Whats the difference ?
Welcome to the latest Hepatitis Scotland e-Bulletin.
On March 19 in Stirling, Hepatitis Scotland and The Hepatitis C Trust are organising a conference for people across Scotland who have been diagnosed with Hepatitis C, whether they currently have the virus or have previously cleared it. The agenda includes a keynote address by the Minister for Public Health, an overview of new treatments emerging into the market and a presentation on patient activism. View the conference details and access booking forms here.
View map here.
Following the European Medical Agency's recommendation for approval of sofosbuvir, trade name Sovaldi, for treatment of Hepatitis C, the European Commission has now given it final approval to be marketed within the EU. It becomes the first all oral treatment for Hepatitis C, with increased cure rates and shorter treatment durations.
Sovaldi is now due for submission to the Scottish Medicines Consortium. Patient Interest Group submissions are due by March 31st and SMC advice will be given on June 9th 2014 meaning that Sovaldi could be available to patients in Scotland late this year.
Sovaldi (sofosbuvir) will be available along with peginterferon and ribavirin for patients with Hepatitis C genotype 1, 4, 5 and 6 and as an interferon free treatment alongside ribavirin for patients with Hepatitis C genotypes 2 and 3.
2 studies presented at the The Liver Meeting 2013 have delivered very positive results for Hepatitis C infected liver transplant patients. In one study the combination of sofosbuvir and ribavirin used pre-transplantation prevented recurrence of the Hepatitis C virus in 64% of patients.Used after transplantation SVR rates of 77% 4 weeks after treatment were reported.
Reinfection of a transplanted liver is highly likely in Hep C positive liver transplantation patients and Hepatitis C infection recurrence is the main cause of death or transplant failure in this patient group.
Following FDA approval of Sofosbuvir in late 2013, Gilead has now applied for approval of a once daily combination pill of sofosbuvir and their other Hepatitis C drug, Ledipasvir, for treatment of Hepatitis C genotype 1. Data from phase 3 trials showed that the combination therapy was able to cure people of the virus in as little as 8-12 weeks with no need for interferon injections or ribavirin which would make it the first all oral treatment for Hepatitis C.
Gilead has already submitted an application to the European Medicinces Agency for accelerated approval of Ledipasvir and Sofosbuvir.
The European Medicines Agency has given an opinion on the compassionate use of Gilead's combination therapy of Ledipasvir and Sofosbuvir, with or without ribavirin, to give patients who are at high risk of liver decompensation within 12 months without treatment. The assessment report and conditions of use are due to be published on the EMA website shortly.
Further to trials conducted in 2012 which showed excellent results, Bristol Myers Squibb's new Hepatitis C drug daclatasvir has again been trialled alongside Gilead's sofosbuvir with clearance rates at 12 weeks of up to 98% for genotype 1 infection and up to 92% and 89% for genotypes 2 and 3 respectively.
These trials continue to indicate that this all oral combination Hepatitis C treatment is the most effective prospective Hepatitis C treatment in all genotypes.
Bristol Myers Squibb's all oral Hepatitis C drug combination of daclatasvir and asunaprevir for treatment of Hepatitis C genotype 1b has received 'Breakthrough Therapy designation' from the US FDA. 'Breakthrough Therapy designation' is intended to speed up the development and review of drugs for life threatening conditions. The designation was made based on data from the company's ongoing phase III clinical trial program.
Abbvie Inc expects it's new Hepatitis C drug regimen to be approved and go on sale in late 2014. The treatment is an all oral combination therapy of 5 pills per day. Whilst not as convenient as Gilead's sofosbuvir/ledipasvir combination, one pill taken once a day, phase 3 trial results showed cure rates of up to 98% in Genotype 1.
Scientists at Rutgers University in the US have determined the structure of a Hepatitis C surface protein which may help with the development of an effective vaccine. The team of researchers have described an outer region of the Hepatitis C virus that enables it to evade the body's immune system response, causing chronic infection.
Study collaborator Associate Professor Joseph Marcotrigiano said “Viruses are smart and it is a constant battle to keep them out. That’s why the development of a vaccine is so important. It’s always better to prevent infection through an effective vaccine than to treat after a chronic infection has been established."
A recent study published in the Journal of Hepatology has said that achieving SVR (sustained viral response) is less likely to benefit older Hepatitis C patients with less advanced liver fibrosis and suggested that this patient group may be better off delaying treatment until new treatments become available which have fewer adverse side effects.
The findings of the study showed that compared with younger people with more advanced fibrosis, older patients with less advanced fibrosis were less likely to gain additional benefit in terms of extra life years, quality of life years or avoiding liver failure.The results indicated that the benefit of SVR varied widely.
Study authors commented on how this highlighted issues in terms of informed consent before starting treatment with current standard of care therapy: “The question of what value a sustained viral response, in itself, imparts on the patient is often left unstated. Given that many treatment candidates are without symptoms of their infection, patients must be well-informed regarding what, by way of prognosis improvement, [sustained virologic response] can offer. Yet, to date, this issue has received little attention despite being critical to informed consent.”
A meta analysis published in the PloS one Journal has suggested that there may be a link between Hepatitis C infection and stroke. Up to this point no systematic review about Hepatitis C infection and stroke had been performed with previous studies being inconsistent.
The analysis points out that further prospective cohort studies will have to be carried out to prove a link and that the mechanism by which Hepatitis C infection may increase risk of a stroke is not known. However, there is recent evidence that Hepatitis C increases the thickness of arteries and their likelihood of clogging. Chronic inflammation may play an important role in this indicator for stroke.
Hepatitis C has also been shown to increase the risk of metabolic diseases such as type 2 diabetes which can also increase the risk of stroke.
Research published in the PLOSone Journal have shown that 25-OH-Vitamin D levels do not show any significant association to treatment outcome in genotype 1 infected patients. Levels of 25-OH-Vitamin D showed considerable variations across anti-viral treatment duration with peg interferon and ribavirin, but neither pre-treatment or during treatment levels were associated with treatment outcomes.
Among other parameters analysed, age, cholesterol, ferritin and IL28b genotype provided the strongest predictors of treatment response.
Various recent studies have provided conflicting evidence regarding the predictive potential of pre-treatment Vitamin D levels on successful Hepatitis C treatment. Some studies have shown low pre-treatment Vitamin D levels correlating with a poor response to Hep C treatment while others have shown that Vitamin D levels seem unable to predict treatment response. Baseline vitamin D levels also failed to predict treatment response in HIV/HCV co-infected patients.
A recent study has shown that patients with a history of chronic Hepatitis C, even without overt cirrhosis, suffer from sleep disorders, including disruption of circadian rhythm (24 hour body clock). Abnormal circadian rhythm is associated with an altered sleep pattern, insomnia, fatigue, depression, and reduced quality of life.
It was already known that sleep disturbance with the reversal of the day and night cycle was common in patients with liver induced brain disorders regardless of the cause. Insomnia, fatigue, depression and cognitive impairment are common symptoms in patients with chronic liver disease with cirrhosis. This study shows that those with chronic Hepatitis C without cirrhosis may also develop disturbed circadian rhythm.
Sleep patterns are dictated by the 24 hour body clock (subjected to light and darkness cycles) which control numerous activities of the body’s metabolism such as body temperature, blood pressure, melatonin, mood and cognitive abilities.
Inadequate sleep can lead to exhaustion, increased irritability, mood fluctuation such as depression, anxiety or anger, reduced concentration, attention deficit disorder, decreased memory, decreased productivity and creativity, drowsiness, unintended sleep, weight gain, metabolic abnormalities and more.
In previous e-bulletins we have covered other extra hepatic (non liver specific) manifestations of Hepatitis C on which circadian rhythm or sleep pattern may also have an effect.
Indeed, the importance of getting enough sleep is underlined in this video presentation by Professor of Medicine and Chief of Gastroenterology at Eastern Virginia Medical school. The professor reminds us that if you sleep less than 6 hours per day, studies have shown that stroke risk increases by a factor of 4, obesity is increased due to an increase in hunger hormones, diabetes is increased because sleep deprivation increases insulin resistance, cardiac disease increases with chances of cardiac death increasing by 48% and a 4 fold increase in all cause mortality. He also speaks of a recent study in mice which seems to suggest that sleep deprivation may cause cancer tumours to grow and spread more quickly.
For tips on how you can improve your sleep visit the National Sleep Foundation.
Findings from the ETHOS study published in the Jounral of Viral Hepatitis have shown that a lack of physical symptoms of Hepatitis C infection and treatment side effects associated with interferon are acting as barriers for patients receiving opioid substitution therapy.
Study researcher Carla Treloar said “Integrating treatment for hepatitis C within settings that provide treatment for drug dependence minimizes some of the barriers for clients wishing to undertake hepatitis C treatment.”
The Enhancing Treatment for Hepatitis C in Opioid Substitution Settings (ETHOS) study, was designed to evaluate an integrative treatment model for the provision of onsite HCV assessment and treatment at addiction care facilities.
Treloar and colleagues conducted interviews with 57 patients from the ETHOS study to gain an insight into attitudes toward HCV treatment. For patients who had not been assessed for HCV infection, reasons for not engaging in care included the perception that they generally felt well and were experiencing no symptoms. Perceptions of negative side effects from interferon based treatment were another main theme.
Among those who were assessed for HCV infection but who did not pursue treatment, reasons included family responsibility, unstable housing and a general feeling that it was not a priority for them at that time.
Among those who did go on to receive treatment, motivating factors included; awareness of the seriousness of the infection, knowing friends who had suffered from the illness and shared positive experiences of treatment.Presence of an engaged clinician, accessible treatment pathway and availability of support were also rated as important in deciding to start HCV treatment.
Treloar concludes, “Changing the way in which hepatitis C treatment is spoken about is important, particularly providing opportunities for patients who have had positive treatment experiences to discuss these with their peers".
A study published in the Journal of Viral Hepatitis has documented the costs of failed treatments for genotype 1 Hepatitis C versus those who achieve SVR, providing real life data for future cost effectiveness analyses related to the treatment for chronic HCV infection.
The study quantified the medium term difference in health resource usage and costs depending on treatment outcome. 193 patients (108 SVR and 85 non SVR) with a mean follow up of 3.5 (SVR) and 4.9 (non SVR) years were enrolled.
No SVR patient progressed to a more severe liver disease state. Annual transition rates for non SVR patients were 7.4% (chronic hepatitis to cirrhosis) and 4.9% (cirrhosis to de-compensated liver disease). Extrapolating modelled data over a 5 year post treatment period, failure of patients to achieve SVR was associated with a 13 fold (roughly £2,300) increase in costs, whilst for patients who were retreated, the increase was 56 fold, equating to more than £10,000. Achievement of SVR therefore has significant effects on health service usage and costs.
An article published on Medpage Today considers the factors involved in determining prices for new Hepatitis C therapies and whether or not new therapies such as Gilead's sofosbuvir offer value for money.
Gilead have priced sofosbuvir at $84,000 for a 12 week treatment, with Janssen's simeprevir priced at $66,360 for a course of treatment - costs which do not include costs for other drugs which might be used in combination.
However, the article points out that treatments to achieve a Hepatitis C cure have never been cheap and that the percentage of people being cured vs overall cost of therapies needs to be balanced to judge which therapies offer best value. Dr. Andrea Branch of Mount Sinai Hospital in New York looked back at 147 patients treated in her hospital with telaprevir, peg interferon and ribavirin (triple therapy) seeking to find out how much it cost to achieve a cure. In real world use, triple therapy has not proved as effective as hoped.
She found that the median cost for treatment was $83,509 (65% of that going on telaprevir) but only 44% of patients achieved SVR, meaning that the cost per cure was $188,859. With new Hep C drugs promising cure rates of 80% to 90% or higher they could work out as being cheaper to use.
Dr. Branch is quotedas saying, 'If these new drugs perform as expected and the costs are as expected, I think there will be an economic saving compared with previous triple therapy.'
The article also discusses considerations around the expensive annual costs of patients with advanced liver disease and the huge expense involved in liver transplant as other factors to be considered in whether new treatments will be cost effective - also pointing out that with several competitors due to enter the market, it's unlikely this won't have a downward influence on drug prices over time.
Finally it considers the implications for resource poor countries of the high cost of new treatments. Dr Andrew Hill of Liverpool University in the UK, has estimated that a full 12 week course of sofosbuvir would only cost $136 to make - meaning that Gilead has come under pressure to reduce prices in developing countries.
A group of scientists and lawyers, the Initiative for Medicines, Access and Knowledge, has filed a challenge to Gilead's patent application for Sofosbuvir, arguing that it is not innovative enough at a molecular level to be granted a patent under Indian law.
The law in India states that products that are variants of existing chemical compounds are not patentable. Els Torreele, Director of the Open Society Foundations' Access to Essential Medicines Initiative (who provide a grants to the Initiative for Medicines, Access and Knowledge) said, "This is a battle over whether profits or the lives of patients will drive the hepatitis C response."
Gilead is in discussion with Indian pharma companies to produce sofosbuvir there at a fraction of the $84,000 US cost but intends to defend it's patents.
They argue that with 90% of Hepatitis C patients living in low and middle income countries, Gilead's price tag of $1000 a day or $84,000 for a 12 week course will put treatment out of reach for most patients.
If the challenge is successful it would allow Indian companies to produce generic versions of Sofosbuvir and could be the first step toward making the treatment available to other low and middle income countries.
In recent years India have successfully battled high cost pharmaceutical patents using the Trade-Related Aspects of Intellectual Property (TRIPS) section of the 1994 World Trade Agreement, including compulsory licencing where the price of the product was too high to enable reasonable access for all who needed the medicine.
An application for a compulsory licence can be made by any person within a signatory country, including the UK, from 3 years of the granting of a patent.
The US Preventive Services Task Force has said that those in high risk groups ought to be tested for Hepatitis B in a draft recommendation. If approved, it would mainly apply to those born in countries where Hepatitis B prevalence was higher than 2%. However, it would also apply to people born in the US who were not vaccinated as infants but whose parents come from regions of high prevalence.
Those in other high risk groups including those who are HIV positive, injection drug users, men who have sex with men, people with a weakened immune system and those undergoing treatment for kidney failure.
The task force said that there was convincing evidence that Hepatitis B treatment improved intermediate patient outcomes including virologic improvement or clearance of the HBV e antigen (HBeAg) and moderate evidence that it reduced the risk of liver cancer.
In 2004 the task force rejected the idea of screening the general population arguing that the potential benefits were smaller than the risks. The US CDC and American Association for the Study of the Liver Diseases have both recommended screening for HBV infection in high risk groups.
Research published online in Biomed Central has shown that Hepatitis B infection up-regulates the microRNA-181a gene, inhibiting the E2F5 protein (which represses the cell cycle) allowing cells to proliferate - increasing the likelihood of cancer. They also found that HBV itself could cause repression of E2F5. They identified that microRNA-181a positive cells created bigger tumours than microRNA-181a negative cells when injected into mice.
The researchers concluded that HBV repressed E2F5 expression, in part by upregulating microRNA-181a. Up-regulation of microRNA-181a by Hepatitis B in hepatoma (hepato cancerous cells) may contribute to the progression of hepatocellular carcinoma (liver cancer) by targeting E2F5 cells, suggesting that microRNA-181a plays a signifcant role in the development of liver cancer.
Studio 13 and the sexual health and viral hepatitis service at Woolmanhill Hospital are now closed. These services have now transferred over to the newly opened Aberdeen Community Health and Care Village, 50 Frederick Street, Aberdeen, AB24 5HY. This new facility now deals with all sexual health testing and treatment as well as testing and treatment for Hepatitis C, and vaccination, testing and treatment for Hepatitis B.
If you would like to make an appointment call 0845 337 99 00.