Anyone have an idea for a fast viral drop for Joe

[evangelin]

Hi all,
My husband  is at week 25 of his 3rd tx try, this time with Alinia added.  He has compensated cirrhosis so there is an urgent reason to succeed.
  The Alinia has made him a much better responder but it is still falling short as he is responding  too slow.  It was planned to have him stop after the 24th week if he wasn't nondetectible.  At 20 weeks his viral load was 207 and at week 24 it was 250...not good.
The doctor's office  called and said not to quit yet and we have an appointment on December 2nd to decide what to do.  The reason they decided not to stop right now was because his ALT came back as "18" which was certainly a beautiful number to behold.  The treatment has made him sick with lots of nausea most of the time and he looks like a wreck at this point but we know it is a long wait until Teleprevir comes out and we sure don't want to leave any stone unturned if there is any chance of success.  
Does anyone have any brilliant ideas to push Joe to nondetectible?  Yes, I'm asking for a miracle.
We sure would appreciate prayers.
Thanks,
Ev

[Tallahassee]

I doule ditto Gauf!

[gauf]

If it were me (and I am nuts) I would up the procrit to twice a week, DD every 5 days and up riba to 1600. Then I would lock myself in my room until Christmas. If UND at that time, I would scale back to the more reasonable SOC for the long haul.
If not UND at Christmas, then maybe look into maintenence dosing.  In any event I know the supps will keep Joe around a good long time. Godspeace.

[willing]

two thoughts : (1) statins (2) point out to your Drs that the UND-24 criterion is based on 48w tx. If you're willing to tx for  a *long* time - ala bill54 -  it's an artificial cutoff. The last AASLD had a couple of abstracts documenting the correlation between UND-week and extension efficacy. If you're willing to go to 96 or better, UND24, may not be the right cutoff - and that beautiful ALT's likely to be at least an indicator of a promising holding pattern.
All the best

[orleans]

Considering the consequences I had better make sure, I'm gonna try to get the test? thanks guys, jerry

[evangelin]

I'm really thinking about the DD of interferon.  I tried posting to Dr. D but it wasn't allowing more questions.
Joe's Dr. appt. is on Tuesday at St. Louiis University Gastro Dept. and they have been really good.  Joe was very underdosed the first 2 tx's at another Gastro office. He was given 800 mg. of Riba and they repeatedly reduced the dose for anemia.  What a big sorry waste that was.  We had to make the long drive to a teaching hospital to get the kind of care that had any chance of working.  They are willing to push a little to make this work and I've been so thankful to have them.
I appreciate all the support and will report what we do and what happens.
Blessings,
Ev

[CoWriter]

It's called a HOMA test.....which is basically a formula that uses the results from a fasting blood sugar and a fasting insulin to figure out if you have insulin resistance.

Be aware that doing just the fasting blood sugar is not the same.  

Co

[CockSparrow]

Glucose and Insulin are the blood tests you need.
With your viral decline its unlikely you are Insulin Resistant.

Although being stage 3 you could be.
CS

[orleans]

CoWriter, EXACTLY what test would I request to check for insulin resistance?
Evangelin, Hey, we started tx near one another and are Alinia buddies. I don't really have any advise but will (and have) keep ya'll in my prayers. your friend, in Him, jerry

[geterdone]

It also may be the fact that there are some strong master printers floating around that have become resistant to the maxc of the INF dosage being taken. The virus/viron is a master of elusiveness meaning it sometimes changes faster than its environment to defend itself from excitation and mutates to a higher level or resistant of the INF and Riba being taken at the present regimen. I am sure you know how the virus works by now and is surly worth a shot, no pun intended. But yes, talk it over with his doctor before doing anything out of the box.

I did DD with the doc's approval in the first week of treatment and upped my dose of INF 2 weeks in the last 4 weeks of treatment for self assurance that I had killed the Bast***’s. Yeah the blood work went whacky and the doc raised an eyebrow when reviewing the report but at that point it was, don’t ask, don’t tell until the game was over.

Good Luck to both you and especially Joe.  

jasper

[can-do-man]

Well i'm sure not qualified to give you any advice, but any chance the last pcr was wrong? I'm also cirrhotic and i know my hepo worries about how we tx. The last thing they don't want to do is cause us any more liver problems... As always wishing you and joe the very best.

cando

[nygirl7]

Heck yes right now it's all or nothing. A few of us have doubled riba but be warned - the anemia side is brutal so as jim said if doc agrees add on Procrit to try and offset if possible and double dosing peg I didn't find to be as brutal as the riba (but I DD'd riba until week 46 of 72 and only dd'd peg a few times (mostly in error being paranoid about missing shots and twice because it was week 12 and I had not cleared and I wanted that UND bad so I just did it).

But of course under docs supervision and with weekly testing DEFINITELY. I had a 6 point hemo drop in ten days ......... right between my tests and it would have been very helpful from experience had I been having them weekly.

We are all on you (and Joe's side) and I wish there was some miracle advice for you. As someone who didn't clear until somewhere before week 24, having done 72 - I did not have cirrhosis but certainly understand the disappointment. Let's just hope he can get there in the next week or two by upping things.

I don't know what else to say but you know we all wish you the best.

[geterdone]

Might want to post your question on the resident expert forum Dr. Diterich link provided. He may respond if the heading is Dr. D Question? can't hurt.

jasper


http://www.medhelp.org/forums/show/272

My husband is at week 25 of his 3rd tx try, this time. It was planned to have him stop after the 24th week if he wasn't nondetectible.  At 20 weeks his viral load was 207 and at week 24 it was 250...not good. The reason they decided not to stop right now was because his ALT came back as "18" which was certainly a beautiful number to behold. I am planning to talk to the doctor about  Metformin and will ask about Fluvastatin also.  I think Joe is pretty maxed out on Riba at 1400 mg. and takes procrit once a week.  We tried 1600 mg. for a week or so but he was so nauseas and miserable we had to go back to 1400mg.  Joe is 6 ft and weighs around 170 lbs.
Joe's platelets hang out in the high 50's and haven't changed a whole lot during tx .  I think they were 68 when he started and they were in the mid 40's when not on tx.

Dr. Diterich, given the stats below would it be worth the effort to have joe do a double dose in one week? I mean take his normal shot and then three or four days later take another shot? It seems the caboose on this train is doing its job but maybe the locomotive needs a little boost to push him to UND. Any thoughts on this would be greatly appreciated.

[Tallahassee]

I would take a risk and double at least one shot of Interferon.  My platelets were as low as 25 – 28 and I did not have even a nose bleed.  I think official threshold is 30. Apparently, he reached a plateau and something has to be done to shift this equilibrium.  All other measures (statins, etc.) are excellent suggestions, it should be also done, if possible.
There is no way I would stop at this point.  The “undetect” status does not have to be at 24 weeks! Whenever UND was reached (let say at 48 weeks, like in my case, after my viral breakthrough), all you have to do is to add 48 week to that day prior to stopping the treatment.  
Please stay strong, don’t give up.  You are doing a great job in supporting and treating your husband – please continue doing it!!

All the best!

[CoWriter]

In Chronic Hepatitis C (HCV), Pretreatment with Thiazolidinediones (TZDs) or Metformin Decreases Insulin Resistance (IR) and HCV Viral Load and Increases Early Virologic Response (EVR).

M. Adler, J.L. Matloff, A.S. Boxer, H. Han, M. Vachon, D.C. Carriero, D.T. Dieterich, , Mount Sinai School of Medicine, New York, NY; M. Vachon, D.C. Carriero, D.T. Dieterich, Division of Liver Diseases, Mount Sinai School of Medicine, New York, NY;

Background: Chronic HCV is associated with increased incidence of insulin resistance (IR), which leads to a lower rate of sustained virologic response (SVR) following treatment with peginterferon plus ribavirin (IFN + RBV). Romero-Gomez et al. reported an SVR rate of 32.8% in genotype 1-infected patients with IR (HOMA-IR > 2) compared to 60.5% in those without IR. In addition, IR is associated with increased liver fibrosis and is characterized by a higher viral load, two other independent risk factors for decreased response to treatment. A recent study showed 0/5 EVR in patients with IR who were given a TZD at initiation of IFN + RBV. It is unknown if therapeutic intervention to improve insulin sensitivity prior to anti-viral treatment increases response to HCV treatment. Aim: To evaluate the effect of treatment with TZDs or metformin on IR and viral load prior to IFN + RBV and the impact on EVR. Methods: IRB-approved, we retrospectively reviewed charts of patients with chronic HCV from a liver clinic in our center. We included patients with IR treated with either metformin or a TZD for at least 3 months prior to initiating IFN+RBV. We compared HOMA-IR, HCV viral load, liver enzymes and BMI at baseline, after treatment with an insulin sensitizer (IS), and at week 12 of HCV treatment. Results: 17 patients met inclusion criteria. 10 were co-infected with HIV. The average age was 52.2 years, and 82% of patients were genotype 1. 11 patients were treatment-naïve to IFN+RBV. The mean stage of fibrosis was 2.7 on Metavir score in 12 patients. 11 patients received a TZD and 6 received metformin. The mean HOMA-IR decreased from 7.99 to 6.06 after treatment with an IS to 4.60 at 12 weeks of IFN + RBV. There was a significant mean decrease of 0.52 log in HCV viral load on each patient after treatment with an IS (p<0.01). An EVR was achieved in 12 patients (71%). The mean ALT value decreased from 86.2 at baseline to 72.5 (p=0.02) after treatment with an IS to 34.1 IU/L (p=0.01) after 12 weeks of IFN + RBV. BMI significantly decreased from 27.9 to 26.8 kg/m2 (p=0.02) following treatment with an IS. Conclusion: The use of a TZD or metformin improved insulin sensitivity prior to treatment with IFN + RBV. The baseline viral load, a risk factor for decreased response to treatment and until now referred to as an unmodifiable factor, was also significantly lowered. This intervention allowed a 71% rate of EVR in a population of mono and co-infected patients, the majority being genotype 1. This small pilot study suggests that targeting insulin resistance prior to treatment may enhance the chance of response to traditional treatment for chronic HCV.

http://aasld.scientificposters.com/epsAbstract.cfm?id=3

[CoWriter]

This is the info Jim mentioned on insulin resistance.  

1.  Insulin resistance is a strong predictor of non-response.
2.  Insulin resistance results in hyperinsulinemia and high levels of insulin make interferon ineffective.
3.  The third study was done on non-responders and co-infected patients and it showed that treating insulin resistance lowered the viral load and resulted in an EVR of 71%.

Wishing you and your husband all the best,

Co


Insulin-Resistance in Chronic Hepatitis C patients: New Predictor of Sustained Virological Response Independent of HCV Genotype and Liver Fibrosis Stage

Abstract:
Background & Aim: Insulin-Resistance (IR) has been previously shown to impair sustained virological response (SVR) rate in chronic hepatitis (CHC) patients infected with genotype 1 when treated with pegylated interferon and ribavirin. The aim of this study was to assess the independent impact of IR after adjustment to major predictors of SVR, particularly HCV genotype and liver fibrosis stage. Patients and

Methods:
167 consecutive non-diabetic treatment-naïve CHC patients, treated in our centre with pegylated interferon plus ribavirin, were prospectively assessed. Insulin resistance was assessed using the Homeostasis Model (HOMA-IR). HCV genotype was determined by sequencing. Serum HCV RNA was quantified using bDNA (Bayer Versant HCV RNA 3.0 Assay). Liver histology was assessed using the METAVIR score. SVR was defined as undetectable serum HCV RNA 24 months after treatment stopping.

Results:
Baseline characteristics were: male gender (66%), mean age (46±9 years), mean BMI (24±4 kg/m2), excessive alcohol consumption (9%). Blood transfusion and intravenous drug injection were the principal source of transmission (52%). HCV genotype distribution was: 1 (47%), 2 (7%), 3 (24%), and 4 (22%). Mean serum HCV RNA level was 5.5±0.7 log10 IU/mL, and 42% of patients had high serum HCV RNA level (>600 000 IU/mL). Median value of HOMA-IR was 2.1 (IQL range 1.1-4.6). Liver histology showed moderate-severe necroinflammation (METAVIR score A2-A3) in 46%, severe fibrosis (METAVIR score F3-F4) in 32%, and severe steatosis (>30%) in 29% of patients. By univariate analysis, SVR was associated with HOMA-IR, HCV genotype, serum HCV RNA level, liver fibrosis stage and steatosis. Patients with HOMA-IR 2 (72% vs. 44% respectively, p<0.01). Patients infected with genotypes 2 and 3 achieved higher SVR rates than those infected with genotypes 1 and 4 (79% vs. 46% respectively, p<0.001). Patients with low viral load achieved higher SVR rate than those with high viral load (67% vs. 44% respectively, p<0.01). Patients with mild-moderate fibrosis achieved higher SVR rate than those with severe fibrosis (62% vs. 44% respectively, p<0.05). Patients with mild-moderate steatosis achieved higher SVR rate than those with severe steatosis (62% vs. 42% respectively, p<0.05). By logistic regression, SVR was associated only with HCV genotype 2 and 3 (p<0.001, OR=4.5, CI=2.0-9. and with HOMA-IR <2 (p<0.01, OR=2.8, CI=1.4-5.5)   Conclusion: INSULIN RESISTANCE is a MAJOR NEGATIVE PREDICTOR of SVR in chronic hepatitis C patients treated with pegylated interferon plus ribavirin. Impact of insulin resistance is independent of HCV genotype and liver fibrosis stage.




Insulin resistance and hepatitis C.

Romero-Gómez M. Unit for The Clinical Management of Digestive Diseases. Hospital Universitario de Valme. Ctra de Cadiz s/n. Sevilla 41014, Spain.

Insulin resistance is the major feature of the metabolic syndrome and depends on insulin secretion and insulin sensitivity. In chronic hepatitis C, insulin resistance and type 2 diabetes mellitus are more often seen than in healthy controls or chronic hepatitis B patients. Hepatitis C virus (HCV) infection promotes insulin resistance, mainly by increased TNF production together with enhancement of suppressor of cytokine (SOC-3); both events block PI3K and Akt phosphorylation. Two types of insulin resistance could be found in chronic hepatitis C patients: "viral" and "metabolic" insulin resistance. Insulin resistance in chronic hepatitis C is relevant because it promotes steatosis and fibrosis. The mechanisms by which insulin resistance promotes fibrosis progression include: (1) steatosis, (2) hyperleptinemia, (3) increased TNF production, (4) impaired expression of PPARgamma receptors. Lastly, insulin resistance has been found as a common denominator in patients difficult-to-treat like cirrhotics, overweight, HIV coinfected and Afro-American. Insulin resistance together with fibrosis and genotype has been found to be independently associated with impaired response rate to peginterferon plus ribavirin. Indeed, in genotype 1, the sustained response rate was twice (60%) in patients with HOMA  2. In experiments carried out on Huh-7 cells transfected by full length HCVRNA, interferon alpha blocks HCV replication. However, when insulin (at doses of 128 microU/mL, similar that seen in the hyperinsulinemic state) was added to interferon, the ability to block HCV replication disappeared, and the PKR synthesis was abolished. In summary, hepatitis C promotes insulin resistance and insulin resistance induces interferon resistance, steatosis and fibrosis progression.

http://www.ncbi.nlm.nih.gov/pubmed/1713 ... d_RVDocSum


(will continue on next post)

[merryBe]

it's gotta be brutal to hear such news, my heart goes out to you both.

my VL went down and up again, and they were going to pull me of tx.
but I stopped eating fiber with my Riba dose, and stopped all fats and oils (rather on the same principal as the statin theory.

My reasoning was either I had developed awild strain OR my use of healthy oils was giving the virons a better lipid shell and ergo more protection from the meds.
Also, I didn't know at first that fiber could prevent riba absorption until someone in here told me.
Also, while it makes sense to take some fat with Riba for absorption, and I was taking PPC also a good fat capsule to stop fibrosis, it also became apparent after a while that maybe the fat was helping the virus too...(based on some of HR's material).
In any case, as soon as I made those changes I went UND.
He's SO close to it now, it would be a shame to not make the goal.  Remember though he will need to extend tx out at least to 72 weeks if he goes UND now, especially if type 1.
Lord help and be with you both.

mb

[evangelin]

Thanks...you guys are great.
I am planning to talk to the doctor about  Metformin and will ask about Fluvastatin also.  I think Joe is pretty maxed out on Riba at 1400 mg. and takes procrit once a week.  We tried 1600 mg. for a week or so but he was so nauseas and miserable we had to go back to 1400mg.  Joe is 6 ft and weighs around 170 lbs.  I'm a little scared to double up on pegasys with the cirrhosis.  Joe's platelets hang out in the high 50's and haven't changed a whole lot during tx .  I think they were 68 when he started and they were in the mid 40's when not on tx and before HR's supplements gave everything a little boost.  He wasn't even considered well enough to treat again until he took HR's supplements for around 8 or 9 months.
If he has to stop, we will go back to HR's supplement list.  They had Joe feeling better than he has in 5 years.  He feels like doggy- doo right now but we still have hope.
If any other outside the box ideas come up ,let me know.
Have a nice Thanksgiving,
Ev

[copyman]

sorry to hear he has not responded all the way and I would normally say stop. but since there is cirrhosis involved i would continue for awhile. it is obvious that treating is giving his liver a much needed break with the ALT being 18. And with some luck possibly regress a stage from cirrhosis. best of luck

[kickboxingmom]

HiYou two are on my prayer list !Let us know what you guys decide to do.We'll be looking Dec.02.
God Bless,
Tammy

[Trish77]

Hi Ev,

Here's a radical thought that I'll toss out to you...fluvastatin.  It's a statin used to treat high cholesterol but has been found to significantly lower the viral load.  I'll include some links.  There are were initially some concerns about it's impact on the liver but not enough to prevent it's usage for persons with Hep C, only to be aware of it and to monitor .. not much different than monitoring other vitals and bloods while on treatment.  This is covered in the first link I've included.  What the heck, I figure it's worth bringing up.  Out of the box... but so is alinia for that matter.   Rooting for you and Joe, Ev.

Trish

http://formularyjournal.modernmedicine.com/formulary/Clinical+Meetings/From-Digestive
-Disease-Week-2007-Statins-demonstra/ArticleStandard/Article/detail/442867
(put those two lines together)

"Researchers have investigated the effect of statins on hepatitis C for several years, but the treatment is not approved by FDA. In fact, use of many statins is contraindicated in patients with active liver disease. However, FDA recently removed this contraindication from the package inserts of 3 statin agents, and literature reports indicate that only approximately 10% of patients experience deviations in ALT levels with statin use and that any elevation is often temporary, Dr Bader said. "

and in addition also from this article ..

"Dr Bader compared these results with those from a retrospective analysis of the VA Medical Center database and discovered that of 60 patients with hepatitis C, 13 began statin treatment with abnormal ALT values; 12 of these patients experienced improved ALT levels with statin treatment. The remaining 47 patients with hepatitis C had normal ALT levels when statin treatment was initiated, and 45 of these patients maintained normal ALT levels throughout the trial. Two patients developed mildly abnormal ALT levels, but both reported heavy alcohol use.

"The data not only support the lack of harm in this situation, but also seem to suggest a possible salutary effect that needs further study," Dr Bader said.

A retrospective analysis of 104 patients with hepatitis C who received PI+R versus 30 patients who received PI+R plus a statin (simvastatin, n=25; lovastatin, n=2; atorvastatin, n=2; or fluvastatin, n=1) was conducted to measure sustained viral response rates. Overall, a pooled analysis demonstrated a 63% sustained viral response among patients receiving PI+R plus a statin versus a 37% sustained viral response among patients receiving PI+R only (P=.009). The effect was most pronounced for patients with HCV genotype 1 (P=.014), which is the most difficult type of hepatitis C to treat, Dr Bader said. "

A few more random tidbits.....

http://www.physorg.com/news127138395.html

http://www.medicalnewstoday.com/articles/46747.php

http://esciencenews.com/articles/2008/05/14/new.treatment.hepatitis.c

[jmjm530]

Another thought. Has your husband been tested/treated  for insulin resistance (IR)? Treating IR through meds like Metaformin is  showing pontential in terms of SVR. "CoWriter" or some others may hv the studies handy.

[jmjm530]

With doctor on board maximize riba to tolerance coincidental with adding Procrit (epo) to even further raise serum riba levels per tolerance. This requires frequent monitoring and an understanding that sfx can lag dose change by 2-3 weeks. Nausea can be treated with marijuana or other meds like Zofran. The risk here is increased sfx. Also consider double dosing Peg and/or changing Peg type till UND. Ask for weekly sensitive  load tests till UND