Clinical and Pathological Features, and Diagnosis
Sieberhagen Cyril
South West Liver Unit, Derriford Hospital and Plymouth University Peninsula School of Medicine and Dentistry, Plymouth, UK
Search for more papers by this authorMatthew E. Cramp
South West Liver Unit, Derriford Hospital and Plymouth University Peninsula School of Medicine and Dentistry, Plymouth, UK
Search for more papers by this authorSieberhagen Cyril
South West Liver Unit, Derriford Hospital and Plymouth University Peninsula School of Medicine and Dentistry, Plymouth, UK
Search for more papers by this authorMatthew E. Cramp
South West Liver Unit, Derriford Hospital and Plymouth University Peninsula School of Medicine and Dentistry, Plymouth, UK
Search for more papers by this authorHoward C. Thomas BSc, PhD, FRCP, FRCPath, FMedSci
Emeritus Professor of Hepatology, Department of Medicine, Imperial College London, London, UK
Search for more papers by this authorAnna S.F. Lok MD
Alice Lohrman Andrews Research Professor in Hepatology, Director of Clinical Hepatology, Professor of Internal Medicine, Associate Chair for Clinical Research, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI, USA
Search for more papers by this authorStephen A. Locarnini MBBS, BSc(Hons), PhD, FRCPath
Head, Research & Molecular Development, Victorian Infectious Diseases Reference Laboratory, Melbourne, VIC, Australia
Search for more papers by this authorArie J. Zuckerman MD, DSc, FRCP, FRCPath, FMedSci
Emeritus Professor of Medical Microbiology, Formerly Principal and Dean, Royal Free Hospital School of Medicine
Search for more papers by this authorSummary
Hepatitis E virus (HEV) is a common infection worldwide resulting in significant morbidity. It typically results in a self-limiting illness characterized by the development of acute hepatitis, and the treatment is usually conservative. Overall, mortality due to HEV infection is low and arises from occasional cases of acute liver failure or cases with preexisting liver disease. In pregnant women in developing countries, however, it is a serious infection with a high mortality. Recent evidence has suggested that chronicity can occur in the immunosuppressed and that this may lead to progressive liver injury and possible cirrhosis. Extrahepatic manifestations have also been described. There is evidence that treatment may be of benefit in the immunosuppressed and those with extrahepatic manifestations, although further research is required. HEV is increasingly being recognized in developed countries, and it should be considered as a cause in anyone presenting with hepatitis.
References
- Khuroo MS. Study of an epidemic of non-A, non-B hepatitis: possibility of another human hepatitis virus distinct from post-transfusion non-A, non-B type. Am J Med 1980; 68: 818–823.
- Vishwanathan R, Sidhu AS. Infectious hepatitis: clinical findings. Ind J Med Res 1957; 45(Suppl): 49–58.
- Wong DC., Purcell RH, Sreenivasan MA, Prasad SR, Pavri KM. Epidemic and endemic hepatitis in India: evidence for a non-A, non-B etiology. Lancet 1980; 2: 876–879.
- Reyes GR, Purdy MA, Kim JP, et al. Isolation of a cDNA from the virus responsible for enterically transmitted non-A, non-B hepatitis. Science 1990; 247: 1335–1339.
- Khudyakov Y, Kamili S. Serological diagnostics of hepatitis E virus infection. Virus Res 2011; 161: 84–92.
- Tei S, Kitajima N, Takahashi K, Mishiro S. Zoonotic transmission of hepatitis E from deer to human beings. Lancet 2003; 362: 371–373.
- Tei S, Kitajima N, Ohara S, et al. Consumption of uncooked deer meet as a risk factor for hepatitis E virus infection: an age- and sex-matched case-control study. J Med Virol 2004; 74: 67–70.
- Aggarwal R, Naik S. Epidemiology of hepatitis E: current status. J Gastroenterol Hepatol 2009; 24: 1484–1493.
- Dalton HR, Stableforth W, Hazeldine S, et al. Autochthonous hepatitis E in Southwest England: a comparison with hepatitis A. Eur J Clin Microbiol Infect Dis 2008; 27: 579–585.
- Aggarwal R. Clinical presentation of hepatitis E. Virus Res 2011; 161: 15–22.
- Naik SR, Aggarwal R, Salunke PN, Mehrotra NN. A large waterborne viral hepatitis E epidemic in Kanpur. Indian Bull WHO 1992; 70: 597–604.
- Dalton HR, Stableforth W, Thurairajah P, et al. Autochthonous hepatitis E in Southwest England: natural history, complications, and seasonal variation, and hepatitis E virus IgG seroprevalence in blood donors, the elderly and patients with chronic liver disease. Eur J Gastroenterol Hepatol 2008; 20: 784–790.
- Borgen K, Herremans T, Duizer E, et al. Non-travel related hepatitis E virus genotype 3 infections in the Netherlands; a case series 2004–2006. BMC Infect Dis 2008; 8: 61.
- Dalton HR, Thurairajah PH, Fellows HJ, et al. Autochthonous hepatitis E in Southwest England. J Viral Hepat 2007; 14: 304–309.
- Zhang S, Wang J, Yuan Q, et al. Clinical characteristics and risk factors of sporadic hepatitis E in central China. Virol J 2011; 8: 152.
- Takeda HA, Matsubayashi K, Sakata H, et al. A nationwide survey for prevalence of HEV antibody in qualified blood donors in Japan. Vox Sanguin 2010; 99: 307–313.
- Labrique AB. Population seroprevalence of HEV antibodies in rural Bangladesh. Am J Trop Med Hyg 2009; 81: 875–881.
- Cheng PN. Seroprevalence of HEV infection amongst institutionalised psychiatric patients in Taiwan. J Clin Virol 2007; 38: 44–48.
- Aggarwal R, Krawczynski K. Hepatitis E: an overview and recent advances in clincial and laboratory research. J Gastroenterol Hepatol 2000; 15: 9–20.
- Vishwanathan R. Epidemiology. Ind J Med Res 1957; 45(Suppl 1): 1–29.
- Turner J, Godkin A, Neville P, Kingham J, Ch′ng CL. Clinical characteristics of hepatitis E in a “non-endemic” population. J Med Virol 2010; 82: 1899–1902.
- Myint H, Soe MM, Khin T, Myint TM, Tin KM. A clinical and epidemiological study of an epidemic of non-A, non-B hepatitis in Rangoon. Am J Trop Med Hyg 1985; 34: 1183–1189.
- Miyamura T. Hepatitis E virus infection in developed countries. Virus Res 2011; 161: 40–46.
- Kumar A, Beniwal M, Kar P, Sharma JB, Murthy NS. Hepatitis E in pregnancy. Intl J Gynaecol Obstet 2004; 85: 240–244.
- Dalton HR, Bendall R, Ijaz S, Banks M. Hepatitis E: an emerging infection in developed countries. Lancet Infect Dis 2008; 8: 698–709.
- Bernal W, Auzinger G, Dhawan A, Wendon J. Acute liver failure. Lancet 2010; 376: 190–201.
- Lee WM, Brown KE, Young NS, et al. Brief report: no evidence for parvovirus B19 or hepatitis E virus as a cause of acute liver failure. Digest Dis Sci 2006; 51: 1712–1715.
- Mushahwar IK. Hepatitis E virus: molecular virology, clinical features, diagnosis, transmission, epidemiology, and prevention. J Med Virol 2008; 80: 646–658.
- Khuroo MS, Kamili S. Aetiology and prognostic factors in acute liver failure in India. J Viral Hepatol 2003; 10: 224–231.
- Patra S, Kumar A, Trivedi SS, Puri M, Sarin SK. Maternal and fetal outcomes in pregnant women with acute hepatitis E virus infection. Ann Intern Med 2007; 147: 28–33.
- Khuroo MS, Kamili S. Aetiology, clinical course and outcome of sporadic acute viral hepatitis in pregnancy. J Viral Hepat 2003; 10: 61–69.
- Khuroo MS, Kamili S. Clinical course and duration of viraemia in vertically transmitted hepatitis E virus (HEV) infection in babies borne to HEV-infected mothers. J Viral Hepat 2009; 16: 519–523.
- Bhatia V, Singhal A, Panda SK, Acharya SK. A 20-year single-centre experience with acute liver failure during pregnancy: is the prognosis really worse? Hepatology 2008; 48: 1577–1585.
- Rasheeda CA, Navaneethan U, Jayanthi V. Liver disease in pregnancy and its influence on maternal and fetal mortality – a prospective study from Chennai, Southern India. European J Gastroenterol Hepatol 2008; 20: 362–364.
- Magriples U. Hepatitis in pregnancy. Sem Perinatol 1998; 22: 112–117.
- Pastorek JG 2nd. The ABC's of hepatitis in pregnancy. Clin Obstet Gynecol 1993; 36: 843–854.
- Prusty BK, Hedau S, Singh A, Kar P, Das BC. Selective suppression of NF-kBp65 in hepatitis-infected pregnant women manifesting severe liver damage and high mortality. Molecul Med 2007; 13: 518–526.
- Boll G, Reimann J. Estrogen treatment depletes extrathymic T cells from intestinal lymphoid tissues. Scand J Immunol 1996; 43: 345–350.
- Rijhisinghami AG, Thompson K, Bhatia SK, Waldscmidt TJ. Estrogen blocks early T cell development in the thymus. Amer J Reprod Immunol 1996; 36: 267–277.
- Sakaguchi S. Regulatory T cells: key controllers of immunologic self-tolerance. Cell 2000; 101: 455–458.
- Pal R, Aggarwal R, Naik SR, Das V, Das S, Naik S. Immunological alterations in pregnant women with acute hepatitis E. J Gastroenterol Hepatol 2005; 20: 1094–1101.
- Navaneethan U, Al Mohajer M, Shata MT. Hepatitis E and pregnancy: understanding the pathogenesis. Liver Intl 2008; 28: 1190–1199.
- Hamid SS, Atiq M, Shehzad F, et al. Hepatitis E virus superinfection in patients with chronic liver disease. Hepatology 2002; 36: 474–478.
- Monga R, Garg S, Tyagi P, Kumar N. Superimposed acute hepatitis E infection in patients with chronic liver disease. Indian J Gastroenterol 2004; 23: 50–52.
- Kumar Acharya S, Kumar Sharma P, Singh R, et al. Hepatitis E virus (HEV) infection in patients with cirrhosis is associated with rapid decompensation and death. J Hepatol 2007; 43: 387–394.
- Aithal PG, Day CP. The natural history of histologically proved drug induced liver disease. Gut 1999; 44: 731–735.
- Lewis JH. Drug-induced liver disease. Med Clin North Amer 2000; 84: 1275–1311.
- Dalton HR, Fellows HJ, Stableforth W, et al. The role of hepatitis E virus testing in drug-induced liver injury. Aliment Pharmacol Therapeut 2007; 26: 1429–1435.
- Davern TJ, Chalasani N, Fontana RJ, et al Acute hepatitis E infection accounts for some cases of suspected drug-induced liver injury. Gastroenterology 2011; 141: 1665–1672.
- Kamar N, Mansuy JM, Ouezzani L, et al. Hepatitis E virus and chronic hepatitis in organ-transplant recipients. New Eng J Med 2008; 358: 811–817.
- Le Coutre P, Meisel H, Hofman J, et al. Reactivation of hepatitis E infection in a patient with acute lymphoblastic leukaemia after allogeneic stem cell transplantation. Gut 2009; 58: 699:702.
- Ollier L, Tieulie N, Sanderson F, et al. Chronic hepatitis after hepatitis E virus infection in a patient with non-Hodgkin lymphoma taking rituximab. Ann Inter Med 2009; 150: 430–431.
- Pischke S, Suneetha PV, Baechlein C, et al. Hepatitis E virus infection as a cause of graft hepatitis in liver transplant recipients. Liver Transpl 2010; 16: 74–82.
- Gerolami R, Moal V, Colson P. Chronic hepatitis E with cirrhosis in a kidney-transplant patient. New Eng J Med 2008; 358: 859–860.
- Haagsma EB, Van den Berg AP, Porte RJ, et al. Chronic hepatitis E virus infection in liver transplant recipients. Liver Transpl 2008; 14: 547–553.
- Deniel C, Coton T, Brardjanian S, Guisset M, Nicand E, Simon F. Acute pancreatitis: a rare complication of acute hepatitis E. J Clin Virol 2011; 51: 202–204.
- Bhagat S, Wadhawan M, Sud R, Arora A. Hepatitis viruses causing pancreatitis and hepatitis: a case series and review of literature. Pancreas 2008; 36: 424–427.
- Jain P, Nijhawan S, Rai RR, Nepalia S, Mathur A. Acute pancreatitis in acute viral hepatitis. World J Gastroenterol 2007; 13: 5741–5744.
- Jaroszewicz J, Flisiak R, Kalinowska A, Wierzbicka I, Prokopowicz D. Acute hepatitis E complicated by acute pancreatitis: a case report and literature review. Pancreas 2005; 30: 382–384.
- Kamani P, Baijal R, Amarapurkar D, et al. Guillain-Barre syndrome associated with acute hepatitis E. Ind J Gastroenterol 2005; 24: 216.
- Loly JP, Rikir E, Seivert M, et al. Guillain-Barre syndrome following hepatitis E. World J Gastroenterol 2009; 15: 1645–1647.
- Fong F, Illahi M. Neuralgic amyotrophy associated with hepatitis E virus. Clin Neurol Neurosurg 2009; 111: 193–195.
- Kejariwal D, Roy S, Sarkar N. Seizure associated with acute hepatitis E. Neurology 2001; 57: 1935.
- Thapa R, Mallick D, Biswas B. Pseudotumour cerebri in childhood hepatitis E virus infection. Headache 2009; 50: 152–153.
- Kamar N, Bendall RP, Peron JM, et al. Hepatitis E virus and neurologic disorders. Emerg Infect Dis 2011; 17: 173–179.
- Singh NK, Gangappa N. Acute immune thrombocytopaenia associated with hepatitis E in an adult. American J Haematol 2007; 82: 942–943.
- Fourquet E, Mansuy JM, Bureau C, et al. Severe thrombocytopaenia associated with acute autochthonous hepatitis E. J Clin Virol 2010; 48: 73–74.
- Mishra P, Mahapatra M, Kumar R, Pati HP. Autoimmune hemolytic anaemia and erythroid hypoplasia associated with hepatitis E. Indian J Gastroenterol 2007; 26: 195–196.
- Abid S, Khan AH. Severe hemolysis and renal failure in glucose-6-phosphate dehydrogenase deficient patients with hepatitis E. American J Gastroenterol 2002; 97: 1544–1547.
- Au WY, Ngai CW, Chan WM, Leung RY, Chan SC. Hemolysis and methemoglobinemia due to hepatitis E virus infection in patient with G6PD deficiency. Ann Hematol 2011; 90: 1237–1238.
- Kamar N, Abravanel F, Selves J, et al. Influence of immunosuppressive therapy on the natural history of genotype 3 hepatitis E virus infection after organ transplantation. Transplantation 2010; 89: 353–360.
- Kamar N, Garrouste C, Haagsma EB, et al.. Factors associated with chronic hepatitis in patients with hepatitis E virus infection who have received solid organ transplants. Gastroenterology 2011; 140: 1481–1489.
- Kamar N, Rostaing L, Abravanel F, et al. Pegylated Interferon-alpha for treating chronic hepatitis E virus infection after liver transplantation. Clin Infec Dis 2010; 50: e30–e33.
- Haagsma EB, Riezebos-Brilman A, Van den Berg AP, Porte RJ, Niesters HGM. Treatment of chronic hepatitis E in liver transplant recipients with pegylated interferon alpha-2b. Liver Transpl 2010; 16: 474–477.
- Alric L, Bonnet D, Laurent G, Kamar N, Izopet J. Chronic hepatitis E virus infection: successful virologic response to pegylated interferon-alpha therapy. Ann Intern Med 2010; 153: 135–136.
- Mallet V, Nicand E, Sultanik P, et al. Brief communication: case reports of ribavirin treatment for chronic hepatitis E. Ann Intern Med 2010; 153: 85–89.
- Dalton HR, Keane FE, Bendall R, Mathew J, Ijaz S. Treatment of chronic hepatitis E in a patient with HIV infection. Ann Intern Med 2011; 155: 479–480.
- Gerolami R, Borentain P, Raissouni F, Motte A, Soilas C, Colson P. Treatment of severe acute hepatitis E by ribavirin. J Clin Virol 2011; 52: 60–62.
- Malcolm P, Dalton H, Hussaini HS, Mathew J. The histology of acute autochthonous hepatitis E virus infection. Histopathology 2007; 51: 190–194.
- Gupta DN, Smetana HF. The histopathology of viral hepatitis as seen in the Delhi epidemic (1955– 56). Ind J Med Res 1957; 45: 101–113.
- Morrow RH, Smetana HF, Sai FT, Edgcomb JH. Unusual features of viral hepatitis in Accra, Ghana. Ann Intern Med 1968; 68: 1250–1264.
- Halac U, Beland K, Lapierre P, et al. Chronic hepatitis E infection in children with liver transplantation. Gut 2012; 61: 597–603.
- Worm HC, Van der Poel WHM, Brandstatter G. Hepatitis E: an overview. Microb Infect 2002; 2: 657–666.
- Legrand-Abravanel F, Thevenet I, Mansu JM, et al. Good performance of immunoglobulin M assays in diagnosing genotype 3 hepatitis E virus infections. Clin Vacc Immunol 2009; 16: 772–774.
- Bendall R, Ellis V, Ijaz S, Ali R, Dalton H. A comparison of two commercially available anti-HEV IgG kits and a re-evaluation of anti-HEV IgG seroprevalence data in developed countries. J Med Virol 2010; 82: 799–805.
- Chauhan A, Jameel S, Dilawari JB, Chawla YK, Kaur U, Ganguly NK. Hepatitis E transmission to a volunteer. Lancet 1993; 341: 149–150.
- Zhao ZY, Ruan B, Shao H, Chen ZJ, Liu SL. Detection of hepatitis E virus RNA in sera of patients with hepatitis E by polymerase chain reaction. Hepatobil Pancreat Dis Intl 2007; 6: 38–42.
- Baylis SA, Hanschmann KM, Blümel J, Nübling CM, HEV Collaborative Study Group. Standardization of hepatitis E virus (HEV) nucleic acid amplification technique-based assays: an initial study to evaluate a panel of HEV strains and investigate laboratory performance. J Clin Microbiol 2011; 49: 1234–1239.
- Enouf V, Dos Reis G, Guthmann JP, et al. Validation of single real-time TaqMan PCR assay for the detection and quantitation of four major genotypes of hepatitis E virus in clinical specimens. J Med Virol, 2006; 78: 1076–1082.
- Takahashi M, Tanaka T, Azuma M, et al. Prolonged fecal shedding of hepatitis E virus (HEV) during sporadic acute hepatitis E: evaluation of infectivity of HEV in fecal specimens in a cell culture system. J Clin Microbiol 2007; 45: 3671–3679.e
- Bouwknegt M, Rutjes SA, Reusken CB, et al. The course of hepatitis E virus infection in pigs after contact-infection and intravenous inoculation. BMC Veterin Res 2009; 5: 7.
- Gupta P, Jagya N, Pabhu SB, Durgapal H, Acharya SK, Panda SK. Immunohistochemistry for the diagnosis of hepatitis E virus infection. J Viral Hepat 2012; 19: e177–e183.