Aa
EASL, New TX guidelines. 24 weeks for RVR & BX not necessary for all 1's & 4's
Interesting news. Finally after 5 years the guidelines are changing on how to treat HCV patients. Some things that stand out is they will use RVR to have GT 1's stop at 24 weeks and BX is not automatic. I have said all along that any up to date docs already used these guidelines.
Tuesday, April 5, 2011
EASL Issues Clinical Practice Guidelines for Management of HCV
Daniel M. Keller, PhD
April 4, 2011 (Berlin, Germany) — Here at the opening session of the European Association for the Study of the Liver (EASL) 46th Annual Meeting, new guidelines were announced to help healthcare providers, patients, and interested individuals make decisions about the management of patients with acute and chronic hepatitis C virus (HCV) infections.
The guidelines encompass all aspects of the diagnosis and treatment of chronic HCV infection and address the use of diagnostic, therapeutic, and preventive techniques. They are the fifth in a series that the EASL has issued for liver diseases.
As evidenced by a wealth of clinical trial presentations that are being made here at the conference on new drugs in development to treat HCV, it is expected that many more treatments will be licensed in the next few years.
However, the guidelines issued here are restricted to therapies that have been approved at the time of publication. EASL has committed to update the guidelines on a regular basis upon approval of additional therapies.
Antonio Craxi, MD, professor of gastroenterology and internal medicine at the University of Palermo in Italy, and director of gastroenterology and hepatology at the university's Academic Department of Internal Medicine, coordinated the development of the guidelines. He discussed them in a news conference and said that part of the rationale for them is to set standards of diagnosis and treatment for specific patient profiles. They were developed by an expert panel that reviewed the scientific literature on the subject through December 2010. If clinical data were unavailable, expert experience and opinion were included.
The guidelines comprise sections on diagnosis, therapy, follow-up to therapy, measures to improve treatment success rates, and factors to consider when deciding on retreatment if therapy has failed.
Dr. Craxi emphasized that history and physical examination of the patient must be part of diagnosis, and that diagnosis cannot rely solely on serology that identifies anti-HCV antibodies or the level of HCV RNA in the blood.
"We had to . . decide on a very crucial point — whether a biopsy was still necessary to assess the severity of liver disease," Dr. Craxi said.
Although biopsy remains the reference method for assessing the degree of fibrosis, most patients dislike it, and it carries risk for complications. "It won't be acceptable to have a liver biopsy as a prerequisite for all treatment," he said, noting that it can usually be dispensed with for HCV genotypes 2 and 3, which are easier forms of the virus to eradicate with current therapy. And a biopsy is not always necessary for the more difficult-to-treat genotypes 1 and 4, since other methods such as transient elastography (FibroScan) and serum biomarkers are available to determine the degree of liver fibrosis.
Eradication of HCV Infection Is Therapeutic Goal
Eliminating virus from the body can prevent complications such as fibrosis, cirrhosis, liver cancer, and death. The desired end point of therapy is a sustained virological response, determined by undetectable HCV RNA in the blood 24 weeks after the end of therapy, Dr. Craxi noted.
The current standard approach is treatment with a combination of pegylated interferon alfa plus ribavirin. The University of Palermo investigator said large studies have shown that the 2 commercially available pegylated interferons are equivalent, and neither is recommended over the other.
He pointed out that the new guidelines consider the virological response to pegylated interferon/ribavirin to guide therapy, taking into account the speed of response and the degree of viral suppression. "For the first time, there is a clear statement that patients with a rapid response and with genotype 1 can be treated for 24 weeks [and that treatment can be extended] beyond 24 weeks for patients who have a delayed viral response."
Separate decision maps in the published guidelines, which will appear in the Journal of Hepatology, delineate response-guided therapy for genotypes 1 and 4 and for genotypes 2 and 3.
Previous American guidelines were issued more than 5 years ago, Dr. Craxi noted, and they did not involve response-guided therapy. Additionally, ribavirin dosage adjustment according to patient weight is now recommended, since heavier weight adversely affects the response to therapy.
The expert panel made recommendations for the follow-up of untreated patients with or without cirrhosis and for the retreatment of patients for whom previous therapy failed. Dr. Craxi said that patients with resistant disease might respond to some of the new small-molecule drugs currently in development, and it might be worthwhile to delay treatment for some of them until the new drugs are available, depending on their current state of health.
Mark Thursz, MD, EASL vice secretary and professor of hepatology at Imperial College, London, United Kingdom, noted that not recommending a liver biopsy for every patient is an important development for patients. "It's no longer necessary for every patient. In fact, it's probably only appropriate when there's a doubt about the contribution of different diseases," such as heavy alcohol consumption and HCV, or obesity and HCV. Response-guided therapy can also be positive for patients, sparing some of them unnecessary adverse effects if they can be treated for a shorter time. It should have a positive economic impact, as well, he noted.
Dr. Thursz said he reviewed the guidelines before publication but was not involved in their development.
Dr. Craxi reports receiving research support and lecture fees from, and taking part in clinical trials for, Roche, MSD, Siemens, and Abbott. Dr. Thursz has disclosed no relevant financial relationships.
European Association for the Study of the Liver (EASL) 46th Annual Meeting: Opening session. Presented March 31, 2011.
Source
Download PDF: http://www.easl.eu/assets/application/files/d0df9f948c85a72_file.pdf
Tuesday, April 5, 2011
EASL Issues Clinical Practice Guidelines for Management of HCV
Daniel M. Keller, PhD
April 4, 2011 (Berlin, Germany) — Here at the opening session of the European Association for the Study of the Liver (EASL) 46th Annual Meeting, new guidelines were announced to help healthcare providers, patients, and interested individuals make decisions about the management of patients with acute and chronic hepatitis C virus (HCV) infections.
The guidelines encompass all aspects of the diagnosis and treatment of chronic HCV infection and address the use of diagnostic, therapeutic, and preventive techniques. They are the fifth in a series that the EASL has issued for liver diseases.
As evidenced by a wealth of clinical trial presentations that are being made here at the conference on new drugs in development to treat HCV, it is expected that many more treatments will be licensed in the next few years.
However, the guidelines issued here are restricted to therapies that have been approved at the time of publication. EASL has committed to update the guidelines on a regular basis upon approval of additional therapies.
Antonio Craxi, MD, professor of gastroenterology and internal medicine at the University of Palermo in Italy, and director of gastroenterology and hepatology at the university's Academic Department of Internal Medicine, coordinated the development of the guidelines. He discussed them in a news conference and said that part of the rationale for them is to set standards of diagnosis and treatment for specific patient profiles. They were developed by an expert panel that reviewed the scientific literature on the subject through December 2010. If clinical data were unavailable, expert experience and opinion were included.
The guidelines comprise sections on diagnosis, therapy, follow-up to therapy, measures to improve treatment success rates, and factors to consider when deciding on retreatment if therapy has failed.
Dr. Craxi emphasized that history and physical examination of the patient must be part of diagnosis, and that diagnosis cannot rely solely on serology that identifies anti-HCV antibodies or the level of HCV RNA in the blood.
"We had to . . decide on a very crucial point — whether a biopsy was still necessary to assess the severity of liver disease," Dr. Craxi said.
Although biopsy remains the reference method for assessing the degree of fibrosis, most patients dislike it, and it carries risk for complications. "It won't be acceptable to have a liver biopsy as a prerequisite for all treatment," he said, noting that it can usually be dispensed with for HCV genotypes 2 and 3, which are easier forms of the virus to eradicate with current therapy. And a biopsy is not always necessary for the more difficult-to-treat genotypes 1 and 4, since other methods such as transient elastography (FibroScan) and serum biomarkers are available to determine the degree of liver fibrosis.
Eradication of HCV Infection Is Therapeutic Goal
Eliminating virus from the body can prevent complications such as fibrosis, cirrhosis, liver cancer, and death. The desired end point of therapy is a sustained virological response, determined by undetectable HCV RNA in the blood 24 weeks after the end of therapy, Dr. Craxi noted.
The current standard approach is treatment with a combination of pegylated interferon alfa plus ribavirin. The University of Palermo investigator said large studies have shown that the 2 commercially available pegylated interferons are equivalent, and neither is recommended over the other.
He pointed out that the new guidelines consider the virological response to pegylated interferon/ribavirin to guide therapy, taking into account the speed of response and the degree of viral suppression. "For the first time, there is a clear statement that patients with a rapid response and with genotype 1 can be treated for 24 weeks [and that treatment can be extended] beyond 24 weeks for patients who have a delayed viral response."
Separate decision maps in the published guidelines, which will appear in the Journal of Hepatology, delineate response-guided therapy for genotypes 1 and 4 and for genotypes 2 and 3.
Previous American guidelines were issued more than 5 years ago, Dr. Craxi noted, and they did not involve response-guided therapy. Additionally, ribavirin dosage adjustment according to patient weight is now recommended, since heavier weight adversely affects the response to therapy.
The expert panel made recommendations for the follow-up of untreated patients with or without cirrhosis and for the retreatment of patients for whom previous therapy failed. Dr. Craxi said that patients with resistant disease might respond to some of the new small-molecule drugs currently in development, and it might be worthwhile to delay treatment for some of them until the new drugs are available, depending on their current state of health.
Mark Thursz, MD, EASL vice secretary and professor of hepatology at Imperial College, London, United Kingdom, noted that not recommending a liver biopsy for every patient is an important development for patients. "It's no longer necessary for every patient. In fact, it's probably only appropriate when there's a doubt about the contribution of different diseases," such as heavy alcohol consumption and HCV, or obesity and HCV. Response-guided therapy can also be positive for patients, sparing some of them unnecessary adverse effects if they can be treated for a shorter time. It should have a positive economic impact, as well, he noted.
Dr. Thursz said he reviewed the guidelines before publication but was not involved in their development.
Dr. Craxi reports receiving research support and lecture fees from, and taking part in clinical trials for, Roche, MSD, Siemens, and Abbott. Dr. Thursz has disclosed no relevant financial relationships.
European Association for the Study of the Liver (EASL) 46th Annual Meeting: Opening session. Presented March 31, 2011.
Source
Download PDF: http://www.easl.eu/assets/application/files/d0df9f948c85a72_file.pdf
Copyman - no doubt about that on some docs - my second one could probably do that. My first one, not so much. The kind of docs that can are not as common as I'd like but thankfully there are some good ones out there.
"I think that will be up to the insurance companies and medical facilities to work out. Transient elastography (TE) and blood tests when used to determine the degree of fibrosis is more costly then a biopsy. "
Perhaps it depends where and under what circumstances as to the cost factor. This is a study done in France and it seems the Fibroscan comes out as the cheaper option...though I'm not sure about the better option, at least not all the time. It certainly has it's place and I was happy with my Fibroscan done at EOT and felt no need for a biopsy to back it up but I had very little damage going in.
http://www.urc-eco.fr/sites/www.urc-eco.fr/IMG/pdf/POSTER_Isabelle_1_3_.pdf
Perhaps it depends where and under what circumstances as to the cost factor. This is a study done in France and it seems the Fibroscan comes out as the cheaper option...though I'm not sure about the better option, at least not all the time. It certainly has it's place and I was happy with my Fibroscan done at EOT and felt no need for a biopsy to back it up but I had very little damage going in.
http://www.urc-eco.fr/sites/www.urc-eco.fr/IMG/pdf/POSTER_Isabelle_1_3_.pdf
Here are my notes for the "EASL Clinical Practice Guidelines: Management of hepatitis C
virus infection."
1. Based on the importance of an RVR, does a low pre-tx VL hold any weight anymore?
"In patients with a rapid virologic response (RVR) and low baseline viral load (<400,000–800,000 IU/ml), treatment for 24 weeks (genotypes 1 and 4) or 12–16 weeks (genotypes
2/3) can be considered. If negative predictors of response (i.e. advanced fibrosis/cirrhosis, metabolic syndrome, insulin resistance, hepatic steatosis) are present, evidence for equal efficacy of shortened treatment is insufficient."
2. Will tx be discontinued if no cEVR/EVR at 12 weeks, or will extending still be considered, especially beyond 48 weeks?
"The following treatment durations should be applied according to the virological response, regardless of the HCV genotype: (i) Patients infected with HCV genotype 1 who have an RVR should be treated for 24 weeks if they have a low baseline viral level, as suggested by a recent meta-analysis. As uncertainties remain as to which threshold should be used
to distinguish between low and high baseline HCV RNA levels, patients infected with HCV genotype 1 (and possibly also those infected with genotype 4) with a baseline viral level below 400,000–800,000 IU/ml should be treated for 24 weeks, whereas it is reasonable to prolong therapy for a total of 48 weeks in patients with a higher baseline
HCV RNA level.
(ii) Patients infected with HCV genotype 1 (and possibly also those infected with genotype 4) and EVR should be treated for 48 weeks.
(iii) Patients with genotype 1 and a delayed virological response (DVR) can be treated for 72 weeks in the hope of minimizing the risk of relapse, provided that their HCV RNA is undetectable at week 24. Insufficient data exist for other genotypes.
(iv) In patients infected with HCV genotypes 2 and 3 with an RVR and low baseline viral load (<400,000–800,000 IU/ ml), shortening of treatment duration to 16 weeks can be
considered at the expense of a slightly higher chance of post-treatment relapse.
(v) In patients with HCV genotypes 2 and 3 who have advanced fibrosis, cirrhosis or cofactors affecting response (insulin resistance, metabolic syndrome, non-viral steatosis)
shortening of treatment duration to 16 weeks should not be considered even if they have low baseline viral and RVR, due to insufficient evidence for equivalent efficacy.
(vi) Patients with genotypes 2 and 3 and either EVR or DVR or with negative cofactors affecting response could be treated for 48 or 72 weeks, respectively, provided that their HCV RNA is undetectable at week 24."
3. Will cirrhotics have different guidelines (there always seems to be a disclaimer for us)?
All treatment for cirrhotics is similar to past protocols due to reduced chance of SVR.
Assessment of liver disease severity is recommended prior to therapy. Identifying patients with cirrhosis is of particular importance, as their likelihood of responding to therapy and post-treatment prognosis are altered, and surveillance for HCC is required. Assessment of the stage of fibrosis by biopsy is not required in patients with clinical evidence of cirrhosis. Since significant fibrosis may be present in patients with repeatedly normal ALT, evaluation
of disease severity should be performed regardless of ALT patterns. Endoscopy to rule out esophageal varices and portal hypertension should be performed in patients with known
cirrhosis."
"Although decompensated patients should usually not be treated, treatment of patients with advanced liver disease (Child B cirrhosis) whose parameters may lie below label recommendations may be feasible in experienced centers under careful monitoring.
Recommendations
(1) Patients with compensated cirrhosis should be treated, in the absence of contraindications, in order to prevent short to mid-term complications.
(2) Assiduous monitoring and management of side-effects, especially those linked to portal hypertension and hypersplenism, is required. Growth factors are particularly useful
in this group.
(3) Patients with cirrhosis should undergo regular surveillance for HCC, irrespective of SVR."
4. Will Fibroscans become more widely available in lieu of bx's?
I think that will be up to the insurance companies and medical facilities to work out. Transient elastography (TE) and blood tests when used to determine the degree of fibrosis is more costly then a biopsy.
Cheers
Hectorsf
virus infection."
1. Based on the importance of an RVR, does a low pre-tx VL hold any weight anymore?
"In patients with a rapid virologic response (RVR) and low baseline viral load (<400,000–800,000 IU/ml), treatment for 24 weeks (genotypes 1 and 4) or 12–16 weeks (genotypes
2/3) can be considered. If negative predictors of response (i.e. advanced fibrosis/cirrhosis, metabolic syndrome, insulin resistance, hepatic steatosis) are present, evidence for equal efficacy of shortened treatment is insufficient."
2. Will tx be discontinued if no cEVR/EVR at 12 weeks, or will extending still be considered, especially beyond 48 weeks?
"The following treatment durations should be applied according to the virological response, regardless of the HCV genotype: (i) Patients infected with HCV genotype 1 who have an RVR should be treated for 24 weeks if they have a low baseline viral level, as suggested by a recent meta-analysis. As uncertainties remain as to which threshold should be used
to distinguish between low and high baseline HCV RNA levels, patients infected with HCV genotype 1 (and possibly also those infected with genotype 4) with a baseline viral level below 400,000–800,000 IU/ml should be treated for 24 weeks, whereas it is reasonable to prolong therapy for a total of 48 weeks in patients with a higher baseline
HCV RNA level.
(ii) Patients infected with HCV genotype 1 (and possibly also those infected with genotype 4) and EVR should be treated for 48 weeks.
(iii) Patients with genotype 1 and a delayed virological response (DVR) can be treated for 72 weeks in the hope of minimizing the risk of relapse, provided that their HCV RNA is undetectable at week 24. Insufficient data exist for other genotypes.
(iv) In patients infected with HCV genotypes 2 and 3 with an RVR and low baseline viral load (<400,000–800,000 IU/ ml), shortening of treatment duration to 16 weeks can be
considered at the expense of a slightly higher chance of post-treatment relapse.
(v) In patients with HCV genotypes 2 and 3 who have advanced fibrosis, cirrhosis or cofactors affecting response (insulin resistance, metabolic syndrome, non-viral steatosis)
shortening of treatment duration to 16 weeks should not be considered even if they have low baseline viral and RVR, due to insufficient evidence for equivalent efficacy.
(vi) Patients with genotypes 2 and 3 and either EVR or DVR or with negative cofactors affecting response could be treated for 48 or 72 weeks, respectively, provided that their HCV RNA is undetectable at week 24."
3. Will cirrhotics have different guidelines (there always seems to be a disclaimer for us)?
All treatment for cirrhotics is similar to past protocols due to reduced chance of SVR.
Assessment of liver disease severity is recommended prior to therapy. Identifying patients with cirrhosis is of particular importance, as their likelihood of responding to therapy and post-treatment prognosis are altered, and surveillance for HCC is required. Assessment of the stage of fibrosis by biopsy is not required in patients with clinical evidence of cirrhosis. Since significant fibrosis may be present in patients with repeatedly normal ALT, evaluation
of disease severity should be performed regardless of ALT patterns. Endoscopy to rule out esophageal varices and portal hypertension should be performed in patients with known
cirrhosis."
"Although decompensated patients should usually not be treated, treatment of patients with advanced liver disease (Child B cirrhosis) whose parameters may lie below label recommendations may be feasible in experienced centers under careful monitoring.
Recommendations
(1) Patients with compensated cirrhosis should be treated, in the absence of contraindications, in order to prevent short to mid-term complications.
(2) Assiduous monitoring and management of side-effects, especially those linked to portal hypertension and hypersplenism, is required. Growth factors are particularly useful
in this group.
(3) Patients with cirrhosis should undergo regular surveillance for HCC, irrespective of SVR."
4. Will Fibroscans become more widely available in lieu of bx's?
I think that will be up to the insurance companies and medical facilities to work out. Transient elastography (TE) and blood tests when used to determine the degree of fibrosis is more costly then a biopsy.
Cheers
Hectorsf
I have commented many times on this forum that a good liver doc can tell from Labs and Physical exam "close" to what stage fibrosis you are at. I had a top hep doc look at my labs feel my liver and told me flat out I was a stage 1. Damn if he wasn't dead on! I ended up having a BX, fibroScan & fibroSure....ALL stage 1.
Point is a good doc has seen enough labs and felt enough livers to know. Don't ask me how but they are right 85-90% of the time. Same % as the accuracy of a single core BX.
Strange but true.
Point is a good doc has seen enough labs and felt enough livers to know. Don't ask me how but they are right 85-90% of the time. Same % as the accuracy of a single core BX.
Strange but true.
Crap...so unclear...my doc is against drug funding for treatment for Stage 1 and I'm for drug funding for treatment for Stage 1.
willbb: I know Toronto is the centre of the universe for those in Toronto (just hadta throw that one in there :), but wondering how often Fibroscan is really used outside of that? Did your doc say? It's my impression that while TWH as a major liver centre uses them, they're not in widespread use outside of major centres like that and biopsy is still the main diagnostic method across Canada.
Overall, my concern is on what criteria EASL came up with their hotly debated recommendation that biopsy is not necessary prior to treatment and that fibroscan and other serum markers can replace biopsy. Within a publicly funded healthcare environment, docs take those things into account and I'm wondering how much of that kind of consideration influenced this recommendation. Case in point, is my own bone of contention with withholding drug funding for persons with HCV at Stage 1 in Ontario. My respected doc and I disagree on that one, him against it and me for it and his reason? Our healthcare system can't sustain it he says so the funding should go to the ones most in need. I happen to see a definite ROI on treating Stage 1 but that's a whole other matter. Case in point his that his opinion is influenced by the cost burden on the healthcare system and I wonder how much of EASL's recommendation on pre-treatment biopsy is influenced by the same.
Until fibroscans become more available and more accurate, I don't see them becoming widely adopted in place of biopsy for awhile.
Overall, my concern is on what criteria EASL came up with their hotly debated recommendation that biopsy is not necessary prior to treatment and that fibroscan and other serum markers can replace biopsy. Within a publicly funded healthcare environment, docs take those things into account and I'm wondering how much of that kind of consideration influenced this recommendation. Case in point, is my own bone of contention with withholding drug funding for persons with HCV at Stage 1 in Ontario. My respected doc and I disagree on that one, him against it and me for it and his reason? Our healthcare system can't sustain it he says so the funding should go to the ones most in need. I happen to see a definite ROI on treating Stage 1 but that's a whole other matter. Case in point his that his opinion is influenced by the cost burden on the healthcare system and I wonder how much of EASL's recommendation on pre-treatment biopsy is influenced by the same.
Until fibroscans become more available and more accurate, I don't see them becoming widely adopted in place of biopsy for awhile.
for starters it would be nice if treating physicians across the country would make an
effort to monitor response pattern of their patients with the most sensitive RNAs during
the first 12wks FREQUENTLY to catch time of true UND status.
effort to monitor response pattern of their patients with the most sensitive RNAs during
the first 12wks FREQUENTLY to catch time of true UND status.
It seems more and more that the critical point is getting that RVR. I wonder how the IL28B test will be used in conjunction with the rest of the diagnostic tests and response guided therapy. And if higher dosed SOC may be used for some in the early weeks in addition to the DAA's.
Interestting stuff......
Interestting stuff......
I guess if the direction away from biopsy it is more the result of the availability of fibroscan (not widely available in the U.S.) than it is to the new meds. So, what may work for the EASL may not work for the USL.
Hi Pam...I can only comment on what the Hepa"s have told me about your questions2) and 4)
It seems they are finding more and more evidence that extending treatment to 72weeks is becoming a thing of the past. That the increased success rate was minimal over and above the 48 weeks,and I guess with the intro of the DAA's even moreso.
Fibroscans are used in Canada now on a frequent basis,altho still in conjunction with a biopsy. However my own biopsy correlated with the exact same result as the fibro.
My doc feels as the technology improves in the future it could make the biopsy redundant.
I guess just a docs opinion ,however interesting just the same..
Will
Man, what changes in the past few years....
I understand these are "guidelines', but it does leave me with a few unanswered questions if anyone out there has any insight...
1. Based on the importance of an RVR, does a low pre-tx VL hold any weight anymore?
2. Will tx be discontinued if no cEVR/EVR at 12 weeks, or will extending still be considered, especially beyond 48 weeks?
3. Will cirrhotics have different guidelines (there always seems to be a disclaimer for us)?
4. Will Fibroscans become more widely available in lieu of bx's?
Interesting stuff and no doubt, still in flux.
I understand these are "guidelines', but it does leave me with a few unanswered questions if anyone out there has any insight...
1. Based on the importance of an RVR, does a low pre-tx VL hold any weight anymore?
2. Will tx be discontinued if no cEVR/EVR at 12 weeks, or will extending still be considered, especially beyond 48 weeks?
3. Will cirrhotics have different guidelines (there always seems to be a disclaimer for us)?
4. Will Fibroscans become more widely available in lieu of bx's?
Interesting stuff and no doubt, still in flux.
Have an Answer?
You are reading content posted in the Hepatitis C Community
Learn about this treatable virus.
Getting tested for this viral infection.
3 key steps to getting on treatment.
4 steps to getting on therapy.
What you need to know about Hep C drugs.
How the drugs might affect you.
These tips may up your chances of a cure.
A list of national and international resources and hotlines to help connect you to needed health and medical services.
Herpes sores blister, then burst, scab and heal.
Herpes spreads by oral, vaginal and anal sex.
STIs are the most common cause of genital sores.
Condoms are the most effective way to prevent HIV and STDs.
PrEP is used by people with high risk to prevent HIV infection.
