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Hepatitis C Genotype 3: Treatment Update

Treating Hepatitis C Genotype 3: The December 2018 update

Since mid 2015 when I first began working helping people to access affordable Hepatitis C treatment with generic DAAs from India it became clear that Hep C genotype 3 was the most difficult of the 6 common genotypes of Hepatitis C to cure. I learned that not only is Genotype 3 the most difficult variety of Hep C to cure but it also causes the most damage to the liver.

One of the first people I helped with treating Hep C G3 was an English guy living on the Spanish Island of Majorca. He caught Hep C from surgery after a motorcycle accident in India, so he found it ironic that both his disease and the medication for its cure came from India.
In those days the optimum treatment for Hepatitis Genotype 3 was 24 weeks of Sofosbuvir + Ribavirin. It was before generic Daclatasvir became available in India.
A few months prior to when he contacted me he had been ripped off by a couple of Russians who promised to supply him with the Sofosbuvir + Ribavirin for 10,000 Euros. He handed over the money and never saw those two men or the money again.
So he was a little reluctant to send money to me, a person he had never met, living thousands of miles away. But we did manage to work that out and I sent him his HCV genotype 3 treatment from India. It  was great news to hear that 24 weeks later he was cured. The 24 weeks of Ribavirin included in his treatment made the treatment very difficult because Ribavirin can cause unpleasant side effects. But at the end he was cured and he was happy. Not long after this happened generic Daclatasvir became available and the Sofosbuvir 400 mg + Daclatasvir 60 mg combination was hailed as the new wonder cure for Hepatitis C genotype 3, without the side effects of Ribavirin. Then India released generic Epclusa (Sofosbuvir 400 mg + Velpatasvir 100 mg), but I will come back to Epclusa latter.

Hep C G3

Hepatitis C genotype 3 is very common in South East Asia and also in some East European countries such as Serbia.

Hep C Genotype 3: A Global Problem

The Global distribution of Hepatitis C genotype 3 is interesting. In most western countries such as the USA and Europe G3 makes up about 25% of all Hep C infections but in South East Asia G3 is the predominant genotype of Hepatitis C and causes huge problems amongst a population that can ill afford the cost of treatment, even generic treatment.

However in countries that could afford the Sofosbuvir + Daclatasvir treatment doctors began recommending 12 weeks of Sofosbuvir + Daclatasvir to treat genotype 3.

Of course the problem was that 12 weeks of Sofosbuvir cost US$84,000 and 12 weeks of Daclatasvir cost US$54,000, making a 12 week treatment with Sofosbuvir + Daclatasvir cost around US$140,000: so the treatment was out of reach for all but the wealthiest patients. Even wealthy countries could not afford to have the price on the national health services.

Fortunately generic Daclatasvir soon became available from India and treatments began both with generic Sofosbuvir + Daclatasvir and also, in some countries, branded Sovaldi + Daklinza.. But as these new Genotype 3 treatments with Sof + Dac were completed it soon became clear that something was very wrong. The Sofosbuvir + Daclatasvir combination was giving reasonable results but much lower than expected with less than 80% of people being cured.
In other words about 1 in four people with Hep C genotype 3 doing 12 weeks treatment with Sofosbuvir + Daclatasvir was relapsing after the completion of treatment.
There was a lot of talk about this and it was not long before doctors began to prescribe 24 weeks treatment with Sof + Dac for G3.
This certainly lifted the cure rates but not by a huge amount; 24 weeks treatment with Sof + Dac was still only giving a cure rate of 90% or less for G3.
Hep C genotype 3 was proving a really difficult beast to kill.

Sofosbuvir + Velpatasvir for HCV genotype 3

Initial trials showed that treating Hepatitis C G3 with Epclusa was better than Sofosbuvir + Ribavirin. Particularly if the patient did not have cirrhosis.

Epclusa Arrives

Then along came Epclusa, which is Sofosbuvir 400 mg + Velpatasvir 100 mg.
Early trial results indicated that Epclusa was more effective against Hepatitis C G3 than Sofosbuvir + Daclatasvir or Sofosbuvir + Ribavirin but only very slightly, just 1%, which some statisticians would say was statistically insignificant.

The claim was that 12 weeks treatment of Epclusa was an effective treatment for Hep C genotype 3.

However I had heard this before and noticed that trials and “real world” treatments often give very different results. But it was pretty certain that Epclusa was at least as good as the other treatment options for G3 so when generic Epclusa became available I added it to the treatment options available for people with G3 and waited to hear the results.
And now nearly 2 years after the release of generic Epclusa, the results are in… Good news!
It seems that the real world results of treating Hep C G3 with Epclusa and the trial results are close enough to validate each other and that there is now little doubt that Epclusa (Sofosbuvir 400 mg + Velpatasvir 100 mg) is the optimum treatment for Hep C genotype 3 however it is also still the most expensive option when compared to Sofosbuvir + Daclatasvir.
However I would add that there is some evidence to suggest that adding at least an extra four weeks treatment will lift the cure rate. So, if you can afford it, doing 16 weeks instead of 12 weeks looks like being a good idea. Doing 24 weeks is even better but only by a couple of percentage points.
Also if you have cirrhosis then a longer treatment period is recommended. There is no evidence that adding Ribavirin to the Sofosbuvir + Velpatasvir regime will lift cure rates by about 2%. In fact in some trials adding Ribavirin appears to lower cure rates.

Hep C Genotype 3 treatment

This graph shows that Epclusa is only 1% superior to Sofosbuvir + Daclatasvir except where a patient has failed previous treatment. When a patient with genotype 3 has failed previous treatment then Sof + Dac is superior.

 

Epclusa vs Sofosbuvir + Daclatasvir

Epclusa for treating Hep C genotype 3

Summary of Epclusa Trial Results.

The treatment options for HCV genotype 3 patients are  Sofosbuvir + Daclatasvir or Sofosbuvir + Velpatasvir.
It seems from trial results that amongst patients without cirrhosis who underwent 12 weeks of treatment, more achieved SVR when they received Epclusa. . However those who used Sofosbuvir plus Daclatasvir also achieved very high cures. The results vary a little between different trials however it seem that cure rates for Epclusa and Sof + Daclatasvir are so close that there is little between them.
Among patients with cirrhosis, more achieved SVR when they received Sofosbuvir + Velpatasvir for 24 weeks compared with those treated with Sofosbuvir + Velpatasvir for 12 weeks.
From these results it is clear that longer treatment times with either Sofosbuvir + Velpatasvir or Sofosbuvir + Daclatasvir achieves the highest cure rate in Hepatitis C genotype 3.

Hep C genotype 3: Treatment Times

The length of treatment time is very important. Because Genotype 3 is the hardest to treat and even harder to re-treat after a relapse it is important that the first treatment clears the virus completely.

We know that treatment with Sofosbuvir + Velpatasvir (Epclusa) success rates look something like this:

93% @ 12 weeks,

96% @ 16 weeks,

98% at 20 weeks

and 99% at 24 weeks

This means that each extra 4 week of treatment adds  – 3%, 2%, 1% –

For governments and insurance companies they usually will say, because of the high costs,  ” 93% cure rate is good enough”  even when longer treatment provides better results.

As you will see from the email below, it is another example of why a person with Hep C Genotype 3 should do more than 12 weeks. I receive emails like this quite regularly.

Hello Greg,

I hope you are doing great. Just went through your blog and found very helpful.

I am 37 year old male Asian ethnic. HCV GT 3 discovered couple of years back without Cirrhosis.
First treatment was Sofo+Decla for 12 weeks. No viral load detected during treatment. 6 months later same load of 8 millions was back. Second treatment was with Epclusa+Riba for 12 weeks. Viral load undetected during treatment and relapsed after 3 months of treatment end. Current viral load is 1.6 millions.

Though liver still not too bad, I am weighing retreatment options. Can you please share your opinion on below?

Do I need NS5A resistance test?

Since Vosevi is still not in access in my area, would you go for Epclusa+Riba again for 24 weeks this time?

Any other recommendation?

Thanks and Best Regards,

S

 

Footnote:
Caffeine and Taurine and DAA treatment.
There is an enzyme in the body that breaks down most DAAs used in treating Hep C. If you have high levels of this enzyme in your blood you may effectively under dose on your Hep C medication.
There are two things that I know of which will cause high levels of this enzyme in your blood Taurine, a stimulant found in energy drinks such as Red Bull or V and also caffeine. So no energy drinks whilst doing Sof+ Dac and keep daily caffeine consumption low, a couple of cups of coffee or tea a day is fine. For more information of Hep C treatment and caffeine please click here.

 

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Greg Jefferys

Greg Jefferys

13 Comments

  •    Reply

    I always thought geno1a was the most difficult to treat Greg…
    Learning more every day!!!
    thank you for keeping us informed.

    •    Reply

      Lisa, Geno 1 always was the hardest to treat until the new DAA’s arrived……..these offered so many more options for G1 that it was no longer hardest to treat, that particular unfortunate title went to Geno 3. however with the arrival of pan genotypic treatment even G3’s are now easier to treat, things continue to get better and better!

    •    Reply
      sanjay singh kaintura October 12, 2017 at 5:25 pm

      Genotype 1 is easy to treat .Genotype 3 is difficult to treat

  •    Reply

    Greg is there a possibility that my partner can automatically pay an amount into an acct for u ti’ll he has saved enough?

  •    Reply

    High Greg- thanks for the info. I’m week 8 of 12 on Epclusa for G3

  •    Reply
    Andrewchattell@ Hotmail.com January 14, 2018 at 11:25 am

    Have just completed 6 months treatment. With sofosbuvir,daclatasiir and ribavarin this is my first time with these drugs before it was intferon. What’s the percentage cure rate ?

  •    Reply

    I finished Epclusa about 2 weeks ago. Anyone else feel liver tingling post treatment? I was undetected at 8 weeks- the only time I tested the viral load. I still feel good but the right posterior tingling makes me nervous

  •    Reply

    Did 12 weeks sofosbuvir-daclatasvir, I still was detectable at week 8 (hcv-rna quantitative 39) and undetected by week 12 at EOT, on August the 15th 2017. Been undetected ever since. So with me, daclatasvir-sof 12 weeks worked well. Thank God.

  •    Reply

    I treated it with Sov/Dak during past summer, 12 weeks. At week 8 my viral load was still detected at 39 copies, I thought I was failing but by end of therapy I was undetected. 12 weeks post: Und. Six months after, still clear. Guess I been lucky. Naturally I had gen 3…after only 5 years I was already F2. Everything worked good anyways.

  •    Reply

    Evidence for problem with caffeine?

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