access to a safe water supply and the sole consumption of food that has been thoroughly cooked.19

Autoimmune hepatitis is a rare chronic liver disease, clinically characterized by the presence of autoantibodies, hypergammaglobulinemia, and histologically noted for interface hepatitis.20 Autoimmune hepatitis is a clinical diagnosis based on the presence of a combination of clinical findings, laboratory abnormalities, and liver histopathology. Diagnostic scoring systems such as the IAHGSS (Table 2) have been originally developed for adults and subsequently modified for children as research and not as diagnostic tools.810 The simplified scoring system developed for children was noted not only for its moderate sensitivity but also high specificity.21 Of note, if the HEV test results had been available in time, the patient would not have fulfilled the criteria for probable AIH.

The pathogenesis of AIH is only incompletely understood, yet exogenous triggers such as acute infections with hepatitis A virus, hepatitis C virus, Epstein–Barr virus, cytomegalovirus, and HEV have been discussed.22 Hepatitis E virus infection may trigger an immune cascade leading to AIH, and a recent study from Germany found evidence of a significantly higher rate of anti-HEV antibodies in patients with AIH, compared with the general population.23 Although a subsequent larger Dutch study could not confirm that result, this study also demonstrated that about a third of AIH patients had evidence of a silent HEV infection. It was concluded that all AIH patients require careful diagnostic testing to rule out HEV infection.24

Differentiating HEV from AIH clinically may be challenging. There are known phenomena of patients with AIH testing positive for HEV-specific immunoglobulin and patients with HEV temporarily showing immunologic signs suggestive of AIH, as did our patient.25,26 Furthermore, the serologic diagnosis of HEV infection can be problematic as assays vary in performance. The only specific testing which can definitively distinguish HEV from AIH is isolation of HEV viral RNA by PCR, which can only be isolated during a narrow window of viremia.1

This patient’s clinical team was faced with the practical question of how to treat an acutely ill patient whose clinical presentation was suggestive of AIH, who was clinically not improving despite supportive care, and for whom HEV testing results were not immediately available. Although AIH treatment recommendations include timely initiation of corticosteroids with subsequent transition to long-term immunosuppression, immunosuppressive treatment may seem counterproductive for acute HEV.27 In fact, long-term immunosuppression is a known risk factor for developing chronic HEV infection with genotypes 3 and 4.1 However, as the principal mechanism of liver damage in HEV is thought to be immune-mediated rather than due to a HEV-specific cytopathic effect, short-term immunosuppressive treatment may limit immune-mediated liver and extrahepatic damage in HEV.28 In fact, corticosteroids have been successfully used to treat presumed immune-mediated extrahepatic manifestations of HEV such as thrombocytopenia and glomerulonephritis.3 Moreover, there have been three previously published case reports of patients with acute HEV infection, who had been treated with corticosteroids, all of whom had a good clinical outcome (Table 3). Although these case reports, including our case, suggest that the administration of corticosteroids in acute HEV infection may be beneficial, it is possible that the observed improvements might have reflected the natural course of the patients’ HEV infection.30 Moreover, publication bias and lack of analytical studies represent important limitations to the observed beneficial effect of corticosteroid on patients with acute HEV infection. Future investigations need to address the question whether corticosteroids can improve outcome of patients with acute HEV infection associated liver failure, which may carry a significant risk for mortality, and more specifically whether the pediatric end-stage liver disease score would be useful to justify the need for short-term corticosteroid therapy in children with acute HEV infection.31

Table 3

Published cases of acute hepatitis E infection treated with corticosteroids

CasePresumed diagnosisAge, gender, location of caseAIH-related laboratory findingsHEV-specific testsTreatment receivedOutcome
#17Drug-induced liver injury63, male, GermanyANA (+)IgM (−)PDetails lacking on duration of hospitalization and follow-up, but outcome described as good with resolution of the HEV infection.
Anti-SMA (−)IgG (+)
Anti-LKM (−)RNA (+)
Total IgG (+)
#225AIH type 158, female, PortugalANA (+)IgM (+)P and AHospitalized for 2 weeks
Anti-SMA (+)IgG (−)Treated with corticosteroids for 2 months
Anti-LKM (−)RNA (+)Clinically well with normal laboratory values off treatment for 4 months
Total IgG (+)
#329AIH25, female JapanANA (+)IgM (−)M and PHospitalized for 15 weeks
Anti-SMA (+)IgG (+)Treated with corticosteroids for 8 months
Total IgG (+)RNA (−)Clinically well with normal laboratory values off treatment for 1.5 years
IgA (+)

A = azathioprine; AIH = autoimmune hepatitis; ANA = anti-nuclear antibody; HEV = hepatitis E virus; IgA = immunoglobulin A; IgG = immunoglobulin G; LKM = liver kidney microsomal antibody 1; M = methylprednisone; P = prednisolone; SMA = smooth muscle antibody; (+) = positive and/or elevated; (−) = negative and/or within normal limits.

In summary, acute HEV infection is an important diagnosis to consider in pediatric travelers returning ill with fever and a gastrointestinal symptom complex from HEV-hyperendemic regions, especially if they are VFR travelers. Clinical, laboratory, and histopathologic features are not specific for HEV infection and overlap with those of AIH. Consequently, there can be a diagnostic and therapeutic dilemma if HEV diagnostic assays are not readily available and liver function continues to deteriorate. More timely access to HEV-specific assays would be helpful, especially at institutions that frequently serve mobile communities with close ties to HEV-hyperendemic regions. The case reported here and other limited observational reports have shown a potentially positive effect of short-term corticosteroid treatment in patients with acute hepatitis E with progressive hepatic inflammation, and additional research is needed to further assess its impact and safety.

REFERENCES

  • 1.

    Khuroo MS, Khuroo MS, Khuroo NS, 2016. Hepatitis E: discovery, global impact, control and cure. World J Gastroenterol 22: 70307045.

  • 2.

    Kamar N, Izopet J, Pavio N, Aggrawal R, Labrique A, Wedemeyer H, Dalton HR, 2017. Hepatitis E virus infection. Nat Rev Dis Primers 3: 17086.

  • 3.

    Ali G, Kumar M, Bali S, Wadhwa W, 2001. Hepatitis E associated immune thrombocytopaenia and membranous glomerulonephritis. Indian J Nephrol 11: 7072.

    • Search Google Scholar
    • Export Citation
  • 4.

    Pischke S, Hartl J, Pas SD, Lohse AW, Jacobs BC, Van der Eijk AA, 2017. Hepatitis E virus: infection beyond the liver? J Hepatol 66: 10821095.

  • 5.

    Dahl V, Wallenstein A, 2017. Self-reported infectious during international travel and notifiable infections among returning international travellers, Sweden, 2009–2013. PLoS One 12: e0181625.

    • Search Google Scholar
    • Export Citation
  • 6.

    Patel I, Ching Companioni R, Bansal R, Vyas N, Catalano C, Aron J, Walfish A, 2016. Acute hepatitis E presenting with clinical feature of autoimmune hepatitis. J Community Hosp Intern Med Perspect 6: 33342.

    • Search Google Scholar
    • Export Citation
  • 7.

    Sebode M, Pischke S, Lütgehetmann M, Polywka S, Quaas A, Lohse AW, Wege H, 2014. New foe treated with old guns—supportive role of steroids in the treatment of acute severe hepatitis E. BMC Gastroenterol 14: 191.

    • Search Google Scholar
    • Export Citation
  • 8.

    Ebbeson RL, Schruiber RA, 2004. Diagnosing autoimmune hepatitis in children: is the international autoimmune hepatitis group scoring system useful? Clin Gastroenterol Hepatol 2: 935940.

    • Search Google Scholar
    • Export Citation
  • 9.

    Alvarez F 1999. International autoimmune hepatitis group: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol 31: 929938.

    • Search Google Scholar
    • Export Citation
  • 10.

    Hiejima E, Komatsu H, Sogo T, Inui A, Fujisawa T, 2011. Utility of simplified criteria for the diagnosis of autoimmune hepatitis in children. J Pediatr Gastroenterol Nutr 52: 470473.

    • Search Google Scholar
    • Export Citation
  • 11.

    Sugitani M 2009. Detection of hepatitis E virus RNA and genotype in Bangladesh. J Gastroenterol Hepatol 24: 599604.

  • 12.

    Zuckerman JN, 2003. Hepatitis E and the traveller. Travel Med Infect Dis 1: 7376.

  • 13.

    Leder K 2013. GeoSentinel surveillance of illness in returned travelers, 2007–2011. Ann Intern Med 158: 456468.

  • 14.

    Heywood AE 2016. The contribution of travellers visiting friends and relatives to notified infectious diseases in Australia: state-based enhanced surveillance. Epidemiol Infect 144: 35543563.

    • Search Google Scholar
    • Export Citation
  • 15.

    Bradanini L, Youkee D, Fabris P, Roman L, Brunetti E, Giordani MT, 2017. Acute hepatitis E virus infection in a migrant population in north east Italy: a retrospective analysis. Travel Med Infect Dis 20: 3742.

    • Search Google Scholar
    • Export Citation
  • 16.

    Azman AS 2017. High hepatitis E seroprevalence among displaced persons in South Sudan. Am J Trop Med Hyg 96: 12961301.

  • 17.

    Sadarangani SP, Lim PL, Vasoo S, 2017. Infectious diseases and migrant worker health in Singapore: a receiving country’s perspective. J Travel Med 24: tax014.

    • Search Google Scholar
    • Export Citation
  • 18.

    Eick A 2010. Hepatitis E seroprevalence and seroconversion among US military service members deployed to Afghanistan. J Infect Dis 202: 13021308.

    • Search Google Scholar
    • Export Citation
  • 19.

    Teshale EH, 2017. Hepatitis E. Brunette GW, Kozarsky PE, eds. CDC Health Information for International Travel 2018. New York, NY: Oxford University Press.

    • Search Google Scholar
    • Export Citation
  • 20.

    Mieli-Vergani G 2009. Autoimmune hepatitis. J Pediatr Gastroenterol Nutr 49: 158164.

  • 21.

    Arcos-Machancoses JV, Molera Busoms C, Julio Tatis E, Victoria Bovo M, Quintero Bernabeu J, Juamperez Goni J, Crujeiras Martinez V, Martin de Carpi J, 2018. Accuracy of the 2008 simplified criteria for the diagnosis of autoimmune hepatitis in children. Pediatr Gastroenterol Hepatol Nutr 21: 118126.

    • Search Google Scholar
    • Export Citation
  • 22.

    Vergani D, Choudhuri K, Bogdanos DP, Mieli-Vergani G, 2002. Pathogenesis of autoimmune hepatitis. Clin Liver Dis 6: 727737.

  • 23.

    Pischke S 2014. Increased HEV seroprevalence in patients with autoimmune hepatitis. PLoS One 9: e85330.

  • 24.

    Van Gerven NM, van der Eijk AA, Pas SD, Zaaijer HL, de Boer YS, Witte BI, van Nieuwkerk CM, Mulder CJ, Bouma G, de Man RA, 2016. Seroprevalence of hepatitis E virus in autoimmune hepatitis patients in The Netherlands. J Gastrointestin Liver Dis 25: 913.

    • Search Google Scholar
    • Export Citation
  • 25.

    Vieira CL, Baldaia C, Fatela N, Ramalho F, Cardoso C, 2013. Case of acute hepatitis E with concomitant signs of autoimmunity. World J Hepatol 5: 152155.

    • Search Google Scholar
    • Export Citation
  • 26.

    Le Cann P, Tong MJ, Werneke J, Coursaget P, 1997. Detection of antibodies to hepatitis E virus in patients with autoimmune chronic active hepatitis and primary biliary cirrhosis. Scand J Gastroenterol 32: 387389.

    • Search Google Scholar
    • Export Citation
  • 27.

    Cook GC, Mulligan R, Sherlock S, 1971. Controlled prospective trial of corticosteroid therapy in active chronic hepatitis. Q J Med 40: 159185.

    • Search Google Scholar
    • Export Citation
  • 28.

    Wedemeyer H, Rybczynska J, Pischke S, Krawczynski K, 2013. Immunopathogenesis of hepatitis E virus infection. Semin Liver Dis 33: 7178.

  • 29.

    Nagasaki F, Ueno Y, Mano Y, Igarashi T, Yahagi K, Niitsuma H, Okamoto H, Shimosegawa T, 2005. A patient with clinical features of acute hepatitis E viral infection and autoimmune hepatitis. Tohoku J Exp Med 206: 173179.

    • Search Google Scholar
    • Export Citation
  • 30.

    Verghese VP, Robinson JL, 2014. A systematic review of hepatitis E virus infection in children. Clin Infect Dis 59: 689697.

  • 31.

    Ramachandran J, Ramakrishna B, Eapen CE, Abraham P, Zachariah UG, Jayram A, Mathews M, Kurian G, Mukopadhya A, Chandy G, 2008. Subacute hepatic failure due to hepatitis E. J Gastroenterol Hepatol 23: 879882.

    • Search Google Scholar
    • Export Citation

Author Notes

Address correspondence to Stefan H. F. Hagmann, Division of Pediatric Infectious Diseases, Steven and Alexandra Cohen Children’s Medical Center, Northwell Health, 269-01 76th Ave., New Hyde Park, NY 11040. E-mail: shagmann@northwell.edu

Authors’ addresses: Nathan Z. Minkoff, Department of Pediatrics, Steven and Alexandra Cohen Children’s Medical Center, New Hyde Park, NY, E-mail: nathan.minkoff@gmail.com. Kate Buzzi, Division of Pediatric Gastroenterology, Steven and Alexandra Cohen Children’s Medical Center, New Hyde Park, NY, E-mail: kbuzzi@northwell.edu. Alex K. Williamson, Department of Pathology, Steven and Alexandra Cohen Children’s Medical Center, New Hyde Park, NY, E-mail: awilliamson@northwell.edu. Stefan H. F. Hagmann, Division of Pediatric Infectious Diseases, Steven and Alexandra Cohen Children’s Medical Center, New Hyde Park, NY, E-mail: shagmann@northwell.edu.

Save