J. Ampuero1,2, M. Romero-Gómez1 and K. R. Reddy2,*Article first published online: 20 FEB 2014
DOI: 10.1111/apt.12646
Summary
Background
Over the past several years, hepatitis C therapy has been pegylated interferon and ribavirin based. Although protease
inhibitor-based therapy has enhanced response rates in genotype 1, the recent advances in therapy have demonstrated a
challenge in genotype 3, a highly prevalent infection globally.
Aim
To provide a comprehensive summary of the literature evaluating the unique characteristics and evolving therapies
in genotype 3.
Methods
A structured search in PubMed, the Cochrane Library and EMBASE was performed using defined key words, including only full
text papers and abstracts in English.
Results
HCV genotype 3 is more prevalent in Asia and among intra-venous drug users. Furthermore, it interferes with lipid and glucose
metabolism, and the natural history involves a more rapid progression of liver disease and a higher incidence of hepatocellular
carcinoma (HCC). New therapies with protease inhibitors have focused on genotype 1 largely and have demonstrated
enhanced responses, but have limited activity against genotype 3. Thus far, in clinical trials, NS5B and NS5A inhibitors have
performed more poorly in genotype 3, while a cyclophilin inhibitor, alisporivir, has shown promise.
Conclusions
As treatments for HCV have evolved, genotype 3 has become the most difficult to treat. Furthermore, genotype 3 has special
characteristics, such as insulin resistance and alterations in lipid metabolism, which may partly explain the lower treatment
responses. A great deal of emphasis on advancing therapy is needed in this population that appears to have a more rapid
progression of liver disease and a higher incidence of HCC.

This information may be helpfull, 

Hi John,

The relationship between Vitamin D, diabetes and liver fibrosis is complex, and still the subject of research. Optimal levels of blood Vit D are disputed, but 35-40 ng/ml is the most widely accepted. However, genes are also involved, so blood levels are not the only answer. The most popular theories are that decreased Vit D levels are associated with increased liver fibrosis and a poor response the the old SOC treatment. Low levels are also related to increased risk of Type 2 diabetes, due to Beta pancreatic cell effect.

As sunlight provides 90-95% of our Vit D, it's obvious why some have low levels. I had mine checked at SOT and was normal so didn't take supplements. High Vit D levels cause other problems. I rechecked my Vit D after 9 months of Rx as I was mostly indoors, but it remained normal. It's certainly relevant to get your levels checked. However, some patients have gene mutations that affect Vit D, even in the presence of adequate sun exposure. Cheers.

mallani wrote:

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Hi guys,

There is a strong association between HepC and Type 2 Diabetes. Whether this is due to direct viral effect on the pancreas or whether insulin-resistance develops as an auto-immune response, is not certain.

After SVR, Diabetes often regresses and fasting blood sugar drops. My fasting values and GTT showed pre-diabetes before treatment. Now, 15 months post-SVR, my fasting and random blood sugar is normal, and my A1C has dropped from 6.9 to 4.5.

Any diabetic on treatment should have a complete re-evaluation of their diabetic status after SVR, as treatment may no longer be required. Cheers, sweet tooths.

---

I've watched my fasting values slowly creep up towards the pre-diabetes range over the last few years, regardless of exercise, weight control and trying to consume good carbs. I just chalked it up to age and family history of Type 2 diabetes.

My doctor included vitamin D testing because of it's association with severity of liver fibrosis and possible effect on improved SVR rates. Much to my surprise given regular exposure to sunlight, I was at 15 ng/ml at the start of treatment. After 3 months at 2000-3000 IU of vitamin D per day, I'm now at 35 ng/ml which is in the normal range.

I see that their is new research on a link between Type 2 diabetes and vitamin D deficiency because of it's possible effect on pancreatic beta cells and insulin sensitivity. Just curious if Hepatitis C, low vitamin D levels and insulin sensitivity might be interrelated. Any thoughts Malcolm?

My A1C during treatment came back very good at 5.5 but just tested again and was back up to 6.6.

Of course, after the 5.5 came back, I started eating pancakes and waffles with log cabin syrup, and sugar smacks and frosted flakes cereal, and pie and cake and celebrated for a few months. Now, I am back to reality.

Maybe the numbers will drop again if I ever get back to work. Laying around the house all day doesn't help my numbers.

Hi guys,

There is a strong association between HepC and Type 2 Diabetes. Whether this is due to direct viral effect on the pancreas or whether insulin-resistance develops as an auto-immune response, is not certain.

After SVR, Diabetes often regresses and fasting blood sugar drops. My fasting values and GTT showed pre-diabetes before treatment. Now, 15 months post-SVR, my fasting and random blood sugar is normal, and my A1C has dropped from 6.9 to 4.5.

Any diabetic on treatment should have a complete re-evaluation of their diabetic status after SVR, as treatment may no longer be required. Cheers, sweet tooths.

I was diagnosed with diabetes type 2 within the last 7 yrs I've had hep c since the 80's and are type 1a early cirrhosis started triple therapy with sovaldi Ribavirin and Interferon on 1/31/14. and just finished treatment on 4/25/14 and have been undetected since 2/27/14.  Waiting for eot viral load test.  I have been very lax recently about testing my blood sugar levels and when I get serious I test in the morning.  The last two or three tests showed the lowest numbers that I can remember.  A 78 one morning and an 84 the next.  Usually my numbers are around 130.  I think the low numbers are attributed to the hep c being UND.  Hopefully I can reduce my drugs for diabetes. Need to discuss with dr. and I'm sure he'll order an A1C.

Thanks Larry,

Need to schedule appt for that A1C.  I am still on glipizide for diabetes until I see him.  Couldn't take metformin.  Not sure my doctors know much about what to do. Sure hope my diabetes is better--not that it was bad--just a pain to watch my food. 

Have 3 more days on my trial.  Will be glad to get off ribavirin.  !8 weeks is quite a while on meds--at least for me. 

SuziQ   

I am on the 90 day treatment plan. Apparently, I was the first patient in town to get this new sovaldi treatment and got it the very day it arrived in the local pharmacies. The nurse in the doctor's office tells me they are telling all the other patients about me (nameless of course) but I am the pioneer in my town with these drugs.

I have been type two diabetic for 3 years now and pre-diabetic for several years. I just had myself a bowl of chocolate ice cream to celebrate. My doctors are completely surprised about the diabetes aspect of all of this. I saw someone on youtube or on the internet talk about how they no longer had to take insulin shots after they attained SVR and why I decided to seek treatment for hep c. Diabetes really sucks too especially if you have a sweet tooth!

My doctors always told me that I only had inflammation on a scale of 0 to 1 like it was no big deal but my blood labs always indicated changes were going on in my body. I am not overweight at all and quite active so diabetes really surprised me and I always suspected it was related to hep c. It was just a theory but it appears that I was correct and may likely kill 2 birds with one stone so to speak.

Fortunately for me, I am gen 2b which is the most favorable for treatment and cure. However, after 40 years it has been causing me problems lately as with diabetes.

Good luck to you. Keep me posted on your progress. I have had no issues with this treatment at all. 

Larry,  That is GREAT news.  Thanks for sharing.

I am happy to hear that both the Hep C and diabeties seem to be under control.

For those Hep patients that are borderline diabetics and dont know it, maybe the new treatment will keep it from happening. 

Were you originally put on the 12 week plan or longer time frame of the tx.

I am on day 5 and hope to have similar results in 4 weeks.....

Tomorrow I will have completed 4 weeks of treatment with Sovaldi & Ribavirin.

My labs results show my viral load is at 43 down from 1.6 million (almost there) and my diabetes AIC test came back at 5.5 which means (down from 6.5) that I may no longer be diabetic anymore. In fact, the family doctor cut my metformin prescription in half and wants to retest in a couple of months and maybe take me off metformin permanently. It seems that inflammation of the liver causes fat to build up in the liver which prevents the body from breaking down sugar properly which causes hep c patients to be at increased risk to develop diabetes.

I have had no serious side effects except for some restless and sleepless nights which have always plagued me. My doctor prescribed me  ambien yesterday and I slept like a baby all night. Best sleep in years. The whites of my eyes seems to be getting a little whiter too.

I am so happy about this news. I pray that all my friends in this forum can experience similar results.

God Bless All of You!

Hi Jenifer,

CT and Ultrasound are pretty useless in assessing liver damage unless it's extreme.  I'm cirrhotic (F4), and have always had a fairly normal Ultrasound, CT or even MRI.  You really need a biopsy or Fibroscan to tell you your fibrosis stage ( F1 to F4), and then you can decide how quickly you need treatment. Cheers.

my appointment is with a GI doc that has a special interest in Liver disease. but The closest hepa has a satellite office 2 hours away. I might try to get into him though it might be a long wait. I want to get this started no matter what. Is a CT scan as good as a biopsy? I had an ultrasound last year. so I am due for another. 

Hi Jenifer,

A belated welcome from me as well.  If you've had HepC since the 1970's, you may have liver damage, so you would need a biopsy or Fibroscan to determine this.  The results will indicate whether you can afford to wait. Obviously, better treatment combos are around the corner, particularly the Sovaldi/ Ledispavir combo from Gilead.  As Jill said, it treatment is urgent, Interferon injections are not a problem to do at home. Personally, I would give Olysio a miss as there are better drugs available.  You really need to discuss this with an Hepatologist, experienced in treatment.  Good luck.  Cheers.

Hi Jenifer, yes, you`d need interferon and ribavirin with Olysio treatment, the same as you would for the other triple therapies with incivek or victrelis.  I see what you mean about the travelling distance, but if you do decide eventually to go for a treatment that included interferon you would give yourself the weekly injection at home.  It`s very easy to do once you`ve been shown how, and most people don`t find doing it themselves a problem, although of course the side effects can be quite unpleasant. 

One of my other issues is the part where I live far from any major city. so if i had to go each week for an injection would be an issue in the winter. I might not start anyway until after the snow flies up here. As it is the closest GI doc is 45 minutes one way. I thought that the Olysio  was no interferon.  

Sierrajen wrote:

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Thank you all for your warm welcome. When I saw the new drugs that got approved I became so hopeful that finally I can overcome this thing.

I got an appointment in February with a new doc that looks to have a lot of experience and has landed in my neck of the woods. I have had no biopsy but i have had this probably since the mid 70's. My viral load was done 1 year ago after my numbers from the liver panels got to high and the doc said it was time. I am thinking I might be feeling the liver at this point. I know that isn't good. I'm afraid of interferon . I'm a huge sissy about being ill. Maybe the J&J drug that just got approved. Any thoughts on that one?

---

Hi again, Jenifer, I can understand your reluctance to do any treatment containing interferon, especially at this point in time when all-oral treatments for genotype 1 are fast approaching. 

The new drug you mentioned from Johnson and Johnson is Olysio (simeprevir), marketed by Janssen, and it would also require interferon.  The advantage of that over the first generation protease inhibitors (victrlis or incivik) is that it would be one pill a day for the first 12 weeks, (plus ribavirin twice daily and weekly interferon shots), although you`d need to do 24 weeks assuming you responded well and were UND at week 4. 

I`m glad you have an appointment lined up with a new doctor in February, and you`re doing the right thing by finding out as much as you can about the treatment options that will be available to you.  A lot will depend on how soon he thinks you`ll need to start treatment. 

Keep in touch with us and you`ll get all the support you need, we all understand how scary it all seems before you start treatment.  You`ll beat it one way or another, don`t worry! 

Hi Larry,

I felt great the first 4 weeks with no side effects whatsoever.  Now, in my 15th week, the ribavirin is showing its' irritable little head. Actually, it is kinda neat to get a little outrageous now and then and be able to blame it on the riba.   

Compared to what others have gone through--the minor little side effects are nothing.  I feel almost guilty because the newer meds are so easy and have such good results.  Like you, I have great admiration for those who have gone before us.  Their posts give me gratitude for the newer meds and more than gratitude that I am so fortunate to be a part of this new experience with Hep C treatment.  You will be fine.

SuziQ

SierraJen,

I am a huge sissy too and after researching interferon, I didn't want any part of and waited for the FDA to approve Sovaldi. My liver doctor said I had time even though my family doctors were all up in arms about my white and red blood count and bilirubin levels and etc.

There are many in this forum who have bravely underwent the interferon treatment, some multiple times, and they have my admiration, prayers and sympathy combined. The thought of experiencing flu like symptoms for any span of time is beyond my comprehension to imagine and for their sakes, I hope the new drugs are approved quickly.

I think it is very important to do your research and find a liver specialist you trust and have confidence in. You really need to like your doctor and this will help a lot to get through this in my opinion for what little it may be worth. My research narrowed to two doctors locally with one being the state's premiere liver doctor and the other doctor is head of the infectious disease department at a large metropolitan hospital that deals exclusively with HCV and AIDS and all the stubborn stuff. I have two that I trust and that way I can always get a second opinion.

I am into day 5 of sovaldi and ribavirin and I don't want to jinx myself but haven't had any side effects yet at all. Thank God!

I have been worried about ribavirin side effects.

Thank you all for your warm welcome. When I saw the new drugs that got approved I became so hopeful that finally I can overcome this thing.

I got an appointment in February with a new doc that looks to have a lot of experience and has landed in my neck of the woods. I have had no biopsy but i have had this probably since the mid 70's. My viral load was done 1 year ago after my numbers from the liver panels got to high and the doc said it was time. I am thinking I might be feeling the liver at this point. I know that isn't good. I'm afraid of interferon . I'm a huge sissy about being ill. Maybe the J&J drug that just got approved. Any thoughts on that one?

I know I am gonna need support. I so appreciate your time.

Hi Sierrajen and welcome to the forum! You've come to the right place for information on everything HCV. As Jill mentioned, the new plans include many interesting possibilities that involve Sovaldi (Sofosbuvir) and combining it with other new drugs. The recent and new drug trials should impact the future very positively for most hepatitis patients in general. They actually already have! Hopefully future discovery will also determine a cost reducing formula as well.

You also asked about how to add the information to your posts. If you select "User Details" at the top of the page, you can enter your profile (personal info). Select the "signature" section and add the data you would like to share. It's a great way to share history, tests and progress. If you need any additional help, don't hesitate to ask.

Sierrajen wrote:

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I am just getting started finding a new Doc. I am assuming that I need a GI doc to prescribe the new drug. I am gen 1a and wanted Sovaldi without interferon. from the prescribing info I see that for Gen 1a I have to take the interferon. Is that right?

 

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 Hi Jenifer, welcome to the forum! 

Yes that`s right, you`ll need to consult a GI or liver specialist to be prescribed any drugs to treat your Hep C, and as you`re genotype 1 and treatment naive you`ll need interferon along with the Sovaldi and ribavirin.  As Larry 2384 said, this would be a 12 week course.

On the other hand, depending on the state of health of your liver, you could consider waiting for an all-oral interferon-free treatment to become available, for example Gilead`s fixed dose Sovaldi/Ledipasvir, which is likely to be approved by the FDA some time later next year.  There are other new drug treatments in the pipeline too.  Have you had a biopsy or fibroscan in recent times?  That is how you would know whether you have any liver damage and how urgent it is for you to begin treatment, or whether you can afford to wait. 

It might also be possible for you to participate in a clinical trial of one of the new drug combos currently being studied.  Once you find a new doctor you`ll be able to discuss the best options available to you.

Best of luck with finding a new doctor, try to find one who is experienced in treating Hep C if you can. 

I am probably the least qualified here to be giving information but I do believe that for gen 1a, peg-interferon-alfa is required with sovaldi and ribavirin for a 12 week period per Gilead's recommendation. I recall reading some posts about some possible better options coming down the pipe next year for gen1a but again, I will defer to the gurus. I am fortunate to have gen2b which by comparison is much easier to treat and achieve SVR.

You can add your info by editing your profile under the signature section under your account information.

I am just getting started finding a new Doc. I am assuming that I need a GI doc to prescribe the new drug. I am gen 1a and wanted Sovaldi without interferon. from the prescribing info I see that for Gen 1a I have to take the interferon. Is that right?

How do i get my info under the line of my posts?

Hello Larry

Welcome to the forum me me also, you will find a great group of helpful HepcFriends here, so just post and enjoy the insight and fun, humor and discussion.

matt

Hi Tig,

I posted the reply because I have type 2 diabetes as well as Hep C and he was asking if anyone had experience with that and treatment.  Diabetes can (maybe) be a possible side effect of Hep C.  And, yes, my coordinator said treatment could possibly help my diabetes as the virus could be affecting my blood sugar.  No direct correlation between the treatment and diabetes.  There have been studies that said people with Hep C have a higher incidence of Type 2 diabetes.  It would be wonderful if becoming SVR (if I do) would help with diabetes as well---but only time will tell.

SuziQ

Hi and welcome Larry2384,

You have an excellent chance of SVR.  If you want further info on Sovaldi, check the Full Prescribing Information post in Knowledge Base-Useful Information.

I doubt whether HepC is responsible for the eye discoloration. This only happens in jaundice, where high Bilirubin causes a yellow tint to the sclera.

Diabetes type 2 is common in HepC, and is usually related to Insulin Resistance ( I.R.).  This is usually controlled by diet and exercise, and the A1C (Glycated Hb) should be kept below 6.5%. Only 10% of diabetes type 2 patients have a family history.  Surveys of patients after SVR show mixed results, but most agree that this decreases the I.R.    

Best of luck with Rx, but I'm sure you will be fine. Cheers.

I thought you meant HCV because I haven't heard anyone mention using Sofosbuvir as a possible cure for diabetes. I now realize you're hoping that it also provides help with your diabetes. Are you diet or Rx controlled? Good luck with that!

I noticed the Riba irritability was bothersome after the first month and continued through Tx. Some weeks much worse than others. If you feel it coming on, it's best to separate yourself from the irritant, quickly. If you let it consume you during an argument, it can and will get ugly. Not a good situation at all. It can get you while driving too. At least you can yell at the offender if you're by yourself, hopefully with the windows up, lol! Just remember you can't chase them down, ha, ha!

Are your eyes jaundiced? That's not uncommon with liver ailments and I think many people return to normal once things are corrected if the bile levels return to normal. What does your Hepatologist tell you? That's something my doc kept check of since I started seeing him.  

Good luck with your game tonight! If you can keep active during Tx you'll recover faster afterwards and feel better during it as well. Just don't overdue it!

Larry2384...I have been on Interf/Riba for 13 weeks.  I am very high strung and feisty also, so I really worried about the Riba Rage.   I noticed a little more irritability around 6 weeks, but I try really hard stay calm so it has not been to bad.  I have had a couple pretty bad rages at work, but they were at objects, not people.  I do notice little things bother me that didn't bother me before, but I constantly remind myself it is the medication.  Good luck, you will be fine.

SuzieQ,

Thanks for posting this information about your A1C. This is very encouraging! Please keep me posted about your A1C if you wouldn't mind.

How long did you take ribavirin before you experienced the irritability? I am irritable enough without ribavirin so this is a concern for me.

 I am only on my 2nd day of treatment and so far no issues. I am even thinking about playing racquetball this evening.

Larry2384

I actually meant diabetes type 2. My understanding is that diabetes can be a symptom of hcv. It doesn't run in my family at all and I don't feel like I am a candidate to have it except for the HCV. I have been unable to find much information about this topic on the net. I am hoping to kill two birds with one stone with this treatment, so to speak. 

I was also wondering if anyone could tell me if my eyes would become white again after I become undetectable. My eyes haven't been white since I was seventeen years old.

There seems to be very little info about sovaldi and ribavirin trials on the internet except what Gilead wants you to know. I can't find any independent information or personal recounts of the treatment process from those who went through the process. Maybe patients had to sign waivers of secrecy in exchange for the treatment. I don't know but hope to get some information from this forum.

Thanks for responding!

I did have a little bit of problem with insurance initially being denied until I called and asked why. Then they approved it. I am very blessed that my wife has fantastic health insurance. I was anxious to get started on treatment before Obama care ruined any chance of my getting treatment.

Hi Larry,

I am on a Merck trial Without interferon but with ribavirin.  I also have type 2 diabetes.  My trial is 18 weeks.  At first, I felt much better but by now (in 14th week) the ribavirin is affecting my moods--nothing dramatic, just general irritability.

  My A1C was 6.5 going into treatment.  At week 6 got an A1C of 5.1 BUT think that was not accurate.  My coordinator said that being UND may improve diabetes.  I guess time will tell.  I have to go to my regular doctor for my Diabetes check and my insurance only pays for it every three months. 

Congratulations on starting treatment !!!  Everyone here is really helpful.  I use the clinical trial section often for info, but generally read all the new posts every morning. Look forward to your posts along your journey to SVR. 

SuziQ 

Nice. Keep us posted.  Welcome to the forum!!!!!!

Hey Larry, welcome to the forum! This is a great bunch and we're here to help any way we can. Many questions can be answered by using the Search function at the top of each page. If you can't find an answer or just want to talk, please ask away!

I noticed you said you hoped the Sovaldi and Riba would cure your  type 2 Diabetes. I think you meant genotype 2 HCV, right? Your chance for SVR (cure) in GT2 is as Zlikster said, very high. It's one of the easiest to treat, lucky you!! As for Diabetes, I've seen many people mention dealing with it that also had HCV. There may be a link there somewhere but the jury is still out on that one. My glucose level really varied during treatment, it was slightly elevated throughout Tx but has started returning to normal post Tx. I hope that's the case with you as well. I wish you the best and hope you stick around as you progress. Good luck!

Hi Larry, welcome to the forum.  Congratulations on being our first member on Sovaldi treatment!

As it was only approved by the US FDA last week, all we know about it so far is from the clinical trials.  The most common sx from ribavirin include fatigue, headaches, itching and irritability, although it does vary quite a lot from person to person.  It`s likely to be a lot easier for you than the previous standard tx for genotype 2b though, which was the interferon and ribavirin combo.

By the way, did you have any problems with your medical insurance for Sovaldi, if you don`t mind me asking?

Best of luck, and please do keep up updated, we`ll be very interested in following your progress. Your chances of clearing the virus with this treatment are excellent!

I started new treatment today of sovaldi and ribavirin and hoping this treatment might cure my type 2 diabetes problem when I am undetectable. I just took my first day's dose without issues.

I am a new member and this is my first post. I hope to find someone out there to share my experience with and perhaps to find someone who has experience with the sovaldi / ribavirin combo and/or who has diabetes 2. I have heard mixed reviews about ribavirin and rashes, rage, depression, insomnia, and I am a bit concerned about these side effects. I am unemployed and hoping to land a new job and it sounds very daunting while going through treatment. I am cranky enough without any help from ribavirin.

I am 57 and have lived with HCV gen 2b for 40 years exactly without any treatment prior. For years I thought I had hep b and didn't know of the existence of HCV. My liver was  stage 0/1 when I had my last biopsy 2-3 years ago but my bilirubin and enzyme counts have been rocketing the past few years and have developed type 2 diabetes even though it doesn't run in my family at all.

If there is anyone else just starting treatment or wants a friend to share the experience with, feel free to reply or message me.