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Greg Jefferys Hepatitis C blog deals with all the issues associated with hepatitis C

Hepatitis C Relapse

Hepatitis C relapse

What causes relapse after Hepatitis C treatment? This post answers this important question.

Hepatitis C Relapse: How does it happen?

Today in my Facebook Hepatitis C Support group the question below was asked.

“If you are undetectable of hep c then how in the world do people relapse?”

The issue of relapsing after Hepatitis C treatment is one that comes up regularly. Fortunately, we now understand Hepatitis C treatment with Direct Acting Antivirals (DAAs) much better than we did a few years ago and Hep C relapse rates are much lower than they used to be.

When I first started helping people access generic Hep C medicines the relapse rate was about 5%. That is, about 1 in 20 people relapsed after treatment. However, in the past 2 years, I have only had one person relapse after Hep C treatment. That is one out of about 1,000 people treated. Or you can say its a 99.9% cure rate. These are very good results indeed!

However, Hep C relapse is still an issue for people doing Hep C treatment or considering doing it. People have serious concerns about the chance of relapsing after they finish the Hep C treatment.

A Conversation About Hep C Relapse after Treatment: What does “Undetected” viral load mean?

So here is my reply to the question above and the rest of the conversation thread:

“In answer to your question: Its the limit of the detection technology… The best test can only detect around 15 viral particles in one milliliter of blood (one drop). So if levels are below that number < 15 (under 15 particles in a mil) then it is called “undetectable”
Most people doing treatment with DAAs reach “undetectable” within 7 days of starting treatment.
This does NOT mean there are no live Hep C virus particles in your body, it means that there are less than 15 in one drop of blood.
If you have just one single “live ” Hep C virus particle in your body when you finish your Hep C treatment you will relapse.
This is because even only one live viral particle can replicate very fast. One virus can replicate itself so fast that in 24 hours there are tens of millions of virus particles and in a week or so there will billions.
The Hepatitis C virus can hide out anywhere in your body but the most difficult place to reach them with the Hep C medicine is when they are in the liver scar tissue. This is why people with cirrhosis should do a longer treatment than people without cirrhosis.
This is why we must always do the entire treatment time.”

The person then asks:

“So, Greg,  is there any hope of being completely cured?”

My reply:

“The cure rates for Hep c nowadays are above 98percent. if you reach SVR 12 you are cured
Once you have stopped the treatment if there are any virus remaining in your system they will replicate very fast …1 would become millions in just days
There are no low numbers after the end of the treatment
You either have millions or none
This means that if you UNDETECTED 12 weeks after finishing the treatment then there is no virus in your system

The person:

” Greg Jefferys thanks. I was 2.5 million viral load with an F2 liver and had it for 20 years. I have 1 week of treatment of epclusa left. I’ve had a blood test every month and has been undetectable after 1 week of treatment. I have my fingers crossed”

 

“Why does one person relapse from Hep c when another does not?”

 

 What is a Hepatitis C Relapse?

Before we move on to the question of why some people relapse after Hep C treatment, let’s deal with the question: “What is a Hep C relapse? What does it mean?”
 
Relapse means that you completed Hep C treatment but that the treatment did not kill every Hepatitis C virus in your body, one or two or three viruses remained alive somewhere in your body where the medicines did not reach them. Usually, this is in the scar tissue of the liver.
When treatment ends and the DAAs leave your system these few remaining viruses start to reproduce again (replicate). In just a few days those two or three virus particles can become billions and billions of viruses once more breeding in your liver.
 
So a person can have undetectable levels of virus from as early as week four of treatment but if just one hidden pocket of the virus remains when treatment stops then relapse will almost always result. (not always be usually).
 

What are the causes of relapse?

There are two major factors that may cause a person to relapse after Hepatitis C treatment.
One is that the Hep C treatment time was not long enough and the other is something caused the Hep C medicine not to be absorbed properly
People with severe cirrhosis are more likely to relapse.
For this reason, it has become a common practice to extend the length of treatment time for people with severe cirrhosis. Usually, people with cirrhosis require at least 20 weeks of treatment.
Because cirrhosis involves scar tissue in the liver the virus can live in the scar tissue where the DAAs have difficulty reaching because there is very little blood circulation in scar tissue.
The Hep C medicines are carried in your blood, where there is not much blood flow then the drugs do not saturate the tissue easily.
So if you have cirrhosis you should discuss with your doctor whether you might need a slightly longer treatment.
This is certainly the case for genotype 3, which has proven the hardest Hep C genotype to remove.
 
But there is another cause for relapse as well.
 
This is UNDERDOSING, the opposite of overdosing. When the amount of medicine you are taking is less than it should be. This can because by the medicine not being absorbed into your blood properly or by it being broken down too fast when it is in your blood.
Hepatitis C relapse

If you have a high fibrosis level, or cirrhosis you should consider doing a longer treatment time

 

Poor Absorption of Harvoni, Epclusa: Antacids and Magnesium


Sofosbuvir and Ledipasvir (Harvoni) and Epclusa (Sof + Velaptasvir) and all other DAAs are absorbed primarily in the stomach.
Sofosbuvir is quite soluble, it dissolves easily in the stomach However, Ledipasvir and Velpatasvir do not dissolve easily. They do dissolve but not easily. For this reason, Gilead advises against taking an antacid within 4 hours before or after taking Harvoni or Epclusa. So an 8 hour period where no antacid should be taken.
Below is the exact warning from Gilead:
 
“Avoid taking an antacid within 4 hours before or 4 hours after you take Harvoni. This especially includes antacids that contain aluminum or magnesium (Acid Gone, Aldroxicon, Alternagel, Di-Gel, Gaviscon, Gelusil, Genaton, Maalox, Maldroxal, Milk of Magnesia, Mintox, Mylagen, Mylanta, Pepcid Complete, Rolaids, Rulox, and others”

This is because the stomach acid assists in making the Ledipasvir and Velpatasvir soluble and that anything that neutralizes the stomach acid will reduce the amount of Ledipasvir or Velpatasvir that the body absorbs,  resulting in an underdose of the Hep C drug.
 
There is also a heavy emphasis on not consuming magnesium, interestingly the world-famous Mayo Clinic also suggests avoiding magnesium during treatment with Harvoni.
In the past several years, I have begun the habit of asking people who have written to me telling me that they have relapsed if they are taking any dietary supplements. Several of them have responded that they have been taking magnesium supplements and several had taken antacids.
 

Hep C Medicine Being broken Down too Fast: Taurine, Caffeine and DAAs

 
In my post on 21st February 2016 I discussed the discovery of Dr James Freeman that taurine, a common ingredient in energy and bodybuilding drinks, affects the absorption of DAAs because Taurine modulates production of an enzyme called cytochrome P450 3A4 mRNA.
 
In plain English, this article tells us that Taurine increases the levels of the enzyme CYP3A4. This is the enzyme that removes Sofosbuvir, Daclatasvir and other DAAs from your system – in other words, if you are consuming Taurine the effect is like you’re taking a 1/2 dose, or maybe even a 1/4 dose of Harvoni, Epclusa and so on because taurine will reduce the effect of all DAAs significantly!
 
This, in turn, will mean that your chances of clearing the virus are reduced significantly.
 
Now taurine may not be the only thing that causes the body to remove Daclatasvir at increased rates, each and every “… extract” will contain dozens of chemicals, all of which might induce or inhibit CYP3A4.
 
For example, the body uses the enzyme cytochrome to break down caffeine so it might be that high levels of coffee consumption causes elevated cytochrome levels that in turn will effect the amount of Daclatasvir the body can use.
 
One of the things that ties in with relapse is the slow responder.
I was contacted by a lady today who is a slow responder using generic Harvoni and had not reached undetected by 8 weeks. I asked her if she was taking any supplements or other medication and the only medication she is taking is a sleeping tablet, Zopiclone.
Interestingly when I googled Zopiclone + Harvoni I found a paper immediately that mentioned the CYP enzymes again. (Remember CYP3A4 which is the villain for Daclatasvir)
 
Zopiclone is also metabolized predominantly by CYP3A4 and to a lesser degree by CYP2C8 and CYP2C9. Zopiclone concentrations may theoretically be increased by DAAs and require close monitoring. Most other benzodiazepines should be used cautiously in patients on DAAs. Clinicians may consider starting with a decreased benzodiazepine dose and monitoring for benzodiazepine-related toxicity or selecting an alternate agent such as lorazepam, oxazepam or temazepam. Dose reductions are also recommended in patients with severe liver impairment as per product monographs
 
I posted this information in my Hep C Facebook group and almost immediately got a comment from another person who was a slow responder and had relapsed. The only other medication she was taking during treatment was also Zopiclone!
Perhaps a coincidence? Perhaps not?
But here are those same enzymes again and it seems that maybe we need to be much more aware of drug interactions when using DAAs… particularly if there are issues with side effects and slow responding.

Body weight and “One dose fits all.”

Gilead offers a “One does fits all” with its products of Harvoni and Epclusa however this is not exactly correct. Research shows that people with body weights over 120 kilograms will have a higher chance of failing treatment than people with a lower body weight.

If you are a big person who is treating their Hep C you should discuss with your doctor the possibility of doing a longer treatment time.

 

Hepatitis C relapse

Better not to relapse after your first Hepatitis C treatment. There is a plan B and a plan C but each time you have to treat Hepatitis C after a failed treatment the harder it gets to cure. Get your treatment right the first time.

 

Conclusion

The first time that you treat your Hepatitis C is the time when the virus will be easiest to remove. It is super important that you clear the virus on the first attempt. If you do it right you will succeed.
Firstly, get the length of treatment time correct. If you have high fibrosis levels do a longer treatment time.
Avoid food supplements, herbal tonics, or remedies, and “energy drinks” during treatment. Avoid magnesium and antacids. Closely consult with your doctor about possible drug interactions that might occur while you are treating your Hep C.
Avoid taurine and excess caffeine. (I am not saying stop drinking coffee but keep it to a minimum during treatment just in case.) It has been shown that drinking black coffee without sugar will help your body repair liver damage such as cirrhosis.
 
We only get one clear hit at Hep C treatment and we want to optimize our chances of clearing this virus so it is better to be safe than sorry.
If a person relapses there are still treatment options but let’s see if we can avoid relapse and having to go through all that again!!!

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Greg Jefferys

Greg Jefferys

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