Babies with a low birthweight are four times more likely to develop fatty liver disease in later life, new study shows

(16 October 2023, Copenhagen, Denmark) A groundbreaking new study, presented today at UEG Week 2023, has discovered a significant connection between birthweight and the onset of nonalcoholic fatty liver disease*, now known as metabolic dysfunction-associated steatotic liver disease (MASLD), in young people.¹ Most notably, babies with a low birthweight were found to be four times more likely to develop MASLD in childhood, adolescence or young adulthood.¹

To investigate this link, a team of researchers from Sweden used the nationwide ESPRESSO cohort and conducted a population-based case-control study of all people aged 25 years and younger, who had been diagnosed with biopsy-proven MASLD between January 1992 and April 2017, totalling 165 cases.^{1, 2} To minimise confounding factors, each individual with MASLD was matched with up to five controls from the general population based on age, sex, calendar year and county of residence.¹

Strikingly, individuals born with a low birthweight (<2500 g/5 lbs 8 oz) were four times more likely to develop MASLD when compared with those born with normal birthweight.¹ Those born as small for gestational age (SGA), falling below the 10^th percentile, were also over three times more likely to develop MASLD early in life compared with those with an adequate (10th–90^th) birthweight.¹

In addition, the researchers found that individuals with a low birthweight, or those born as SGA, had an up to ~6-fold higher relative risk of developing more severe stages of MASLD in the form of liver fibrosis or cirrhosis.¹

Dr Fahim Ebrahimi, first author of the study, comments, “While previous research has established the link between birthweight and major diseases, such as cardiovascular disease and metabolic syndrome, the connection to MASLD remained unclear. Our study now provides compelling evidence that foetal developmental factors play a significant role in the development of MASLD and progressive liver disease.”

Amidst escalating rates of obesity, MASLD has become the most common cause of chronic liver disease worldwide.³ In Europe alone, it is estimated to affect over 25% of adults, and its prevalence is increasing among obese or overweight young people.⁴ It has also emerged as one of the fastest growing causes of end-stage liver disease, primary liver cancer and liver transplantation.³ However, only few will experience progression of the disease.

Dr Ebrahimi continues, “Further research is needed to fully understand the underlying immunological and metabolic mechanisms. Several studies suggest that both overnutrition and undernutrition during pregnancy can lead to lasting epigenetic changes that can affect an individual’s metabolism for a lifetime.”

“By linking several nationwide registers such as the Swedish Medical Birth Register, we were able to gather detailed data on maternal factors and perinatal characteristics and to adjust for multiple confounders," says Jonas F Ludvigsson, the study's supervisor and paediatrician at Örebro University Hospital and professor at the Department of Medical Epidemiology and Biostatistics at Karolinska Institutet.

“It is deeply concerning that individuals born with a low birthweight face a heightened relative risk of this disease at a young age, as early-onset MASLD often persists into adulthood and has been associated with an increased risk of developing cirrhosis and end-stage liver disease. Moving forward, it is important that we develop proactive and effective strategies, such as early and targeted screening, to identify at-risk individuals and help reduce the burden of this disease,” adds Dr Ebrahimi.

The study was financed by the Swiss National Science Foundation (SNSF) and Karolinska Institutet.

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Notes to Editors

For further information or to arrange an expert interview, please contact Hannah Murray at: hannah.murray@emotiveagency.com or media@ueg.eu.

We kindly ask that a reference to UEG Week 2023 is included when communicating any information within this press release.

Key terms defined:

*Nonalcoholic fatty liver disease: A long-lasting liver condition caused by having too much fat in the liver.⁵ In recent times, a new term, ‘metabolic dysfunction-associated steatotic liver disease’ (MASLD), has been introduced to replace NAFLD.⁶ This change reflects the understanding that most conditions classified as MASLD are closely associated with the metabolic syndrome, which is characterized by obesity, insulin resistance and high levels of cholesterol or lipids.⁶

About Dr Fahim Ebrahimi and Professor Jonas F Ludvigsson:

Dr Fahim Ebrahimi specialised in Gastroenterology/Hepatology at Clarunis - University Center for Gastrointestinal and Liver Diseases in Basel, Switzerland and currently works as postdoctoral researcher in the research group of Prof. Jonas F. Ludvigsson at the Department of Medical Epidemiology and Biostatistics at Karolinska Institutet.

Professor Jonas F. Ludvigsson is a paediatrician at Örebro University Hospital and professor at the Department of Medical Epidemiology and Biostatistics at Karolinska Institutet. He is the coordinator of one of the world’s largest gastrointestinal cohort studies: ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden).

About UEG:

Founded in 1992, United European Gastroenterology (UEG) is the leading non-profit organisation for excellence in digestive health in Europe and beyond with its headquarters in Vienna. We improve the prevention and care of digestive diseases in Europe through providing top tier education, supporting research and advancing clinical standards. As Europe’s home for multidisciplinary gastroenterology, we unite over 50,000 engaged professionals from national and specialist societies, individual digestive health experts and related scientists from all fields. With our innovative online platform, the ‘myUEG Community’, we enable digestive health professionals from across the globe to connect and benefit from a plethora of outstanding free resources and educational activities. Our offers include UEG Week, our annual congress, online and face-to-face educational experiences, research support, a scientific journal and a range of opportunities in the form of fellowships and grants. We provide numerous guidelines, standards and quality improvement initiatives and campaign at the European level to ensure continued resources for research into digestive health while working closely with patient organisations. 

Find out more about UEG's work by visiting: www.ueg.eu. 

References:

1. Ebrahimi F, et al. Perinatal characteristics of nonalcoholic fatty liver disease in children, adolescents and young adults – a nationwide population-based case-control study. Presented at UEG Week 2023; 16 October 2023; Copenhagen, Denmark.
2. Karolinska Institutet. ESPRESSO. June 2023. Available at: https://ki.se/en/meb/espresso (Accessed: September 2023).
3. Medpage Today. Fahim Ebrahimi on Increased Infection Risk With Nonalcoholic Fatty Liver Disease. June 2023. Available at: https://www.medpagetoday.com/reading-room/aga/lower-gi/104953 (Accessed: September 2023).
4. Cholongitas E, et al. Epidemiology of nonalcoholic fatty liver disease in Europe: a systematic review and meta-analysis. Ann Gastroenterol. 2021;34(3):404–414.
5. British Liver Trust. MASLD, NASH and fatty liver disease. Available at: https://britishlivertrust.org.uk/information-and-support/liver-conditions/non-alcohol-related-fatty-liver-disease/ (Accessed: September 2023).
6. British Liver Trust. Introduction of new terminology for fatty liver diseases. June 2023. Available at: https://britishlivertrust.org.uk/introduction-of-new-terminology-for-fatty-liver-diseases/#:~:text=The%20goal%20was%20to%20create,original%20description%20of%20the%20condition/ (Accessed: September 2023).