Progress towards elimination of hepatitis C

Only a handful of countries are on course to achieve the World Health Organization (WHO) target of eliminating hepatitis C virus (HCV) as a major public health concern by 2030, according to a study published in the Journal of Virus Eradication.

In 2016, WHO set the target of treating 80% of people with HCV by 2030 to reduce the rate of new infections by 90% in that year. If achieved, this would eliminate HCV as a major public health concern.

This is potentially achievable as treatment with direct-acting antivirals (DAAs) can cure at least 90% of people. It has already been shown that increasing treatment rates can lead to lower infection rates.

Investigators estimated progress towards elimination by examining 2016 data on rates of cure after therapy with DAAs, HCV-related deaths and new HCV infections.

An annual net cure rate of 7% would be needed to meet the WHO target of eliminating HCV as a major public health concern by 2030.

An overall reduction in prevalence of 0.71% was observed in the 91 countries included in the study, and global prevalence fell by just 0.4%.

Regionally, net cure rates ranged from 7% in North America to 4.3% in Central and Eastern Europe.

The investigators believe their findings have a number of important policy implications:

  • Current treatment rates are not high enough. More, therefore, needs to be done to make DAAs more affordable.
  • Further resources need to be devoted to HCV diagnosis and prevention.
  • Investment is needed in health service capacity in low- and middle-income countries so they can cope with the intensive healthcare monitoring needed during DAA therapy.

“The inflated prices of DAAs pose a barrier to treatment in many countries,” conclude the authors.

Global Burden of Disease study shows viral hepatitis causes more deaths than HIV or TB

According to the Global Burden of Disease study released in September, deaths caused by viral hepatitis have surpassed all chronic infectious diseases including HIV, malaria and tuberculosis (TB).

The study illustrates that in 2016, the total deaths caused by viral hepatitis, including liver cancer, acute cases, cirrhosis, hepatitis A, B, C, D and E, account for 1.34 million deaths globally, exceeding TB (1.2 million), HIV (1 million) and malaria (719,000).

Debate: Not all drug preparation equipment may contain infectious HCV

Needle exchange and distribution programmes that provide sterile syringes have substantially reduced transmission of blood-borne diseases including HIV, hepatitis B and hepatitis C among people who inject drugs.

These viruses – especially hepatitis C virus (HCV), which is able to live outside the body longer than HIV – can potentially be transmitted through any item that comes into contact with blood. Most harm reduction programmes therefore offer drug preparation equipment such as cookers (bottle caps or other small receptacles used to mix drugs), filters (cotton or other material used to strain a drug solution) and clean water, in addition to syringes.

According to a study recently published in The Journal of Infectious Diseases, sharing other drug preparation paraphernalia such as cookers may not significantly contribute to HCV transmission among people who inject drugs. 

In an experiment designed to mimic real-world injection practices, the researchers were unable to detect HCV in cookers, and seldom able to do so in filters, after these items were exposed to the contents of syringes known to be contaminated with the virus.

This contradicts previous studies, which have suggested that cookers and filters can transmit HCV. For example, a meta-analysis looking at HCV incidence in people who inject drugs found that sharing of drug preparation containers, of filters, of water or of any combination of these items was strongly associated with an increased risk of acquiring HCV, even if people did not share needles or syringes.

A study carried in Scotland between 2008 and 2010, which tested users of needle and syringe programmes for recent HCV infection, found that sharing containers or filters – but not water – was associated with an increased risk of acquiring HCV, even if people did not share needles or syringes.

A previous German study found that in laboratory conditions, HCV survived in water at room temperature at infectious levels for 21 days. The researchers also found that infectious quantities of HCV could survive in the water container, even if the water was emptied from it. Infectious quantities of HCV could also be found in filters 48 hours after they had been exposed to the virus.

However, it is unclear if HCV infections linked to sharing paraphernalia reflect contamination of the paraphernalia itself, or if the virus spreads through syringes when drugs are shared. To test which of these routes of transmission is more plausible, researchers from Yale University designed an experiment to mimic real-world injection practices.

Often people will jointly obtain a bag of heroin, for example, which one individual mixes in his or her syringe, and the solution is then portioned out to the others. Older and more experienced people – who have had more opportunities to acquire HCV – may be more likely to do this drug preparation. When the prepared drug is drawn up into a syringe that has already been used, it could be contaminated by HCV that remains in the syringe or the needle.

The residual contents of ‘input’ syringes known to be contaminated with HCV were passed through cookers and filters and transferred into a second ‘receptive’ syringe. The study tested syringes with detachable needles and those with fixed needles (e.g. disposable insulin syringes). All items were then tested for the presence of infectious HCV.

HCV could not be recovered from cookers, regardless of cooker design or the type of syringe used.

HCV was seldom found in filters, but this happened more often when detachable needles were used compared with fixed needles. Finally, HCV was about twice as likely to be detected in the receptive syringe if the input syringe had a detachable instead of a fixed needle.

The authors say that the reason their results differ from those of a previous laboratory experiment could be because that experiment used 100 times the amount of HCV found in syringes in real-world drug injecting conditions.

However, the findings do not rule out the possibility that both drug sharing and the sharing of drug preparation equipment could each independently lead to HCV transmission.

The researchers suggested that in light of these results, syringe access programmes should not spend their limited funds on cookers and filters, but should instead focus their efforts on distributing more syringes with fixed needles.

Daniel Raymond of the Harm Reduction Coalition said that at a time when the demand for harm reduction services is growing faster than funding, "any discussions or decisions about scaling back on purchasing or provision of cookers, etc, should be driven by people who inject drugs and program participants, who may place values on these supplies independent of their utility in HCV prevention."

Women who inject drugs at greater risk of HCV

A newly published analysis examining data from more than 1800 people suggests that women who inject drugs have a 38% higher risk of contracting hepatitis C virus (HCV) than their male counterparts. Interestingly, while sharing of syringes and other injection equipment is a significant risk factor for HCV, differences in these behaviours did not account for the higher risk among women. The research was funded by the National Institute on Drug Abuse (NIDA), part of the US National Institutes of Health.

Nivolumab (Opdivo) approved for hepatocellular carcinoma treatment in the United States

The US Food and Drug Administration last week granted accelerated approval for nivolumab (Opdivo), an immunotherapy drug that restores T-cell anti-tumour activity, for people with hepatocellular carcinoma (HCC).

Nivolumab is a human monoclonal antibody that interferes with PD-1 (programmed death protein 1), a cell-signalling molecule on T-cells. PD-1 regulates immune responses by suppressing excessive immune activation. Some cancers can hijack PD-1 to disable immune responses against them. By blocking PD-1, checkpoint inhibitors like nivolumab can restore T-cell activity against cancer cells.

Approval was supported by findings from the CheckMate 040 study presented at The Liver Meeting 2016, organised by the American Association for the Study of Liver Diseases. While response rates in this study were not particularly high, there are few good existing options for people with this type of cancer, especially those with recurring disease.

The study showed that 14% of people who had experienced tumour progression despite treatment with sorafenib showed some degree of response, or tumour shrinkage, when treated with nivolumab.

Bristol-Myers Squibb has decided to delay seeking a European Union licence for the use of Opdivo for HCC until it has data from further clinical trials. A licensing application was withdrawn in July 2017 after the scientific committee of the European Medicines Agency (EMA) concluded that the lack of data from studies comparing nivolumab to other therapies made it impossible to determine whether the benefits of treatment with the drug outweighed the risks.

Janssen halts hepatitis C drug research

Janssen, a Johnson & Johnson company, announced in September that it will stop development of a new hepatitis C drug combination consisting of AL-335, odalasvir and simeprevir. Janssen had licensed the development rights to AL-335 and odalasvir from Achillion. Janssen decided to stop development because available pangenotypic drug combinations cure over 95% of hepatitis C infections and it was hard to see how another combination could improve on those results.

Janssen will continue to market simeprevir (Olysio), a hepatitis C virus protease inhibitor.

Next month: news coverage of The Liver Meeting 2017

Next month, infohep will be providing news coverage from The Liver Meeting 2017, organised by the American Association for the Study of Liver Diseases (AASLD). The conference is taking place in Washington DC, USA from 20-24 October.

We will be publishing news online and the October infohep bulletin will be dedicated to news from the conference.

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