Fatal hepatitis B reactivation following discontinuation of nucleoside analogues for chronic hepatitis B.
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PMID: 12235087 Owner: NLM Status: MEDLINE
BACKGROUND: Nucleoside analogues such as lamivudine for chronic hepatitis B have an excellent safety profile while patients are on therapy but reactivation flares occur in 19-50% of patients after stopping therapy, some of whom develop liver decompensation. AIMS: To describe and report three cases who developed fatal hepatitis B reactivation after stopping nucleoside analogue therapy. SUBJECTS AND RESULTS: Three patients are described who developed hepatitis B reactivation and liver decompensation after stopping therapy. One of the three patients was participating in a famciclovir trial and the other two were receiving lamivudine therapy for active hepatitis B infection. All three patients had documented hepatitis B flares, and all had hepatitis B virus DNA detected at that time. All patients developed decompensated liver disease despite one patient having had a prior liver biopsy showing absence of cirrhosis. Reintroduction of lamivudine therapy failed to halt progression of liver decompensation even after hepatitis B virus DNA had been demonstrated to be absent. Sequencing for lamivudine resistant mutants in two cases where serum was available failed to show evidence of mutations associated with lamivudine resistance. CONCLUSION: Hepatitis B virus reactivation, leading to decompensation and death, are possible complications of treatment withdrawal and patients should be monitored closely if therapy is ceased.
Thanks, I did not see the word "fatal". It is scary, especially in the case of the patient without cirrhosis. I noticed the ALTs were normal when therapy was stopped, then rose after stopping. Even when lamivudine was resumed, it did not stop the rise in ALT, which then down eventually, but the bilirubins did not. May be compensated cirrhosis patients should never stop therapy, and those on lamivudine should switch to a drug with a higher barrier to mutation?
i think studies like that in rome could be very useful.......
i actually called for an hbvdna with imprved sensibility at 6 iu/ml but the biologist said it is no use to go lower than that because we have full genome check so we can say how the drug is doing despite the hbvdna levels and predict resistance or how the drug performs
if the quasispieces changes stop etv showed hbsag clearance and this is a very interesting finding
Yes, it was a 2002 paper, hopefully treatments have advanced since. Just read this in the HBV Journal Review, Oct 1, 2011:
The antiviral lamivudine (Epivir-HBV) has fallen out of favor as an antiviral treatment for hepatitis B because it causes drug resistance.
However, a study reported in the Digestive Diseases and Sciences found the antiviral was effective when administered in high doses in patients with cirrhosis.
Researchers treated six people with HBV-related cirrhosis with lamivudine doses raised from the normal dose of 100 mg daily to 200 or 300 mg daily, based on their viral load. Previously, nearly all of these patients had developed lamivudine resistance at the lower, 100 mg-dose, and had failed to improve even after the antiviral adefovir (Hepsera) (10 mg daily) was added to their ongoing lamivudine treatment.
The HBeAg-negative patients continued to receive adefovir, but the lamivudine dose was hiked for 12 months. All achieved a “significant” decrease in HBV DNA, three of the patients achieved undetectable viral load within six months. All achieved normal ALT levels, indicating no liver damage. The higher dose did not adversely impact their kidney function, nor were any other side effects noted.
The researchers suggested that increased doses of any antiviral—not just lamivudine—may be effective in hard-to-treat patients with life-threatening cirrhosis or liver damage.
So increased doses of antiviral may help. Frequent monitoring after stopping antivirals is essential, I think.
we should have biopsy to check cccdna so that we know if we can stop safely but biopsy is so bad....they wanted to make it to me to see all virus parameters correctly but i really dont like it, i felt so bad after biopsies in the past, the first time almost lost all my hair and i was only 19yo....
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