Genotype 3 Treatment

[Marcia2202]

We now know that geno 3 should not be treated like geno 2. Someone (sorry, I cannot remember who) on this forum gave me this valuable information, according to latest studies of:

Columbia University, MD, special research for G3

NOT   UND at       W 4 48 weeks tx
High VL UND     at       W 4        36 weeks tx
Low VL UND at       W 4        24 weeks tx

If anyone has more information and experience treating genotype 3, I would be very thankful to hear about it.

Marcia

[Marcia2202]

K. thanks

[CockSparrow]

Nah dont think you can blame fatty liver for those symptoms.
Its funny just had a G2 complain about the same thing after having a Junk food weekend.

More a symptom of HepC than anything else. Its quite common.
But nah i dont have that problem. I live on Cheese.

CS

[Marcia2202]

Thank you so much. Now I am even more anxious to get the biopsy.

Now another question, are there any special symptoms associated with viral steatosis? Like I was talking about aversion of fatty foods. I actually feel quite off when I have fatty foods. Heated butter is the worst, I can't even look at it. Milk makes me really sick. All kinds of heated oils I avoid, as they also make me nauseas. I can tolerate raw cheeses in moderation. Virgin Coconut Oil I can heat. Virgin Olive Oil is good in it's fresh form, but I don't tolerate it as well when heated. Do you have any of these problems?

Marcia

[CockSparrow]

Marcia
A couple of articles for you

Hepatocellular fat accumulation and low serum cholesterol in patients infected with HCV-3a

The American Journal of Gastroenterology
Volume 97 Issue 11 Page 2880 - November 2002

OBJECTIVE:
The aim of this study was to prospectively investigate the prevalence of hepatic steatosis in chronic hepatitis C patients with respect to viral genotype, hepatic iron concentration, total body iron, body mass index, and serum lipid parameters. Furthermore, the effect of hepatitis C virus (HCV) eradication by antiviral therapy on serum cholesterol levels was studied.

METHODS:
Hepatocellular fat and hepatic iron were determined in liver biopsies obtained from 137 interferon-naïve patients with chronic hepatitis C (100 men, 37 women, mean age 40.8 ± 10.7 yr) enrolled in two prospective clinical trials of interferon/ribavirin therapy. Body mass index and fasting cholesterol levels were determined at baseline, during, and after therapy.

RESULTS:
Marked steatosis (>20% of fat-containing hepatocytes) was found in 74.5% of patients infected with HCV-3a compared with 17.9% in HCV-1 and 21.7% in HCV-4-infected patients (p< 0.01). Steatosis in HCV-3a-infected patients did not correlate with the body mass index, hepatic iron content, ferritin, or transferrin saturation. At baseline, serum cholesterol was lower in patients infected with HCV-3a (147 ± 42 mg/dl; p< 0.01) compared with HCV-1 (188 ± 36) or HCV-4 (172 ± 35). In contrast to HCV-1- or HCV-4-infected patients, serum cholesterol increased in HCV-3a virological responders at the end of treatment and 6 months after therapy (baseline 146 ± 38, end of treatment 166 ± 29, p< 0.05, sustained virological response 200 ± 34, p< 0.01). However, serum cholesterol remained unchanged in HCV-3a nonresponders.

CONCLUSIONS:
Our data suggest that, in addition to inducing steatosis, HCV-3a lowers serum cholesterol. This metabolic effect is fully reversible after successful HCV-3a eradication. This unique property is not shared by other HCV genotypes.


Here are a couple of links from MedScape. They are free but you have to register

Impact of Hepatic Steatosis on Viral Kinetics and Treatment Outcome During Antiviral Treatment of Chronic HCV Infection
http://www.medscape.com/viewarticle/553011_print

Hepatitis C and Steatosis: A Reappraisal
http://www.medscape.com/viewarticle/525585

If you search Medscape for steatosis you will find quite a bit

CS

[Marcia2202]

I have finally been able to find some stuff on this subject. This is the conclusion of one of them. They also talk about hypocholesterol in this study. It's good to know though that viral steatosis it goes with tx, if SVR is achieved.

CONCLUSION
The relationship between HCV and steatosis in terms of fibrosis and disease progression is unclear. HCV genotype 3 is clearly associated with steatosis ("viral steatosis"). It seems that in some patients, steatosis may be associated with fibrosis progression. The mechanisms underlying this association are unknown. The challenge for the clinician in care of patients with chronic HCV infection and steatosis is to be able to differentiate between those with pure steatosis alone and a benign course from those with progressive disease (the same challenge in separating NASH from NAFLD).

There remain many unanswered questions and there is a need for large prospective studies on hepatitis C patients, using multivariate analysis, which take into account confounding factors for steatosis, insulin resistance, fibrosis, and response to treatment. A meta-analysis of individual patient data (the HCV MAID Study) is ongoing to investigate the relationship between steatosis, inflammation, and fibrosis in chronic hepatitis C. Moreover, we need to develop experimental models using different HCV genotypes in order to understand the mechanisms leading to steatosis.

Thanks for getting me onto this wagon, I love this forum and all you people who make it so great!

Marcia

[Marcia2202]

Thanks. Wow, do you mean low cholesterol...as in lower than lower limit? My cholesterol is 4,0 mmol/l, (154.44mg/dL) normal range here is 4,0 - 7,3.

(I think I have been infected for 25 years.)

Where do you find all the info about steatosis and g 3

Marcia

[CockSparrow]

Cant say for sure but length of infection doesnt seem to come into it much either.

I had steatosis after being infected 13 years, which was when i found out.
Low Cholesterol is related to steatosis at least with us 3s so that might be an indicator.

CS

[Marcia2202]

Wow, I sure don't want to hear that.

The life style NASH, I cannot have, the alcohol one neither, as I don't drink

So if I had the G3 one, I could get rid of it through tx. Well, only the biopsy will tell that one. Does it have to do with how long you've had the virus or is it just as random as with the grade and stage.

Sorry I'm buggin you with all these questions, but it is getting darn interesting.

Marcia

[CockSparrow]

Thanks for the verification on this one. Was just wondering, did they consider overweight, hypertension, diabetes etc...

Yes. Alcohol, being overweight etc the only statistically significant factor with steatosis and G3 was being G3.

We can get both type of steatosis though.
The G3 one goes away with svr. The life style form has to be gotten rid of thru diet and excercise

CS

[meki]

"I also think that IVDU gets the blame for a lot of medical transmission.
Saves a lot of money and red faces, saying you got it from IVDU and not medical treatment."

Also stops a lot of lawsuits.

I'm checking into my batch of Rhogam - and waiting for the medical record papers - when I was down in Anchorage - I got the exact date and time - and it completely correlates with what I believe was an ACUTE phase (which I had attributed to being pregnant and on a cruise ship).

I also am getting the batch number and I specifically let the records person KNOW that I had HCV - type 3a - that I was researching to see if I could have obtained it through that means --- AND that I was going to attempt to contact others who may have taken that batch during that time frame. I advised them that I was going to take out a personal's ad in the Anchorage Newspaper... Once I knew the batch number -  And spread the word around that the possibility exists - that if someone got a shot of Rhogam during that time frame - they MAY have HCV and should be checked.

My way of thinking is that:

A) either the batch was contaminated ...but - keep in mind that I was given that in 1996/January so it was either an OLD batch,

B)one that had been re-used with a syringe that had already been injected --- like maybe the first person's shot wasn't enough and they re-used the same syringe....

OR....

C)Maybe they really weren't following clearance procedures.


Just so you know - she advised me I would have my records and the batch number by MONDAY --- ahem... It's now Sunday the following week past that Monday.

Methinks Providence Hospital is seriously checking into it.

Which --- to me --- means a lot -- because there could be several other folks out there that have 3a here in ALASKA --- which they have told me is a pretty uncommon genotype here.

And I think those folks need to be aware that it is a possibility that they could have it too.

It's IMPERATIVE to me that people know they should be checked out. This disease needs to be stopped - and people who do not know they have it may be engaging in behavior which could transmit this disease to others.

If it's not the Rhogam - I certainly have no other earthly idea where it could have come from... I didn't have any transmission factors --- no cuts, except with family --- no transfusions - no major dental work... Nothing that could point to it. No outside the marriage unprotected sex --- no kissing anyone else... NADA... No needle sticks from EMT work --- no blood on me -- I was mostly the transporting crew --- so I was there just to read guages and pat people on the back --- no really serious blood scenes...

Just absolutely NOTHING that could point to a transmission route except that - in that amount of time --- since knowing I was clear.

So - yeah ---- I can see where doctors or the medical industry would want to say it comes more from IVDU than their practices.

I don't blame anyone tho --- I mean - people are just now learning how things are spread --- how contamination starts -- how to kill this disease and others.

We're a very young society medically - and we're learning more every day.

So there is no blame.

For me --- there is just a need to make sure that anyone else who may have been infected can take care of themselves and not pass it on.

This disease needs to be eradicated from the world.

Love to you all... thanks for listening... LOL!

Meki

[ladybug52]

Thanks so much for the info. I had always read about the geographical distribution of hepc genotypes which still left me wondering where I got hep c.
It doesn't matter, and I will never know.

I have several risk factors, one of which is working in the medical community since '82, and performing sharp debridement on wounds. Pulled off those darn gloves at times maybe when I shouldn't have. They always get in the way, but I leave them on nowadays!

I have always wondered if my time spent in the Air Force had something to do with the geographical distribution, (not that I thought you had to travel to Asia of Europe to get hep c) I never went out of the states during my 4 yrs, but perhaps shared blood tainted materials with those who did.
Thanks again for all the info,and thanks Marcia for starting this thread.
Nice of you to point out Adiamos post to mar too.
Can I just give one big group hug?:)
Bug

[Marcia2202]

Thanks for the verification on this one. Was just wondering, did they consider overweight, hypertension, diabetes etc... when they made the statistics that 71% of geno 3's have steatosis? I believe that being geno 3, one is more prone to it than other genos, but how much more, as all those other factors play a big role, too. Especially since there is a big tendency to those other illnesses.

Another thing, I tried to find out about the symptoms of NASH. They are all the same as hep c. So no way to tell. I just wonder, if aversion to fatty foods could be a symptom of steatosis or a symptom of being prone to it. Maybe the body just tells you, stay away from that stuff, cause I can't digest it properly....
I'm very sensitive, and can most times just look at food, to know if I'm gonna be able to take it.

My GP told me that aversion to fatty foods has to do with the gall bladder and can be an indication to gall bladder stones. I had an ultra sound scan, and no gall bladder stones.

Marcia

[CockSparrow]

or even a large portion of the HCV community obtained the virus through IVDU.
I just don't believe that.
----------------------------------------
Oh I do. The stats for IVDU are just too high.

I think more of it is from the medical treatments people have obtained
----------------------------------------
I also think that IVDU gets the blame for a lot of medical transmission.
Saves a lot of money and red faces, saying you got it from IVDU and not medical treatment.

CS

[CockSparrow]

Steatosis is associated with G3a. Dont need any other risk factors for it.
Other 3 subtypes are also prone to it but not to the same extent.
Us 3s are lucky re the Fatty Liver It goes away with successful Tx.
It does slow down the viral kinetics somewhat though.

Thanks for clarification. 1a & 3a can be caught in a number of ways. IVDU just being one.
It was more about genotype distrubition changing and its being blamed on drug use.

CS

[Marcia2202]

The study came up as pdf file straight from your link. Very interesting!

It is a little contradictory to the  suggestion of the Columbia University MD, suggesting to treat 36 weeks for High VL, if UND at week 4. it does suggest to prolong tx in certain cases, but unfortunately doesn't mention any time frames. Obviously they are still treading in muddy waters, concerning 'custom tx' for geno 3s. Considering dosing of meds, the studies done in Italy, could probably not really be applied to the US, as ppl are generally smaller in Italy. It could be applied to me, as I am about average Italian size.

Anyway, i will hopefully get a biopsy soon and then will be able to put down all the data and discuss how to attack this dragon.

Marcia

[Marcia2202]

Just wanted to comment  on a few things.

Distribution of certain genotypes in IV drug users. This does not mean that you must have gotten it though IV drug use. So please, anyone who has never done IV drugs, don't get offended. It is just that these types at a certain times where introduced into that specific group of people and was easily spread though out that group. It makes perfect sense, as often utensils for using the drugs are shared. One does not even have to share the actual needle. Sharing spoons and cotton wool is already enough to get infected. So this is the spread seen locally.

Then one can look at the geographic situation.

Geno 3 and NASH. I read in a medical report, that fatty liver has been found in 71% of Hep c geno 3s.  I cannot find it now, but had taken notes of, as it might be in my interest to get this matter checked. After what I researched on it, I found out that I am at low risk considering that my bmi is usually around 20.8 and has never been higher than 23.4. My normal blood pressure is low. And I don't have any other of the possible causes listed.

It's unclear exactly what causes nonalcoholic fatty liver disease. But many researchers believe that metabolic syndrome — a cluster of disorders that increase the risk of diabetes, heart disease and stroke — likely plays an important role in its development. Signs and symptoms of metabolic syndrome include:

    * Obesity, particularly around the waist (abdominal obesity)
    * High blood pressure (hypertension)
    * One or more abnormal cholesterol levels — high levels of triglycerides, a type of blood fat, or low levels of high-density lipoprotein (HDL) cholesterol, the "good" cholesterol
    * Resistance to insulin, a hormone that helps to regulate the amount of sugar in your blood


mar148....  Andiamo1 started a thread called 'Should forum members offer diagnosis?' on the Hepatitis Social/Living with Hepatitis Forum a couple of days ago . Check it out, there is some good discussion going on.

Marcia

[CockSparrow]

Bug
the link below gives a really account of what is happening in Europe.
You will have to register with elsevier but it is free

http://download.journals.elsevierhealth.com/pdfs/journals/0168-8278/PIIS0168827807005739.pdf

It was already known that genotype distribution was associated with the mode of transmission, with subtypes 1a, 3a and 4 being mostly IDU-related and
genotypes 1b and 2 associated with blood transfusion and unsafe medical procedures

CS

[CockSparrow]

Heres a study from Iran
http://www.comparative-hepatology.com/content/5/1/4#B28
Distribution of hepatitis C virus genotypes in patients infected by different sources and its correlation with clinical and virological parameters: a preliminary study

Genotypes 3a and 1a are more prevalent in IVDU in Europe and USA. In the present study, 18 (40%) and 17 (37.8%) patients with IVDA had genotype 1a and 3a respectively. It seems that there is a high similarity between the pattern of genotype in IVDU in Europe and United States when compared with Iran. However, it can not be due to migration of these people to these countries because the history of travel abroad was only seen in 6 cases (13.3%).

From http://www.wjgnet.com/1007-9327/14/1237.pdf
Hepatitis C virus genotypes distribution and transmission risk factors in Luxembourg from 1991 to 2006

Genotype 3 was significantly associated to IVDU

One pattern, characterized by high genetic diversity, involves geographically discrete areas where HCV has been endemic for a long time such as
West Africa with types 1 and 2,
Central Africa with type 4, and
Asia with types 3 and 6.

Another pattern involves areas with a few subtypes circulating in specific risk groups, e.g. subtype 3a in drug addicts.

The third pattern involves areas where a single subtype is present, such as in Egypt with subtype 4a and South Africa with subtype 5a.


Other molecular epidemiology studies have shown that HCV subtype 3a is significantly associated with transmission through injecting drug use in industrialized countries[22-24] and explain the prevalence of subtype 3a in many North and South American and European countries. HCV subtype 3a originates from Asia and has spread widely among injecting drug users[25,26].

Mechanisms of subtype 3a transmission remain poorly defined. Genotype 3 was not associated with a high level of HCV RNA as compared to the others genotypes in our cohort. Nevertheless, the relative homogeneity of NS5B sequences of injecting drug users from France, South America, Australia and California have indicated that HCV subtype 3a has been transmitted from a common origin through a unique worldwide epidemic among the drug user communities[27].

In this study, the authors reported region specific HCV 3a variants suggesting local transmission among intravenous drug users from the same geographical area. Therefore, the intrinsic characteristics of the transmission network of IVDU (unsafe injecting practices, drug preparation materials, needle or syringe exchange) together with the importance of the social context of drug injections may explain the efficiency of HCV genotype 3 transmission in Luxembourg.

Our study shows that the main risk factor for infection by genotype 3 is IVDU whereas the main risk factor for infection by genotype 1 is medical-related transmission.

The age of infected individuals may be a direct variable for the genotype distribution. Nevertheless, our data did not show that patients infected by genotype 1 were older than 40 years. This would mean other routes of infection by genotype 1 such as IVDU.

One from France
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1233931
The epidemiology of HCV infection in southeast France changed radically during the study period in relation to modifications in the etiology of infection. We observed the emergence of new epidemic subtypes (subtypes 1a and 3) linked to intravenous drug use and a decrease in the types linked to blood transfusion and nosocomial infection (epidemic subtype 1b and endemic type 2).

Replacing G1b and 2 with 1a and 3a is occurring worldwide. In the West anyway.
Its what is happening here in Aust.

All the Best
CS

[eureka254]

My understanding of genotype distribution was that it was mostly geographically linked:  1a & 1b most common in the US, genos 2 & 3 most common in Europe, and genos 4 most common in Asia/Africa.  I've started seeing more investigation into the *nature* of each genotype, but I don't think there are any conclusive agreements ... yet.

My husband's hx fits your theory, though... we guess that he's probably had the disease close to 40 years, just diagnosed last year (asymptomatic, geno 1, stage 4).  There's been some conjecture that HCC is more common in geno 1s, but like I said, there's a dirth of info on the subtypes.

I tend to think that the disease (and also its treatments) affects individuals so very differently because of all the variables:  (1) the varying types (2) the varying states of health of the host (3) the length of infection and (4) the contributory environment.  

I often wonder why docs focus studies only on the "actively infected" population?  I've entertained the idea that the medical community might have some more success if they researched the population that contracts AND clears hepatitis WITHOUT treatment.  If we could only figure out what makes those ~30% who are exposed to HCV  "spontaneously" clear it, we'd be golden!

eureka

[meki]

Interesting. I didn't know that genotypes were more prone to being from specific transmission routes.

Very interesting.

I know I didn't get mine from IVDU --- or any other drug usage --- so I think that it's interesting that the medical community has associated any genotype with drug usage.

But --- I've never researched the amounts or percentages.

Maybe I'm naive in my thinking - but I don't think everyone or even a large portion of the HCV community obtained the virus through IVDU.

I just don't believe that.

I think more of it is from the medical treatments people have obtained.

I truly believe that everyone who has HCV probably obtained it from some sort of medical operation or injection.

Meki

[mar148]

I am concerned that people do read this forum and while there are some interesting pieces of information shared from what people have learned along the way, it should not be confused as a medical forum for physicians and researchers.  I would hate anyone to rely to heavily on any information but use it to ask good questions when dealing with their own qualified doctor.  

Also, many people who become SVR with type 3 or other types are not on this forum.  People who are treating for the first time or determining whether to retreat are often times on message boards to gain new information and treatment strategies.  So those of us here do not represent a valid cross section of hep c patients.

[ladybug52]

I've learned a lot from this discussion, which always leads to more questions.....
First, I was surprised when you stated:
We now know that geno 3 should not be treated like geno 2.
I didn't know!
Also, I didn't know the formula for clearing or length of tx. My viral load was 11 million to start, but I had cleared by week 3. I think I was just extremly lucky, blessed to still be und  6 months after a 16 week tx. (would never advocate shortened tx to anyone else)
Here's the part that is really a mystery to me:

"G1a and G3a worldwide are associated with drugs.
They are the 2 genos that seems to have gotten into the drug user community. "
OK, what does that mean?
If you can explain this comment I would really appreciate it. Obviously, I don't spend enough time on the "brainy" side of the forum:)
Bug

[Marcia2202]

Hector, you amaze me each time with the info you are supplying to this forum. Thank you so much, I will get to it immediately.

Marcia

[HectorSF]

Below is a link to a debate between leading US Hepatologists about optimizing treatment for genotypes 2/3. (You may have to sign up on their site to get this doc but it is free).

http://www.medicalcrossfire.com/onlineLearning/cme/2006/06-LC-27-M-100.pdf

Chronic Hepatitis C
"Strategies for Optimizing Current Treatment and the Potential Impact of Emerging Therapies"

PANELISTS
Adrian M. Di Bisceglie, MD - Saint Louis University Saint Louis, Missouri
Michael W. Fried, MD - University of North Carolina at Chapel Hill Chapel Hill, North Carolina
David R. Nelson, MD - University of Florida Gainesville, Florida
Mitchell Shiffman, MD - Virginia Commonwealth University Medical Center Richmond, Virginia

SPECIAL EDITION
Release Date: February 12, 2007 • Expiration Date: February 12, 2008
This activity is supported by an educational grant from Roche Pharmaceuticals.

MODERATOR
Emmet B. Keeffe, MD, MACP Stanford University School of Medicine Palo Alto, California
Jointly Sponsored by The American Academy of CME, Inc. and
Medical Crossfire®/Liberty Communications Network.

****( Text starts on Page 7 of PDF)****
"Genotype 2 and 3 Patients:
Presenting the Data"


All the best for SVR!!!
Hector