Liver Disease with Undetectable HCV RNA

[dointime]

People infected with HCV (as indicated by antibodies in the blood) who have an undetectable viral load are usually considered to have inactive disease, and undetectable HCV RNA six months after completion of treatment is regarded as a cure. But a study in the December 2008 Hepatology suggests hidden HCV may still cause liver disease progression. M. Hoare and colleagues studied 172 HCV antibody positive but HCV RNA negative individuals who underwent liver biopsies between 1992 and 2000. After 102 were excluded for having other possible causes of liver damage, the remaining 70 participants were analyzed after a median seven years of follow-up.

Within this group, 5.7% became HCV RNA positive during follow-up, but the rest had continued undetectable viral load. Only five participants had normal liver biopsies; 82% had some fibrosis, with 24% having moderate to advanced fibrosis (Ishak stage 2-3). HCV RNA negative individuals had fewer CD4 T-cells and more CD8 T-cells than uninfected control subjects, but the same number as patients with detectable viral load. These findings suggest that HCV antibody positive people with undetectable HCV RNA have an ongoing immune response in the liver, supporting the view that the virus may persist in the liver in a majority of these cases.

[Rockerforlife]

The word occult actually means 'hidden'...this is a very interesting thread...this virus is insidus...evil all the way....it even hides in 'steatlh mode' doining its dirty work..thats if the studies on this topic are real and accuate...a little depressing indeed...but the goods news is....if one does get SVR....odds are very high one will die from a gun shot living in a big city or killed by a moose in newfoundland

ive be having a beer the day i SVR...life is too dammn short

[geterdone]

Very interesting topic indeed, replication below detectable limits and persistent damage over a longer period of time. One would have to wonder if after being hammered by the boosted interferon during treatment that the virus had adapted to replicate at just above the threshold of its extinction.

jasper

[dointime]

"There's some glimmer of hope that  IFN-assisted HCV reduction is more effective than spontaneous"

This brings the whole question of 'how important is interferon in hepC tx' right back into focus.

I believe that the whole vaccine approach was predicated on some people being able to have spontaneous clearance.  If this is in fact a myth then will vaccines ever be effective enough without interferon?

What about the ideal of being able to treat with a cocktail of drugs like for HIV, without using riba or inf.?  It's all about whether it is possible to stop replication 100% and over time that's the end of it, or whether it will always be necessary to enlist the immune system (and inf.) for total clearance.  

Well, lots of speculation and big implications for tx going forward, but no answers as yet.  Very frustrating,

dointime

[willing]

thanks for posting - an interesting addition to the unfolding story. Unlike some of the recent technical lab-oriented,did/did-not mitogen stimulate PBMC skirmishes, it presents data with much broader implications. Basically, it sounds as if there's a *lot* of people out there who may think they cleared spontaneously but are heading down the same path as those with chronic infection (82% with biopsy-demonstrated fibrosis) albeit at a slower pace.

The methods section emphasizes they were careful to exclude all patients in which an alternate cause of liver diseases could be suspected (weight,alcohol,HBV, etc.).

From their conclusions:
"With the aid of liver biopsy in all of these patients and critically, careful subsequent exclusion of all patients with a possible alternative cause of chronic liver disease, we have been able to challenge the view that nonviremic HCV-exposed patients have resolved infection. First, viremia was detected eventually in 5.7% of this group, a proportion that may increase with time; second, just 7.5% of patients had normal histology; third, 92% of patients had inflammation within the liver, while 82% had fibrosis, which in about a quarter would have been sufficient to prompt consideration of antiviral therapy if the patients had been viremic; finally, when cases without viremia were compared with viremic patients matched for grade of inflammation and stage of fibrosis, the phenotype of the inflammatory infiltrate was similar and distinct from that in healthy controls."

None of these patients had been exposed to IFN. What bearing does this have for SVRs? There's some glimmer of hope that  IFN-assisted HCV reduction is more effective than spontaneous : 5.7% is way higher than the SVR durability stats usually reported. They do cite one 2006 study in which 11.8% of SVRs relapsed but I think there's much more data going the other way.  

Overall, I think this makes a pretty good case for an eventual post-SVR bx, not so much to check on fibrosis regression as to check presence/absence of inflammatory infiltrate

"Perhaps the most important question to address in this cohort is why such cases have lower levels of viral replication. The long-term histology in those treated successfully with pegylated interferon- and ribavirin will be of interest in this context, because loss of the inflammatory infiltrate would be consistent with eradication of HCV, while ongoing inflammation, as in this series, would be indicative of low-level HCV replication."

[dointime]

I was dismayed to read this study.  I've been following the debate here on the board about whether the virus persists even after SVR and naturally I didn't want that to be true.  However I had to admit that the jury is still out on it and more studies need to be done.  So when I came across this study I felt it was important to add it to the pool of knowledge we have on the subject.

On a pragmatic level I agree with you Mike, it is surely better to be SVR than not.  On a psychological level, the idea that I might never be rid of this virus, even if I SVR, is hard to take, but it could be the reality.  This one study does not settle the question but I think any advancement is welcome.

dointime

[Bobby1952]

  As some of you may remember I finished TX 10 months ago and SVR'd about 4 months ago. I was a genotype 3a, had been infected aproximately 30 years and was a stage 3 fibrosis at my biopsy 7 years ago. So I was probably a late stage 3 or early stage 4 when treating as my blood tests were normal except for elevated ALT and AST.
  
   What I am getting at is I drank occasionally on treatment. I am not reccomending this but I would drink about 6 beers on a friday night every month or 6 weeks depending on how I felt. This did not stop me from attaining SVR. So who really knows.