Some time ago we saw some very bad science published. This suggested that treating Hepatitis C confers no benefits. While experts around the world expressed their firm view this was complete and utter rubbish here is something simple to understand. Get treated, get SVR and... you are far less likely to die of liver cancer.
This slide came from a presentation on Clinical Care Options entitled "Current HCV Therapy". The full slides are attached here:
This is just one of the reason treating your Hepatitis C sooner rather than later is a good idea. Push for coverage and appeal, but if you can't get access we know with 100% certainty that generic HCV medications deliver the same results - only the price is different (they are affordable).
KUALA LUMPUR/GENEVA – 13th November 2017 – Malaysian pharmaceutical company Pharmaniaga Logistics Sdn Bhd (Pharmaniaga), Egyptian pharmaceutical company Pharco Pharmaceuticals (Pharco) and non-profit research and development organization Drugs for Neglected Diseases initiative (DNDi) have signed a collaboration agreement to supply a new hepatitis C treatment regimen to be sold for US$300 in the public sector in Malaysia.
“It is estimated that there are around 450,000 people living with hepatitis C in Malaysia but most of them have been unable to access effective new hepatitis C treatment because of its very high price,” said Dato’ Farshila Emran, Managing Director of Pharmaniaga. “This agreement enables access to cheaper alternatives for patients in Malaysia, and we are proud to be embarking on this collaboration with DNDi and Pharco that would not have been possible without the Ministry of Health’s support.”
In partnership with the Malaysian Ministry of Health, DNDi is currently running clinical trials testing a potentially pan-genotypic treatment, combining the drug candidate ravidasvir, produced by Egyptian drug manufacturer Pharco Pharmaceuticals, with the existing hepatitis C medicine sofosbuvir. The clinical trial is ongoing in six hospitals and is co-sponsored by the Malaysian Ministry of Health, with initial results expected in early 2018.
“We applaud the Malaysian government in its efforts and commitment to make available affordable access to safe and effective treatments for hepatitis C,” said Jean-Michel Piedagnel, Head of DNDi South-East Asia. “The strategic investment from the Ministry of Health in helping develop a public health approach to the epidemic is remarkable.”
The agreement covers the supply of ravidasvir, once approved in Malaysia, and supply of sofosbuvir. A Government Use licence issued by the Malaysian Ministry of Domestic Trade, Co-operatives and Consumerism in September 2017 enables the importation of generic sofosbuvir in order to make this drug available in the public health system throughout the country at affordable prices.
“We hope that our collaboration with Pharmaniaga and DNDi to develop a treatment regimen that costs less than US$1 per day will lead to widespread access to safe, effective, and affordable treatment for hepatitis C patients in Malaysia and around the region,” said Dr. Sherine Helmy, CEO of Pharco Pharmaceuticals.
Currently a full 12-week course of treatment is available in Malaysia for around US$70,000. With the combination of generic sofosbuvir and ravidasvir, the cost for the same treatment will be made affordable with an almost 100% decrease in price.
We have the power to FixHepC, but the real question is... Do we have the willpower?
This was how Dr James Freeman ended his presentation at the World Hepatitis Summit in Brazil.
You can watch the full presentation on YouTube.
In essence, if we applied the same effort to HCV as we do to HIV this epidemic could be over within a single year. Currently, we treat 18 million patients with one year's supply of multiple antiviral drugs. That would translate to 72 million 3 month treatment courses - enough to treat every man woman and child with HCV.
We still have the enormous challenge of finding those patients in time, but we clearly have the funding capacity and the industrial capacity to get it done.
One year, that's all it would take.
The slides are attached below:
Hepatitis C is a disease that can make you feel old before your time. While there is no doubt that treatment with the new generation of direct acting antivirals like Harvoni is by far the best option this is not available to everyone, either because they don't qualify under their insurance, don't have insurance, or can not afford the $1250 cost to get generic hepatitis c treatment.
This guest blog was written by the Outreach Team at Disability Benefits Help and outlines how you can get help if you have become too sick to work. This includes both financial support and the potential to access to subsidised treatment.
Qualifying for Social Security Disability Benefits With Hepatitis C
If you have been diagnosed with Hepatitis C and will be unable to work for at least one year, you might be eligible for Social Security disability benefits. The Social Security Administration (SSA) offers financial resources for people who are unable to work for an extended period of time due to a serious illness. Hepatitis C will not automatically qualify, and unfortunately, most people with the condition will not be approved. Severe cases will qualify though, meaning you could be eligible for payments to help with your daily living expenses, as well as access to health insurance to pay for your hepatitis treatments.
12 Months and Social Security Disability
Social Security disability benefits are never temporary. They’re only available for people who expect to have a disability that lasts at least a year. This means that if you’ve recently been diagnosed with hepatitis C and have a good prognosis with minimal liver damage and a strong treatment plan, you likely won’t qualify. You also will not qualify if you’ve had hepatitis C for years but your symptoms are managed well. The SSA will not consider you to be “disabled” unless you are completely unable to earn at least $1,170 per month (in 2017). If you expect to be finished with treatments within a few months, or your condition is well managed, it’s not advisable to apply for disability benefits.
Qualifying Via the Blue Book
For those with severe liver damage, medical qualification is possible and potentially guaranteed, depending on your liver function. The SSA evaluates all hepatitis C applicants under its own medical guide, known as the Blue Book. The Blue Book is a manual listing all potential disabling conditions, plus the symptoms you’d need to qualify. Hepatitis c would fall under Section 5.05: Chronic liver disease. Chronic liver disease is arguably the most complicated listing in the Blue Book. There are actually seven ways to qualify under this listing, and all require medical tests evaluating your serum levels, blood quality, and more. The Blue Book was written for medical professionals and is available entirely online, so please review the listing with your hepatologist! He or she can help you navigate the guide and determine if your hepatitis c meets any liver disease listings. If you require a liver transplant, rest assured that your liver disease will qualify. You will also automatically qualify for disability benefits for at least 12 months after a liver transplant surgery.
Starting Your Application
Most people can apply for Social Security disability benefits online. If you’d prefer, you can also apply in person at your closest office by scheduling an appointment at 1-800-772-1213. There are over 1,000 offices across the US.
You’ll usually hear back from the SSA within three to five months. If your application is denied, do not give up! The SSA has a thorough appeals process, which allows you to fight your claim. While just 30% of applicants are initially applied, nearly 70% are eventually approved after pursuing their claims further.
About 1 in 100 people, from all walks of life, have Hepatitis C so it is pretty common. Because it is a highly stigmatised disease, linked in the public mind to IV drug use, most patients choose to keep their diagnosis confidential. Despite the fact that the evidence shows most patients were infected too young to have been involved in IVDU, and many patients got it from blood transfusions, tattoos, and unsafe medical procedures, changing the stigma is probably an impossible task.
What this means is that having Hepatitis C is a very lonely experience for many people. Having to deal with the symptoms is one thing, but having to do it alone just adds to the burden. The good news is that help is out there!
One of the great things about the Internet is it allows people from across the globe to connect with other people with a common interest and with complete anonymity.
To find people like you, who have walked in your shoes and know how it feels, please visit the FixHepC forum - https://fixhepc.com/forum
You can browse the forum without logging in but to post you do need to create a login. Most people just use an anonymous email address to do that so there is no problem about maintaining your annonymity.
There are now highly effective treatments available with minimal side effects. For some patients, insurance and Medicaid can come to the rescue. For others, it might be a patient assistance program or the parallel importation of generics (these are the same medications but with a $1000 price tag for the whole treatment rather than a single pill). It is a cruel and unusual punishment to know that cure exists, but not for you.
Drop in to the FixHepC forum and find out how people just like you have navigated the varying processes that can see you get supported, treated and cured.
Just out of embargo for AASLD 2017 is the rather innocuous sounding Abstract 1078 which says, in brief, that these generic DAAs are inarguably proven the same as the originator DAAs.
Bioequivalent pharmacokinetics for generic and originator Hepatitis C Direct Acting Antivirals
Andrew M. Hill1, Loai Tahat2, Mohammed Khalil Mohammed3, Sanjay Nath4, Rabab Fayez Tayyem3, James A. Freeman5, Ismahane Benbitour7, Sherine Helmy6; 1Department of Translational Medicine, University of Liverpool, Liverpool, United Kingdom; 2Pharmaceutical Research Unit, Amman, Jordan; 3ACDIMA BioCentre, Amman, Jordan; 4Faculty of Medicine, Imperial College London, London, United Kingdom; 5GP2U Telehealth, Hobart, TAS, Australia; 6R&D Project Innovations, Pharco, Cairo, Egypt; 7BEKER Laboratories, Algiers, Algeria
Background: Mass production of low-cost generic directacting antivirals (DAAs) will be required to achieve targets of eliminating hepatitis C (HCV) by 2030. Gilead and Bristol-Myers Squibb have granted voluntary licenses to generic companies to mass-produce the DAAs sofosbuvir and daclatasvir at low cost. However generic manufacturers need to demonstrate bioequivalent pharmacokinetics for their generic DAAs compared to the originator versions, to fulfil World Health Organization standards for pre-qualification.
Methods: Randomised, single-dose, two-way, two-period pharmacokinetic studies were performed in 35-54 healthy volunteers, to compare generic forms of sofosbuvir and daclatasvir with the originator versions. Generics evaluated were from Pharco (Egypt), Beker (Algeria) and Hetero (India), versus originator sofosbuvir (Gilead) and daclatasvir (Bristol-Myers Squibb). All studies were conducted under Good Clinical Practice (GCP). Plasma concentrations of each DAA were assessed over 24 hours. Maximum concentration (Cmax) and Area Under the Curve (AUC) were calculated for each subject. Geometric mean ratios and associated 90% confidence intervals were used to compare each generic DAA with the originator version. Pre-specified limits for the 90% confidence intervals were 80% to 125% of the originator pharmacokinetic concentrations for AUC, and 69-145% for Cmax.
Results: Table 1 shows summary Geometric mean ratios for generic versus originator versions of sofosbuvir and daclatasvir. NB Results from Natco and Virchow came in after the deadline for AASLD submission, but are included here.
Table 1: Geometric mean ratio (90% confidence intervals) for generic versus originator HCV DAAs
|Sofosbuvir||Pharco||36||101.0 (88.1-115.7)||103.5 (97.6-109.7)|
|Sofosbuvir||Beker||35||95.4 (84.7-107.5)||98.5 (91.6-106.0)|
|Daclatasvir||Beker||35||35 104.1 (93.1-116.3)||103.0 (94.4-112.4)|
|Sofosbuvir||Hetero||54||95.7 (97.2- 105.2)||100.8 (96.2-
|Sofosbuvir||Natco||N/A||96.1 (81.0-114.0)||100.7 (94.2-107.8)|
|Daclatasvir||Natco||N/A||94.5 (83.1-107.4)||96.5 (87.1-106.8)|
|Sofosbuvir||Virchow||24||94.8 (83.3-107.9)||95.8 (86.9-105.7)|
All three (now expanded to 5) generic forms of sofosbuvir met pre-specified bioequivalence criteria. The Cmax and AUC of daclatasvir were bioequivalent in both cases. There were no serious adverse events observed.
Conclusions: The pharmacokinetics of generic sofosbuvir and daclatasvir were bioequivalent to the originator versions, in three independent single-dose PK studies. WHO pre-qualification of bioequivalent generic DAAs could then permit their export to high-burden countries for mass treatment programmes.
Disclosures: James A. Freeman - Advisory Committees or Review Panels: Pharco Pharmaceuticals, Beker Pharmaceuticals, Beacon Pharmaceuticals; Stock Shareholder: FixHepC, GP2U Telehealth
Ismahane Benbitour - Management Position: BEKER Laboratories
Sherine Helmy - Board Membership: Presidio Pharmaceuticals; Stock Shareholder: Pharco Pharmaceuticals
The following people have nothing to disclose: Andrew M. Hill, Sanjay Nath
Bye bye limitatio (and generics) - Open access to the new Hepatitis C medications for all Swiss patientsWritten by Super User
Switzerland has just announced that all limitations on access to the new DAAs will be abolished allowing treatment for all. Great news for Swiss patients. Here is an article from the Swiss Hepatitis C Association about it. If you are not lucky enough to live in Switzerland generic versions of the new medications are available for 1% of the originator prices. It's interesting to see that all the countries that have parallel imported generics at scale have managed to strike great pricing deals that allow things like this to happen. Australia, Canada, New Zealand, Italy, Switzerland... The list is growing.
Bye bye limitatio – People with hepatitis C are relieved
The rationing of hepatitis C drugs laid down by the Federal Office of Public Health (FOPH) about three years ago will be abolished as of 1 October 2017. For the first time, all patients can be treated regardless of the type of virus and disease progression.
The rationing of Gilead’s hepatitis C medicines will also be discontinued on October 1,2017. Harvoni and Epclusa can thus be prescribed to all hepatitis C patients for the first time, regardless of liver damage. This was after the rationing had already been abolished for Zepatier on July 1 and for Viekirax/Exviera on August 1 for all those affected with genotypes 1 or 4.
The abolition of rationing was accompanied by substantial price reductions, which are now also expected for Gilead products. Since Gilead’s Epclusa can be used for all 6 genotypes, all hepatitis C patients, regardless of their stage of development, can be treated and cured with a very high probability from October 1. This is excellent news for affected patients and represents an important step towards the elimination of hepatitis C in Switzerland.
This concludes a sad chapter in the history of the Swiss healthcare system. For years, leading representatives of the FOPH have claimed that it makes no sense to treat “healthy people”. As a result, thousands of people with hepatitis C were left untreated and continued to suffer from the symptoms of their disease for years. We welcome the latest developments and are extremely pleased with the change of heart in the FOPH. With the abolition of rationing, the core requirement of the SHCA patient organisation and the Positive Council, the “treatment of all HCV patients”, has finally been fulfilled.
This is the demand we have made since our petition to Federal Councillor Berset in July 2015.
The FOPH will boast of having achieved price reductions. This confirms our accusation that the Federal Office fought a price war on the back of the patients for years. This is ethically untenable and we warn against pursuing the same strategy for other life-threatening diseases. Under no circumstances should those affected be the victims of such price wars. We demand that our Parliament develops the necessary instruments to enable the Federal Office to conduct future price negotiations more constructively and transparently.
We would like to thank the experts of the Swiss Hepatitis Strategy, who have worked tirelessly with us to promote the well-being of those affected, and we regard the case of the limitation as a joint success for civil society.
We would also like to thank the industry, whose medicines have cured us and hopefully will now enable many other hepatitis C patients to lead a new life. Their willingness to compromise in the negotiations with the FOPH made it possible to abolish rationing.
What exactly is chronic HCV? In a nutshell, it refers to ongoing inflammation of your liver. But it can lead to symptoms throughout your body. Over time, living with this condition can cause your body to be especially vulnerable to serious health complications. Here is a great infographic from Healthline about the effects of Hepatitis C on your body.
Last week there was some celebrations after Under pressure, Gilead expands Sovaldi licensing deal to four middle-income countries.
So great news, right? Not exactly, because in order for a country to have PRACTICAL ACCESS the product needs to be registered for sale there.
Now Sovaldi hit the market in late 2013 and back in February 2015 Gilead announced Gilead is committed to increasing access to its medicines for all people who can benefit from them, regardless of where they live or their ability to pay and providing a list of 91 countries where generics would be available. That list has since been expanded to include 101 countries.
That was 2 and a half years ago, so surely Sovaldi must be available in all the original 91 by now, afterall, Sovaldi was fast tracked by the FDA with one of the most rapid approvals ever seen...
Nope. To date Sovaldi is only registered in 26 of those 101 countries, with applications filed in another 6. That's 32/101 countries filed in 2 1/2 years.
- Without filing, there can be no registration.
- Without registration, there can be no availability.
- Without availability, there can be no patients treated.
This is the reality behind Gilead's PR-access. It is PR, it is not access.
By Priti Krishtel
Last week, the FDA approved AbbVie’s Mavyret—a new hepatitis C virus (HCV) drug that treats all genotypes of the disease and cures more than 90% of patients within just 8 weeks of treatment. This has been reported as a threat to Gilead Sciences’ dominant position in the market, sparking rumors of a potential price war that could lower prices on the infamously expensive treatments.
There is reason to be tentatively optimistic. The initial published price on Mavryet was lower than expected at $13,200 per month—or $26,400 for a full course of treatment—appearing on the surface to be a significant discount from the $94,500 per-treatment course costs of Harvoni, Gilead’s market-leading treatment.
And while the published price is a step in the right direction to getting more people the treatment they need, it isn’t the whole story. The set Mavryet price is reflective of the current market conditions. With behind-the-scenes payer negotiations, the announced price on Mavyret is only an approximately 15% discount to the current net price paid for Gilead’s products.
While AbbVie’s pricing is now the lowest for a curative HCV drug, it is not a radical undercutting of Gilead prices. Millions of Americans with HCV—and tens of millions globally—are already blocked from getting treatment at the current exorbitant prices set by the pharmaceutical industry and the subsequent rationing of treatment approval by payers.
The United States is currently facing an HCV epidemic. There are an estimated 3.6 million Americans with HCV—and that number is expected to rise in the coming years. There is a cure, but every day 48 people in the United States die from HCV, the deadliest infectious disease in America. That’s because 2 out of every 3 Americans who have been diagnosed with HCV do not receive treatment, largely due to the high costs. States such as Louisiana and Pennsylvania are forced to ration treatment to the sickest of patients, and many insurers refuse to cover it because of the high price.
A week out from the FDA’s approval, it is not clear what the introduction of Mavyret will do to change this situation. What is clear, however, is that people should not die of an entirely treatable illness. One of the root causes of the unaffordability crisis is the fact that pharmaceutical companies such as Gilead over-patent drugs, including extending its market monopoly on Sovaldi for at least the next 2 decades.
Gilead’s initial price on Sovaldi has skewed what the market considered a fair price for HCV treatment. I doubt we would see this level of praise for AbbVie now if Gilead hadn’t launched this lifesaving medicine at $84,000 for a single course of treatment.
Until we address the core of the drug pricing problem—unjustified patents—pharmaceutical companies will be able to abuse the system to obtain monopolies on the market and charge astronomical prices that prevent people from getting access to disease-curing medicines.
About the Author
Priti Krishtel is co-founder and co-director of the Initiative for Medicines, Access & Knowledge (I-MAK), a US-based nonprofit group of scientists and lawyers working globally to get people lifesaving medicine. Prior to founding I-MAK, Krishtel obtained her law degree from New York University School of Law worked as a health attorney in the United States, Switzerland and India.
"To our knowledge, this is the first large-scale study to demonstrate the effect of newer DAA regimens upon survival. Treatment with 2 commonly used DAA regimens, PrOD and LDV/SOF, was associated with significant improvements in survival within the first 18 months of treatment, compared with demographically and clinically similar untreated HCV-infected controls. Treatment with either PrOD or LDV/SOF was associated with a 57% reduction in mortality, and attainment of SVR was associated with a 43% reduction in mortality….Benefits of treatment at a population level are expected to be substantial…..similar benefit can be expected with other DAA-based regimens"
Effect of Paritaprevir/Ritonavir/Ombitasvir/Dasabuvir and Ledipasvir/Sofosbuvir Regimens on Survival Compared With Untreated Hepatitis C Virus–Infected Persons
Adeel Ajwad Butt Peng Yan Tracey G. Simon Abdul-Badi Abou-Samra
Clinical Infectious Diseases, cix364, https://doi.org/10.1093/cid/cix364
Published: 20 July 2017
Interferon-based regimens are associated with a substantial survival benefit for persons infected with hepatitis C virus (HCV). Survival data with direct-acting antiviral agents are not available. We conducted this study to quantify the effect of paritaprevir/ritonavir, ombitasvir, dasabuvir (PrOD) and ledipasvir/sofosbuvir (LDV/SOF) regimens upon mortality.
In the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES), a well-established national cohort of HCV-infected Veterans, we identified HCV-infected persons initiated on PrOD or LDV/SOF, excluding those with human immunodeficiency virus, hepatitis B surface antigen positivity, hepatocellular carcinoma, or missing HCV RNA or FIB-4 scores. For each case, we identified a propensity score–matched control never initiated on treatment. Primary outcome was survival. Outcomes were assessed using frequency of events, Kaplan-Meier curves, and Cox proportional hazards regression analyses.
We identified 1473 persons on PrOD, 5497 on LDV/SOF, and 6970 propensity score–matched untreated persons. Treated persons were more likely to be obese and have cirrhosis, but less likely to have stage 3–5 chronic kidney disease (CKD), alcohol or drug abuse or dependence diagnosis, and anemia. The proportion of persons who died was higher in the untreated group compared with either treatment group (PrOD, 0.3%; LDV/SOF, 1.4%; untreated controls, 2.5%; P < .001). A significantly larger percentage of treated patients survived to 18 months of follow-up, compared with untreated controls (P < .001). In multivariable Cox regression analysis, treatment with either regimen (hazard ratio [HR], 0.43; 95% confidence interval [CI], .33–.57) and attainment of sustained virologic response (SVR) were associated with significantly lower mortality (HR, 0.57; 95% CI, .33–.99).
Treatment with PrOD or LDV/SOF and SVR are associated with a significant mortality benefit, apparent within the first 18 months of treatment.
Here is a copy of the presentation, called "Practivism, it's the new black", given by Dr James Freeman at the International AIDS society meeting in Paris today.
Here is the text that went with the images.
Crisis, What Crisis?
This crisis. Look at this price comparison. I mean seriously?
We only have to look at Egypt to know these medications can be made affordably
Pricing negotiations are one sided and conducted by bandits
Our funders simply can not afford to cover the costs so…
We have rationing that sees only the sickest patients treated
And virtually nothing is being done for high burden populations like prisoners
And People Who Inject Drugs
Politicians pay lip service to the issue
Many advocacy groups are directly funded by Big Pharma*.
And in the Ukraine earlier this year generics were shot down by data exclusivity
Treatment rates are similar to infection rates
In short we are currently going nowhere fast.
Patients are stigmatized and don’t speak out so in the zeitgeist there is no crisis
But we desperately need a new balance between patent rights and patient lives
And now seven seconds of silence to remember those of us for whom treatment will come too late
One second for each patient who died during the time it's taken to give this presentation
Was it really only 50 years ago our Statesmen talked like this and the crowds came to listen?
What we call the “big picture” is really just the product of what each and every one of us chooses to do.
What we do as individuals, thinking globally but acting locally, exhibits a butterfly effect so I would like to suggest adopting this butterfly symbol and a simple slogan like "Wear if you care"
Over the past year there has been quite a lot of discussion about the risk of liver cancer following treatment with Direct Acting Antivirals like Harvoni® and Sovaldi®.
Here is a quick explanation and the latest thinking from the academic gurus.
First, the risk of Hepatocellular Carcinoma (HCC aka liver cancer) only starts to rise when patients develop cirrhosis, so for patients without cirrhosis there is little to worry about.
In patients with cirrhosis, and untreated Hepatitis C the annual risk of developing liver cancer is 3%. With SVR (cure) following treatment this risk falls to around 1%, so is much less.
In patients who have already had one HCC, treatment increases their short term risk of getting another one (this is probably one they already have but is simply too small to see) and demands very close monitoring both during and immediately after treatment.
So the bottom line is pretty simple. Treat before you get cirrhosis, but if you already have cirrhosis, you are still better off treating. If you have previously had an HCC you can still treat but need very close follow up.
Below you will find the text of a press release from EASL 2017. EASL is the European Association for Study of Liver Diseases and represents the best experts in the world telling it how they see it.
ILC 2017: Is direct-acting antiviral therapy for Hepatitis C associated with an increased risk of liver cancer? The debate continues
Eight studies being presented at The International Liver Congress™ 2017 demonstrate contrasting evidence on the potential link between direct-acting antiviral treatment for Hepatitis C and liver cancer
April 20, 2017, Amsterdam, The Netherlands: According to data from eight studies being presented at The International Liver Congress™ 2017 in Amsterdam, The Netherlands, there remains continued debate on whether patients are at risk of developing liver cancer after achieving sustained virologic response (SVR) with a direct-acting antiviral (DAA) regimen for Hepatitis C virus (HCV). Investigators will present the results of their studies that show both sides of the argument – DAA therapy is associated with a higher risk of liver cancer compared with interferon-based therapy, versus there is no difference in liver cancer risk following cure with either therapy.
Whilst remarkable progress has been made in the development of successful antiviral therapies for HCV infection, some recent studies suggest that curing patients does not eliminate the risk of developing liver cancer. There also appears to be an unexpectedly high rate of liver cancer (also known as hepatocellular carcinoma [HCC]) recurrence in patients who previously had their tumour treated successfully and had received DAAs.
This claim was further supported by a Spanish study led by Dr Maria Reig and Dr Mariño, Hospital Clinic Barcelona, Spain in which patients with HCV and HCC who had previously been cured of HCC received DAA therapy. After a median 12.4 month follow-up, following treatment with DAAs, the rate of HCC coming back (recurrence) was 31.2% (24/77) and of those who received HCC treatment at recurrence, 30% (6/20) of patients presented progression in the immediate 6-month follow-up. This is an update of the study that will be published in the May 2017 issue of Seminars in Liver Disease, and is available here: https://www.thieme-connect.de/products/ejournals/html/10.1055/s-0037-1601349.
“Our study offers further support to previous findings that there is an unexpected high recurrence rate of hepatocellular carcinoma associated with DAAs, and that this association may result in a more aggressive pattern of recurrence and faster tumour progression,” said Dr Maria Reig, Barcelona Clinic Liver Cancer Group, Hospital Clinic Barcelona, Spain, and lead author of the study. “These data indicate that there needs to be further research conducted in this area, clarifying the mechanism for the association between liver cancer recurrence and DAA therapy.”
Identifying those patients at risk of liver cancer is essential, a task that Dr Etienne Audureau, Public Health, Henri Mondor University Hospital, Créteil, France, and colleagues attempted to achieve by developing a prognostic tool for HCC. They found that in patients with severe scarring of the liver due to HCV (compensated cirrhosis), failure to achieve SVR was the most influential factor in predicting liver cancer. In addition, risk factors for liver cancer differ according to SVR status. The investigators recommend that in patients with compensated cirrhosis, eradication of HCV should be achieved before liver function is impaired and people who have achieved SVR should be monitored for liver cancer after 50 years of age.
The mechanisms behind the development of liver cancer following HCV cure are not yet understood. One group of investigators led by Prof Thomas Baumert, Inserm Institute for Viral and Liver Diseases, University of Strasbourg, France, aimed to investigate if HCV infections produce epigenetic and transcriptional changes that persist after the infection is cured, and whether these epigenetic changes drive liver disease and HCC following cure. They found that the epigenetic and transcriptional changes are only partially reversed by DAAs and persist after HCV cure, suggesting that these changes are a driver for liver cancer that develops after HCV infection has been cured. The investigators concluded that these findings open a new perspective to develop novel biomarkers to identify patients at high risk of HCC and provide an opportunity to develop urgently needed strategies for HCC prevention.
On the other side of the debate, a systematic review, meta-analyses, and meta-regression study, by Prof Gregory Dore and Dr Reem Waziry from The Kirby Institute, UNSW Sydney, and colleagues, found no evidence for higher risk of HCC occurrence or recurrence following DAA treatment, compared with interferon-based HCV therapy. A total of 41 studies, including 26 on HCC occurrence and 15 on HCC recurrence (in total, n=13,875 patients) were included. In studies assessing HCC occurrence, average follow up was shorter and average age was higher in DAA studies compared to interferon studies; incidence was lower with longer follow-up and younger age. In studies assessing HCC recurrence, average follow up was also shorter. Ultimately, in the meta-regression analysis, no evidence in favour of a differential HCC occurrence or recurrence was found between DAA and interferon regimens, after adjusting for study follow-up and age.
“Recent studies have reported contradicting evidence on risk of hepatocellular carcinoma following direct-acting antiviral therapy; our aim was to bring some clarity to this,” said Prof Gregory Dore, Kirby Institute and lead author of the study. “These data show the higher incidence of HCC observed following DAA therapy can be explained by the shorter duration of follow-up and older age of participants, rather than the DAA treatment regimen.”
A Scottish study, led by Dr Hamish Innes, School of Health and Life Sciences, Glasgow Caledonian University, Scotland, found that the risk of liver cancer following SVR was not associated with the use of DAAs, but baseline risk factors. Furthermore, risk of HCC development was similar in patients taking interferon-free regimens versus interferoncontaining regimens, following a multivariate adjustment (IRR: 0.96, p=0.929) and no significant differences in HCC risk were found when treatment regimen was defined in terms of DAA containing regimens versus DAA free regimens. These data indicate that rather than the treatment regimens themselves, it is the baseline risk factors that determine risk of hepatocellular carcinoma.
Another interesting study in Japanese patients with HCV genotype 1 infection, found a reduced incidence of liver cancer following achievement of SVR after 12 weeks of therapy with an interferon-free regimen (ledipasvir plus sofosbuvir) to a similar degree as that obtained with an interferon-containing regimen (simeprevir with peginterferon plus ribavirin). This study, which was conducted by Dr Masaaki Korenaga, Kohnodai Hospital, National Center for Global Health and Medicine, Chiba, Japan, and colleagues, also found that unexpected development of liver cancer following SVR in patients without previous liver cancer could potentially be predicted by imaging procedures (computer tomography or enhanced magnetic resonance imaging).
Similarly, a Chinese study led by Dr George Lau, from the Beijing 302-Hong Kong Humanity and Health Hepatitis C Diagnosis and Treatment Centre, in Beijing, China, found no increase in the incidence of liver cancer in patients who achieved SVR12 with DAA compared to peginterferon plus ribavirin.
A Sicilian study conducted by Dr Vincenza Calvaruso, University of Palermo, Palermo, Italy, and colleagues, demonstrated that patients who achieved SVR with DAAs had a similar risk of developing liver cancer when compared to historical controls of patients with compensated cirrhosis who achieved SVR after interferon-based therapy. In addition, those who achieved SVR with DAAs had a lower risk of developing liver cancer than those patients whose HCV infection was not cured.
“The original observations made by researchers from the Barcelona Clinic Liver Cancer Group have sparked a huge number of studies aimed at verifying the potential association between DAA treatment and increased HCC recurrence after cure,” said Prof Francesco Negro, Divisions of Gastroenterology and Hepatology of Clinical Pathology, University Hospital of Geneva, and EASL Governing Board Member. “At this stage, there is no reason to alter treatment guidelines until the issue is definitively clarified. We cannot exclude, however, that we may have to revise post-SVR surveillance in some specific patient subgroups.”
- Ends -
About The International Liver Congress™
This annual congress is the biggest event in the EASL calendar, attracting scientific and medical experts from around the world to learn about the latest in liver research. Attending specialists present, share, debate and conclude on the latest science and research in hepatology, working to enhance the treatment and management of liver disease in clinical practice. This year, the congress is expected to attract approximately 10,000 delegates from all corners of the globe. The International Liver Congress™ 2017 will take place from April 19 – 23, at the RAI Amsterdam, Amsterdam, The Netherlands.
Here is the response from EASL to the recent Cochrane review. http://www.journal-of-hepatology.eu/pb/assets/raw/Health%20Advance/journals/jhepat/CochraneEASLJMP003.pdf
EASL, the European Association for the Study of the Liver, one of the world leading associations of liver specialists, feels compelled to express its serious concerns after the recent publication of a Cochrane Group systematic review entitled “Direct acting antivirals for chronic hepatitis C” by Jakobsen et al. After reviewing 138 clinical trials, including 25,232 participants, the authors conclude that: “Overall, direct acting antivirals (DAAs) on the market or under development do not seem to have any effects on risk of serious adverse events. […] we could neither confirm nor reject that DAAs had any clinical effects. DAAs seemed to reduce the risk of no sustained virological response. The clinical relevance of the effects of DAAs on no sustained virological response is questionable, as it is a non-validated surrogate outcome. All trials and outcome results were at high risk of bias, so our results presumably overestimate benefit and underestimate harm. The quality of the evidence was very low.”
The inability of the authors of the Cochrane review to determine a clinical benefit of DAA-based treatment of hepatitis C unfortunately reflects their flawed methodological approach and their ignorance of the natural history of hepatitis C virus (HCV) infection and associated systemic diseases. The review examines the intervention in a clinical vacuum that fails to accept that DAA treatment to attain an SVR is a pivotal outcome of treatment, and does not accept the likelihood that an SVR will reduce the risks of long-term outcomes of hepatitis C.
With this deduction comes responsibility. The uncertainty created by the illconceived Cochrane group’s conclusions and the attendant press publicity could grievously affect policy making, and constrain the gathering momentum for diagnosis, testing and linkage to care of individuals with hepatitis C. It will create dangerous confusion in the mind of patients treated or about to be treated and their families. The World Health Organization (WHO) has published an authoritative Global Hepatitis Report, expressing its alarm at the burden of disease, and has promulgated critical targets for global elimination of hepatitis C by 2030. In the absence of a prophylactic vaccine, the Cochrane review jeopardises treatment as a necessary intervention to reduce the global morbidity, mortality and prevalence of chronic hepatitis C.
The primary endpoint in DAA investigational drug development trials has been the sustained virological response (SVR), i.e. undetectable HCV RNA 12 or 24 weeks after completion of treatment, which corroborates permanent elimination of the viral infection. The Cochrane review evaluated the effect of DAA treatments on several outcome measures, including hepatitis C-related mortality, all-cause mortality, serious adverse events, no SVR and health-related quality of life (HRQOL). Most of their conclusions are flawed.
- The report from 32 trials including 7115 participants indicates that a total of 1180/1692 (69.7%) patients in the DAA groups and 915/5194 (17.6%) patients in the control group had “no SVR” during the observation period. This can only be an error as the authors deduce that meta-analysis showed that DAAs “seemed to reduce the risk of no SVR (risk ratio=0.44, p <0.00001) […]“.
- It is inappropriate to have pooled the data to include 57 trials that included drugs that have been withdrawn or discontinued. These are experimental drugs that have been discarded for lack of safety or inferior efficacy and that have been superseded by more effective and safer drugs, making the review dated and ignorant of current clinical decisions and guidelines in the context of a rapidly progressing field. Including treatments that are not or no longer used, and/or overly heterogeneous introduces a bias in the meta-analysis.
- From 43 trials involving 15,817 patients, the authors report serious adverse events (SAEs) in 2.7% of DAA-treated patients versus 5.5% in the control group during the observation period. They conclude that there is no firm evidence that DAAs reduce risk of SAEs. However, the terminology is clouded as the authors fail to clearly indicate whether they consider drug-related SAEs or clinical SAEs, i.e. clinical events resulting from the natural history of HCV infection which would happen months to years after the period of observation of the clinical trials.
- The HRQOL analysis has missed many recent studies. Several systematic reviews have been performed which have shown significant improvement in quality of life parameters with DAA therapy. The results show improvement over interferon and ribavirin-based treatments and are an encouraging aspect of an SVR with chronic hepatitis C, that further support the use of the SVR as surrogate. Very detailed and comprehensive analyses have been compiled before, during and after treatment objectively demonstrating improved patient-reported outcomes.
- The major weakness of the Cochrane review is that results are only assessed at “maximum follow-up”. These are of course short-term results for a disease with a long clinically latent period. A meta-analysis should only evaluate the primary endpoint selected by the clinical studies. The trials were not designed or powered to capture long-term outcomes such as hepatitis C-related morbidity or all-cause mortality, but to establish whether infection, reflected by persistent viremia, could be safely and effectively terminated.
The risk of clinical liver outcomes increases with aging and duration of disease. It is the result of chronic production of viral antigens during ongoing infection which incite host immune responses. The resulting hepatic inflammation in turn triggers fibrogenesis, the basis of liver disease progression towards aggravating fibrosis, cirrhosis and, ultimately, decompensated cirrhosis and hepatocellular carcinoma. The harmful effects of chronic hepatitis C take years to develop in patients that generally remain asymptomatic for long periods of time. Thus, although there is variation in rates of progression of fibrosis, early disease does not indemnify an individual from subsequent progressive disease, that can be accelerated by various cofactors and comorbidities. The authors of the Cochrane review have unfortunately not considered the possibility, the necessity and feasibility of arresting progression of early stage disease to more advanced fibrosis, cirrhosis, decompensated cirrhosis, or the ultimate development of HCC.
Achieving SVR, i.e. eliminating the infection, removes the trigger, thereby halting or considerably slowing the progression of liver disease. Terminating active infection also alters the natural history of a number of HCV-induced extrahepatic morbidities, such as diabetes and renal insufficiency. This has been clearly demonstrated by long-term follow-up studies in patients with chronic hepatitis C cured of their persistent infection during the interferon era. An SVR is associated with normalization of serum aminotransferases and improvement or disappearance of liver necroinflammation and fibrosis in patients without cirrhosis. Hepatic fibrosis generally regresses and the risk of complications such as hepatic failure and portal hypertension is reduced in patients with severe liver disease. Recent data showed that the risk of HCC and all-cause mortality is significantly reduced (although not eliminated to zero) in patients with cirrhosis who clear HCV compared to untreated patients and non-sustained virological responders. For the first time, DAAs have allowed patients with decompensated cirrhosis access to anti-HCV therapy, improving their liver function and reducing the indications for liver transplantation in a large proportion of cases, with a major impact on transplant programs already evident. Moreover, the possibility to treat patients after solid organ transplantation with high infection cure rates has opened the door to the use of HCVpositive grafts, increasing transplantation rates, reducing on-list mortality and containing healthcare costs for management of patients on the transplant waiting list.
National and international regulatory authorities have accepted the primary endpoint of an SVR and demonstrable safety as evidence for DAA licencing. Because the complications of chronic hepatitis C take years to occur, depending on the stage of liver disease, and clinical trials with new DAAs with SVR as main endpoint last only a few months, the benefits in terms of clinical outcomes of achieving an SVR cannot be measured in these trials. The Cochrane group’s conclusion is therefore illogical and inappropriate, as it fails to respect the methodology this organization has developed. The Cochrane review also ignores the opportunity of reducing the risk of transmission from viremic individuals, particularly in highrisk groups. Overall, the Cochrane review displays a lack of understanding of hepatitis C and drug development in the context of a transmissible infectious disease with a long natural history.
The Cochrane review authors’ conclusion that “randomised clinical trials assessing direct effects of DAA are needed” suggests an ethical anathema of leaving patients untreated to accrue increasing hepatic fibrosis, in the face of treatments that are likely to arrest viral replication in the overwhelming majority. This conclusion evokes memories of the infamous Tuskegee study conducted by the United States Public Health Service, in which patients with syphilis were left untreated to observe the natural history even after advent of and proven efficacy of penicillin. This unethical approach is unacceptable in a context where: (i) the HCV treatment landscape has markedly altered with the introduction of DAA-based regimens which in both clinical trials and real-world data have shown remarkable SVR (i.e. infection cure) rates in treatment-naïve and -experienced patients with or without cirrhosis across all genotypes; (ii) modelling has clearly demonstrated the benefits of DAA-based therapies in reducing long-term hepatitis C-related morbidity and mortality as compared to no treatment (individual benefit) and reducing HCV transmission (collective benefit). In summary, to arrive at such a flawed conclusion reflects the squandering of a vast amount of considerable time-consuming endeavour and significant public funding. The premise of the Cochrane review will be viewed as so egregiously mistaken that the conclusions will rightly be disregarded. As the findings do not assist or advance the field, they will not be pertinent to clinical decision making or guidelines.
EASL will continue to emphasize and reinforce the fight against HCV and to lend its support to the international efforts aimed at eliminating HCV, a major aetiology of severe liver and extra-hepatic diseases, complications and related mortality, by 2030. There is no precedent for a disease to be eliminated only 40 years after the discovery of its causal agent thus far. This chance cannot, and will not be missed.
This article was just published in the Lancet
The introduction of direct-acting antiviral (DAA) medicines in 2013 revolutionised the treatment of chronic hepatitis C virus (HCV) infection. The efficacy of DAA therapy is impressive—in many clinical trials HCV cannot be detected by sensitive laboratory assays in more than 90% of people who complete DAA therapy, and observational studies have documented similar results.1, 2 High efficacy combined with low rates of adverse events have led WHO to include DAAs in the WHO Model List of Essential Medicines.3 Several countries, including Australia, Georgia, Iceland, and Morocco, have started national DAA-based treatment programmes to eliminate HCV infection, and WHO has called for the expansion of HCV therapy with DAAs as part of its global hepatitis elimination strategy.4
HCV is an important contributor to global mortality, causing an estimated 399 000 deaths each year worldwide, and as HCV treatment expands, it is anticipated that mortality from HCV infection will decline.5 However, because the annual risk of death from HCV infection is low and the DAAs were introduced only recently, there are limited data on how these drugs affect mortality. Clinical trials that evaluate the efficacy of DAAs do not assess mortality as an outcome but rather a surrogate outcome called the sustained virological response (SVR). An SVR is defined as the absence of detectable HCV by nucleic acid testing of blood samples obtained 12–24 weeks after completion of HCV therapy. An SVR is deemed equivalent to a cure because once an SVR is achieved, it is maintained in more than 99% of patients, even after years of follow-up.6 Also, an SVR is associated with resolution of cirrhosis in about half of patients with cirrhosis followed-up clinical trials.7
However, documenting in a clinical trial that DAAs result in an SVR is not the same thing as showing that they reduce mortality or morbidity. A recent systematic review by Jakobsen and colleagues8 from the Cochrane Hepatobiliary Group sought evidence from clinical trials of HCV therapies to assess this issue. The authors reviewed randomised clinical trials that used SVR as the primary outcome in people receiving DAA therapy compared with those either not treated or treated with other regimens (primarily interferon-based therapy). Jakobsen and colleagues concluded that DAAs were effective in producing an SVR (relative risk 0·44, 95% CI 0·37–0·52); however, the analysis did not find a reduction in morbidity or mortality after DAA therapy. At first sight, this conclusion seems to contradict systematic reviews of observational data that show that people who have an SVR after treatment with interferon and ribavirin had a 50% (95% CI 37–67) reduction in overall mortality and 76% (95% CI 69–82) reduction in the incidence of hepatocellular carcinoma as compared with people who were treated but did not achieve an SVR.9, 10 The reduction in overall mortality was even greater (81% [95% CI 72–87]) when persons with an SVR were compared with those not treated.9 Other studies have shown improvements in extrahepatic manifestations of HCV infection and quality of life among people with an SVR after DAA treatment.11, 12 Data on the effect of DAA therapy are also beginning to be reported from national programmes that are scaling up HCV therapy. In England where HCV therapy increased by 48% in 2015, compared with 2014, there were reductions in the incidence of HCV-related cirrhosis (42%), liver transplantations (32%), and deaths (8%).13
Observational studies are biased towards showing an effect of treatment since treatment decisions are based on the likelihood of a successful outcome, and people achieving an SVR may be predisposed to a better outcome for reasons unrelated to the treatment. However, the magnitude and consistency of health benefits across studies and outcomes support the conclusion that HCV therapy resulting in an SVR substantially reduces mortality and morbidity.
How to explain these apparently contradictory results? An important difference between the studies reviewed by Jakobsen and colleagues is the duration of follow-up, which was short at an average of 34 weeks compared with an average of more than 5 years in the other reviews.9, 10 Simply put, the clinical trials included in the systematic review by Jakobsen and colleagues were not designed to answer the question posed by the authors about the effect of DAA treatment on morbidity or mortality. These studies generally followed up patients for only 24–48 weeks after the completion of DAA therapy, and the risk of HCV-related disease and death during such a short period is extremely low because the harmful effects of chronic HCV infection take years to develop. In fact, no morbidity was reported, and only 16 deaths occurred among the 2996 patients enrolled in all the DAA trials that were assessed by Jakobsen and colleagues. Thus, the statistical power to show a difference between the two groups is very low. In addition, the non-intervention groups in many of the studies included in Jakobsen and colleagues' systematic review did in fact receive HCV therapy, primarily an interferon-based regimen, which would minimise any mortality benefit of DAA therapy. Finally, Jakobsen and colleagues' study included early, less effective DAA regimens that were discontinued or withdrawn before marketing. They propose that, to resolve definitively whether DAA therapy reduces morbidity and mortality, randomised clinical trials with a non-treatment comparator group be done with clinically relevant outcomes such as death. Clearly, with the ready availability of safe and effective DAAs and ample evidence showing the health benefits of achieving SVR, such a study design is unethical and would be unacceptable to institutional review boards and harmful to patients' health. Several organisations, such as patients' groups and international hepatology associations, have expressed their concerns about the methods and conclusions of the Jakobsen review.14, 15, 16
People who are knowledgeable in the field of HCV therapy can readily ascertain the limitations of the approach taken in the systematic review by Jakobsen and colleagues and will be able to place their results in the proper context relative to other data that document the health benefits of DAA therapy. But for some patients, health-care providers, and decision makers who may be less knowledgeable about HCV therapy, this type of analysis, especially as reported in the mainstream media,17 could lead to conclusions that DAA therapy has no benefit, resulting in decisions to decline to prescribe or take DAA therapy or to decline to approve budgets for DAA treatment programmes, particularly in view of their expense. This would be a tragic outcome, as it would lead to preventable deaths. Public-health policy makers who must decide on budget allocations for HCV treatment cannot wait for perfect data on mortality endpoints, since the types of trials that would generate these data will never be done. Rather, they must assess available, albeit imperfect, data from observational studies and trials using surrogate outcomes that are reliably predictive of clinically important outcomes. Based on the fact that DAA therapy is safe and effective in achieving SVRs, that the SVRs are durable in most patients, that HCV-induced liver damage improves after SVR, and that observational data show a large reduction in morbidity and mortality, health-care decision makers and providers can take comfort that the evidence is strong in favour of treatment. A more definitive assessment of impact on morbidity and mortality will take time, but this should not be used as a reason for denying HCV therapy and delaying efforts to eliminate HCV infection.
About 1 in 5 patients taking Direct Acting Antivirals will get insomnia. Here is a post of mine from some years ago about how to manage it.
Insomnia is a common and often frustrating problem. Part of the reason it's frustrating is that, unless an accurate diagnosis of the root cause(s) is made, treatments tend to be temporary band aid solutions and rapidly lose their effectiveness.
Do you have an underlying medical problem?
There are a range of medical condition that can cause insomnia.
Chronic pain, sleep apnoea or a need to urinate frequently caused by an enlarged prostate gland can all cause insomnia.
Diseases like arthritis, cancer, heart failure, lung disease, gastroesophageal reflux disease (GERD), overactive thyroid, Parkinson's disease and Alzheimer's disease have all been implicated.
Mental health problems like stress, anxiety and depression can also cause problems.
Many of these issues are amenable to treatment, and by fixing the root cause, sleep patterns can return to normal.
Are your medications to blame?
- SSRI antidepressants
- ACE inhibitors
- Cholinesterase inhibitors
- H1 antagonists
Note that you should consult with your doctor before stopping any prescribed medications.
Are your daily habits contributing?
There are many habits and work patterns that promote poor sleep
- Not enough light at midday and too much light (device screens) at night
- Shift work - this scrambles your body clock (circadian rhythm)
- Eating late in the evening
- Fluids in the evening (we were all trained as children to wake up and not wet the bed)
- Excess caffeine, nicotine and other stimulant (ie Red Bull) consumption
- Using stimulants in the afternoon and evening
- Not getting enough exercise
- Too much alcohol - although alcohol is a sedative it prevents entry into deep sleep
Could your sleep hygiene be improved?
If you use your bedroom for other activities than sleep and sex you are missing the opportunity to program your thinking along the lines of go to bed, go to sleep.
You will sleep better if:
- You have got a good dose of daylight during the day, and less light at night
- Your bedroom is pitch black
- Your bedroom is quiet
- You bedroom is not too hot, not too cold
- You have a comfortable mattress
- You have a comfortable pillow - not too high or too low, too soft or too firm - get one that's just right (and remember they wear out over time)
- You have enough blankets so you're not too hot when you go to bed, but also don't wake up freezing when it cools off in the early morning
What can my doctor do for me?
For a start, any doctor worth his/her salt can discuss everything with you and look for root causes. It's always best to fix the source(s) of problems.
A simple plan (from Dr Margaret Hardy)
- Work out average amount of actual sleep per night from sleep diary
- Choose a regular wake-up time
- Set a regular bedtime by subtracting average sleeping hours from the planned wake-up time
- Review at weekly intervals and, if tired, increase time in bed by going to bed 30 minutes earlier
Your doctor can also provide medications including:
- Melatonin (which re-sysncs your body clock and is thus really good for shift work and jetlag
- First generation sedating antihistamines (promethazine, doxylamine)
- Benzodiazepines (temazepam, zopiclone, zolpidem and many others) which are good for short term (particularly stress related insomnia). Long term you become first tolerant (needing ever increasing doses) and then addicted (needed the medication or you won't be able to sleep)
- Antidepressants like amitriptyline and mirtazipine which are used (usually in low doses) not to treat depression but for their common sedating side effect. Their advantage over benzodiazepines is that tolerance is far less of an issue, so they can be used longer term.Don't despair. Most people can get
Don't despair. Most people can get a far better nights sleep with a few simple changes.
Talk to your doctor, or see one of our expert GPs online from the convenience of home.
Dr James Freeman
Yesterday the Guardian published an article called 'Miracle' hepatitis C drugs costing £30k per patient 'may have no clinical effect'
The problem with this sensationalist headline is that while it is reporting what was said by the Cochrane Collaboration what they looked at was trial specifically designed to test SVR rates, and not specifically designed to look at long-term outcomes.
Here is a commentary from Dr Andrew Hill and the study to which he refers which was presented at AASLD in 2015 and published in Clinical Infectious Diseases.
There is some really interesting stuff happening in the "reverse liver fibrosis" realm.
Here is state of the art in 2009 (great review of the mechanism) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2702953/ where we had no clear candidates, and
Here is state of the art in 2015 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4703795/ where we have literally hundreds of candidates (coffee and milk thistle (silymarin) and resveratrol are in there), and
Here is the state of the art in 2016 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754444/ in an article called Promising Therapy Candidates for Liver Fibrosis
I like this bit from the conclusion:
Since both animal experiments and clinical studies have revealed that liver fibrosis, even early cirrhosis, is reversible, treating patients by combined therapies on underline etiology and fibrosis simultaneously might expedite the regression of liver fibrosis and promote liver regeneration.
Here is a copy of the generic hep c medication presentation given by Dr James Freeman at EASL 2017 today.
Mostly the presentation followed the slides.
The last words, with the last slide were "I want everyone to join the club, not the hep c buyers club, this club, the hep C cure club."
“The Liver Meeting”, or AASLD 2011, was taking place at the great, glass-fronted Moscone West Convention Center in downtown San Francisco. Almost 9,000 people were there – family doctors, hepatologists, gastroenterologists, academics, drug salesmen, public health officials – all networking, trudging the escalators, wandering the beige exhibit halls, trying to stay on top of an avalanche of medical information. Across five days in early November, no fewer than 2,200 liver-related scientific abstracts were being presented, at sessions that ran from 6.30am until 9pm. Specialists in hepatitis C, an awkward, under-recognised health problem, were used to finding their way to the back rooms, the less-glamorous receptions.
Many felt it was time the disease moved up the agenda. Since it was identified in 1989, “Hep C” or “HCV” to those who work on it, has only confounded those who underestimate it. Transmitted through blood, the virus is now thought to infect around 2.5 per cent of the world’s population, or 170 million people. Of those, around a quarter will develop liver cirrhosis, or cancer, within a decade or two. In the UK, deaths from hepatitis C have trebled since 1996 and more than 200,000 people are infected. No one knows what to do about the coming demand for liver transplants. For the past decade at least, scientists have used phrases such as “gathering storm” and “silent epidemic” to try to bring attention to the subject.
There has also been a torrent of new data to keep up with. Despite its orphan status, the sheer numbers of people infected with hepatitis C have made it the subject of hundreds of millions of dollars of medical research – particularly by pharmaceutical companies, working on a new generation of drugs. And AASLD, as the world’s premier liver event, has become the occasion when information on those drugs – known as “direct-acting antivirals” – is often shared for the first time. In recent years, hepatitis C delegates had got used to turning up to must-see presentations that were filled way beyond capacity.
One look at the 2011 programme told conference-goers that a session on the Sunday afternoon – “HCV: Refining the Use of Direct-Acting Antivirals” – was going to be mobbed. Room 2001, on the second floor of the convention centre, only held about 400 people. Dr Ed Gane, a 51-year-old hepatologist and transplant specialist from New Zealand, who was to give the fourth of six presentations in the session, arrived about 10 minutes before it was due to begin. “It was packed to the gunwales,” he told me. Conference staff began setting up a video link to adjoining rooms to cope with the spillover.
The cognoscenti were there to hear Gane. An unshowy, respected doctor, he had been working on hepatitis C since the early 1990s, and for the past year, had been carrying out a clinical trial of a particularly promising new drug developed by a small American pharmaceutical company called Pharmasset. The drug was known by its laboratory name, “PSI-7977”, and today, Gane was to give an update on the trial, called ELECTRON.
An article with the title: Importation of generic hepatitis C therapies: bridging the gap between price and access in high-income countries just made it into the Lancet print edition:
There is a PDF of it here
This article about the rationale for using generic hepatitis C medication has just been published in Liver International in their section "Debates in Hepatology".
James A. D. Freeman1 and Andrew Hill2
1 GP2U Telehealth, Hobart, Tas., Australia
2 St Stephens AIDS Centre, Chelsea and Westminster Hospital, London, UK
Liver Int. 2016; 36: 929–932. DOI: 10.1111/liv.13157
Hepatitis C, hepatitis B, HIV, TB and malaria are the five major causes of infectious disease death worldwide. In a breakthrough that rivals the invention of penicillin, drugs that cure hepatitis C, with minimal side effects and high success rates, have reached the market, but, in what must be one of the greatest tragedies of modern times, these life-saving medications are not being deployed on a mass scale. Pharmaceutical patents are gifted to private corporations by governments for the dual purposes of protecting R&D expenditure and encouraging innovation. Unfortunately the monopoly pricing power these patents provision currently lacks adequate checks and balances, is open to abuse, and is quite clearly being abused. The sort of legislative changes required to deliver on the original goals of pharmaceutical patents will take years or even decades to eventuate. Parallel importation of generic medication offers hope to the millions of patients with HCV unable to afford access to vastly overpriced originator medications. Doctors prescribing and monitoring patients taking generics can take comfort from the fact that the REDEMPTION trial results show, like the HIV generics that came before them, that HCV generics deliver robust clinical results.
Read the full article at: http://onlinelibrary.wiley.com/doi/10.1111/liv.13157/full
To find out more about generic hepatitis C medication please visit our forum where you can read the stories of patient successfully accessing and treating their hepatitis C with affordable generic medication.
Another US State Foots the Hepatitis C Bill - Where can you turn for therapy if you're not from Delaware?Written by Marko
Added pressure will not be enough
Ever since Obama Administration and lawsuits assumed office, most States are considered to be under pressure from the Delaware's case. For instance, Harvard Law School's Center for Health Law and Policy Innovation had threatened litigation to abandon money in response to policies that limits treatment of sick patients with expensive new medications.
However, many US citizens are waiting for their respective State to come up with a legislation that would cover the high costs of Hepatitis C treatment. Delaware is not an insulated case; but there is a long way from legislation to actual treatment. Hepatitis C patients are advised to seek treatment as quickly as possible in order to prevent further liver decay - and by far quickest method of getting Hepatitis C medicines with a considerable discount is by using Fix Hep C Buyers Club.
Hepatitis C patients can talk with Dr. Freeman about procuring the following medicines:
- sofosbuvir + ledipasvir (Harvoni®)
- sofosbuvir (Sovaldi®)
- daclatasvir (Daklinza®)
- ribavirin (Ibavyr®)
Hepatitis C overviewOver three million Americans are likely to be infected with hepatitis C, a bloodborne virus spread viа blood аnd bоdу-fluid contact ѕuсh аѕ blood, ѕеmеn, bоdу fluid, IV drug abusers ѕhаring needles or ѕоmеоnе uѕing tainted needles. Hераtitiѕ C uѕеd tо be thе mоѕt соmmоn tуре оf hераtitiѕ аcquirеd thrоugh blood trаnѕfuѕiоnѕ until a tеѕt fоr it bесаmе аvаilаblе in thе 1980ѕ.
Hераtitiѕ C саuѕеѕ inflаmmаtiоn оf the liver rеѕulting in liver damage that саn lead tо cancer. It аlѕо соmmоnlу lеаdѕ tо chronic livеr inflаmmаtiоn аnd ѕlоwlу dаmаgеѕthе livеr оvеr a lоng period оf time bеfоrе lеаding tо cirrhosis оf thе liver, that means scar tiѕѕuе rерlасing normal, healthy tiѕѕuе in rеѕult оf blocking thе flоw оf blood thrоugh the livеr and preventing it from frоm working аѕ it ѕhоuld.
Delaware Hepatitis C coverageThe Delaware State issue can be likened to that of New Jersey in that evidence is still required prior to liver damage approval treatment.
The new initiative policy permits a specific severity restrictions by July 1 and holds a requirement for patients on drugs abuse, thus bring in line with medical standard recommended for treatment and prevention of such infectious diseases.
Other changes will occur, for all hepatitis C-infected patients on Medicaid in Delaware who are eligible. The treatment new legislation takes effect on Jan. 1, 2018. The change as announced on Tuesday at Harvard was confirmed by a spokeswoman from Delaware Department of Health and Human Services that the State will definitely change its policy.
This initiative policy changes has already been embarked by other states. As it stands, an advisory committee set in Pennsylvania recommended that the state Medicaid initiative policy should treat all patients in that regard; a decision yet to be confirmed.
For all other patients, it is best to seek help using Fix Hep C Buyers Club. Contact us today and get your medications within a month.
Мы рады представить некоммерческий проект «ГЕПАТИТКА», созданный группой активистов для поддержки, помощи и общения людей, затронутых вирусными гепатитами B, C и D.
Начало этого проекта было положено в марте 2012 года пациентом из Москвы во время того, как он проходил курс лечения гепатита С пегилированнымиинтерферонами и рибавирином. Чтобы облегчить проживание сложных побочных эффектов, связанных с лечением, молодой человек начал взаимодействовать с людьми, затронутыми гепатитом С. Он делился своим опытом, рассказывал, как передается гепатит С, мотивировал лечиться, а не ждать развития фиброза, пояснял, как можно поддержать человека на лечении, организовывал совместное времяпровождение и он-лайн взаимодействие людей, связанных с гепатитом С. Вокруг него образовывалось сообщество людей, связанных с гепатитом С. Сообщество разрасталось, вышло за пределы Москвы и в октябре 2013 года его товарищ из Минска, замотивированный на лечение гепатита С, создал группу в социальной сети фейсбук. Этой группе далось запоминающееся название – ГЕПАТИТКА.
В 2015 году проект переформатируется, благодаря присоединению к работе и разносторонней поддержке коллег из ITPCru. Весной 2015 года в группе ГЕПАТИТКА в фейсбуке начала появляться информация о прорыве в лечении хронического гепатита С в виде появления на рынке препаратов для лечения гепатита С с принципиально новым принципом действия, с почти 100% эффективностью, легких по переносимости и с сокращенным сроком лечения. ГЕПАТИТКА была одним из первых ресурсов, где появились новости по доступу к лечению ВГС в мире новыми безинтерфероновыми схемами, где были опубликованы перечни доступных безинтерфероновых генерических препаратов для лечения ВГС с указанием цен и производителей. Ресурс подкреплял новостную информацию о препаратах переводенными на русский язык международными клиническими рекомендациями по лечению новыми схемами, а также результаты КИ по ним. При этом составом координатором ГЕПАТИТКИ было принято решение поддерживать исключительно традиционные мировые методы диагностики и лечения. Благодаря выкладываемой информации, постоянной работе с пациенстким сообществом и опыту первопроходцев, кто уже не мог откладывать лечение и воспользовался новыми препаратами, появилось много информации о ходе лечения новыми препаратами в режиме он-лайн, и как следствие, много возможностей расширения доступа к лечению гепатита С для всех нуждающихся и очевидная необходимость развития проекта ГЕПАТИТКА в разных направлениях.
На июнь 2016 года проект представлен в следующих ресурсах:
- закрытая группа фейсбук (3477 участников): https://www.facebook.com/groups/NAHCV/
- закрытая группа в ВКОНТАКТЕ (475 участников): https://vk.com/gepatitkaru
- сайт http://gepatitka.ru/, где доступен пациентский форум, а также последние мировые рекомендации по лечению ВГС и бесплатное медицинское консультирование по вопросам хронических гепатитов в режиме он-лайн.
На сегодня проект ГЕПАТИТКА координируется небольшой группой активистов из Москвы, Санкт-Петербурга и Минска. В планах стоит расширение развития в регионах ВЕЦА, в проекте на ежедневной основе задействованы активисты из РФ, Украины и Латвии. В проект вовлечены два медицинских специалиста, практикующих гепатолога, из Германии и России.
Добро пожаловать всем, кто затронут вопросами гепатитов на площадки проекта ГЕПАТИТКА. Вы сможете найти много полезной информации и общения там.
Dear all, especially Russian speaking audience,
We are pleased to present a non-profit project "GEPATITKA" for the Russian audience. Project was created by a group of activists to support and to coordinate communication between people, affected by viral hepatitis B, C and D.
Project started in March 2012 while a patient from Moscow (Russian Federation) was undergoing pegylated interferon and ribavirin treatment for hepatitis C. In order to handle tough side effects and not to stay alone with his condition, he started to share his experience with others, started to learn more about HCV and to share his knowledge. Very soon a community of patients grew around him. He treated his HCV and continued his activities to help others. He motivated his friend from Belarus to start treatment as well and in October 2013 the project appeared on-line, on FACEBOOK, and got it name – GEPATITKA (Gepatit means Hepatitis in Russian).
In 2015 the project GEPATITKA was reformatted (got a new structure), due to the joining of ITPCru. GEPATITKA started to spread out information about new landscapes in HCV treatment, about the DAA appearance in the world with almost 100% efficiency, easy portability and a reduced period of treatment. GEPATITKA was one of the first resources in the EECA region, where information about PEG-IFN-free regimens was published and lists with DAA generics with prices and producers appeared. Project supports its publications with the international clinical guidelines, and only traditional methods of HCV diagnosis and treatment. Due to the strong informational work and very attentive and intense approach to the patient’s community project GEPATITKA became very popular in the Russian speaking countries, especially in Russia, Belarus and Ukraine.
In June 2016 GEPATITKA project is presented in the following resources (only in Russian language):
- Private group on Facebook (more than 3500 participants): https://www.facebook.com/groups/NAHCV/
- Private group in a Russian social network VKontakte (around 500 participants): https://vk.com/gepatitkaru
- at the web site GEPATITKA: http://gepatitka.ru/
This web site provides not only the latest world updates for HCV treatment and free medical consultations for chronic hepatitis in the online mode, but also a platform for the patient’s forum.
Today GEPATITKA project is being coordinated by a small group of activists from Moscow, Saint Petersburg and Minsk (Belarus). They plan to expand in the EECA regions. A number of volunteers, who are affected by hepatitis, from Russia, Ukraine and Latvia are involved in this project on a daily basis. Two medical specialists, hepatologists from Germany and Russia answer questions on the web site free of charge on the daily basis.
Resources of GEPATITKA are very friendly and patient - oriented and warmly welcomes everyone who is affected by hepatits.
Efforts are being done to expand the insurance coverage to all Hepatitis C patients but it is an uphill battle. It is our hope that in some years, insurance companies will include Hepatitis C coverage in the majority of healthcare plans; however, Hepatitis C patients can't afford to wait for years on end to get the medicines.
FixHepC Buyers Club works much quicker. We can supply every Hepatitis C patients, regardless of fibrosis score, with an affordable Hepatitis C drugs (sofosbuvir, ledipasvir, daclatasvir, ribavirin). For everybody in need of Hepatitis C drugs, please do contact Dr. Freeman via email or phone and you will be able to discuss the proper course of treatment and how to obtain the medications.
Washington Judge Orders Medicaid to Save All Hepatitis C Patients
A federal judge has ordered Washington state’s Medicaid provider to cover expensive hepatitis C drugs for all patients with the liver-destroying disease, not just those who are sickest. Up till now, the coverage included only the patients with the most problematic fibrosis score. This has left thousands of patients in Washington alone without the access to the medications; not many could fetch up more than $80,000 for the medicines.
U.S. District Court Judge John C. Coughenour granted a preliminary injunction Friday that forces the state Health Care Authority (HCA) to halt a 2015 policy that restricted access to the drugs based on a fibrosis score, a measure of liver scarring.
Fibrosis ScoreHepatitis C drugs are expensive; so much so that many of health insurance companies would go down if they had to cover the expenses of all Hepatitis C patients.
This is why a sieve was created to determine which Hepatitis C patients need the medicines the most. The state of liver plays a key role in this selection process. Fibrosis score is used to get a basic understanding in how good a shape a liver is, and the decision process for many health insurance companies is as follows:
- 'Good' Fibrosis Score - No insurance coverage of Hepatitis C drugs
- 'Bad Enough' Fibrosis Score - Insurance covers Hepatitis C drugs
FixHepC Buyers Club - We Cure Everybody Regardless of Fibrosis ScoreWe all know that Hepatitis C is a deadly disease if left untreated. Why should only patients with a bad fibrosis score get the medical coverage? This is exactly what Washington Judge John C. Coughenour pointed out. Eventually, even people with the best fibrosis score will have their liver damaged beyond repair and looking for help then will be too late.
FixHepC has organized itself as a safe establishment to procure the necessary Hepatitis C medications to every patients.
- 'Bad' Fibrosis Score - We will help you get the medications (patients with bad fibrosis score need it the most)
- 'Good' Fibrosis Score - We will help you get the medications (patients with good fibrosis score will have their liver damaged in years to come - the time to act is now!)
The Washington CaseThe injunction was a response to a class-action lawsuit filed in February on behalf of two clients of Apple Health — and nearly 28,000 other Medicaid enrollees with hepatitis C.
The two patients, a 53-year-old Seattle woman and a 47-year-old Lakewood man, were prescribed the drug Harvoni to treat their hepatitis C infections. But they were denied the drug, which costs about $95,000 for a 12-week treatment, because of its cost, the complaint said.
The injunction orders HCA to begin covering Harvoni “without regard to fibrosis score.” The judge ruled that the agency’s policy was not consistent with existing state and federal Medicaid requirements that drugs be dispensed based on medical need.
“For people who have been living with this disease and feeling like there’s no hope if they can’t get this cure, this is life-changing,” said Ele Hamburger, a lawyer with the firm Sirianni, Youtz, Spoonemore and Hamburger, which filed the lawsuit. Co-filers included Columbia Legal Services and the Center for Health Law and Policy Innovation at Harvard Law School.
It’s not clear how soon Medicaid patients with hepatitis C may begin filling prescriptions for Harvoni and other direct-acting antiviral drugs. The ruling orders all parties to report back within 60 days.
HCA officials are reviewing the injunction, a spokeswoman said. But the state Medicaid director, MaryAnne Lindeblad, estimated in a letter to the U.S. Senate last fall that paying for hepatitis C treatment for all Medicaid clients in Washington would be three times the agency’s current $1 billion drug budget.
Medical guidelines had previously supported limiting the drugs to the sickest patients, but that changed last year. Experts in liver treatment and infectious disease now agree that drugs such as Harvoni should be used to treat all patients, including those with mild disease.
Time to Act is NowWaiting for your liver to have a bad enough fibrosis score for insurance company to cover Hepatitis C costs is literally playing with your own life.
We can help you to get the Hepatitis C medications within a month. Send us an email and we will help you get over Hepatitis C once and for all.
What Happened to the Indian Official that Rejected the US Drug Company Gilead’s Patent Application in 2015?
It appears that being a man of honour is less valued than it should be.
Hardev Karar, I salute you as a man of honour and integrity.
Dr James Freeman
End of Hepatitis C Tourism?For more than a year, Hepatitis C patients who could not afford the high price tag of the novel Hepatitis C drugs in their respective countries, could go to India and buy the medicines they needed to get well for about $2,000. This window that cured thousands and thousands of patients is about to close, as the result of Indian patent office ruling on drug Sovaldi (400mg sofosbuvir).
Gilead Sciences, the pharmaceutical company that makes Sovaldi, failed to show the inventiveness and novelty sufficient to grant a patent on Sovaldi. Since they did not wish to lose such a big market as India, they gave licences to 11 generic manufacturers in India to produce and distribute the low-cost sofosbuvir pills as their plan B (getting a patent being a plan A).
According to Reuters, Gilead appealed against the ruling that refrained Indian patent office from giving them a patent on sofosbuvir molecule. In a dramatic change of heart, Indian patent office just gave Gilead what they wanted all along - a patent. With the plan A in play now, Gilead might choose and forgo plan B - this would mean that there would be no more low-cost sofosbuvir pills to import from India and would leave millions to choose between fetching out more than 80,000$ for the original medicine, or face the lethal consequences of untreated Hepatitis C.
Fix Hep C Buyers Club supply of Hep C drugs is not affectedThe Fix Hep C Buyers Club remains one of the strongest providers of low-cost Hepatitis C medicines. Since sofosbuvir the buyers club provider is supplied from China, not India, the supply chain will not be affected and every Hepatitis C patient can seek help they need by contacting us (click here).
Why did the Indian patent office change its mind?In direct contradiction to its earlier order, the Controller General of Patents, Designs and Trademark granted American pharmaceutical company Gilead Sciences the patent for the blockbuster Hepatitis C drug Sofosbuvir (brand name Sovaldi) in India. An application for the same patent was first rejected in January 2015 as lacking inventiveness and novelty.
On Monday, however, the patent office dismissed all pre-grant oppositions and stated that it found, “claimed compounds are novel, inventive and patentable under Patents Act.” The decision is a major blow to the access to drug movement, said Leena Menghaney, South Asia head of Médecins Sans Frontières (MSF). “There has been excessive pressure building up on the Indian government to dilute the independent functioning of the patent office to ensure that patent claims are granted far more easily to U.S. firms. In the process, the patent office has completely ignored recent proceedings in the U.S. against Gilead regarding the same application which have been found to infringe two of Merck’s patents, clearly defeating Gilead’s claim that its application on the drug was novel,” added Ms Menghaney.
How obtaining a patent works
“These are very scary times for the patient communities globally who rely on affordable generic medicines coming from India. The government’s “Make in India” campaign seems to be only for foreign companies and not for Indian generic industry which has been the lifeline for people across the world,” said Loon Gangte with the Delhi Network of Positive People
Gilead, in a statement, welcomed the move, but said it will have no impact on availability of the compound, which is already licensed to 11 generic manufacturers in India for distribution in 101 developing countries.