Tuesday, October 31, 2017

MSF secures generic hepatitis C treatment at $120 compared to $147,000 launch price tag

MSF secures generic hepatitis C treatment at $120 compared to $147,000 launch price tag
Report from Médecins Sans Frontières

Tuesday, October 31, 2017 — Dramatic price drops should allow countries to provide treatment for millions of people

Reading Material: Not Even Close: This issue brief provides information on currently available HCV diagnostics and treatments, including pricing and registration information from manufacturers of DAAs www.msfaccess.org/hep-c-not-even-close

Geneva/Sao Paolo, 31 October 2017—On the eve of the World Hepatitis Summit in Sao Paolo, the international medical humanitarian organization Médecins Sans Frontières (MSF) today announced that it had secured deals for generic hepatitis C medicines for as low as US$1.40 per day, or $120 per 12-week treatment course for the two key medicines sofosbuvir and daclatasvir.

In the US, pharmaceutical corporation Gilead launched sofosbuvir at $1,000 per pill in 2013, and Bristol-Myers Squibb (BMS) launched daclatasvir at $750 per pill in 2015, leading to the original price tag of $147,000 for a person’s 12-week combination treatment course. The corporations have also been charging exorbitant prices in many developing countries, paralyzing the launch of national treatment programs and causing treatment rationing in many countries around the world.

“What good is a breakthrough medicine that people cannot afford?” asked Jessica Burry, Pharmacist for MSF’s Access Campaign. “Pharmaceutical corporations price hepatitis C medicines far out of reach for people paying out of pocket around the world, and also for many governments struggling to provide treatment in the public sectors; but the prices for generic versions keep coming down. Governments must use every tool in their toolbox to fight for access to lower-priced generics so they can scale up treatment for the millions of people who need it; they should follow the lead of countries like Malaysia and issue compulsory licenses when patents block people’s access to this life-saving treatment.”

In 2015, MSF started procuring sofosbuvir and daclatasvir from Gilead and BMS through their ‘access programs’ at a price of $1,400 to $1,800 per 12-week treatment. Today, MSF pays a fraction of that, at $120, sourced from quality-assured generic manufacturers.

An estimated 71 million people have chronic hepatitis C infection worldwide, 72 per cent of whom live in low- and middle-income countries. Direct-acting antiviral medicines (DAAs) represent a treatment breakthrough for people with hepatitis C, with cure rates of up to 95%, and with far fewer side effects than previous treatments. Yet access to DAAs has remained limited because pharmaceutical corporations charge unaffordable prices, leading many countries to reserve treatment only for people with the most advanced stages of the disease. By the end of 2016, three years after sofosbuvir was launched, only an estimated 2.1 million people globally had been treated with the medicines, leaving 69 million people still without access.

These high prices have also put a major strain on health systems in wealthy countries, in particular those enacting universal health care. Treatment is being rationed in countries such as Australia, Canada, Italy and the US, in addition to developing countries, and is a stark reminder of the early days of HIV treatment.

“Almost two decades ago, MSF and others worked hard to get access to generics and bring down prices for HIV medicines,” said Mickael Le Paih of MSF in Cambodia, where MSF treats people living with hepatitis C. “History is repeating itself with hepatitis C—the medicines we need are again too expensive, but we are finding ways to make treatment affordable so that our patients can be cured.”

MSF treats people with hepatitis C in 11 countries. Since 2015, MSF has provided DAA treatment to nearly 5,000 people with hepatitis C. Of those who have completed treatment to date, the overall cure rate – measured by ‘sustained viral response’ – is 94.9 per cent.

Reading Material: Not Even Close: This issue brief provides information on currently available HCV diagnostics and treatments, including pricing and registration information from manufacturers of DAAs

Close to 3 million people access hepatitis C cure

Close to 3 million people access hepatitis C cure

World Hepatitis Summit 2017 calls for accelerated action to eliminate viral hepatitis

31 October 2017 | São Paulo, Brazil - On the eve of the World Hepatitis Summit in Brazil, WHO reports increasing global momentum in the response to viral hepatitis. A record 3 million people were able to obtain treatment for hepatitis C over the past two years, and 2.8 million more people embarked on lifelong treatment for hepatitis B in 2016.

"We have seen a nearly 5-fold increase in the number of countries developing national plans to eliminate life-threatening viral hepatitis over the last 5 years," says Dr Gottfried Hirnschall, Director of WHO's Department of HIV and Global Hepatitis Programme. "These results bring hope that the elimination of hepatitis can and will become a reality."

Hosted by the Government of Brazil, the World Hepatitis Summit 2017 is being co-organized by WHO and the World Hepatitis Alliance. The Summit aims to encourage more countries to take decisive action to tackle hepatitis, which still causes more than 1.3 million deaths every year and affects more than 325 million people.

"We cannot lose sight of the fact that last year 194 governments committed to eliminating viral hepatitis by 2030. For sure we are still a long way from this goal but that doesn’t mean it’s some unattainable dream. It’s eminently achievable. It just requires immediate action," says Charles Gore, President of World Hepatitis Alliance. "The World Hepatitis Summit 2017 is all about how to turn WHO’s global strategy into concrete actions and inspire people to leave with a ‘can do’ attitude."

"Brazil is honored to host the World Hepatitis Summit 2017 – and welcomes this extraordinary team of experts, researchers, managers and civil society representatives to discuss the global health problem posed by viral hepatitis," says Dr Adele Schwartz Benzaken, Director of the Brazilian Ministry of Health’s Department of Surveillance, Prevention and Control of STIs, HIV/AIDS and Viral Hepatitis."Brazil is committed to taking recent advances in its response to hepatitis forward – on the road to elimination."
Progress in treatment and cure

Many countries are demonstrating strong political leadership, facilitating dramatic price reductions in hepatitis medicines, including through the use of generic medicines—which allow better access for more people within a short time.

In 2016, 1.76 million people were newly treated for hepatitis C , a significant increase on the 1.1 million people who were treated in 2015. The 2.8 million additional people starting lifelong treatment for hepatitis B in 2016 was a marked increase from the 1.7 million people starting it in 2015. But these milestones represent only initial steps – access to treatment must be increased globally if the 80% treatment target is to be reached by 2030.

However, funding remains a major constraint: most countries lack adequate financial resources to fund key hepatitis services.
Diagnosis challenge

To achieve rapid scale-up of treatment, countries need urgently to increase uptake of testing and diagnosis for hepatitis B and C. As of 2015, an estimated 1 in 10 people living with hepatitis B, and 1 in 5 people living with hepatitis C, were aware of their infection. Countries need to improve policies, and programmes to increase awareness and subsequent diagnosis.
Prevention gaps

Countries need to provide a full range of hepatitis prevention services that are accessible to different population groups, particularly those at greater risk.

Largely due to increases in the uptake of hepatitis B vaccine, hepatitis B infection rates in children under 5 fell to 1.3% in 2015, from 4.7% in the pre-vaccine era.

However, the delivery of other prevention services, such as birth-dose vaccination for hepatitis B, harm reduction services for people who inject drugs, and infection control in many health services, remains low. This has led to continuing rates of new infections, including 1.75 million new hepatitis C cases every year.
Need for innovation

Innovation in many aspects of the hepatitis response must continue. New tools required include a functional cure for hepatitis B infection and the development of more effective point-of-care diagnostic tools for both hepatitis B and C.

"We cannot meet the ambitious hepatitis elimination targets without innovation in prevention interventions and approaches, and implementing them to scale,” said Dr Ren Minghui Assistant Director-General for Communicable Diseases, WHO. “The great successes of hepatitis B vaccination programmes in many countries need to be replicated and sustained globally in the context of moving forward to universal health coverage."
Implementation of elimination strategy

The World Hepatitis Summit 2017 will be attended by over 900 delegates from more than 100 countries, including Ministers of Health, national programme managers, and representatives from organizations of people affected by viral hepatitis. The Summit will review progress and renew commitments by global partners to achieve the elimination of viral hepatitis by 2030 – a target reflected in WHO's elimination strategy and the UN Sustainable Development Goals.

Monday, October 30, 2017

Fatty Liver Common After Direct-Acting Antivirals for Hep C

Medscape Conference Coverage: The Liver Meeting 2017: American Association for the Study of Liver Diseases (AASLD)

Fatty Liver Common After Direct-Acting Antivirals for Hep C
Damian McNamara
October 30, 2017

WASHINGTON, DC — Evidence of steatosis is found in almost half the patients with hepatitis C who achieved a sustained virologic response after treatment with direct-acting antivirals, results from a prospective study show.

"Fatty liver is very common now that hepatitis C is being treated effectively," said Mazen Noureddin, MD, from Cedars-Sinai Medical Center in Los Angeles.

American and European guidelines state that a patient can be discharged from care in the absence of cirrhosis and elevated liver enzymes, but "we wanted to see what happens after direct-acting antiviral treatment," he said.

Steatosis was "very prevalent" in the study population, "although liver enzymes were normal," Dr Noureddin reported here at The Liver Meeting 2017.

Monitoring people for steatosis after a sustained virologic response is not common practice, he told Medscape Medical News, but these findings suggest that long-term monitoring is warranted.

Long-term Monitoring Needed
In their study, Dr Noureddin and his colleagues compared transient elastography findings (FibroScan, Echosens) in 101 patients — 49 men and 52 women — before and after they were treated with direct-acting antivirals. After each participant achieved a sustained virologic response, the researchers used the controlled attenuation parameter (CAP) to assess liver fat.

Mean age of the participants was 60 years and mean body mass index (BMI) was 28 kg/m². In addition, 36% of the patients were white, 25% were Hispanic, and 90% had diabetes. The hepatitis C infection was genotype 1 in 86% of the patients, genotype 2 in 13%, and genotype 4 in 1%. People with genotype 3 infection were excluded from the analysis because the etiology of hepatic steatosis is different in this population.

Decreases were significant in alanine transaminase (ALT) and aspartate transaminase (AST) levels and fibrosis scores from baseline to the achievement of sustained virologic response (P < .05).
In the study cohort, 48% of the patients showed evidence of steatosis after treatment, 6% of whom had advanced fibrosis. None of the 52% of patients without steatosis showed evidence of advanced fibrosis, defined as a score of at least 11 kPa.

For patients with steatosis, weight did not change during the study period. However, there were significant differences between these patients and those without steatosis.

Table. Mean Values After Patients Achieved a Sustained Virologic Response

ParameterPatients With SteatosisPatients Without SteatosisP Value
BMI29 m/kg²26 m/kg²<.05
Glucose level108 mg/dL96 mg/dL<.05
ALT level20 mg/dL15 mg/dL<.05
CAP score297 dB/m214 dB/m<.05
Fibrosis score7.0 kPa5.3 kPa<.05

"We need more follow-up," said Dr Noureddin. "We looked at patients 8 weeks after treatment. Next, we want to follow patients longitudinally to see if more patients with a fatty liver also develop fibrosis."

The study showed that even after achieving a cure for hepatitis C, approximately 50% of those patients demonstrated evidence of NAFLD.
"This is one of the most important studies presented at this meeting," said Naim Alkhouri, MD, from the Texas Liver Institute in San Antonio.

"The treatment of chronic hepatitis C infection has been revolutionized by the introduction of highly effective direct-acting antivirals, with cure rates of 95% or higher," he told Medscape Medical News. "However, the study showed that even after achieving a cure for hepatitis C, approximately 50% of those patients demonstrated evidence of NAFLD, which may increase their risk for liver cirrhosis and liver cancer."

"The use of FibroScan with CAP to assess for the presence of NAFLD and fibrosis progression should be considered in patients who are cured from hepatitis C infection," Dr Alkhouri said.

Dr Noureddin is a speaker and advisor for EchoSense. Dr Alkhouri has disclosed no relevant financial relationships.

The Liver Meeting 2017: American Association for the Study of Liver Diseases (AASLD): Abstract 2155. Presented October 23, 2017.

Follow Medscape Gastroenterology on Twitter @MedscapeGastro and Damian McNamara @MedReporter

https://www.medscape.com/viewarticle/887760#vp_1

Modeling cost-effectiveness and health gains of a “universal” versus “prioritized” hepatitis C virus treatment policy in a real-life cohort

In Case You Missed It

Hepatology 2017

Modeling cost-effectiveness and health gains of a “universal” versus “prioritized” hepatitis C virus treatment policy in a real-life cohort
Loreta A. Kondili, Federica Romano, Francesca Romana Rolli, Matteo Ruggeri, Stefano Rosato, Maurizia Rossana Brunetto, Anna Linda Zignego, Alessia Ciancio, Alfredo Di Leo, Giovanni Raimondo,

First published: Full publication history
DOI: 10.1002/hep.29399

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View Online

Abstract
We evaluated the cost-effectiveness of two alternative direct-acting antiviral (DAA) treatment policies in a real-life cohort of hepatitis C virus–infected patients: policy 1, “universal,” treat all patients, regardless of fibrosis stage; policy 2, treat only “prioritized” patients, delay treatment of the remaining patients until reaching stage F3. A liver disease progression Markov model, which used a lifetime horizon and health care system perspective, was applied to the PITER cohort (representative of Italian hepatitis C virus–infected patients in care). Specifically, 8,125 patients naive to DAA treatment, without clinical, sociodemographic, or insurance restrictions, were used to evaluate the policies’ cost-effectiveness. The patients’ age and fibrosis stage, assumed DAA treatment cost of €15,000/patient, and the Italian liver disease costs were used to evaluate quality-adjusted life-years (QALY) and incremental cost-effectiveness ratios (ICER) of policy 1 versus policy 2. To generalize the results, a European scenario analysis was performed, resampling the study population, using the mean European country-specific health states costs and mean treatment cost of €30,000. For the Italian base-case analysis, the cost-effective ICER obtained using policy 1 was €8,775/QALY. ICERs remained cost-effective in 94%-97% of the 10,000 probabilistic simulations. For the European treatment scenario the ICER obtained using policy 1 was €19,541.75/QALY. ICER was sensitive to variations in DAA costs, in the utility value of patients in fibrosis stages F0-F3 post–sustained virological response, and in the transition probabilities from F0 to F3. The ICERs decrease with decreasing DAA prices, becoming cost-saving for the base price (€15,000) discounts of at least 75% applied in patients with F0-F2 fibrosis.

Conclusion: Extending hepatitis C virus treatment to patients in any fibrosis stage improves health outcomes and is cost-effective; cost-effectiveness significantly increases when lowering treatment prices in early fibrosis stages. (Hepatology 2017)

HCV Cirrhosis - Liver-related morbidity and mortality with and without sustained virologic response

Liver-related morbidity and mortality in patients with chronic hepatitis C and cirrhosis with and without sustained virologic response
Sofie Hallager,1 Steen Ladelund,2 Peer Brehm Christensen,3 Mette Kjær,4,5 Birgit Thorup Roege,6 Karin Elmegaard Grønbæk,7 Erika Belard,8 Toke S Barfod,9 Lone Galmstrup Madsen,10 Jan Gerstoft,11 Britta Tarp,12 Henrik Bygum Krarup,13 Nina Weis,1,5

Accepted for publication 5 July 2017
Published 24 October 2017 Volume 2017:9 Pages 501—516
DOI https://doi.org/10.2147/CLEP.S132072

Full-Text

Background: Chronic hepatitis C (CHC) causes liver cirrhosis in 5%–20% of patients, leading to increased morbidity and mortality. This study aimed to estimate liver-related morbidity and mortality among patients with CHC and cirrhosis in Denmark with and without antiviral treatment and sustained virologic response (SVR). Furthermore we aimed to estimate the rate of hepatocellular carcinoma (HCC) and decompensation associated with certain prognostic factors.

Materials and methods: Patients with CHC and cirrhosis registered in the Danish Database for Hepatitis B and C were eligible. Cirrhosis was based on liver biopsy, transient elastography, and clinical cirrhosis. Data were extracted from nationwide registries. The study period was from 2002 until 2013.

Results: Of 1,038 patients included, 716 (69%) were male and the median age was 52 years. Median follow-up was 3.8 years, 360 patients died, and 233 of 519 treated patients achieved SVR. Alcohol overuse and hepatitis C virus genotype 3 were associated with an increased incidence rate (IR) of HCC, whereas diabetes and alcohol overuse were associated with increased IRs of decompensation. Achieving SVR reduced all-cause mortality (adjusted mortality rate ratio 0.68 [95% CI 0.43–1.09]) and liver-related mortality (mortality rate ratio 0.6 [95% CI 0.36–1]), as well as liver-related morbidity with adjusted IR ratios of 0.37 (95% CI 0.22–0.62) for HCC and 0.31 (95% CI 0.17–0.57) for decompensation. The IRs of HCC and decompensation remained elevated in patients with alcohol overuse after SVR.

Conclusion: Alcohol overuse, hepatitis C genotype 3, and diabetes were associated with liver-related morbidity in patients with CHC and cirrhosis. SVR markedly reduced liver-related morbidity and mortality; however, special attention to patients with alcohol overuse should continue after SVR.

Saturday, October 28, 2017

Alcoholic liver disease confers a worse prognosis than HCV and non-alcoholic fatty liver disease among patients with cirrhosis

Alcoholic liver disease confers a worse prognosis than HCV infection and non-alcoholic fatty liver disease among patients with cirrhosis: An observational study
Astrid Marot, Jean Henrion, Jean-François Knebel, Christophe Moreno, Pierre Deltenre
Published: October 27, 2017 https://doi.org/10.1371/journal.pone.0186715

In conclusion, patients with cirrhosis related to alcoholic liver disease (ALD) have a lower incidence of HCC but die more frequently from decompensation of cirrhosis than patients with cirrhosis related to chronic HCV infection or non-alcoholic fatty liver disease (NAFLD). Cirrhosis related to ALD should be considered as a condition associated with a poor outcome. This population should deserve specific patient care focused on the management of complications related to liver failure. The impact of HCC surveillance on mortality remains to be established in ALD patients.

Full-Text

Abstract
Background
Cirrhosis is a heterogeneous clinical condition that includes patients at wide-ranging stages of severity. The role of the underlying liver disease on patient prognosis remains unclear.

Aim
To assess the impact of the underlying liver disease on the occurrence of hepatocellular carcinoma (HCC) and death.

Methods
Data related to the occurrence of HCC and death were collected during a 21-year period among patients with cirrhosis related to alcoholic liver disease (ALD) (n = 529), chronic hepatitis C virus (HCV) infection (n = 145) or non-alcoholic fatty liver disease (NAFLD) (n = 78).

Results
At inclusion, ALD patients were younger than HCV and NAFLD patients (56 vs. 67 vs. 63 years; p<0.001) and had worse liver function (percent of patients with Child-Pugh stages B or C: 48% vs. 8% vs. 17%; p<0.001). During follow-up, 85 patients developed HCC and 379 died. The 10-year cumulative incidence rate of HCC was lower in ALD patients than in HCV and NAFLD patients (8.4% vs. 22.0% vs. 23.7%; p<0.001). The 10-year cumulative incidence rates of mortality were not statistically different between ALD, HCV and NAFLD patients (58.1% vs. 47.7% vs. 49.9%; p = 0.078). Alcohol abstinence and viral eradication were associated with reduced mortality among ALD and HCV patients, respectively. In multivariate analyses, ALD was associated with a reduced risk of HCC (0.39; 95% CI, 0.20–0.76; p = 0.005) but with a higher risk of mortality (1.53; 95% CI, 1.20–1.95; p<0.001). ALD patients died more frequently from decompensation of cirrhosis.

Conclusion
Despite a lower incidence of HCC, patients with ALD-related cirrhosis have a worse outcome than those with chronic HCV infection or NAFLD-related cirrhosis.

Friday, October 27, 2017

A new study shows that liver cancer in Asia is linked to herbal remedies

A new study shows that liver cancer in Asia is linked to herbal remedies Researchers have uncovered widespread evidence of a link between traditional Chinese herbal remedies and liver cancer across Asia, a study said Wednesday.

The findings suggest stronger measures are needed to prevent people from consuming chemicals called aristolochic acids (AA), which are derived from the woody vines of the Aristolochia plant family, said the report in the journal Science Translational Medicine.

The acids can be found in some traditional Chinese medicines that are given during childbirth, to prevent parasites and promote healing.
Read the article.....

Full Text Article
Science Translational Medicine

Aristolochic acids and their derivatives are widely implicated in liver cancers in Taiwan and throughout Asia
Alvin W. T. Ng1,2,3,*, Song Ling Poon4,*, Mi Ni Huang1,2, Jing Quan Lim4,5, Arnoud Boot1,2, Willie Yu1,2, Yuka Suzuki1,2, Saranya Thangaraju4, Cedric C. Y. Ng4, Patrick Tan2,6,7,8, See-Tong Pang9, Hao-Yi Huang10, Ming-Chin Yu11, Po-Huang Lee12, Sen-Yung Hsieh10,†, Alex Y. Chang13,†, Bin T. Teh2,4,7,14,† and Steven G. Rozen
Science Translational Medicine  18 Oct 2017:Vol. 9, Issue 412, eaan6446
DOI: 10.1126/scitranslmed.aan6446

The dark side of an herbal medicine
Aristolochic acid, an herbal compound found in many traditional medicines, had been previously linked to kidney failure, as well as cancers of the urinary tract. Because of these known toxicities, herbs containing this compound have been restricted or banned in some countries, but it is still available on the internet and in alternate formulations. By analyzing numerous samples from Taiwan and other countries in Asia and elsewhere, Ng et al. demonstrated the effects of aristolochic acid in hepatocellular carcinoma, a much more common tumor type. The authors showed that the use of this drug remains widespread in Asia and particularly in Taiwan, and that it appears to increase the risk of multiple different cancer types.

Abstract
Many traditional pharmacopeias include Aristolochia and related plants, which contain nephrotoxins and mutagens in the form of aristolochic acids and similar compounds (collectively, AA). AA is implicated in multiple cancer types, sometimes with very high mutational burdens, especially in upper tract urothelial cancers (UTUCs). AA-associated kidney failure and UTUCs are prevalent in Taiwan, but AA’s role in hepatocellular carcinomas (HCCs) there remains unexplored. Therefore, we sequenced the whole exomes of 98 HCCs from two hospitals in Taiwan and found that 78% showed the distinctive mutational signature of AA exposure, accounting for most of the nonsilent mutations in known cancer driver genes. We then searched for the AA signature in 1400 HCCs from diverse geographic regions. Consistent with exposure through known herbal medicines, 47% of Chinese HCCs showed the signature, albeit with lower mutation loads than in Taiwan. In addition, 29% of HCCs from Southeast Asia showed the signature. The AA signature was also detected in 13 and 2.7% of HCCs from Korea and Japan as well as in 4.8 and 1.7% of HCCs from North America and Europe, respectively, excluding one U.S. hospital where 22% of 87 “Asian” HCCs had the signature. Thus, AA exposure is geographically widespread. Asia, especially Taiwan, appears to be much more extensively affected, which is consistent with other evidence of patterns of AA exposure. We propose that additional measures aimed at primary prevention through avoidance of AA exposure and investigation of possible approaches to secondary prevention are warranted.
Full Text Article - http://stm.sciencemag.org/content/9/412/eaan6446.full

Why the VA is so Successful Tackling HCV

Why the VA is so Successful Tackling HCV
by Pippa Wysong
Contributing Writer, MedPage Today

VA experts tell how they get high-risk patients engaged, nationally
The U.S. Department of Veterans Affairs (VA) is a leader in its ability to reach hepatitis C virus (HCV)-infected patients and engage them in care. Here, the secrets to its success are laid bare.

According to a recent paper in the Annals of Internal Medicine, the VA is the country's largest care-provider for HCV-infected patients and is well on its way to eliminating the disease in its population.

As of July 2017, a total of 51,000 veterans remain potentially eligible for treatment, a significant drop from more than 168,000 only 3 years ago. The number of people infected is decreasing by an estimated 30,000 per year...
Read the article at... MedPage Today

Expert Critique
Michelle Long
Assistant Professor of Medicine, Department of Medicine, Section of Gastroenterology
Boston University School of MedicineBoston, MA
With the success of direct-acting antiviral (DAA) medication for the treatment of hepatitis C virus (HCV), the challenges now are in linking patients with hepatitis C to care. The U.S. Department of Veterans Affairs (VA) has been very successful in treating patients infected with HCV, and the number of people infected within the VA care system is decreasing by about 30,000 people per year. The VA is well suited to treat HCV since it has a single integrated, electronic health record and a large case registry to link patients to care. Using these systems, the VA is able to screen high-risk populations and monitor disease incidence and prevalence. Patients who were eligible for screening were reached via letters or phone calls or through partnerships with shelters. The VA also has utilized care-delivery teams that personalize care delivery to different clinical settings and allowed outreach to patients in remote locations. The VA also was able to place DAA medications on the formulary, which lowered costs and allowed better access to medications.