Liver diseases are complex and varied, leading to significant burden and different treatment challenges. In many western countries, alcohol abuse is one of the main causes of liver diseases, resulting in considerable amounts of resources employed by healthcare systems and important social consequences. In contrast, some lower income countries also experience burden of lifestyle-related liver disease, but face challenges with meeting costs associated with treatment. Finding the best regimen for each patient is problematic in many situations.
Unanswered clinical and ethical questions are ongoing issues in liver disease management, and here we report some of the latest findings discussed at ILC 2016.
HIV and global Hepatitis
Gottfried Hirschnall opened the conference by focusing on the need to scale up viral hepatitis response, an issue that still causes considerable health and economic burden worldwide.
Increase in advocacy and new ways to deliver treatment are necessary to keep momentum, and to turn current plans and studies into real action.
Gottfried Hirschnall
Treating hepatitis is a challenge in every setting, but we must remain optimistic as the cost of drugs is decreasing and treatments are easier to administer. Increase in advocacy and new ways to deliver treatment are necessary to keep momentum, and to turn current plans and studies into real action.
Hepatitis C – one combination of drugs for all?
Hepatitis C is notoriously difficult to treat. Viral genotype plays a fundamental role, but individual patient condition and comorbidities can influence treatment success or failure.
Carlos Fernandez Carrillo presented results (abstract GS01) from the Hepa-C registry on Spanish patients with advanced cirrhosis and awaiting liver transplant, looking at the risk of using direct-acting antivirals (DAA) in decompensated cirrhosis patients.
Treatment regimens were combinations of antiviral drugs (e.g.: sofosbuvir, simeprevir, daclatasvir). Sustained virologic response data at 12 weeks (SVR12) results report that patients with decompensated cirrhosis present worse outcomes compared to compensated patients, highlighting the risk of DAA treatment in the former subgroup. Larger studies are needed to confirm these findings, however caution is needed when treating patients with advanced liver disease.
Also largely unknown are the long term outcomes in liver transplant recipients from Hepatitis C virus (HCV) cohorts. At a press conference, Zobair Younossi explained that the use of HCV positive organs for liver transplantation has tripled between 1995 and 2013 due to organ shortages, but the risks are not yet clear.
Presenting data from the Scientific Registry of Transplant Recipients, he argued that HCV-positive grafts could be a reasonably safe option for patients awaiting transplant and with chronic HCV infection, and HCV status of the liver did not affect post-transplant mortality (see abstract PS040). Future studies are required to confirm these preliminary conclusions, as results on long term mortality were not statistically significant.
Resource allocation and ethics in end-stage liver disease.
Cirrhosis and organ failure are often associated with high mortality, and therapy during end-stage liver disease can be problematic. Katrine Lindvig argued that at advanced stages of disease, treatment may be futile or unethical. To assist clinicians’ decision making, she presented a theoretical algorithm (abstract PS059) based on premorbid liver function and Acute-on-Chronic Liver Failure (ACLF).
Based on MELD, Child-Pugh and CLIF-SOFA scores and data from 354 patients with acute decompensation, the algorithm takes into account premorbid liver function and acute-on-chronic liver failure (ACLF), dividing patients into likely to survive ICU or unlikely to benefit from further treatment.
Lindvig stated that although the algorithm has its limitations and clinicians’ judgment is always final, it can be used to make clinical decisions more objective. These new findings are likely to spark further debate in the field and we look forward to future studies on the reliability of decision-making tools.
Hard drinking and genetics – should you avoid the last call?
Half of all cirrhosis deaths in the western world are due to excessive alcohol consumption, but do genes also contribute? Stephen Atkinson explained that most liver disease patients are asymptomatic, and they wanted to find out why not everyone develops severe alcoholic hepatitis.
Their GWAS study (Abstract GS03) on alcoholic hepatitis and healthy patients from the UCL consortium reveals the rs738409 variant in the PNLPA3 gene is significantly associated with a higher risk of developing severe hepatitis in heavy drinkers. Importantly, they also identified variations in the SLC38A4 gene as a potential novel risk loci to develop alcoholic hepatitis.
Both gene variants are common in the general population, highlighting the increased risk of severe liver disease after alcohol abuse in certain individuals and the immense healthcare burden. Further studies will clarify if some patients will benefit from tailored treatments more than others.
Updated WHO guidelines for Hepatitis C management
On Friday 15 April, the World Health Organization released the updated guidelines for screening and treatment, from the 2014 edition. New treatment drugs have been approved in the past few years, treatment costs are lower than before and more accessible in low income countries.
The new recommendations mainly focus on disease treatment and the use of generics, and take into account liver disease severity. It is widely hoped that the introduction of generic drugs will sharply increase chances for people who are now unable to afford treatment.
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