A common liver condition thought to be harmless could be dramatically increasing the risk of heart disease, kidney failure and premature death, according to a new review led by University of Manchester and Northern Care Alliance NHS Foundation Trust researchers.
Fatty liver disease, they find, has been overlooked in current approaches to assessing cardiometabolic health, despite growing evidence that it can play a central role in facilitating damage across different organs.
The condition which affects up to one in three adults worldwide and known technically as metabolic dysfunction-associated steatotic liver disease (MASLD), is already one of the world's fastest-growing health problems and is expected to affect more than half of adults globally by 2040.
Many scientists argue that the liver should be recognised alongside the heart, kidneys and metabolic system in a new framework they call cardiovascular-renal-hepatic-metabolic (CRHM) syndrome.
The review, published in Current opinion in nephrology and hypertension, highlights evidence showing that people with fatty liver disease face increased risks of cardiovascular disease, chronic kidney disease and early death, particularly when liver scarring, known as fibrosis, develops.
The studies they assessed, which involved millions of patients, found that fatty liver disease can predict heart and kidney complications independently of traditional risk factors such as diabetes, high blood pressure and obesity.
And having both liver and kidney disease appears to create a particularly dangerous combination.
A fatty liver releases substances into the bloodstream that promote inflammation, damage blood vessels, interfere with how the body uses energy.
That can influence the health of other organs through harmful fat deposits, chronic inflammation, hormonal signalling and changes in the gut microbiome amongst other things.
The review also points to a wave of new treatments that could transform care for patients affected by the interconnected conditions.
Drugs originally developed for obesity and type 2 diabetes are now showing benefits across the liver, heart and kidneys simultaneously.
Semaglutide, best known as a weight-loss treatment, has become the first medicine to demonstrate benefits, while newer drugs including tirzepatide and retatrutide are producing promising results in clinical trials.
The researchers say routine liver screening should become part of kidney and cardiovascular assessments, particularly in patients with obesity, diabetes or other metabolic risk factors.
They also call for major clinical trials and healthcare services to move beyond treating diseases organ by organ and instead adopt integrated approaches reflecting how these conditions interact in the real world.
Dr Will Marshall clinical research fellow at The University of Manchester and senior author of the study, said: "For many years we have viewed heart disease, kidney disease and liver disease as separate conditions managed by different specialists.
"The evidence now shows that these organs are deeply interconnected through shared biological pathways driven by obesity, insulin resistance and chronic inflammation."
Dr Marshall, who is also based at Salford Royal added: "Fatty liver disease is not simply a consequence of metabolic ill health, it is an active contributor to it.
"Recognising the liver as a core component of cardiometabolic disease could help clinicians identify high-risk patients earlier, improve treatment decisions and ultimately prevent thousands of serious complications and premature deaths."
· This paper is a peer reviewed narrative review which cites 55 references in its bibliography, covering epidemiological studies, clinical trials, meta-analyses, guidelines, reviews, and expert commentaries.
- The study Integrating the liver into the cardiovascular-kidney-metabolic syndrome: pathophysiology and therapeutic implications is published in journal Current Opinion in Nephrology and Hypertension DOI 10.1097/MNH.0000000000001225
