阿地耐药后会导致大量病毒突变和严重肝衰竭(2005.5 DDW)

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Resistance to Adefovir Dipivoxil (Hepsera) Can Be Associated with Significant Virologic Breakthough and Fatal Hepatic Decompensation

Adefovir dipivoxil/ ADV (Hepsera) resistance occurs less frequently and later in the course of treatment compared to lamivudine/LAM (Epivir-HBV). Susceptibility of ADV-resistant hepatitis B virus (HBV) mutants is only reduced by 3-10 fold, suggesting that virologic breakthrough (BT) and clinical deterioration are unlikely.

However, there are very little data regarding the clinical course and response to salvage therapy in ADV-resistant patients. The aim of this study was to describe the clinical course of hepatitis B patients found to have ADV-resistant mutations.

Surveillance for ADV-resistant mutation was performed on patients receiving ADV, who had a suboptimal response (<2 log decrease in HBV DNA or HBV DNA >4 log after 1 year of treatment), and in those with virologic BT (>1 log increase in HBV DNA after initial suppression).

HBV DNA was quantified using a PCR assay.

ADV-resistant mutation was detected using a line probe assay and confirmed by direct sequencing of the HBV polymerase gene.

Results

?span style='font:7.0pt "Times New Roman"'> Seven male patients, mean age 49?/span>13 years, were found to have ADV resistance between 9/03 and 9/04.

?span style='font:7.0pt "Times New Roman"'> All patients had prior treatment with LAM for 27?/span>14 months and BT infection or genotypic resistance to LAM was confirmed in 6 patients.

?span style='font:7.0pt "Times New Roman"'> At the start of ADV, median ALT was 75 IU/L (range, 27-1161); mean HBV DNA was 7?/span>1 log copies/ml;

?span style='font:7.0pt "Times New Roman"'> 4 patients were HBeAg+ve; and 2 had liver transplants.

?span style='font:7.0pt "Times New Roman"'> Six patients were switched to ADV with <1 month overlap with LAM; 1 patient continued to receive LAM.

?span style='font:7.0pt "Times New Roman"'> During treatment, 6 patients had a suboptimal virologic response.

?span style='font:7.0pt "Times New Roman"'> At the time of ADV resistance, which occurred at a mean of 19 ?/span> 8 months after treatment initiation, median ALT was 51 IU/L (range, 6-906) and HBV DNA increased to over 6 log copies/ml in 6 patients.

?span style='font:7.0pt "Times New Roman"'> After detection of ADV resistance, hepatic decompensation occurred in 2 patients, 1 of whom died.

?span style='font:7.0pt "Times New Roman"'> Salvage therapy with LAM, entecavir or tenofovir was given to 6 patients; 3 of 5 patients with > 6 months of follow-up had > 3 log reduction in HBV DNA.

Conclusions

The authors conclude, 揜esistance to ADV is not rare and may be associated with substantial increases in HBV DNA level and fatal hepatic decompensation.?/span>

揝urveillance for ADV resistance and institution of salvage therapy should be considered in immunosuppressed or cirrhotic patients.?/span>

Lab Values at the Time of ADV Resistance

Patient

Time to Res. (mos)

Mutation

HBV DNA

(log copies/ml)

ALT?(IU/L)

1

18

rtA181T

4.4

45

?2*

17

rtA181V

9.8

161

3

19

rtA181V

8.1

51

4

13

rtA181V

5.6

6

5

14

rtA181V

8.4

906

6

19

rtN236T

6.8

97

7

36

rtN236T

5.2

32

* Patient died

S Fung and others. Resistance To Adefovir (ADV) Can Be Associated With Significant Virologic Breakthough (BT) and Fatal Hepatic Decompensation. Abstract M921. Digestive Disease Week 2005. May 14-19, 2005. Chicago, IL.

青竹

更加可怕，看起来靠这类药抑制病毒也不是长久之计

frostriver

我现在就是忽然黄疸和alt升高

frostriver

6号全面复查 忽然又没事儿了 奇怪

kevie

唉 看的打击人啊

用拉米一年多了， 已经产生变异了 医生说变异的情况还好，不严重，准备给偶用阿地的。。。你说这咋办呢？