Secondary hemophagocytic lymphohistiocytosis mimicking sepsis in hepatitis A–E coinfection: spontaneous recovery with supportive care
https://orcid.org/0000-0002-2693-1298
Bijan Basak
https://orcid.org/0009-0003-3562-6652
Ashif Ali Ahmed
https://orcid.org/0009-0004-9767-2133
Abstract
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome caused by dysregulated immune activation. Viral infections, particularly Epstein–Barr virus, are well-known triggers; however, HLH associated with acute viral hepatitis is rare, especially in the setting of hepatitis A (HAV) and hepatitis E (HEV) coinfection. A 30-year-old male presented with fever following the onset of jaundice, along with fatigue and dyspnea. Laboratory evaluation revealed severe hyperbilirubinemia, markedly elevated transaminases, anemia, hyperferritinemia, and hypertriglyceridemia. He also had hemolysis due to glucose 6 phosphate dehydrogenase (G6PD) deficiency. Bone marrow examination demonstrated hemophagocytosis. Viral markers confirmed HAV and HEV coinfection. Although he fulfilled five out of eight HLH-2004 criteria, sepsis markers like raised procalcitonin and leukocytosis posed diagnostic challenge. He was managed with supportive care alone, and showed spontaneous clinical and biochemical improvement without immunosuppressive therapy. This case highlights a probable HLH spectrum disorder triggered by HAV–HEV coinfection. It underscores the importance of considering HLH in patients with acute viral hepatitis who develop persistent fever and cytopenia, while also recognizing that selected patients may improve with supportive care alone.
##plugins.themes.bootstrap3.article.details##
Hemophagocytic Lymphohistiocytosis, Hepatitis A, Hepatitis E, Secondary HLH, Hyperferritinemia, Acute viral hepatitis
2. Gupta S, Weitzman S. Primary and secondary hemophagocytic lymphohistiocytosis: clinical features, pathogenesis and therapy. Expert Rev Clin Immunol. 2010 Jan;6(1):137-54. doi: 10.1586/eci.09.58. PMID: 20383897.
3. Jordan MB, Allen CE, Weitzman S, et al. How I treat hemophagocytic lymphohistiocytosis. Blood. 2011 Oct 13;118(15):4041-52. doi: 10.1182/blood-2011-03-278127. Epub 2011 Aug 9. PMID: 21828139; PMCID: PMC3204727.
4. Patel NH, Chen AY, Osiowy C, et al. Hepatitis B Virus Variants and Cytokine Patterns in Acute Liver Failure and Transplant-Free Survival. Liver Int. 2025 Jul;45(7):e70175. doi: 10.1111/liv.70175. PMID: 40540404; PMCID: PMC12180610.
5. Konkol S, Killeen RB, Rai M. Hemophagocytic Lymphohistiocytosis. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025. Available from: http://www.ncbi.nlm.nih.gov/books/NBK557776/ PubMed PMID: 32491708.
6. Giri S, Mishra C, Gore P, et al. Secondary hemophagocytic lymphohistiocytosis associated with acute viral hepatitis A - A case series. Trop Doct. 2025 Jul;55(3):251–4. doi:10.1177/00494755251343390 PubMed PMID: 40462675.
7. Mallick B, Daniel P, Dutta U. Hepatitis A infection related haemophagocytic syndrome: a case report and systematic review. Trop Doct. 2019 Jul;49(3):234-238. doi: 10.1177/0049475519834804. PMID: 30871416.
8. Desai N, Vetal D, Kulkarni A, Karnik N, Trivedi T. Hemophagocytic Lymphohistiocytosis: A Rare Complication of Acute Hepatitis E Infection. J Assoc Physicians India. 2024 Apr;72(4):91-93. doi: 10.59556/japi.72.0499. PMID: 38881088.
9. Henter JI, Horne A, Aricó M, et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007 Feb;48(2):124-31. doi: 10.1002/pbc.21039. PMID: 16937360.
10. La Rosée P, Horne A, Hines M, et al. Recommendations for the management of hemophagocytic lymphohistiocytosis in adults. Blood. 2019 Jun 6;133(23):2465–77. doi:10.1182/blood.2018894618 PubMed PMID: 30992265.
11. Tuon FF, Gomes VS, Amato VS, et al. Hemophagocytic syndrome associated with hepatitis A: case report and literature review. Rev Inst Med Trop Sao Paulo. 2008;50(2):123–7. doi:10.1590/s0036-46652008000200012 PubMed PMID: 18488094.
12. Watanabe M, Shibuya A, Okuno J, et al. Hepatitis A virus infection associated with hemophagocytic syndrome: report of two cases. Intern Med. 2002;41(12):1188–92. doi:10.2169/internalmedicine.41.1188 PubMed PMID: 12521213.
13. Desai N, Vetal D, Kulkarni A, et al. Hemophagocytic lymphohistiocytosis: a rare complication of acute hepatitis E infection. J Assoc Physicians India. 2024;72(4):91-3. doi: 10.59556/japi.72.0499. PMID: 38881088.
14. Uemura M, Huynh R, Kuo A, et al. Hemophagocytic Lymphohistiocytosis Complicating T-Cell Lymphoma in a Patient with HIV Infection. Case Rep Hematol. 2013;2013:687260. doi: 10.1155/2013/687260. PMID: 24073345; PMCID: PMC3773377.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Archive of Clinical Cases is protected by copyright and may be used in accordance with copyright and other applicable laws. Content available at www.clinicalcases.eu and our digital applications is intended for personal noncommercial use.
Authors who submit a manuscript for publication in Archive of Clinical Cases agree to the following terms: a. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal. b. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal. c. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) only after the final version of the manuscript was accepted and published, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access). d. It is compulsory that before submission authors ensure that their work was not published in any other medical journals or pending acceptance for publication and that "Archives of Clinical Cases" is the only beneficiary at that moment if their work/case will be accepted by us.
Guidelines for linking to www.clinicalcases.eu a. The main purpose of the site linking to the Archive of Clinical Casess site should be educational. b. Links should be made to the Archive of Clinical Casess home page (www.clinicalcases.eu) or to the articles abstract. c. It is forbidden to use the Archive of Clinical Casess cover by outside organizations unless permission has been granted in advance, notifying our Secretary. d. Material owned by the Archive of Clinical Cases (including the name, logo, cover, and text) may not be used in any manner that may induce the idea or suggest that the Archive of Clinical Cases is in some way recommending a specific company, product or service. e. You must not use or allow others to access or use, all or any part of our Site or the contents and/or applications on it for commercial purposes without our permission. To seek permission to do anything prohibited by or not contained in these TERMS, or which requires our prior consent or agreement, you can contact us.