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Golden Milk: The Simple Drink That Could Change Your Life
http://themindunleashed.org/2014/05/golden-milk-simple-drink-change-life.htmlz
Please accept my apology. I am sorry that I wrongly attributed the remark to you.
Hi Stephen,
I think you should be careful when you read posts:)
I wrote that comment for monster_in_my_dna (it was indiacted such), as he seemed to get quite aggressive.
I agree, we shouldn't mislead (with no intention of course) the others. I added "Antiviral" specifically to Safi's list of treatments in another thread some days earlier, just for this reason.
Nevertheless, we all agree that the effect of NUCs mono on decreasing HBsAg is quite limitted. Interferon addon seems to be the right way to go. But we have to take NUCs for quite long time (three to five years) before we can do that. Maybe even longer if the decrease in HBsAg is slower since we should have lower than 1000ui to have higher chance of clearance. So meanwhile, why shouldn't we be proactive to try useful suppliments together with NUCs? Maybe they will work for us, maybe not, we should at least try.
We are living in countries with good health care where we don't pay a penny for expensive drugs. We don't care how long we take the drugs, but there are many people who just simply can't afford to buy these drugs. Of course the duration of the treatment with NUCs is very important for them, as we know stoppping the usage of NUCs when one shouldn't can be very dangerous.
I think you should be careful when you read posts:)
I wrote that comment for monster_in_my_dna (it was indiacted such), as he seemed to get quite aggressive.
I agree, we shouldn't mislead (with no intention of course) the others. I added "Antiviral" specifically to Safi's list of treatments in another thread some days earlier, just for this reason.
Nevertheless, we all agree that the effect of NUCs mono on decreasing HBsAg is quite limitted. Interferon addon seems to be the right way to go. But we have to take NUCs for quite long time (three to five years) before we can do that. Maybe even longer if the decrease in HBsAg is slower since we should have lower than 1000ui to have higher chance of clearance. So meanwhile, why shouldn't we be proactive to try useful suppliments together with NUCs? Maybe they will work for us, maybe not, we should at least try.
We are living in countries with good health care where we don't pay a penny for expensive drugs. We don't care how long we take the drugs, but there are many people who just simply can't afford to buy these drugs. Of course the duration of the treatment with NUCs is very important for them, as we know stoppping the usage of NUCs when one shouldn't can be very dangerous.
I think you should be careful with your accusation that I have been a bit harsh. Safi made the statement that antivirals have no direct effect on HBSAg. That is untrue, so I cited research to support my rebuttal. Antivirals are, together with Interferon, the main standard treatment for chronic Hepatitis B and they are very effective too. To suggest that they cannot cure but some supplements can, is very misleading, to say the least, to first time readers seeking information from this forum. Why treat when you can get cured?
Someone asked, what is the harm of these natural supplements? I want to ask, what is the benefit in terms of treating Hepatitis B?
Someone asked, what is the harm of these natural supplements? I want to ask, what is the benefit in terms of treating Hepatitis B?
What I saw from Dr Kennedy's talk is that the extrapolated years for HBsAg loss with NUCs only (normal ALT) is over 35 years!!!!!
Safi managed in just one year!
People talk about lucky 5%, but why they are lucky? because they have faith in GOD? They pray when they take each pill?
Do the reseachers ever looked into their overall health conditions? their life style, diet etc? I don't think so.
Safi managed in just one year!
People talk about lucky 5%, but why they are lucky? because they have faith in GOD? They pray when they take each pill?
Do the reseachers ever looked into their overall health conditions? their life style, diet etc? I don't think so.
I think you are a bit harsh. Thanks to Safi, we (at least I) learnt Black Cumin is a useful suppliment. There are many research articles showing its strong antioxidant property. it is very kind of him to be around even he already got cured. He is not trying to sell anything here. Just sharing his experience. Maybe it is a special case( his body condition, his prior desease history etc). In any case, just as we need VitD for our immune support, we need antioxidants for healthy liver function. It is up to you to adopt his regimen, but it is not polite to attack someone who is trying to help others.
Basically, the authors argued convincingly:
1. Complete suppression of hbv replication by potent antiviral should lead to cure because the pool of cccDNA is not being refilled and the pool of cccDNA will eventually disappear due to natural liver cells turnover. This is not the case for most patients because some of their infected liver cells are refractory to the antiviral, and some infected liver cells maybe slower to die or subdivide.
2. Use of antivirals can restore T-cell immmunity. For some patients, this restoration may help them to clear the virus, for some to control the virus after stopping antivirals, but for most, the restoration of T cell immunity is not sufficient.
If you can accept these research, you will understand why the treatment method of long term antiviral use then with added Interferon can significantly increase the rate of clearing the infection. Most important, it also explains why some patients can be cured by antiviral treatment alone.
1. Complete suppression of hbv replication by potent antiviral should lead to cure because the pool of cccDNA is not being refilled and the pool of cccDNA will eventually disappear due to natural liver cells turnover. This is not the case for most patients because some of their infected liver cells are refractory to the antiviral, and some infected liver cells maybe slower to die or subdivide.
2. Use of antivirals can restore T-cell immmunity. For some patients, this restoration may help them to clear the virus, for some to control the virus after stopping antivirals, but for most, the restoration of T cell immunity is not sufficient.
If you can accept these research, you will understand why the treatment method of long term antiviral use then with added Interferon can significantly increase the rate of clearing the infection. Most important, it also explains why some patients can be cured by antiviral treatment alone.
4.5. Dysfunction of antiviral immune response
Due to the failure of nucleos(t)ide analog therapy to completely eliminate HBV infected cells, viral infection can be restored within a few weeks to several months after the cessation of antiviral therapy. Hence, cure or durable control of a chronic infection by HBV replication inhibitor therapy may not be possible in a host that lacks an antiviral immune response capable of producing antibodies to neutralize residual viruses and cellular immune response that eliminate infected cells and keeps the reservoirs under immune surveillance.
Although failed to resolve HBV infection, specific humoral and cellular immune responses against HBV antigens are readily detectable in chronic HBV carriers, which is distinct from the immune responses observed in patients who resolve transient HBV infection28 and 29. For instance, although antibodies against core proteins, HBeAg, polymerase and X protein can be detected in all or a portion of chronic HBV carriers, antibodies against three envelope proteins are not produced or exist in forms of immunocomplexes. Concerning T cell response, HBV persistence is always associated with defective HBV-specific CD4 and CD8 T cell functions68. Despite the phenotypes of the altered immune response in HBV chronic carriers in the different clinical stages have been extensively characterized, the mechanism of HBV infection to induce the dysfunctional immune responses leading to a persistent infection remains elusive29. However, it is generally believed that the defective T cell function is maintained primarily by the effect of the prolonged exposure of T cells to high quantities of viral antigens and by the tolerogenic features of hepatocytes and liver resident cells69 and 70. These two combined mechanisms can result in the deletion of HBV-specific T cells or in their functional inactivation (exhaustion), which is characterized by an increased expression of negative co-stimulatory molecules and a dysregulation of co-stimulatory pathways, such as PD-1/PDL1, affect the quality and intensity of the antiviral T cell response71.
Considering the critical role of the prolonged exposure of T cells to high quantities of viral antigens in the maintenance of HBV-specific T cell dysfunction, it is anticipated that reduction of HBV antigen load through long-term antiviral therapy to significantly reduce cccDNA should help improve T cell function, which might, in turn, lead to sustained suppression or functional cure of HBV infection. However, although as expected that long-term nucleoside analog therapy at least partially restores the function of HBV specific T cells, a durable control of HBV infection could still not be achieved in the majority of the treated patients72, 73 and 74. Hence, although reduction of HBV antigen load is helpful, restoration of functional T cell immune response requires the correction of additional defects in the priming, expansion and differentiation of HBV specific T cells.
Due to the failure of nucleos(t)ide analog therapy to completely eliminate HBV infected cells, viral infection can be restored within a few weeks to several months after the cessation of antiviral therapy. Hence, cure or durable control of a chronic infection by HBV replication inhibitor therapy may not be possible in a host that lacks an antiviral immune response capable of producing antibodies to neutralize residual viruses and cellular immune response that eliminate infected cells and keeps the reservoirs under immune surveillance.
Although failed to resolve HBV infection, specific humoral and cellular immune responses against HBV antigens are readily detectable in chronic HBV carriers, which is distinct from the immune responses observed in patients who resolve transient HBV infection28 and 29. For instance, although antibodies against core proteins, HBeAg, polymerase and X protein can be detected in all or a portion of chronic HBV carriers, antibodies against three envelope proteins are not produced or exist in forms of immunocomplexes. Concerning T cell response, HBV persistence is always associated with defective HBV-specific CD4 and CD8 T cell functions68. Despite the phenotypes of the altered immune response in HBV chronic carriers in the different clinical stages have been extensively characterized, the mechanism of HBV infection to induce the dysfunctional immune responses leading to a persistent infection remains elusive29. However, it is generally believed that the defective T cell function is maintained primarily by the effect of the prolonged exposure of T cells to high quantities of viral antigens and by the tolerogenic features of hepatocytes and liver resident cells69 and 70. These two combined mechanisms can result in the deletion of HBV-specific T cells or in their functional inactivation (exhaustion), which is characterized by an increased expression of negative co-stimulatory molecules and a dysregulation of co-stimulatory pathways, such as PD-1/PDL1, affect the quality and intensity of the antiviral T cell response71.
Considering the critical role of the prolonged exposure of T cells to high quantities of viral antigens in the maintenance of HBV-specific T cell dysfunction, it is anticipated that reduction of HBV antigen load through long-term antiviral therapy to significantly reduce cccDNA should help improve T cell function, which might, in turn, lead to sustained suppression or functional cure of HBV infection. However, although as expected that long-term nucleoside analog therapy at least partially restores the function of HBV specific T cells, a durable control of HBV infection could still not be achieved in the majority of the treated patients72, 73 and 74. Hence, although reduction of HBV antigen load is helpful, restoration of functional T cell immune response requires the correction of additional defects in the priming, expansion and differentiation of HBV specific T cells.
4.4. HBV reservoirs or extrahepatic infection
While it is possible that a fraction of infected hepatocytes with slower rates of turnover may serve as reservoirs for HBV after immune resolution of transient HBV infection or long-term antiviral therapy, the existence of extrahepatic reservoirs also cannot be ruled out. In fact, although there are reports claiming the existence of HBV DNA or antigens in peripheral lymphocytes and other tissues, productive HBV infection of cell types other than hepatocytes has not yet been convincingly approved61 and 62. However, DHBV and WHV have been demonstrated to have an unanticipated broad cell tropism in vivo. For instance, WHV DNA replication intermediates and/or mRNA can be detected in lymphoid cells of spleens, peripheral T and B lymphocytes upon activation 63. In addition to liver, DHBV antigen expression, DNA replication intermediates and/or mRNA can also be detected in the brain, lung, heart, intestine, kidney, pancreas and spleen 64. In situ hybridization showed evidence of viral replication in the lung epithelium, germinal center of spleen, acinar cell of pancreas and tubular epithelium of kidney 65. Moreover, DHBV infects both pancreatic α and β endocrine cells and impairs the arginine-stimulated insulin response 66. Intriguingly, treatment of DHBV congenitally infected ducks with the guanosine analog, ganciclovir, efficiently reduced intrahepatic viral core DNA and reduced core antigen-positive hepatocytes. However, the treatment did not affect viral antigen expression in the bile duct epithelial cells, putative oval cells and DHBV-infected cells in extrahepatic sites such as the pancreas, kidney and spleen 67. The studies thus showed that cure of HBV infection requires combination therapies targeting all types of infected cells, but not only hepatocytes. However, due to the intrinsic stability of cccDNA in non-dividing cells, control of HBV replication in the long-lived cell types may require elimination of the “reservoir” cells or silence the viral gene expression and replication by host immune response.
While it is possible that a fraction of infected hepatocytes with slower rates of turnover may serve as reservoirs for HBV after immune resolution of transient HBV infection or long-term antiviral therapy, the existence of extrahepatic reservoirs also cannot be ruled out. In fact, although there are reports claiming the existence of HBV DNA or antigens in peripheral lymphocytes and other tissues, productive HBV infection of cell types other than hepatocytes has not yet been convincingly approved61 and 62. However, DHBV and WHV have been demonstrated to have an unanticipated broad cell tropism in vivo. For instance, WHV DNA replication intermediates and/or mRNA can be detected in lymphoid cells of spleens, peripheral T and B lymphocytes upon activation 63. In addition to liver, DHBV antigen expression, DNA replication intermediates and/or mRNA can also be detected in the brain, lung, heart, intestine, kidney, pancreas and spleen 64. In situ hybridization showed evidence of viral replication in the lung epithelium, germinal center of spleen, acinar cell of pancreas and tubular epithelium of kidney 65. Moreover, DHBV infects both pancreatic α and β endocrine cells and impairs the arginine-stimulated insulin response 66. Intriguingly, treatment of DHBV congenitally infected ducks with the guanosine analog, ganciclovir, efficiently reduced intrahepatic viral core DNA and reduced core antigen-positive hepatocytes. However, the treatment did not affect viral antigen expression in the bile duct epithelial cells, putative oval cells and DHBV-infected cells in extrahepatic sites such as the pancreas, kidney and spleen 67. The studies thus showed that cure of HBV infection requires combination therapies targeting all types of infected cells, but not only hepatocytes. However, due to the intrinsic stability of cccDNA in non-dividing cells, control of HBV replication in the long-lived cell types may require elimination of the “reservoir” cells or silence the viral gene expression and replication by host immune response.
4.3. Turnover of HBV host cells
The rate of infected cell turnover is one of the key parameters of HBV infection dynamics in vivo. Hepatocyte death, initiated through attack by antiviral cytotoxic T-lymphocytes (CTL), and compensatory hepatocyte proliferation, are both believed to be major contributing factors in the loss of virus DNA during immune resolution of transient infections. Although non-cytolytic cure of infected hepatocytes have been approved to occur, it is estimated that a minimum of 0.7–1 and approximately 2 complete random turnovers of the hepatocyte population of the liver occurs during the resolution of WHV infection in woodchucks 50 and HBV infection in chimpanzees 48, respectively. Hepatocyte turnover also plays an important role in viral pathogenesis and immune selection of hepatocytes infected with mutant strains of HBV and in the emergence of hepatocytes that appear refractory to HBV infection through clonal expansion. Under the condition of therapeutic inhibition of ongoing HBV DNA replication, the rate of HBV infected cell turnover is a critical determinant of cccDNA decay kinetics 41 and 58. Accordingly, hepatocyte turnover has been investigated on the variety of pathobiological conditions by either directly measuring hepatocyte proliferation activity from liver biopsies or mathematic modeling of viral dynamics. These studies from multiple laboratories reveal that while the half-life of hepatocytes in the healthy adult liver is approximately half a year, the median half-lives of infected hepatocytes in patients with chronic hepatitis B are 257 h (=10.7 days) (n=9, range 112–762 h) 59 and 7 days in patients with chronic hepatitis B under lamivudine treatment 60. The results thus imply the overall rate of hepatocyte turnover is significantly accelerated in patients with chronic hepatitis B, which should favor the eradication of cccDNA with viral replication inhibitor therapies.
The rate of infected cell turnover is one of the key parameters of HBV infection dynamics in vivo. Hepatocyte death, initiated through attack by antiviral cytotoxic T-lymphocytes (CTL), and compensatory hepatocyte proliferation, are both believed to be major contributing factors in the loss of virus DNA during immune resolution of transient infections. Although non-cytolytic cure of infected hepatocytes have been approved to occur, it is estimated that a minimum of 0.7–1 and approximately 2 complete random turnovers of the hepatocyte population of the liver occurs during the resolution of WHV infection in woodchucks 50 and HBV infection in chimpanzees 48, respectively. Hepatocyte turnover also plays an important role in viral pathogenesis and immune selection of hepatocytes infected with mutant strains of HBV and in the emergence of hepatocytes that appear refractory to HBV infection through clonal expansion. Under the condition of therapeutic inhibition of ongoing HBV DNA replication, the rate of HBV infected cell turnover is a critical determinant of cccDNA decay kinetics 41 and 58. Accordingly, hepatocyte turnover has been investigated on the variety of pathobiological conditions by either directly measuring hepatocyte proliferation activity from liver biopsies or mathematic modeling of viral dynamics. These studies from multiple laboratories reveal that while the half-life of hepatocytes in the healthy adult liver is approximately half a year, the median half-lives of infected hepatocytes in patients with chronic hepatitis B are 257 h (=10.7 days) (n=9, range 112–762 h) 59 and 7 days in patients with chronic hepatitis B under lamivudine treatment 60. The results thus imply the overall rate of hepatocyte turnover is significantly accelerated in patients with chronic hepatitis B, which should favor the eradication of cccDNA with viral replication inhibitor therapies.
4.2. Incomplete suppression of viral replication
Although clinical studies on the antiviral efficacy of nucleos(t)ide analogs under the variety of clinical conditions demonstrate striking reduction of viral load in peripheral blood, intrahepatic HBV core DNA and cccDNA are still detectable after long-term antiviral therapy36, 37 and 38. Moreover, sequential accumulation of drug resistance mutations during apparently effective nucleos(t)ide analog therapy provides additional evidence suggesting that residual HBV replication and de novo cccDNA synthesis occur under long-term DNA polymerase inhibitor therapy 57. Interestingly, analyses of viral DNA replication intermediates and core antigen-positive hepatocytes in the livers of WHV-infected woodchucks under the therapy of clevudine demonstrated that after more than 30 weeks of therapy, the predominant WHV DNA species in the liver is cccDNA. However, core-associated viral DNA replication intermediates, such as partial single-stranded DNA, are also clearly detectable. Intriguingly, while the vast majority of hepatocytes become core antigen-negative, a small fraction of hepatocytes expresses core antigen at the level similar to that in the pre-treated hepatocytes 40. This observation indicates that while majority of infected hepatocytes have been cured after long-term nucleoside analog therapy, the residual viral DNA replication and cccDNA synthesis occur in discrete hepatocytes. In another word, the failure to cure HBV infection is most likely due to a fraction of HBV infected cells that are refractory to nucleoside analog therapies.
Why should this be? Because the nucleoside analogs are prodrugs that require activation by host cellular nucleoside kinases in virally infected cells, it is thus possible that the cells refractory to the therapy are incapable of activating the nucleoside analogs. Alternatively, considering the important role of cell division in elimination of pre-existing cccDNA41, it is also possible that the refractory cells are long-live cells and have not divided during the therapy. Nevertheless, further understanding the biological feature of the refractory cell population is important for the treatment of chronic HBV infection.
Although clinical studies on the antiviral efficacy of nucleos(t)ide analogs under the variety of clinical conditions demonstrate striking reduction of viral load in peripheral blood, intrahepatic HBV core DNA and cccDNA are still detectable after long-term antiviral therapy36, 37 and 38. Moreover, sequential accumulation of drug resistance mutations during apparently effective nucleos(t)ide analog therapy provides additional evidence suggesting that residual HBV replication and de novo cccDNA synthesis occur under long-term DNA polymerase inhibitor therapy 57. Interestingly, analyses of viral DNA replication intermediates and core antigen-positive hepatocytes in the livers of WHV-infected woodchucks under the therapy of clevudine demonstrated that after more than 30 weeks of therapy, the predominant WHV DNA species in the liver is cccDNA. However, core-associated viral DNA replication intermediates, such as partial single-stranded DNA, are also clearly detectable. Intriguingly, while the vast majority of hepatocytes become core antigen-negative, a small fraction of hepatocytes expresses core antigen at the level similar to that in the pre-treated hepatocytes 40. This observation indicates that while majority of infected hepatocytes have been cured after long-term nucleoside analog therapy, the residual viral DNA replication and cccDNA synthesis occur in discrete hepatocytes. In another word, the failure to cure HBV infection is most likely due to a fraction of HBV infected cells that are refractory to nucleoside analog therapies.
Why should this be? Because the nucleoside analogs are prodrugs that require activation by host cellular nucleoside kinases in virally infected cells, it is thus possible that the cells refractory to the therapy are incapable of activating the nucleoside analogs. Alternatively, considering the important role of cell division in elimination of pre-existing cccDNA41, it is also possible that the refractory cells are long-live cells and have not divided during the therapy. Nevertheless, further understanding the biological feature of the refractory cell population is important for the treatment of chronic HBV infection.
"Barracuda and other nuts do not direct or have effect on qHBSAG. Their mail aim is to lower the HBVDNA." - I am afraid you are completely wrong on this. Do read the following paper to understand why:
http://www.sciencedirect.com/science/article/pii/S2211383514000513
I will post extracts from the article.
4. Obstacles to a functional cure
4.1. The intrinsic stability of HBV cccDNA
Treatment of chronic hepatitis B patients with nucleoside analogs for more than a year reduces HBV load in plasma by more than 4 logs. However, analyses of intrahepatic viral DNA indicate that the antiviral therapies only reduce the cytoplasmic HBV core DNA and nuclear HBV cccDNA by approximately 2 and 1 log, respectively36, 37 and 38. These observations are well corroborated with the inability of nucleoside analogs to significantly reduce the level of HBsAg antigenemia39, which is quantitatively correlated with the level of cccDNA. Similarly, extensive analyses of intrahepatic woodchuck hepatitis virus (WHV) and duck hepatitis B virus (DHBV) DNA intermediates under nucleoside analog therapy clearly demonstrated that cccDNA become the predominant form of viral DNA replication intermediates upon long-term suppression of viral DNA replication40 and 41. These findings strongly suggest that cccDNA is the most stable HBV replication intermediate and elimination of cccDNA is the key to cure HBV infection.
As stated above and illustrated in Fig. 1, cccDNA is initially synthesized from the rcDNA from the incoming viral nucleocapsids during HBV infection of a hepatocyte. In the early phase of infection, additional cccDNA are produced from newly synthesized cytoplasmic rcDNA through an intracellular amplification pathway24 and 42. These two pathways culminate in the formation of a regulated steady-state population of 5–50 cccDNA molecules per infected hepatocyte20, 22 and 43. Obviously, persistent infection of hepadnaviruses relies on the stable maintenance and proper function of the cccDNA pool in the nuclei of infected hepatocytes as the source of viral RNAs and therefore, cure of HBV infected hepatocytes requires elimination of cccDNA24, 42, 44 and 45.
Because cccDNA cannot amplify itself via semiconservative DNA replication, complete inhibition of cytoplasmic rcDNA synthesis by viral polymerase inhibitors should preclude de novo cccDNA synthesis. Hence, the cure of HBV infected hepatocytes by nucleoside analogs relies on the decay of pre-existing cccDNA. Accordingly, extensive efforts have been made to determine the half-lives of cccDNA under the variety of condition and obtained apparently contradictory results ( Table 1), implying that the rate of cccDNA metabolism varies under different pathobiological conditions. Concerning the potential mechanisms of cccDNA decay, recent studies suggest that inflammatory cytokines, such as IFN-α and lymphotoxin-β, induce intrinsic cellular response to promote the decay of cccDNA through APOBEC3 family enzyme-catalyzed cytidine deamination and subsequent DNA repair process 51 and 52. In addition, cccDNA can be diluted during cell division and cccDNA-free cells could arise through multiple rounds of cell division and unequal partitioning of cccDNA molecules into daughter cells 53 and 54. Furthermore, studies with integrated WHV DNA as a genetic maker of virally infected hepatocytes during transient and chronic WHV infection of woodchucks unambiguously demonstrated that virus-free hepatocytes can be derived from infected cells 55 and 56. In another word, WHV-infected hepatocytes are indeed curable in vivo. However, it is not yet clear if the division of infected hepatocytes is required for the host immune response to purge cccDNA in vivo.
Based on the mechanistic analyses of cccDNA metabolism, failure of long-term antiviral therapies with viral DNA polymerase inhibitors to eliminate cccDNA is most likely due to either incomplete suppression of HBV rcDNA synthesis, which allows for continuous replenishment of cccDNA pool via intracellular amplification pathway, or slow turnover of at least a subpopulation of HBV infected cells that serve as reservoirs of the virus.
http://www.sciencedirect.com/science/article/pii/S2211383514000513
I will post extracts from the article.
4. Obstacles to a functional cure
4.1. The intrinsic stability of HBV cccDNA
Treatment of chronic hepatitis B patients with nucleoside analogs for more than a year reduces HBV load in plasma by more than 4 logs. However, analyses of intrahepatic viral DNA indicate that the antiviral therapies only reduce the cytoplasmic HBV core DNA and nuclear HBV cccDNA by approximately 2 and 1 log, respectively36, 37 and 38. These observations are well corroborated with the inability of nucleoside analogs to significantly reduce the level of HBsAg antigenemia39, which is quantitatively correlated with the level of cccDNA. Similarly, extensive analyses of intrahepatic woodchuck hepatitis virus (WHV) and duck hepatitis B virus (DHBV) DNA intermediates under nucleoside analog therapy clearly demonstrated that cccDNA become the predominant form of viral DNA replication intermediates upon long-term suppression of viral DNA replication40 and 41. These findings strongly suggest that cccDNA is the most stable HBV replication intermediate and elimination of cccDNA is the key to cure HBV infection.
As stated above and illustrated in Fig. 1, cccDNA is initially synthesized from the rcDNA from the incoming viral nucleocapsids during HBV infection of a hepatocyte. In the early phase of infection, additional cccDNA are produced from newly synthesized cytoplasmic rcDNA through an intracellular amplification pathway24 and 42. These two pathways culminate in the formation of a regulated steady-state population of 5–50 cccDNA molecules per infected hepatocyte20, 22 and 43. Obviously, persistent infection of hepadnaviruses relies on the stable maintenance and proper function of the cccDNA pool in the nuclei of infected hepatocytes as the source of viral RNAs and therefore, cure of HBV infected hepatocytes requires elimination of cccDNA24, 42, 44 and 45.
Because cccDNA cannot amplify itself via semiconservative DNA replication, complete inhibition of cytoplasmic rcDNA synthesis by viral polymerase inhibitors should preclude de novo cccDNA synthesis. Hence, the cure of HBV infected hepatocytes by nucleoside analogs relies on the decay of pre-existing cccDNA. Accordingly, extensive efforts have been made to determine the half-lives of cccDNA under the variety of condition and obtained apparently contradictory results ( Table 1), implying that the rate of cccDNA metabolism varies under different pathobiological conditions. Concerning the potential mechanisms of cccDNA decay, recent studies suggest that inflammatory cytokines, such as IFN-α and lymphotoxin-β, induce intrinsic cellular response to promote the decay of cccDNA through APOBEC3 family enzyme-catalyzed cytidine deamination and subsequent DNA repair process 51 and 52. In addition, cccDNA can be diluted during cell division and cccDNA-free cells could arise through multiple rounds of cell division and unequal partitioning of cccDNA molecules into daughter cells 53 and 54. Furthermore, studies with integrated WHV DNA as a genetic maker of virally infected hepatocytes during transient and chronic WHV infection of woodchucks unambiguously demonstrated that virus-free hepatocytes can be derived from infected cells 55 and 56. In another word, WHV-infected hepatocytes are indeed curable in vivo. However, it is not yet clear if the division of infected hepatocytes is required for the host immune response to purge cccDNA in vivo.
Based on the mechanistic analyses of cccDNA metabolism, failure of long-term antiviral therapies with viral DNA polymerase inhibitors to eliminate cccDNA is most likely due to either incomplete suppression of HBV rcDNA synthesis, which allows for continuous replenishment of cccDNA pool via intracellular amplification pathway, or slow turnover of at least a subpopulation of HBV infected cells that serve as reservoirs of the virus.
I think it is important to take in consideration the experience of each one here in forum because all of us we are looking for cure.the but of forum is to share good ideas and new information.and each one is free to take these substances or not
Barracuda and other nuts do not direct or have effect on qHBSAG. Their mail aim is to lower the HBVDNA.
If you do not use black seed in a proper way or if you do not live healthy, black seed cannot do anything...So, by writing me that I am making false dream, you may be preventing someones' cure.
If you do not use black seed in a proper way or if you do not live healthy, black seed cannot do anything...So, by writing me that I am making false dream, you may be preventing someones' cure.
for me i still have hbsag, but i take black seed, and black seed oil, i have inactive hbv. i do not take nuc. maybe black seed work for active hbv? i dont know. maybe if more people try it we can know for sure.
Hi
Monster so for You no change with taking black seed?and do your condition go worst?i asl because want to learn about expériences.and do you take antivirals?thanks
Monster so for You no change with taking black seed?and do your condition go worst?i asl because want to learn about expériences.and do you take antivirals?thanks
most of the countries in the world who eat circumin everyday in diet are some of the countries with high hbv infaction if circumin cure hbv then many of these countries would not be endemic
you use baraclude, i think has more to do with your cure, some people cure with nuc, its not new thing.
because you are 1 person who use black seed, it not means everybody can cure with it.
you get message everyday people want to learn more dos not mean black seed works, i think its good for my health but has not cured my hb.
why say if i have better options please write them, you are making false dream for peoples, start a forum, black seed user forum.
because you are 1 person who use black seed, it not means everybody can cure with it.
you get message everyday people want to learn more dos not mean black seed works, i think its good for my health but has not cured my hb.
why say if i have better options please write them, you are making false dream for peoples, start a forum, black seed user forum.
This site has more than 6 million member on Facebook and is one of the big publishers on the net.
We are here because we want to get rid of HBV and they are what I read before I am cured. I am responsible to reach as many as HBVers to inform them.
Everyday new persons learn that they are HBV patients and they search on Google and find this site. They also have rights to learn these.
Furthermore, everyday I got 7-8 private message which proofs that people want to learn more.
If you have better options than mine, please write them.
If you read my posts, black seed is one of my supplements. Your life style should be totally designed for HBV
Are you sure that you use black seed in a right way?
Everyday new persons learn that they are HBV patients and they search on Google and find this site. They also have rights to learn these.
Furthermore, everyday I got 7-8 private message which proofs that people want to learn more.
If you have better options than mine, please write them.
If you read my posts, black seed is one of my supplements. Your life style should be totally designed for HBV
Are you sure that you use black seed in a right way?
on every post you put the same thing.
we appreciate you are cured, well done to you, but you comment on every post, the same thing.
i take black seed, black seed oil, circumin for many years i still have hbsag over 12000 iu/ml always the same, black seed or no black seed.
we appreciate you are cured, well done to you, but you comment on every post, the same thing.
i take black seed, black seed oil, circumin for many years i still have hbsag over 12000 iu/ml always the same, black seed or no black seed.
From RationalWiki
themindunleashed.org is a pseudoscientific, woo-peddling, clickbait website with a propensity to misrepresent data from studies and present it as scientific fact for their own gain. With just a soupçon of bigotry for flavor.
Neither the site itself nor the whois say anything about who owns and runs the place.
themindunleashed.org is a pseudoscientific, woo-peddling, clickbait website with a propensity to misrepresent data from studies and present it as scientific fact for their own gain. With just a soupçon of bigotry for flavor.
Neither the site itself nor the whois say anything about who owns and runs the place.
Thanks. I've read it somewhere that heat and piperine increase turmeric bioavalability by hundreds. Very good idea!
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