Over one million people treated for hepatitis C in low- and middle-income countries Over one million people in low- and middle-income countries
have been treated for hepatitis C with direct-acting antivirals in the past two
years, the World Health Organization (WHO) said this week in its Global Report on Access to Hepatitis C
Treatment. Around two-thirds of those treated are in Egypt.
Argentina, Brazil, Georgia, Indonesia, Morocco, Nigeria,
Pakistan, the Philippines, Romania, Rwanda, Thailand and Ukraine have also made
important progress towards providing wider access to hepatitis C treatment, the
WHO report shows.
The report also shows that the price of hepatitis C
treatment has fallen most sharply in countries where generic competition is
possible. The report outlines the options available to countries to improve
access to hepatitis C treatment including: - price negotiations, price controls and price
transparency
- competitive tendering
- patent oppositions
- voluntary licensing
- compulsory licensing.
FDA hepatitis B reactivation warning, and hepatitis B testing for people taking hepatitis C treatment People considering direct-acting antiviral (DAA) therapy for
hepatitis C should first be tested for hepatitis B virus (HBV) and monitored
throughout therapy, as elimination of hepatitis C virus (HCV) can lead to HBV
reactivation and worsening of liver disease, according
to recent updates to American and European hepatitis C treatment guidelines.
On 4 October the US Food and Drug
Administration (FDA) issued a new safety warning about the risk of HBV
reactivation in people treated with DAAs, which in a few cases has led to
serious liver problems or death.
An FDA review identified 24 confirmed cases of HBV
reactivation – either reported to the agency or described in published
literature – in people with HBV/HCV co-infection treated with DAAs between November
2013 and July 2016. HBV reactivation usually occurred within 4 to 8 weeks
(average 52 days) after starting DAA therapy, and was seen in people with both
detectable and undetectable HBV DNA at baseline.
Updated American and European guidelines now recommend
testing for HBV with HBsAg, anti-HBs and anti-HBc, and those who are antigen or
anti-HBc antibody positive should also have an HBV DNA viral load test to see
if the virus is actively replicating.
Panels from the American Association for the Study of Liver Diseases (AASLD)/Infectious Diseases Society of America (IDSA) and the European Association for the Study of the Liver (EASL) both recommend that people who
meet criteria for treatment of active HBV infection should start
nucleoside/nucleotide antivirals such as entecavir (Baraclude) or
tenofovir (Viread) at the same time as – or before – initiating
hepatitis C DAA therapy.
People with low or undetectable HBV DNA levels should be
monitored at regular intervals during hepatitis C treatment and post-treatment
follow-up to check for HBV reactivation, and started on hepatitis B antivirals
if they meet treatment criteria.
Hepatitis B elimination Hepatitis B virus (HBV) could be eliminated as a global health
threat with a scale-up of vaccination coverage, enhanced efforts to prevent
vertical (mother-to-child) transmission and expansion of testing and treatment,
according to
a modelling study published in The Lancet Infectious Diseases. With these
interventions, incidence of new chronic infections could be reduced by 90% and
mortality rates by two-thirds between 2015 and 2030. HBV-related mortality
could be eliminated in Western Europe as soon as 2017 but it would take until
2090 to achieve this goal in sub-Saharan Africa. The total cost of the strategy
would be approximately $88 billion, but this would fall if a cure were
developed.
"Maintenance of a business as usual approach will not end the
epidemic and will lead to 17 million avoidable deaths over the next 15 years,"
comment the authors. "A comprehensive and ambitious package of interventions
that tackle prevention and treatment could lead to a 90% reduction in incidence
of new chronic infections and a 65% reduction in worldwide mortality by 2030."
European action plan for the health sector response to viral hepatitis Image credit: Image by ECDC, European Centre for Disease
Prevention and Control.
States in the European Region adopted
a World Health Organization (WHO) action plan for the health sector response to viral
hepatitis in September 2016.
The plan sets the ambitious goal of eliminating viral
hepatitis as a public health threat in the Region by 2030. This is to be achieved
by reducing new infections and deaths from viral hepatitis and its
complications, and ensuring equitable access to recommended preventive,
testing, care and treatment services for all. It proposes priority actions for
Member States, accompanied by supporting actions for WHO, in five strategic
directions: information for focused action, interventions for impact,
delivering for equity, financing for sustainability and innovation for
acceleration.
Commenting
on the goals set out in the action plan, the European Centre for Disease
Prevention and Control (ECDC) emphasises the importance of national testing and
screening programmes to identify people with the infection and improve estimates of
prevalence. Making testing available to populations at higher risk of viral
hepatitis, especially people who inject drugs and migrants from countries with
a high burden of viral hepatitis, will be especially important.
Larger-scale treatment access is also essential, not just to
reduce the burden of disease and death but also to limit transmission. Public
Health England (which is not responsible for providing treatment) notes
that although deaths due to hepatitis C-related end-stage liver disease or
liver cancer fell by 11% in 2015 in England and Wales, probably due to
targeting treatment at those with advanced liver disease, treatment needs to be
much more widely available to reduce transmission.
Reinfection risk Reinfection with the hepatitis C virus (HCV) after successful treatment has been
raised as a concern regarding treatment of people who inject drugs and men who
have sex with men. A
recent European study found that a quarter of men who have sex with men
cured with a 12-week regimen of pegylated interferon and ribavirin were
subsequently reinfected at least once.
Findings presented at the 5th International Symposium on
Hepatitis Care in Substance Users (INHSU 2016) in September showed that approximately
4% of people who took part in the C-EDGE CO-STAR study were reinfected with HCV
within 24 weeks of achieving an undetectable viral load on treatment. The
C-EDGE CO-STAR study recruited people who had a history of injecting drugs and
who were currently receiving opioid substitution therapy. People were not
excluded from the study if drug testing showed evidence of illicit drug use
during the trial. Participants received a 12-week course of treatment with
grazoprevir/elbasvir (Zepatier)
either immediately or after a 12-week delay.
Six reinfections were detected. These were distinguished
from viral rebound by checking whether the rebounding virus was genetically
different from the virus present before treatment. In three cases reinfection
was cleared spontaneously, without treatment. The researchers calculated that
the reinfection rate was 4.6 per 100 person-years of follow-up, and the rate of
chronic reinfection requiring treatment was 3%.
The rate seen in this study was fairly similar to rates seen
in previous studies.
Dr Håvard Midgard of Akershus University, Oslo, stressed to
the conference the importance of acknowledging the occurrence of HCV
reinfection without stigma and discrimination, which could drive people away
from care. Education and counselling about the possibility of reinfection are
needed, as are ongoing post-treatment surveillance and harm reduction efforts.
Mortality risk after SVR in Scotland Direct-acting antiviral therapy or interferon-based therapy
eliminates hepatitis C infection and has been shown to reduce liver-related and
all-cause mortality. A new study raises the question whether successful
treatment also reduces the risk of death in older people with advanced liver
disease or people with heavy drug/alcohol use.
A
study of a large population of people in Scotland who received treatment
with interferon-based therapy and who achieved sustained virologic response (SVR)
between 1996 and 2011 has shown that factors unconnected with the liver damage
caused by hepatitis C infection may be the most important causes of death after
treatment.
Hepatitis C infection is strongly associated with a history
of injecting drug use in Scotland. Alcohol consumption is a major cause of
liver disease in Scotland regardless of hepatitis C virus infection.
The study of 1824 people found that the risk of death
remained approximately twice as high in those cured as in the general
population during the post-treatment follow-up period. Although liver cancer
accounted for approximately a quarter of all deaths, drugs contributed to death
in 42% of people, and were even more likely to be the cause of death in
under-50s.
Having cirrhosis and being older before starting treatment
predicted an increased risk of death after being cured, but so did a history of
drug use, heavy alcohol use or hospitalisation for drug or alcohol
intoxication. The study authors say that their findings suggest the need for
greater attention to risk factors such as alcohol consumption, drug use and
resumption of injecting drug use in people at the time of hepatitis C
treatment, and in post-treatment follow-up. Better linkages between specialist
care and primary care in order to support people after being cured of hepatitis
C may be necessary to avoid drug and alcohol-related harm.
Shortening treatment Direct-acting antiviral therapy that combines drugs
targeting different steps of the hepatitis C virus (HCV) lifecycle – usually
taken for 12 weeks – is highly effective, but researchers continue to explore
new combinations that can be used for a shorter duration, thereby improving
convenience and reducing cost.
Two studies of shorter-duration treatment regimens were
presented last month at the New
Perspectives in Hepatitis C Virus Infection – The Roadmap for Cure
conference in Paris.
A
triple regimen containing two experimental hepatitis C drugs – AL-335 and
odalasvir – plus simeprevir taken for either 6 or 8 weeks cured all
participants with previously untreated genotype 1 hepatitis C who did not have
cirrhosis in a small study, while a dual regimen without simeprevir cured 90%.
A larger phase 2b trial (NCT02765490) evaluating
800mg AL-335 + 25mg odalasvir + 75mg simeprevir, all once-daily for 6 or 8
weeks, is expected to begin enrolment this autumn for treatment-naive and
treatment-experienced people without cirrhosis who have HCV genotypes 1, 2, 4,
5 and 6.
The combination is being developed by Janssen in partnership
with Achillion.
AbbVie
presented results of a study of a shortened treatment duration for people with genotype 1b using its '3D' regimen. The 3D regimen (marketed as Viekirax/Exviera
in Europe and Viekira Pak or Viekira XR in the US) consists of
the HCV protease inhibitor paritaprevir boosted with ritonavir, the NS5A
inhibitor ombitasvir and the NS5B polymerase inhibitor dasabuvir. The approved
indication in the EU and US is 12 weeks of the 3D combination alone for people
with HCV genotype 1b with or without liver cirrhosis, 12 weeks of 3D plus
ribavirin for people with harder-to-treat genotype 1a without cirrhosis and 24
weeks of 3D plus ribavirin for people with genotype 1a and compensated
cirrhosis.
AbbVie’s paritaprevir-based 3D regimen taken for just 8
weeks without ribavirin led to sustained virological response in 98% of
easier-to-treat people with HCV genotype 1b who did not
have cirrhosis, according to findings from the GARNET study.
Based on these findings, the hepatitis C
treatment recommendations newly released by the European Association for the Study of the Liver (EASL) now say that previously untreated people with
genotype 1b and without cirrhosis can be treated with the 3D regimen for either
8 or 12 weeks.
Access to treatment A Canadian
study of access to hepatitis C treatment shows that 85% of provinces and
territories apply restrictions on who can obtain hepatitis C treatment, with
almost all limiting access to those with F2 fibrosis or above, and denial of
access to sofosbuvir in Quebec province. The regional variations are due to the
lack of national strategy on hepatitis C control, say researchers from the
Canadian Network on Hepatitis C.
In the United States access to hepatitis C is partly
determined by whether an individual has private or public insurance coverage.
Yet, even for people with insurance coverage, co-payment charges can pose a
huge financial barrier to treatment. A study by one
clinic in New York state has found that patients were required by their
insurer to pay an average of $320 from their own pocket as co-payment for a
course of hepatitis C treatment. The study found huge variation between
insurers in co-payments and patients experienced long delays attempting to
negotiate assistance from pharmaceutical companies or reductions in
co-payments.
In England and Wales the
Hepatitis C Trust has decided to end a legal challenge to the restriction on
the number of people who will receive hepatitis C treatment. NHS England is
providing treatment for 10,000 people in the 2016/17 financial year with a
monthly limit on the number of patients each regional network of hospitals can
treat.
The decision follows the
rejection of a judicial review request by Hepatitis C Trust. In his ruling
Justice Blake said that the monthly limit was lawful and represented a rational
means of ensuring that treatment was available for people with the highest
unmet clinical need.
Next month: news coverage of The Liver Meeting 2016 Next month, infohep will be providing news coverage from The Liver Meeting 2016, organised by the American Association for the
Study of Liver Diseases (AASLD). The conference is taking place in Boston, USA from 11-15 November. We will be publishing news online and the November infohep bulletin will be dedicated to news from the conference.
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