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What Causes Post Treatment Side Effects (Page 1 of 2)

Oct 30, 2013 - 25 comments



what causes






post treatment






innate immunity




leaky gut


Toll Like Receptors


inflammatory cytokines

(***For educational purposes only.  Not to be taken as medical advice or used to try to sell anything.  My sincere thanks to George Henderson for joining me in attempting the impossible)

Post treatment sides are caused by TLRs (Toll-Like Receptors).  TLRs are transmembrane proteins expressed by cells of the innate immune system, which recognize common structures on pathogens, known as pathogen associated molecular patterns (PAMPs), and activate signaling pathways that launch immune and inflammatory responses to destroy the invaders (see attached picture). TLR 2 and 4 interact with viruses and stimulate various pro-inflammatory and antiinflammatory cytokines.

In other words, TLRs recognize the Hepatitis C virus when it first infects you and mobilize different cells (macrophages, NK cells, etc) and pro inflammatory cytokines (like interferon) to defend you against the virus.

Things that activate TLR's.

1. Interferon
2. Endotoxin from LEAKY GUT
3. The Hepatitis C virus
4. Cortisol


Interferon is pro-inflammatory. That's how it elicits a response from the immune system to fight invaders.


When my kids were little, I went to a conference on Hepatitis C and brought back a coloring book with pictures of the liver for my son to color. As he started coloring he asked me, "What's a liver?".

I explained to him that the liver was the organ that got rid of everything we put in our body whether it was drugs, medications, alcohol, creams we rubbed on our skin and the pollution we inhaled. I showed him a picture of a tired liver on the coloring book and told him that's what happened to our liver when we made it work too hard.

The next day I was in the bathroom spraying deodorant under my arms when my son ran in the bathroom, grabbed the can of deodorant and threw it in the trash screaming, "No mommy, you're killing your liver!"I was very proud of him, he had the right idea and I'd never even mentioned deodorant.

So we all know that the liver gets rid of toxic substances we put in our bodies, but how do toxins get to the liver and how does the liver detoxify them?  How  does it relate to TLRs and the innate immune system?

The liver is the first organ that encounters venous blood from the small and large intestines via the portal vein. So that makes the liver vulnerable to exposure of bacterial products coming from the intestines. Translocation of large amounts of gut-derived products is usually prevented by an intact barrier system made strong by intestinal epithelial cells. So in a healthy organism only minor quantities of bacterial products reach the liver. In general, the liver tolerates small amounts of bacterial products in order to avoid harmful responses, but damage of the intestinal epithelial barrier results in a leaky gut that lets large amounts of bacterial products reach the liver.

Bacterial products, otherwise called Lipopolysaccharide are large molecules consisting of a lipid and a polysaccharide found on the outer membrane of gram negative bacteria. When they reach the liver, they act as ENDOTOXIN and elicit a strong reaction from our immune system. In other words, TLR's recognize bacterial products and activate the immune system cells that reside in the liver (like macrophages and NK cells) to defend you.

Activated TLR signalling induces innate immune responses including cytokine and type I IFN production in the liver. Alarmins, the products released from damaged cells or tissues (like the damaged cells caused by necrosis) also trigger TLR signalling and cause inflammation. Thus, the activation of TLR signalling by microbial products from leaky gut can contribute to the initiation and progression of liver disease.

What can cause a LEAKY GUT?

Dyslipidemia (high cholesterol)
Insulin resistance/Diabetes
NASH (NonAlcoholic Steatohepatitis)  
Alcohol use
GI problems (like stomach ulcers, diarrhea, Barrett's esophagus, H,Pylori infection, colitis, etc)
Antibiotics disrupting normal intestinal flora.


HCV's core protein interacts with TLR2 and TLR4 and stimulates various pro-inflammatory and antiinflammatory cytokines. NS3/4A disrupts TLR3 and RIG-1 signaling pathways by blocking TRIF and CARDIF and NS5A interacts with TLR4 and impairs NK cell function.  Levels of TLRs 2, 6, 7, 8, 9 and 10 are upregulated in both monocytes and T cells in HCV patients. TLR4 is upregulated in T lymphocytes, and TLR5 is increased in monocytes. MD-2, a TLR4 co-receptor, is increased in monocytes and T cells.

TLR2 correlates significantly with the hepatic necroinflammatory activity grade while TLR4 correlates with the fibrosis stage. TLR 4 expression in pancreatic beta cells affects cell viability and insulin homeostasis. Iit contributes to the development of insulin resistance and inflammation through its activation by elevated fatty acids and lipopolysaccharide (metformin is a TLR4 inhibitor, probably the reason it raises SVR). Plus there's TLR7 signaling impairment seen in non-responders.


During interferon treatment, CORTISOL is produced as part of the stress response and both cytokines (interferon) and cortisol enhance TLR 2 expression. Cortisol increases free fatty acids and blood sugar (to increase energy resources) and both those things increase TLR2 expression. High blood sugar, insulin resistance, obesity and lack of sleep cause a low grade chronic inflammation which is associated with expression of TLR4.

Lipopolysaccharide from leaky gut (caused by cirrhosis, IR, dyslipidemia, diarrhea, ulcers, Barrett's esophagus, etc) directly stimulates cortisol secretion. Add to that the other factors that increase cortisol like fear, fever, PTSD, pain, coffee, smoking and you can see how patients can end up with increased levels of cortisol and expression of TLRs.

Continual excess cortisol release eventually causes cortisol receptors to become desensitized leading to increased activity of pro-inflammatory immune mediators and disturbances in neurotransmitter transmission. Unregulated inflammation that can lead to dangerous pathologies long after you finish treatment with interferon.

There is a fine line between "protection from TLRs" and "damage from TLRs". .TLR signaling induces the production of inflammatory mediators and anti-microbial peptides to eradicate invading microorganisms from the host as well as to bridge the acquired immunity to amplify immune responses. However, abnormal activation of innate immune signaling may also cause chronic inflammation, autoimmune diseases, tissue and organ injuries, fibrosis and carcinogenesis. Hepatic inflammation can then cause systemic inflammation followed by the destruction of the intestinal barrier causing leaky gut and bacteria to go from the intestine to the liver. That induces a second activation of TLR signaling in the liver which can cause liver damage long after you finish treatment.

Because one thing is for sure, expression of TLRs doesn't stop the day you finish treatment.

Post a Comment
317787 tn?1473358451
by Dee1956, Jan 22, 2014
Hi, this is an amazing collection, thank you so much for sharing this!  I am blown away by all you have  on here.
I have not been on here much since I ruptured a disc  before Thanksgiving, then had surgery Christmas
It appears I have a lot to catch up on :)

747988 tn?1396536878
by otterwatcher, Nov 05, 2014
and then there's ribavirin and mitochondrial dysfunction...thanks for the info will read it at least 20 more times in order to absorb it!

568322 tn?1370165440
by CoWriter, Nov 09, 2014
To Dee and otterwatcher

I spent over a year researching this topic and collected so much information I found it hard to condense it and I'm afraid I didn't do a very good job explaining it.

Because if I had, people would have asked me how to stop the damage caused by TLRs. But nobody has..

So please allow me to explain....

TLRs are proteins that recognize invaders (like bacteria and viruses) when they first infect you and activate different cells and inflammatory cytokines (like interferon) to try to protect you from the invaders.  So to protect you, they activate inflammation.  If TLRs remain active, then they can cause damage.

Think of TLRs as the sensors in a complex burglar alarm system that can wake up the neighbors if there's a robber, call the cops and warm up your dinner if it senses you coming home.  But if they stay on, they will keep the neighbors up all night, keep calling the cops, and burn your dinner and perhaps the house.  

So TLRs defend you but they can also cause damage and there are several things that can activate TLRs:  the Hep c virus, cortisol, bacteria from leaky gut....and interferon treatment.

That's why you end up with post treatment side effects.  Because interferon activated TLRs and they remained active and are now causing damage.

Since you need TLRs to defend you against other invaders, you don't want to turn them off completely, you just want to regulate them.  Reset them so to speak.  

Avatar universal
by michniak, Nov 09, 2014
Would this explain why my mother suddenly had horrible blood issues after solved / olysio 12 week treatment.  She started bleeding, had horrible fatigue, bloody noses, gums, hospitalized 2x, needed platelets, plasmaphereisis, it was a complete nightmare.  On 10/6/14 she had a massive stroke and died on 10/13/14.

We are in shock and disbelief and pissed.  She was fine before the sovaldi / olysio medicine.

Can you help me understand how this treatment made her so sick?

317787 tn?1473358451
by Dee1956, Nov 11, 2014
Michniak, I am so very sorry for your loss.  I am in shock right now so don't know what to say about what happened to your Mom.  I am not very skilled on here,  though I try to look things up to help people and I will try to do this for you..  Is it possible that your Mom had compensated cirrhosis before treating and the treatment caused her to decompensate?
I am so sorry, I will try to find some information.

I had come back to let Cowriter know that I thought the TLR's were what caused my cyroglobunemia which is bleeding under the skin, swelling, pain which I was told was caused by my body trying to fight off the HCV.  Odd plasmaphersis  is something I read about when I had the cyroglobulinemias.  I read that if it got too bad I would need that as well.
All signs of it are gone now..

Avatar universal
by michniak, Nov 12, 2014
Dee1956, all of her scans were fine before the treatment.  Her hep doctor never said her cirrhosis was chronic :(  She was feeling fine and he recommended to her that she go on the medicine... and because she was always such a go getter, positive, she said 'sure!'.  Oh how I wish we could turn back that day :(

6 weeks into treatment she got horribly tired.  12 weeks after the treatment she couldn't walk. The doctors found nothing.  We were desperate for answers and her hep doctor had no idea. She was in remission from lymphoma from 10 years prior so he referred her to her oncologist but no cancer showed after results. The two doctors went back and forth all summer, never giving us a direct answer, it was such a nightmare.  In July she collapsed and was hospitalized and they then found her blood was thick and started the plasmapheresis, etc.  That's when it all started to get ugly and bad.  Weekly blood draws, bi weekly platelet fusions.  It was horrible.  October they hospitalized her again because of her thick blood and did three treatments of plasmapheresis when she had her stroke.

Tomorrow is one month she died :(  It's so horribly sad I'm shocked I'm still alive.  The only thing that keeps me going is hoping to find an answer for my Mom :(  

Perhaps we need to go back to her hep doctor and ask him why he thought it was a good idea to put her on that medicine... maybe we'll get answer there who knows.  Thanks for replying, it feels good to be heard. I've been kicked off so many forums telling my story.  The administrators of the forums don't want the dark side to be told of this medicine.  The forum I was chastised because of my story and banned.  So thanks for listening, it helps a great deal.

317787 tn?1473358451
by Dee1956, Nov 12, 2014
Hey there, no one should be banned, we all want to know what is happening, we all want to hear the truth.  There may be some who would be helped.  Have you ever looked at the proscribing information for the Sovaldi and Olysio?  when your Mom was doing it, it was an off label tx which means the FDA had not approved it for tx of HCV together.  It has just been approved this week and I wonder if that proscribing information might give you some help as it might have more warnings together than separately.  Sorry just kind of brainstorming.
I am concerned that the drug manufacturers are saying that the new treatments are so much easier. When I see someone complain about the awful side effects, I see others telling them it could not possibly be related.
Did the hep doctor give you any information?  I am assuming that the tx is not being blamed for what happened to her when it clearly (to me any way) should be.
I have seen some information about one of the drugs causing a rise in bilirubin though I don't know what that means.
3 people in Japan have just died but there the Olysio is made a little differently.  The chemical composition is not exactly the same.  With all the drug names being one name all through research then changing for market I sometimes confuse the two, I hope I don't do it this time :)
I admire you for being on here, I will continue to search and try to find some help.  You may want to send Cowriter a private message to ask for guidance.

9662954 tn?1405606159
by Dbzc2, Nov 12, 2014
Michniak, I wish I had done S&O before I had any complications! Up to a year ago I had no cirrhosis, no issues just fatigue here and there. When I was diagnosed with cirrhosis oct 2013 I was against doing S&O because I was not going to do yet another treatment and with S&O go broke too!  So I put off doing anything for almost 6 months. By then cirrhosis had kicked in with portals hypertension, memory loss, ascites, Hepatic encephalopathy...all the side effects of cirrhosis.  They came fast and hard!

Apr 4 I went on S&O because I finally found out I did not have to go broke!  That the insurance and pharmeuceutical company would save my life.  Well they saved my life and now I'm stuck with all these God-would symptoms that are affecting my life and if staying in bed 70% of the time is considered a great life, well I don't think so.

Had I done this treatment before I got this sick I might feel better about my future.  The reason docs tell patients to do the treatment before you get sick is so you'll have a life worth living.

I'm sorry abot what happened to your mum. About 1 to 4% of the population that do ANY drug will experience horrific side effects or death-- no drug is 100% safe.  However, had your mum not had any complications, (which sounds like a immune reaction to S&O,)  she would have had a really great life.  

Again, I'm sorry your mum died. It could happen to anyone.  You asked why do the meds when you are not sick? It's because cirrhosis and all its horrible side effects symptoms whatever are NOT cured by S&O.  Only hep C is.  I'm upset I put off doing S&O for so long that I now have a compromised life. It is what it is.  I hope your faith gets you through this and you can find some comfort there and with your family.

Sincerely, Debe

568322 tn?1370165440
by CoWriter, Dec 07, 2014
Dear michniak:

I am very sorry for your loss. I lost my mother to liver disease when she was 64 and a few years later I lost my younger brother to Aids so I understand your need for getting answers..

What do I think about your mother's case?

In medicine, when the the risk, by far outweighs the possible benefit, then the answer is not to do it.  

I, personally, wouldn't recommend treatment for someone who is 80 years old, has a history of lymphoma and is doing very well with no apparent risk from the hepatitis C.  The possibility of complications simply because of the age would be considerable. I would have been afraid of it reactivating the lymphoma, which may be what happened since Waldenstrom's is a type of lymphoma.

However, there will be people who are willing to take the risk because it's the only option they have to try to save their life.  It is from those brave people that we learn more about the virus and how to do things better.  So your mother didn't die in vain.  What happened to her is teaching us how to keep the others safe.  

I know two people who have had lymphoma in the past and are now on the new treatments so I will tell them about your mother so they can alert their doctors.  We'll know what to watch for.  So I thank you for sharing your story with us and not giving up when other forums banned you.  You must have gotten that from your mother.  She didn't give up and neither do you.


2059648 tn?1439766665
by dontworry_behappy1, Dec 08, 2014
How do you stop the damage damage done by TLRs?

Avatar universal
by Livelife777, Dec 08, 2014
Dontworry you read my mind.  I was going to ask that same question and also why doesn't everyone who's taken Interferon in the past have negative issues as well?   I have a few friends that took Interferon and are doing great.

568322 tn?1370165440
by CoWriter, Dec 10, 2014
To Livelife777:  Everybody is different.  Different genes, some have leaky gut and others don't and some continue doing things that increase cortisol and others do things that decrease it.  I also think that whether you responded to interferon or not makes a difference.  I think non-responders have more damage from interferon.


568322 tn?1370165440
by CoWriter, Dec 31, 2014
To dontworry_behappy1 and  Livelife777

I'm sorry it took me so long to get back.  This is part of the email I sent Dr Gish to see if he agreed with me (he's  familiar with TLRs since he participated in a trial using ANA775, a TLR7 agonist).

But I would like to remind you that I am a nurse NOT a doctor and nobody should take anything without first checking with their doctor.

(from my email to Dr Gish)

"What can help stop post treatment sides caused by TLRs?

Naltrexone....Because IFN-alpha acts at opioid receptor sites and naltrexone is a long-acting opioid antagonist. A study showed that 7 out of 9 patients experienced complete or moderate relief of neurotoxic side effects. Naltrexone is also a TLR4 antagonist.

Spirulina, (which BTW obtained an SVR in 4 out of 30 patients with low viral load in a trial), and chlorella because their PAMPs have activity on TLR2.

Prebiotics .....Recent studies showed that besides being a TLR4 inhibitor, metformin lowers glycemia by targeting microbiota, induces a profound shift in microbial community, and increases regulatory T cells (tregs) within the adipose depot.  So that means metformin works like a pro-prebiotic and other prebiotics might have a similar effect.  Like  Del Immune V (lactobacillus rhamnosus) and Elizabeth McKenna's genCix (you met with her a while back).   I know because my research partner (George Henderson) and I were involved in doing the research for her product.    

What do you think Dr Gish?  Do I have it right this time?"

Dr Gish's answer said,  "Great  research information.  Let us wait for clinical trial data".

My sources:

Treatment of neurotoxic side effects of interferon-alpha with naltrexone

Spirulina platensis versus silymarin in the treatment of chronic hepatitis C virus infection. A pilot randomized, comparative clinical trial

Efficacy and safety of Chlorella supplementation in adults with chronic hepatitis C virus infection

The Antidiabetic Gutsy Role of Metformin Uncovered?,  Remi Burcelin, Gut, July 9, 2013

An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice pubmed/23804561

The potential use of Toll-like receptor agonists to restore the dysfunctional immunity induced by hepatitis C virus.

Any role for probiotics in the therapy or prevention of autoimmune diseases? Up-to-date review


317787 tn?1473358451
by Dee1956, Dec 31, 2014
Dear Co....thank you so much for this information.  I really appreciate.  I used probiotics in the past and it did seem to help.  It also seemed to help another person on here.  At least she said she felt better than she had in a long time.
I realized after reading this that I have slacked off.  I am starting back up again.
Thank you so very much

317787 tn?1473358451
by Dee1956, Dec 31, 2014
Kim I agree with you, I know people who treated and they seem fine but of course they may just be to embarrassed to say anything.  I know one guy who says he a lot more emotional than he used to be but that is all he would say about it.

10175413 tn?1427170251
by Ekkiemom, Dec 31, 2014
Thanks Co. This is some very interesting information. This seems to put a name on a few things I have been dealing with since my interferon days. I attributed it to getting older or afraid I sounded like I was complaining about seemingly insignificant changes in my body. I was one that only lasted 5 Wks on inf/inciv/rib due to passing out at any moment, anemia,critically low potassium, trips to the hospital resulting in transfusions. So I refused to continue.
This is all starting to make sense. I can't say I'm surprised in a way by the data and I cannot speak for anyone else but I knew in my heart that these treatments might have some lasting sides that hopefully would dismish with time but never fooled myself that they just might not, and I accepted that.

I do have a question Co..
Since stopping INF just over 2 yrs ago I have been plagued with deep bone pain in the pelvic/hip area. Been to the chiropractor,acupuncture no relief and I refuse to be pumped full of drugs at a pain mgmt facility. Is there any data you are aware of that address this issue. Also the sheath on my left wrist is spontaneously disintegrating leaving me with DeQuervains disease. I was told by my specialist that he is almost sure it was the INF. would you have data on that as well?
Sorry to ask so many darn questions and for lengthy post
Happy & Healthy New Year and Thank you

568322 tn?1370165440
by CoWriter, Jan 02, 2015
To Ekkiemom

It's interesting that you mention low potassium and DeQuervains.  Let me show you part of the email I sent Dr Gish.....

"Yesterday I was at one of the Hepatitis C online forums and read a story written by a man who treated for 48 weeks (and failed) and said he "ended up with post treatment side effects for years".  He complained bitterly because he said health care professionals either didn't believe him or ignored his symptoms.

The man complained of having:  Fatigue, insomnia, depression, bleeding gums, stomach problems, arthritis- like aches and pains and impotence,

Then I remembered the other things people complain about after treatment : unresolved anemia, low white cells, (and getting sick with things like the flu more often), fatigue, weakness, muscle loss, cramping, "brain fog", impaired memory, irritability, mood swings, anxiety, inability to sleep but feeling "wired", weight gain (even though their thyroid tests are normal), low testosterone, low libido, impotence, synovitis, tendonitis, trigger fingers, De Quervain's Tenosynovitis, and even Peyronie's disease.

The more symptoms I added, the surer I became.  They are all symptoms that can be caused by high cortisol.  High cortisol causes low potassium, that would account for the cramping.  Cortisol increases the adhesion of synovial fibroblasts to fibronectin so that would account for the synovitis/tendonitis problems."  

So you're not the first one to complain of De Quervains.  TLRs cause inflammation but I also think that after treatment you end up with antioxidant and vitamin deficiencies.  Hep c patients usually have low vitamin B and Vitamin D.  Interferon also lowers B vitamins.  Bone pain can be caused by low vitamin D. But do NOT take anything without checking with your doctor.

"Bone pain often also occurs in the lower back, hips, pelvis, thighs and feet."


317787 tn?1473358451
by Dee1956, Jan 07, 2015
Years ago I was having hip bone pain, using a book by Adelle Davis, among other things, on nutritional healing.  I read that hip pain can be a sign of calcium deficiency.
When I failed tx the first time it took me over two years to feel right again.  Of course everyone said it could not be from Interferon.  But....I felt great right before treating, had just been diagnosed with diabetes, lost 30 lbs in 3 months.  I was feeling so good.
So.... post tx just destroyed me.  Who would ever think they would feel worse after tx.  I tried to blame it on relapsing in 4 weeks, having the HCV come back so quickly, then cyros came back so bad it was no longer red dots but purple splotches as large as a tennis ball in some places.  Now that I am cured it has all cleared up, despite being told that the iron stains from the blood leaking were like tattoos and would never go away.

Thank you Co for sharing all of this with us.  I really appreciate.  Like I said before, the second time I treated I knew the information about IR, from you, so was really good about taking the Metformin, I believe it helped me to get to SVR and stay there, thank you.
I was just thinking, after the first time I treated my Hep Doc saw my little finger that is bent from tearing a tendon, he panicked thinking, I guess, that the tx had done damage.  He didn't say that but the way he acted was like nothing he had ever done before.
Thanks again, Dee

317787 tn?1473358451
by Dee1956, Jan 09, 2015
He Co! I am looking into the gut brain connection as you mentioned.  I came across this is Science Daily.  I think this place comes up with information much faster than others.  I remember when my sons were small I read that NutraSweet could cause seizures in children, when I ask a neurologist about it he agreed.  Yet they continue to sell. I hope you don't mind me sharing with this. Dee

317787 tn?1473358451
by Dee1956, Jan 10, 2015
I'm back, sorry about that, I am wondering if prebiotics would help me. So I have been looking at a lot of things.   It seems to be timely as I have come across all of this information recently about the gut - brain connection.  Now there is this article from 6 days ago.  I realize that I was taking the pre and pro back in 2013, was doing very well that Spring, then something happened I quite taking and was right back where I started. I looked at your photos but could not read them very well.
Thank you for your help, sorry if I am getting off the track. Dee

568322 tn?1370165440
by CoWriter, Jan 10, 2015

As a matter of fact, you're right on track and that thrills me no end.  I leave with a smile on my face after reading your comments.  Sometimes all I have to do is start something and people continue on their own and that's  what you've done.  

Look at some of the sources I listed, you'll find great information there.  Also, the note I just posted in my journal called "Beating BRAIN FOG".  You'll see how it's all connected.


317787 tn?1473358451
by Dee1956, Jan 10, 2015
If this helps me I will sing your praises  every where.  Bless you, Dee

568322 tn?1370165440
by CoWriter, Nov 13, 2016
To Dee1956

Our recommendation was for
1.  Metformin
2.  Prebiotics
3.  Naltrexone
4.  Spirulina
5.  Chlorella

Guess what?  Metformin just got proven right!  It helps the hypothyroidism caused by interferon!$=activity

Prebiotics do help bones and depression

317787 tn?1473358451
by Dee1956, Nov 13, 2016
OH my gosh! This is just great news!  I am so grateful to you and others for sharing so much of themselves.
I'm going to go read right now
Thank you so much!!

Avatar universal
by Willy50, Nov 13, 2016
Hiya Co !!
Have you looked into Wahls protocol?
Info on utube and facebook.


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