Aa
SVR persons:Persistence of HCV After Successful Treatment of Chronic Hepatitis C: Is HCV Infection for Life?
Persistence of HCV After Successful Treatment of Chronic Hepatitis C: Is HCV Infection for Life?
It is presumed that resolution of hepatitis C reflects virus eradication, as evidenced by normalization of liver function tests and disappearance of hepatitis C virus (HCV) RNA from serum, as determined by conventional laboratory assays.
In this study, researchers in Poland examined the expression of the HCV genome in the sera, peripheral blood mononuclear cells (PBMC), and, on some occasions, monocyte-derived dendritic cells (DC) long after resolution of hepatitis C by using a highly sensitive reverse transcription (RT)-polymerase chain reaction-nucleic acid hybridization (RT-PCR-NAH) assay.
The samples obtained from 16 randomly selected patients (5 with spontaneous resolution and 11 with treatment-induced resolution), monitored for up to 5 years, were studied by qualitative and semi-quantitative RT-PCR-NAH and by real-time RT-PCR to detect the HCV RNA positive strand.
The replicative HCV RNA negative strand was examined in PBMC after culture with a T cell proliferation stimulating mitogen.
Results
The findings show that HCV RNA was carried in the convalescent-phase sera and/or PBMC in all 16 individuals investigated.
Also, DC from six of seven patients were reactive for the HCV genome. Importantly, traces of the HCV RNA negative strand, suggesting progressing virus replication, were detected in the majority of mitogen-stimulated PBMC, including four samples collected 5 years after recovery.
Sequencing of the HCV 5' untranslated region fragment revealed genotype 1b in four of nine individuals examined and genotypes 1a and 2a in three and two patients, respectively.
In conclusion, these results imply that HCV RNA can persist at very low levels in the serum and peripheral lymphoid cells and that an intermediate replicative form of the HCV genome can persist in PBMC for many years after apparently complete spontaneous or antiviral therapy-induced resolution of chronic hepatitis C.
Warsaw Medical Academy, Poland.
It is presumed that resolution of hepatitis C reflects virus eradication, as evidenced by normalization of liver function tests and disappearance of hepatitis C virus (HCV) RNA from serum, as determined by conventional laboratory assays.
In this study, researchers in Poland examined the expression of the HCV genome in the sera, peripheral blood mononuclear cells (PBMC), and, on some occasions, monocyte-derived dendritic cells (DC) long after resolution of hepatitis C by using a highly sensitive reverse transcription (RT)-polymerase chain reaction-nucleic acid hybridization (RT-PCR-NAH) assay.
The samples obtained from 16 randomly selected patients (5 with spontaneous resolution and 11 with treatment-induced resolution), monitored for up to 5 years, were studied by qualitative and semi-quantitative RT-PCR-NAH and by real-time RT-PCR to detect the HCV RNA positive strand.
The replicative HCV RNA negative strand was examined in PBMC after culture with a T cell proliferation stimulating mitogen.
Results
The findings show that HCV RNA was carried in the convalescent-phase sera and/or PBMC in all 16 individuals investigated.
Also, DC from six of seven patients were reactive for the HCV genome. Importantly, traces of the HCV RNA negative strand, suggesting progressing virus replication, were detected in the majority of mitogen-stimulated PBMC, including four samples collected 5 years after recovery.
Sequencing of the HCV 5' untranslated region fragment revealed genotype 1b in four of nine individuals examined and genotypes 1a and 2a in three and two patients, respectively.
In conclusion, these results imply that HCV RNA can persist at very low levels in the serum and peripheral lymphoid cells and that an intermediate replicative form of the HCV genome can persist in PBMC for many years after apparently complete spontaneous or antiviral therapy-induced resolution of chronic hepatitis C.
Warsaw Medical Academy, Poland.
Could you just shorten this for me - I have ADHD now, I think... LMAO!
Anyhow - what is the consensus...
Does it stick around?
Is it gone?
Anyhow - what is the consensus...
Does it stick around?
Is it gone?
Thanks but you and I know it's not likely to change bad behavior, especially in the old timers. It took a long time for them to get the way and it will take more than anything we say to enlighten them. They're just lost and lonely and rather silly too - make that very silly or better - pathetic. Mike
The way this whole Abbas episode has evolved has been fascinating. At first people were so kind to him, sharing experiences, offering advice, and then gradually realizing that he was playing some sort of sick game.
My 21 year old niece says he's not a spammer - he's a troll. Trolls are people who come onto groups and forums with one purpose in mind: to start a fight. And when we respond to Abbas' posts, we're giving him exactly what he wants. I think we shouldn't pay any attention to him, and maybe he'll go away.
My 21 year old niece says he's not a spammer - he's a troll. Trolls are people who come onto groups and forums with one purpose in mind: to start a fight. And when we respond to Abbas' posts, we're giving him exactly what he wants. I think we shouldn't pay any attention to him, and maybe he'll go away.
Hepatitis C Positivity May Increase Risk for End-Stage Renal Disease CME
News Author: Laurie Barclay, MD
CME Author: D
News Author: Laurie Barclay, MD
CME Author: D
7-Gene Signature Predicts Cirrhosis Risk in Patients With Chronic Hepatitis C
Laurie Barclay, MD
Information from Industry
PROTONIX
Laurie Barclay, MD
Information from Industry
PROTONIX
mike
is there anyway to put those reports in
simple laymens terms
i dont think i could read those on a good day
let alone with this dam brain fog i now have
thanks
ron
is there anyway to put those reports in
simple laymens terms
i dont think i could read those on a good day
let alone with this dam brain fog i now have
thanks
ron
Occult hepatits C virus persistence:
identification and characteristics
By Tram N.Q. Pham, PhD, and Tomasz I. Michalak, MD, PhD
Hepatitis C virus (HCV) is a single-stranded RNA virus
of the Flaviviridae family that replicates by making the
so-called
identification and characteristics
By Tram N.Q. Pham, PhD, and Tomasz I. Michalak, MD, PhD
Hepatitis C virus (HCV) is a single-stranded RNA virus
of the Flaviviridae family that replicates by making the
so-called
I think you have found the ultimate cure for spammers. My hat off to you, I tried being bitchy, being reasonable, being sarcastic, but your approach works very well. Isolate and overwhelm, I love it.
Good day's work, dude.
Willow
Good day's work, dude.
Willow
Thank you both. I had to eat or I could have gone on and on. I don't like the board junked up with the same stuff over and over again so I thought I'd add some of my stuff - I have a ton of it. Mike
Statins Slow Lung Function Decline in Smokers
Martha Kerr
Information from Industry
NSCLC Treatment StrategiesFor 1st-line chemotherapy treatment, learn more about GEMZAR
Martha Kerr
Information from Industry
NSCLC Treatment StrategiesFor 1st-line chemotherapy treatment, learn more about GEMZAR
In the present study, we found that surgical procedure, number of tumours, size of the largest tumour, vascular invasion, stage of fibrosis, and hepatic steatosis were important risk factors associated with tumour recurrence by univariate and multivariate analysis.
Desmet et al.[13] proposed a historical classification of chronic hepatitis including necroinflammatory activity and fibrosis. This scoring system of non-cancerous tissue is considered useful in predicting the risk of recurrence after complete resection of primary HCC.[2, 3] Furthermore, necroinflammatory activity and fibrosis were reported to be responsible for the development of multicentric HCC.[18] The stage of fibrosis was reported to be more important for postoperative tumour recurrence than the grade of necroinflammatory activity.[2] The present study showed that the grade of steatosis and the stage of fibrosis were independent risk factors for postoperative recurrence of HCV-associated HCC. Interestingly, the grade of steatosis did not correlate with the stage of fibrosis (data not shown). According to our data, the cumulative rates of HCC recurrence for steatosis and non-steatosis seemed similar in the first 2 years after surgery but became statistically different after 3 years. Therefore, hepatic steatosis may predict newly developed HCC and not the recurrence of the original tumour. Further investigations of the non-cancerous tissue, as well as the cancerous tissue, are necessary to evaluate postoperative tumour recurrence.
Ohata et al.[11] reported liver steatosis to be a risk factor for primary HCC in a cohort study. In this study, the tumour recurrence rate for steatosis-positive patients was significantly higher than that for steatosis-negative patients. These results suggest the possibility that liver steatosis may be a factor for carcinogenesis in HCV-related liver disease. Moriya et al.[10] reported that in animal models, HCV core protein induced hepatic steatosis, and was responsible for the development of HCC. HCV core protein increased reactive oxygen species and lipid peroxidation products, and induced genetic damage that was a cause of carcinogenesis.[19]
In contrast to these results, Kumar et al.[20] did not find that hepatic steatosis is a risk factor for HCC in patients with chronic HCV infection. The difference of the results from our study may caused by the ethnical difference. Nguyen et al.[21] suggest that liver cancer risk among patients with chronic hepatitis C and cirrhosis is four-fold higher in Asians and may be doubled in African-American men, compared with Caucasians. Therefore, the study conducted among Caucasians may need more patients than Asians to find out the difference statistically.
In Japan, an annual rate of HCC occurrence was 5-9% in HCV-related liver cirrhosis,[22,23] and multicentric occurrence was observed particularly in patients with HCV-associated HCC.[24] An annual rate of intrahepatic recurrence 2 years after the first resection was 25-35%.[25] Therefore, in those patients in whom HCC has occurred once, there is a several-fold increase in the risk of HCC as compared with those lacking a history of HCC. Thus, despite the small sample size in this study, significant differences can be observed between steatosis-positive groups and steatosis-negative groups for tumour recurrence rates.
Hepatic steatosis is commonly associated with obesity, insulin resistance, heavy alcohol consumption, and other components of metabolic syndrome.[26] Hepatic steatosis is also commonly found in subjects with chronic HCV infection, occurring in approximately 30-70%.[7-9] In addition, hepatic steatosis was associated with progression of fibrosis.[27] Both host and viral factors contribute to the development of steatosis in chronic HCV. While steatosis is more prevalent and severe in patients infected by HCV genotype 3,[28] the explanation for this effect remains unclear. Furthermore, HCV genotype 3-related steatosis was associated with a higher rate of progression of fibrosis than other genotypes-related steatosis.[29]
Overweight patients have significantly more steatosis than lean patients irrespective of viral genotype.[30] In the present study, severe steatosis (Grade 3 steatosis; >66% of hepatocytes affected) was not observed, because genotype 3 is not common in Japan, and obesity of patients in this study was not severe compared with other studies [average BMI=22.4 in this study, compared with 28.5 and 24.6 in other studies[31,32]]. Ohata et al.[11] could not find an effect for HCV genotype on hepatic steatosis, because the majority of patients in the study were infected with genotype 1. HCV genotypes were determined in 76 of 88 patients in the present study, and all were type 1 or 2. A relationship between the postoperative recurrence and HCV genotype was not detected in the present study.
Limitations of this study include the dependence on a retrospective approach and small sample size. Although there were no significant differences between the steatosis-positive group and the steatosis-negative group with respect to the background characteristics including known risk factors for HCC, the existence of several biases is unavoidable. Large numbers of prospective studies are necessary to eradicate bias.
In conclusion, hepatic steatosis at the time of curative resection might serve as a useful predictor of postoperative HCC recurrence. These results indicate that patients with underlying hepatic steatosis, as well as fibrosis require careful monitoring for the recurrence of HCC.
CLICK HERE for subscription information about this journal.
Desmet et al.[13] proposed a historical classification of chronic hepatitis including necroinflammatory activity and fibrosis. This scoring system of non-cancerous tissue is considered useful in predicting the risk of recurrence after complete resection of primary HCC.[2, 3] Furthermore, necroinflammatory activity and fibrosis were reported to be responsible for the development of multicentric HCC.[18] The stage of fibrosis was reported to be more important for postoperative tumour recurrence than the grade of necroinflammatory activity.[2] The present study showed that the grade of steatosis and the stage of fibrosis were independent risk factors for postoperative recurrence of HCV-associated HCC. Interestingly, the grade of steatosis did not correlate with the stage of fibrosis (data not shown). According to our data, the cumulative rates of HCC recurrence for steatosis and non-steatosis seemed similar in the first 2 years after surgery but became statistically different after 3 years. Therefore, hepatic steatosis may predict newly developed HCC and not the recurrence of the original tumour. Further investigations of the non-cancerous tissue, as well as the cancerous tissue, are necessary to evaluate postoperative tumour recurrence.
Ohata et al.[11] reported liver steatosis to be a risk factor for primary HCC in a cohort study. In this study, the tumour recurrence rate for steatosis-positive patients was significantly higher than that for steatosis-negative patients. These results suggest the possibility that liver steatosis may be a factor for carcinogenesis in HCV-related liver disease. Moriya et al.[10] reported that in animal models, HCV core protein induced hepatic steatosis, and was responsible for the development of HCC. HCV core protein increased reactive oxygen species and lipid peroxidation products, and induced genetic damage that was a cause of carcinogenesis.[19]
In contrast to these results, Kumar et al.[20] did not find that hepatic steatosis is a risk factor for HCC in patients with chronic HCV infection. The difference of the results from our study may caused by the ethnical difference. Nguyen et al.[21] suggest that liver cancer risk among patients with chronic hepatitis C and cirrhosis is four-fold higher in Asians and may be doubled in African-American men, compared with Caucasians. Therefore, the study conducted among Caucasians may need more patients than Asians to find out the difference statistically.
In Japan, an annual rate of HCC occurrence was 5-9% in HCV-related liver cirrhosis,[22,23] and multicentric occurrence was observed particularly in patients with HCV-associated HCC.[24] An annual rate of intrahepatic recurrence 2 years after the first resection was 25-35%.[25] Therefore, in those patients in whom HCC has occurred once, there is a several-fold increase in the risk of HCC as compared with those lacking a history of HCC. Thus, despite the small sample size in this study, significant differences can be observed between steatosis-positive groups and steatosis-negative groups for tumour recurrence rates.
Hepatic steatosis is commonly associated with obesity, insulin resistance, heavy alcohol consumption, and other components of metabolic syndrome.[26] Hepatic steatosis is also commonly found in subjects with chronic HCV infection, occurring in approximately 30-70%.[7-9] In addition, hepatic steatosis was associated with progression of fibrosis.[27] Both host and viral factors contribute to the development of steatosis in chronic HCV. While steatosis is more prevalent and severe in patients infected by HCV genotype 3,[28] the explanation for this effect remains unclear. Furthermore, HCV genotype 3-related steatosis was associated with a higher rate of progression of fibrosis than other genotypes-related steatosis.[29]
Overweight patients have significantly more steatosis than lean patients irrespective of viral genotype.[30] In the present study, severe steatosis (Grade 3 steatosis; >66% of hepatocytes affected) was not observed, because genotype 3 is not common in Japan, and obesity of patients in this study was not severe compared with other studies [average BMI=22.4 in this study, compared with 28.5 and 24.6 in other studies[31,32]]. Ohata et al.[11] could not find an effect for HCV genotype on hepatic steatosis, because the majority of patients in the study were infected with genotype 1. HCV genotypes were determined in 76 of 88 patients in the present study, and all were type 1 or 2. A relationship between the postoperative recurrence and HCV genotype was not detected in the present study.
Limitations of this study include the dependence on a retrospective approach and small sample size. Although there were no significant differences between the steatosis-positive group and the steatosis-negative group with respect to the background characteristics including known risk factors for HCC, the existence of several biases is unavoidable. Large numbers of prospective studies are necessary to eradicate bias.
In conclusion, hepatic steatosis at the time of curative resection might serve as a useful predictor of postoperative HCC recurrence. These results indicate that patients with underlying hepatic steatosis, as well as fibrosis require careful monitoring for the recurrence of HCC.
CLICK HERE for subscription information about this journal.
Final ID: 393
A Prospective, Double-Blinded Neuropsychiatric Comparison of Pegylated Interferons Alfa-2a and Alfa-2b
D. Sylvestre; 1, 2; A. Smith; 2; L. Barrett; 2; D. Greene; 2;
1. University of CA, San Francisco, Oakland, CA, USA.
2. OASIS, Oakland, CA, USA.
Abstract Body: Background: Inter-study evidence using interferon alfa as a standard suggests that pegylated interferons alfa-2a (PI2a) and alfa-2b (PI2b) may have different neuropsychiatric toxicity profiles. Because of its potential importance to the many HCV-infected patients with comorbid mental illness, we conducted a prospective, double-blinded pilot study of PI2a vs. PI2b in patients undergoing treatment for HCV. Endpoints included psychiatric discontinuations; initiation and adjustment of psychiatric medications; monthly Beck Depression Inventory (BDI) and SF-36 Quality of Life scores, and self-reported depression (D), anxiety (A), and irritability (I).
Methods: 40 patients were randomized to treatment with ribavirin and either PI2a or PI2b at standard dosing. Selfreported D, A, and I scored on a 0-10 scale were recorded weekly. The BDI and SF-36 were administered every 4 weeks.
Results: 39 subjects initiated treatment and 1 was discontinued due to inadvertent unblinding. The average age was 48, 23 (57%) were male, and 27 (67%) had genotype 1. None of these measures differed between the cohorts. 15 in
each cohort (75%) reported a pre-existing psychiatric diagnosis. 26 were taking a psychiatric medication at treatment initiation, 12 (67%) in the PI2a cohort and 14 (70%) in the PI2b cohort (p=0.55).27 (71%) completed treatment and there were 11 (29%) discontinuations. 4 patients had psychiatric discontinuations,
1 taking PI2a and 3 taking PI2b (p=0.32). New psychiatric medications were initiated in 9 (50%) taking PI2a and 14(70%) taking PI2b (p=0.18), and they were adjusted in 12 (67%) taking PI2a and 15 (75%) taking PI2b (p=0.41). BDI, SF-36, and self-reported depression, anxiety, and irritability scores were not statistically different at baseline, nor were there significant differences when analyzed on a monthly basis. However, the PI2b cohort had a significantly higher cumulative BDI score, 16.3 vs 13.1 (p=0.01), and a lower SF-36 score, 40.8 vs 48.5 (p=0.004). Additionally, those taking PI2b reported significantly higher overall depression, 2.4 vs 2.1 (p=0.04), and anxiety, 2.8 vs 2.2 (p <0.001), but
not irritability, 2.9 vs 2.7 (p=0.32).
Conclusion: This small but rigorous study provides the first direct evidence that PI2a and PI2b may elicit small but measurable differences in depression, anxiety, and quality of life during HCV treatment. It is unclear, however,
whether these will translate to meaningful differences in major neuropsychiatric outcomes. A larger study is needed to assess the magnitude of the differences in the psychiatric toxicity profiles of these medications and to assess any impact on HCV outcomes.
A Prospective, Double-Blinded Neuropsychiatric Comparison of Pegylated Interferons Alfa-2a and Alfa-2b
D. Sylvestre; 1, 2; A. Smith; 2; L. Barrett; 2; D. Greene; 2;
1. University of CA, San Francisco, Oakland, CA, USA.
2. OASIS, Oakland, CA, USA.
Abstract Body: Background: Inter-study evidence using interferon alfa as a standard suggests that pegylated interferons alfa-2a (PI2a) and alfa-2b (PI2b) may have different neuropsychiatric toxicity profiles. Because of its potential importance to the many HCV-infected patients with comorbid mental illness, we conducted a prospective, double-blinded pilot study of PI2a vs. PI2b in patients undergoing treatment for HCV. Endpoints included psychiatric discontinuations; initiation and adjustment of psychiatric medications; monthly Beck Depression Inventory (BDI) and SF-36 Quality of Life scores, and self-reported depression (D), anxiety (A), and irritability (I).
Methods: 40 patients were randomized to treatment with ribavirin and either PI2a or PI2b at standard dosing. Selfreported D, A, and I scored on a 0-10 scale were recorded weekly. The BDI and SF-36 were administered every 4 weeks.
Results: 39 subjects initiated treatment and 1 was discontinued due to inadvertent unblinding. The average age was 48, 23 (57%) were male, and 27 (67%) had genotype 1. None of these measures differed between the cohorts. 15 in
each cohort (75%) reported a pre-existing psychiatric diagnosis. 26 were taking a psychiatric medication at treatment initiation, 12 (67%) in the PI2a cohort and 14 (70%) in the PI2b cohort (p=0.55).27 (71%) completed treatment and there were 11 (29%) discontinuations. 4 patients had psychiatric discontinuations,
1 taking PI2a and 3 taking PI2b (p=0.32). New psychiatric medications were initiated in 9 (50%) taking PI2a and 14(70%) taking PI2b (p=0.18), and they were adjusted in 12 (67%) taking PI2a and 15 (75%) taking PI2b (p=0.41). BDI, SF-36, and self-reported depression, anxiety, and irritability scores were not statistically different at baseline, nor were there significant differences when analyzed on a monthly basis. However, the PI2b cohort had a significantly higher cumulative BDI score, 16.3 vs 13.1 (p=0.01), and a lower SF-36 score, 40.8 vs 48.5 (p=0.004). Additionally, those taking PI2b reported significantly higher overall depression, 2.4 vs 2.1 (p=0.04), and anxiety, 2.8 vs 2.2 (p <0.001), but
not irritability, 2.9 vs 2.7 (p=0.32).
Conclusion: This small but rigorous study provides the first direct evidence that PI2a and PI2b may elicit small but measurable differences in depression, anxiety, and quality of life during HCV treatment. It is unclear, however,
whether these will translate to meaningful differences in major neuropsychiatric outcomes. A larger study is needed to assess the magnitude of the differences in the psychiatric toxicity profiles of these medications and to assess any impact on HCV outcomes.
YOU GO GUY!!!!!!!!!!!!!!!!!!!!!!!!!!!! Woooooooo WHOOOOOOOO!!!!!!
When they realise that they are dummer than most of us here, maybe they will shut up.
Keep it up, I am still laughing.
Cajun
When they realise that they are dummer than most of us here, maybe they will shut up.
Keep it up, I am still laughing.
Cajun
whoa, Mike, you're on a roll today! Those following the ongoing saga of persistent, post-SVR, HCV infection might also be interested in a recent sudy
http://tinyurl.com/24u4r7
by Bernandin et al. They tracked individuals who had no hcv antibodies but chronic and high HCV serum levels, sequenced the HCV RNA and found that though the 5' end of the genome, which includes the short, highly conserved, stretch used for commercial HCV RNA VL tests was largely identical to that of "standard" HCV genomes , there were *large* chunks (~2000 bases) missing, from the 3' region.
The implication here is such fragmented HCV virions are functional enough to happily reproduce in the body, but somehow escape detection by the immune system (or at least antibody production). Since damage to the liver is not caused by the virus but by the body's attempt to elimninate it, these guys were also quite healthy with normal ALTs. As far as I know this is the first evidence for persistence of not fully functional hcv genomes. It's been speculated that the HCV RNA detected by Pham, Radkowski, Castillo, etc. in the cell tissue of serum UND individuals etc. could be associated with replicating but non-viable virus. Hopefully someone will get around to sequencing this persistent HCV RNA in the near future...
PS
another recent study showing that serum VL, though predictive of SVR, doesn't seem to be strongly correlated with anything else..
http://tinyurl.com/2ma4fl
http://tinyurl.com/24u4r7
by Bernandin et al. They tracked individuals who had no hcv antibodies but chronic and high HCV serum levels, sequenced the HCV RNA and found that though the 5' end of the genome, which includes the short, highly conserved, stretch used for commercial HCV RNA VL tests was largely identical to that of "standard" HCV genomes , there were *large* chunks (~2000 bases) missing, from the 3' region.
The implication here is such fragmented HCV virions are functional enough to happily reproduce in the body, but somehow escape detection by the immune system (or at least antibody production). Since damage to the liver is not caused by the virus but by the body's attempt to elimninate it, these guys were also quite healthy with normal ALTs. As far as I know this is the first evidence for persistence of not fully functional hcv genomes. It's been speculated that the HCV RNA detected by Pham, Radkowski, Castillo, etc. in the cell tissue of serum UND individuals etc. could be associated with replicating but non-viable virus. Hopefully someone will get around to sequencing this persistent HCV RNA in the near future...
PS
another recent study showing that serum VL, though predictive of SVR, doesn't seem to be strongly correlated with anything else..
http://tinyurl.com/2ma4fl
Thanks for the links. My credit card has been compromised despite the fact that I always use virtual numbers online and cash everywhere else so I can not buy the article right now. I am interested very much in reading the rest of it and seeing if anything there applies to me. I assume that if it's bad it will apply but that may be due to my heavily jaundiced viewpoint. Do you have any further ideas about this persistence? I would love to hear anything you are thinking. Mike
Mike - I emailed you the pdf, let me know if it doesn't show up. I wouldn't say there was anything worrisome about this find and I'm also curious to hear any thoughts others have on the topic. It just seems like another insight into the strange and amazingly flexible survival stragegies of this virus. The authors speculate that the function of the missing proteins is rescued by a low background level of full-length virus detected in cells but not in serum:
"The long-term stable detection of HCV subgenomes in
plasma reported here may therefore reflect the occasional
generation of intracellular replicons whose deleted structural
functions, including envelope glycoproteins, can be provided
by trans-complementation in cells co-infected with wild-type
helper HCV. Resulting subgenome RNA containing particles
released into the bloodstream from co-infected cells would be
competent for cell entry and further RNA replication into new
target cells thereby amplifying truncated genomes and sustaining
the high and chronic plasma levels seen here."
what I don't get is that if (1) only the truncated sub-genome particles are circulating in plasma, (2) these are capable of cell entry but (3) need to enter a cell co-infected with full-length, wild-type, to make up the functionality of the "missing" proteins necessary for replication (glycoprotein coat etc.) then
*how are the full-length wild-type virions getting from cell to cell?*
the observation seems to (indirectly) confirm plasma UND replication of the wild-type virus, though the authors don't actually say this. The other interesting item about the article, which was news to me, is that such sub-genomic virions have been previously reported among quite a few other viral species (west-nile, dengue, etc.)
"The long-term stable detection of HCV subgenomes in
plasma reported here may therefore reflect the occasional
generation of intracellular replicons whose deleted structural
functions, including envelope glycoproteins, can be provided
by trans-complementation in cells co-infected with wild-type
helper HCV. Resulting subgenome RNA containing particles
released into the bloodstream from co-infected cells would be
competent for cell entry and further RNA replication into new
target cells thereby amplifying truncated genomes and sustaining
the high and chronic plasma levels seen here."
what I don't get is that if (1) only the truncated sub-genome particles are circulating in plasma, (2) these are capable of cell entry but (3) need to enter a cell co-infected with full-length, wild-type, to make up the functionality of the "missing" proteins necessary for replication (glycoprotein coat etc.) then
*how are the full-length wild-type virions getting from cell to cell?*
the observation seems to (indirectly) confirm plasma UND replication of the wild-type virus, though the authors don't actually say this. The other interesting item about the article, which was news to me, is that such sub-genomic virions have been previously reported among quite a few other viral species (west-nile, dengue, etc.)
I did get the article and I thank you so much for sending it to me. I will study it carefully and, if you have no objection, I will forward it to my surgeon, although it is quite possible he's already seen it. If I or he has any additional insight I will post it here and email it to you but it may take me a while to digest it. Again Willing, thank you very much. It is rather curious that a thread that started like this one evolved to this level. It has me in a state of wonderment. Mike
Thanks for saying that but I sure ain't the best. I just try to be as decent as I can but it get hard sometimes just to be civil. Mike
Kraus MR, Al-Taie O, Schafer A, Pfersdorff M, Lesch KP, Scheurlen M.
Medizinische Klinik und Poliklinik II, Department of Gastroenterology and Hepatology, University of Wurzburg, Wurzburg, Germany. kraus_m***@****-wuerzburg.de
BACKGROUND & AIMS: Interferon-induced depression is a major complication in antiviral therapy of chronic hepatitis C. Little is known about underlying mechanisms and reliable predictive factors associated with cytokine-induced depressive symptoms. METHODS: In a cohort of 139 hepatitis C-infected outpatients treated with interferon alfa-2b, we investigated the impact of functional gene variants of the cerebral serotonin (5-HT) signalling pathway previously implicated in depression risk. Depression was monitored using the Hospital Anxiety and Depression Scale (HADS). All patients were genotyped for functional variations in the 5-HT(1A) receptor (HTR1A), 5-HT transporter (SLC6A4, 5-HTT), and tryptophan hydoxylase-2 (TPH2). RESULTS: Homozygosity for the HTR1A-1019G variant significantly increased both incidence and severity of interferon-induced depression. Maximum increases in HADS depression scores during antiviral therapy correlated with HTR1A variation (P = .011). Clinically relevant depression was significantly associated with the HTR1A-1019G genotype (P = .017; OR, 2.95). 5-HTT and TPH2 variations did not contribute significantly to the prediction of interferon-induced depression by HTR1A (sensitivity, 35.9%; specificity, 84.0%). CONCLUSIONS: Our findings suggest an impact of allelic variation in 5-HT(1A) receptor expression on the development of interferon alfa-induced depression during antiviral treatment of chronic hepatitis C. Prediction models of interferon-induced depressive symptoms based on HTR1A variation offer a perspective for an antidepressant selective serotonin reuptake inhibitor prophylaxis in patients genetically at risk for interferon-induced depression.
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