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

 

Daclatasvir/sofosbuvir

Ledispasvir/sofosbuvir

Sofosbuvir/ribavirin

Genotype 1

12 weeks

12 weeks

 

Genotype 2

   

12 weeks

Genotype 3

12 weeks

   

Genotype 4

12 weeks

12 weeks

 

Genotype 5

 

12 weeks

 

Genotype 6

 

12 weeks

 

Patients with cirrhosis: WHO preferred regimens

 

Daclatasvir/

sofosbuvir

Daclatasvir/

sofosbuvir

/ribavirin

Ledipasvir/

sofosbuvir

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

24 weeks

12 weeks

24 weeks

12 weeks

 

Genotype 5

   

24 weeks

12 weeks

 

Genotype 6

   

24 weeks

12 weeks

 

WHO alternative regimens: patients without cirrhosis

 

Simeprevir/

sofosbuvir

Daclatasvir/

sofosbuvir

Ombitasvir/

paritaprevir/

ritonavir/

dasabuvir

Ombitasvir/

paritaprevir/

ritonavir/

ribavirin

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

 

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

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.

Is this your copy of the infohep news bulletin?

Is this your copy of the infohep news bulletin, or did you receive it from a friend or colleague, or find it online?

You can sign up to receive this monthly email bulletin, free of charge, on our website, where you can also find an archive of all the infohep news bulletins.