Locally Acquired Chronic Hepatitis E Followed by Epstein-Barr Virus Reactivation and Burkitt Lymphoma as a Suspected Extrahepatic Manifestation in a Liver Transplant Recipient

Abstract

BACKGROUND Hepatitis E virus (HEV) is a common cause of acute hepatitis in developing regions. In high-income countries, hepatitis E is an emergent zoonotic disease of increasing concern. Clinically, the infection is usually acute and self-limited in immunocompetent individuals, although rare chronic cases in immunocompromised patients have been reported. Both acute and chronic infections have been recently associated with several extrahepatic manifestations, including neurological and hematological disorders. CASE REPORT A case of autochthonous chronic HEV infection in a liver-transplanted man from a non-endemic country is presented. Phylogenetic analysis revealed a swine origin of the HEV human infection. Chronic hepatitis E was treated with a 9-week course of ribavirin, after which viral clearance was achieved. Subsequently, the patient developed a post-transplant lymphoproliferative disorder (PTLD) in the form of Burkitt lymphoma. At the time of lymphoma diagnosis, the patient had shown a strong reactivation of Epstein-Barr virus (EBV) infection. After additional antiviral ganciclovir therapy and chemotherapy, the patient had a complete recovery with no sequelae. CONCLUSIONS The differential diagnosis of persistently elevated transaminases in transplanted and/or immunocompromised patients should include testing for HEV by appropriate nucleic acid techniques (NATs). Cases of HEV infection with an atypical clinical outcome, such as the one presented herein, highlights the need for increased awareness of chronic hepatitis E and its association with a wide range of extrahepatic manifestations.

Figure 1.

Paraclinical data and therapeutic interventions in the 21-month follow-up of the 62-year-old LT patient. Oscillation of liver enzymes levels are graphed. Hepatitis E Virus (HEV) and Epstein-Barr (EBV) PCR results are shown. Periods of increasing and decreasing immunosuppression (IS) are indicated. RBV – ribavirin therapy; ChT – chemotherapy; AST – aspartate aminotransferase; ALT – alanine aminotransferase; RNA – ribonucleic acid; ^* u/d – undetectable (DNA copies/mL slightly higher than the cut-off value). See text for detailed information.

Figure 2.

Histologic changes in the liver biopsies from the 62-year-old LT patient. Main histological findings observed throughout the study are shown. Hematoxylin-eosin stain. (A) Lobular inflammatory infiltrate composed mainly of neutrophils, compatible with acute hepatitis, observed at 1 year and 6 months after LT (original magnification 40×). (B) Dense portal inflammatory infiltrate composed mainly of lymphocytes with piecemeal necrosis, compatible with chronic hepatitis observed concomitantly with the detection of HEV RNA (10×). (C) Sinusoidal dilatation with megakaryocytes compatible with extramedullary hematopoiesis (20×).

Figure 3.

Phylogenetic tree based on the partial 287-nt region within the ORF1. The tree was generated using the neighbor-joining algorithm, using Tamura-Nei as the best substitution model as tested by ModelTest v3.7 tool. The robustness of the trees was determined by bootstrap for 1000 replicates. Only values ≥60% are shown. HEV-3 strain isolated form the patient, named HEV-BL (GenBank accession number MG182431) is shown in bold.