SOC

[chevyelcam79]

I have a friend (truly) that has been recently diagnosed with HCV 1A.  I was successful with tx about 6 years ago and have achieved SVR with the SOC interferon and riba.  

My friend has an appt with hepatologist this month.  I was wondering since I have been out of the loop for quite some time, what the SOC is now.  Peg, Riba and boce, 48 weeks?  I also heard that the FDA may approve another treatment.... is this for 1a?

I just want to be there, be supportive and tell him everything is going to be ok.  Also, do my research on the newer meds in case that is the route the doc takes.  I am sure he will have many many questions..

Thanks to all!

[mikesimon]

The New Paradigm of Hepatitis C Therapy

"....Noninvasive methods of assessing histology are becoming more widely used. These include measurement of serum biomarkers of fibrosis and measurement of liver stiffness through elastography (Table 2). The noninvasive methods have practically no complications and can be performed repeatedly to dynamically monitor progression of fibrosis. The rate of adoption of noninvasive diagnostic tests for liver fibrosis differs between international regions, and the United States lags behind Europe in this regard. The 2012 European Association for the Study of the Liver (EASL) guidelines for treating chronic hepatitis C suggest that while liver biopsy is still regarded as the reference method for grading inflammation and staging fibrosis, transient elastography can be used to assess liver fibrosis, and noninvasive serum markers are recommended for detecting significant fibrosis (METAVIR score F2-F4).[37]

In 2004, the biomarker assay FibroSure (named FibroTest in Europe) was launched in the United States for assessing fibrosis and necroinflammatory activity. The assay, which can only be performed in validated laboratories, predicts a histology score on the basis of patient age, sex and results for serum haptoglobin, α2-macroglobulin, apolipoprotein A1, γ-glutamyltransferase and bilirubin analyses.[38] In a review of 25 studies in chronic HCV, FibroTest had an AUROC of 0.79 (0.70–0.89) for diagnosis of significant fibrosis (F ≥ 2) and 0.86 (0.71–0.92) for liver cirrhosis.[38]

If the birth-cohort screening to enhance diagnosis of HCV infection is fully implemented, it has been estimated that as many as 800 000 additional cases of HCV infection would be identified.[26] Should there be such a large-scale influx of newly diagnosed patients, tests of serum biomarkers will likely be a more practical approach to liver disease staging than one restricted to liver biopsy-based staging. In the United States, the FibroSure test costs approximately $250, which is a fraction of the cost of biopsy. The biomarker assay AST-to-Platelet Ratio Index (APRI) is not proprietary and costs no more than a routine blood draw and routine liver function tests. APRI is calculated as (AST/upper limit of normal range)/platelet count (109/L) × 100. However, a recent large meta-analysis suggested that APRI can identify hepatitis C-related fibrosis with only a moderate degree of accuracy (AUROC of 0.77 for significant fibrosis and 0.80 for severe fibrosis).[39] Alternate in vitro diagnostic testing for liver fibrosis was subsequently developed, including FibroIndex and Forns index.[38] For identifying cirrhosis, the age-platelet index, APRI and Hepascore have median AUROCs of 0.80 or greater (range 0.80–0.91).[38]

Transient elastography, using the FibroScan device (Echosens, Paris, France), is widely used in several European countries and has more recently been adopted in Asia and Canada. In April of 2013, FibroScan was approved by the FDA for use in the United States. The main limitation of FibroScan use in practice is its limited applicability (80%), mostly due to patient obesity or limited operator experience.[40] Results of a meta-analysis suggest FibroScan is a reliable method for diagnosing significant fibrosis (AUROC = 0.84), severe fibrosis (0.89) and particularly cirrhosis (0.94).[41] However, for diagnosing significant fibrosis, a high variation of the AUROC was found depending on the type of underlying liver disease.[41] When compared and validated externally in a multicenter prospective study, FibroScan outperformed serum biomarkers of fibrosis for the prediction of cirrhosis (AUROCS 0.89–90 vs 0.77–0.86) but had similar performance for the diagnosis of significant fibrosis.[42] Both FibroScan and FibroTest have a prognostic value similar to liver biopsy for predicting complications and outcome of liver disease.[43,44] Combining FibroScan with Fibrotest may increase diagnostic performance for significant fibrosis,[45,46] and this approach has been recommended in the 2012 EASL Guidelines as first line evaluation of liver fibrosis in patients with chronic hepatitis C.[37]

The Think Tank recognized that the goals of liver staging are changing and that there is an urgency to revise guidelines accordingly. The accurate exclusion of cirrhosis has been recommended as the most important role for HCV staging in clinical practice, and an algorithm has been proposed on how to best utilize noninvasive tests to achieve this goal.[47]...."

http://www.medscape.com/viewarticle/812827_4?nlid=37625_805

[willbb]

Advising the Patient
In a nutshell, my answers were: 1) no, a biopsy is not essential, and 2) maybe you will need interferon, but if your liver is in good shape, then you can wait. My response may seem a bit paradoxical—I care very much about the liver disease stage when making a decision to treat or wait but I don’t think we need a piece of liver tissue to get the information. I still recommend a fair number of liver biopsies but, with interferon-free, all-oral therapies on the near-term horizon (2014?), I am increasingly comfortable relying on patient history, physical exam, routine laboratory tests, and liver imaging as well as noninvasive serum markers to obtain a picture of liver health. In the United States, we do not yet have routine access to transient elastography but, in many regions, this would also be a mainstay of liver staging.
-----------------
Mike.

It seems many Hepa's have been adopting this attitude ,negating the need  often for biopsy ,,especially in light of new treatment paradigms.

It was good to see that the FDA has finally aprroved the Fibroscan .as we have been using it relatively succesfully in Canada for years,often in combination with the "Fibrosure"  blood marker.

Thanks for posting the above.....

Will

[mikesimon]

The Age-Old Debate of Whether to Biopsy in HCV: My Answer for 2013
Mark S. Sulkowski, MD - 1/23/2013

As Raymond T. Chung, MD, pointed out in a recent Clinical Thought, the US Centers for Disease Control and Prevention now recommend that all persons born between 1945 and 1965 undergo a 1-time screening for HCV. The idea is that this will identify persons who are infected and offer them the opportunity for management of their hepatitis C infection, in turn reducing the risk of cirrhosis, end-stage liver disease, and hepatocellular carcinoma. Management of HCV disease can include a number of things, including reduction in alcohol intake and, in some patients, reduction in body weight. It also includes consideration of HCV treatment but, in 2013, does it include a liver biopsy?

A Recent Case
A few days ago, I met a new patient who had just been diagnosed with HCV after screening by the primary care physician based on the patient’s date of birth. The test was positive prompting an effort by the patient to become highly informed about HCV and its management. At the visit, many questions were raised but the two most prominent inquiries were: 1) do I have to undergo a liver biopsy, and 2) do I need to take interferon? Not unexpectedly, the patient was not enthusiastic about either of these interventions.

"Advising the Patient
In a nutshell, my answers were: 1) no, a biopsy is not essential, and 2) maybe you will need interferon, but if your liver is in good shape, then you can wait. My response may seem a bit paradoxical—I care very much about the liver disease stage when making a decision to treat or wait but I don’t think we need a piece of liver tissue to get the information. I still recommend a fair number of liver biopsies but, with interferon-free, all-oral therapies on the near-term horizon (2014?), I am increasingly comfortable relying on patient history, physical exam, routine laboratory tests, and liver imaging as well as noninvasive serum markers to obtain a picture of liver health. In the United States, we do not yet have routine access to transient elastography but, in many regions, this would also be a mainstay of liver staging.

Identifying Minimal Disease
In any event, if all of these factors point to minimal liver disease—no history of heavy alcohol, no exam findings of cirrhosis, normal platelet count, minimally elevated ALT > AST, normal liver ultrasound, and minimal fibrosis by a commercially available fibrosis marker—I am comfortable telling the patient that we can monitor over the next year without liver biopsy and plan treatment following the FDA approval of interferon-free therapies as foreshadowed in the New England Journal of Medicine on January 3. Of course, if concerns regarding more advanced disease are found, I will take the step of recommending biopsy and/or treatment with current triple therapy."

http://www.clinicaloptions.com/Hepatitis/Treatment%20Updates/ClinicalThought/Thought11.aspx

[pooh55811]

The current SOC for Genotype 1 is Interferon, Ribavirin, and a Protease Inhibitor (either Telaprevir or Boceprevir). Depending on the liver fibrosis stage and the response to treatment, treatment length can be as short as 24 weeks or as long as 48 weeks.

However, your friend was diagnosed at a good time. After he/she gets a biopsy and determines what stage of fibrosis he/she has, then he/she can best decide how urgent it is to treat and which treatment avenue to take.

There are new drugs in the pipeline and some of them may be approved later this year or early next year. Being that your friend is treatment naive, he/she may be able to take advantage of some of the new drug treatments.

The following is data from one trial with Sofosbuvir, Ribavirin, and Inteferon. There are also several other drugs in the process of being approved and perhaps others will post about some of them.

From NCBI:

Sofosbuvir for previously untreated chronic hepatitis C infection.

Abstract
BACKGROUND:

In phase 2 trials, the nucleotide polymerase inhibitor sofosbuvir was effective in previously untreated patients with chronic hepatitis C virus (HCV) genotype 1, 2, or 3 infection.
METHODS:

We conducted two phase 3 studies in previously untreated patients with HCV infection. In a single-group, open-label study, we administered a 12-week regimen of sofosbuvir plus peginterferon alfa-2a and ribavirin in 327 patients with HCV genotype 1, 4, 5, or 6 (of whom 98% had genotype 1 or 4). In a noninferiority trial, 499 patients with HCV genotype 2 or 3 infection were randomly assigned to receive sofosbuvir plus ribavirin for 12 weeks or peginterferon alfa-2a plus ribavirin for 24 weeks. In the two studies, the primary end point was a sustained virologic response at 12 weeks after the end of therapy.
RESULTS:

In the single-group study, a sustained virologic response was reported in 90% of patients (95% confidence interval, 87 to 93). In the noninferiority trial, a sustained response was reported in 67% of patients in both the sofosbuvir-ribavirin group and the peginterferon-ribavirin group. Response rates in the sofosbuvir-ribavirin group were lower among patients with genotype 3 infection than among those with genotype 2 infection (56% vs. 97%). Adverse events (including fatigue, headache, nausea, and neutropenia) were less common with sofosbuvir than with peginterferon.
CONCLUSIONS:

In a single-group study of sofosbuvir combined with peginterferon-ribavirin, patients with predominantly genotype 1 or 4 HCV infection had a rate of sustained virologic response of 90% at 12 weeks. In a noninferiority trial, patients with genotype 2 or 3 infection who received either sofosbuvir or peginterferon with ribavirin had nearly identical rates of response (67%). Adverse events were less frequent with sofosbuvir than with peginterferon.

http://www.ncbi.nlm.nih.gov/pubmed/23607594

[willbb]

  "new therapies coming avail..."

[willbb]

Congrats on achieving SVR.

Since spring 2011 SOC has been considered a triple therapy of PEG/RIBA and one of the protease inhibitors  ,either Incivek or Victrelis.

These therapies are response guided and range from 26  to 48 weeks in duration ,depending on many factors( incl. any prior response to therapy,amount of fibrosis) as well as early response mentioned.

There are many new drugs being investigated currently and there  new therapies avail...some in the near future that still will include PEG/RIba and some farther down the line that do not contain PEG(possibly in the next year or thereabouts).

Welcome..
Will