PMC5088542_01
The clinical course of this patient. (A) The clinical course during chemotherapy after the diagnosis of lymphoma. The x axis represents time from the diagnosis of lymphoma. The normal line and dotted line show ALT and AST, respectively. The arrows, white arrow, and closed square represent transfusion, hepatitis E virus (HEV)-contaminated transfusion, and chemotherapy, respectively. (B) The clinical course after the end of chemotherapy. Black and white arrowheads represent the liver biopsy and supplementation of gamma globulin, respectively. "Consultation" represents the time point when the patient visited the Department of Gastroenterology and Hepatology.
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A peak elevation of aminotransferases (AST 98 U/L, ALT 347 U/L) was observed 20 days after the initiation of her 5th chemotherapy course (Fig. 1A). Similarly, transient liver dysfunction was observed during the 6th and 7th chemotherapy courses (Fig. 1A). Moreover, continuous elevation of aminotransferase was observed (Fig. 1B). Improvement in the patient's liver dysfunction was achieved after the administration of ribavirin for 5 weeks (Fig. 1B).
Histological findings of a liver biopsy. (A) Hematoxylin and Eosin staining shows mild piecemeal necrosis and moderate inflammation around the portal vein, demonstrating chronic hepatitis. Scale bar: 50 mum. (B) Masson's trichrome staining shows the progression of periportal fibrosis. Scale bar: 200 mum.
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A liver biopsy demonstrated that her histologic findings were consistent with chronic active hepatitis, hepatic activity index (HAI) score 7, and fibrosis stage 2 (Fig. 2).
Phylogenetic analyses. A phylogenetic tree of HEV nucleotide sequences was constructed using the CLUSTAL W version 1.4 and MEGA version 4.0 software programs. For the phylogenetic analysis of HEV nucleotide sequences, we included sequences of several common and/or widespread strains. Each sequence name includes the genotype (Gt) and accession number. The dark box represents the sequence of the present case.
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The amount of viral RNA was 6.7 log copies/mL, and a phylogenetic tree analysis revealed that HEV in her serum was genotype 3 (Fig. 3).
Changes in the serum HEV RNA levels after the diagnosis of HEV viremia. Serum HEV RNA decreased after ribavirin therapy, however, it was not eliminated after 6 months of ribavirin administration. The x axis represents time from the diagnosis of lymphoma. The amounts of serum HEV RNA were quantified by quantitative RT-PCR.
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Her serum HEV RNA levels were markedly decreased by -3 log copies/mL (Fig. 4).