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In this issue: This edition of the ILC 2018 daily news has a major emphasis on the hepatology community’s commitment to eliminating viral hepatitis, as well as coverage from Saturday’s plenary session, late breaking abstracts, and key highlights of the latest scientific advances in liver transplantation, autoimmune and choleostatic diseases, and metabolic and rare diseases.

In the second of this week’s award ceremonies, EASL presented a prestigious series of accolades in support of young hepatologists. With special recognition for their outstanding achievements in liver disease research, the EASL Governing Board and Young Investigator Concerted Action Group granted 2018 EASL Young Investigator Awards to Professor Pierre-Emmanuel Rautou (France) and Dr Jesús M. Banales (Spain).

Two EASL Registry Grants were awarded, providing funding to help with the organization of consortia groups dedicated to furthering liver research, and, to encourage young researchers in the development of their careers, other funding awards and studentships included:

  • EASL Postgraduate Fellowships Sheila Sherlock
  • EASL PhD Studentships Juan Rodes
  • EASL Daniel Alagille Award, which promotes biomedical research in paediatric and adult cholestatic diseases

Final plenary draws a huge audience

Exciting new clinical trial and public health data featured in today’s general session. While it is well known that DAAs are highly effective in terminating active HCV infection, we lack evidence on the impact of DAAs on severe liver morbidity at a population level. A study utilizing the Scottish HCV Clinical Database provides the first country-level data to show that an immediate and considerable reduction in the incidence of HCV-related decompensated cirrhosis is associated with a national scale-up of DAAs targeting patients with advanced liver fibrosis.

Other promising clinical trial and registry data presented in this session:

  • A Phase 2 study of NGM282 in biopsy-confirmed NASH saw significant and clinically meaningful reductions in non-invasive markers of liver disease, with unprecedented improvement in anti-fibrotic activity and a large proportion of patients with improved histology after 12 weeks of treatment
  • Givosiran, an RNA interference therapeutic, shows potential for the treatment of a rare metabolic disorder, acute intermittent porphyria, with clinically meaningful responses in Phase 1/2 and open-label extension studies. These encouraging data support further clinical development and a Phase 3 study is currently enrolling patients
  • Long-term data from the DALTON Cirrhosis Registry demonstrated that the majority of patients with decompensated cirrhosis showed improvement in Child–Pugh Score, improvements in liver stiffness occurred early and were maintained, and the incidence of HCC declined with achievement of SVR

Clinical potential of the neonatal Fc receptor

Karl Wilhelm von Kupffer basic state-of-the-art: Beyond albumin and IgG – the unexpected prospects of the neonatal Fc receptor (FcRn)

The FcRn has emerged as an exciting and potentially important clinical target in adult autoimmune disease, mucosal immunity, and tumour immune surveillance, and is currently under investigation in several clinical scenarios, including haemophilia B. In this cutting-edge presentation, Dr Richard Blumberg introduced the function of FcRn as a central regulator of IgG and albumin – its two main ligands – and the clinical opportunities that have emerged from this understanding.

Moving toward elimination of viral hepatitis

Elimination of viral hepatitis: EASL can count on WHO as collaborators

The goal of viral hepatitis elimination was the focus of today’s EASL–WHO joint symposium. An expert faculty reviewed progress towards this goal and highlighted the challenges that remain. Progress is being made and the momentum is encouraging but both need to be maintained. Clinicians have a pivotal role to play by presenting compelling health economic arguments and ensuring that national plans are implemented. In particular, a concerted effort is required by the international community to ‘find the missing millions’ of undiagnosed patients highlighted by Michael Ninburg during the opening session on Thursday. The collaboration between EASL and WHO is as mutually valued as it is needed to drive progress towards elimination of viral hepatitis as a public health threat by 2030.

Positive long-term impact of DAAs on HCV-related disease outcomes

More large-scale data on the long-term impact of DAAs are needed and two studies presented today provided insight into the effect of these regimens on disease course:

  • In the prospective RESIST-HCV cohort, 3-year data in over 4000 patients showed that those with Child–Pugh A cirrhosis and SVR had reduced overall mortality and a lower risk of liver-related deaths versus non-SVR patients, whereas those with Child–Pugh B cirrhosis retained a significant risk even after SVR
  • In another propsective study, despite SVR being associated with a progressive reduction in portal pressure in patients with HCV-related cirrhosis and clinically significant portal hypertension (CSPH), a large proportion still presented with CSPH and remained at risk of clinical decompensation.

Are we moving from a treatable to a curable disease?

Despite an effective vaccine and potent antiviral treatments, hepatitis B remains a significant global public health issue. The HBV symposium tackled some of the burning questions in HBV management:

  • Vaccination coverage and access to treatment remain unsatisfactory in highly endemic areas and public health systems are often fighting the virus with limited resources. Dr Maud Lemoine concluded that to achieve HBV elimination in resource-limited settings we need significant scale up in PMTCT (birth dose coverage and peripartum treatment) together with more effective screen-and-treat interventions
  • HBsAg loss remains the highest treatment goal but is reached only in small numbers of patients with current antivirals. Dr Florian van Boemmel presented the pros and cons of stopping Nuc therapy – a strategy suggested by EASL’s 2017 HBV CPG for consideration in non-cirrhotic HBeAg-negative patients with long-term virologic suppression, provided close monitoring can be guaranteed
  • New therapies for HBV are essential to attaining functional cure and a huge body of research has identified both virologic and immunologic approaches to targeting HBV. At EASL 2018, numerous proof-of-concept studies have shown promising results with several new therapeutic agents and combinations

Novel treatment strategies need to be explored in hepatitis D

Currently, PEG-IFNα is the only treatment option for HDV. HBV entry inhibition, prenylation inhibition and blocking particle formation may represent potential therapeutic strategies in this patient population with few treatment options. Promising, albeit early, results were observed in Phase 2 studies, with significant virological suppression in response to the HBV entry inhibitor myrcludex B and the prenylation inhibitor lonafarnib.

Don’t miss
Viral hepatitis and the community: Dynamics of the viral hepatitis epidemic – Saturday, 10:00–11:30, South 3

Late breakers showcase novel therapies

An exciting range of novel therapies featured in today’s late breaker abstract session, with interesting preliminary outcomes reported in the treatment of:

  • HBV: capsid assembly modulator JNJ-6379 and core protein allosteric modulator RO7049389
  • Non-alcoholic steatohepatitis: TLR-4 receptor antagonist JKB-121 and galectin-3 inhibitor GR-MD-02
  • Primary sclerosing cholangitis: NGM282, an engineered analogue of FGF19
  • Primary biliary cholangitis: non-bile acid FXR agonist tropifexor

Phase 3b data for glecaprevir/pibrentasvir in genotype 1 HCV patients who had failed prior DAA therapy were also presented, showing high SVR rates that suggest a potential treatment regimen for this challenging, difficult-to-treat population.

Finally, primary outcome results from the SORAMIC trial showed that addition of selective internal radiation therapy to sorafenib offers no additional survival benefit over sorafenib alone in patients with advanced HCC, although subgroup analyses did suggest a potential clinical benefit for younger patients, and patients presenting with non-alcoholic aetiology, or without cirrhosis.

Parallel sessions: Latest advances in hepatology

Animal models herald future improvements in liver transplant

In a study in pigs, benefits of normothermic ex vivo liver perfusion over static cold storage in reducing ischaemia/reperfusion injury in transplanted livers were shown to result from reduced platelet aggregation. An intriguing proof-of-concept study transplanting mouse-rat chimeric livers into baby rats demonstrated the potential for growing transplantable patient-like organs in animals.

Clinical developments in autoimmune disease and cholestasis

Results from a Swedish, register-based cohort showed that statins are associated with a reduced risk of death, liver transplantation and severe adverse liver events in primary sclerosing cholangitis. In a separate study, serum metabolomic profiling showed promise as a non-invasive approach to distinguish intrahepatic cholangiocarcinoma from primary sclerosing cholangitis and HCC.

New developments in rare metabolic diseases

A proof-of-concept study on autologous cell/gene therapy using hepatocytes created from genetically corrected patient-specific induced pluripotent stem cells is being developed as an alternative to liver transplant for the treatment of haemophilia B, a genetic condition of impaired Factor IX, which is synthesized in hepatocytes. The preclinical use of RNA interference therapy, ARO-AAT, for the treatment of orphan disease alpha-1 antitrypsin deficiency – a storage disease of the liver – shows potential and is now in Phase 1 studies.

Improving survival outcomes in patients with cirrhosis  

Chinese researchers have shown that early use of transjugular intrahepatic portosystemic shunt in patients with cirrhosis and acute variceal bleeding led to improvements in both short- and long-term survival. In the prospective CLEVER study, in patients with decompensated cirrhosis receiving nonselective β-blockers, lower cardiac output, worse liver function and higher baseline HVPG were associated with an increased risk of death.

Industry symposia – looking to the future: new horizons in hepatology

MSD: A future without hepatitis C: What will it take?

Professor Tarik Asselah and colleagues explored the feasibility of reaching the WHO’s target for HCV elimination by 2030 and considered the action needed to effect global change, highlighting the requirement for programmes that improve awareness and prevention and help remove current barriers to diagnosis and treatment.

Gilead: Shaping tomorrow together – addressing the challenges in the management of advanced fibrosis due to non-alcoholic steatohepatitis (NASH) 

Professor Lawrence Serfaty led an expert panel to examine the evolving burden of NASH-related liver disease and the challenges faced by today’s clinician and discuss current and future research into improving diagnostics and treatment options to manage this growing patient population.

Don’t miss
Sheila Sherlock 100th year anniversary ILC 2018 wrap up session – Sunday,  11:30–13:00, North 1

Acknowledgements

The ILC daily news was supported by grants from: Abbvie, Alexion, Boehringer Ingelheim, Gilead, Janssen, MSD and Pfizer.