Seeking early clues to alcohol-linked liver damage

Doctors worry that many people with alcohol-associated liver disease are diagnosed too late. By the time tests and scans spot trouble, the liver can already be badly scarred or cancerous.

In a new review in the journal Clinical and Molecular Hepatology, a team of VCU-led researchers describe new research that aims to find earlier, easier ways to tell who is at risk and who needs help now.

What alcohol-associated liver disease does

Alcohol can damage the liver in stages, starting with a build-up of fat. Then, inflammation and cell injury can lead to scarring that over time can turn into cirrhosis and raise the chance of liver cancer. Some people with a sudden bad flare, known as alcohol-associated hepatitis, can become very ill fast.

Why earlier tests matter

If doctors could detect disease sooner, more patients could get treatment and reduce drinking before the damage becomes severe. Currently, many blood tests and imaging tools only identify major problems. New markers could give a clearer picture much earlier. Promising blood tests and scans

• New blood markers look at liver scarring and cell death. Tests that measure fragments of cytokeratin-18 and Pro-C3 (serum biomarkers used to test for fatty liver disease), and the enhanced liver fibrosis (ELF) score do better than older simple scores for spotting advanced fibrosis.
• Elastography scans to measure stiffness in the liver are precise. Devices like vibration-controlled transient elastography (TE) and magnetic resonance elastography (MRE) can detect the stiffness that signals fibrosis. TE works well at the bedside, while MRE is very accurate in specialist centers.
• MRI methods are best for measuring liver fat. A cheaper option, the Controlled Attenuation Parameter score (CAP), when paired with TE works well and often better than ultrasound.

New biology that helps predict who will get worse

Researchers are finding many biological signals tied to ALD:

• Genes: Variations in genes (PNPLA3, TM6SF2, MBOAT7 and HSD17B13) change a person’s lifetime risk of scarring and cancer. Putting many genetic markers together into a polygenic risk score can help predict who is most likely to develop serious liver disease.
• Sex and hormones: Men and women may respond differently to alcohol, and hormones like testosterone, cortisol and thyroid hormones affect risk and disease progress.
• Gut microbes: The mix of bacteria in the gut changes with heavy drinking. Lower amounts of helpful bacteria like Faecalibacterium prausnitzii and Akkermansia muciniphila, and shifts in the balance of major groups of bacteria, link to liver inflammation and scarring. Tiny molecules the microbes make, such as short-chain fatty acids, bile acids and others, also matter.
• Other new signals: Small particles released from cells, the extracellular vesicles; microRNAs in the blood; and many proteins and metabolites are being tested as early signs of disease.

Big-picture tools: multi-omics

Scientists can now look at many layers of biology at once: genes, RNA messages, proteins, fats and small molecules. These “multi-omics” profiles can create precise signatures that point to active inflammation, scarring, or early cancer before usual tests catch them.

How this helps patients and clinical trials

Using several markers together can identify patients at the right stage for early treatment and help doctors choose therapies that match a person’s biology. It allows researchers to run better drug trials that test whether a treatment changes the exact process causing damage and can spot early signs that a treatment is working.

Challenges ahead

But before these new tools are used everywhere, scientists must develop consistent tests whose results are the same from lab to lab and prove they work in many different groups of people. New tests must also be cost-effective and practical for physicians, and also fit into medical rules and guidelines.

Bottom line

New blood tests, scans, genetic scores, gut-microbe signals, hormone measures and multi-omics profiling offer great promise to catch alcohol-related liver damage earlier and more precisely. If these tools are validated and adopted, doctors could diagnose disease sooner, tailor care to each person, and speed development of better treatments. That could prevent many cases of cirrhosis and liver cancer worldwide.