Aa
etv resistance, not sure we can rescue by tdf
i got this from s stephen post in chinese forum
Virologic breakthrough in a patient with chronic hepatitis B by combination treatment with tenofovir disoproxil fumarate and entecavir.
Suzuki F1, Sezaki H2, Akuta N2, Suzuki Y2, Kawamura Y2, Hosaka T2, Kobayashi M2, Saitoh S2, Arase Y2, Ikeda K2, Kobayashi M3, Watahiki S3, Mineta R3, Suzuki Y3, Kumada H2.
Author information
Abstract
Tenofovir disoproxil fumarate (TDF) is widely used to treat hepatitis B virus (HBV) patients in the USA and Europe. No confirmed report of resistance selection during treatment with TDF in treatment-naïve and nucleoside / nucleotide analog-treated chronic hepatitis B patients has yet been reported. Here, we report for the first time a patient with chronic hepatitis B and cirrhosis who emerged with virologic breakthrough during combination therapy with TDF and entecavir (ETV), against ETV-resistant virus. A 51-year-old Japanese woman with hepatitis B e-antigen (HBeAg), whose genotype was C, received ETV monotherapy continuously followed by TDF and ETV combination therapy, because her HBV DNA levels had been> 3.5 log copies / mL. At the start of combination therapy, amino acid substitutions of the reverse transcriptase (rt) gene, rtL180M, rtT184I / M, and rtM204V, were detected. After this, serum HBV DNA decreased to less than 2.1 log copies / mL and remained at this level until 31 months of combination therapy, when it again began to increase. Amino acid substitutions of rtL180M, rtS202G, and rtM204V emerged and were associated with an increase in serum HBV DNA at virologic breakthrough. Long-term therapy with TDF against the ETV-resistant virus has the potential to induce virologic breakthrough and resistance, and careful follow-up should be carried out.
Virologic breakthrough in a patient with chronic hepatitis B by combination treatment with tenofovir disoproxil fumarate and entecavir.
Suzuki F1, Sezaki H2, Akuta N2, Suzuki Y2, Kawamura Y2, Hosaka T2, Kobayashi M2, Saitoh S2, Arase Y2, Ikeda K2, Kobayashi M3, Watahiki S3, Mineta R3, Suzuki Y3, Kumada H2.
Author information
Abstract
Tenofovir disoproxil fumarate (TDF) is widely used to treat hepatitis B virus (HBV) patients in the USA and Europe. No confirmed report of resistance selection during treatment with TDF in treatment-naïve and nucleoside / nucleotide analog-treated chronic hepatitis B patients has yet been reported. Here, we report for the first time a patient with chronic hepatitis B and cirrhosis who emerged with virologic breakthrough during combination therapy with TDF and entecavir (ETV), against ETV-resistant virus. A 51-year-old Japanese woman with hepatitis B e-antigen (HBeAg), whose genotype was C, received ETV monotherapy continuously followed by TDF and ETV combination therapy, because her HBV DNA levels had been> 3.5 log copies / mL. At the start of combination therapy, amino acid substitutions of the reverse transcriptase (rt) gene, rtL180M, rtT184I / M, and rtM204V, were detected. After this, serum HBV DNA decreased to less than 2.1 log copies / mL and remained at this level until 31 months of combination therapy, when it again began to increase. Amino acid substitutions of rtL180M, rtS202G, and rtM204V emerged and were associated with an increase in serum HBV DNA at virologic breakthrough. Long-term therapy with TDF against the ETV-resistant virus has the potential to induce virologic breakthrough and resistance, and careful follow-up should be carried out.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4085295/ (read the case report part).....this woman discontinued therapy on her own for 1 year after getting etv resistant......may be because of this reason she didn't respond to combo treatment as the situation got worse after stopping treatment suddenly.
who knows it has such low response on mono and not the best option for cirrhosis, it may deteriorate liver
So you had fortunate luck Steff. Glad to hear that.
It worked for you but not the lady in China! Wonder why?
Thinking about that lady in China maybe when if ARC 520 is successful then it might be her best bet?
Would interferon be an option for her?
It worked for you but not the lady in China! Wonder why?
Thinking about that lady in China maybe when if ARC 520 is successful then it might be her best bet?
Would interferon be an option for her?
no 21iu/ml, infact being ex cirrhotic and still having nodules histologically me and doctors agreed immediately to go on a combo etv plus tdf which proved much more potent on me allowing also hbsag decline
appeared at 21 log? after 2 years. Just goes to show really that we never know what chemical reaction something will have in our body until we do it. As anything in life there is no guarantees apart from one day everyone dies
Horror story indeed, she has cirrohsis.i have no idea what options left.
as you say...rare event does not mean safe because anyone of us could be that rare event.this is why i was scared as hell when entecavir was increasing my hbsag and hbvdna appeared at 21 even after 2 years of etv
as you say...rare event does not mean safe because anyone of us could be that rare event.this is why i was scared as hell when entecavir was increasing my hbsag and hbvdna appeared at 21 even after 2 years of etv
Well its very rare but for the person its happening to it would be like a horror story..
I would kind of assume TDF & ETV combined would be even more potent. Got to feel sorry for the woman its happened to. What could she do next? Interferon?
I thought in 99% of cases even if there has been previous resistance to other drugs that tdf was still the perfect bullet so t speak?
I would kind of assume TDF & ETV combined would be even more potent. Got to feel sorry for the woman its happened to. What could she do next? Interferon?
I thought in 99% of cases even if there has been previous resistance to other drugs that tdf was still the perfect bullet so t speak?
I simply mean no antivirals that can accumulate resistance mutations must be used and start naive with tdf so 0% resistance is ensured
this report is like anoother report of tdf not working, like for this case there wasn t one single resistance mutation that makes tdf ineffective but cumulative resistance mutations making tdf ineffective.the other case used lam, adv and etv with multiple resistance mutations to all these antivirals in the end tdf didn t work
this report is like anoother report of tdf not working, like for this case there wasn t one single resistance mutation that makes tdf ineffective but cumulative resistance mutations making tdf ineffective.the other case used lam, adv and etv with multiple resistance mutations to all these antivirals in the end tdf didn t work
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