What is the percentage that relapse from SVR12 to 24?

[Jorah]

Just curious because there must be a reason some doctors are going from 12 to 24 in declaring cure.

Thank you

[Mike]

This is a hard topic to research and several factors need to be considered: First, reinfection accounts for a large percentage of those who attained a SVR12-24 and test positive after a protracted aviremia status. Risk for reinfection/HCV contraction must also be considered.

When looking at 5-year relapse rates, the following is noted:

The  "incidence rates led to estimated 5-year recurrence rates of 0.95%, 10.67%, and 15.02% in the low-risk, high-risk, and coinfection groups, respectively. Thus, despite higher recurrence rates in those with identified ongoing risk behaviors and/or HIV infection, SVR is durable, and the great majority of patients have SVR at 5 years post-treatment.

https://academic.oup.com/cid/article/62/6/683/2462988/Risk-of-Late-Relapse-or-Reinfection-With-Hepatitis

Best wishes, Mike

[Jorah]

Thank you Mike. Very interesting ..I thought that before... at the time of interferon they waited 6 months to declare cure. Then went to 12 and appears now they're going back to 24, I wonder if the 12 weeks are not holding well 

[Gaj]

Hi Jorah,

With the old peg/riba treatments 24 weeks was considered the gold standard but these DAAs give similar success rates at 12 weeks and much better ongoing which was why this is generally seen as the new 'cure' timing. The figures for sofosbuvir* based treatments are that about 99.7% who are SVR12 will go on to reach SVR24. Unfortunately that leaves 0.3% who don't but we should remember this small group may include reinfections so assuming you aren't in an at risk group such as IDU then your odds are probably even better. I haven't seen doctors as a group changing their position regarding what is considered a cure but suspect that it is much like monitoring while on treatment where some doctors will want more testing done than others....although it is natural that any doctor who has experienced a patient relapse will probably be more cautious.

Of the 779 patients with an SVR12, 777 (99.7%) also achieved an SVR24,

CONCLUSION:
Data from phase III studies demonstrate that with SOF-based regimens, with or without interferon, SVR12 and SVR24 correlate closely. Thus, SVR12 can be used effectively to determine "cure" rates in trials and in clinical practice.

https://www.ncbi.nlm.nih.gov/pubmed/25314116

Having said the above, my current treatment finishes tomorrow which means that I will know my SVR12 results in August. Assuming I am undetected at that time I will go forward with confidence of cure but will still check again at 24 weeks just for my own reassurance.


* (sorry, I don't have non-sofosbuvir results but believe they are fairly similar)

[Jorah]

Thanks Gaj  lets cross fingers for you ..wish you the best.
I'm also 3a, today its 2 weeks with Epclusa, hopefully it will be the first and last TX. But I know how insidious this virus could be..I've had it for a long time too..that's what worries me.
I will also feel safer at 24 weeks, I know I'll be happy at 12 (if I get there) but I know it will be in the back of my mind...and knowing how much of a worrier I am I'll feel even safer at 9 months....

But thanks for the information...

[Mike]

One of the theories of relapse after protracted SVR is that the HCV virus may hide in a small pool within the nervous system (much like HIV or the herpes virus), only to reappear at a later date. The virus may also mutate and become undetectable only to mutate back to a detectable form years later.

These theories arise from cases were reinfection is ruled out by viral DNA analysis (secured from the original infection) and then the original virus (confirmed by DNA) returns after a protracted absence. In these rare cases, the HCV may very well "hide."

Best wishes, Mike

[Gaj]

Hi Mike,

I suspect you mean viral RNA analysis rather than DNA? My understanding is that this testing only completely rules out relapse with the original virus if another genotype/subtype is determined but it still leaves somewhat of a question mark for those who redetect for the original genotype. In some cases of rare genotypes or viral mutations this may be a good clue to relapse but still isn't definitive.

While the theories you mention have been suggested as possible causes of unexplained relapse they are just theories that have been put forward, there is no solid evidence yet to support them. In the case of mutating then mutating back, that would not result in being undetectable during RNA testing but it is possible that a resistant mutation could be insufficiently "fit" to replicate to levels able to be detected with our current assays. If it was then to mutate again to a more "fit" form it may have potential to replicate at sufficient levels to become detectable but, again, this is just theory.

Where does that leave us as patients? Well, I think the science shows that SVR12 is a robust measure for DAAs and at least comparable with the older SVR24 standard but I understand all too well that for some of us (and our doctors) there will be a little nervousness and a desire to get SVR24 tests just to make absolutely sure we aren't in the 0.3% regardless of our risk profile.

[Mike]

When reinfection is ruled out, a "hidden  pool" or "mutation" thesis seems very probable - especially, when the original virus (verified through genetic testing) reappears years after aviremia status is documented.

Best wishes, Mike

[Mugwump]

When reinfection is ruled out, a "hidden  pool" or "mutation" thesis seems very probable - especially, when the original virus (verified through genetic testing) reappears years after aviremia status is documented.

Best wishes, Mike

It would be scary indeed if the rna structure of HCV could act like a rotating clock and mutate to a form that can encapsulate go dormant and not break down, then over time resolve back to a viable virus. This, in a way is how spores work in nature but they are a based upon much more complicated DNA mechanisms that then go on to create much more complicated organisms. Although in host cyclical mutations that are not deadly to the virus itself might very well be part of the mechanisms of an active infection to trick the human immune system. And could be part of the reasons why HCV is so hard for the immune system to remove once it has reached a more advanced state of infection. 

It is known that the encapsulation of HCV regardless of genotype breaks down in the body quite quickly and this is why it needs to get to a suitable host cell inject itself and replicate very quickly or the body will simply discard it. Where it might hide yet remain intact hidden from the bodies mechanisms of garbage disposal and O² exposure, is a matter of debate. One suspected place is in the aqueous humor of the eyes. However the virus ebola, which has been detected in the human eye post cure, is not as susceptible to being broken down by exposure to O² in the blood and must be dealt with by the human immune system very quickly indeed or the infected individual has little chance of recovery.

It seems that HCV on the other hand cannot survive long in the body if it is not in constant replication in the liver. Here is hoping that there are indeed no post svr relapses possible with HCV! 

Cheers
Eric