News from the 2017 International Liver Congress

The annual meeting of the European Association for the Study of the Liver (EASL), also known as the International Liver Congress, took place in Amsterdam from 19-23 April.

You can find comprehensive reporting on the meeting at – and some of the highlights are below.

WHO Global Hepatitis Report 2017

New data from the World Health Organization (WHO) reveal that an estimated 325 million people worldwide are living with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. The WHO Global hepatitis report, 2017 indicates that the large majority of these people lack access to life-saving testing and treatment. As a result, millions of people are at risk of a slow progression to chronic liver disease, cancer, and death.

Viral hepatitis caused 1.34 million deaths in 2015, a number comparable to deaths caused by tuberculosis and HIV. But while mortality from tuberculosis and HIV has been declining, deaths from hepatitis are on the increase.

Approximately 1.75 million people were newly infected with HCV in 2015, bringing the global total of people living with hepatitis C to 71 million. This figure represents a substantial reduction in the global estimate.

The report notes that just 9% of all HBV infections and 20% of all HCV infections were diagnosed in 2015. An even smaller fraction – 8% of those diagnosed with HBV infection (1.7 million people) were on treatment, and only 7% of those diagnosed with HCV infection (1.1 million people) had started curative treatment during that year.

WHO’s Global hepatitis report, 2017 demonstrates that, despite challenges, some countries are taking successful steps to scale-up hepatitis services.

China achieved high coverage (96%) for the timely birth dose of HBV vaccines, and reached the hepatitis B control goal of less than 1% prevalence in children under the age of 5 in 2015. Mongolia improved uptake of hepatitis treatment by including HBV and HCV medicines in its National Health Insurance scheme, which covers 98% of its population. In Egypt, generic competition has reduced the price of a 3-month cure for hepatitis C, from US$900 in 2015, to less than US$200 in 2016. Today in Pakistan, the same course costs as little as US$100.

Improving access to hepatitis C cure received a boost at the end of March 2017, when WHO prequalified the generic active pharmaceutical ingredient of sofosbuvir. This step will enable more countries to produce affordable hepatitis medicines.

New hepatitis B clinical guidelines from EASL

EASL guidelines panel at the International Liver Congress 2017. Photo by Liz Highleyman,

The European Association for the Study of the Liver (EASL) presented revised clinical practice guidelines for the management of hepatitis B virus (HBV) infection – the first update since 2012 – during a special session at its International Liver Congress last week in Amsterdam. For the first time the guidelines include tenofovir alafenamide and present evidence about when and how to stop antiviral therapy.

The updated version reflects a better understanding of the natural history of hepatitis B. Experts now recognise that during the so-called ‘immune tolerant’ phase, people may experience liver disease progression and be at risk for liver cancer.

The guidelines recommend treatment for everyone with HBV DNA above 2000 IU/ml, elevated ALT, and at least moderate liver inflammation or fibrosis. In addition, people with cirrhosis should start treatment regardless of viral load (if detectable) or ALT level, while those with high HBV DNA (>200,000 IU/ml) and elevated ALT should start regardless of fibrosis stage.

The guidelines state that the treatment of choice is a potent nucleoside/nucleotide analogue with a high barrier to resistance. These include entecavir (Baraclude), tenofovir disoproxil fumarate (TDF) (marketed as Viread) and tenofovir alafenamide (TAF) (marketed as Vemlidy).

HCV reimbursement criteria in Europe

England, Malta, Slovakia, Hungary and Croatia have the tightest restrictions on who can receive direct-acting antiviral (DAA) treatment for hepatitis C, while France, Ireland, Portugal, Germany, Poland and the Netherlands are the least restrictive, research presented at the International Liver Congress in Amsterdam shows. The study looked at access arrangements in the European Economic Area (which covers the European Union, Switzerland, Norway and Iceland).

The researchers looked at national policies between November 2016 and February 2017 to check which patients were eligible to receive treatment with direct-acting antiviral combinations recommended in EASL’s 2016 hepatitis C treatment guidelines (all those products currently licensed in the European Union, plus the combinations of sofosbuvir and daclatasvir, and sofosbuvir and simeprevir).

The researchers also looked at whether restrictions were placed on access to treatment regarding drug and alcohol use, HIV co-infection or by prescriber type.

Drug and alcohol restrictions are common in Central Europe. Bulgaria, Croatia, Hungary, Poland and Slovakia place restrictions on access to hepatitis C treatment for active users of drugs or alcohol, as does Cyprus.

Direct-acting antivirals and liver cancer risk

Gregory Dore at the International Liver Congress 2017. Photo by Liz Highleyman,

People with hepatitis C who take treatment with direct-acting antivirals (DAAs) do not appear to have a higher risk of developing liver cancer compared to those treated with interferon, and the seemingly higher rates seen in some studies may be attributable to risk factors such as older age and more advanced liver disease, according to a set of studies presented last week at the International Liver Congress in Amsterdam.

At last year's EASL meeting, researchers reported the first data suggesting that people who achieve sustained response with DAAs might be at greater risk for liver cancer. Italian researchers reported that hepatitis C patients with cirrhosis who were treated with DAAs had a higher likelihood of developing liver cancer, but this was limited to recurrence in people with a prior history of hepatocellular carcinoma (HCC), the most common type of liver cancer. A Spanish study published in the October 2016 edition of Journal of Hepatology also saw a higher than expected rate of HCC recurrence.

In contrast, a study presented at the American Association for the Study of Liver Diseases (AASLD) Liver Meeting in November found that treatment with DAAs was not linked to higher HCC risk in a Northern Italian cohort. However, there was some evidence that, if people treated with the new drugs do develop HCC, they may experience more aggressive tumour progression.

Gregory Dore of the Kirby Institute at the University of New South Wales presented results from a systematic review and meta-analysis of more than 40 studies of initial or recurring HCC following DAA treatment.

People who had taken DAA treatment who initially developed liver cancer were older, on average, than those treated with interferon (60 vs 52 years). The age difference was less pronounced for people with recurrent HCC (64 vs 66 years, respectively).

People treated with DAAs also had more advanced liver disease.

Taking these differences into account, the meta-analysis found no significant difference in the risk of developing liver cancer between people treated with DAAs and people treated with interferon-based regimens.

New studies from France, China, Japan and Scotland presented at the meeting similarly found no increased risk of liver cancer.

However, Spanish researchers reported a higher rate of recurrence of liver cancer in people who had undergone DAA treatment.

Taken together, these study findings underscore the need for ongoing liver cancer monitoring for people who had cirrhosis before starting hepatitis C treatment and for people with a prior history of HCC – even after they are cured of hepatitis C – and support early DAA treatment before people develop advanced liver disease.

Hepatitis C treatment for children

Karen Murray at the International Liver Congress 2017. Photo by Liz Highleyman,

The US Food and Drug Administration (FDA) on 7 April approved the first direct-acting antivirals for the treatment of chronic hepatitis C virus (HCV) infection in adolescents aged 12 to 17 years. Sofosbuvir/ledipasvir (Harvoni) is now indicated for adolescents with HCV genotypes 1, 4, 5 or 6, while sofosbuvir (Sovaldi) plus ribavirin is approved for those with genotypes 2 or 3.

Results of a study of Harvoni in children aged 6 to 11 years were presented at the International Liver Congress. The study showed that half the adult dose of Harvoni, specially formulated for children, cured 89 out of 90 children and none discontinued treatment due to side-effects.

AbbVie combination

Xavier Forns at the International Liver Congress 2017. Photo by Liz Highleyman,

Results of two phase III studies of AbbVie’s second-generation direct-acting antiviral (DAA) combination, presented at the International Liver Congress, show that the combination is highly effective in people traditionally considered harder to treat.

The combination consists of a protease inhibitor and an NS5A inhibitor. Glecaprevir is an NS3/4A protease inhibitor active against all genotypes of hepatitis C virus (HCV). Pibrentasvir is an NS5A inhibitor also active against all genotypes of hepatitis C.

A study in people with genotype 3 infection without cirrhosis showed that the combination cured 95% of people after 8 or 12 weeks of treatment, and 12 weeks of treatment with glecaprevir/pibrentasvir matched the cure rate achieved with sofosbuvir/daclatasvir.

A study in people with cirrhosis with genotype 1-6 infection, but excluding genotype 3, showed a 99% cure rate after 12 weeks of treatment.

The combination is expected to receive marketing approval in the United States and European Union later this year.

HCV treatment reduces cardiovascular risk

Hepatitis C infection increases the risk of cardiovascular disease – events such as heart attack, stroke, peripheral artery disease and heart failure – especially in older people and those with diabetes or high blood pressure. What has been less clear so far is whether hepatitis C treatment and sustained virologic response after treatment affect the risk of cardiovascular diseases.

A large French study presented last week at the International Liver Congress in Amsterdam now shows that curing hepatitis C reduces the risk of cardiovascular events in people with compensated cirrhosis

The French study looked at people with early-stage cirrhosis who were followed for an average of five years. Having a sustained virologic response (SVR) to treatment during the follow-up period reduced the risk of a cardiovascular event by 65%. This reduction in risk began to become apparent after three years of follow-up, and was very pronounced after six years.

Presenting the findings, Patrice Cacoub of Hôpital Pitié-Salpêtrière, Paris, stressed the importance of thinking of hepatitis C as a systemic disease that affects the heart, the kidneys, blood vessels, the brain and glucose metabolism through mechanisms that are still to be fully understood. Hepatitis C is also associated with an increased risk of non-hepatic cancers, especially non-Hodgkin lymphoma.

Parkinson’s disease and hepatitis

Parkinson’s disease is more common among people with hepatitis B or C than in the general population in England, a cohort study that looked back from 1999 to 2011 has found. The researchers say it is unlikely that the increased risk is due either to drugs used in treatment or to cirrhosis.

Statins reduce the risk of decompensation

Treatment with statins reduces the risk of decompensated liver disease for people with cirrhosis caused by hepatitis B virus (HBV) and hepatitis C virus (HCV), investigators from Taiwan report in the online edition of Hepatology. The treatment also modestly reduced the risk of decompensated disease for people with alcohol-related cirrhosis.

Antibiotic prophylaxis reduces mortality in decompensated cirrhosis

Richard Moreau at the International Liver Congress 2017. Photo by Liz Highleyman,

Long-term prophylaxis with the antibiotic norfloxacin significantly reduced the incidence of deaths in people with decompensated cirrhosis over a six-month follow-up period, a French randomised trial reported last week at the International Liver Congress in Amsterdam.

Coming soon: HR17

The 25th International Harm Reduction Conference (HR17) is being held in Montréal, Canada from 14-17 May 2017.

We'll be bringing you news from the conference. The programme is available on the official conference website.

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