Alcoholic liver disease replaces hepatitis C infection as the leading cause of liver transplantation in patients without hepatocellular carcinoma in the USA

11 April 2018, Paris, France: Two independent studies have today reported that alcoholic liver disease has now replaced hepatitis C virus (HCV) infection as the leading cause of liver transplantation in the USA in patients without HCC. Non-alcoholic steatohepatitis (NASH) is also on the increase, now ranking second as a cause of liver transplantation due to chronic liver disease.

Chronic HCV infection has remained the leading indication for liver transplantation in the USA for the last two decades.1 However, the availability of second-generation direct-acting antiviral agents (DAAs) in late 2013 led to a decline in the number of HCV-related liver transplant waiting list registrations and surgeries from 2015 onwards.2,3 Alcohol consumption began to increase markedly in the US during the 1990s and early 2000s, with data highlighting dramatic rises in alcohol use and high-risk drinking in recent years.4

The two studies presented this week at The International Liver Congress™ 2018 in Paris, France, were conducted to evaluate recent trends in the aetiology of liver disease among liver transplant recipients in the USA in view of the changing landscape of potential risk factors. In the first study, data from the United Network for Organ Sharing (UNOS) between 2005-2016 were analyzed, looking at four indications for chronic liver disease: alcoholic liver disease (ALD), NASH, HCV infection, and HCV/ALD combined. According to the results of the study, the number of liver transplant recipients with HCV peaked in 2014 (1,905 individuals) and has been declining ever since. In contrast, the number of liver transplants due to ALD and NASH has been steadily increasing and, in 2016, there were 1,624 liver transplants performed as a result of ALD, compared with 1,535 due to HCV, 1,334 due to NASH, and 424 due to HCV/ALD.

'Although we found that, overall, alcoholic liver disease became the leading indication for liver transplantation in the US in 2016, NASH was not far behind', said Dr Jennifer Wang from the California Pacific Medical Center in San Francisco, USA, who presented the study findings. 'Importantly, NASH is now the leading cause of liver transplantation in women, which is not entirely surprising given the higher rates of metabolic syndrome in women and the resultant increased risk of non-alcoholic fatty liver disease'.

'In African Americans and those with hepatocellular carcinoma, HCV remains the leading cause of transplantation and a major burden'.

The second study presented today also evaluated data from the UNOS registry, looking at first liver transplants performed in individuals without HCC between January 2012 and October 2017. As in the first study, HCV infection remained the leading aetiology for liver transplant recipients until 2016, when ALD surpassed it, accounting for 24% of liver transplants performed compared with 19% for NASH and 18% for HCV. In 2017, ALD, NASH, and HCV were responsible for 24%, 18%, and 17% of liver transplants, respectively, according to the results of this study.

'One of our most worrying findings was that patients with ALD are being listed for liver transplantation at a much younger age and with more severe disease than patients with either HCV infection or NASH', said investigator, Dr George Cholankeril from Stanford University Medical Center, California, USA. 'These are very ominous trends and we need to take aggressive action to address these rising rates of liver transplantation in patients with alcoholic liver disease'.

'So far, alcoholic liver disease has received much less attention with regards to clinical and basic research than either hepatitis B or C',5 said Prof. Helena Cortez-Pinto from the University Hospital of Santa Maria, Lisbon, Portugal, and EASL Governing Board Member. 'It is time to change and turn our attention to ALD, both in research and of course in policies that have been shown to reduce consumption, such as increases in taxation, in order to decrease affordability'.

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About The International Liver Congress™

This annual congress is the biggest event in the EASL calendar, attracting scientific and medical experts from around the world to learn about the latest in liver research. Attending specialists present, share, debate and conclude on the latest science and research in hepatology, working to enhance the treatment and management of liver disease in clinical practice. This year, the congress is expected to attract approximately 10,000 delegates from all corners of the globe. The International Liver Congress™ 2018 will take place from 11¬-15 April 2018 at the Paris Convention Centre, Paris, France.

About The European Association for the Study of the Liver (EASL)

Since its foundation in 1966, this not-for-profit organization has grown to over 4,000 members from all over the world, including many of the leading hepatologists in Europe and beyond. EASL is the leading liver association in Europe, having evolved into a major European association with international influence, and with an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.

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Onsite location reference

Session title: Poster presentations Time, date and location of session: Poster area (Hall 7.2) Presenters: Jennifer Wang and George Cholankeril, USA Abstracts: Alcoholic liver disease surpasses hepatitis C virus in 2016 to become the leading indication for liver transplantation among adults without hepatocellular carcinoma in the United States (13 April 2018 9:00-17:00) and Alcoholic liver disease replaces HCV infection as the leading indication for liver transplantation in the United States (14 April 09:00-17:00)

Author disclosures

Jennifer Wang: None reported

Robert Gish: Dr. Gish has received Grants/Research Support from AbbVie, Benitec Biopharma, Gilead Sciences, and Merck & Co. Dr. Gish has performed as Consultant and/or Advisor to AbbVie, Akshaya Pharmaceuticals, AstraZeneca, Bristol-Myers Squibb, Genentech, Gilead Sciences, Hoffman-LaRoche, Ltd., Ionis Pharmaceuticals, Janssen, Merck & Co., Nanogen Biopharmaceutical, and Presidio Pharmaceuticals. Dr. Gish has current activity with the scientific or clinical advisory boards of AbbVie, AstraZeneca, Genentech, Gilead Sciences, Janssen, Merck & Co., and Nanogen Biopharmaceutical. Dr. Gish is a member of the Speakers Bureau for AbbVie, Bristol-Myers Squibb, Gilead Sciences, and Merck. Dr. Gish is a minor stock shareholder of Cocrystal Pharma.

Benny Liu: None reported

Taft Bhuket: None reported

Robert Wong: Dr Wong receives research funding from Gilead Sciences and AbbVie, has served as a consultant and member of the advisory board for Gilead Sciences, and serves on the speaker's bureau for Gilead Sciences, Salix, and Bayer. Dr Wong is also funded by an AASLD Foundational Clinical and Translational Research Award in Liver Diseases.

George Cholankeril and co-authors: None reported

References

1. Cholankeril G, Ahmed A. Alcoholic liver disease replaces hepatitis C virus infection as the leading indication for liver transplantation in the United States. Clin Gastroenterol Hepatol. 2017; doi: 10.1016/j.cgh.2017.11.045 [Epub ahead of print].

2. Goldberg D, et al. Changes in the prevalence of hepatitis C virus infection, nonalcoholic steatohepatitis, and alcoholic liver disease among patients with cirrhosis or liver failure on the waitlist for liver transplantation. Gastroenterology. 2017;152(5):1090-9.e1.

3. Flemming JA, et al. Reduction in liver transplant wait-listing in the era of direct-acting antiviral therapy. Hepatology. 2017;65(3):804-12.

4. Grant BF, et al. Prevalence of 12-month alcohol use, high-risk drinking, and DSM-IV alcohol use disorder in the United States, 2001-2002 to 2012-2013: results from the National Epidemiologic Survey on Alcohol and Related Conditions. JAMA Psychiatry. 2017;74(9):911-23.

5. Ndugga, N, et al. Disparities between research attention and burden in liver diseases: implications on uneven advances in pharmacological therapies in Europe and the USA. BMJ Open. 2017;7(3):e013620; doi: 10.1136/bmjopen-2016-013620 [Epub ahead of print].

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