Saturday, December 30, 2017

The Long Road To Safe and Effective HCV Drugs: A Tribute To The People Who Helped Us Get There

The Long Road To Safe and Effective HCV Drugs

Soon we will be ringing in the New Year, will 2018 be your best year yet? I sincerely hope so.

As for me, I had my best year in 2000, the year I successfully treated the hepatitis C virus (HCV).

A time when curing HCV wasn't the norm, today that has all changed.

Although before we look ahead, I thought we might look back. Why? So that we may never forget just how far we've come, and the people who helped us get there.

Finding Support
In the mid-1990s members from around the globe who joined various HCV online support groups shared information, we became a wide circle of close friends. In the U.S. the National Hepatitis C Coalition dedicated a memorial to those friends we lost, which began in 2000 and updated until 2012. The site is no longer online, but the memorial has been saved, you can view it, here. A lovely memorial dedicated to the memory of Canadians who have died of hepatitis C is available online as well.

Today, according to The World Health Organization (WHO); globally, an estimated 71 million people have chronic hepatitis C infection. A significant number of those who are chronically infected will develop cirrhosis or liver cancer. Approximately 399 000 people die each year from hepatitis C, mostly from cirrhosis and hepatocellular carcinoma.

The Long Road To Safe and Effective HCV Drugs
In 1991 the FDA approved the first alfa interferon (Intron A) to treat hepatitis C, with cure rates  between 6 and 10 percent. In 1998 ribavirin was added, cure rates increased for people with HCV genotype 1 to around 23.6%. Finally, in 2001 Pegylated interferon plus ribavirin was approved, cure rates jumped to around 46%, again for genotype 1 patients.

Here in the U.S. because interferon was an injectable, some of us were put through a mound of paperwork before treatment was covered by our insurance provider. In Canada, many patients with normal ALT and AST levels were denied treatment, prompting some patients to consume alcohol before tests were administered. During that time with such low cure rates, some people treated not once, but twice, again requiring more paperwork. A summary of those triumphs, and let downs is represented in a post I keep updated, you can find it here, a record capturing past and current advances on the road to safe and effective HCV therapies.

Side Effects - We All Had Them
Both interferon and ribavirin had side effects, including flu-like symptoms, depression, weight loss, rage, joint pain, depression and other abnormalities of bloodwork; anemia, neutropenia, and thrombocytopenia (low levels of platelets). People needed rescue drugs to remain on therapy, for instance Procrit for anemia, an injectable that promotes red blood cell production and neupogen for severe neutropenia (low white blood cell count). We were confused, frightened, but determined.

Newer Agents - Better Cure Rates With Dangerous Side Effects 
Later, newer agents in clinical trials were looking better, to us anyhow. I remember how excited we were when Incivek, a drug by Vertex, administered in combination with pegylated interferon and ribavirin was FDA approved in 2011. Although side effects during clinical trials were reported, (new side effects) in particular a serious skin reaction, one that could be fatal, we were still encouraged. The SVR rates were high at the time for HCV genotype 1, at 69-75%, as mentioned, compared to Pegylated interferon plus ribavirin alone, at 46%. A large majority of people had liver damage, so treatment was a necessary evil. We didn't have a choice. We celebrated when our friends who treated previously achieved SVR, especially our sickest friends.

The Dark Side
We watched in horror as Bristol-Myers' BMS094 trials were discontinued, the drug was halted in 2012, after one person died and eight more were hospitalized. I remember corresponding with one of the trial participants who dropped out of the trial early, it was a dark time for HCV patients. Hell, the whole decade was a horrific time for patients.

The Stigma
The stigma was alive back in the day, HCV was associated with IV drug use, some of us, not all, were exposed to medical discrimination. As an example, asking for antidepressants under the influence of interferon wasn't always easy (my physician was amazing). Many of our friends in Canada, some here in the U.S. were denied treatment for up to 6 months because of past alcohol or drug use.

Not So Fast
In 2016 a study published in Lancet Infectious Diseases reported the high rate of HCV transmission in persons born between 1945 and 1965, the baby boomer generation (that would be us) was from hospital transmissions and reuse of medical injecting equipment rather than from injecting drugs. This study was important to everyone, because finally people were more likely to get tested. Let's face it, when it comes to stigma associated with HCV, we continue to run around in circles, only to end up back where we started.

In 2012, thirteen years after I was diagnosed, HCV was recognized in the U.S. by public health organizations, and awareness with screening strategies were firmly implemented; the CDC recommend all "baby boomers" should be tested one time for HCV.

Watershed Moment
Without scientist Michael Sofia, the devolvement of safe and effective new direct-acting antiviral therapy may have taken a bit longer. Sofia, created Sovaldi, which at the time (2013) was the first approved interferon-free treatment regimen for people with HCV genotypes 2 and 3, and approved for use in genotypes 1 and 4, in combination with PEG-IFN and ribavirin. Ugh. We still needed interferon.

Big Pharma - Barriers To Treatment
Although we recognize the enormous contribution made by the pharmaceutical industry; newer HCV drugs developed by Gilead, AbbVie, Merck, and Bristol-Myers Squibb has saved millions of lives around the world. However, before we could celebrate affordability became our next nightmare, Gilead's Sovaldi was set at $84,000 per treatment (price has come down but it took five years) leaving patients with access restrictions by third party payers. Some providers and insurers may still decline treatment for people with ongoing illicit drug or alcohol use, or limit treatment to those with advanced liver disease, although these restrictions are slowly improving across the U.S.

Hepatitis C: State of Medicaid
In October of 2017, the National Viral Hepatitis Roundtable (NVHR) together with The Center for Health Law & Policy Innovation of Harvard Law School (CHLPI) launched, Hepatitis C: State of Medicaid, the document offered: An in-depth evaluation of treatment access in each state’s Medicaid program, while highlighting successes in access expansion as well as ongoing challenges. Over half of Medicaid programs received a “D” or an “F” for imposing discriminatory restrictions on hepatitis C cures.

2017 Global Hepatitis Report
WHO published the Global Hepatitis Report, 2017, outlining the baseline for the drive towards elimination. The report sets out global statistics on viral hepatitis B and C, the rate of new infections, the prevalence of chronic infections and mortality caused by these two high-burden hepatitis viruses, as well as coverage of key interventions, all current as of the end of 2015.

Treat All
According to the HCV treatment guidelines published by the American Association for the Study of Liver Diseases, the Infectious Diseases Society of America and the International Antiviral Society, the only contraindication to current chronic HCV treatment is in a patient with a short life expectancy that cannot be lengthened with treatment, with liver transplant, or with any other treatments.

Overtime we have learned that treating people with lower-stage fibrosis increases SVR rates, and for persons who inject drugs, adherence and efficacy rates are comparable to those of patients who do not use injected drugs. In other words, treat all.

HCV & The Opioid Epidemic
Newer trends behind the surge of hepatitis C infections in our young people is America’s growing opioid epidemic. To date six U.S. states have declared their opioid-overdose situation an emergency, according to an article recently published in The New England Journal Of Medicine, NEJM also published: The Public and the Opioid-Abuse Epidemic. In addition; Authorities Are Cracking Down on Opioid-Peddling Doctors. Over at MedPage Today Molly Walker writes about - What's Next in Infectious Diseases? reporting that the opioid epidemic will likely continue to drive new HIV and hepatitis C infections.

Disease Progression
The rate of developing cirrhosis can evolve in 10–20% of chronic hepatitis C cases over a period of 20 to 30 years. However, longer duration of infection, infected at a later age in life, alcohol consumption, HCV genotype, male sex, fatty liver disease, diabetes, and coinfection with human immunodeficiency virus (HIV) or chronic hepatitis B (HBV), increases the risk for developing cirrhosis as high as 25% to 50%. In addition, burden of disease can be significant for those people with HCV-related cirrhosis, putting them at risk for hepatocellular carcinoma, liver failure, and in some cases a need for liver transplantation. In 2013, data presented at IDWeek, reported people with hepatitis C virus (HCV) die 15 years earlier and have a 12-times greater risk of death when compared with those without the virus.

New Era Of HCV Drugs
Today we have effective drugs to cure HCV, across all six HCV genotypes, including direct-acting antiviral therapy for people with severe liver damage, such as compensated cirrhosis, or kidney disease. HCV eradication is associated with the reversal of fibrosis, improvement of fibrosis and quality of life, as well as overall reduction of liver cancer, liver failure, risk of liver transplant, and liver-related mortality, including extrahepatic manifestations of HCV in patients who achieve SVR.

More importantly the controversy over direct-acting antiviral therapy increasing the risk of developing liver cancer was addressed at The Liver Meeting 2017. At the end of 2017 Healio reported on this retrospective study that found: Liver cancer incidence after HCV therapy linked to risk factors, not treatment. Read a collection of articles on the subject, here.

On A Personal Note -Thank You
Douglas T. Dieterich, MD, Anna Suk-Fong Lok, MD, Stuart Gordon, MD, Nezam H. Afdhal, MD, Paul Kwo, MD, Mitchell Shiffman, MD, Mark Sulkowski, MD, Donald M. Jensen, MD and each person and site mentioned, here.

HCV Advocate - Our Saving Grace
I offer my sincere gratitude to the dedicated staff at HCV Advocate for providing decades of education and support. In 1999, after numerous emails back and forth to the good people at HCV Advocate, I was encouraged to seek out a specialist. In 2000 under the care of Stuart Gordon, MD and Anna Suk-Fong Lok, MD, (thank you) I entered into a clinical trial at Beaumont Hospital in Royal Oak, Michigan, and achieved my SVR status. Without the Hepatitis C Support Project the long-term effects of living with hepatitis C, for me, most certainly would have taken its toll.

Happy Anniversary HCV Advocate
HCV Advocate made a real difference in the lives of countless people across the globe, changing the course of this serious and sometimes deadly disease, one person at a time. Featured in the January 20th Anniversary Edition of HCV Advocate's Newsletter is a look back at how it all began and the people who made the Hepatitis C Support Project possible.

Wishing you all a happy and healthy New Year!

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