Case report: chronic hepatitis B infection susceptible to adefovir despite the rtI233V mutation
Abstract number: R2485
Capobianchi M.R., Vairo F., Solmone M., Vincenti D., Iacomi F., Mariano A., Zoulim F., Antonucci G.
The mutation I233V in HBV polimerase has been associated with primary resistance to adefovir dipivoxil treatment (ADV). We report a chronic hepatitis B which responded to ADV although bearing I233V.
Italian man born in 1930, affected by HBeAg-negative chronic hepatitis B; HDV-HCV-HIV negative. He had a bronchial adenocarcinoma resection in 2001 and is on chronic treatment with interleukin-2 for the first week of each odd month since then. Hepatitis B was unsuccessfully treated with interferon in 1998. Treatment with lamivudine 100 mg qd, started in November 1999, initially suppressed viraemia but a viral breakthrough occurred at 3 years of therapy and lamivudine was stopped.
In May 2003: HBVDNA was 20,680,000 IU/ml (TaqMan Roche); ALT 122 IU/L; the pol gene sequencing and clonal analysis showed that all clones analysed had both I233V and S159T mutations, Y141H and V142G were present in 6/11 clones, M204V in 6/11 clones (3 in association with L180M). ADV 10 mg qd was started in June 2003. At one year of treatment: HBVDNA was 971,000 IU/ml; ALT 50 IU/L; sequencing and clonal analysis were unchanged compared to baseline, except that M204V was detected only in 1/11 clones. ADV was stopped in September 2004 (15 months of therapy). In November 2004: ALT increased to 111 IU/L; HBV DNA decreased to 127,000 IU/ml; genotypic analysis showed that I233V, S159T, Y141H, V142G and M204V were present in almost all clones. ADV was restarted in February 2005 and it is ongoing. At the time of ADV restart ALT had spontaneously declined to 40 UI/L, and HBV DNA to 700 IU/ml; I233V, S159T, Y141H and V142G were present in almost all clones, M204V was not detected. During this second course of ADV ALT are always normal; HBVDNA is always <12 IU/ml; HBsAg is still positive.
HBVDNA had a 1.3 Log decline of at one year of ADV despite I233V mutation. HBVDNA further decreased when ADV was stopped and it is persistently undetectable during the 2nd course of ADV. It seems that the patient shifted from a highly replicative to an inactive carrier status. Other mutations detected (S159T, Y141H, V142G) might play a role in reducing viral fitness and possibly restore ADV antiviral activity. Complementarily, interleukin-2 regularly taken by the patient might have enhanced ADV activity and played a role in this unexpected "change of status".
The real impact of I233V mutation on ADV anti-HBV activity needs to be better defined, especially when in combination with other mutations.
|Session name:||18th European Congress of Clinical Microbiology and Infectious Diseases|
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