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Originally published August 19, 2026
Last updated August 19, 2026
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The dramatic drop in viral hepatitis–related liver transplants has been a genuine good-news story in the healthcare world. With direct-acting antivirals boosting hepatitis C cure rates north of 95%, the proportion of U.S. patients undergoing transplantation for HCV-associated liver disease fell from 22.6% in 2011 to 4.7% ten years later. And in the case of hepatitis B, modern antivirals like tenofovir and entecavir have made a 20%-25% decline in HBV-related waiting-list registration possible.
But the cloud to this silver lining is a concurrent rise in transplant demand among patients with metabolic dysfunction–associated steatotic liver disease (MASLD) and its progressive inflammatory form, metabolic dysfunction–associated steatohepatitis (MASH). MASLD and MASH now rank second among leading indications for liver transplants domestically, and the number of transplants attributable to the conditions is estimated almost to quadruple by 2050 if effective prevention and treatment were not available.
Yet Liyun Yuan, MD, a transplant hepatologist with the USC Liver Health Center and USC Liver Transplant and Comprehensive Liver Disease Care Center, both part of Keck Medicine of USC, believes that MASLD/MASH’s impact on liver transplants can be a good-news story, too.
“Most patients may never need a transplant if they manage their condition early,” she insists. “That’s why it helps to have a consistent champion to monitor their trajectory and achieve the best outcomes available.”
MASLD/MASH affects at least one-third of U.S. adults. And while Yuan ascribes the rising rates in part to greater awareness of and screening for the conditions, core drivers remain the obesity, type 2 diabetes and associated systemic metabolic dysregulation that compromises and ultimately injures the liver.
The process begins when excess intrahepatic triglycerides trigger oxidative stress, lipotoxicity and chronic liver inflammation. As the liver tries to repair the damage, scar tissue builds up slowly — sometime over decades — and accumulated fibrosis separates the liver into small nodules, forming cirrhosis. At that point, increased risk for hepatocellular carcinoma (HCC) and complications of ascites, confusion and variceal bleeding arise. Yuan says, “When complications of cirrhosis occur and the liver can no longer function, the patient needs a liver transplant.”
Unfortunately, because MASLD/MASH progresses so slowly, it can remain largely asymptomatic until significant damage has occurred. Yet when a patient presents to primary care with a constellation of pressing metabolic concerns like obesity, type 2 diabetes, hypertension, dyslipidemia and more, latent MASLD/MASH can get lost in the clinical shuffle.
Even AST (aspartate aminotransferase) and ALT (alanine aminotransferase) tests can be deceiving, as levels can be normal in affected patients because the markers reflect current liver stress and not preexisting fibrosis or its severity.
All of which is why Yuan impresses upon primary care teams to keep MASLD/MASH in mind when evaluating patients.
“When they have diabetes, high blood pressure or excess weight,” she says, “we need to look at the liver component early so we can start helping them improve their metabolic issues and navigate weight loss before liver failure develops.”
Because if MASLD/MASH patients do reach the transplant stage, they face a tough road.
This patient population normally presents at an older age and often with cardiovascular comorbidities in addition to MASLD/MASH’s hallmark metabolic concerns. “As a matter of fact,” Yuan notes, “the number one cause of death for patients with MASLD is cardiovascular disease, before and after transplant.”
MASLD/MASH patients may also suffer from chronic kidney disease — particularly diabetic nephropathy — which can necessitate a combined liver and kidney transplant. And while it’s not uncommon to encounter BMIs as high as 45 in this population, weight loss can actually hamper outcomes rather than improve them.
“We call it sarcopenic obesity,” Yuan explains. “Their BMI may be very high, but they don’t have much muscle or strength. They’re in a catabolic state because of cirrhosis and chronic illness, so they’re in no condition to lose more weight. This makes it challenging to go through a liver transplant, and we have to screen patients intensively and try to optimize their condition before transplant.”
Once transplantation occurs, recovery poses further difficulties. “Patients may have a new liver,” Yuan cautions, “but their diabetes, high cholesterol, heart problems and high blood pressure don’t go away.” Rapid weight gain as patients’ appetite and stamina return in the first three to six months post-surgery is another development that physicians should attend.
The best way to do so, Yuan argues, is to pool efforts in a team approach to shepherding MASLD/MASH patients through liver transplants and beyond.
“This is such a quiescent disease,” she says. “If we intervene early when patients aren’t too sick, we can avoid having to focus energy on decompensated cirrhosis and put that energy toward providing comprehensive options instead. At Keck Medicine of USC, we have a multidisciplinary team of cardiovascular and renal health specialists, endocrinologists, and even nutritionists, weight-loss programs and physical therapy that not only mitigate metabolic issues and reduce cardiovascular complications but may also rejuvenate patients’ livers and keep them well so they don’t need a transplant in the first place.” That’s a good-news story we’d all like to hear.
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