Abstract
A woman in her late 70 s was diagnosed with liver injury at a health examination. Despite treatment with ursodeoxycholic acid at a nearby hospital, her transaminase levels elevated in two peaks. She was transferred to our hospital 77 days after the health examination. She weighed 42 kg and had a low body mass index of 19.8 kg/m2. Viral markers, including immunoglobulin A (IgA) against hepatitis E virus (anti-HEV IgA), were negative. Drug-induced liver injury was negligible. We suspected autoimmune hepatitis because of the patient’s female gender and positive antinuclear antibody. However, prednisolone and azathioprine failed to completely improve her hepatitis. On day 643, anti-HEV IgA was re-evaluated and found to be positive. She was diagnosed with autochthonous chronic hepatitis E because the virus strains in the preserved serum on day 77 and the serum on day 643 had identical nucleotide sequences (genotype 3a). Following prednisolone and azathioprine discontinuation, ribavirin (RBV) was administered for 3 months. HEV RNA disappeared and remained negative for more than 6 months after the cessation of RBV. The HEV RNA titer of 6.2 log10 copies/mL on day 77 was unusually high 2.5 months after the onset, suggesting that hepatitis E had already been chronic before immunosuppressive treatment for possible autoimmune hepatitis. After getting married at 23 years old, she had been a housewife and had no comorbidities that might deteriorate her immunity. Chronicity should be kept in mind when encountering HEV infection in elderly and underweight patients.
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References
Clemente-Casares P, Pina S, Buti M, et al. Hepatitis E virus epidemiology in industrialized countries. Emerg Infect Dis. 2003;9:448–54.
Meng XJ, Wiseman B, Elvinger F, et al. Prevalence of antibodies to hepatitis E virus in veterinarians working with swine and in normal blood donors in the United States and other countries. J Clin Microbiol. 2002;40:117–22.
Takahashi M, Okamoto H. Features of hepatitis E virus infection in humans and animals in Japan. Hepatol Res. 2014;44:43–58.
Ticehurst JR, Pisanic N, Forman MS, et al. Probable transmission of hepatitis E virus (HEV) via transfusion in the United States. Transfusion. 2019;59:1024–34.
Satake M, Matsubayashi K, Hoshi Y, et al. Unique clinical courses of transfusion-transmitted hepatitis E in patients with immunosuppression. Transfusion. 2017;57:280–8.
Yamazaki Y, Naganuma A, Arai Y, et al. Clinical and virological features of acute hepatitis E in Gunma prefecture, Japan between 2004 and 2015. Hepatol Res. 2017;47:435–45.
Kamar N, Selves J, Mansuy JM, et al. Hepatitis E virus and chronic hepatitis in organ-transplant recipients. N Engl J Med. 2008;358:811–7.
Koenecke C, Pischke S, Beutel G, et al. Hepatitis E virus infection in a hematopoietic stem cell donor. Bone Marrow Transplant. 2014;49:159–60.
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 Intern Med. 2009;150:430–1.
Bauer H, Luxembourger C, Gottenberg JE, et al. Outcome of hepatitis E virus infection in patients with inflammatory arthritides treated with immunosuppressants: a French retrospective multicenter study. Medicine (Baltimore). 2015;94:e675.
Dalton HR, Bendall RP, Keane FE, et al. Persistent carriage of hepatitis E virus in patients with HIV infection. N Engl J Med. 2009;361:1025–7.
Grewal P, Kamili S, Motamed D. Chronic hepatitis E in an immunocompetent patient: a case report. Hepatology. 2014;59:347–8.
zu Siederdissen CH, Pischke S, Schlue J, et al. Chronic hepatitis E virus infection beyond transplantation or human immunodeficiency virus infection. Hepatology. 2014;60:1112–3.
Wang Y, Liu S, Pan Q, Zhao J. Chronic hepatitis E in an immunocompetent patient. Clin Res Hepatol Gastroenterol. 2020;44:e66–8.
Colson P, Schleinitz N, Vely F, et al. Chronic hepatitis E in absence of severe immune deficiency. Clin Res Hepatol Gastroenterol. 2020;44:e1-4.
Alvarez F, Berg PA, Bianchi FB, et al. International autoimmune hepatitis group report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol. 1999;31:929–38.
Hennes EM, Zeniya M, Czaja AJ, et al. Simplified criteria for the diagnosis of autoimmune hepatitis. Hepatology. 2008;48:169–76.
Takahashi M, Hoshino Y, Tanaka T, et al. Production of monoclonal antibodies against hepatitis E virus capsid protein and evaluation of their neutralizing activity in a cell culture system. Arch Virol. 2008;153:657–66.
Takahashi M, Kusakai S, Mizuo H, et al. Simultaneous detection of immunoglobulin A (IgA) and IgM antibodies against hepatitis E virus (HEV) is highly specific for diagnosis of acute HEV infection. J Clin Microbiol. 2005;43:49–56.
Mizuo H, Suzuki K, Takikawa Y, et al. Polyphyletic strains of hepatitis E virus are responsible for sporadic cases of acute hepatitis in Japan. J Clin Microbiol. 2002;40:3209–18.
Inagaki Y, Oshiro Y, Tanaka T, et al. A nationwide survey of hepatitis E virus infection and chronic hepatitis E in liver transplant recipients in Japan. EBioMedicine. 2015;2:1607–12.
Owada Y, Oshiro Y, Inagaki Y, et al. A nationwide survey of hepatitis E virus infection and chronic hepatitis in heart and kidney transplant recipients in Japan. Transplantation. 2020;104:437–44.
Kurihara T, Yoshizumi T, Itoh S, et al. Chronic hepatitis E virus infection after living donor liver transplantation via blood transfusion: a case report. Surg Case Rep. 2016;2:32.
Miyoshi M, Kakinuma S, Tanabe Y, et al. Chronic hepatitis E infection in a persistently immunosuppressed patient unable to be eliminated after ribavirin therapy. Intern Med. 2016;55:2811–7.
Mitsui T, Tsukamoto Y, Suzuki S, et al. Serological and molecular studies on subclinical hepatitis E virus infection using periodic serum samples obtained from healthy individuals. J Med Virol. 2005;76:526–33.
Hasegawa I, Nakano T, Koguchi H, et al. Subclinical hepatitis E virus (HEV) infection detected by nucleic acid amplification test on blood donation: short-term positivity for immunoglobulin G class of antibody against HEV. Clin J Gastroenterol. 2022;15:750–4.
Liu G, Rusling JF. COVID-19 antibody tests and their limitations. ACS Sens. 2021;6:593–612.
Le Cann P, Tong MJ, Werneke J, et al. Detection of antibodies to hepatitis E virus in patients with autoimmune chronic active hepatitis and primary biliary cirrhosis. Scand J Gastroenterol. 1997;32:387–9.
Nagasaki F, Ueno Y, Mano Y, et al. A patient with clinical features of acute hepatitis E viral infection and autoimmune hepatitis. Tohoku J Exp Med. 2005;206:173–9.
Kanda T, Yasui S, Nakamura M, et al. Recent trend of hepatitis E virus infection in Chiba area, Japan: 3 of 5 cases with rheumatoid arthritis. Case Rep Gastroenterol. 2015;9:317–26.
Gui H, Wang W, Li Q, Li Z, Lu J, Xie Q. Autoimmune liver disease-associated serologic profiling in Chinese patients with acute hepatitis E virus infection. Immunol Res. 2021;69:81–9.
Elfert KA, Qasim HM, Faisal MM, et al. Hepatitis E viral association with autoimmune hepatitis: a viral trigger or cross-reactivity. Case Rep Gastroenterol. 2021;15:115–22.
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;45:3671–9.
Matsubayashi K, Kang JH, Sakata H, et al. A case of transfusion-transmitted hepatitis E caused by blood from a donor infected with hepatitis E virus via zoonotic food-borne route. Transfusion. 2008;48:1368–75.
Matsui T, Kang JH, Matsubayashi K, et al. Rare case of transfusion-transmitted hepatitis E from the blood of a donor infected with the hepatitis E virus genotype 3 indigenous to Japan: viral dynamics from onset to recovery. Hepatol Res. 2015;45:698–704.
Okano H, Nakano T, Ito R, et al. The spontaneous clearance of hepatitis E virus (HEV) and emergence of HEV antibodies in a transfusion-transmitted chronic hepatitis E case after completion of chemotherapy for acute myeloid leukemia. Clin J Gastroenterol. 2020;13:252–9.
Tanaka T, Akamatsu N, Sakamoto Y, et al. Treatment with ribavirin for chronic hepatitis E following living donor liver transplantation: a case report. Hepatol Res. 2016;46:1058–9.
Cederholm T, Jensen GL, Correia MITD, et al. GLIM criteria for the diagnosis of undernourished—a consensus report from the global clinical nutrition community. J Cachexia Sarcopenia Muscle. 2019;10:207–17.
Lesourd BM. Nutrition and immunity in the elderly: modification of immune responses with nutritional treatments. Am J Clin Nutr. 1997;66:478S-S484.
Peron JM, Danjoux M, Kamar N, et al. Liver histology in patients with sporadic acute hepatitis E: a study of 11 patients from South-West France. Virchows Arch. 2007;450:405–10.
Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. Hepatology. 1996;24:289–93.
Beer A, Holzmann H, Pischke S, et al. Chronic hepatitis E is associated with cholangitis. Liver Int. 2019;39:1876–83.
Lenggenhager D, Pawel S, Honcharova-Biletska H, et al. The histologic presentation of hepatitis E reflects patients’ immune status and pre-existing liver condition. Mod Pathol. 2021;34:233–48.
Kamar N, Lhomme S, Abravanel F, et al. Treatment of HEV infection in patients with a solid-organ transplant and chronic hepatitis. Viruses. 2016;8:222.
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;140:1481–9.
Kamar N, Izopet J, Tripon S, et al. Ribavirin for chronic hepatitis E virus infection in transplant recipients. N Engl J Med. 2014;370:1111–20.
Debing Y, Emerson SU, Wang Y, et al. Ribavirin inhibits in vitro hepatitis E virus replication through depletion of cellular GTP pools and is moderately synergistic with alpha interferon. Antimicrob Agents Chemother. 2014;58:267–73.
Todt D, Gisa A, Radonic A, et al. In vivo evidence for ribavirin-induced mutagenesis of the hepatitis E virus genome. Gut. 2016;65:1733–43.
Yamazaki Y, Uehara D, Kanayama Y, et al. Characteristics of cases of hepatitis E in 2019 in Gunma prefecture: a small epidemic caused by the same subgenotype 3a strain. Kanzo. 2020;61:478–81 ((in Japanese)).
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This study was supported in part by the Research Program on Hepatitis from Japan Agency for Medical Research and Development, AMED (to H.O., JP22fk0210075).
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Takakusagi, S., Takagi, H., Yamazaki, Y. et al. Chronic hepatitis E in an elderly immunocompetent patient who achieved a sustained virologic response with ribavirin treatment. Clin J Gastroenterol 16, 206–215 (2023). https://doi.org/10.1007/s12328-022-01733-2
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DOI: https://doi.org/10.1007/s12328-022-01733-2