WHO guidelines update The World Health Organization (WHO) has
issued updated recommendations on the treatment of hepatitis C. The new
recommendations urge the use of direct-acting antivirals, not interferon-based
regimens, and recommend against the use of the first-generation protease
inhibitors boceprevir and telaprevir on account of the high rate of adverse
events in people treated with these drugs.
The new recommendations set out an updated list of preferred
regimens to be used in the treatment of genotypes 1-6.
WHO arrived at its recommendations by carrying out
meta-analyses and systematic reviews to assess the comparative efficacy and
safety of regimens, and also rated their acceptability to patients according to
whether they contained drugs that cause frequent adverse events (interferon and
ribavirin), dosing frequency and potential for drug-drug interactions.
The recommended regimens are intended to simplify treatment
and reduce the risk of treatment discontinuation due to adverse events.
Genotyping will still be necessary in order to identify which regimen is
suitable. Patients without
cirrhosis: WHO preferred regimens
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Daclatasvir/sofosbuvir
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Ledispasvir/sofosbuvir
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Sofosbuvir/ribavirin
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Genotype 1
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12 weeks
|
12 weeks
|
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Genotype 2
|
|
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12 weeks
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Genotype 3
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12 weeks
|
|
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Genotype 4
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12 weeks
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12 weeks
|
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Genotype 5
|
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12 weeks
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Genotype 6
|
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12 weeks
|
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Patients with
cirrhosis: WHO preferred regimens
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Daclatasvir/
sofosbuvir
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Daclatasvir/
sofosbuvir
/ribavirin
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Ledipasvir/
sofosbuvir
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Ledipasvir/
sofosbuvir/
ribavirin
|
Sofosbuvir/
ribavirin
|
Genotype 1
|
24 weeks
|
12 weeks
|
24 weeks
|
12 weeks
|
|
Genotype 2
|
|
|
|
|
16 weeks
|
Genotype 3
|
|
24 weeks
|
|
|
|
Genotype 4
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24 weeks
|
12 weeks
|
24 weeks
|
12 weeks
|
|
Genotype 5
|
|
|
24 weeks
|
12 weeks
|
|
Genotype 6
|
|
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24 weeks
|
12 weeks
|
|
WHO alternative
regimens: patients without cirrhosis
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Simeprevir/
sofosbuvir
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Daclatasvir/
sofosbuvir
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Ombitasvir/
paritaprevir/
ritonavir/
dasabuvir
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Ombitasvir/
paritaprevir/
ritonavir/
ribavirin
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Sofosbuvir/
pegylated interferon/
ribavirin
|
Genotype 1
|
12 weeks
|
|
12 weeks
|
|
|
Genotype 2
|
|
12 weeks
|
|
|
|
Genotype 3
|
|
|
|
|
|
Genotype 4
|
12 weeks
|
|
|
12 weeks
|
|
Genotype 5
|
|
|
|
|
12 weeks
|
Genotype 6
|
|
|
|
|
12 weeks
|
WHO alternative
regimens: patients with cirrhosis
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Simeprevir/
sofosbuvir
|
Simeprevir/
sofosbuvir/
ribavirin
|
Daclatasvir/
sofosbuvir
|
Sofosbuvir/
pegylated interferon/
ribavirin
|
Genotype 1
|
24 weeks
|
12 weeks
|
|
|
Genotype 2
|
|
|
12 weeks
|
|
Genotype 3
|
|
|
|
12 weeks
|
Genotype 4
|
24 weeks
|
12 weeks
|
|
|
Genotype 5
|
|
|
|
12 weeks
|
Genotype 6
|
|
|
|
12 weeks
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Counterfeit Harvoni in Europe Counterfeit packs of the
preparation Harvoni have been
discovered in Israel. The plastic bottles, which originate in India, were
imported via a Swiss trading company and contain white instead of genuine
yellow film-coated tablets. The Swiss Agency for Therapeutic Products,
Swissmedic, is working with other European authorities to establish whether Harvoni packs with counterfeit contents
have also been imported into other countries.
Swissmedic
warns that medicines ordered over the internet may
not contain the active ingredient as advertised. This risk is especially high
where a normally expensive branded product is being offered at a very low
price.
It is important to make a
distinction between counterfeits of branded products – such as Harvoni – and generic versions of the
same product produced under voluntary licence in India. The same potential exists
for producing counterfeit versions of legitimate generic drugs as it does for
originator products such as Harvoni.
Where products are produced
under voluntary licence or by generic manufacturers without a voluntary licence
the product must contain the active ingredients and manufacturing processes
must pass inspection in order for a product licence to be granted in the
country where it is manufactured. A stringent product review by the World
Health Organization (WHO), called prequalification, is the best guarantee that
generic versions of direct-acting antivirals contain the correct levels of active
ingredient. To date no direct-acting antiviral product produced by a generic
manufacturer has been prequalified by WHO, although several are being marketed
in India.
The rules regarding
importation of generic versions of branded products differ between countries
and it is essential that anyone planning to pay for these products checks their
local customs regulations before paying to import direct-acting antivirals.
Hepatitis B prevalence Although nearly 70 million people in the US have been
vaccinated against hepatitis B virus (HBV), there are still 847,000 people with
evidence of infection, about 400,000 of whom are Asian, according to the latest
National Health and Nutrition Examination Survey (NHANES) results published in
the February
edition of Hepatology.
An effective HBV vaccine became available in the early 1980s
and is now part of the routine childhood immunisation series in many countries.
Hepatitis B can be treated with antivirals or interferon, but these usually do
not lead to a cure. Over years or decades, hepatitis B can cause serious liver
disease including cirrhosis and hepatocellular carcinoma.
Chronic hepatitis B prevalence in the US is affected by the
shrinking number of young people who are susceptible to infection as
vaccination coverage rises. It is estimated that about 25% of the overall US
population – but 90% of young children – have vaccine-induced immunity, the
authors noted as background. However, this is offset by people immigrating from
countries where the virus is endemic. An estimated 3.9 million foreign-born
people from these countries currently reside in the US, and they may account
for as many as 70% of all hepatitis B cases.
These findings indicate both the success and the limits of
hepatitis B vaccination programmes. A long-term international increase in migration
means that national policies on vaccination will not be adequate to reduce the
global burden of hepatitis B – ensuring that all countries are able to
implement successful hepatitis B vaccination programmes is the only way to
ensure that the powerful tool of vaccination can limit the burden of hepatitis
B for each country.
HIV and HCV co-infection An estimated 2.3 million people
living with HIV are co-infected with hepatitis
C virus (HCV) globally, a new study by the University of
Bristol and the
London School of Hygiene & Tropical Medicine has found.
Of these, more than half, or 1.3
million, are people who inject drugs. The study also found that
HIV-positive people are on average six times more likely than HIV-negative
people to have hepatitis C, pointing to a need to improve integrated HIV/HCV
services.
Globally, there are 37 million
people living with HIV, and around 115 million people with chronic HCV infection. This study is the first systematic review of studies reporting the
prevalence of co-infection.
Treatment of acute HCV infection Jürgen Rockstroh presenting at CROI 2016. Photo by Liz Highleyman, hivandhepatitis.com
In the
era of interferon-based therapy, hepatitis C was easier to eliminate
in people recently infected with the virus, if treatment was started within
weeks of hepatitis C becoming detectable. Therefore treatment during
acute infection has been considered to give the best chance of being cured of
hepatitis C.
The introduction of direct-acting antivirals has improved
the chances of cure for everyone, and no regimens are approved specifically for
use in the treatment of acute infection. It is unclear whether treatment could
be given for a shorter period during acute infection or with fewer drugs.
Several studies in people with hepatitis C
co-infection presented at recent conferences provide more information on the subject.
A 12-week combination of sofosbuvir (Sovaldi) and
ribavirin cured more than 90% of hepatitis C in people living with HIV and
acute hepatitis C virus (HCV) infection in a small study, but a similar trial
of the same regimen saw a much higher relapse rate, according to a pair
of presentations at the 2015 AASLD Liver Meeting in November. Both studies
were small and the reasons for the lower response rate in one study are
unclear.
An interferon- and ribavirin-free regimen of
sofosbuvir/ledipasvir (Harvoni) taken for just 6 weeks was enough to
cure hepatitis C in HIV-positive people with recent HCV
infection if their HCV viral load was low, but those with high HCV levels may
need longer treatment, according to study findings presented at the Conference
on Retroviruses and Opportunistic Infections (CROI 2016) last month in Boston.
Presenter Jürgen Rockstroh of the University of Bonn predicted that HCV viral
load will become a key factor when making decisions about treating acute
hepatitis C.
Genotype 4 Imam Waked presenting at CROI 2016. Photo by Liz Highleyman, hivandhepatitis.com Genotype 4 hepatitis C is the predominant form of
hepatitis C in Egypt and much of the Middle East. The NS5A inhibitor
ravidasvir, formerly known as PPI-668, is being co-developed by Pharco
Pharmaceuticals in Egypt and Presidio Pharmaceuticals in San Francisco, as a
treatment for genotype 4 infection in combination with sofosbuvir.
Sofosbuvir plus ravidasvir, with or without ribavirin, cured
95 to 100% of people with hepatitis C virus (HCV) genotype 4, the most common
type in Egypt, according to findings from the Pyramid 1 study presented at the Conference
on Retroviruses and Opportunistic Infections (CROI 2016) last month in Boston.
Treatment was generally safe and well-tolerated. A minority
of patients reported adverse events such as headaches, abdominal discomfort,
fatigue, itching or diarrhoea. One patient discontinued treatment due to a
serious adverse event (bradycardia = slow heartbeat), which resolved after the
medication was stopped.
HCV and lymphoma Hepatitis C virus (HCV) infection doubles the relative risk
of cancers of the lymphoid system, according to Taiwanese
research published in Hepatology. Investigators compared the
incidence of lymphoma-like cancers between matched people with and without HCV;
after taking into account all potential confounders, HCV infection was
associated with a twofold increase in the risk of any lymphoid cancer, with a
similar increase in the risk of non-Hodgkin lymphoma (NHL).
Lymphoid cancers include non-Hodgkin lymphoma, Hodgkin
lymphoma, multiple myeloma, acute lymphoblastic lymphoma and chronic
lymphocytic leukaemia.
Screening for hepatitis C Screening emergency department patients for hepatitis C virus
(HCV) based on birth cohort and risk profile might not be enough, and a quarter
of undiagnosed infections would remain undetected, according to United States research
published in the online edition of Clinical Infectious Diseases. The authors therefore recommend that emergency
departments should expand their screening to more patients, even if they are
outside of the current Centers for Disease Control and Prevention (CDC) testing recommendations.
It has been
estimated that at least 2.2 to 3.2 million individuals in the United States are
living with HCV infection and that the majority of these patients are unaware
of their infection status. HCV prevalence is especially high in the 1945-65
birth cohort, often called the 'baby boomer' generation. Therefore in 2012 the
CDC issued guidance recommending one-off HCV testing for all patients in this
age group. The guidelines also recommend the screening of patients considered
to be at high risk of HCV infection, including individuals with a history of
injecting drug use, people living with HIV, and recipients of blood
products.
Emergency
departments are an ideal venue for the implementation of expanded HCV
screening. They serve diverse populations and are often used as a healthcare
safety net, therefore treating patients who do not access other medical
providers. Emergency departments have also successfully implemented routine HIV
screening policies.
Upcoming event at ILC 2016: Transforming HCV Care Together At this month’s International Liver Congress
(ILC) 2016 in Barcelona, Spain, infohep is partnering with HCV stakeholders to
host a special session for patient advocates from across Europe and around the
world. Along with the European Liver Patients’ Association (ELPA), World
Hepatitis Alliance (WHA), the World Federation of Science Journalists (WFSJ), Deusto
Business School and with support from AbbVie, HCV stakeholders will convene for
an invitation-only event, 'Transforming HCV Care Together', to discuss
strategies to keep HCV high on the public and political agenda.
Attendees will learn about practical applications
for mobilising HCV efforts at the national level and beyond, hear from global
experts and patient advocates on new resources and best practices that could
effect change for HCV, connect with other attendees and discuss how to
prioritise the transformation of HCV care. The event will also feature a
discussion with leading health journalists, a national patient advocate and EU
policymaker on ways that stakeholders can better work together to effect change
and combat the disease.
Stay tuned for an update from the discussion and outcomes later this
month.
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