Building Systems to Catch Liver and Other Cancers in Patients With MASLD

Metabolic dysfunction–associated steatotic liver disease (MASLD) now affects roughly a third of adults, and its links to both hepatocellular carcinoma (HCC) and extrahepatic cancers are reshaping who is responsible for cancer screening and surveillance.

At The Liver Meeting® 2026, CancerNetwork® spoke with Hashem B. El-Serag, MD, MPH, vice president of the Learning Health System and chair and professor of the Department of Medicine at Baylor College of Medicine in Houston, Texas, about putting the evidence from his session on MASLD and cancer risk into practice.

El-Serag began by explaining why hepatologists now share responsibility for age-appropriate cancer screening in patients with MASLD and how health systems can keep those patients from falling through the cracks. He then outlined a fibrosis-based pathway for identifying patients who need HCC surveillance, described when to move from ultrasound to MRI, and reviewed the evidence for statins, glucagon-like peptide-1 (GLP-1) receptor agonists, and metformin as potential chemoprevention. El-Serag also discussed how to approach surveillance for patients with F3 fibrosis and how clinicians should screen for and address alcohol use.

CancerNetwork: Extrahepatic cancers are about 8 times more common than HCC in patients with MASLD.¹ Who on the care team, from primary care to oncology, should own cancer screening for these patients, and how can we keep it from falling through the cracks?

El-Serag: For extrahepatic cancers with a recommended screening, like colorectal or breast cancer, it is the duty of everyone in the health care system to make sure screening is done. Typically, it is a primary care responsibility, and in cases with a family history or a strong predilection for that cancer or another cancer, it falls within the oncologist’s domain. Gastroenterologists and hepatologists have been relatively insulated from these cancers until these emerging data. MASLD, our most common chronic liver disorder, is now filling the clinics of hepatologists and gastroenterologists, and it is associated with a small but meaningful increase in some of these common cancers, like colon and breast cancer. Therefore, the responsibility to ensure age-appropriate screening for these cancers now also falls on the hepatologist. In my opinion, it should be part of the package of managing patients with MASLD. We cannot ignore this emerging evidence, and we should be responsible for ensuring that screening is completed.

It is easy to say these things. What we need are systems that are not heavily dependent on human reaction or attention. For age-appropriate screening, we are at a prime time, with electronic health records, large systems, and AI [artificial intelligence]–related algorithms and agents, to ensure an implementation that, at least from the system side, makes sure patients do not fall through the cracks. There is a part that eventually falls on the patient in terms of adherence and completion.

Most patients with MASLD will never need HCC surveillance. What practical steps, from the fibrosis-4 index (FIB-4) to elastography, should clinicians use to find the minority who do, and where does that pathway break down in practice?

MASLD now affects anywhere from 30% to even 40% of the entire population, depending on where you go. Of this massive proportion of people, only a small proportion will ever develop HCC, based on what we know right now. The strongest risk factor for developing HCC is the severity of hepatic fibrosis, with the stages called F3 and F4. F4 is cirrhosis, and F3 is called advanced fibrosis. Those 2 entities carry most of the risk for HCC.

Our job in primary care, gastroenterology, hepatology, and endocrinology is to go through those masses of patients, who on any given day would constitute a third to a half of anyone’s practice, and screen them in an automated, sensitive, efficient way. Then, we need to ensure that those who initially screen positive for a high likelihood of advanced fibrosis receive additional testing to confirm it, and channel those high-risk patients into a pathway that ensures prevention and surveillance.

The most common tools we have right now are noninvasive tests. The simplest, most available, and cost-free is FIB-4. It is calculated from available laboratory values, and most electronic health records and health care systems can calculate it automatically on all comers. A high FIB-4 would trigger a second layer of noninvasive testing with liver elastography, using either vibration-controlled transient elastography [VCTE] or magnetic resonance elastography [MRE]. The combination of those 2 tests identifies the group at high risk of advanced fibrosis or cirrhosis, and that is how we pick them up.

It is easy to say that, but when a condition needs to be looked for, screened, and followed up in a third to a half of your practice, we need systems that allow us to do this. Again, I am excited about the possibilities of electronic health records, AI, and clinical cascades to efficiently identify the groups of patients we can focus on for further prevention and surveillance.

Ultrasound misses many HCCs in patients with obesity and steatosis. When should radiologists and hepatologists move to MRI, and is abbreviated MRI ready for routine use?

Ultrasound is our go-to test for HCC surveillance among patients with cirrhosis. In this group, ultrasound is an OK test, with high specificity but not-so-great sensitivity. However, its sensitivity and specificity drop markedly in the condition we are now dealing with most frequently, which is MASLD-related cirrhosis, because on top of a test that is not great, you now have obesity and steatosis that obscure the ultrasound signal. It is estimated that a quarter to a third of all ultrasounds performed in MASLD may be of low quality.²

There are well-publicized scores that radiologists or the radiology technicians who perform these studies can use to grade any ultrasound based on quality, from A to C, with C being the poor category. Step number 1 is to ensure that your facility uses some sort of quality measurement for ultrasound. After 1 poor-quality ultrasound, it is reasonable to repeat it, perhaps with a different operator, to see whether it improves. After 2 poor-quality ultrasounds, one should shift to another modality for HCC surveillance. CT is an option, but it carries a high radiation load, so MRI is the other option.

Conventional MRI remains the one most people use. Abbreviated MRI is a promising modality that is still being tested for this purpose. The early results are promising, but I do not think it is ready for prime time without a solid base of data to support its use.

Statins, GLP-1 receptor agonists, and metformin all show signals for lower HCC risk in observational data. What would it take to test them as true chemoprevention, and what should clinicians tell patients now?

Observational data certainly have meaning, and lots of observational data with different designs, like cohort and case-control studies, strengthen the signal when combined. However, the gold standard, especially for something like this, has to be randomized controlled trials. There are ongoing trials of GLP-1 receptor agonists among patients with cirrhosis, so I hope we will get some answers soon. There are also trials ongoing with statins among patients with cirrhosis, and we may get some answers from those. I am not aware of trials of metformin.

What do we do in the meantime? Focusing on the underlying indication and treating it in the best possible way is the way to go. Any additional benefit in terms of reducing HCC risk can be secondary, or perhaps a cofactor in prescribing these medications, but I would not prescribe them for the sole reason of reducing HCC risk.

As it happens, [semaglutide, a GLP-1 receptor agonist, is FDA approved for] metabolic dysfunction–associated steatohepatitis [MASH], which is the severe form of MASLD.³ [GLP-1 receptor agonists] show evidence of reversing fibrosis, and I use them extensively to treat patients with advanced MASLD. Metformin is a fantastic medication for prediabetes, which happens to be a very strong risk factor for MASLD, so I would encourage people to use it. If it pans out that it reduces the risk of cancer, that is great.

My message on statins, particularly for nonhepatologists, is that there is still residual concern that using statins in people with liver disease might worsen the liver or increase liver enzymes. Yes, statins sometimes increase liver enzymes, but overall, they are highly beneficial for the primary indication, which is cardiovascular risk reduction. Mounting evidence shows that statins are either neutral to the liver or possibly beneficial in terms of reducing the risk of liver cancer.

Up to 30% of MASLD-related HCC may arise without recognized cirrhosis.⁴ How should teams approach patients with F3 fibrosis, and which markers could help decide who needs surveillance?

This is an important and difficult question, because a third of all MASLD-related liver cancers do not arise in the typical high-risk group we focus on for surveillance, which is patients with cirrhosis. The converse of that argument is that patients with MASLD and no cirrhosis number in the hundreds of millions globally, so it is impossible, inefficient, and ineffective to perform surveillance on all of them. F3 is the subgroup of patients without cirrhosis that has acquired the most attention, because their risk of liver cancer, while not elevated to the degree seen in cirrhosis, is higher than the rest.

In my opinion, which is not currently based on solid data, F3 coupled with additional risk factors for MASLD and a good life expectancy may merit surveillance. These additional risk factors are metabolic. If someone with F3 has diabetes, overweight or obesity, high blood pressure, and dyslipidemia, that would move me toward surveillance.

There are tools being studied that may soon become part of routine practice, like genetic testing panels. A patient who has the high-risk variants of PNPLA3 might sway me toward surveillance. We are also eagerly awaiting risk calculators that many groups are developing, which put in numbers what I just said in words: combining age, genetics, metabolic risk factors, and alcohol in 1 equation for patients with F3, dividing them into higher- and lower-risk groups, and focusing on the higher-risk group.

In summary, this is still a difficult area. It is reasonable to perform surveillance, particularly in the presence of additional risk factors, with an individualized discussion with the patient and their family about the benefits and risks.

Alcohol roughly doubled liver cancer risk in patients with metabolic dysfunction and alcohol-associated liver disease (MetALD).⁵ How should hepatologists, oncologists, and primary care clinicians screen for and address alcohol use in patients with MASLD?

This is an important issue. Part of the reason MASLD replaced the old name, nonalcoholic fatty liver disease [NAFLD], is that we discovered quickly that few people have purely nonalcoholic fatty liver disease. MetALD describes the range where alcohol consumption is not zero but is not in the range that causes alcohol-associated liver disease. It highlights a couple of things. First, alcohol plus MASLD is a worse combination than either alone. Second, which I may not have mentioned in the talk, just a couple of alcoholic drinks per day is not what many people, practitioners included, consider harmful.

Therefore, it starts with providers, who need to transmit this to patients and their families. Most experts, me included, would recommend complete abstinence from alcohol in the presence of any degree of fibrosis. There is probably some room for flexibility in the absence of cirrhosis, or maybe at F1, but it is a slippery slope. It is our duty to present the data to people, advocate for what the evidence shows, and serve as educators.

I want to wrap up by going back to systems. It is difficult to obtain a precise, reliable alcohol intake history, so systems are needed to properly implement alcohol screeners and act on them. In real life, some systems use the Alcohol Use Disorders Identification Test–Consumption [AUDIT-C], a set of questions you can ask patients; if they answer yes to a certain number of them, it indicates with high reliability who might have alcohol use disorder. Some systems implement these, which is good, but the flag remains there, and little action follows.

What to do when someone is flagged requires motivational interviewing, verifying the condition, looking at risk factors, and treating alcohol use disorder. It is a complicated clinical issue, and others and I are working on system-related solutions for these multistep processes, in which the human factor inevitably delays or prevents some of the steps. I look forward to a near future in which our health care systems will enable us to provide better care for many of the issues we discussed.

References

1. Thomas JA, Kendall BJ, Dalais C, Macdonald GA, Thrift AP. Hepatocellular and extrahepatic cancers in non-alcoholic fatty liver disease: a systematic review and meta-analysis. Eur J Cancer. 2022;173:250-262. doi:10.1016/j.ejca.2022.06.051
2. Huang DQ, Fowler KJ, Liau J, et al. Comparative efficacy of an optimal exam between ultrasound versus abbreviated MRI for HCC screening in NAFLD cirrhosis: a prospective study. Aliment Pharmacol Ther. 2022;55(7):820-827. doi:10.1111/apt.16844
3. FDA approves treatment for serious liver disease known as ‘MASH’. News release. FDA. August 15, 2025. Accessed November 7, 2026. https://tinyurl.com/yyprrd59
4. El-Serag HB. MASLD and cancer risk—hepatic and extrahepatic malignancies: what clinicians need to know. Presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, CO.
5. Park Y, Jung J, Han S, Kim GA. MASLD and MetALD increase the risk of liver cancer and GI cancer: a nationwide cohort study. Aliment Pharmacol Ther. 2024;60:1599-1608. doi:10.1111/apt.18286