Fatal Fulminant Hepatitis E in a Diabetic Patient on Metformin

Abstract

Hepatitis E is mostly autochthonous in Western developed countries, eating pig-derived products being the most frequently documented source. Hepatitis E virus (HEV) infection is usually asymptomatic or self-limiting, but it can cause acute liver failure. HEV serological testing was performed using EUROIMMUN immunoenzymatic assays. HEV RNA in the serum was determined using an in-house real-time reverse transcriptase PCR procedure. The HEV genotype was determined through phylogenetic analysis after Sanger sequencing was performed using an in-house procedure. The case patient, an immunocompetent patient in his 60s with type 2 diabetes and no documented chronic liver disease, was hospitalized in February 2021 in an intensive care unit due to an initially unexplained coma. He presented metformin overdose and fulminant hepatitis E (HEV RNA in the serum was 4,140,000 copies/mL) that evolved toward death. The HEV genotype was 3f. We identified eight previous hepatitis E in diabetic patients, but with no metformin excessive plasma concentration, in the literature. Three patients were liver transplant recipients and three died. HEV infection can be severe and life-threatening in diabetic patients, which warrants HEV testing in this special population in the case of an altered general condition and/or liver cytolysis.

Keywords: death; diabetes; fulminant hepatitis; hepatitis E; metformin.

Figure 1

The fragment of the ORF2 gene encoding for the capsid protein was 315-nucleotide long and corresponded to nucleotides 6016–6330 of the HEV genome GenBank accession no. JQ953664. The HEV sequence obtained by Sanger sequencing from the present case is indicated by a white bold font and a black background. The 10 sequences with the highest BLAST scores recovered from the NBCI GenBank nucleotide sequence databases (http://www.ncbi.nlm.nih.gov/nucleotide/, accessed on 17 September 2022), indicated by bold font, were incorporated in the phylogeny reconstruction, in addition to reference sequences for the HEV genotypes [2]. Nucleotide alignments were performed using the MUSCLE software (http://www.ebi.ac.uk/Tools/msa/muscle/, accessed on 17 September 2022). The evolutionary history was inferred in the MEGA6 software (http://www.megasoftware.net/, accessed on 17 September 2022) using the Neighbor-Joining method and the Kimura 2-parameter method. The percentage of replicate trees in which the associated taxa clustered together in the bootstrap test (1000 replicates) is shown next to the branches. The tree is drawn to scale, with branch lengths in the same units as those of the evolutionary distances used to infer the phylogenetic tree; the scale bars indicate the number of nucleotide substitutions per site. Bootstrap values > 50% are labeled on the tree.