Saturday, May 12, 2018

Controversy over Cochrane Review on HCV Direct-acting antivirals

All Updates: Controversy over Cochrane Review on HCV Direct-acting antivirals
May 16, 2018
A review by the Cochrane Collaboration published June 6, 2017/updated September 8 2017, cast doubt on the effectiveness of new hepatitis C treatments, on May 12, 2018, BMJ published; Do direct acting antivirals cure chronic hepatitis C ? by Cochrane author Janus Christian Jakobsen. BMJ talk medicine also aired this disturbing podcast with Jakobsen; New antivirals for Hepatitis C - what does the evidence prove? On May 16, 2018 the experts weighed in, read the response: Experts Respond To Latest BMJ Article: Do direct acting antivirals cure chronic hepatitis C?

On Twitter
On Twitter, Henry E. Chang has kept the HCV community updated since 2017, pointing out each expert response to the Cochrane review, view his latest tweet about the above mentioned podcast, here. When Cochrane's HCV DAA review was originally published, the European Association for the Study of the Liver (EASL) published a response, view all history and rebuttals at the bottom of this post.

March 3, 2018 - Cochrane Review Of HCV Drugs - The Controversy Continues

On This Blog:
View each expert rebuttal and ongoing controversy 
Rebuttal over Cochrane Review of DAAs

Nov 15, 2017
The Cochrane Review Conclusion for Hepatitis C DAA Therapies Is Wrong
Welcome, Autumn is just a day away, as the season changes so did one systematic review, one that was highly debated by researchers, clinicians, and HCV advocates this summer.  This past June/2017 a Cochrane Review concluded that achieving SVR (cure) for patients using hepatitis C direct-acting antivirals (DAAs) doesn't correlate with any long term benefits. Soon a Guardian article was in widespread circulation across social networks, with this glaring headline; Hepatitis ‘wonder drug’ may be clinically ineffective, say experts. Patients were confused, experts disappointed, and the HCV community was blindsided.

Follow Henry E. Chang
on Twitter
The Controversy Is Archived On Twitter
While advocates and clinicians were in the process of writing a rebuttal, Henry E. Chang put together a nice collection of tweets during the controversy: "Reactions from Hepatitis C Community on a Recent Cochrane Review of DAAs." Thank you for continuing to make the conversation easy to follow, especially for patients.

New On Twitter - Cochrane Update
Updated Nov 15, 2017
The Cochrane Review Conclusion for Hepatitis C DAA Therapies Is Wrong

*Article shared by Henry E. Chang‏ today on Twitter.


Oct 19, 2017
Another update from Mr. Chang: "Benefits of Direct-Acting Antivirals for Hepatitis C," published in Annals of Internal Medicine.
In light of the World Health Organization and National Academies of Sciences, Engineering, and Medicine goals to eliminate HCV by 2030 (9), we believe the Cochrane review does a grave disservice to these efforts and to patients living with chronic HCV infection
September 20, 2017
Yesterday on Twitter we were updated, again thanks to Henry E. Chang.
Recently, authors of Cochrane DAA review "changed" their conclusions but remain amazingly tone-deaf to what HCV community & experts are saying.
View the tweet here, and changed conclusions with links below.

Full Text
A message from Mr. Chang with the full-text Cochrane review articles http://jmp.sh/qF4tI1Y (pub 2) and http://jmp.sh/mma5f2c (pub 3).

Changed Conclusions - September 18, 2017
Version 3
Direct-acting antivirals for chronic hepatitis C
Janus C Jakobsen, Emil Eik Nielsen, Joshua Feinberg, Kiran Kumar Katakam, Kristina Fobian, Goran Hauser, Goran Poropat, Snezana Djurisic, Karl Heinz Weiss, Milica Bjelakovic, Goran Bjelakovic, Sarah Louise Klingenberg, Jian Ping Liu, Dimitrinka Nikolova, Ronald L Koretz, Christian Gluud

First published:
Editorial Group: Cochrane Hepato-Biliary Group
DOI: 10.1002/14651858.CD012143.pub3  View/save citation
Cited by (CrossRef): 0 articles Last updated
Authors' conclusions
The evidence for our main outcomes of interest come from short-term trials, and we are unable to determine the effect of long-term treatment with DAAs. The rates of hepatitis C morbidity and mortality observed in the trials are relatively low and we are uncertain as to how DAAs affect this outcome. Overall, there is very low quality evidence that DAAs on the market or under development do not influence serious adverse events. There is insufficient evidence to judge if DAAs have beneficial or harmful effects on other clinical outcomes for chronic HCV. Simeprevir may have beneficial effects on risk of serious adverse event. In all remaining analyses, we could neither confirm nor reject that DAAs had any clinical effects. DAAs may reduce the number of people with detectable virus in their blood, but we do not have sufficient evidence from randomised trials that enables us to understand how SVR affects long-term clinical outcomes. SVR is still an outcome that needs proper validation in randomised clinical trials.

Initial Conclusions - June 6, 2017
Version 2
Janus C Jakobsen, Emil Eik Nielsen, Joshua Feinberg, Kiran Kumar Katakam, Kristina Fobian, Goran Hauser, Goran Poropat, Snezana Djurisic, Karl Heinz Weiss, Milica Bjelakovic, Goran Bjelakovic, Sarah Louise Klingenberg, Jian Ping Liu, Dimitrinka Nikolova, Ronald L Koretz, Christian Gluud

First published:
Editorial Group: Cochrane Hepato-Biliary Group
DOI: 10.1002/14651858.CD012143.pub2

Authors' conclusions
Overall, DAAs on the market or under development do not seem to have any effects on risk of serious adverse events. Simeprevir may have beneficial effects on risk of serious adverse event. In all remaining analyses, we could neither confirm nor reject that DAAs had any clinical effects. DAAs seemed to reduce the risk of no sustained virological response. The clinical relevance of the effects of DAAs on no sustained virological response is questionable, as it is a non-validated surrogate outcome. All trials and outcome results were at high risk of bias, so our results presumably overestimate benefit and underestimate harm. The quality of the evidence was very low.


Janus C Jakobsen, Emil Eik Nielsen, Joshua Feinberg, Kristina Fobian, Kiran Kumar Katakam, Goran Hauser, Goran Poropat, Snezana Djurisic, Karl Heinz Weiss, Milica Bjelakovic, Goran Bjelakovic, Sarah Louise Klingenberg, Jian Ping Liu, Dimitrinka Nikolova, Ronald L Koretz, Christian Gluud
Article first published online: 5 Apr 2016 | DOI: 10.1002/14651858.CD012143

The Experts Weigh In: Rebuttals
The European Association for the Study of the Liver (EASL) published a response to the Cochrane Systematic Review, as did the Lancet in this June editorial, and in the July issue of the Lancet; What is the impact of treatment for hepatitis C virus infection? The American Association for the Study of Liver Diseases (AASLD) and Infectious Diseases Society of America (IDSA) put out this statement. In Australia a joint Position Statement was released by Australian Health Organisations urging medical professionals and patients not to be influenced by the report. Here is an Australian podcast as well; The Cochrane Collaboration assessment of hepatitis C drug trials comes under review from our resident hep C expert Carla Treloar. In addition Hepatitis C Trust responded with concern over media coverage, citing a Guardian article. Finally, under letters the Guardian published; Hepatitis C antiviral drugs are effective, with this subtitle, "The Cochrane analysis casting doubt on this life-saving therapy is flawed and may deter patients from seeking it, say clinicians and scientists."

Moving on, Lucinda K. Porter explained Cochrane’s findings in an easy to read article: Horrendous Hepatitis Headlines. Published over at ACGBLOG at the end of June, experts wrote; The Cochrane Review Conclusion for Hepatitis C DAA Therapies is Wrong.  MedPage Today's article was all about a show of support from the medical community and advocates; Hep C Experts Condemn Cochrane Review Dissing Direct Antivirals. Commentary was offered over at HIV and ID Observations; Mystifying Cochrane Library Review on HCV Therapy Elicits Strong Response from IDSA and at Healio; IDSA, AASLD critical of Cochrane review of HCV drugs, as well. 

Recommended Reading
Justin Chan • Neliswa Gogela • Hui Zheng • Sara Lammert • Tokunbo Ajayi • Zachary Fricker • Arthur Y. Kim • Gregory K. Robbins • Raymond T. Chung
Treatment of chronic HCV with modern DAA therapy was associated with a significant improvement in LSM by VCTE measurement, suggesting possible early improvement in liver fibrosis along with resolution of inflammation over the first year after treatment completion....
Link Tweeted By @HenryEChang

Treatment with DAAs reduces the risk of mortality in the first 18 months after the completion of treatment
Michael Carter
Published:10 August 2017
The study – published in Clinical Infectious Diseases – matched people who received therapy with all-DAA regimens with untreated controls. Mortality rates in the first 18 months after therapy were significantly lower among people who received DAAs. After controlling for other factors, treatment with DAAs was associated with a 57% reduction in the risk of death....

May 1, 2018 |
Reduced Risk for Hepatocellular Carcinoma After Successful Anti-HCV Therapy in Patients with Cirrhosis 
Atif Zaman, MD, MPH reviewing Calvaruso V et al. Gastroenterology 2018 Apr 12
There is now ample evidence to support this treatment benefit...

Photo of Mr. Chang gently borrowed from his twitter feed, thinking he sort of looks like a superhero. Well, he is and does to me!
Tina

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