What is the rationale for the Harvoni + Ribavirin combination treatment?

[maneman]

Hello All,

I'm new here and I'm from England as it seems this is an American forum. Just happened to find this forum and it's been really interesting even though only read a fraction of the posts on here.
In England we are well behind the US in experience and drug availability as far as HCV goes but not as far as infection it seems.
I have been waiting over a year for treatment and to avoid the Interferon/Ribavirin/Telaprevir from confirmed diagnosis and have been lucky enough to start on Harvoni + Ribavirin today.
However, I cannot understand why I have been prescribed Ribavirin as the evidence appears to show that it does little if anything to enhance efficacy and/or cure rates but definitely increases adverse events.
The only glimmer of a reason appears to be those with decompensated Cirrhosis and/or type 3 HCV.
Can anyone help as I'm a little confused with the reason this combo is prescribed for so many on here.

FYI I have type 1A HCV c/w early compensated cirrhosis and all the blood tests appear to indicate chronic advanced liver disease but no real nasty issues with the liver, kidneys, stomach, oesophagus, pancreas etc. No oedema, ascites, yellowing. My fibroscan score was elevated at 24 mean and ultrasound has clearly indicated no fatty liver but certainly abnormal and consistent with expectations from blood tests.
I have been taking Milk Thistle (Silymarin) and Dandelion Root in capsule form and been advised to stop in case of interaction with treatment.
Those two supplements I cannot recommend highly enough as they really helped me control itching, muscle aches and general malaise associated with this condition and daily living re: diet etc.

Anyhow I've probably written too much for a first posting and would really appreciate some feedback, help and advice as we are rather naive here in England re: HCV.

[gnatcatcher]

First off, welcome, maneman. As you can see from my signature file, we're at a pretty similar liver level, although my Fibroscan score was 19,5 (a.k.a. 19.5) contradicted by an F2 Fibrosure and rosy ultrasounds over the years that made the Fibroscan F4 quite a surprise. Do I understand correctly that, other than taking Milk Thistle and Dandelion Root, you have had no prior treatment for Hep C (a.k.a. you are "treatment naive")? Unless your viral load or liver enzymes (ALT, AST, etc.) are off the charts or there's some other reason, it is puzzling that you are being given more than just Harvoni. Still, all of us taking Harvoni now are, to borrow a computer term, "beta testers" who are supplying the cure vs. relapse data that will show in hindsight which country made the better treatment recommendations.

I'm hoping Lynn K will post a reply. Not only is she a fount of information, but she (also 1a) has just recently been cured using Harvoni + Ribavirin after failing four prior therapies. In the meantime, you could find any post by her, click on her name, then click Show Posts to skim through her replies to other threads -- they often contain useful links, too.

[Bree]

Hi Maneman... I have the same curiosity about adding Ribavirin.  I had just posted a new thread right before I saw yours.  I am on Harvoni only and think that is enough for me (I'm F1-2) and almost midway through a 12 week treatment. 

Since I have seen so many on this forum who have ribavirin added either at the onset of treatment or later during treatment, I was wondering if I should too just to increase the chances, if that is what it does.  I have riba in the past with interferon... so our situation is a bit different and it seems like those with cirrhosis have riba added, and some on clinical trials had it added.

My doctor will if I request it but just not sure it is necessary in my case. 

Best of luck to you!  I'm hoping that some of the experts reply to both of our threads.  Bree

[sickpuppy]

Hello All,

I'm new here and I'm from England as it seems this is an American forum. Just happened to find this forum and it's been really interesting even though only read a fraction of the posts on here.
In England we are well behind the US in experience and drug availability as far as HCV goes but not as far as infection it seems.
I have been waiting over a year for treatment and to avoid the Interferon/Ribavirin/Telaprevir from confirmed diagnosis and have been lucky enough to start on Harvoni + Ribavirin today.
However, I cannot understand why I have been prescribed Ribavirin as the evidence appears to show that it does little if anything to enhance efficacy and/or cure rates but definitely increases adverse events.
The only glimmer of a reason appears to be those with decompensated Cirrhosis and/or type 3 HCV.
Can anyone help as I'm a little confused with the reason this combo is prescribed for so many on here.

FYI I have type 1A HCV c/w early compensated cirrhosis and all the blood tests appear to indicate chronic advanced liver disease but no real nasty issues with the liver, kidneys, stomach, oesophagus, pancreas etc. No oedema, ascites, yellowing. My fibroscan score was elevated at 24 mean and ultrasound has clearly indicated no fatty liver but certainly abnormal and consistent with expectations from blood tests.
I have been taking Milk Thistle (Silymarin) and Dandelion Root in capsule form and been advised to stop in case of interaction with treatment.
Those two supplements I cannot recommend highly enough as they really helped me control itching, muscle aches and general malaise associated with this condition and daily living re: diet etc.

Anyhow I've probably written too much for a first posting and would really appreciate some feedback, help and advice as we are rather naive here in England re: HCV.

Oy! It's like I found me brother. Mini-me!

I'm in your exact situation. From England, F4, prescribed 12 weeks Harvoni + Ribavirin, had been previously taken Silymarin and Dandelion root (I was having Dandelion root coffee, really nice). I too recommend these immensely. Forget the 'inconclusive' studies. They are really good.

I was DX-ed straight decompensated at a very young age (around 11). I continued to have decompensation issues up until I was put on Silymarin and Propranolol for varices. Later on I started dandelion root coffee which helped.

Since then I went back to compensated, and my liver has actually improved. You're lucky to be compensated with 24 Fibroscan. My Fibroscan showed 16.2 and keep in mind, I had already had 4 very violent bleeding varices episodes 7 years ago!

In any case, Ribavirin. I have read and went through all of those studies you've read myself. Day after day. I too came up to the conclusion that it seems worthelss. I actually printed all of them and confronted my liver specialist about it and I was told that we're adding Ribavirin as an insurance. They are aware it doesn't seem to make much difference, but it did make it in some very advanced liver disease patients, like ourselves right here. They said it's to do with how Ribavirin works, basically acting as a scissors to the virus. And they think that while it doesn't actually help with Harvoni's process (which inhibits reproduction) it does help with destroying the ones that are already created, ergo, reach SVR early and stay that way. Again, they said 'we have the chance to bring out all the guns'. Ideally they said, 24 weeks of Harvoni would have been the real deal, but unfortunately, here in England we only have 12 approved regardless of status of patient, so they add Ribavirin.

This is the real reason why we're adding Ribavirin in the UK. Because there were differences between 12 week and 24 week Harvoni, but when you add Ribavirin to the 12 week Harvoni, you approach the same SVR rate as 24 week Harvoni.

I've also read a nice article from a very good doctor in the US, and I sent him an email and asked him about whether I'm on the right TX. He said that based on my bloods and kPa score and everything I told him, he would recommend 24 weeks of Harvoni or 12 weeks of Harvoni + Ribavirin. So he was of the same opinion.

I don't know if Ribavirin had anything to do with it or not, but I reached undetected in 12 days. I'm glad I have the Ribavirin and the side effects are not existant. I had none of the ones you read online. I'm symptomatic anyway as a cirrhotic, so I wouldn't even know if they were from Ribavirin or just business as usual.

I've had a blood count and my hemoglobin went from 14.9 to 13.5 in two weeks. I was told they are happy with that decrease, and expect it to level off around 12 at week 4 and stay that way, which is completely fine for another 8 weeks.

I maybe felt a little shortness of breath, or maybe just in my head. I'm in London, I walk 1-2 hours every day, London style, I commute 1.5 hours each day by Tube, overground, etc. Had no issues. Didn't faint, didn't need to sit down. My legs do seem weaker a bit.

This is the article that I mentioned: http://www.healio.com/infectious-disease/hepatitis-c/news/print/hcv-next/%7B5a302f58-1018-4a5f-bc38-8c80c2772a32%7D/a-matter-of-compensation-hcv-and-cirrhosis

Read it. It's really good and about your situation (and mine) exactly. There are 5 pages, read them all. I wrote to the doctor (Brown) on page 3.

This is an interesting quote:

"There are three main factors involved in the debate about whether it will ultimately be preferable to treat patients for longer durations or to treat patients with more drugs, according to Brown. “One is that we may not be getting drugs into every place we need to because of fibrosis or portosystemic shunting. The second is that there may be impaired immune function leading to viral persistence,” he said. “The third is that cirrhotics have had the disease longer. The first two argue for longer therapy and the last one argues for more drugs.”

Then it goes on to discuss whether doctors should focus on longer duration or on more drugs and shorter duration. It's an interesting discussion and kind of revealing at what's happening behind closed doors between high-ranking doctors and how they reach certain criteria and guidelines. I personally would advocate for a longer duration of TX, simply because I think it's a matter of allowing the drugs to reach the right places, which takes time in cirrhotics, and which more drugs cannot solve no matter how much better they are. More drugs just puts more strain on the liver. Anyway, I'm digressing.

Why Ribavirin? Because the UK has decided to side with Brown's opinion, not with Feld, which advocated for longer duration (hence, 24 weeks of Harvoni, instead of 12 weeks + Ribavirin at a 1% SVR trade-off).

Why Ribavirin? Because money and NHS.

Why Ribavirin? Because it's been around for 40 years. Old habits die hard.

Why Ribavirin? Because it seems like a puppy when not in combination with Interferon. It was the combination that was horrible, not Ribavirin by itself.

Why Ribavirin? Because why not? If you can take it, and can handle it, and you don't have another option, then well, the decision has already been made for you.

I'm in London at St. Mary's. I hope you SVR man. I was told I have an 85% chance SVR. Also, don't overdose, lose a pill, or anything of the like. You will not be given a replacement no matter what. I've complained to the NHS, the Hep C trust, Gilead UK, lawyers, ombudsman, etc. Nothing. We do not have a contingency plan for missed, lost doses, not even when it's Gilead themselves advising to re-dose if vomit occurs less than 5 hours after dosing. You will be told to skip a day instead. It's insane.

Welcome to forced healthcare. 350$ a month for it, without the option to stop paying into it and go private. You can go private, but still have to pay the buggers, even though they won't offer you the best treatment available.

[maneman]

Sickpuppy, gnatcatcher and bree,

Thank you very much for your replies to my posting on here.

A lot of new light has been thrown onto my question concerning the co-prescribing of Ribavirin, it's interesting reading.

I feel now at the current moment that there is reasonable justification for the use of Ribavirin with Harvoni; after all, who am I, the patient, I'm not a doctor or a pharmacologist.

Interesting the comments regarding Sylimarin and Dandelion Root, helped me a lot for sure and no doubting the effectiveness. However, I've had to stop taking them as my doctor advised that there is no evidence of lack of interactions with Harvoni + Ribavirin and no experience of all used together. Plus they need an uncomplicated regimen to assess progress, side effects and blood tests properly. Fair comment really, seems to make sense.

Day 2 and I already feel different, somewhat strange but not unpleasant; more energy and sort of a feeling as if something is going on that is okay. Side effects if there are any as such, I can't say as anything at the moment is bothering me. After all day to day HCV c/w cirrhosis is not always pleasant with various levels of itching, muscle cramps and pains, headaches sometimes, intolerance to heat, visual disturbance, red palms with dry hard cracked sore skin patches has been my main issues.

Being treatment naive until now I am hoping for a successful outcome and am pleased I have this opportunity of treatment with the newer drugs and not the Interferon based regime.

My heart goes out to all of you out there that sail in the same boat as me (so to speak) of this dreaded silent killer HCV a really nasty virus that should be treated as early as possible. Alas, money as often is the deciding factor.

If interested I will continue my progress through treatment as a reference and help for others on here?

[gnatcatcher]

Yes, maneman, by all means post about your progress through treatment. Your experiences not only help others, but they also strengthen the sense of community amongst all of us. Every good wish during your Tx.

sickpuppy, thank you for all the solid information you have provided in this and other threads. I hope even after you get cured, you'll continue to post answers for the sake of those entering Tx after us.

[maneman]

Gnatcatcher,

I echo all your comments in your last post and wish you well.