Governments commit to eliminating viral hepatitis by 2030 at World Health Assembly

Image from the World Hepatitis Alliance video

On 28 May, 194 Member States made a historic commitment to eliminate viral hepatitis by 2030. At the 69th World Health Assembly, governments unanimously voted to adopt the first ever Global Viral Hepatitis Strategy, signalling the greatest global commitment in viral hepatitis to date.

The Strategy, developed by the World Health Organization (WHO), sets a goal of eliminating hepatitis B and C by 2030 and includes a set of prevention and treatment targets which, if reached, will reduce annual deaths by 65% and increase treatment to 80%, saving 7.1 million lives globally by 2030.

“The adoption of WHO Viral Hepatitis Strategy signals the first step in eliminating viral hepatitis, an illness which affects 400 million worldwide. We congratulate governments for showing great ambition,” Raquel Peck, CEO of the World Hepatitis Alliance said. “If governments remain committed, we will witness one of the greatest global health threats eliminated within our lifetimes.”

The World Hepatitis Alliance (WHA) and its 230 member states will continue to work to ensure that countries honour their commitment and that they implement measures to reach the targets. On World Hepatitis Day (28 July, 2016), WHA will launch NOhep, the first global movement aimed at galvanising support toward the elimination of viral hepatitis by 2030.  

The World Hepatitis Alliance has issued an animated video to showcase the importance of the World Health Organization's Global Viral Hepatitis Strategy. To watch the animated video click here.

Two new DAA combinations set for approval in the European Union

Two new combinations of direct-acting antivirals for treatment of hepatitis C virus (HCV) have received a positive review from the scientific committee of the European Medicines Agency, and should receive European Union marketing approval later this year.

Zepatier is a fixed-dose combination product containing elbasvir, an HCV NS5A inhibitor, and grazoprevir, an HCV NS3/4A protease inhibitor, and is indicated with or without ribavirin for treatment of chronic HCV genotype 1 or 4 infection in adults. Zepatier is manufactured by Merck Sharp & Dohme (MSD). Full details of the indication for prescribing will become available at the time of marketing approval.

Epclusa is a fixed-dose combination product containing the nucleotide analogue polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir. Epclusa has been approved for use in genotypes 1-6 with or without ribavirin. Epclusa is manufactured by Gilead Sciences. Full details of the indication for prescribing will become available at the time of marketing approval.

The European Association for the Study of the Liver (EASL) is due to issue new hepatitis C treatment guidelines that will include the two new combinations at a special meeting in September 2016.

Hepatitis B treatment

Hepatitis B research presented at the 2016 International Liver Congress focused on optimising antiviral treatment for hepatitis B and new approaches to treatment of hepatitis B.

Nucleoside/nucleotide analogues like tenofovir can effectively suppress hepatitis B virus (HBV) replication during treatment, but they usually do not lead to a cure – as indicated by hepatitis B surface antigen (HBsAg) loss and development of anti-HBs antibodies – so long-term therapy is generally needed.

Gilead Science’s tenofovir disoproxil fumarate (Viread) is one of the most effective antiviral drugs for hepatitis B and one of the most widely used antiretrovirals for HIV. It is generally considered safe and well tolerated, but it can cause a small amount of bone loss soon after starting therapy and can lead to kidney problems in susceptible people.

Tenofovir alafenamide (TAF) is a new pro-drug formulation that produces high levels of the active drug (tenofovir diphosphate) in hepatocytes and CD4 T-cells with smaller doses than tenofovir disoproxil fumarate (TDF), which means lower concentrations in the blood and less drug exposure for the kidneys, bones, and other organs and tissues.

Results of two phase III studies presented at last month’s International Liver Congress showed that TAF is as potent against HBV as the current TDF formulation, but with fewer detrimental effects on bone and kidney biomarkers.

A retrospective study conducted in South Korean hepatitis B 'e' antigen (HBeAg) positive people with early hepatitis B infection, no cirrhosis, moderate liver enzyme elevations but high viral load, found that early treatment in this patient population was associated with a two-thirds reduction in the risk of cirrhosis, an 80% reduction in the risk of developing hepatocellular carcinoma and an 86% reduction in the risk of death during a six-year follow-up period.

The investigators concluded that treating hepatitis B in people with high viral load but little evidence of liver inflammation – so-called immune-tolerant patients – resulted in improved survival and cancer prevention, and may be cost-effective in some countries.

Researchers also discussed the prospects for curing hepatitis B infection. Hepatitis B presents significant challenges to researchers who hope to develop a cure, because the virus inserts itself into the nucleus of cells, where a form called cccDNA maintains persistent infection.

Curative approaches are likely to combine antiviral treatment to suppress virus production and immunological treatment to improve the ability of the immune system to identify and kill HBV-infected cells. It is unknown whether total clearance might be possible, or whether a 'functional' cure, in which HBV replication can be controlled without elimination, is a more realistic prospect.

An experimental drug, NVR 3-778, being developed by Novira Therapeutics, is a first-in-class small molecule that directly targets the HBV core protein, which plays key roles in viral replication and persistence. The protein is responsible for assembly of the viral nucleocapsid and enables replenishment of HBV cccDNA. Depletion of HBV cccDNA is likely to prove critical in attempts either to cure hepatitis B completely or to achieve a functional cure, whereby hepatitis B virus replication is permanently controlled without treatment.

NVR 3-778 appears to inhibit HBV by multiple mechanisms, offering a new approach to hepatitis B treatment. Current therapy using nucleoside/nucleotide analogue antivirals or interferon can suppress HBV replication long-term, but seldom leads to a cure as indicated by hepatitis B surface antigen (HBsAg) loss and development of anti-HBs antibodies.

An early phase 2 trial testing various doses of NVR 3-778 in combination with pegylated interferon found that the experimental drug produced substantial reductions in HBV DNA after one month of treatment. Further studies will investigate the effect of longer treatment courses and use in combination with first-line HBV treatments such as tenofovir and entecavir.

Hepatitis C burden of disease

The number of deaths due to hepatitis C is at an all-time high in the US and exceeds those attributable to 60 other infectious diseases including HIV and tuberculosis, according to new surveillance data released in May by the Centers for Disease Control and Prevention (CDC). However, a related Italian study found that hepatitis C patients who are successfully treated have a life expectancy similar to that of the general population.

The new preliminary CDC surveillance data show that there were 19,659 deaths associated with hepatitis C in 2014, up from 11,051 in 2003 – a 78% increase over the past decade. The hepatitis C death rate was especially high among people aged 55 to 64 years.

Access to hepatitis C treatment

Gilead has been granted a patent for its direct-acting antiviral sofosbuvir in India despite opposition by advocacy groups. The patent decision is unlikely to affect the price of sofosbuvir in India, where voluntary licensing and competition between generic manufacturers has brought the cost of the drug down to around $350 for a three-month course of treatment. The decision will have a negative effect on access to low-cost generic versions of the drug in other countries because the only companies that will be permitted to manufacture sofosbuvir in India will be those which have negotiated a voluntary licence.

The terms of the voluntary licence prohibit exports of the drug to countries not covered by Gilead’s access scheme for lower-income countries, which means that middle-income countries will be unable to obtain the drug from Indian manufacturers. Manufacturers of active pharmaceutical ingredients (APIs) are also covered by voluntary licensing, and the patent decision will affect the ability of some Indian manufacturers to export active pharmaceutical ingredients for sofosbuvir to pharmaceutical companies in Argentina, Bangladesh, Egypt, Pakistan and Ukraine.

“Indian Patent Office’s decision to grant the patent on the base compound of sofosbuvir this week has provided Gilead with the tools to disrupt and stop future exports of the API from India, giving it significant control on the supply of API globally,” Leena Menghaney of MSF India said in Hindu Business Line.

Advocates in India have challenged the patent decision in the High Court.

HIV and hepatitis C

Approximately one-third of people with HIV have hepatitis C virus (HCV) co-infection. Individuals with co-infection experience more rapid liver disease progression on average than people with hepatitis C alone, and in the era of interferon-based therapy they did not respond as well to treatment. But some recent studies have suggested that this disparity in treatment response does not apply to interferon-free direct-acting antiviral (DAA) regimens.

Two large studies presented at the 2016 International Liver Congress offered contradictory evidence regarding the effect of HIV infection on responses to DAA treatment.

On the one hand, a study of 9604 people receiving care through the Department of Veterans Affairs in the United States found no significant difference in responses to DAA treatment between people with co-infection and those without. Cure rates exceeded 88%.

On the other hand, a Spanish study of 1276 people, almost half of whom had HIV and HCV co-infection, found that people with co-infection were less likely to be cured after a course of DAA treatment (95% versus 89%) and more likely to experience viral relapse.

Experimental treatment for cirrhosis

Several pharmaceutical companies are working to develop treatments to improve cirrhosis, not just for people with viral hepatitis but also for those with cirrhosis due to alcoholic liver disease. Cirrhosis of the liver represents a state of severe inflammation and liver cell damage. Liver damage due to viral hepatitis may not be entirely reversible and in some cases people with cirrhosis may continue to experience progression of liver disease despite being cured of hepatitis C.

Emricasan (IDN-6556) is a first-in-class pan-caspase inhibitor that has been shown to decrease biomarkers of apoptosis and inflammation in people with liver disease. Caspases are protease enzymes that play a role in apoptosis (programmed cell death) and inflammation, contributing to progression of chronic liver disease.

A phase 2 trial of emricasan in 74 people with compensated cirrhosis presented at the International Liver Congress found that three months of treatment with emricasan reduced liver inflammation but did not have a significant effect on MELD score, which measures the overall health of the liver and is used to prioritise people for liver transplant.

Head and neck cancers

Infection with hepatitis C virus (HCV) is associated with an increased risk of head and neck cancer, investigators from the United States report in the Journal of the National Cancer Institute. The risk of certain cancers was especially high for people who also had human papillomavirus (HPV).

The most common forms of head and neck cancers are cancers of the mouth, pharynx and larynx. These cancers are most commonly caused by smoking, high alcohol consumption or HPV. The study found that after adjusting for other risk factors oropharyngeal cancers were twice as common in people with HCV infection. HCV was associated with an increased risk of HPV-related cancers but not non-HPV-related tumours.

The study investigators say that oncologists treating patients with head or neck cancers should consider testing patients for HCV to enable early identification and linkage to care for this disease to prevent progression of underlying liver disease.

The 5th International Symposium on Hepatitis Care in Substance Users

The 5th International Symposium on Hepatitis Care in Substance Users is being held in Oslo, Norway from 7-9 September 2016.

The symposium is the leading international conference focused on the management of hepatitis among substance users and attracts health professionals, researchers, community organisations, people who use drugs and policy makers.

This year’s conference focuses on issues related to:

  • Epidemiology and public health
  • Treatment and care
  • Access and implementation.

Earlybird registration closes on 17 June.

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.