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30 percent have reached the inflammatory state of MASH,” says Bril. “And of those, 20 percent have reached MASH stage F2 or higher.” Trends in Disease Burden & Mortality The fat accumulation, inflammation, fibrosis, and cirrhosis that occur in the liver from MASLD/MASH are usually clinically silent. “Symptoms usually don’t become noticeable until it’s very advanced,” says Shravan Dave, MD, a board- certified gastroenterologist and transplant hepatologist at University of California San Diego who specializes in treating acute and chronic liver diseases. So, patients are unlikely to come in asking to be evaluated for this specific condition. “Although some patients can progress more quickly, it may take 10 to 15 years after diagnosis for progression to translate into visible signs like sarcopenia and jaundice,” explains Dave. In advanced stages, by the time that fibrosis has increased and cirrhosis or hepatocellular carcinoma are present, there are fewer, if any, options to treat. “We’re not in a position yet to say that we can reverse cirrhosis and there are no medications currently that are approved to do this,” explains Dave. “But fibrosis is treatable and can regress and improve.” Lifestyle changes, such as improved diet and exercise, along with FDA-approved medications can reverse early stage fibrosis and decrease steatosis. 9 Early identification of
events start increasing once you hit that threshold,” says Bril. MASH is the leading cause of liver transplantation in women and the second leading cause in men (after alcohol-associated liver disease 8 ). Risks of adverse outcomes rise meaningfully once fibrosis progresses to stages F2 and F3, with corresponding increases in all-cause and liver-related mortality. Compared Early identification of fibrosis remains critical to enabling early intervention, treatment, and slowing, or even reversal, of disease progression. with stage F0, all-cause mortality is approximately 50 percent higher at stage F2 and rises substantially with advanced fibrosis. Liver-related mortality increases more sharply across stages.7 Obesity remains a major driver of disease burden, with a substantial portion of individuals developing inflammation and fibrosis—and a significant subset progressing to clinically significant fibrosis (F2). 8 Recent therapeutic advances have expanded treatment options, making identification of patients with F2 and F3 fibrosis increasingly important.
fibrosis remains critical to enabling early intervention, treatment, and slowing, or even reversal, of disease progression. Without systematic screening, many cases may go undetected, notes Bril, adding: “MASH is not only highly prevalent, it’s worsening—and if we get to the party too late, these patients will have already developed cirrhosis or will be needing a liver transplant.” MASH stage F2 reflects a critical crossroad in disease progression, marking the onset of clinically significant fibrosis. “There is an inflection point between F1 and F2 where overall mortality and liver-related
MASLD OCCURS EARLY ON IN THE PROGRESSION OF METABOLIC DISEASE
MASLD with T2DM
MASLD with MetS
MASLD without MetS
T2DM Hyperinsulinemia
Metabolically Healthy Obesity
Dyslipidemia Hypertension IFG, IGT
Intramyocellular Lipid Accumulation B-Cell Dysfunction
MASLD
Dysfunctional Adipose Tissue Overweight/Obesity
PROGRESSION
Adapted from Bril F, et al., Clin Liver Dis. 2023;27(2):187-210.
Healthful Living Rx 11
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