New Hepatitis C treatment, again, maybe!



Now in 2011, I have another treatment breakthrough to talk about-- its more of a traditional antiviral therapy (protease inhibitor), and it works (especially on a variant of HepC that is difficult to treat, in racial populations that are difficult to treat), but Ive still got a Star-Wars-esque 'bad feeling about this...'

Boceprevir for Untreated Chronic HCV Genotype 1 Infection

Boceprevir for Previously Treated Chronic HCV Genotype 1 Infection

Long story short-- We have very limited options for treating HepC infections. Two drugs. Lots of people cannot finish the drug course due to side-effects. Even those who can tolerate the side-effects arent guaranteed a 'cure'-- depending on the HepC variant, ~25-50% people cannot clear the virus. This leads to extensive liver damage, the need for a liver transplant, and lots of HepC related deaths via chronic liver disease, cirrhosis, or cancer.

Merck created an anti-HCV drug, Boceprevir, that apparently works well against a particularly difficult HCV variant to treat, Genotype 1. It is a protease inhibitor, a phrase many on ERV will already be familiar with, but just in case youre a newb or forgot-- we use protease inhibitors against HIV-1 all the time. Lots of RNA viruses are what I call 'sheet cake' viruses-- One promoter, 'one' mRNA (which can get cut into lots of different mRNAs), and 'one' protein (which gets cut into lots of different proteins). If a virus can cut up its mRNA and proteins into the appropriate slices of 'cake', it has a fun party. If take away the viruses knife (protease) via a protease inhibitor, it cannot cut up its proteins/caek, no one gets a slice, and the virus has a crappy party.



Except... like I said... I have a bad feeling about this. Viral evolution is what I do... So what happened to the virus in the people who were treated with Boceprevir, but did not clear the virus?

Boceprevir resistant HCV.


This is an RNA virus we are talking about, here. Quasispecies. You cant just treat with 'one' protease inhibitor and not expect this to happen. And then we have no idea if this resistance comes at any fitness cost, some escapes might, some might not, which means we are just *asking* Boceprevir resistant HCV to replace 'regular' HCV on the global scale.



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There's a few more drugs in the works at least, we'll hopefully get enough different ones to have a HAART equivalent within the next few years. Resistance is a problem with all of them tho, we collaborate with a few of the companies and know of a few resistance mutations that arise with passage in culture.

On a more hopeful note, one lab (Mankouri et. al., PNAS 2010) did find that a common diabetes drug, metformin, can seriously knock down the virus (or subgenomic replicon) in culture, due to the weird crap the virus does with AMP kinase. There's a short trial underway for that at the moment since it's such a well characterised drug already.

Yes, wait none of you morons can even describe the experiments that prove hepatitis C does anything, its probably just the alcohol ruining people's livers, but you can't make any money off that so invent some virus with a 50 year latent period

I call poe.

Describe the experiments that prove hepatitis causes liver failure etc ya deranged wackaloon. If you cite references describe them so people know you even read them. According to Duesberg the whole thing was a scam by Chiron, but you gotta make billions for them being a mindless shill though.........Duesberg breaks down the multi billion dollar scam by Chiron.

There Isn't one "expert" in the world that can describe the experiments that hepatitis c does anything, what a joke. Everybody is just a technician following orders from drug companies and ignorant public health officials.


Obvious poe is now obviouser .

Your link is broken, yaq.

What's wrong with a bit of good-old-fashioned epidemiology? If you look two groups of people (eg liver disease vs controls) and find the virus more in cases than controls, then you have to assume it's a risk factor. Stick the virus into an animal model, look to see if it causes the symptoms of the disease, and you start to work out if it's causative (rather than just correlated). Not rocket science...

I shouldn't deal with the poe/troll but...

I had a relative who had Hep C (well, back in the day it was called Non-A Non-B). No one is sure how she got hepatitis in the first place - but as a girl in the 1940s she picked it up somewhere. She never drank. She died of liver failure. Explain that one, yaq.

Damn it... I knew you were gonna say "Boceprevir resistant HCV" long before you said it.

By Kemanorel (not verified) on 06 Apr 2011 #permalink

"According to Duesberg". Fuck off.

I suppose I really shouldn't bite further but...


My PhD was supposed to have industrial involvement with Pfizer. After one initial meeting with them we heard nothing for the next year and then they announced they were closing down their main UK research site, including all their HepC work. If they're supposed to be issuing orders to me and all my colleagues they've done a pretty lousy job of it so far... Hey, send me the proof that it's all a scam and I can just make up some results for my PhD instead of working 70 hours a week!



Also Duesberg points out how the latent period has been extended to 50 years to explain away all the healthy people who have the virus. All you're left with is some vague correlation, but there isn't one study that looks at people who are healthy and not alcoholics, drug addicts etc who are infected with Hepatitis C and get sick. Duesberg destroyed the hypothesis in the link I had above, the link works for me.

And someone mentioned anecdotal evidence as proof? Give me a break. There are lots things that can ruin your liver Alcohol, drugs, obesity etc, and there isn't one study that controls for all these factors to see if hepatitis c is to blame.

The problem today is that medical students don't read primary sources, they just follow orders. For example when infectious disease "experts" are taught in medical school about hepatitis c they are never shown the compelling experiments that prove Hepatatis c is pathogenic. They just believe it because it's in a unreferenced textbook and the medical school supports the hypothesis because the CDC says so.

In 1999 Science magazine wrote a piece about how no one knows anything about hepatitis c. One study looked at people who tested positive between 1948-1954 out of 17 who tested positive only one had signs of liver disease decades later! Probably a alcoholic or someone who's in poor health anyways. The whole thing is a scam by a Chiron, they've made billions off their gigantic hustle.

yaq isnt a Poe. Its cooler. I dont know why he changed his handle-- hes not b& here. *shrug* But this is and The Analyst is what I get for commenting at Oracs place.





Cooler is a chronic cherry-picker.


I just read all of Dr. Lindenbach's "chimpanzee hepatitis" papers available through Google Scholar. Not a single one states that. It appears that instead, he was looking for a method to reliably replicate the virus itself - until recently, it was difficult to replicate in cell culture. Rather than discussing markers for liver disease (enzymes, necrosis, cancer, etc.), he discusses markers for infection (presence of antibodies, RNA, viremia, etc.).

Here's what another researcher had to say about HCV and chimps:




It isn't the result of a conspiracy, it's rather that science in America is no longer democratic. Science today seems to have a military structure (CDC officials wear military uniforms) where if, when it comes to an infectious disease, if the CDC says so its true and if they don't it is not true.

So all the Chiron corporation had to do is use their substantial resources and connections with the CDC (one of CDC workers Bradley also worked with Chiron to promote the new theory and made a hefty sum for the "discovery.") to promote a bogus hypothesis.

Once the CDC supports the hypothesis all medical schools don't even bother to verify anything, which is why no medical schools teach medical students the compelling experiments that prove hepatitis C's pathogenicity (they don't exist) and in Orwellian fashion everyone believes it for they are following CDC/drug company protocols. Any scientist who speaks out will be ignored.



Here is the entire Lindenbach study where he injected Chimpanzees with Hep c. "Cell culture-grown hepatitis C virus is infectious in vivo and can be recultured in vitro." Heres a quote


Even when mice are given human liver grafts they still don't get sick with Hep c.



The germ theory question may have seemed a bit silly, but there are total germ-theory denialists out there, mainly among alt-med types. Then there's the ones who believe pharma deliberately created dangerous viruses in order to make money... I guess you have problems with any disease without full Koch postulates? So all the cancer links like HPV, HTLV, EBV, Kaposi's sarcoma herpesvirus etc?

I'm not in America, and so not subject to any 'militarisation' of the CDC. The main centres for HepC research outside the US are in Japan (Wakita), Germany (Bartenschlager) and smaller labs in the UK where I'm based. There's other groups in Australia, Pakistan, and France that I can remember off the top of my head. Are we all unquestioningly following the word of the CDC? We have our own numbers in our countries for liver failure and how it correlates with HepC infection so aren't reliant on US data. In the UK HepC infection is the 2nd most common reason for liver transplants, after alcohol.

I know there was some weirdness with Chiron patenting the first HepC genome, but in research we don't use that sequence as far as I know (for one thing that first attempt is missing some sequence, mainly the untranslated regions i think). I'm also not sure if the patents would only have applied in the US, I would need to check but certainly the European patent office these days is a lot less keen on broad patents on stuff like genes (and computer software). I personally use the JFH1 patient isolate from Japan from 2005, the genotype 1B consensus sequence, the prototype H77 genotype 1A sequence and a bunch of patient isolates for my viral gene of interest.

I'm on the molecular bio side of things so patient stuff isn't really my field, but here's one bit I can remember for evidence of HCV causing harm. You'll probably call this anecdote since I can't name the lab involved (heard my supervisor bitching about it, but he didn't name the place), but one lab did have an accident with the JFH1 strain and someone got infected. Thankfully it's a 2a strain that responded to treatment in that case.

Kevin, thanks! Annoys me when I can't place a memory...

Anyone who cites Duesberg to claim such and such doesn't "exist|is harmless|is a scam|is invented|etc" is deluded and probably incapable of a single critical thought. What do you eat?

@neil nerdrage lol

I suspect some of the variation in exposure to HepC and developing liver disease could come down to host variation, as well as strain variation - eg much as some people spontaneously clear the virus and that seems to be associated with a particular SNP and other SNPs are associated with a poor treatment outcome, I imagine there are polymorphisms in the human genome for developing/not developing hepatocellular carcinoma or cirrhosis.


It's more like a kid that shouts, "I'm going to build a rocket ship and fly too the moon!" except you're not a little kid, but you still think it's possible.

It's pity we feel for you, not rage.

By Kemanorel (not verified) on 07 Apr 2011 #permalink

I'm stunned. Damn poedar. Rage? Pity? Is lol a feeling?



That's projection. You're just angry we give you a metaphorical pat on the head and a juice box, then ignore your inane babbling.

*pats Yaq on the head* Run along, Scamp.

*chuckles* Oh, kids... They just say the darnedest things.

*Goes back to doing real science*

By Kemanorel (not verified) on 08 Apr 2011 #permalink

You're right I'm so impressed with all the compelling experiments you guys have described, oh wait, you can't do that because your beliefs are based on mindlessly believing what you are told not on thinking for yourself, nerds have a hard time being smart, since most smart people are not nerds :)

Not taking the treatments for at least 10 years. Why? I feel great and I don't see any reason to make my life crap b4 my time. They will have much more advanced drugs out in just a few years.. Maybe people should focus more on living everyday to its fullest instead of obsessing over 'getting treated'. Stop drinking, stop eating crap, eat healthy, change your lifestyle and retire early. (I'm retiring at 34 and focusing on having kids).

What's worse, living an extremely fulfilling life for 40 or 50 years or living like a slave, paranoid about a potentially life threatening virus until your 80... hmm I know which I'd rather have.

When you compare the number of HEALTHY people who have died because of HEP C worldwide to say the number of HEALTHY people who have died due everything else... the chances of survival are pretty damn good.

If you're reading this and have HEP C, eat right, exercise, get rid of stress and go on with your life.. don't jump on Interferon cause the doc says so... IT IS NOT A DEATH SENTENCE, it IS a kick in the ass from god to tell you to start LIVING YOUR LIFE TO THE FULLEST.

So far I've managed to see 17 countries and meet all kinds of great people with nothing more than a backpack, a pair of sneakers and a couple thousand bucks in the bank. This is my 'treatment'.

By HepCarrier (not verified) on 19 Apr 2011 #permalink



Just because you are, by chance, in the 'lucky' category, doesnt give you the right to belittle other people for not being lucky ("U JUS GOTTAH EATS RITE!!") or the right to dole out medical advice ("DUNT TAEK MEDICINE! I RETIRING!").

Congratulations. You are a lucky fuck. And thats it.


"(I'm retiring at 34 and focusing on having kids)."

"....a couple thousand bucks in the bank."

This is what feels confident giving advice?


I guess you can have one that is transplant compatible and one you can sell. You've got it covered for when you start to turn yellow.

I hate people.



Yet around noon (when they start to wake up) all sorts of 20-30 somethings will be calling to check on the status of their parent's trusts and asking questions about money that isn't theirs because they are getting dangerously close to being forced to confront reality/work or live within their means.

Ugh. Yea, have some kids....big fucking buckets of them.

By Prometheus (not verified) on 20 Apr 2011 #permalink

1) There is no correlation between the viral load and disease outcome. Bad guys aren't suppose to be bad? In fact, how can you label somebody ill, having hepatitis which means liver inflammation, without having any symptom for inflammation, just a number on your blood test?

It is your decision, it is in your own hands.

Good luck! and... Gesundheit!!!

By HappyHepCCarrier (not verified) on 09 May 2011 #permalink


By SSJijingi (not verified) on 06 Jul 2011 #permalink

Hey everyone i just wanted to tell everyone if you have hep c its not the end of the world trust me i start treatment today and im absolutly scared shitless and im also a type 1 diabetic and im 20 years old ...... if any of yall have some reasuring messages for me that would be great i dont know anyone my age that has a matter of fact i only know 1 other person that does have it back at my home town and she was 53 years old and isnt doing to well and im just really scared of what its gonna do as i get older ... im going to school to become a medical assistant but im still kinda not sure about it all really and thats whats worrying me the most so if yall have any info please get in touch with me i would greatly appricate it.

By Kari Queen (not verified) on 28 Jul 2011 #permalink

by the way i dont know if yall have my e-mail its please keep in touch so i can make it thru all this its kinda depressing having to deal with it alone...i know im not alone i have family which keeps me alive but for the part of being depressed i need to meet other people who have it and can discuss it with me thank yall so much!!!



I have read many of the posts here and I am sorry, but many of you sound ignorant, poorly educated and victims of a 'conspiracy mentality' which, fair or unfair, I tend to associate with people of limited mental powers and paranoid tendencies. Also, the ones who talk about the attempts of the drug companies creating viruses in order to market expensive drugs sound a little wacky to me. You sound like those poor SOB's who actually think the Moon walk was a hoax. It just can't be, and neither does it seem rational to think that the CDC would 'militarise' the creation of deadly virsues in order to help the drug companies make a quick buck, including AIDS and HCV. Things just aren't that far gone.


Like I said, the side effects of these drugs make you feel like hell much of the time but I have great confidence in my doctor who always knows what he is talking about and, to his credit, has never lied to me. Knowing that HCV can turn easily into cirrhosis or liver cancer is a terrifying thought and so I think the treatment is worth the trouble and the risk. If you're too cowardly or doubtful to undergoe the treatment, then that is your problem (and your misfortune) but don't take on a superior attitude because you think you know the 'truth' which is one of distinguishing features of people caught up in a conspiracy mentality. That is, they piously tell you that THEY have access to the 'truth' while you are lost in ignorance and are a victim of your own naivete. Actually, the opposite is closer to the truth. I say this is nonsense and if anybody takes the trouble to actually READ and talk to an experienced physician, they will come to the conclusion that, as my dad once said, "Its easy to get sick, but its tough to get well." I guess my own experiences prove this to be a hard but valuable truth.

Good luck to you all and remember that, "Knowledge is more than equivalent to force." (Dr. Samuel Johnson)

Good luck and God bless you all.

Alec Markov