Abstract
IntroductionThere seem to be no published data concerning the clinical impact of populations of hepatitis B virus (HBV) in the hepatic and extrahepatic compartments of HIV-infected people with severe acute hepatitis.Case presentationA 26-year-old Caucasian man presenting to our hospital with clinical symptoms suggesting acute hepatitis was found to have an acute hepatitis B profile upon admission. He developed fatal fulminant hepatitis and was found to be heavily immunocompromised due to HIV-1 infection. He had a high plasma HBV and HIV load, and analysis of the partial pre-S1/pre-S2 domain showed the presence of mixed infection with D and F genotypes. Analysis of the point mutations within this region revealed the presence of HBV strains with amino acid substitutions at the immunodominant epitopes involved in B or T cell recognition. A homogeneous population of a pre-core mutant strain harbouring the A1896G and A1899G affecting HBeAg expression was invariably found in the liver tissue, plasma and peripheral blood mononuclear cells despite active HBeAg secretion; it was the dominant strain in the liver only, and was characterised by the presence of two point mutations in the direct repeat 1 domain involved in HBV replication activity. Taken together, these mutations are indicative of a highly replicative virus capable of evading immune responses.ConclusionThis case report provides clinical evidence of a possible association between the rapid spread of highly replicative escape mutants and the development of fulminant hepatitis in a heavily immunocompromised patient. Virological surveillance of severe acute hepatitis B may be important in establishing an early treatment strategy involving antiviral drugs capable of preventing liver failure, especially in individuals for whom liver transplantation is not accepted as a standard indication.
Highlights
There seem to be no published data concerning the clinical impact of populations of hepatitis B virus (HBV) in the hepatic and extrahepatic compartments of HIV-infected people with severe acute hepatitis.Case presentation: A 26-year-old Caucasian man presenting to our hospital with clinical symptoms suggesting acute hepatitis was found to have an acute hepatitis B profile upon admission
We investigated the hepatic and extrahepatic patterns of HBV infection in a patient who was infected with HIV and who was participating in a prospective study of acute hepatitis B, which fatally evolved into fulminant hepatitis B (FHB)
A sequence analysis of 20 independent clones propagated from liver revealed the presence of a homogeneous preC mutated population showing the A1896G stop codon and the A1899G substitution, which stabilised the epsilon structure better, avoiding a possible decrease in viral replication; only three clones had a divergent sequence with additional nucleotide point mutations
Summary
This is the first report describing a case of acute hepatitis B with a fulminant course in a heavily compromised HIVpositive patient showing the dominance of HBV genotype D over genotype F in plasma, and the selection of preC mutant strains with different genetic characteristics in hepatic and extrahepatic sites. It would be interesting to determine whether this virological pattern may be related to severe FH by extending this analysis to a larger number of patients with acute severe hepatitis B as this could add important information for its management. Early treatment with antiviral drugs could prevent the need for liver transplantation or prevent a fatal outcome
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