Medscape New HCV Video Series - Hepatitis C Virus: Containing the Threat

Medscape - New Video Series
Hepatitis C Perspective

Hepatitis C Virus: Containing the Threat

About this Series
In the past few years, a new class of direct-acting antiviral agents has made the treatment of HCV easier and more effective than ever before, with cure rates nearing 100%, even among HIV-positive patients. But not all patients with HCV who are eligible for antiviral treatment are identified, and even fewer are being referred for care. Thus, HCV infection remains a significant risk for progression to cirrhosis, liver failure, and hepatocellular carcinoma. Liver specialists at two prestigious Chicago medical centers confront the key issues in the management of patients with chronic HCV infection.

View: Episode 1/ Strides and Obstacles

Coming Soon

Begin here
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Watch Dr. Douglas Dieterich - Importance of Hepatitis C Screening and Treatment

Importance of Hepatitis C Screening and Treatment
Health Power for Minorities

Published on May 18, 2017

Dr. Douglas Dieterich, Director of The Institute for Liver Medicine at Mount Sinai Health System in New York City and Bob Rice, who was cured of chronic hepatitis C after medical treatment and a liver transplant, discuss the importance of hepatitis C screening and treatment with Health Power's president, Dr. Norma Goodwin.

The fact that hepatitis C is now curable is a major medical accomplishment because "hep C" without treatment is linked to cirrhosis of the liver, liver cancer and at times, even death.

Getting Up to Speed on HCV Therapies - Experts discuss HCV before, during and after treatment.

Good day folks, if you have been diagnosed with HCV and either considering treatment, on treatment or have completed treatment you may benefit greatly from viewing this easy to follow video program over at Clinical Care Options.

The presentation; "Getting Up to Speed on HCV Therapies"offers a look see at various HCV patient scenarios. Experts discuss the use of current HCV therapies before, during and after treatment.

As an example in the first video "Treatment for HCV" a noncirrhotic 50-year-old genotype 1a patient who would prefer to be treated with sofosbuvir/ledipasvir is reviewed. In the second module it's all about pre-treatment considerations in patients taking other medications. Next up an overview of adherence during treatment and finally in the post-treatment section "Cure" is defined. In addition experts discuss the benefit of SVR in relation to reducing liver-related mortality in persons with advanced liver damage. Closing with the importance of follow up care, testing, liver wellness, and alcohol use.

Sit back and view experts; Sherilyn C. Brinkley, MSN, CRNP; Elizabeth K. Goacher, PA-C, MHS; Jennifer Katzianer, PharmD, BCPS; and Andrew J. Muir, MD, discuss the following topics

• Considerations Influencing Choice of Oral Therapy for HCV Infection
• Pretreatment Support for HCV-Infected Patients
• On-Treatment Management of HCV Therapy
• Posttreatment Care Following HCV Cure

During the presentation participants can easily skip follow up questions by clicking the "NEXT" button located at the bottom of the page or click on the "Table of Contents" to continue with the activity.

Free registration is required, begin here, view video module, here.

Hepatitis C: what treatments work?

Patient information from the BMJ Group 

Hepatitis C: what treatments work? 

Hepatitis C is an infection that can harm your liver. Many people don't know they have it, because there are often no symptoms for many years.Treatments can get rid of the virus. 

What happens when you have hepatitis C? 

The virus that causes hepatitis C is carried in human blood.You can catch it if blood from someone with the virus gets into your bloodstream and the virus is carried to your liver. Some people's bodies fight off the virus naturally, without any treatment. 

This happens for between 15 and 45 in every 100 people who are infected with the virus. But many people aren't able to fight off the virus on their own. If you have had the infection for more than six months, doctors say you have chronic hepatitis C. 

Some people live for many years with chronic hepatitis C, without having any health problems. But it can cause scarring in your liver and stop your liver working properly. 

If your liver isn't working properly, all the jobs that it does are affected. These include breaking down waste products in your body, fighting infection, and breaking food down into a form your cells can use for energy. 

Up to 20 in every 100 people who have chronic hepatitis C eventually get scarring in their liver (cirrhosis) if they don't have treatment. Over time, cirrhosis can cause life-threatening problems, including liver cancer. 

Should I have treatment - and when? 

Treatment for hepatitis C takes several months, and it can have some unpleasant side effects. So it can sometimes be difficult to decide if, and when, to have treatment. Here are some of the things you need to think about.You can talk them over with your doctor to decide what is best for you. 

Were you infected recently? 

If you have recently been infected with hepatitis C, you and your doctor may decide to hold off on treatment to see whether your body is able to fight off the infection on its own. You will need to have regular tests to check on the virus. If you have had the infection for six months or longer, it is unlikely that your body will get rid of the virus without treatment. 

How old are you? 

If you are younger than 18 or older than 60, the benefits of treatment may not be as clear as they would be for someone at a different age. For example, not much research has looked at the effects of hepatitis C medicines in children. And someone who is older might have other health issues that could make treatment more difficult, or harmful.These are issues you should discuss with your doctor. 

Is your liver damaged? 

If you have hepatitis C, but you don't have any signs of liver damage, your doctor may say you don't need treatment now. But you might get liver damage in the future.You need to keep in touch with your doctor and have regular tests. 

If you have mild liver damage, there's a better chance that treatment will work than if your liver damage is more serious.You need to weigh up the chance that liver damage may get worse, against the side effects of treatment. 

If you have serious liver damage, your doctor will probably suggest that you have treatment as soon as you can. 

Will you be able to cope with the side effects? 

You may get unpleasant side effects during treatment, which can be difficult to cope with. However, this is less likely with newer medicines for hepatitis C (see below). It's important that you fully understand the possible side effects, so you can weigh these against the possible benefits of treatment.

What treatments work? 

Medicines can help you get rid of the hepatitis C virus. This may stop any liver damage from getting worse and prevent future damage. 

Types of medicines 

Interferon used to be the main medicine for hepatitis C. However, there are several newer treatments that often work better than interferon, cause fewer side effects, and require a shorter length of treatment. 

Another advantage of the newer treatments is that you take them as tablets or capsules. Interferon requires an injection. 

The newer medicines include: 

• Dasabuvir 

• Ledipasvir 

• Ombitasvir 

• Paritaprevir 

• Ritonavir 

• Simeprevir 

• Sofosbuvir

You take these medicines once or twice a day.You might take more than one of these drugs at a time, or combine them with older medicines called peginterferon (a type of interferon) and ribavirin. People also sometimes have treatment just with peginterferon combined with ribavirin.

Treatment usually lasts between 12 and 24 weeks. However, if you have peginterferon and ribavirin on their own, treatment lasts for 48 weeks. 

What treatments your doctor recommends depends on a few things. 

What type of hepatitis C virus do you have? 

There are six types of hepatitis C virus.They are called genotypes, and they are numbered 1 to 6. What genotype you have affects which medicines are most likely to work for you. Most people with hepatitis C in Western Europe have genotype 1, 2, or 3.You will have a blood test before you have treatment to find out which genotype you have. 

Do you have certain medical conditions? 

If you are pregnant, taking some of these medicines may harm your baby. Talk to your doctor about your options.You may want to wait until after you've had your baby to start treatment. 

If you have kidney disease, heart disease, or bad liver damage, you may not be able to take ribavirin. That's because it can make these conditions worse. 

Have you been treated for hepatitis C before? 

Treatment for hepatitis C doesn't always work. And, sometimes, it works for a while and then the virus flares up again. If you have had treatment for hepatitis C before, you can have treatment again. However, you may be offered different medicines. 

What medicines are available where you live? 

The newer medicines for hepatitis C have not yet all been approved in some countries. You can talk to your doctor about what treatments are available where you live. 

Medicine side effects 

The newer treatments for hepatitis C can cause side effects, but these are usually not serious. Side effects can include tiredness, problems sleeping, a rash, itching, headaches, diarrhoea, and nausea. 

The older hepatitis C medicines - peginterferon and ribavirin - have several side effects, which can be difficult to cope with. 

Common side effects of peginterferon include tiredness, aches and pains, nausea, losing weight, feeling irritable and depressed, and losing your hair (but it grows back). 

Common side effects of ribavirin are tiredness, feeling irritable, skin rashes, a stuffy nose, and coughing. These medicines can also cause more serious problems. 

They include anaemia (you have too few red blood cells), problems with your thyroid gland; serious infections; a problem where your body makes hardly any white blood cells; a problem where your body makes hardly any platelets, which help your blood to clot; and severe depression. 

While you are taking these treatments, you will have regular blood tests to check for some of these problems.

Follow-up 

The only way to see if treatment is working is to have blood tests to check for the virus. If your test is positive, you still have the virus in your blood. If your test is negative, you have no sign of the virus in your blood. 

Most people have blood tests for the virus after four and 12 weeks of treatment. People with genotype 3 have an additional test after 24 weeks. If there is no sign the medicines are working, your doctor will probably advise you to stop taking them. 

The virus can come back after treatment is over. To be certain that the treatment has worked, doctors test for the virus again six months after you finish treatment. If there is no sign of the virus, doctors say you have a sustained virological response (SVR for short). 

Among people with the most common genotypes (1, 2, and 3), those with genotype 1 used to have a much lower chance of getting rid of the virus through treatment than people with genotype 2 or 3. However, the newer treatments have changed this. Now, the vast majority of people have no sign of the virus six months after they finish treatment

© BMJ Publishing Group Limited 2015. All rights reserved. Last published: Mar 04, 2015

 

This information is aimed at a UK patient audience. This information however does not replace medical advice. If you have a medical problem please see your doctor. Please see our full Conditions of Use for this content. For more information about this condition and sources of the information contained in this leaflet please visit the Best Health website, http://besthealth.bmj.com . These leaflets are reviewed annually.

HCV Weekend Video - Basic facts on hepatitis C

HCV Weekend Video:

Basic facts on hepatitis C 

Good morning everyone, today we have two videos offering basic information on hepatitis C and the liver. Topics range from transmission, testing, to new treatments. 

Hepatitis C 

Uploaded by Gastrointestinal Society

Updated To Include Press Release - Feb 10 2015
Gastrointestinal Society Releases New Video about Hepatitis C

Published on Jan 20, 2015

Hepatitis C is a liver disease caused by the Hepatitis C virus, this video discusses screening, symptoms, treatments, and more about this curable disease.

For more free information on this and other digestive diseases and disorders the Society covers, please visit our website http://www.badgut.org/

Chronic Hepatitis C

Uploaded by Rajmuf

Published on Jan 17, 2015
References:
http://www.hcvguidelines.org/
http://www.jabfm.com/content/27/2/284...

Detailed Overview: Transmission, testing, management, and new treatments. 

Hepatitis C Weekend Reading: "Not without a fight Kim!" A Mothers Story

Good day everyone, hope you all have a safe and enjoyable weekend. Tomorrow I begin a new chapter in my life, I'm moving across the state, only five minutes from my children and grandchildren. Here comes trouble!

I am so grateful to be healthy, after watching Kim Bossley share her story today on Second Opinion, I was reminded this morning of just how fortunate I am.

* I successfully treated HCV soon after being diagnosed in 2000 

Summary  
Kim's Story and The Bonnie Morgan Foundation
Kim's story begins with her mother, Bonnie Morgan, who suffered with kidney disease since birth. Later in life when she needed a kidney transplant, Bonnie's mother Ruth proved to be a suitable match, the transplant was a success. Against all odds, three years after Bonnie's transplant, she gave birth to Kim, a mothers dream came true. Tragically, sometime later Bonnie found out both she and her child contracted hepatitis C through an earlier blood transfusion. The story continues, but should be read firsthand at The Bonnie Morgan Foundation, Co-Founded by Kim Morgan Bossley, in honor of her mother.

Full Episode 

PBS Program - Second Opinion

Kim Bossley on New York City's PBS show, Second Opinion. In addition Kim has published many wonderful articles online at www.hepmag.com.

Thank you Kim for being such a strong voice for everyone living with and battling hepatitis C.

Be Hip To Hep: Dispelling old myths and discovering the hopes for those with hepatitis C

Be Hip To Hep: Dispelling old myths and discovering the hopes for those with hepatitis C

Good morning folks, over at DentistryIQ an insightful article about living with hepatitis C now available for your reading pleasure.

Dr. Muñoz, professor of English at Cosumnes River College writes from a patients perspective about living with HCV.

The article offers information about; diagnosis, transmission/sexual transmission, risk factors, blood tests, stigma - "In addition to work difficulties, my personal life disintegrated. I felt a sense of shame as I listened to a friend unwittingly joke how Pamela Anderson was repulsive. Not because of her famously exaggerated cup size, but rather (and solely) because she had the misfortune of contracting HCV." as well as treatment, and advice for persons living with the virus.

Be hip to hep

Dispelling old myths and discovering the hopes for those with hepatitis C

BY HEIDI EMMERLING MUÑOZ, PhD

"You have hepatitis C."

Those words turned my life upside down. I tell this story not to elicit sympathy but to illustrate what it means to live with hepatitis C (HCV): the physical as well as the emotional. Only now, because I am out of clinical hygiene and because there is a cure in sight, do I feel safe in telling my story.

I also tell this story to urge screening and to give hope to anyone living with HCV.

Continue reading....

Karen Hoyt: Your Best Friends Guide To Hepatitis C

 

HCV Advocate Karen Hoyt

Meet the creator of; Your Best Friends Guide To Hepatitis C, Karen Hoyt, an inspirational woman, HCV advocate, and author who is living with hepatitis C and cirrhosis. Karen embraces life with an infectious spirit she generously shares online with you, her friends. With her blog Karen has created a safe haven for anyone living with this sometimes cruel and unpredictable illness. Exuding pure devotion Karen gently guides us through each HCV test, symptom, and every emotion this disease has to offer.

In addition to her blog, IhelpC.com, a series of four exceptional videos appropriately deemed "True Champions" featuring Karen were recently launched by HealthiNation. If you haven't seen them you're in for a treat. 

True Champions: Hepatitis C Videos

In each of these video segments Karen takes us on an incredible journey beginning with her own battle with HCV.  In the video "Advocates" Karen interviews author Lucinda Porter, another loved and respected HCV advocate who has educated our community for over a decade. 

Begin Here........... 

Stay connected with both Karen and Lucinda on Twitter

Hepatitis C Virus can affect your liver and your health

HEPATITIS C (HCV) by Dr. Robert Gish

In this mini lecture, Dr. Gish examines the Hepatitis C and how the Hepatitis C Virus can affect your liver and your health. 

Dr. Gish explains the importance of talking to your healthcare provider about starting treatment now or waiting, he urges patients to keep up with new therapies and data.  



Uploaded Oct 6 by Bob Gish

Documentary - Breaking the Silence: Voices of Chronic Hepatitis C

Hi Folks,
As once a hepatitis C patient myself, I was deeply touched while viewing this awe inspiring documentary from Janssen Therapeutics.  For 17 minutes the viewer with hepatitis C is not alone, for 17 minutes normal people just like you and me share their story, diagnosis and family struggles. Support of family and friends is critical, but no matter how much our loved ones may empathize with us - connecting with other people living with the virus is invaluable.

 

**View the video or read the transcript here.

Next in Breaking the Silence: Voices of Chronic Hepatitis C

Published on Aug 16, 2013

As part of our commitment to hepatitis C, Janssen Therapeutics has created Breaking the Silence: Voices of Chronic Hepatitis C, which focuses on the experiences that patients, caregivers, and providers face during their journey with hepatitis C. We hope you enjoy this special documentary.
 

Newly Diagnosed -Where do you begin to search for hepatitis C information on the Internet?

When diagnosed with a serious disease such as hepatitis C, it's normal to feel completely out of  control. Life as you know it has changed.

The initial diagnosis is nothing less then traumatic, what ensues is a unexpected life adjustment, but not before going through several challenging phases. The first phase for me was shock, then came the denial, fear, and eventually acceptance. Not until the latter was achieved was I able to begin my journey to wellness and regain back some control over my life.

After testing positive for HCV most of us imagine the worst-case scenario, which is easily validated after spending a few hours online pouring over conflicting research. Although, some of the information provided to us is reliable and up to date; some is not. Today, I hope to point the newly diagnosed in the right direction by providing a few substantial links to relevant HCV information.

Where do you begin to search for hepatitis C information on the Internet?
Knowing the buzz words or the key words are essential for a successful search. Let us begin at the beginning - with the natural history of hepatitis C.

*Reference applies to HCV-positive untreated population.  

So What Will I Find Out About Hepatitis C?
The Natural History Of Hepatitis C - Topics will include the following

1- The acute phase of hepatitis C - Acute hepatitis C infection involves short-term illness that happens within the first six months after a person has been exposed to the HCV virus.

2-What spontaneous viral clearance means- Approximately 25% of patients acutely infected with HCV will clear the virus spontaneously, and 70-85% of patients will develop chronic infection.

3- All about chronic hepatitis C - A persistent hepatitis C infection with periodic evidence of HCV RNA in the blood for at least 6 months.

4-  Symptoms

5-Extrahepatic conditions - Conditions outside the liver associated with Hepatitis C infection. Several extrahepatic complications have been associated with HCV including hematologic and dermatologic diseases as well as autoimmune and kidney diseases.

6- Finally, information on disease progression and how host factors influence the progression - The rate of disease progression in hepatitis C infection is influenced by both virus- and host  

A Few Links To Get You Started
Review
2006 - The Natural History of Hepatitis C Virus (HCV) Infection

Natural History Of Hepatitis C
2013 - A collection of articles and research 

What About Liver Health, Support and Treatment?
Provided below are helpful links to additional information on HCV including: Testing, disease progression, liver health, diet, transmission, books, videos, treatment with current direct-acting antivirals and investigational antivirals, lastly support.

What  to do with a positive hep C test 
 Lynn Rapsilber, MSN, ANP-BC, APRN
September 13, 2012
HCV antibody testing is sensitive and inexpensive. Anti-HCV screening assays include the enzyme immunoassay (EIA) or the enhanced chemiluminescence immunoassay (CIA). Positive results are reportable and should be confirmed with a repeat test. The recombinant immnunoblot assay (RIBA), a more specific serologic anti-HCV assay, is no longer used. Once the antibody test is positive, HCV-polymerase chain reaction (PCR) RNA test measures how much HCV is in the bloodstream. 

Continue reading........ 

May 20, 2012
Hepatitis C Testing- the Fine Print
A positive Hep C Antibody test (the screening test) cannot tell you how long you have been infected. More testing is now required. The next step will be to have a different blood test that measures "viral load"- actually looking for the amount of Hep C virus present in your system. Other blood tests will measure your liver "function" to see if it looks inflamed. Your doctor may also test to determine the subtype of Hep C in order to better advise you regarding the potential response to therapy. By the way, All positive tests for Hep C will be reported to the health department. This should not to make you paranoid, as your insurance company will obviously know as well, but simply something to note.
Continue reading.. 

The Disease 
Liver disease in people with hepatitis C affects everyone differently, while it may progress slowly in most people, it can also progress quickly in others. A few host factors including duration of infection, co-infection with HBV or HIV, age, race, gender, genotype, alcohol use, smoking, other underlying disease (diabetes), all have an impact on liver disease progression.

Beyond the Basic: Understanding Hepatitis C

Clinical Features of Hepatitis C Virus Carriers With Persistently Normal Alanine Aminotransferase Levels

Conditions outside the liver associated with Hepatitis C infection

The High Comorbidity Burden of the Hepatitis C Virus Infected Population in the United States
Chronic hepatitis C (HCV) disease can be complicated with comorbid conditions that may impact treatment eligibility and outcomes.  The aim of the study was to systematically review comorbidities and symptoms in an HCV infected population, specifically assessing  comorbidities associated with HCV anti-viral treatment and disease, as well as comparing comorbidities between an HCV infected  and uninfected control  population

Liver Health - 2013

Meal consumption confounds liver stiffness measurements in patients with chronic HCV

Hepatitis C-Moderate, excessive or heavy alcohol consumption:each is significantly associated with increased mortality

Coffee and Liver Disease

Consumption of coffee associated with reduced risk of liver cancer: a meta-analysis

Some Omega-3 Oils Better Than Others for Protection Against Liver Disease

Binge drinking can dramatically amplify damage to the liver

Ways You Can Take Care of Your Liver

Managing Your Medications

Natural Approaches to Hepatitis C and Liver Health

Diet
Dr. Galati- Watch: Is there a Special Diet for Hepatitis C?

HCV Education - CME activities
HCV-Education
Includes CME activities in various media formats covering the following topics: treatment regimens, resistance, current direct-acting antivirals, investigational antivirals, interferon alfa-free regimens, effects of HCV on the liver, diet,drug-drug interactions, and managing side-effects

Transmission
Sexual transmission of HCV among monogamous heterosexual couples: The HCV partners study

Need Some Answers?
Updated 2012
Best List Of HCV FAQs
Informational site providing resources, education, and support for the hepatitis C community.
168 Pages Of Hepatitis C FAQs

Treatment
A ‘Killer’ of a Reason to Treat Hepatitis C
Dr. David Johnson stresses the importance of treating patients with hepatitis C and advanced hepatic fibrosis, given that those with sustained treatment response have a lower all-cause mortality rate.

Update on the Management and Treatment of Hepatitis C Virus Infection
Recommendations from the Hepatitis C Resource Center and the National Hepatitis C Program Office, May 2012

Guidance for Hepatitis C Treatment Monitoring
Monitoring Patients on Pegylated Interferon + Ribavirin ± Protease Inhibitor (Boceprevir or Telaprevir), March 2012

An Update on Treatment of Genotype 1 Chronic Hepatitis C Virus Infection: 2011 Practice Guideline by the American Association for the Study of Liver Diseases
Ghany MC, Nelson, DR, Strader, DB, et al. Hepatology, Vol. 54, No. 4, 2011, 1433-1444.

Potential IFN-Free Regimens For HCV
Enthusiasm is growing for the various interferon (IFN)-free therapies on the horizon for patients with hepatitis C virus (HCV) infection. At the recent annual meeting of the American Association for the Study of Liver Diseases (AASLD), The Liver Meeting 2012, four of the six late-breaking abstracts and a slew of other studies discussed new oral regimens that can be used to achieve high rates of sustained virologic response (SVR) in a variety of HCV patient cohorts, including null responders.

Current Prospects for Interferon-free Treatment of Hepatitis C in 2012
Numerous other DAAs are in clinical development, and phases 2 and 3 trials are evaluating interferon-free combination DAA therapy. Interferon-free sustained virologic responses have now been achieved with combinations of asunaprevir and daclatasvir; sofosbuvir and ribavirin; sofosbuvir and daclatasvir; faldaprevir and BI207127; ABT-450, ritonovir and ABT-333; ABT-450, ritonovir and ABT-072; miracitabine, danoprevir and ritonavir; and alisporivir and ribavirin. Some drugs are genotype-specific in their activity, whereas others are pan-genotypic, and differential responses for the genotype 1 subtypes 1a and 1b have emerged with many DAA combinations. Viral breakthrough and resistance are important considerations for future trial design. The prospect of interferon-free combination DAA therapy for hepatitis C virus is now finally becoming a reality.

Treatment Action Group publishes Guide to  Clinical Trials for  People With Hepatitis C
There are many new hepatitis C drugs being  studied in clinical trials. People with hepatitis C have many options to choose  from. Whether you have hepatitis C or another medical condition, deciding to  participate in a clinical trial can be complicated. Having more information can  help you decide whether or not to participate in a clinical trial, and which  trial, or trials, may be right for you....

Do I Need To Treat? Should I Wait? Or Treat Now?
Treat Now or Wait?
The debate rather to treat HCV now or wait is ongoing, in the journal "Liver International" factors which affect the decision to treat now or delay therapy are discussed.  

Excerpt From The Article-
When deciding whether to treat a patient with HCV now, or to defer treatment, most clinicians would decide to treat patients with bridging fibrosis and cirrhosis (Metavir stages 3 and 4) now because they have an increased risk of hepatic decompensation and hepatocellular carcinoma. There is a feeling by many that patients with less severe fibrosis can wait for better or less toxic therapies. The irony of this approach is that HCV treatment is more successful in patients with mild than advanced fibrosis. This is true whatever the baseline factors including genotype, race and IL28B status and whether patients are being treated with PEG-IFN/RBV dual therapy or triple therapy with a protease inhibitor [2-5]. Future HCV treatments will probably also be less effective in patients with advanced fibrosis and cirrhosis. Excluding patients with mild fibrosis from treatment now will only reduce the overall SVR rate in the treated population, increase the overall cost per SVR, and most importantly increase the risk that a patient who could be ‘cured’ of HCV now fails to achieve SVR in the future.

View the article here: Patients with HCV and F1 and F2 fibrosis: treat now or wait?

Updated March 2013
A collection of articles available @ Hepatitis C New Drug Research and Liver Health:
Chronic hepatitis C: Treat or wait?

Where Can You Find An Easy To Understand Website With Accurate Information ?
HCV Advocate is the go to site for all your questions, filled with information, news, HeathWise articles, fact sheets, new drugs currently in the pipeline, clinical trials, and a monthly newsletter.

The Links
HeathWise articles can be found in the HCV Advocate Newsletter, Fact Sheets , HCV Drug Pipeline , News Updates , Clinical Trials, and Hepatitis C -Everything You Need to Know

Personal Experience
Lucinda K. Porter, RN
Starting 12 weeks of sofosbuvir, GS-5885, and ribavirin

Defeating Hep C
Contracted HCV genotype 1a via blood transfusion during chemotherapy treatment for leukemia at age 12 (acute myelocytic leukemia). 

Books
Lucinda K. Porter, RN:
FREE FROM HEPATITIS C

Coming in September 2013
A second book authored by Lucinda K. Porter, RN:
Hepatitis C Treatment One Step at a Time: Inspirational Readings and Practical Tips for Successful Hepatitis C Treatment

Curing Hepatitis C - View Chapter 6
Curing Hepatitis C, View Chapter 6: The Future of HCV Treatment-Beyond Triple Therapy
Chapter six of the new book "Curing Hepatitis C" written by Gregory T. Everson, M.D. is available for downloading.
To order the book click here. 

Multimedia
For the hands on reader check out the Multimedia section of the web site. This page contains udpated HCV educational podcasts, and videos.

Hepatitis C – What Are Your Treatment Choices: New Webinar

If you have hepatitis C and need more information on your treatment choices, there is a new tool available on the American Liver Foundation Hepatitis C website. Watch as Dr. Joseph K. Lim, Associate Professor of Medicine and Director of the Yale Viral Hepatitis Program at the Yale University School of Medicine shares with you treatment options for viral Hepatitis C.

Need To Talk To Someone ?
Help is available, recently "Project Inform" announced the launch of a new national helpline, 877-HELP-4-HEP (877-435-7443), run by and for people affected by hepatitis C. The helpline operates Monday through Friday 9am to 7pm EST. To learn more, visit www.help4hep.org or email info@help4hep.org.

Online Support - Message Boards
HCV Support

"HCV Support gives me the strength, knowledge and support that I need to fight this disease. The members genuinely care about one another and they completely understand how you feel."

 

Med Help

Thanks to all the members who are an integral part of the community, MedHelp has become a destination for people looking for answers to their medical questions. As the community has grown, so has the number of questions on the site. While the top community members devote time each day to helping others get answers or support in their time of need, there seem to always be more questions than answers.

 

Hepatitis Central
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.

 

Daily Strength Hepatitis C Support

Discuss Hepatitis C with others who understand what you're going through

 

HepC Nomads Forum

Help, Support and Information For Those Affected By Hepatitis C

WebMD® Hepatitis Community

Have Questions About Hepatitis?

 

Hep C Friends

Articles, general discussions relating to Hep C and treatment

 

Yahoo HepCWarriors
This group is for ALL PEOPLE AFFECTED BY HEPATITIS C (HCV), who spend time researching the web for info on Hep C. We are "Web Warriors". We fight the "dragon" with a vengeance. Knowledge is vital to surviving or defeating Hepatitis C. HepCWebWarriors is is a valuable resource for the latest HCV news, published papers, treatment and new drug trials.

Hep Mag
Welcome to the Hep Forums, a round-the-clock discussion area for people who have Hepatitis B, C or a co-infection, their friends and family and others with questions about hepatitis and liver health. Check in frequently to read what others have to say, post your comments, and hopefully learn more about how you can reach your own health goals.

May you find a way to manage the uncertainty and new changes this disease can bring. Wishing you a successful and safe journey.

ALF- New HCV Website and Adds HCV Specialist To HelpLine

NEW HEPATITIS C TOOLS AVAILABLE - HELPING YOU GET TO A CURE

July 28th marks the second World Hepatitis Day. As part of the activities surrounding this important day of awareness about viral hepatitis, the American Liver Foundation will launch its new hepatitis C information and education support program titled, “Hepatitis C: Diagnosis, Treatment, Support.”

With the introduction of two new treatments for hepatitis C, this is a disease that can be cured. The goal of the Hepatitis C: Diagnosis, Treatment and Support program is to provide the necessary information so those individuals considering treatment have answers to their questions, can identify the resources available to them and look at avenues of support.

New Hepatitis C Website to Be Launched

The Hepatitis C: Diagnosis, Treatment, Support website is about to be launched. This will be the most comprehensive place on the web to find information for those who are diagnosed with hepatitis C and looking for information on treatments. The website will be found at www.hepc.liverfoundation.org.

American Liver Foundation HelpLine Service Adds a Dedicated Hepatitis C Specialist and Expands Hours

1-800-GOLIVER (1-800-465-4837

After receiving a diagnosis of hepatitis C, everyone has questions. And there are times you need someone to help sort through those questions and provide information.

To answer this need, the American Liver Foundation has added a hepatitis C specialist and expanded the HelpLine hours.

Callers can now reach someone at the Helpline from 9:00 AM to 7:00 PM Eastern time, Monday – Friday. In addition, questions sent on e-mail to info@liverfoundation.org will be promptly answered.

Hepatitis C- Accurate, clinically relevant information for patients with viral hepatitis

Hepatitis C Information

Learning about HCV or deciding on a treatment plan after being diagnosed can be an overwhelming task.

Hours and hours of searching the Internet for accurate easy to understand information often ensues. Finding the right creditable web site with relevant information is invaluable.

Here are a few links pointing you in the right direction, starting with Clinical Care Options (CCO)

CCO Hepatology in Practice™ is a unique Web site designed to provide easy access to accurate, clinically relevant information to improve care for patients with viral hepatitis. The program was launched in 2011 and the contents are reviewed and updated on an ongoing basis.

This site is available for use after a free, one-time registration.
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The information available to patients at CCO is abundant, here are just a few topics of interest.

Hepatology - Management of Hepatitis C Infection

Released: 12/13/11

Last Reviewed: 12/13/11

In patients with chronic hepatitis C virus (HCV) infection, the goal of therapy is virologic cure. Eradication of HCV RNA, which persists long-term off therapy, is referred to as a sustained virologic response (SVR). Although SVR is equivalent to virologic cure, the term cure has traditionally been avoided. Initially, there was concern that despite undetectable HCV RNA following treatment, there might potentially be dormant virus that could return in the future. However, long-term follow-up data show that patients with an SVR following treatment with peginterferon and ribavirin have a relapse rate < 1% after a mean of 1.8 years from the end of antiviral treatment,^{[Swain 2010]} and early data with protease inhibitor–based triple therapy indicate that SVR achieved in patients treated with telaprevir plus peginterferon and ribavirin is durable (< 1% relapse) through a median of 21 months of follow-up.^{[Sherman 2011b]} A further concern with the term cure is that underlying liver disease may not be fully reversed even if HCV infection is eradicated. Obtaining SVR is associated with decreases in all-cause mortality,^{[Backus 2011]} liver-related death, liver-related complications, the need for liver transplantation, and in the incidence of hepatocellular cancer.^{[Morgan 2010; Veldt 2007]} In patients without advanced fibrosis before treatment, SVR represents cure. For those with advanced fibrosis, particularly cirrhosis, SVR is a virologic cure associated with improved outcomes, but adverse events, particularly the development of liver cancer, may still occur. The positive outcomes observed are an effect of permanent HCV RNA eradication, as viral suppression by long-term HCV therapy without SVR does not have the same impact on clinical outcomes.[Shiffman 2009]

Protease Inhibitors

Released: 12/13/11

Last Reviewed: 12/13/11

In 2011, the novel agents boceprevir and telaprevir were approved by the US Food and Drug Administration and the European Medicines Agency for use in combination with peginterferon/ribavirin in treatment-naive and treatment-experienced patients chronically infected with genotype 1 hepatitis C virus (HCV). Both of these agents are NS3/4A inhibitors and act against an HCV-encoded serine protease that is required for cleavage of the viral polyprotein during and after translation. By preventing this important step in the viral lifecycle, both of these drugs potently inhibit HCV replication. Unfortunately, single mutations in the viral genome lead to high-level resistance to these agents, and so their use as monotherapy is not an option; boceprevir and telaprevir must each be given with peginterferon and ribavirin. The efficacy of each agent is discussed later, and indirect comparisons are made, as there have been no head-to-head trials comparing these 2 agents. For patients with non–genotype 1 HCV, the current standard of care remains dual therapy with peginterferon/ribavirin.......click here to continue

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CCO-Latest Hepatology Updates

1/12/12 - Hepatitis C Management in Special Populations
Updated to include new data on the pharmacokinetics of boceprevir coadministration with cyclosporine or tacrolimus

12/13/11 - Hepatitis C Virus Epidemiology, Pathogenesis, Diagnosis, and Natural History
Now available: Francesco Negro, MD, provides an in-depth review of past and current HCV transmission trends, the latest understanding of HCV pathogenesis, key assays and recommendations for the diagnosis of HCV, and the natural history of both acute and chronic HCV infection.

12/13/11 - Other Viruses That Affect the Liver
Now available: Joshua Levitsky, MD, MS, and Lisa B. VanWagner, MD, MS, outline the epidemiology, clinical presentation, diagnosis, and clinical management of the secondary and exotic hepatotropic viruses in patients with solid organ transplantations.

The Liver Meeting® 2011 Educational Webcast of selected sessions 
If you haven't yet explored the "LiverLearning" section available @ the AASLD web site you're missing out on the November meeting webcasts, video podcasts, abstracts and more. Free registration is required, start the process by clicking Here. 

Once this is accomplished click here to view webcasts and more.

Other HCV Sites:
These links will take you to the premier Hepatitis C sites and keep you informed with breaking news, clinical studies, new drugs, podcasts, newsletters, support, personal experiences, chat rooms, forums and more.

NEJM;Chronic Hepatitis C Infection-new directly acting antiviral agents in treatment regimens

From The NEJM Blog;

Posted by Abigail Place • June 24th, 2011

The latest article in our Clinical Practice series, Chronic Hepatitis C Infection, (see below) reviews the evaluation and initial management of chronic hepatitis C infection, with particular attention to the use of new directly acting antiviral agents in treatment regimens.

Infection with HCV affects an estimated 180 million people globally. It is a leading cause of chronic hepatitis, cirrhosis, and liver cancer and a primary indication for liver transplantation in the Western world.

Clinical Pearls
• What are the predominant risk factors for hepatitis C virus infection?
The predominant risk factor for HCV acquisition is injection-drug use; among U.S. adults 20 to 59 years of age with any history of illicit injection-drug use, the prevalence of HCV infection is greater than 45%. Other risk factors include blood transfusion before 1992, high lifetime number of sexual partners, and iatrogenic transmission, including through dialysis; in large series, 15 to 30% of patients report no risk factors.

• Approximately what percentage of patients with chronic hepatitis C virus infection have progression to cirrhosis?
Although the natural history of HCV infection is highly variable, an estimated 15 to 30% of patients in whom chronic infection develops have progression to cirrhosis over the ensuing three decades. A number of factors, including a longer duration of infection, an older age at the time of exposure, male sex, coinfection with other viruses such as HIV, and daily alcohol consumption, but not viral level or genotype, have been consistently associated with an increased risk of fibrosis.

Table 1. Predictors of a Favorable Response to Treatment with Peginterferon and Ribavirin.

Morning Report Questions
Q: What methods can be used to quantify hepatic fibrosis?
A: Several methods have been used to quantify hepatic fibrosis, including the simple aspartate aminotransferase:platelet ratio index and commercially available assays of some or most of the following biomarkers: (alpha)2-macroglobulin, (alpha)2-globulin, (gamma)-globulin, apolipoprotein A-I, (gamma)-glutamyltransferase, total bilirubin, and hyaluronic acid.

Q: What treatment is the standard of care for all HCV genotypes?
A: Over the past decade, on the basis of considerable data from randomized trials, pegylated interferon (peginterferon) plus ribavirin became the standard of care for all HCV genotypes. Regardless of the infecting genotype, the likelihood of a sustained virologic response is lower among patients with a high pretreatment HCV RNA level and higher among patients with better adherence to antiviral therapy.


Chronic Hepatitis C Infection

Hugo R. Rosen, M.D.

N Engl J Med 2011; 364:2429-2438 June 23, 2011

This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author's clinical recommendations.

A 45-year-old man undergoing a routine examination for life insurance is noted to have an aspartate aminotransferase level of 80 U per milliliter (normal range, 9 to 40) and an alanine aminotransferase level of 110 U per milliliter (normal range, 7 to 52). He reports a remote history of intravenous drug use. Tests for hepatitis C antibody and hepatitis B surface antibody are positive, and tests for hepatitis A and human immunodeficiency virus (HIV) antibodies are negative. Genotyping of the hepatitis C virus (HCV) reveals genotype 1b; the viral load is 2,460,000 IU per milliliter. The complete blood count is normal; the platelet count is 220×10⁹ per liter. An abdominal ultrasonogram is normal. How should this patient's case be managed?

The Clinical Problem

Infection with HCV affects an estimated 180 million people globally. It is a leading cause of chronic hepatitis, cirrhosis, and liver cancer and a primary indication for liver transplantation in the Western world.1 There are at least six major HCV genotypes whose prevalence varies geographically. Genotype 1 accounts for the majority of infections in North America, South America, and Europe.2 The predominant risk factor for HCV acquisition is injection-drug use; among U.S. adults 20 to 59 years of age with any history of illicit injection-drug use, the prevalence of HCV infection is greater than 45%.3 Other risk factors include blood transfusion before 1992, high lifetime number of sexual partners, and iatrogenic transmission, including through dialysis4,5,; in large series, 15 to 30% of patients report no risk factors.

The host immune response largely determines whether HCV is eradicated spontaneously or persists (as it does in the majority of patients).6 Although the natural history of HCV infection is highly variable, an estimated 15 to 30% of patients in whom chronic infection develops have progression to cirrhosis over the ensuing three decades.7 A number of factors, but not viral level or genotype, have been consistently associated with an increased risk of fibrosis

 (Figure 1)

Figure 1

Natural History of Hepatitis C Virus (HCV) Infection.). 8,9
Patients with HCV-related cirrhosis warrant surveillance for complications, including hepatocellular carcinoma, which develops in 1 to 3% of such patients per year.10 For patients with clinically significant hepatic fibrosis (Metavir stage ≥2 or Ishak stage ≥3)

(Figure 2)
Figure 2

Histologic Features of HCV Infection, According to Different Scoring Systems.), there is widespread agreement that antiviral therapy is indicated because of the high risk of cirrhosis.2,12
Prospective data indicate that the stage of fibrosis predicts clinical outcomes; the cumulative 6-year incidence of liver transplantation or liver-related death ranges from 4% for an Ishak fibrosis score of 2 to 28% for an Ishak score of 6.11 Because of the extended interval between infection and the emergence of complications, the HCV-related disease burden is projected to increase severalfold over the next 20 years.13

The hepatitis C virus, an enveloped flavivirus, was first cloned in 198914; the positive-stranded viral RNA (with approximately 9600 nucleotides) encodes a polyprotein precursor of approximately 3000 amino acids

(Figure 3A)

Figure 3

Hepatitis C Virology, Intracellular Innate Immune Response and Evasion Tactics, and Hepatic Immune Lymphocyte Response to Infection.). After binding to the cell surface, HCV particles enter the cell by receptor-mediated endocytosis. Cytosolic recognition of specific motifs in viral products (known as pathogen-associated molecular patterns) induces the production of interferons and proinflammatory cytokines, leading to the recruitment of a signaling complex to activate transcription factors (Figure 3B).15

Subsequent expression of interferon-β, interferon regulatory factor 3 (IRF-3) target genes, and probably lambda (type III) interferons induce innate immune programs and drive the maturation of adaptive immunity for the control of infection.15,16

The coordinated activities of CD4+ T cells and cytotoxic CD8+ T cells, primed in the context of HLA class II and I alleles, respectively, on antigen-presenting cells, are critically important for the control of acute HCV infection. Mutations in viral epitopes that are targeted by cytotoxic CD8+ T cells can allow the virus to escape immune-mediated clearance. Up-regulation of inhibitory receptors on exhausted (functionally impaired) T cells is another mechanism of T-cell dysfunction during chronic infection (Figure 3C).17,18

Strategies and Evidence

Diagnosis and Clinical Staging

Liver biopsy remains the standard for assessment of hepatic fibrosis and is helpful for prognostication and decision making. The histologic pattern of HCV infection consists of lymphocyte infiltration of the parenchyma, lymphoid follicles in portal areas, and reactive bile-duct changes. However, liver biopsy is costly and invasive, and it carries a risk of complications (e.g., 1 to 5% of patients who undergo the procedure require hospitalization).19 Additional limitations of biopsy include sampling error and interobserver variability.

Several methods have been used to quantify hepatic fibrosis, including the simple aspartate aminotransferase:platelet ratio index (APRI) and commercially available assays of some or most of the following biomarkers: α₂-macroglobulin, α₂-globulin, γ-globulin, apolipoprotein A-I, γ-glutamyltransferase, total bilirubin, and hyaluronic acid.19-21 (For more information on APRI, see Table 1 in the Supplementary Appendix, available with the full text of this article at NEJM.org.) The sensitivity and specificity of these assays for the detection of clinically significant fibrosis range from 41 to 94% and from 44 to 95%, respectively,21,22 and the assays are typically much better at detecting advanced fibrosis and cirrhosis than mild-to-moderate fibrosis. Combining assays (e.g., APRI and FibroSURE or HepaScore) appears to increase the diagnostic accuracy and may eliminate the need for liver biopsy in more than half of patients.12,22,23 Optimal cutoff values for establishing the accurate diagnosis of fibrosis may vary across populations, depending in part on the prevalence of advanced fibrosis.23

Management

Interferon-Based Antiviral Therapy

Substantial progress has been made in the treatment of HCV infection. The goals of therapy are to prevent complications and death from HCV infection; regardless of the stage of fibrosis, symptomatic extrahepatic HCV (e.g., cryoglobulinemia) is an indication for therapy.2 Over the past decade, on the basis of considerable data from randomized trials, pegylated interferon (peginterferon) plus ribavirin became the standard of care for all HCV genotypes.24-26

The two licensed peginterferons (Pegasys, Roche, and PegIntron, Merck) have been shown in head-to-head comparison to be equivalent in efficacy and to have similar safety profiles.27 Among patients with genotype 1 who are treated with peginterferon at the standard weight-based dose of ribavirin (1000 or 1200 mg per day) for 48 weeks, 40 to 50% have a sustained virologic response (defined as an undetectable HCV RNA level 24 weeks after the cessation of antiviral therapy). A shorter course of treatment and a lower ribavirin dose are associated with lower rates of sustained virologic response (and higher relapse rates) among genotype 1–infected patients.24-26 In contrast, patients with genotype 2 or 3, who account for approximately one quarter of HCV-infected patients in the United States, have rates of sustained virologic response in the range of 70 to 80% after taking peginterferon and ribavirin at a reduced dose (800 mg per day) for 24 weeks.25 A sustained virologic response is associated with permanent cure in the vast majority of patients.

(Table 1)

Table 1

Predictors of a Favorable Response to Treatment with Peginterferon and Ribavirin. shows virus-specific and patient-specific factors that affect the likelihood of a sustained virologic response. 2,24-26,28-30 Regardless of the infecting genotype, the likelihood of a sustained virologic response is lower among patients with a high pretreatment HCV RNA level (with a high level defined as >600,000 IU per milliliter in some studies and >800,000 IU per milliliter in others) and higher among patients with better adherence to antiviral therapy (receiving 80% of total interferon and ribavirin doses for 80% of the expected duration of therapy). Adherence can be problematic because of the plethora of side effects, including fevers, influenza-like symptoms, headache, cytopenias, fatigue, anorexia, depression, and anxiety.31

On-treatment viral kinetics have emerged as important predictors of the likelihood of response and are used to guide the duration of therapy.2 An early virologic response is defined as a decrease in the HCV RNA level of at least 2 log₁₀ IU per milliliter or the complete absence of serum HCV RNA at week 12 of therapy.2 The lack of such a response in a patient has a very high negative predictive value for a sustained virologic response. Among patients with previously untreated genotype 1 infection, more than 97% of those who do not have an early virologic response to treatment will not have a sustained response. A rapid virologic response, defined as an undetectable HCV RNA level (<50 IU per milliliter) at week 4 of treatment, has been shown to predict a sustained virologic response, as well as to identify those patients for whom the duration of therapy can be shortened without compromising the virologic response. A recent meta-analysis of seven randomized trials has shown that genotype 1–infected patients with a low baseline HCV RNA level (<400,000 IU per milliliter) who have a rapid virologic response may discontinue therapy at 24 weeks rather than continue for the standard 48 weeks.32 A reduction of the treatment duration has the added benefits of decreased costs and side effects.2,32

Race is another important predictor of response to antiviral therapy. Black patients have significantly lower rates of sustained virologic response than white patients (28% vs. 52%).33 Although the reasons for this difference have been uncertain, recent data from genomewide association studies have indicated that single-nucleotide polymorphisms (SNPs) on chromosome 19 in or near the interleukin-28B gene (IL28B, encoding interferon lambda-3) are highly predictive of successful antiviral treatment.34 In an analysis that was adjusted for other predictors, the chance of cure was more than doubled with homozygosity for the C allele at the rs12979860 SNP, as compared with the TT genotype (78% for the CC genotype, 38% for the TC genotype, and 26% for the TT genotype). The C allele is much more frequent in white and Asian populations than in black populations. Moreover, in the Viral Resistance to Antiviral Therapy of Chronic Hepatitis C study (VIRAHEP-C; ClinicalTrials.gov number, NCT00038974), which involved patients infected with HCV genotype 1, pretreatment HCV-specific CD4+ T-cell responses were significantly lower in black patients than in white patients and correlated with lower rates of a sustained virologic response.35 This study also showed that the expression level of the programmed death 1 (PD-1) receptor, with higher levels reflecting greater functional impairment of HCV-specific CD8+ T cells, was inversely associated with the likelihood of a sustained virologic response.36

Directly Acting Antiviral Agents

The molecular characterization of the virologic features (Figure 3A) and life cycle of HCV has led to the development of directly acting antiviral agents, with the goal of improved efficacy and fewer adverse effects as compared with interferon-based regimens.37 All the HCV enzymes, which are essential for HCV replication, are potential targets; the nonstructural 3 (NS3) serine protease inhibitors are the furthest along in development. In addition to ablating replication, protease inhibition blocks the ability of the NS3/4A serine protease to cleave the HCV polyprotein and interferon-β promoter stimulator 1, thus restoring innate immune signaling within hepatocytes (Figure 3B).15 Two protease inhibitors, telaprevir and boceprevir, were recently approved by the Food and Drug Administration (FDA).

In the Protease Inhibition for Viral Evaluation 1 trial (PROVE1, NCT00336479)38 and PROVE2 trial (NCT00372385),39 which involved genotype 1–infected patients who had not previously received treatment, the rates of sustained virologic response were 61% and 69%, respectively, among those who received a 12-week course of telaprevir, an orally bioavailable inhibitor of NS3/4A,38 in combination with peginterferon–ribavirin, which was continued for an additional 12 weeks (total duration of antiviral therapy, 24 weeks; T12PR24 in (Figure 4)

Figure 4

Study Design and Results of Five Published Trials of a Combination of a Protease Inhibitor and Peginterferon–Ribavirin in Patients with Chronic HCV Infection Who Had Not Previously Received Treatment.). As compared with standard therapy with peginterferon–ribavirin, the addition of telaprevir resulted in a shorter median time to achieve an undetectable HCV RNA level (<30 days, vs. 113 days).39 Major side effects of telaprevir included rash, pruritus, anemia, and gastrointestinal symptoms. The observation that viral relapse (detectable HCV RNA level during the 24-week posttreatment period in patients with an end-of-treatment response) occurred in 48% of patients who did not receive ribavirin (T12P12 in Figure 4) underscores the critical role of this agent in preventing relapse and the emergence of telaprevir resistance.39,43

The ADVANCE (A New Direction in HCV Care: A Study of Treatment-Naive Hepatitis C Patients with Telaprevir) trial (NCT00627926), a phase III randomized trial reported in this issue of the Journal, incorporated on-treatment response to tailor the duration of additional peginterferon–ribavirin.40 Telaprevir and peginterferon–ribavirin were administered for the first 12 weeks or for 8 weeks, followed by 4 weeks of placebo. Extended rapid virologic response was defined as an undetectable HCV RNA level (<25 IU per milliliter) at week 4 and week 12 of therapy37; patients who did not have an extended rapid virologic response received 36 additional weeks of peginterferon–ribavirin, for a total of 48 weeks. More than half of the telaprevir-treated patients had an extended rapid virologic response, and 24 weeks of total therapy was associated with a rate of sustained virologic response that was higher than 80% among these patients. As in all the other telaprevir studies, virologic failure was more common in patients with genotype 1a than in those with genotype 1b. The REALIZE (Re-treatment of Patients with Telaprevir-based Regimen to Optimize Outcomes) study (NCT00703118), also reported in this issue of the Journal, showed that the addition of telaprevir to peginterferon–ribavirin significantly increased the rate of sustained virologic response among patients who had previously received treatment, particularly in prior relapsers (patients with an undetectable HCV RNA level at the end of a prior course of peginterferon–ribavirin therapy but with a detectable HCV RNA level thereafter).44

The Serine Protease Inhibitor Therapy 1 trial (SPRINT-1, NCT00423670)41 and the SPRINT-2 trial (NCT00705432)42 have shown the efficacy of boceprevir in combination with peginterferon alfa-2b and ribavirin in genotype 1–infected patients who had not previously received treatment (Figure 4); another recent report in the Journal showed the efficacy of this regimen in patients who had previously received treatment.45 These trials included groups with a 4-week lead-in phase of peginterferon–ribavirin before the addition of boceprevir in order to lower viral levels, theoretically reducing the risk that drug-resistant mutations would emerge.42,45,46 SPRINT-2 used a response-guided antiviral strategy; patients whose tests for HCV RNA were negative by week 8 and remained so up to week 24 were given 24 weeks of boceprevir with peginterferon–ribavirin after the lead-in phase. Rates of sustained virologic response were 63% and 66% among patients receiving a total of 28 or 48 weeks of therapy, respectively, with higher rates among whites than among blacks. Patients in whom the HCV RNA level decreased by less than 1.0 log₁₀ IU per milliliter during the lead-in phase had significantly higher rates of virologic failure. Principal side effects of boceprevir included anemia (necessitating treatment with erythropoietin analogues in many patients) and dysgeusia, which appeared to be more common than previously reported with telaprevir; rash was reported less frequently than in the telaprevir trials.37

Mathematical modeling has projected that if the rate of response to antiviral therapy increases to 80%, which appears to be likely in the foreseeable future,13 treatment of half of HCV-infected persons would reduce cases of cirrhosis by 15%, cases of hepatocellular carcinoma by 30%, and deaths due to liver disease by 34% after just 10 years.13

Areas of Uncertainty

Transient elastography (FibroScan, Echosens) is a novel noninvasive technique that measures liver stiffness by assessing the velocity of a shear wave created by a transitory vibration.23 Thresholds for a high likelihood of clinically significant fibrosis (Metavir score ≥2) have been defined. The technique has an increased failure rate among obese patients, and it has not been approved by the FDA. Whether modifications of existing technologies (e.g., computed tomography and magnetic resonance imaging) will provide sensitive differentiation of levels of hepatic fibrosis requires further study.

Although peginterferon–ribavirin is likely to remain the backbone of antiviral therapy for the foreseeable future, options for treating HCV are expected to expand rapidly in upcoming years. The optimal combination of agents (including nucleoside and nonnucleoside polymerase inhibitors, inhibitors of NS4B and NS5A proteases, modulators of the immune response, and medications that interfere with lipid metabolism, which is essential for the assembly and maturation of HCV particles) and duration of therapy will need to be defined, in order to maximize rates of sustained virologic response while minimizing the risk that resistance will develop.46,47 A recent pilot study of a combination of directly acting antiviral agents suggests the possibility of treating HCV infection with an interferon-free, oral approach.48 Further study is needed in subgroups of patients with lower response rates, including black patients, patients without a response to prior treatment, liver-transplant recipients, and those who have coinfection with HIV, a high baseline viral load, advanced fibrosis, or insulin resistance.

Guidelines

The American Association for the Study of Liver Diseases2 and the American Gastroenterological Association49 have published guidelines for the assessment and management of chronic HCV infection, but these guidelines were issued before the publication of data from randomized trials of directly acting antiviral agents. Newer European guidelines take these data into account50; the recommendations provided below are generally consistent with these guidelines.

Conclusions and Recommendations

The patient described in the vignette has HCV genotype 1 with a high viral load. He should be vaccinated for hepatitis A because of an increased risk of liver failure among patients with chronic hepatitis C infection; hepatitis B vaccination is also indicated in those without evidence of prior exposure.2 Possible contraindications to treatment (e.g., depression) should be determined, and the patient should be informed about potential side effects of antiviral therapy.31,37-39,41,42 Although some clinicians would administer treatment without performing a liver biopsy, I would recommend a biopsy to assess the degree of fibrosis.31 For a patient with clinically significant fibrosis (Metavir score ≥2), triple antiviral therapy with peginterferon–ribavirin and an NS3/4A protease inhibitor, either telaprevir or boceprevir, should be recommended.

On the basis of data from recent randomized trials, a reasonable initial regimen would be telaprevir with peginterferon–ribavirin for 12 weeks. If tests for HCV RNA were negative at weeks 4 through 12 (indicating an extended rapid virologic response), only 12 additional weeks of peginterferon–ribavirin would be recommended, whereas if an extended rapid virologic response were not achieved, peginterferon–ribavirin would be continued for an additional 36 weeks.37 If boceprevir were used, according to new FDA guidelines, a 4-week lead-in phase of peginterferon–ribavirin would be followed by peginterferon–ribavirin and boceprevir for 24 weeks (a total of 28 weeks) if tests for HCV RNA were negative at weeks 8 through 24 of treatment. If the tests were positive between weeks 8 and 24 but negative at week 24, peginterferon–ribavirin and boceprevir would be continued for an additional 8 weeks, followed by an additional 12 weeks of peginterferon–ribavirin (a total of 48 weeks).

Alternatively, if the patient has milder fibrosis and is reluctant to receive treatment, it would be reasonable to wait and reevaluate as new therapeutic agents become available.46,47

Disclosure forms provided by the author are available with the full text of this article at NEJM.org.

No potential conflict of interest relevant to this article was reported.

An audio version of this article is available at NEJM.org.

I thank Greg Everson, M.D., and Jean-Michel Pawlotsky, M.D., Ph.D., for discussions and review of an earlier version of the manuscript.

Source Information

From the Division of Gastroenterology and Hepatology, Department of Medicine, University of Colorado School of Medicine, Aurora, and Eastern Colorado Veterans Affairs Medical Center, Denver.

Address reprint requests to Dr. Rosen at the Division of Gastroenterology and Hepatology, University of Colorado, Denver, B-158 Academic Office Bldg. 1, 12631 E. 17th Ave., Rm. 7614, Aurora, CO 80045, or at hugo.rosen@ucdenver.edu.

http://www.nejm.org/doi/full/10.1056/NEJMcp1006613