Novel mutation in YMDD motif and direct neighbourhood in a child with chronic HBV-infection and clinical lamivudine and adefovir resistance - a scholarly case.
BACKGROUND
Chronic HBV infection is a major cause of hepatocellular carcinoma (HCC) which meanwhile has become the 5th most reason for a fatal outcome of cancer. Worldwide, approximately 350 million people are chronically HBV infected and as such of risk to develop HCC, of those an estimated high rate of children. Treatment of chronic infection is sufficient to reduce the rate of HCC but the rate of sustained virological response remains to low, not at least due to emergence of resistant virus strains. Less is known on HBV infection in children despite the extremely high rate of chronicity.
The case of a nine years old male with a 6 year history of chronic HBV infection, of those 5 years with antiviral treatment is described.
Before our lab was consulted, the patient was unsuccessfully treated with interferon, an obscure drug named Hepon, which should activate antiviral immune response, and Lamivudine, the latter most likely becoming ineffective due to the mergence of resistant subpopulations (rtL180 M, rtV207 M, two strains with stop codons at position rt188 and rt198, rtM204V (YVDD), rtM204K (YKDD)). Replacement of Lamivudine by adefovir displayed no advantage despite the lack of resistance mutations, thus no decrease in viremia was observed under adefovir treatment.


CONCLUSIONS
Novel mutations in the YMDD motif and its direct neighbourhood were observed, both being compatible with Lamivudine resistance. No mutations were found that are associated with ADF resistance. Both, the clinical course of treatment and the genotypic resistance profile emphasize the need for systematic analyses of the HBV resistance mechanisms and structured therapy concept also for children chronically infected with HBV.
Schildgen
Verena
V
Institute for Virology, University Hospital Essen, Essen, Germany. schildgeno@kliniken-koeln.de
Ziegler
Susanne
S
Tillmann
Ramona L
RL
Schildgen
Oliver
O
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000627:therapeutic use*; D002648:Child; D024882:Drug Resistance, Viral; D006515:Hepatitis B virus / Q000737:chemistry / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D063065:Organophosphonates / Q000627:therapeutic use*; D016415:Sequence Alignment
D000998:Antiviral Agents; D063065:Organophosphonates; D019259:Lamivudine; C053001:adefovir; D000225:Adenine