Engaging HIV-HCV co-infected patients in HCV treatment: the roles played by the prescribing physician and patients'beliefs (ANRS CO13 HEPAVIH cohort, France)

Published on: 2012-03-12

Treatment for the hepatitis C virus (HCV) may be delayed significantly in HIV/HCV co-infected patients. Our study aims at identifying the correlates of access to HCV treatment in this population.

Methods: We used 3-year follow-up data from the HEPAVIH ANRS-CO13 nationwide French cohort which enrolled patients living with HIV and HCV.

We included pegylated interferon and ribavirin-naive patients (N = 600) at enrolment. Clinical/biological data were retrieved from medical records.

Self-administered questionnaires were used for both physicians and their patients to collect data about experience and behaviors, respectively.

Results: Median [IQR] follow-up was 12[12-24] months and 124 patients (20.7%) had started HCV treatment. After multiple adjustment including patients'negative beliefs about HCV treatment, those followed up by a general practitioner working in a hospital setting were more likely to receive HCV treatment (OR[95%CI]: 1.71 [1.06-2.75]).

Patients followed by general practitioners also reported significantly higher levels of alcohol use, severe depressive symptoms and poor social conditions than those followed up by other physicians.

Conclusions: Hospital-general practitioner networks can play a crucial role in engaging patients who are the most vulnerable and in reducing existing inequities in access to HCV care. Further operational research is needed to assess to what extent these models can be implemented in other settings and for patients who bear the burden of multiple co-morbidities.

Author: Dominique Salmon-CeronJulien CohenMaria WinnockPerrine RouxFirouze Bani-SadrEric RosenthalIsabelle Poizot-MartinMarc-Arthur LokoMarion MoraPhilippe SogniBruno SpireFrancois DabisMaria Patrizia Carrieri

Credits/Source: BMC Health Services Resear

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My Story

By Daryl Luster

I would like to begin my story with a salute to all of those people that have helped me, and others diagnosed with HCV. It has never mattered to me how someone was infected. I know people that used drugs and shared needles, as well as people that have received the virus through tainted blood transfusions, and none of it matters to me. What matters most is that people with HCV need help, and that help takes many forms. I am fortunate enough not to have the severe financial burden that many with this disease face. I can’t imagine what it must feel like to face HCV without medical options as well as any semblance of a support system, which I believe is so very important. I am deeply discouraged by the stigma that we all face when we are diagnosed with HCV.

I never knew many things about this disease until I was diagnosed .I began a journey toward understanding and knowledge, and ultimately ridding my body of this terrible virus.

The journey actually began when I was hospitalized almost 4 years ago with extreme abdominal pain. After three days in the hospital, and many scans and tests later, all that they came up with was that I needed to have a hernia repair. They asked several times “why was I there”. I am otherwise a healthy person, with the exception of having asthma that is treated successfully.

In the next several months I underwent many tests that included colonoscopy, gastroscopy, many blood tests, a CT scan, and finally while being pre-screened for the hernia repair it was discovered that my iron levels were high. This finally led my primary care doctor to check for hepatitis with more blood work. The preliminary screen showed that I might have the virus.

The second blood test confirmed that I did have HepC.

That was in July 2009.

I was devastated by this news.

The next couple of months were very difficult for me. In my mind my life was over. I was 55 years old, with so much more that I wanted to do in my life, and now I am going to die. That went through my mind over and over. As I began to research the virus, it didn’t get much better, because it seemed like it was all bad news. I was obsessed with it, and I couldn’t get it off my mind.

The next step was to see a Hepatologist. More blood work was ordered to determine my genotype, etc. It came back as genotype 1b, and I was told that it was the most resistant to treatment. It was just more bad news. It seemed like that was the only news I was going to get.

The next step was a liver biopsy in early December 2009. That produced some good news about my liver. I was happy to learn that I was stage 0-1,which means that there is little damage to my liver from the disease. I was so happy to finally hear something positive, and it was a great relief for my wife and family. The next step was to plan for treatment. I was asked if I would be interested in participating in a drug trial along with standard treatment. The Hepatologist gave me three options actually. The first was to do nothing, the second was standard treatment, and the third was with the drug trial. I decided that I would go into the trial because the drug had shown a substantial increased chance of clearing the virus, and reaching SVR. Since deciding to be a part of the trial I have undergone many screening tests to determine if I am suitable.

The only thing they found during screening was that I have a condition called optic nerve drusen. I am scheduled to start treatment in a few days, and as far as I know I have been accepted to participate.

As I begin the next stage of my journey, I have a sense of relief mixed with anxiety about how the drugs affect me. I want to continue to work as much as I can, and keep my life as real as possible.

I want to continue to be myself, and not be defined by this disease. Something that is very important to me is that there be more awareness and education about HCV so that people will get tested, get treated, and get better, without all of the added burden of stigma, isolation, and financial hardship.

I wrote this before I started treatment in 2010.

My treatment was 48 weeks, and that was a challenge at times, but I was undetectable at 5 weeks, and went on to reach SVR at 24 weeks post Tx. I just had my one year PCR a couple of weeks ago, and I remain clear of the virus, and continue to feel better and better…as time goes by.

I am more involved than ever in trying to spread awareness and understanding about HCV, and will remain committed to this for as long as I possibly can. There are some new drugs that have shown amazing results, and newer ones will show even greater promise, and one day a vaccine!

I wish for all to have the possibility for a better quality of life, and a disease free existence.

Hope and Peace

KURT’S CONTINUING HEP-C/TRANSPLANT STORY

2008

In May Kurt was taken to the emergency room with severe abdominal pain.  That was the beginning of the many hospital visits and admittances to help combat the Hepatitis C virus that was ravaging his body. Various treatments to make him comfortable and send him home only to be taken back again in a matter of weeks.   VCU doctors then told us the news that he would only get worse and that unless he had a liver transplant, he would die. One doctor told us he would need a living liver donor as the wait for deceased donors was in the hundreds of thousands and he would not be moved up on the MELD score until he was critical. He said “Kurt could die waiting for a liver transplant”.

Those words prompted me to send an email to friends and family to ask for prayer and to put the word out that Kurt needed a living liver donor. That email was sent throughout the community by well meaning friends who also contacted the media and the next thing we knew, we were receiving emails from all over the country with prayers, with encouragement and even people who did not know Kurt personally, that were willing to be a donor for him

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DO YOU KNOW A HERO? I DO!

By Kathie Beach

In 1988, my husband Kurt, a Smithfield Police Officer, responded to an emergency call and tried to save a child's life who had been born with spina bifida and had a trachometry in her throat to be able to breathe. On this day, the child was not breathing and her heart had stopped. Kurt proceeded mouth to trach breaths and CPR on her having to suck the blood and mucous out of the airwaves to try to give her oxygen. It was to no avail, the child, sadly died. The mother of that precious child knew Kurt did everything within his power to save her. She considers Kurt a hero. So do I.

In 1988 the police department was not trained on blood pathogens and Hepatitis C had not even been classified yet, being called Non A and Non B Hepatitis. Kurt's attempt to save a life put his life in jeopardy. Later, he found out the terrible news that he had contracted this disease when he came in contact with the child's infected blood due to multiple blood transfusions her condition had demanded.

All these years God has kept His hand on Kurt. Although he was diagnosed with Hepatitis C and aggressive chronic liver disease, he was able to work and go about his life. He worked hard and gave tirelessly of whatever was required of him. He endured countless tests, procedures and experimental therapies to try to rid his body of the disease. The doctors were amazed by his stamina, his faith and his encouraging ways. He bounced back again and again and I suppose we always thought he would.

Then in May of this year he ended up at Obici hospital for a five day stay. From there he went to MCV where his team of doctors did extensive tests and evaluations. Another stay at Obici and another round at MCV and then finally this week we are told by his team of doctors that Kurt needs a new liver and we need to prepare him for a live donor as a wait for a DD (deceased donor) is in the 100,000s. They did not mince words that Kurt could die waiting for a liver donor.

Kurt needs a living donor liver transplant.

This is a procedure that involves the removal of the recipient's (Kurt) native liver and replacing it with a potion of the living donor's liver. Both Kurt's and the donor's livers will regenerate to normal functional volume within weeks. AMAZING!

Kurt has a wonderful team of doctors who have monitored him over the years and when they convened they said he is a perfect candidate for this operation. The doctor went so far as to say 'Kurt, you will feel like a new man. Able to work, play and live and you will feel better than you have in years.'

My hero needs a hero, he needs a living donor.

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January 30,  2009



Kurt has been home since September maintaining until we get that longed for call.  Though his body is weak,  his spirit is strong.  VCU is keeping him monitored by monthly visits and local weekly blood tests indicate how to adjust his medications. It has been quite a balancing act.   Kurt is on a low sodium diet, juicing, eating mainly fresh vegetables and fruits with a little lean meat and fish.  God has given us wisdom on how to keep him as strong as possible while we wait and our goal is to keep him out of the hospital until he goes for the liver transplant. 

VCU's policy  will not allow them to give us any information on potential donors. They are steady screening and have been since late October, 2008.  We know of 10 so far who have gone for screening but was not a match for Kurt. There may have been more, but, those are ones we know of.   Even as I write, someone is probably being run through the diligent and detailed tests that every donor candidate has to pass to be a match for someone.   You can't imagine how grateful and humbled we are by their act of selflessness.  The fact they could not donate due to one reason or another, does not diminish their courageous act.  In God's eyes, what is purposed in the heart is as if it were done.  So it is with Kurt and myself.  We know they were willing to lay aside personal comfort, schedules, possibly even paychecks and undergo surgery!  That makes them our hero!

We had a beautiful Christmas time, God's presence and love in our lives reminded us daily of why we celebrate the season and the birth of His Son, Jesus.   Kurt was feeling well enough to visit with family in Hampton.  Here is a picture of our family at his mom's!

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January 31,  2009

Whew!  Rough couple days.  I had to take Kurt to the emergency room on Friday afternoon, he was in a lot of pain and very weak.  BUT GOD, His army of prayer warriors and doctors endowed by His wisdom and direction, intervened and today he was feeling MUCH better and completely pain free.  Thank You, Jesus!  The doctor's are doing alot of tests and working closely with VCU to coordinate Kurt's unending balancing act of meds, methods and methologies.  (is that a word?) not to be confused with mythology. :)  They are keeping him for now to further study him and make sure he is well stabilized.  I'm believing he will come home tomorrow or Monday latest.  Our heart felt thanks to all who are praying.


BIG Happy Smile!!!!!!!

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February 4,  2009

Kurt is home!  I brought him home from VCU yesterday afternoon.  He is very happy to be in his own environment.  News 3 was in Richmond covering the two Kurt Beach Bills and was able to interview Kurt leaving the hospital.  The compensation bill HB2243 that Delegate Barlow put in for us, passed unanimously!  However, we learned later that evening that the workmen's compensation bill HB2252 was killed. That was so dissapointing.   I am still waiting to hear the details as I was at the hospital with Kurt and couldn't be in the committee meeting.  I am told HB2243 will go to the house and then the senate.  I am putting together a list of names and emails to forward to our TEAM and keep the momentum going on this.

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February 6,  2009

We received a call from Melissa, Kurt's transplant coordination nurse.  She gave us the news that Kurt had moved up to #22 on the national transplant list.  His low sodium levels placed him in a more critical mode and he could end up with a deceased donor before they find a living donor for him. We did not expect that and it was a sobering thought, one we hadn't thought out because we were fully expecting to find our living donor by now.  What that means is we could get a call anytime and have to be ready to hit the road immediately to travel to VCU for the transplant.  On one hand we are grateful that he is closer to getting a donor, either deceased or living.  On the other, we don't like the reason behind his being moved up the list.  We still feel Kurt's donor will be a living one, but, either way we are grateful.  Today Kurt felt stronger than he has in weeks.  His voice, his eyes, his energy level all much improved.  God is good, prayer is great and our friends are such an encouragement to us.  We are still waiting the outcome of Kurt Beach bill HB2243 as it goes to the House  & then Senate. 

Our hopes are high! God has given us much favor with man who has rallied on our behalf and who have heard our story and given their approval.  We are in the waiting mode on both these subjects.....liver donor and passing bill.

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February 13, 2009

What a busy week we had!  Busy and one of the best weekends we've had in months, NO, years!  Kurt had prayed to have the strength to personally make the fundraisers our town put on for him on Saturday and Sunday.  God answered that prayer and some! He ate his first hotdog in 6 months at the TrueValue 1,000 hotdog event and then tasted some fine BBQ and chicken at the Center on Sunday.  But, more importantly, he tasted the love of God through sooooo many people that he was overwhelmed with emotions and the love he received and felt towards them.  What an awesome community we live in.  Thousands of people from all over Isle of Wight County and friends past and present from as far away as Charlottesville, VA. (Hi Jim!)

I was told more than 5,000 people came and went throughout the day and they turned over 600 people away that didn't have tickets.  WOW!  Talk about a party!

Woo hoo!  It was great, exciting, fun and Kurt and I will never forget it.

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February 24,  2009

Kurt is still home, staying strong and even attended church Sunday!  We celebrated another holiday at home, Valentine's Day.



It was a beautiful weekend and we even got away to OBX for a couple days.  Peace, quiet and lots of rest.



Men, beware.....this is what happens when your wife gets you away for a couple days with no phone or TV.....buwa ha ha !

Yesterday I found out the compensation bill passed through the Senate and now it goes to the Governor to sign.  Not sure when that will happen, but, will be informed so Kurt and I can be present for the signing.  It's pretty amazing to think that the compensation will come out of workmen's compensation...the very organization that denied Kurt all those years he had to pay out of pocket medical expenses.

Another neat thing happened today, Kurt has been nominated for America's Most Wanted All Star Contest.  His bio is on their webpage.   There is a weekly winner and a grand prize finalist.  You can vote once a day every day until April 12th.  You know I already voted for my Hero!
 http://www.amw.com/allstar/2009/nominee_detail.cfm?id=6067

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March 5,  2009

TEST RUN

We made our first "test run" to VCU to get ready for a transplant.  We got the call at 5pm that a deceased donor liver was on it's way to Richmond and Kurt needed to get there and get prepped for surgery.  In spite of frozen roads and lots of snow on Richmond streets,  News 3's, Jeremy Crider, beat us there and it was really exciting thinking of the prospect of Kurt finally getting that procedure that would save his life.   We all joked how it felt like we were having a "baby" FINALLY! 

We found out the hospital runs differently at night and finding our way around to the Hume-Lee Transplant Center and to the team that was waiting on Kurt to arrive, took more time than we thought, but, we did make it.   They got him into a room and started inserting IV's and running tests.  I made myself comfortable in the waiting room where another transplant family member, Kelly, was waiting.   Kelly's mom was in critical condition and desperately needing a new liver.  Her call had come that day as well.  There were two livers on the way to our two family members. 

Neither Kurt or myself could sleep that night, not just because the nurse kept coming in and out of his room, but, because we were too excited.   At about 4:00 am, the doctor came in and told us Kurt would not be having the surgery.  The liver upon final examination was not healthy enough for the doctor's satisfaction.  We were released to go home and wait for the next try.  Kelly’s mom did get hers. That was good news to hear!

It was disappointing, my Hero would have to wait.  But, we felt God's hand ever directing the outcome and knew HE knew best for us.  We will wait and the right one will come.  In the meantime we will stay packed and ready to roll as we have been told Kurt has moved up to 1st on the list and we cannot go too far from home if that phone call comes.  Time is of the essence.


 
Me, Jeremy, Kurt, Eric

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March 8,  2009

ANOTHER TEST RUN!

Things are really cranking up now that Kurt is high on the list for ANY donor, living or deceased.  We had another call for a deceased donor on Thursday in the wee hours of the morning.   Kurt and I both didn't get a go on it from the Lord, so we declined.  Yes, we did!  We just didn't have peace about it and so we chose to say no to it.    Then Saturday at 11 pm, we got another call for a potential deceased donor.  This one we went for.  We ran home, threw our suitcases in the back of the car and took off for VCU to be there by 2 pm for prepping.  Once there a flurry of activities, blood work, IV's,  introduction of nurses, anesthestic tech, sample this, sample that, hooking Kurt up and then........wait.   and wait......and wait.    The potential liver had been examined on site that was sending it, but once it gets to the doctors at VCU, then they biopsy it and check for hidden dangers to Kurt, like disease, weakness, etc.  If it passes that far, the surgeons themselves will look at it to see if it meets their standard.  In this case, the liver didn't pass the biopsy stage.  We found out a little after 12 midnight (well really 1am since time jumped ahead an hour)   We were not discouraged.  We thanked the staff for their diligence to cover Kurt so well and we thanked God for protecting Kurt from a liver that was not meant to be his donor liver.  We also prayed for the man (and loved ones of the man) who had lost his life but had  been willing to pass on part of his body to help someone else. 

So we left VCU, bags in hand around 2 am, stopped for breakfast at IHOP as Kurt was starving.  He hadn't had anything solid to eat for 15 hours and was feeling weak from lack of food and just generally being in the hospital twice in one week for such an endeavor.  We both crashed at 4 am as our heads hit our own pillows. 

Today was beautiful and we took advantage of getting more things in order so when we do get that ONE phone call that will take us to the next level.....the organ transplant itself, we will be ready!

Kurt getting ipod ready....praise music and healing scriptures at his command!

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March 29,  2009

Kurt was admitted to VCU via emergency room on Sunday, March 15th.  He spent 5 days there while they treated him for infection in his blood.  I traveled back and forth to Richmond every day and each day he got better.  ( 1 ½ hr. drive) While there, he received the best of care and personally got to know all his caretakers, nurses and doctors by their names and faces.  We both were impressed by their compassion and their willingness to work with Kurt's teams of doctors in Hepatology.  He was discharged on Friday afternoon and was looking forward to stopping in Hampton for some seafood as he had been craving fish all week. 

Friday night we attended the Black & White Crystal Gala event at Smithfield Center.  Kurt was an honoree and awarded for his assistance in getting Mission of Hope started and his work with the homeless.  He and I dressed up for the first time in over a year and went out on the town,  the town of Smithfield!  We had so much fun

Today, Kurt's mom is picking him up so he can visit with some relatives that have stopped in town.  I am starting the task of moving items out of the house and getting rid of some things that collect dust and that Kurt can't have around after his transplant.  At least for 6 months.  No more live plants.  All fake ones are being moved out.  Ideally the carpet should come up and hardwood floors put down, but as a compromise, we are having a man come and clean all the furniture and carpet with organic compounds.  no harsh chemicals.  Another man will come and clean the vents and we have purchased air purifiers to help keep dust, and germs at a low minimum.

This is going to be quite a task, as my house is stock full of stuff and let's be real.....it's spring time in Virginia!  Pollen, flowers, grass, dust, is EVERYWHERE!  But, God!  There He goes again.  No worries here.  It will get done.

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April 1,  2009

I took Kurt to his sister's (Eva) house in Kitty Hawk to spend several days recouping while I came home to get the house dust free and post transplant ready.  We are steadily moving towards that day, still not knowing for sure, but surely knowing it will come.
 

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April 7,  2009

Governor Tim Kaine signed the Kurt Beach Compensation Bill today!  After years of out of pocket medical expenses,  ( Kurt was denied  workmen's compensation due to statute of limitation law)  today he received justification and a wrong was righted!  The Governor was originally going to sign all bills on Wednesday but we had to be at VCU for an appointment for Kurt.  Instead, they arranged to have us meet on Tuesday and we were able to be there, along with News 3, Jeremy Crider and side kick cameraman, Eric.   We are still pinching ourselves. :)

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April 10,  2009

What a GOOD FRIDAY!   It's official!  Kurt is back on the transplant list.  The abdominal tap on Wednesday showed there was no infection and he is clear to go!  Go God Go!

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April 13,  2009

My Hero got his Hero!



On Good Friday, April 10th, Kurt received the news he was put back on the transplant list after being taken off due to infection.  We were also told our potential living donor was a go and they wanted to schedule us to come in on Easter Sunday.  So we checked into Hume-Lee Transplant Center on Resurrection Sunday for preparation for transplant surgery on Monday.  The surgery went well for Kurt and his hero donor, who wants to remain anonymous.   Dr. Fisher told us he was the "perfect match".  We never doubted God had the perfect match for Kurt. 

We have met our Hero Donor and his wife.  They are beautiful people as you would expect.  Very humble and giving, the both of them.

Kurt and I are so grateful for these wonderful people and ALL the people who called the transplant center to be considered as a living donor for Kurt.  Words are hard to express.  We are BLESSED!

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April 29,  2009

It's been quite a learning experience since Kurt was discharged and we have had to be responsible for the medications, everything from anti-rejection to pain.  All the procedures, blood pressure, blood sugar, temperature and weight having to be done throughout the day.  Kurt is on insulin for now, we are believing over time his blood sugar will normalize.  Right now, it's a small inconvenience to give himself shots to be able to have a new shot at life.  (pun intended :)

Kurt came home today and what a great day it is.  So good to be in an environment of peace and appreciation.  He was met by family and some of his fellow officers.  There were many cards, prayers and well wishes waiting for him.

We are blessed and so happy.

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May 5,  2009

WOW!  We received the report of the Lord from the good doctor today!  We met with Dr. Fisher and he told us that Kurt's liver is fully grown and all his tests show good results!  "Just keep on doing what you're doing, Kurt!"    Kurt says, “I can’t take credit, it’s God, it’s prayers!”

  Removing stitches

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May 20,  2009

We were invited guests at WTKR on Monday evening to be part of the evening newscast and have opportunity to give glory to God for bringing us through and to meet with the news 3 team and thank them personally for all they have done to help get not just Kurt's story out, but the story of organ donation.

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August 19,   2009

Kurt went back to work part time about a month ago.  Light duty, partial hours, as he could tolerate.  Well....for the past two weeks he has been working FULL days, 40 hour weeks and is gaining strength, stamina, every day!  He is sharp mentally and able to swing into full time investigations right where he left off over a year ago.
 


We are so thankful for the prayers and support we have received from so many and one way we are sharing our testimony to God and others is by exhibiting our very first personal license plates!
   

This plate is a double read.  It says "GREAT LOVE" in reference to our Hero Donor whom we know is a man of compassion and sacrifice, just like the scriptures say....."greater love hath no man than to lay down his life for a friend." 

It also stands for "GREAT TO LIVE!"  which Kurt and I give thanks daily to God and make this a routine saying over dinner or whenever we are giving thanks throughout the day!  We will never forget!

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JANUARY 24,  2010



We've made it past the 1st month, 3rd month, 6th month and shooting for the 1st year post transplant mark.  These are important landmarks to pass and we are so grateful for a new life, renewed life and don't take one day for granted.  We have celebrated holidays, enjoyed Thanksgiving and Christmas with family and friends, and even a wedding in which Kurt was the sound man.  Throughout it all Kurt has been strong in mind and spirit as he is getting his body strength up as well with a personal trainer at the Y.  There have been some treatments and therapies we didn't expect,  CMVIG treatments every week for 6 weeks and we nearly spent Christmas in the hospital when Kurt's levels elevated and they thought his liver could possibly be rejecting.  An ultra sound and liver biopsy later indicated this wasn't the case.  Thank God!  We will be seeing the doctor next month and find out what the next preventative maintenance step will be.  The goal now is to keep the Hep-C virus at bay with Kurt's immune system being suppressed.

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FEBRUARY 9,  2010

Kurt and I had a very busy week last week.  We met with Dr. Stravis, head of Hepatology at VCU and was given the game plan on combatting Kurt's Hep-C with his immunity being driven down by the anti-rejection drugs.  A catch 22 scenario for sure.

But, there is hope in that there are current trial drugs/therapies being administered with high numbers of success rates in stopping the progression of Hep-C altogether.  Unfortunately, at this time, Kurt will not be a candidate for this trial as they are looking for pre-transplant patients until it is FDA approved.  So, we're praying it will be within the next three years .  That is the time line we are given that his Hep C could begin to cause serious problems with him again.

He is scheduled to have outpatient surgery next Monday to remove stents that were suppose to dissolve but did not.  They say it is a simple procedure.

We also went to Richmond on Thursday to advocate on the passing of HB1346.  News 3 gave their support and met us there to film the vote. 

This bill was our second attempt to have the current workman's compensation statute of limitation law amended to ensure first responders that come into contact with Hep C in the line of duty, would have time to file claim.  I will post the link to the bill so you can read it yourself. 

Unfortunately, the bill was killed, or let lie, tabled, whatever you want to call it, for the second time. 

I will also post my letter to my delegates concerning their vote so you can get an understanding of what transpired.

Kurt and I, though very disappointed with the outcome, are not giving up on this subject.  It's an unfair law, outdated and needs to be amended so that those first line responders will get the support they deserve when they need it.

Dear Delegate ...,

Kurt and I are very passionate about getting the current workmen's compensation statute of limitations law amended.  As it stands now, it is a slap in the face to all first responders in Virginia.   There was no physical impact statement attached to the bill so can you please explain to me why this bill was tabled?  Yes, I heard the wide range of statistics that the insurance lobbyists threw out there.  In fact, one got his information the night before while spending all of one half an hour on his pc.  The fact that he threw out enormous numbers that have nothing to do with first responder statistics didn't seem to matter as not one of you even questioned the facts or asked Kurt anything pertaining to his experience. 

HCV is a blood borne virus.  It is not spread through kissing or casual contact.  You cannot catch it through sneezes or coughs.  Kurt contracted it by sucking blood and mucous out of a Spina Bifada child’s trache.  He ingested some of that phlegm while trying to save the child’s life.  Later, doctors were able to prove with medical certainty that was the point of contact with the virus.  Workmen’s Compensation couldn’t deny the facts provided but said it didn’t matter because the current law’s statute of limitation for a workmen’s compensation claim was enough to deny Kurt.  The current law reads a claim must be made two years AFTER diagnosis of the disease or five years from the DATE of the last injurious exposure in employment , WHICHEVER COMES FIRST!  Since Kurt was asystematic, showing no symptoms until nearly 7 years later, he fell through the loop hole, in spite of medical proof!

HB1346 Worker’s Compensation bill will establish a limitations period for claims for hepatitis.  Other diseases already have this limitations period in place.  Today there are precautions in place for first responders to prevent them from coming in contact with this virus.  Early tests for those exposed also provide options and therapies to help keep the virus from becoming a danger to them.  In fact, there are two trial therapies being done right now that are providing near 95% success rate of stopping the virus’s production altogether. 

The current Workmen’s Comp law is outdated, not having been amended in over 21 years and needs to be brought up to current status with medical science.

Several local papers have called to interview us and our local television channels may want to do a segment as well.  I have been asked why the bill was tabled.  Please give me the courtesy of your response.

Thank you,
Kathie Beach

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FEBRUARY 15th,  2010

Kurt had ERCP surgery on Monday.  Basically, it is removing the stents in his billiary ducts that did not leave his system all these months.  When they went in, they removed two stents and then did a small incision to put a balloon up a duct that had deflated.  Everything went well.  He was released the same day and will have a couple days to rest before going back to work.  We are hoping these stents are the reason his levels have been so high.  We will know more next week.

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APRIL, 2010

Met with Dr. Fisher and got the good news that he had never seen such a beautiful transplant scar and that Kurt's vitals looked good.  He likes what he sees enough to pass him off to Hepatology for the next 6 months AND we can do local labs ! YAY! We took doughnuts to the staff and talked with new patients, a few old friends and Kurt was even asked to pose for a picture for a man's mom who was inspired by his story. We are smiling :)

Thank you, Jesus!  God is still showing off through Kurt.  So, things are getting onto a more "normal" routine for us.  More time to attend to life stuff that continues to happen and get the focus off us for now.
  

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JULY 14,  2010



Kurt continues to gain strength.  We are both hitting the walking trails and YMCA to get these old bodies back in shape.   While watching his, I neglected mine!  Now with doctor's orders for him and sensibility for me, we have goals to reach.  He is working maybe too much.  Long days, lots of cases and he worked every weekend n June except one and all of 4th of July weekend.  That will have to slow down.  Most people would have difficulty keeping up with that schedule, let alone a post transplant patient.  Virginia's spring and summer have been very hot for this time of year as well.  That is something we are be careful with as well.  Kurt cannot tolerate sun and in fact has to cover up with 50+sun block and a huge straw hat (I finally convinced him to wear) so as to keep sun exposure to a minimum.  The doctor says skin cancer is a concern for post transplant patients due to their immune systems being so low.  When we do go to the beach, we go late afternoon, take plenty of water and bring a big umbrella!   All in all, we are living life and loving it!  Thank you, God.  Can't say it enough.

---

DECEMBER 6, 2010

Since my last report, Kurt and I experienced our first high school reunion together.  We celebrated with Kecoughtan Warriors from the 70's.  It was awesome to reconnect with friends from the past and meet new friends that have supported us in our time of need.  We also celebrated his cousin Richard's wedding, got to fly to Orlando to do a working, vacation of sorts and just spent Thanksgiving at his mom's.  That was particularly good in that his mom was in the hospital for quite a while earlier in the year.  She is so much better and we were able to thank God for His hand on us all. 

My daughter, Joy and her husband Josh, left for London after being here with us in Virginia for several years.  They had come for a visit that turned into them being my back up caregivers for Kurt.  November 8, they headed for the UK to pick up where they had left off in their new life together. 

We had dinner with our Hero Donor & Hero Donor's wife (who is also a hero of course!)  just last weekend.  I look at that man and woman and see God's compassion at work in their lives.  Such kind and gentle people.  Thank You, God, for hearts such as theirs.

Kurt is working hard, taking care to take care of himself and listening to what the doctors say.  He has some challenges coming after the first of the year and we will be looking at the doctor's plans for him then.  Still, he is amazingly well and for that we are so grateful!

---

SEPTEMBER 6,  2011

So much happening this past year that I am sorry to say I've neglected these updates.  Actually, I was waiting to update because Kurt's story continues to unfold and I wanted to be able to give specifics.

Kurt has been steady working and our family has been rolling with life changes.  We have moved from our home of 26 years and that was no easy feat.  LOTS of weekends spent giving away, taking away, moving out and moving in.  Though we still have a couple rooms with boxes stacked in the corners, we are comfortable and busy making a home.

Kurt is busy at work and that will be changing as well this year.  His doctors have approved him to begin a new viral inhibitor protocol to stop the virus from attacking his new liver.  The immuneo drugs allow the Hep C free reign in his system and the hope is this new protocol will stop the attack against his liver.   Because the protocol is a "heavy hitter" and because Kurt is going to have to slow down a bit and be able to get the rest he needs when he needs it...he will be retiring this year.  Lots of emotions going on right now and we are once again placing our lives in the capable hands of our Heavenly Father.

Kyle, our Hero Donor and his Hero Wife, Karmen are well.  We saw Kyle recently at VCU clinic for his checkup and Kurt's Dr. appointment.  Karmen is a teacher and has started back to school already.  We thank God every day for Kyle, Karmen and all the wonderful people who have helped us in our journey.

To Be Continued …..

New Hep C meds may override watchful waiting for patients with no symptoms

3.11.12 | Michael Kirsch, MD

I seemany patients with hepatitis C (HCV). None of them are under treatment and they all feel quite well. Why don’t I treat them? After all, potential consequences of HCV include:

• Cirrhosis
• Hepatocellular carcinoma. or liver cancer
• End stage liver disease with all the trimmings
• Liver transplantation
• Death

One would think that a portentous list like this would justify any treatment, even hazardous therapies. But, I’ve never seen it this way, and my hepatitis C patients are all doing well under periodic observation.

Yes, I know that the disease can be serious. I recall one patient with advanced disease whom I referred for consideration of a liver transplant many years ago. There may have been one or two others along the way who received treatment for the disease also.

The vast majority of hepatitis C patients I see in my community practice feel entirely well and the diagnosis was discovered by accident. In other words, these patients did not exhibit symptoms or abnormal findings on the physical examination that led a physician to suspect a liver condition, which then led to testing for hepatitis C. Some of them were picked up by the blood bank when their gift of life was declined. Sometimes, a life insurance company makes the diagnosis during their health assessment as they try to cull out from their enrollees those destined to ascend skyward prematurely. In most cases, patients are diagnosed with hepatitis C when physicians like me order diagnostic HCV blood test to evaluate abnormal liver blood tests. Nearly all of these patients have no symptoms of liver disease and the abnormal liver blood tests may not be a HCV manifestation.

What should we advise patients with HCV who feel perfectly well? Of course, patients should make the call after they have been informed of the risks and benefits of treatment. In my experience, after this discussion, none of these patients wants to proceed. Hopefully, I am meeting my obligation to present the issues to them fairly. I am certainly aware of my bias, and do my best to compartmentalize it.

I think that there has been a rush to treatment with these patients. Academic centers tend to be more enthusiastic about racing for the HCV cure with toxic medicines, although in fairness, their HCV population is very different from mine. Their patients are much more ill, so the risk/benefit analysis of treatmentmay calculate out differently. Nevertheless, academicians in writing and on the speaking circuit tend to extol the virtue of treatment, which they regard as the default response. Watchful waiting just doesn’t have the red meat appeal for liver gurus. They argue that eradicating the virus will prevent the dire consequences I listed at the top of this post. However, when there was only treatment available 20 years ago -injectable interferon - academics were gaga over this it, which had a full page of side effects and was effective in less than 20% of patients treated. I’m amazed that interferon slid by the FDA. Now,HCV can be cured in a majority of patients, according to data from two drugs approved in 2011 to treat the disease, although there remains substantial toxicity from the medications.

Even experts acknowledge that only a minority of HCV patients will develop serious complications. I’m not persuaded that we have a reliable method to determine who will progress and who won’t. And if we did, how firm is the evidence that treating a patient who is destined for cirrhosis will avert this outcome? Those who believe in HCV treatment will find data to support their view and practice. And those of who are skeptics will do the same. That’s the beauty of medicine. There’s always conflicting studies to choose from to support any view.

What would Newton say?

Many of my HCV patientscan date with some precision whenthey contracted the virus. The event may have been a blood transfusion decades ago or from intravenous drug use during a youthful period of hard times and bad judgement.Many of these patients, therefore, have had the virus for decades and are not suffering any illeffects. While I cannot guarantee a sanguine outcome, I view this in Newtonian terms.

An HCV virus that is asleep tends to remain asleep.

Other physicians don’t share my approach and may be dismissive of my nihilism. I wonder how many of them would accept a treatment with enormous toxicity and cost for themselves as readily as they prescribe it to others? This question applies to all physicians, including me, who prescibe medicine and advise patients. Remember, we physicians discuss the risks of all treatments with patients in advance. But, we don’t suffer the complications.

HCV patients, get informed. Make sure the treatment won’t be worse than the disease.

Source

‘Women constitute 75% Auto Immune Hepatitis patients’

Smriti Sharma Vasudeva : Chandigarh , Sun Mar 11 2012, 04:45 hrs

THE INDIAN EXPRESS

While Hepatitis B and C have acquired almost an epidemic status in our country, Auto Immune Hepatitis is largely overlooked in the list of liver diseases. Known to mostly affect women, AIH incidentally does not have any specific symptoms, making it a potential threat for Indian population.

World renowned couple Dr Giorgina Mieli-Vergani, emeritus professor of paediatric hepatology, King’s College Hospital, London and her husband Dr Diego Vergani, emeritus professor of liver immunopathology, King’s College Hospital London, said, “AIH is a progressive inflammatory liver disorder affecting mainly females, characterised by the presence of auto antibodies. As a result, our body’s infection fighting mechanism cells start behaving just the opposite. By the time, it is diagnosed, much of the damage to the liver is already done.”

If left untreated, AIH generally progresses rapidly to cirrhosis and liver failure. The peak incidence of the disease is before puberty and 75 per cent of the patients are girls.

“In fact researches have established that patients of Hepatitis C are at greater risk of developing AIH and since India has a significant number of patients of Hepatitis C virus, therefore it assumes larger significance”, said Dr Giorgina.

Top identify AIH patients in this part of the country, already a team of experts at the department of Immunopathology, PGIMER is on board a project with the doctor couple. “The only hindrance is about transportation of samples. We are working out on a modalities for the smooth continuation of the research to find out the pathogenesis of Indian patients with this condition,” said Dr Diego.

Already, the two are working on a research to find a possible cure for AIH wherein regulatory cells from the body of the patient suffering from AIH are taken out and developed in a controlled environment to outnumber the count of antibodies responsible for AIH.

The duo has even received funding of one million pounds from the British government agency to carry out the research.” It may take a few years and already a PhD student working with us on the research is undergoing a year’s training at Boston for the purpose,” added the duo.

Source

The effect of pegylated interferon-alpha2b and ribavirin combination therapy for chronic hepatitis C infection in elderly patients

Published on: 2012-03-10

The clearance of hepatitis C virus infection by interferon therapy significantly reduces the incidence of hepatocellular carcinoma and death in elderly chronic hepatitis patients. However, there are few reports concerning the efficacy and safety of pegylated interferon-alpha2b plus ribavirin combination therapy in elderly patients.

The aims of the present study were to examine the effect and safety of pegylated interferon-alpha2b plus ribavirin combination therapy in 427 patients with chronic hepatitis C infection. We compared the rates of sustained virological response--defined as the absence of detectable hepatitis C virus in serum 24 weeks after the treatment ended--and the treatment discontinuation rate between 319 younger patients aged <65 years and 108 elderly patients aged [greater than or equal to]65 years.

We also examined the factors contributing to a sustained virological response.

Results: There was no significant difference in the sustained virological response rate between younger patients and elderly patients according to their hepatitis C virus genotype (41.5% (100/241) and 40.7% (35/86) for genotype 1; P = 0.899, 89.7% (70/78) and 86.4% (19/22) for genotype 2; P = 0.703, respectively). There was also no significant difference in the treatment discontinuation rate between the two age groups (10.3% (33/319) and 13.9% (15/108), respectively; P = 0.378).

There were no serious adverse events requiring hospitalization. The factors contributing significantly to a sustained virological response in elderly patients were gender, hepatitis C virus genotype, platelet count, and the presence of a rapid or early virological response (undetectable hepatitis C virus in serum at weeks 4 or 12 of treatment, respectively).

However, upon multivariate analysis, the presence of an early virological response was the only significant factor (odds ratio: 0.115, 95% confidence interval: 0.040-0.330, P <0.001).

Conclusions: The efficacy and safety of pegylated interferon-alpha2b plus ribavirin combination therapy in elderly patients are not always inferior to those in younger patients. Obtaining an early virological response may be essential to achieve a sustained virological response in elderly patients with chronic hepatitis C infection.

Author: Hiroki NishikawaEriko IguchiYorimitsu KoshikawaSoichiro AkoTadashi InuzukaHaruhiko TakedaJun NakajimaFumihiro MatsudaAzusa SakamotoSinichiro HenmiKeiichi HatamaruTetsuro IshikawaSumio SaitoRyuichi KitaToru KimuraYukio Osaki

Credits/Source: BMC

Source

Use of Protease Inhibitors in Liver Transplant Recipients

Gastroenterology & Hepatology Volume 8, Issue 3 March 2012

Gary L. Davis, MD, and Jacqueline G. O’Leary, MD
Liver Consultants of Texas
Baylor University Medical Center and
Simmons Transplant Institute
Dallas, Texas

G&H What is the currently approved therapy for treatment of hepatitis C virus infection in liver transplant recipients? How effective is such therapy?

GLD/JGO Hepatitis C virus (HCV) infection persists in all viremic HCV-infected persons who undergo liver transplantation, and reinfection is a major problem. Although recurrence can occasionally be severe, as in cases of fibrosing cholestatic hepatitis, recurrence typically results in less severe but varying degrees of inflammation of the graft. However, fibrosis progresses much faster in patients who have undergone liver transplantation than in nonimmunosuppressed individuals. Indeed, 20–40% of liver transplant recipients progress to cirrhosis within 5 years of transplantation, and graft failure ensues within 12 months in approximately 40% of these cases. Thus, curative antiviral treatment could have a major positive impact in patients with progressive liver injury. Unfortunately, pegylated interferon and ribavirin are poorly tolerated in this group, cytopenia is problematic, and sustained virologic response (SVR) occurs in fewer than 30% of patients who attempt therapy.

G&H How are liver transplant recipients different from HCV-infected patients who have not undergone transplantation?

GLD/JGO Although patients who have undergone liver transplantation are often highly motivated, treatment of this group is difficult and labor-intensive for several reasons. Liver transplant recipients tend to have higher viral loads, more pronounced cytopenia, and some degree of renal insufficiency. All of these factors contribute to more frequent dose reductions, greater need for use of growth factors such as erythropoietin and filgrastim (Neupogen, Amgen), and lower response rates. In addition, many of these patients have already failed antiviral therapy before they undergo transplantation.

G&H Do these factors alter clinicians’ therapeutic goals for HCV treatment in liver transplant recipients?

GLD/JGO No, the goal of therapy for a liver transplant recipient is the same as for any HCV-infected individual: namely, viral eradication. Viral suppression in the absence of complete viral eradication does not provide a documented benefit in liver transplant recipients. The only possible exception is in patients with fibrosing cholestatic hepatitis; viral suppression in these patients may improve liver function and be life-saving, even if SVR is not achieved.

G&H Why might protease inhibitors be considered to treat HCV infection in liver transplant recipients?

GLD/JGO Direct-acting antiviral agents—including the recently approved HCV protease inhibitors boceprevir (Victrelis, Merck) and telaprevir (Incivek, Vertex)—can dramatically increase the chance of achieving SVR. This  increase is most apparent in patients who have the lowest response rates when treated with interferon and ribavirin alone, such as patients with high viral loads or previous nonresponders. For example, the addition of a protease inhibitor to standard therapy leads to a doubling of SVR rates in white patients, but it triples SVR rates in black patients (who have lower response rates when treated with interferon and ribavirin alone). Therefore, patients who are at the greatest disadvantage have the most to gain from the addition of a direct-acting antiviral agent.

G&H What are the risks associated with such therapy?

GLD/JGO First, it is important to mention that HCV protease inhibitors have not been studied in liver transplant recipients; as a result, the US Food and Drug Administration has not approved the use of protease inhibitors in such patients. Furthermore, in addition to the aforementioned obstacles associated with interferon and ribavirin therapy, there are a number of specific obstacles to using protease inhibitors in the liver transplant patient population. Most importantly, protease inhibitors are potent CYP3A4 and p-glycoprotein inhibitors, and they dramatically increase exposure to drugs that are metabolized by these pathways. For example, exposure to calcineurin and mammalian target of rapamycin (mTOR) inhibitors, the foundation of immunosuppression in transplant recipients, is dramatically increased when recipients receive protease inhibitors, making drug toxicity a real possibility.

G&H Are there any ways to reduce these risks?

GLD/JGO Clearly, if clinicians choose to treat liver transplant recipients, the levels of patients’ calcineurin and mTOR inhibitors must be followed extremely closely, and the doses of these immunosuppressant drugs would need to be adjusted downward accordingly. In addition, the patient’s medication list would need to be closely reviewed to ensure that no other drug-drug interactions occurred.

G&H Have there been any published cases of liver transplant recipients who received protease inhibitor therapy? What were the outcomes in these cases?

GLD/JGO A small case series by Mantry and colleagues was recently presented at the HEPDART 2011 meeting in Koloa, Hawaii. This series documented early experiences in post–liver transplantation patients who were treated with triple drug therapy. Of 7 patients, 4 patients experienced  rapid virologic response (RVR), 2 patients did not achieve RVR but remained on treatment, and 1 patient experienced early virologic failure and stopped therapy. One patient died of sepsis with a negative viral load.

G&H What is the current consensus regarding the use of protease inhibitors in liver transplant recipients?

GLD/JGO Clearly, given the increased risk of progressive liver disease in liver transplant recipients, there is a great need for effective therapy, which may well include protease inhibitors. However, such treatment will be clinically challenging, with real dilemmas (dosing and drug-drug interactions) and risks of adverse events. Given clinicians’ limited experience with protease inhibitor therapy in this population to date, it would be premature to make any specific recommendations regarding therapy.

G&H Would other new HCV drugs be subject to the same risks associated with protease inhibitors, or might future drugs be more suitable for use in liver transplant recipients?

GLD/JGO Certainly, side effects and drug-drug interactions will differ among the new compounds. Ideally, we would like medications with minimal side effects, more convenient dosing regimens, and fewer drug-drug interactions. However, such drugs are not available at this time.

G&H What further studies are needed regarding treatment of HCV infection in liver transplant recipients?

GLD/JGO Any new agents that are approved for treatment of HCV infection will need to be studied in liver transplant recipients. In the future, more potent drugs may allow eradication of virus in a very short period of time; such therapy might pave the way to clearing virus before or at the time of transplantation and avoid the problem of recurrence altogether.

Suggested Reading

Garg V, van Heeswijk R, Lee JE, Alves K, Nadkarni P, Luo X. Effect of telaprevir on the pharmacokinetics of cyclosporine and tacrolimus. Hepatology. 2011;54:20-27.

Charlton M. Telaprevir, boceprevir, cytochrome P450 and immunosuppressive agents—a potentially lethal cocktail. Hepatology. 2011;54:3-5.

Roche B, Samuel D. Hepatitis C virus treatment pre- and post-liver transplantation. Liver Int. 2012;32(suppl 1):120-128.

Limaye AR, Firpi RJ. Management of recurrent hepatitis C infection after liver transplantation. Clin Liver Dis. 2011;15:845-858.

Source

CROI 2012: Pipeline Asset Update for Daclatasvir (DCV; BMS-790052)

Pipeline Asset:
Discovered by Bristol-Myers Squibb through a genomics approach, daclatasvir, also known as BMS-790052 or DCV, is the first NS5A replication complex inhibitor to be investigated in hepatitis C clinical trials.

Current Phase of Development:
Phase III

Meeting or Publication:
Conference on Retroviruses and Opportunistic Infections (CROI)

Study Title:
Assessment Of HIV Antiretroviral Drug Interactions with the HCV NS5A Replication Complex Inhibitor BMS-790052 Demonstrates a Pharmacokinetic Profile Which Supports Coadministration with Tenofovir, Efavirenz and Atazanavir/Ritonavir

Presentation Number:
Poster Number 618

Date/Time of Presentation:
Thursday, March 8, 2012 from 2:00 – 4:00 PST

Study Objective:
To evaluate the potential for drug-drug interactions (DDI) between daclatasvir (DCV) and HIV antiretrovirals (ARVs) in healthy subjects prior to beginning clinical trials in HIV-HCV co-infected patients, establishing dosing modifications, if needed.

Study Conclusion:

Daclatasvir (DCV) plus tenofovir (TDF) had no clinically relevant drug-drug interactions.

A dose adjustment for daclatasvir is necessary when administered with atazanavir boosted with ritonavir (ATV/r) and when administered with efavirenz (EFV). A daclatasvir dose adjustment of 30 mg QD with atazanavir plus ritonavir (300/100 mg QD) and 90 mg QD with efavirenz (600 mg QD) is expected to generate daclatasvir exposure similar to that for 60 mg of daclatasvir administered alone.

Safety profiles were unremarkable in all three ARVs. No unexpected safety signals were observed. See full safety analysis in adverse events section below.

Table 1: Daclatasvir and tenofovir gave similar C_max and AUC_tau for each drug relative to administration alone (See Table 1)

Table 2: Daclatasvir and atazanavir/ritonavir

• Dose-normalized increases in daclatasvir maximum plasma concentrations (C_max) and area under the concentration-time curve in one dosing interval (AUC_tau) were observed when dosed with ATV/r (See Table 2):
  • Geometric mean ratios (GMR) for Cmax and AUCtau of daclatasavir 20 mg when coadministered with atazanavir/ritonavir vs. daclatasvir 60 mg alone were below the predicted estimations. Non-normalized GMR for Cmax and AUCtau for the adjusted doses were less than 1.0 with atazanavir/ritonavir
  • Dose normalized (60 mg DCV) C_max and AUC_tau were 35% and 110% higher, respectively, when daclatasvir was co-administered with atazanavir/ritonavir
  • Based on linear pharmacokinetics, extrapolated doses of daclatasvir 30 mg once daily with atazanavir/ritonavir are estimated to give AUC_tau similar to the daclastasvir 60 mg dose administered alone
  • Exposure of atazanavir was similar to historical data

Table 3: Daclatasvir and efavirenz

• Dose-normalized decreases in daclatasvir maximum plasma concentrations (C_max) and area under the concentration-time curve in one dosing interval (AUC_tau) were observed when dosed with efavirenz (See Table 3):
  • Geometric mean ratios (GMR) for Cmax and AUC_tau of daclatasavir 120 mg when coadministered with efavirenz vs. daclatasvir 60 mg alone were above the predicted estimations. Non-normalized GMR for C_max and AUC_tau for the adjusted doses were significantly greater than 1.0 with efavirenz
  • Dose normalized (60 mg DCV) Cmax and AUCtau were 17% and 32%, lower, respectively, when daclatasavir was co-administered with efavirenz.
  • Based on linear pharmacokinetics extrapolated doses of daclatasvir 90 mg once daily with efavirenz are estimated to give AUC_tau similar to the daclastasvir 60 mg dose administered alone
  • Exposure of efavirenz was similar to historical data

Adverse Events:

Most Common Adverse Events (>25% in Any Study) by System Organ Class and Treatment:

^aCombined data from studies AI444032, AI444033 and AI444034 (exposure 4–7 days); ^bAll subjects initially received EFV with DCV 60 mg (9 days) then 120 mg (5 days); ^cInter-study incidence range 33% to 45%; ^dInter-study incidence range 25% to 40%

Overall:

• No serious adverse events occurred in any study
• 2/17 subjects enrolled to AI444034 discontinued for adverse events (treatment-unrelated myalgia, day 15; treatment-related dizziness, nausea and panic attack, day 7) and were not included in the evaluable population for DDI assessment
• 1/21 subjects enrolled to AI444033 discontinued for adverse events (vomiting and syncope on daclatasvir alone considered treatment related) and was not included in the evaluable population for DDI assessment
• Events in the most common classes on daclatasvir alone (GI and nervous system) occurred at similar rates in subjects receiving tenofovir alone

Daclatasvir (DCV) Background:

Daclatasvir (DCV) or BMS-790052 is an investigational, potentially first-in-class, highly selective hepatitis C virus replication complex inhibitor with broad genotypic coverage and picomolar potency in vitro.

Daclatasvir is one of several molecules Bristol-Myers Squibb is studying for the potential treatment of hepatitis C. The portfolio of investigational compounds, which also includes an NS3 inhibitor, an NS5B nucleotide polymerase inhibitor, and PEGInterferon Lambda, fits into the company’s overall R&D focus on diseases where there is unmet medical need.

Future studies are warranted to evaluate daclatasvir in HCV/HIV coinfected patients. Further DDI studies for daclatasvir plus boosted darunavir and daclatasvir plus lopinavir are planned.

Study Background:

These three open-label studies in healthy subjects evaluated steady-state pharmacokinetic interactions between daclatasvir and representative antiretroviral agents: nucleoside/tide reverse transcriptase inhibitors (or NRTI; tenofovir disoproxil fumarate), non-nucleoside reverse transcriptase inhibitors (or NNRTIs; efavirenz), and boosted protease inhibitors (or boosted PIs; atazanavir/ritonavir).

Three open-label studies in healthy subjects were evaluated for this assessment:

• DCV + ATV/r: 14 healthy subjects received daclatasvir 60 mg, once daily on days 1 – 4; and then received daclatasvir 20 mg, once daily plus atazanavir/ritonavir 300 mg/100 mg, once daily, on days 5 – 14
• DCV + EFV: 15 healthy subjects received daclatasvir 60 mg, once daily on days 1 – 4; then received daclatasvir 60 mg, once daily plus efavirenz 600 mg once daily on days 5 – 13; then received daclatasvir 120 mg plus efavirenz 600 mg once daily on days 14 - 18
• DCF + TDF: 20 healthy subjects received daclatasvir 60 mg, once daily, or tenofovir 300 mg once daily or both for seven (7) days in a 3x3 crossover design

Key Inclusion Criteria:

• Men and women, 18 to 49 years of age, inclusive
• Healthy subjects as determined by no clinically significant deviation from normal in medical history, physical examination, vital signs, ECGs, and clinical laboratory determinations
• Body Mass Index (BMI) of 18.0 to 32.0 kg/m2, inclusive

Key Exclusion Criteria:

• Any significant acute or chronic medical illness
• Current or recent (within 3 months of study drug administration) gastrointestinal disease indicated as clinically relevant by the Medical Investigator
• Smoking more than 5 cigarettes per day
• Recent (within 6 months of study drug administration) drug or alcohol abuse as defined in DSM IV, Diagnostic Criteria for Drug and Alcohol Abuse
• History of cardiac conduction abnormalities
• Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations beyond what is consistent with the target population
• Positive blood screen for hepatitis C antibody, hepatitis B surface antigen, HIV viral load, or HIV-1, -2 antibody
• Pregnancy or lactation

Request for More Information and Media Interviews:
Investors: John Elicker, 609-252-4611, john.elicker@bms.com
Media: Cristi Barnett, 609-252-6028, cristi.barnett@bms.com

Supporting information:
The abstract and the presentation can be viewed on the CROI website.

Source

Hepatitis C drug is 'a step change'

A new drug to combat hepatitis C, hailed as the biggest step forward in the fight against the disease for a decade, is likely to be approved for use on the NHS.

By Stephen Adams, Medical Correspondent

6:45AM GMT 09 Mar 2012

Boceprevir, which can clear the most common form of the hepatitis C virus from up to 70 per cent of patients, has been recommended for prescription by the National Institute for Health and Clinical Excellence (Nice).

Tens of thousands of patients could benefit if Nice confirms the final draft guidance that it has issued today, as is expected.

Around 200,000 people in Britain are thought to carry the hepatitis C virus, of which up to half have the most common subtype, called Genotype 1. However, only about half know they are hep C positive.

At the moment those diagnosed are offered two drugs together, peginterferon alfa and ribavirin.

Dr Stephen Ryder, a Nottingham-based consultant hepatologist, said these managed to cure about 40 per cent of new patients. Adding boceprevir to the drug treatment boosted that to about 70 per cent, he said.

"This is a big deal," he said. "It's the biggest step since standard treatment was introduced, about a decade ago."

He hoped it would prompt those at high risk of being carriers to come forward to be tested.

He said many did not because the chances of being cured were relatively low.

"It's a big psychological thing to say, 'This is more likely to work than not," he added.

Adding boceprevir, marketed as Victrelis by developer MSD, to the drug regime increases treatment cost from about £10,000 to £25,000, he said. However, Nice has decided this "represents a cost-effective use of NHS resources".

Charles Gore, chief executive of the Hepatitis C Trust, described the drug as "a step change" in treatment.

"It's the first step into a new era. While peginterferon alfa and ribavirin boost the immune system, this targets the virus itself and stops it replicating."

Hepatitis C, which causes liver damage including cirrhosis and can trigger cancer, is normally contracted from a contaminated blood transfusion or intravenous drug use.

Some people go decades without developing symptoms, while others show them quickly. Many are plagued by poor health without knowing the underlying cause, leading it to be dubbed the "silent epidemic".

Source

CROI 2012: NATAP Updates and Slides

19th Conference on Retroviruses and
Opportunistic Infections
Seattle, WA March 5 - 8, 2011

Provided by NATAP

1. CROI: GS-7977 + Ribavirin in HCV Genotype 1 Null Responders: Results from the ELECTRON Trial - (03/7/11)
   
   
2. CROI: PHARMACOKINETIC INTERACTION BETWEEN THE HCV PROTEASE INHIBITOR BOCEPREVIR AND RITONAVIR-BOOSTED HIV-1 PROTEASE INHIBITORS ATAZANAVIR, LOPINAVIR, AND DARUNAVIR - (03/7/11)
   
   
3. CROI: The Pharmacokinetic Interactions of HCV Protease Inhibitor TMC435 with Rilpivirine, Tenofovir, Efavirenz or Raltegravir in Healthy Volunteers - (03/7/11)
   
   
4. CROI: Evaluation of NS3 Amino Acid Variants in a Phase 1b Study of GT 1 Infection with the HCV Protease Inhibitor, MK-5172 - (03/7/11)
   
   
5. CROI: Influence of the HCV Protease Inhibitor Boceprevir on the Pharmacokinetics of the HIV Integrase Inhibitor Raltegravir - (03/7/11)
   
   
6. CROI: Telaprevir in Combination with Peginterferon Alfa-2a/Ribavirin in HCV/HIV Co-infected Patients: SVR12 Interim Analysis - (03/7/11)
   
   
7. CROI: Boceprevir Plus Peginterferon/Ribavirin for the Treatment of HCV/HIV Co-Infected Patients - (03/7/11)
   
   
8. CROI: HCV PI Boceprevir Lowers Levels of Three Key HIV PIs - written by Mark Mascolini - (03/7/11)

Merck's hepatitis C drug wins UK cost endorsement

LONDON, March 9 | Thu Mar 8, 2012 7:01pm EST

LONDON, March 9 (Reuters) - U.S. drugmaker Merck & Co's new hepatitis C drug Victrelis was recommended for use within Britain's state health service on Friday, despite its hefty price tag.

The National Institute for Health and Clinical Excellence, which often spurns expensive new medicines on cost grounds, said significant improvements seen with Victrelis made it a cost-effective option.

The drug, also known as boceprevir, is designed for use in combination with peginterferon alfa and ribavirin for patients with liver disease due to genotype 1 chronic hepatitis C, the most common form.

It costs 30,800 pounds ($48,400) for a 44-week course, with the other two drugs increasing the bill by around 11,000 pounds.

The draft guidance from NICE is now open for consultation before the agency finally issues it.

Source

The long-term horizon: Patients who will remain untreated in the era of triple therapy

Clinical Liver Disease

Volume 1, Issue 1, pages 20–23, February 2012

Andrew Aronsohn M.D., Donald Jensen M.D.^‡,*

Article first published online: 6 MAR 2012

DOI: 10.1002/cld.5

Copyright © 2012 the American Association for the Study of Liver Diseases

Abstract

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The direct-acting antivirals (DAAs) telaprevir and boceprevir have revolutionized hepatitis C virus (HCV) therapy by improving therapeutic outcomes for many patients. Although DAA-based therapy is a great leap forward, it is not a panacea, and many patients will not be appropriate candidates for this treatment. This review defines the patients who will remain untreated and explores emerging challenges in the era of triple therapy.

Patients with Contraindications to Pegylated Interferon (PEG) and Ribavirin (RBV)

PEG and RBV remain part of the current DAA-based therapy; therefore, patients with contraindications to the previous standard-of-care treatment are unlikely to be candidates for triple therapy (Table 1). This includes patients with previous adverse reactions to PEG or RBV and patients with uncontrolled autoimmune disease.1 In addition, interferon-induced bone marrow suppression, in combination with the hemolytic effects of RBV, can result in significant anemia and pancytopenia, and this makes patients with preexisting cytopenias, severe peripheral vascular disease, pulmonary disease, or coronary artery disease potentially unsuitable candidates for treatment.1 Finally, depression has been reported to occur in 23.2% of patients undergoing interferon therapy.2 Although patients tend to respond well to antidepressants during HCV therapy, severe uncontrolled depression remains a contraindication to treatment.1

DAA, direct-acting antivirals; HCV, hepatitis C virus; HIV, human immunodeficiency virus; PEG, pegylated interferon; RBV, ribavirin; SVR, sustained virological response.

Patients with Contraindications or Limited Responses to DAA Therapy

Boceprevir and telaprevir have significant interactions with both cytochrome P450 3A and p-glycoprotein, and these result in significant drug-drug interactions (Table 2).3, 4 A thorough medication history should be taken before treatment, and it is possible in many cases to substitute or hold a contraindicated drug during HCV therapy. However, in rare instances, patients who are taking a contraindicated medication that cannot be modified may not be candidates for current DAA-based therapy.

Although triple therapy is highly effective in most patients, response rates among patients with cirrhosis (especially previous null responders) remain relatively low. In the Sprint (Serine Protease Inhibitor Therapy) 2 study, cirrhosis was a significantly negative predictor of sustained virological response (SVR) in patients treated with boceprevir [odds ratio = 2.5 (1.4–4.6), P = 0.003].5 Furthermore, in the REALIZE study, investigators performed a subgroup analysis of patients with cirrhosis who were treated with telaprevir-based therapy and were previous null responders, and they found an SVR rate of only 29%.6 Clearly, many patients with HCV-related cirrhosis (especially previous nonresponders) will have limited success with the current therapy and will require treatment beyond what is currently available.

Understudied Populations

HCV affects many patients who have unique characteristics that are beyond the scope of currently published phase 3 registration trials of DAAs. These patients may benefit from DAA therapy but will pose a significant challenge to clinicians because there are limited data (if any) for guiding their care (Table 3).

Patients Coinfected With Human Immunodeficiency Virus (HIV)

At least 17% of patients with HIV are coinfected with HCV.7 Progression to cirrhosis is more rapid in coinfected patients, and hepatic failure is an increasingly common cause of death in this patient population.8 The treatment of HCV in the setting of HIV is a longstanding clinical challenge because previous standard-of-care therapy with PEG/RBV has resulted in suboptimal SVR rates. In 2004, the AIDS Pegasys Ribavirin International Co-Infection Trial study group performed a multicenter, international study of HCV therapy in 868 patients coinfected with HIV. In genotype 1 patients, the SVR rate was 29%, which is lower than the published rates for PEG/RBV-based therapy in the non–HIV-infected population.9, 10 Currently, there are no available data describing DAA-based therapy in the HIV/HCV-coinfected population, and although improved treatment outcomes are anticipated, safety concerns (primarily involving drug-drug interactions) must first be addressed.

Liver Transplant Recipients

Patients with chronic HCV who undergo liver transplantation universally experience HCV recurrence in the transplanted liver. This leads to inferior posttransplant patient and graft survival in comparison with many other indications for liver transplantation.11 HCV therapy with PEG/RBV after liver transplantation has been largely unsuccessful because of poor SVR rates and significant adverse events, which include acute rejection.12, 13 Theoretically, direct-acting agents should be ideal in an immunocompromised host because there is less reliance on the host immune system for antiviral activity. Telaprevir and boceprevir are strong inhibitors of the enzyme cytochrome P450, which also plays a key role in the metabolism of the immunosuppressants commonly used in liver transplantation: cyclosporine and tacrolimus. Pharmacokinetic studies investigating the interaction between telaprevir and cyclosporine yielded extremely high drug concentrations of immunosuppressants when they were tested in healthy controls (a 70-fold increase in the tacrolimus concentration and a 4.6-fold increase in the cyclosporine concentration).14 Further prospective studies will be needed to determine safe and efficacious dosing strategies when these medications are used together.

Patients With Decompensated Cirrhosis

Successful HCV treatment in patients with cirrhosis has been shown to increase survival and decrease the development of ascites, esophageal varices, and hepatic encepaholpathy.15 Unfortunately, few decompensated patients with genotype 1 or 4 who undergo HCV treatment with PEG/RBV will achieve SVR (7%); therapy is often poorly tolerated, and frequent dose reductions and discontinuations are required.16 Current guidelines from the American Association for the Study of Liver Diseases recommend that for patients with decompensated cirrhosis, attempts at treatment should be “administered by experienced clinicians with vigilant monitoring for adverse events preferably in patients who have already been accepted as candidates for liver transplantation.”1 The risk of further decompensation along with the low SVR rates means that the previous standard-of-care treatment with PEG/RBV is rarely a viable option. With the use of more potent antiviral agents, SVR rates may increase; however, DAA metabolism appears to be different in patients with advanced cirrhosis versus patients with earlier stages of disease, and the tolerability and safety in this population remain largely unknown. Decisions to treat these patients with triple therapy rely solely on anecdotal accounts, and they should be made with extreme caution and should be based on physician experience and unique patient characteristics.

Pediatric and Elderly Populations

Recent National Health and Nutrition Examination Survey data suggest that approximately 0.2% to 0.4% of children up to 14 years old are infected with HCV.17 The majority of pediatric HCV infections occur as a result of maternal-fetal transmission. Because of the shorter period of chronic infection, pediatric patients usually have earlier stage disease at the time of diagnosis in comparison with adults; however, progression to cirrhosis and hepatocellular carcinoma has been reported.18, 19 In a pilot study of 62 patients between the ages of 2 and 17 years who were treated with PEG and RBV, 48% of the patients with genotype 1 achieved SVR.20 Although the results are based on limited data, the treatment outcomes appear to be similar to those of the adult population, and so are the adverse events during therapy, with the exception of spastic diplegia, which is a severe form of neurotoxicity seen in infants treated with interferon-α.17 The pediatric population would very likely tolerate and benefit from more potent agents; however, to date, there are no data on the use of telaprevir, boceprevir, or other new HCV therapies in this population. The current Food and Drug Administration treatment for patients who are 18 or less years old remains interferon plus RBV three times a week (3–18 years old) or PEG plus RBV once a week (5–18 years old).

In upcoming years, the highest prevalence of HCV infection will be seen in patients who are 65 years old or older.21 Older patients with HCV have a faster rate of progression to cirrhosis and have a higher incidence of hepatocellular carcinoma; this indicates a significant therapeutic need in this understudied population.22, 23 Patients more than 65 years old are more likely to be cirrhotic and have comorbidities that make treatment with PEG/RBV less effective. This was shown by Huang et al.24 in a study of 70 HCV patients older than 65 years who were treated with PEG/RBV. In comparison with younger cohorts, older patients had significantly inferior SVR rates and higher rates of dose reduction and therapy discontinuation. DAAs may improve response rates; however, there are significant concerns about the tolerability of triple therapy in this population and especially in patients who have been unable to tolerate PEG/RBV in the past. The consideration of alternate dosing schedules and treatment algorithms may be key to the use of DAA-based therapy in this population.

Patients With Previous DAA Exposure

Unlike dual-therapy treatment with PEG/RBV, treatment failure with DAAs is complicated by the emergence of resistant variants. Pawlotsky25 defined three major factors that influence the clinical ramifications of resistance: the genetic barrier to resistance, the fitness of the resistant variant, and the attainable drug exposure. First-generation protease inhibitors such as telaprevir and boceprevir have a low genetic barrier to resistance; however, after the discontinuation of therapy, the wild-type virus typically regains dominance, possibly to the point of the complete eradication of the resistant variants over time. Patients who develop resistant variants while they are being treated with one protease inhibitor will not likely be candidates for treatment with the other available protease inhibitor because boceprevir and telaprevir have been shown to share cross resistance in vitro. In addition, the emergence of resistance is also related to interferon insensitivity, which would hinder successful therapy with any DAA that requires interferon as part of the therapeutic regimen. As more DAAs become available, the treatment of patients who develop resistant variants may become similar to HIV treatment, in which combinations of agents are selected on the basis of viral resistance profiles.

Overcoming Current Challenges with DAA Therapy

This review describes many groups of patients who are underserved by currently available DAA therapy (Fig. 1). Fortunately, there are robust basic, translational, and clinical investigations aimed specifically at addressing these shortcomings. For those with limited responses or contraindications to telaprevir- or boceprevir-based treatment, ongoing clinical trials are evaluating the safety and efficacy of the next generation of protease inhibitors, polymerase inhibitors, and other novel agents such as cyclophilin inhibitors and short interfering RNA. In addition, many new agents are being investigated in interferon-free combinations that are targeted at patients who have deferred interferon-based treatment because of their own preference or medical contraindications. Finally, active research is taking place through both sponsored trials and investigator-initiated studies evaluating current DAA-based therapy in many of the understudied populations mentioned in this review.

Figure 1. Treatment algorithm for difficult-to-treat patients.

Chronic HCV progresses slowly, and most patients do not develop advanced liver disease until at least 2 to 3 decades after the time of infection. Within understudied and difficult-to-treat populations, patients with early-stage disease will have the luxury of waiting for safer or more effective therapies; however, patients who already have advanced disease will have limited options and will remain a challenge, even in the era of DAA therapy.

References

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