Saturday, March 10, 2012

Hepatitis C Spring Forward - Weekend Reading For March 10

 The reader

Hello Folks,
Another Saturday is upon us, a time to spring forward and maybe improve your knowledge and understanding of hepatitis C. Most weekends this blog offers up a few substantial links to relevant HCV information. This month HCV advocate published a new fact sheet on "Stress and the Liver", please do go take a look here. As noted on the blog yesterday, a new liver disease journal has been made available online. The new publication called "Clinical Liver Disease"-(CLD)  is an official digital educational resource from the American Association for the Study of Liver Diseases. To view the complete information click here.

For me, the downside to accessing information online is the all time consuming registration process. Often the best source for HCV information requires registration, especially on the websites that offer continuing medical education (CME).

When I reflect back to the time of my own diagnosis, twelve years ago, the Internet wasn't a tool available in my arsenal to fight HCV. Until, after many trips to the library and returning home empty handed, my father suggested I go online - on what? I took his advice, the next week my family signed onto the Internet. I still remember that sound of freedom.


What followed were hours spent looking for information on hepatitis C. With the help of HCV advocate, I soon learned how to read an abstract and find my way around the four phases of a clinical trial.  It took far to long before I finally registered at Clinical Care Options CCO, which by the way is a great resource to keep informed on the newest HCV developments.

Today, I wanted to point you to "or back" to  "Projects In Knowledge". The site is great source for easy to understand information, although like any site offering CME, it requires a free quick  registration. Treating HCV with the two new FDA approved drugs requires the HCV patient to understand a confusing protocol. In the videos from "Projects In Knowledge" case studies are discussed, making it easier to understand who should be treated, when, and the stats for achieving a cure. Make sure you check out last months video (see below), and the new video coming soon.
Coming Soon-
Case Studies: Direct-Acting Antiviral Agents in the Practice Setting—Video 2 —Video Case Vignette (HCV-VC01.02) 2080.02
Younossi Mar 2012
As always to view the videos mentioned below free registration is required. The links on this page will work once this is accomplished, blah ,blah.

February Video

 Last months video is ready view, in this video two different hepatitis C patients are discussed. (the transcript of one case is available on the blog below)

Case Studies: Direct-Acting Antiviral Agents in the Practice Setting—
Video 1
Published on February 17, 2012 VideoFaculty: Steven L. Flamm, MD
Medical Writer: Nancy J. Nordenson, MT (ASCP), MFA

Join Steven L. Flamm, MD, as he models initiating and managing new anti-HCV triple therapy in two patients, one treatment-naive and the other a prior partial responder. Each case highlights common issues that clinicians may encounter in their practice, including identifying contraindicated drugs, determining treatment duration based on HCV RNA levels at specific timepoints, and managing adverse effects.

A little peek at one case study from Video 1. Which this blogger shamelessly borrowed with love from "Projects In Knowledge."

PDF can be download here.

Case One: Patient Presentation
The first case is a 46-year-old white female who was diagnosed with chronic hepatitis C virus infection approximately 10 years ago after elevated liver enzymes were noted upon routine blood testing. Additional workup was undertaken at the time, and she was found to have hepatitis C virus, genotype 1. She subsequently underwent a liver biopsy, and this revealed a mild lymphatic histologic inflammation, grade 1, and stage 2 fibrosis.

The patient heard about the availability of new medications for chronic hepatitis C and she’s referred for evaluation. She has not been previously treated. She opted to defer antiviral therapy in the past
because of the poor response rates that were present with the previous standard of care. She does not complain of fatigue, abdominal pain, pruritus, or arthralgias. She has no peripheral edema, increased abdominal girth, encephalopathy, or GI bleeding. She consumes alcohol only on a rare basis.

Hepatitis C virus risk factors include a short-lived period of intravenous drug use when she was 19. She has no history of intranasal drug use or blood transfusion. Her past medical history is only remarkable for a tonsillectomy at age 8. The only medication she takes is a multivitamin. She’s married, has two healthy children, and works in human resources for an accounting firm. She does not smoke cigarettes.

On physical examination, she’s well appearing. Her height is five feet five inches, her weight is 166 pounds. She has anicteric sclerae. Her neck has no lymphadenopathy. Her lungs are clear. Her cardiac examination reveals a regular rate and rhythm without rubs or gallops. Her abdomen is soft, nontender, and she does not have hepatosplenomegaly to palpation. Her extremities are without edema, and she has no spider angiomata or asterixis. On labs, her white blood cell count is 5400, her hemoglobin is 13.8 g/dL, and her platelet count is 260,000. Her BUN is 10, her creatinine is 0.9, and her total bilirubin is 1.3. INR is 1.1. Her liver enzymes are mildly elevated with an ALT of 88 and an AST of 76. Her alkaline phosphatase is normal at 118. Her TSH is 3.3.

Hepatitis C virus testing was then performed and revealed a hepatitis C virus RNA level of 900,000 IU. And she was found to have genotype 1b. Ultrasound was performed to visualize the liver and revealed a normal appearing liver and spleen. No other abnormalities were described. Now, this leads us to our first decision point.

Case One: Decision Point One
Should the patient be treated now, or should she be counseled to wait for interferon-free medical regimens?

Her options include, or our options, include the following: First, should we wait to treat until an interferon free regimen is available; two, should we treat now with pegylated interferon alfa and ribavirin; or three, should we treat now, but with triple therapy—pegylated interferon alfa, ribavirin, and either one of the protease inhibitors, telaprevir or boceprevir?

The first option—wait to treat until an interferon-free regimen is available—is not the best option for this woman. First of all, she has advancing fibrotic liver disease with stage 2 fibrosis. While there’s a lot of excitement about the prospects of interferon-free medical regimens in the future, we have no idea, for sure, if such regimens will become available. And if they do, we don’t know when they will become available. It could be many many years from now. And in a person with stage 2 fibrosis, it may not be in her best interests to wait for therapy.

The second option—treat now with pegylated interferon alfa and ribavirin—is also not the best choice. Pegylated interferon alfa and ribavirin is approved for treatment of patients with HCV genotype 1 who are treatment-naive, but the sustained response rates are not that high, and it’s not the current standard of care.

The third option—treat now with triple therapy, including pegylated interferon alfa, ribavirin, and either one of the protease inhibitors, telaprevir or boceprevir—is the correct option. Why? This is a young patient who has fibrotic liver disease, as I mentioned before, stage 2 fibrosis. There are no contraindications to antiviral therapy. And with this new triple regimen, very high sustained response rates are to be expected, with results ranging from 66% to 79% in published studies for patients with hepatitis C virus genotype 1.

Case One: Decision Point Two
The case continues. The patient is treated with antiviral therapy. She’s started on pegylated interferon alfa-2a at a dose of 180 μg/week, ribavirin weight-based dosing 1000 mg/day and divided dosages for this person, and it was opted to use telaprevir in this case, 750 mg, three times daily. One could also have used boceprevir, 800 mg, three times daily, for this case as well.

On therapy, the patient develops fatigue and arthralgias, but she generally tolerates the regimen well. She’s advised to take anti-inflammatory agents and to drink plenty of water, both of which are helpful for these systemic symptoms of fatigue and arthralgias on antiviral therapy. Blood testing is performed at weeks 1, 2, and 4. At week 4, the hemoglobin declines to 10.0 from 13.8 that it started at.

 Fortunately, liver enzymes have normalized: ALT is now 28 and AST is 22. And better news yet, hepatitis C virus RNA is now undetectable and unquantifiable. At week 4, the patient complained about having difficulty meeting the requirements to eat food containing 20 grams of fat with each dose, because telaprevir, one of the recommendations is that you are to take 20 grams of fat with each dose of the medication. Now, examples of food had been provided to her that would be appropriate, such as bagels with cream cheese, potato chips, peanuts, these kinds of foods. But she was having some trouble adjusting to this change in her diet. My nurse spoke to her on several occasions and told her that while it may at first not appear to be palatable, that she really has to do the best she can, because taking 20 grams of fat with each dose of telaprevir optimizes absorption.Blood testing was performed at week 6, 8, 10, and 12. The hemoglobin fortunately remains stable and was noted to be 10.1 at week 12. Hepatitis C virus remained unquantifiable and undetectable at week 12.

And this leads us to our second decision point. 
What is the complete duration of therapy for this patient? Twelve weeks is choice number one; 24 weeks is choice number two; and 48 weeks is choice number three.

The first option—12 weeks of triple therapy—is incorrect. There was a study group in a European trial with treatment-naive hepatitis C virus patients genotype 1, called the PROVE 2 trial, in which they looked at triple therapy for 12 weeks only, and sustained response rates in this group were not the highest, so this is not a good choice.

The second option—24 weeks—is correct. This patient achieved what is now known as an extended rapid virologic response, an eRVR. Now, that means the patient had undetectable and unquantifiable virus at week 4 and at week 12. This is a new term, one that we haven’t used before in treatment of hepatitis C. Studies have shown that if a treatment-naive hepatitis C virus genotype-1 patient achieves an eRVR, that they only require 24 weeks of antiviral therapy. Now, the antiviral therapy is 12 weeks of the triple therapy with telaprevir and then 12 additional weeks of double therapy with pegylated interferon alfa and ribavirin only. This, by the way, is called response-guided therapy, which is another new term for patients that are treated with the protease inhibitors. When patients have a brisk response like this one, they can receive a shorter course of therapy than we previously used in patients with genotype 1; 24 weeks in this case.

And consequently, the third option—48 weeks—is incorrect. There is no benefit from extension of antiviral therapy beyond 24 weeks to 48 weeks if a treatment-naive patient has an extended rapid virologic response. And this was actually proved beyond a shadow of a doubt in the ILLUMINATE trial, which was done to actually assess this particular issue.

Case One: Decision Point Three
Now, for this lady, telaprevir was discontinued at the end of week 12, as per the approved therapeutic regimen that I just mentioned. Pegylated interferon alfa and ribavirin were continued. The patient complains, not surprisingly, of ongoing fatigue and arthralgias, but she remains  active. Her hemoglobin remains stable, ranging from 10.0 to 10.4, and the CBC, by the way, was followed on a monthly basis.

The RNA level was again obtained at week 24 and was found to be unquantifiable and undetectable still. As I mentioned before, because of the response-guided therapy paradigm, antiviral therapy was discontinued at week 24. Flu-like symptoms resolved rather quickly, within a month or so. Hepatitis C virus RNA was checked again at week 48, 24 weeks after therapy was discontinued, and it was found again to be unquantifiable and undetectable. This leads us to decision point three.

The patient asks if there was information available about the durability of a sustained virologic response, which she now is. She’s now a sustained responder since she has undetectable virus 6 months after stopping antiviral therapy.

So what do we tell her? How do we answer her question? One, do we say information is not available; two, information is available, and the durability of an SVR after 1 year is approximately 80%; or 3, information is available, and the durability of an SVR over a period of approximately 2 years is greater than 99% with telaprevir.

The first option—that information is not available—is incorrect. There are data available regarding durability of response with telaprevir.

The second option—that the durability of SVR with telaprevir is 80% after 1 year—is also incorrect.

The third option—the durability of SVR with telaprevir is greater than 99% after approximately 2 years—is correct.

Preliminary presentations of data from the EXTEND trial, during which patients who have been on telaprevir within the context of phase II and phase III trials and who achieved SVR and have been followed over the long term, have been reported. And patients have been followed on average nearly 2 years, and there have been over 200 patients with SVR followed. Only one patient suffered from late relapse, meaning that they were designated as an SVR, or sustained responder, and then later the virus came back. Interestingly, that patient received only 10 weeks of antiviral therapy total, so they didn’t get a full course; yet, they were designated as an SVR and followed as per the EXTEND protocol. That’s the only patient in over 200 patients that had what we call a late relapse. So durability of SVR with telaprevir is excellent.

Case One: Conclusion
What are our take-home messages?
One, antiviral therapy with the protease inhibitors offers high sustained virologic response rates in patients who are treatment-naive with genotype 1. Antiviral therapy should be recommended. We should not warehouse patients, particularly in patients with fibrotic liver disease.

Two, patients with extended rapid virologic response, undetectable virus at weeks 4 and 12 who were treatment-naive, should be offered a truncated therapeutic regimen of 24 weeks. And three, sustained virologic response with a telaprevir-based therapeutic regimen is durable.

Please register and view both case vignettes in the February video. As for the second "video-2" a reminder will be posted on the sidebar of this blog when it becomes available. 

Connect with "Projects In Knowledge" at facebook


If you're looking for support, check out a few HCV forums. This online platform is a great way to communicate with people living with HCV or treating with the newly FDA approved drugs.

Hepatitis C Support Forums  

Providing Knowledge, Support and Encouragement
Living with hepatitis C can be a difficult and frustrating experience.
Boceprevir (Victrelis) and Telaprevir (Incivo, Incivek)
Treatment section for patients with Geno type 1 on the new PIs.
Hepatitis-Central is providing this board only as a forum for discussions on hepatitis, treatments, etc.
This message board will allow you to keep in touch with other patients, or caregivers, exchange ideas, as well as give and receive support.
A few topics-
Boceprevir or Telaprevir?
Clinical trial GS-7977 and BMS-790052
Any tricks for getting rid of corner of the mouth sores?

Cirrhosis/ESLD Support

Our goal is to provide friendly support and reliable information to those dealing with advanced liver disease or liver transplant. It's a friendly group made up of patients and caregivers. Some are dealing with complications (ascites, varices, encephalopathy, etc.), some are waiting for liver transplant, some have already received their liver transplant.

I realize these links may be redundant for the savvy HCV patient, but they could be beneficial for anyone who has just been diagnosed.

Have A Lovely Weekend

No comments:

Post a Comment