TITLE: Seven Years of Treatment with Tenofovir DF for Chronic Hepatitis B Virus Infection is Safe and Well Tolerated and Associated with Sustained Virological, Biochemical and Serological Responses with no Detectable Resistance
AUTHORS (FIRST NAME, LAST NAME): Patrick Marcellin1, Edward J. Gane2, Naoky Tsai3, Robert Flisiak4, Joerg Petersen5, Selim Gurel6, Iskren A. Kotzev7, John F. Flaherty8, Phillip Dinh8, Anuj Gaggar8, Kathryn M. Kitrinos8, Mani Subramanian8, John G. McHutchison8, Jacob George9, Maria Buti10
INSTITUTIONS (ALL): 1. Hopital Beaujon, Clichy, France.
2. Auckland City Hospital, Auckland, New Zealand.
3. University of Hawaii at Manoa, Honolulu, HI, United States.
4. Medical University of Bialystok, Bialystok, Poland.
5. Asklepios Klinik St. George, University of Hamburg, Hamburg, Germany.
6. Uludag Universitesi Tip Fakultesi, Bursa, Gorukle, Turkey.
7. University Hospital Sveta Marina, Varna, Bulgaria.
8. Gilead Sciences, Foster City, CA, United States.
9. Storr Liver Unit, Westmead Hospital, Sydney, NSW, Australia.
10. Hospital General Universitari Vall d’Hebron and Ciberehd, , Barcelona, Spain.
ABSTRACT BODY: Background:
We previously reported that 5 years of tenofovir DF (TDF) therapy in treatment naïve patients results in sustained viral suppression with no development of resistance and was associated with either the halting or regression of fibrosis in 96%, and reversal of cirrhosis in 74% of previously cirrhotic patients. Here we present 7 year results from these two ongoing 8 year studies (Studies 102 and 103).
After 48 weeks of double-blind comparison of TDF to adefovir dipivoxil, all patients undergoing liver biopsy were eligible to continue open-label TDF. Patients were assessed every 3 months for safety and efficacy with annual resistance surveillance. Annual assessments of bone mineral density (BMD) by DXA were added to both studies starting at year 4.
In a total 641 patients who were initially randomized and treated, 585 (93%) entered the TDF extension phase at Year 1, and at Year 7, 437 (68%) remain on study. Efficacy results at Year 7 are shown in the table. Overall (both studies combined), TDF was well tolerated over the 7 year evaluation period. Less than 2.5% of patients discontinued TDF due to an adverse event, and ≤ 1.7% experienced a confirmed renal event (≥0.5 mg/dL increase in serum creatinine from baseline, or phosphorus <2 mg/dL, or CrCL <50 mL/min). BMD assessments (lumbar spine and hip T scores) were stable over 3 years of evaluation. No resistance to TDF has been detected through Year 7.
In these two trials, TDF remains safe and effective over a 7 year treatment period with no detectable resistance to TDF; a relatively low rate of renal events and no evidence of clinically relevant bone loss were also observed.
TITLE: A European multicentre analysis of long term tenofovir (TDF) monotherapy for chronic hepatitis B in real life setting: efficacy, safety and HCC incidence
AUTHORS (FIRST NAME, LAST NAME): Florian van Boemmel1, Robert A. de Man2, Karoline Rutter3, Katja Deterding4, Christoph Sarrazin5, Viola Weich5, Marc Bourlière6, Christoph P. Berg7, Heiner Wedemeyer4, Michael Waizmann8, Bernd Moeller10, Michael Biermer1, 10, Dietrich Hueppe10, Eckart Schott11, Christoph Eisenbach12, Stefan Mauss13, Ulrich Spengler14, Johannes Wiegand1, Karin C. Van Nieuwkerk15, Kerstin Stein16, Anna Schweinberger1, Marcus Schuchmann17, Peter Ferenci3, Andreas Erhardt18, Pauline Arends2, Christoph R. Werner7, Renate Heyne10, Thomas Berg1
INSTITUTIONS (ALL): 1. University Hospital Leipzig, Leipzig, Germany.
2. 1Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands.
3. Medical university of Vienna, Vienna, Austria.
4. Department of Gastroenterology, Hepatology, and Endocrinology, Medical , Hannover, Germany.
5. Johann Wolfgang Goethe University Hospital Frankfurt, Frankfurt a.M., Germany.
6. Service d Hepato Gastroenterologie, Hopital Saint Joseph,, Marseille, France.
7. Medicine I, University of Tuebingen, Tübingen, Germany.
8. Schwerpunktpraxis Infektiologie und Hepatologie, Leipzig, Germany.
10. Gastroenterologische Schwerpunktpraxis Herne, Herne, Germany.
10. Praxiszentrum am Checkpoint, Berlin, Germany.
11. Charité University Hospital Berlin, Berlin, Germany.
12. University Hospital Heidelberg, Heidelberg, Germany.
13. Center for HIV and Hepatogastroenterology, Duesseldorf, Germany.
14. University Hospital Bonn, Bonn, Germany.
15. Dept. of Gastroenterology and Hepatology, VU Medisch Centrum, Amsterdam, Netherlands.
16. University Hospital Magdeburg, Magdeburg, Germany.
17. University Hospital Mainz, Mainz, Germany.
18. Petrus Hospital Wuppertal, Wuppertal, Germany.
ABSTRACT BODY: Background: Monotherapy with TDF is safe and effective in suppressing HBV replication in treatment-naïve patients. However, long term treatment with TDF as second or third line treatment has not been studied in many patients. We have investigated efficacy, safety, the influence of prior treatments and the incidence of hepatocellular carcinoma (HCC) in a European real life cohort of patients treated with TDF.
Methods: 798 patients (565 male, mean age 47±19[range, 18-78] years) receiving TDF monotherapy for a duration > 6 months were included in 28 centres and evaluated over a mean period of 54±24 [6-141]months. At the start of treatment 369 patients (46%) were HBeAg positive, 404 (51%) had previously received lamivudine, 308 (39%) adefovir and 13 (1.6%) entecavir for mean durations of 15±21[3-120], 21±28[5-174] and 26±15[3-54] months, respectively, 345 (43%) were treatment-naïve. 44 patients (5.5%) had liver cirrhosis and 42 patients (5.3%) had impaired kidney function. HBV DNA was expressed in IU/mL (lower detection limit 68 IU/mL). Glomerular filtration rate was estimated by MDRD formula.
Results: Mean HBV DNA levels decreased from baseline to months 6, 12, 24, 36, 48 and 60 from 7.7±9[3.1-10] to 3.1±3[1.8-4.8], 1.9±1[1.8-2.2], 1.9±1[1.8-2.1], 1.8±1[1.8-2.1], 1.8±2[1.8-2] and 1.8±2[1.8-2] log10 copies/mL. Detectable HBV DNA beyond month 12 was associated with prior use of adefovir (p=0.04) or baseline HBV DNA levels >7 log10 copies/mL (p=0.01). 26 patients received add-on treatment due to persistent viremia with entecavir (n=12), lamivudine (n=13) or telbivudine (n=1). Re-increases in HBV DNA levels were found in 16 patients; however HBV DNA levels also spontaneously decreased. HBeAg loss and seroconversion occurred in 148 (40%) and 136 patients (36%). HBsAg loss was observed in 21 HBeAg positive patients (6%). TDF treatment was stopped due to suspected association with tiredness (n=5), muscle pain (n=1), dry skin (n=1), joint pain (n=1), decreased kidney function (n=1) or maldigestion (n=3). Glomerular filtration rates (GFR) changed from normal to pathologic values in 3 patients. There was no significant decrease in GFR in patients with pre-existing kidney dysfunction. HCC was detected in 8 patients (1%) after a mean treatment period of 32±31[3-68] months. Factors associated with HCC were age >55 years. Pre-treatment with other antivirals was not associated with frequency of adverse events, with changes in GFR rate or with HCC incidence.
Conclusion: Long term second and third line monotherapy with TDF was comparably safe and effective as in treatment-naïve patients.
btw, there is no resistance to interferon ever period..
I still don;t see any point in using nucs for HBV treatment for most people. When in fact they developed these drugs to slow down the spread of cancer cells originally.
These drugs are highly toxic, cause mitochondrial toxicity, which further shuts down the immune system. Over time build of toxins causes cancers in other areas of the body.
So what is accomplished here? Just blocking viral DNA replication in blood does nothing in terms of cure. If they have very little effect on the surface antigen, that damages the liver cells even while on the medication.
None of these NUC drugs can be ever as effective as interferon. So all this statistic data on TDF, LAM or ETV is really meaningless - they are generating information for an argument that these medications are actually good for us and safe..
Yet nobody, reports the data, how many quit these drugs, from terrible sides, like high blood pressure, and developed steatosis to name the few. All that is being reported by the HIV crowd on these drugs long ago.
HBV treatment is totally steered sideways.. instead of immune therapies that work even from available agents already, they are giving us more TDF or ETV..
I took ETV for 7 years.. And what did I accomplish? Nothing, the virus is still there, plus developed high blood pressure, and fatty liver, body hair stopped growing too. Is that good treatment? Safe? Will they ever include stories of patients like me in their statistical reports?
Sorry for rant though.. BUt in light that there is Replicor medication that can cure HBV in several months with interferon combo or zadaxin.. I think it is really pointless talking about HOW good TDF is.
We should focus on the immune therapies.. and educate patients and doctors to actually know what is best for the patient rather then a drug company..
Stefan. But with interferon one can be cured - achieve svr. With tdf chances of this are slim.
From my own experience I can tell you that my body stopped tolerating etv at about 7 years mark.
With all these new meds they are testing we should be focused on them rather then nucs along. Kidney damage from tdf is a problem that many doctors wont even prescribe it. Although it is more potent then other nucs.
I would rather focus on Replicor medication. Or GS9620 and way to get it approved for use faster.
They have found many cures already for hbv. They are.just not being used. Cure is healthy immune system. And they are not doing immune therapies. Gcmaf is not used in the big pharma controlled medicine. So is zadaxin and interlukin boosters. Only very rich people in private clinics can try cutting edge stuff. Stem cell therapy can regenarate liver cells and help rapidly clear hbv with the use of nucs to block viral assmbly in blood.
Replicor drug works too. So there are much much better treatments that should be used instead of nucs as the main choice.
Also peptides that break the envelope of the virus are reported to work directly on the virus.
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