Steatotic Liver Disease: Steatotic Liver Disease: MASLD to Drug Therapy

0:00Welcome to Board Pearls. This is episode one of two of the Steatotic Liver Disease chapter, in the Liver Disease module. This episode is metabolic dysfunction-associated steatotic liver disease, MASLD, from diagnosis to drug therapy. A woman with a bright liver on ultrasound shows why the names changed, what the diagnosis requires, how alcohol measured in grams a week decides the category, why fat becomes injury, why some patients progress, and why fibrosis stage predicts the outcome. A lean man and a woman with cirrhosis and no fat on her biopsy show the two presentations most often missed. A man with diabetes who came to his FibroScan straight from lunch shows how to stage fibrosis without a biopsy: the Fibrosis-4 index, FIB-4, FibroScan and what fools it, and magnetic resonance, MR, elastography. A woman who asks how much weight she needs to lose shows weight loss as a dose, diet and exercise, and bariatric surgery, and a man with cirrhosis shows when surgery is still safe. And a man with stage three fibrosis shows the two approved drugs, where pioglitazone and vitamin E fit, and why a statin is never withheld.

1:11Here's the first patient. A forty-nine-year-old woman of Mexican descent has a bright liver on an ultrasound done for gallstones. Her body mass index, BMI, is twenty-nine, her triglycerides one hundred eighty, and her hemoglobin A1c, HbA1c, five point nine percent. Her alanine aminotransferase, ALT, is forty-one. She drinks about one glass of wine a night. She's been told before that her liver tests were "a little high, nothing to worry about."

1:42Steatosis on ultrasound with metabolic risk factors and modest drinking is MASLD, and "nothing to worry about" isn't a conclusion anyone can draw yet. The name itself is new. In twenty twenty-three, a multi-society Delphi consensus retired the labels nonalcoholic fatty liver disease, NAFLD, and nonalcoholic steatohepatitis, NASH, and named the disease by what it is rather than what it isn't. Steatotic liver disease is now the umbrella term for any liver with steatosis on imaging or histology. Within it, MASLD replaces NAFLD, metabolic dysfunction-associated steatohepatitis, MASH, replaces NASH, and metabolic dysfunction and alcohol-associated liver disease, MetALD, names the patient with metabolic risk who also drinks moderately.

2:35The change matters because it makes the diagnosis positive. The word nonalcoholic defined the disease by an exposure that was absent rather than by its driver, metabolic dysfunction, and fatty liver carried stigma without diagnostic content. MASLD is now diagnosed from what's found, not from what's excluded.

2:57The diagnosis requires hepatic steatosis on imaging or biopsy plus at least one of five cardiometabolic criteria. The first is obesity: a BMI over twenty-five, or over twenty-three in Asians, or a waist over ninety-four centimeters in men or eighty in women, with lower cutoffs in South Asian and Hispanic populations. The second is glucose: a fasting glucose over one hundred, an HbA1c of five point seven percent or more, type two diabetes, or treatment for diabetes. The third is a blood pressure of one hundred thirty over eighty-five or more, or treatment for it. The fourth is triglycerides of one hundred fifty or more, or treatment. The fifth is a high-density lipoprotein, HDL, under forty in men or fifty in women, or treatment.

3:43One criterion is enough, unlike the three that metabolic syndrome requires, because any single cardiometabolic feature with steatosis carries the same metabolic biology. She has steatosis plus a BMI over twenty-five, triglycerides over one hundred fifty, and an HbA1c over five point seven: three criteria where one would do.

4:05Her nightly glass of wine decides which category she's in. Alcohol is now a continuous variable measured in grams a week, at fourteen grams per standard United States drink. Pure MASLD is steatosis with cardiometabolic criteria and alcohol under one hundred forty grams a week in women or two hundred ten in men, roughly under one and a half to two drinks a day. Alcohol-associated liver disease is three hundred fifty grams a week or more in women and four hundred twenty or more in men, roughly three and a half and four drinks a day. MetALD is the band between them, in a patient with cardiometabolic risk.

4:40Her seven drinks a week are about one hundred grams, under one hundred forty, so she has MASLD. Three glasses a night, close to three hundred grams, would make it MetALD. MetALD looks like MASLD on biopsy and imaging, with a heavier inflammatory component, it behaves like neither pure disease, and it's managed with a heavy emphasis on cutting alcohol, even below the threshold for alcohol-associated disease.

5:05With the label settled, the next question is whether her fat is injuring her liver. MASLD is a disease of insulin resistance with genetic susceptibility layered on top. Insulin-resistant adipose tissue fails to suppress lipolysis, which floods the liver with free fatty acids. High insulin drives de novo lipogenesis through sterol regulatory element-binding protein 1c, SREBP-1c. And dietary fructose bypasses the early steps of glycolysis and feeds straight into triglyceride synthesis. Triglyceride accumulates because it forms faster than the liver can export it as very-low-density lipoprotein, VLDL, and the result is bland steatosis.

5:51MASH develops when the load shifts to lipotoxic intermediates: ceramides, diacylglycerols, free cholesterol, and oxidized fatty acids. They disrupt mitochondria, generate reactive oxygen species, deplete glutathione, and drive endoplasmic reticulum stress. Hepatocytes undergo apoptosis, Kupffer cells and macrophages release tumor necrosis factor alpha, TNF-alpha, and the interleukins IL-6 and IL-1 beta, and stellate cells lay down fibrosis. The old two-hit model has given way to a network of many hits: metabolic flux, lipotoxicity, mitochondrial dysfunction, gut dysbiosis with a leaky barrier, and adipokine signaling, with high leptin and low adiponectin. All of it rests on a mismatch between the supply of fatty acids and the hepatocyte's capacity to dispose of them.

6:44Her ancestry matters, because genetics largely explains why some patients progress. PNPLA3 I148M impairs the breakdown of triglyceride in lipid droplets and accelerates steatosis, MASH, fibrosis, cirrhosis, and liver cancer. Homozygosity roughly doubles the risk of cirrhosis and triples the risk of liver cancer in MASLD, and it amplifies alcohol-associated disease too. Its allele frequency of about fifty percent in Hispanic populations helps explain their more severe disease, which is relevant to her.

7:19The other variants act differently. TM6SF2 E167K impairs VLDL secretion, trapping triglyceride in the liver while lowering serum low-density lipoprotein, LDL, and cardiovascular risk, so a carrier has a fatty liver with a reassuring lipid panel. A loss-of-function HSD17B13 variant protects against fibrosis and cirrhosis in both MASLD and alcohol-associated disease and has been a drug target, while MBOAT7 adds risk, particularly in alcohol-associated disease. Genetic testing isn't routine.

8:03One thing predicts her outcome above all, and it isn't her ALT. At any time, about seventy to seventy-five percent of MASLD is bland steatosis, called MASL, and twenty-five to thirty percent is MASH, with ballooning and lobular inflammation. MASH is the form that drives fibrosis, and about one in five patients with MASH progresses over the long term. The strongest predictor of liver-related death is the fibrosis stage, not the inflammatory grade, with liver mortality rising steeply at each stage to about twenty-three per thousand person-years at stage four. Her ALT of forty-one says almost nothing about her future, her fibrosis stage says nearly everything, and staging it is her next step.

8:48Two other patients show the presentations most often missed. A forty-three-year-old Korean man with a fatty liver has a BMI of twenty-two, a waist of ninety-five centimeters, and triglycerides of two hundred. His BMI is under the Asian cutoff of twenty-three, but his waist over ninety-four and his triglycerides over one hundred fifty make this MASLD. He has lean MASLD, which makes up ten to twenty percent of MASLD worldwide and is overrepresented in Asian populations. It carries the same insulin resistance and visceral fat, deposited inside the abdomen and liver rather than under the skin, where the BMI can't see it.

9:26Lean MASLD isn't benign. Cardiovascular and liver mortality are at least as high as in obese MASLD, and some studies suggest faster progression, perhaps because the normal BMI reassures patient and doctor alike. His weight loss target is three to five percent rather than seven to ten, because he has less to lose, but the strategy is the same: a calorie deficit, exercise, and treatment of his cardiometabolic risk.

9:55The second patient's liver has lost the fat that would have named it. A sixty-four-year-old woman with obesity, diabetes, and hypertension has cirrhosis without steatosis on biopsy and a negative workup, so it's been labeled cryptogenic. Most such cases are burned-out MASH. The fat disappears as the liver scars and loses its lipid-storing hepatocytes, and the inflammation may quiet. Cryptogenic cirrhosis with cardiometabolic features is MASH cirrhosis until proven otherwise, which is supported by steatosis recurring after transplant in about a third of these patients. Most cryptogenic liver cancers likewise arise on MASH cirrhosis or, less often, on MASH without cirrhosis.

10:35Staging is the step every patient needs, and the fourth patient shows how it's done without a biopsy. A sixty-two-year-old man has MASLD with type two diabetes and a BMI of thirty-seven. His aspartate aminotransferase, AST, is forty-eight, his ALT fifty-five, and his platelets one hundred sixty thousand. His ultrasound shows a bright liver. He came straight from lunch to his FibroScan appointment.

11:00He has MASLD with diabetes and obesity, and what he needs is a fibrosis stage. The question in MASLD isn't steatosis but advanced fibrosis. A biopsy carries a one to three percent rate of symptomatic complications, samples a tiny fraction of the organ, and suffers from disagreement between pathologists on inflammation and ballooning. So staging is tiered and noninvasive, with biopsy kept for patients who are still uncertain after blood tests and elastography.

11:29The first test is FIB-4, which is essentially free, calculated from age, AST, ALT, and platelets. A value under one point three rules out advanced fibrosis with a negative predictive value of about ninety percent, a value over two point six seven means high risk, and the range between is indeterminate and needs a second test. Its area under the curve for advanced fibrosis in MASLD is about zero point seven eight to zero point eight zero, good for a screen but not a final answer. Over sixty-five, the lower cutoff rises to two point zero, because age weighs heavily in the formula and would otherwise overclassify older patients. A low-risk FIB-4 is repeated in one to three years. His is about two point five, which is indeterminate, isn't reassuring, and calls for a second test.

12:18His second test is elastography. Some pathways use the enhanced liver fibrosis, ELF, test, with a MASLD cutoff of nine point eight, but most use vibration-controlled transient elastography, VCTE, called FibroScan. It times a low-frequency shear wave through the liver and reports stiffness in kilopascals, with cutoffs specific to the cause of liver disease. In MASLD, a stiffness under eight kilopascals effectively rules out advanced fibrosis, meaning stage three to four, a value over twelve to fourteen is consistent with cirrhosis, and eight to twelve is indeterminate. The same probe's controlled attenuation parameter, CAP, measures fat, not stiffness: about two hundred forty-eight decibels per meter means any steatosis, and about two hundred eighty means moderate to severe steatosis.

13:11His reading has to be judged against what falsely raises it. Stiffness is falsely raised by obesity, which causes failure rates of three to twenty-seven percent and is worst at a BMI over thirty-five, and by severe steatosis, hepatic congestion, biliary obstruction, acute hepatitis, and food within three hours. His reading is thirteen kilopascals, which suggests cirrhosis, but he ate within the hour, his BMI is thirty-seven, and his CAP shows severe steatosis, so the reading can't label him cirrhotic.

13:45The same reading also answers the portal hypertension question. Under the Baveno seven criteria, a stiffness of twenty-five or more rules in clinically significant portal hypertension, and a stiffness under twenty with platelets over one hundred fifty thousand allows screening endoscopy to be skipped. Even taken at face value, his thirteen kilopascals and his one hundred sixty thousand platelets mean no endoscopy now. Chapter twenty-three covers portal hypertension.

14:13Because his FibroScan can't be trusted, he moves to the next test. MR elastography is the most accurate noninvasive fibrosis test, and it's used when VCTE is indeterminate or unreliable, which in MASLD usually means severe obesity. Magnetic resonance imaging, MRI, proton density fat fraction, PDFF, is its counterpart for measuring fat. A biopsy now would expose him to complication risk before the noninvasive sequence is finished. His MR elastography shows stage two fibrosis, not cirrhosis. That puts him in the range for drug therapy, and spares him the cancer surveillance and portal hypertension workup that a cirrhosis label would have brought.

14:54The twenty twenty-three American Association for the Study of Liver Diseases, AASLD, MASLD guidance and the American Gastroenterological Association, AGA, Clinical Care Pathway, updated in twenty twenty-five, use the same order: FIB-4, then VCTE, then MR elastography, with biopsy reserved. Concordant low results, a FIB-4 under one point three and a VCTE under eight, effectively rule out advanced fibrosis and keep the patient on lifestyle care. Concordant high results, a FIB-4 over two point six seven and a VCTE over twelve to fourteen, make a biopsy unnecessary in many patients, who are managed as advanced. Discordant results, an indeterminate VCTE, or any clinical question that the stage would change go to MR elastography or biopsy.

15:47A patient with concordant results shows the other outcome. A fifty-seven-year-old woman has a FIB-4 of three point two and a fasting FibroScan of sixteen kilopascals at a BMI of thirty-one. Her results agree, without confounders, so she's managed as advanced fibrosis, probably cirrhosis, with liver cancer surveillance and portal hypertension assessment. Her sixteen kilopascals neither rules in clinically significant portal hypertension nor lets her skip screening endoscopy.

16:17Once the stage is known, treatment follows it, and the next patient shows the first step. A forty-four-year-old woman has MASH with stage two fibrosis on MR elastography. Her BMI is forty-one and her HbA1c six point one. She drinks two glasses of wine on weekends and two cans of soda a day. She's tried diets before and lost little. She asks how much weight she needs to lose for it to matter.

16:44Her question has a precise answer, because weight loss works like a dose. Lifestyle change is the only intervention with evidence of histologic improvement across the whole MASLD spectrum. Losing about five percent of body weight reduces liver fat. Seven to ten percent resolves MASH in sixty to ninety percent of patients and reduces ballooning and lobular inflammation. Ten percent or more regresses fibrosis in about forty-five percent. Less than five percent rarely changes the histology. So five percent is the floor and seven to ten the practical goal for MASH. With stage two fibrosis, her goal is ten percent, a large amount at a BMI of forty-one.

17:25Diet and exercise deliver that dose. The Mediterranean pattern has the strongest evidence: olive oil as the main fat; fish, vegetables, legumes, whole grains, and nuts; and limited red and processed meat. It cuts the saturated fat and refined carbohydrate that drive lipogenesis, and it adds omega-three fatty acids and polyphenols with anti-inflammatory effects. Commercially produced fructose, in sweetened drinks and ultra-processed foods, and red and processed meat should go, so her two sodas a day are the first specific, measurable change. Low-carbohydrate, intermittent fasting, vegan, and paleo diets improve the liver in proportion to their calorie deficit. The Mediterranean pattern is preferred for its cardiovascular benefit, but a diet she'll keep beats one she abandons.

18:17Exercise reduces liver fat even without weight loss, through glucose uptake by muscle that doesn't depend on insulin. The target is one hundred fifty to three hundred minutes a week of moderate exercise, or seventy-five to one hundred fifty of vigorous exercise, with resistance training added. Aerobic and resistance training reduce liver fat similarly, aerobic training burning more energy and resistance training preserving lean mass, so the combination is best, and it's prescribed from the first visit rather than after the weight comes off.

18:45Two smaller measures complete her plan. Coffee is associated with slower fibrosis progression in MASLD and alcohol-associated disease and is a cheap, low-risk recommendation. Alcohol should be restricted or eliminated, because its injury adds to the metabolic injury, and stopped entirely with significant fibrosis, so with stage two fibrosis her weekend wine stops too.

19:08After a year she's lost four percent, under the floor, so surgery comes up, not as a failure of effort but because the dose she's achieved isn't the dose her liver needs. Bariatric surgery is the most effective weight loss for severe obesity, and AASLD guidance considers it in MASLD patients who meet standard bariatric criteria, rather than as a primary treatment for MASLD. The twenty twenty-two American Society for Metabolic and Bariatric Surgery, ASMBS, and International Federation for the Surgery of Obesity and Metabolic Disorders, IFSO, indications recommend surgery at a BMI of thirty-five or more regardless of comorbidity, and support considering it at thirty to thirty-four point nine with metabolic disease such as type two diabetes. They replaced the old threshold of forty, or thirty-five with a comorbidity.

20:01Its liver results are large. At one year, steatosis improves in about eighty-eight percent, MASH resolves in about fifty-nine percent, and fibrosis improves in about thirty percent. Roux-en-Y gastric bypass tends to produce more weight loss and more diabetes remission, sleeve gastrectomy has fewer complications and is now more common, and adjustable banding is largely abandoned because it fails in the long term. Her HbA1c is in the prediabetic range, so the sleeve's lower complication rate decides it. A year later she's lost twenty-two percent, and her MR elastography shows stage one fibrosis.

20:38Patients who won't have surgery have other options. Intragastric balloons and endoscopic sleeve gastroplasty give ten to fifteen percent weight loss at six to twelve months, and glucagon-like peptide one, GLP-1, drugs have approached surgical weight loss in some trials.

20:56Cirrhosis doesn't automatically rule surgery out, and the next patient shows what does. A fifty-six-year-old man with MASH cirrhosis and a BMI of forty-three has been told his cirrhosis rules surgery out. Compensated MASH cirrhosis can undergo bariatric surgery at an experienced center when synthetic function is preserved, the Model for End-Stage Liver Disease, MELD, score is low, there's been no decompensation, and there's no clinically significant portal hypertension. A hepatic venous pressure gradient over ten millimeters of mercury excludes surgery in most centers, a gradient over fifteen is an absolute contraindication, and a gradient of ten to fifteen, or non-bleeding varices, is decided case by case by hepatology and hepatobiliary surgery together.

21:41His MELD is eight, his platelets are normal, he's never decompensated, and his gradient is seven, so he can proceed at an experienced center. The gradient, not the BMI or the diagnosis, decides. Some programs also consider bariatric surgery before transplant, or combined or staged with it. Chapter twenty-four covers transplant.

22:02When lifestyle change alone can't reach the dose, drugs come in, and the next patient shows how they're chosen. A fifty-seven-year-old man has MASH with stage three fibrosis on MR elastography and no cirrhosis. His BMI is thirty-four. He has type two diabetes on metformin with an HbA1c of seven point eight, and a high LDL on atorvastatin eighty milligrams. He's lost four percent with lifestyle changes. His primary care doctor wonders whether the statin is hurting his liver.

22:33He has MASH with stage three fibrosis, without cirrhosis, and lifestyle change hasn't reached the dose, so he's a candidate for drug therapy. In March twenty twenty-four, resmetirom became the first drug approved by the Food and Drug Administration, FDA, for MASH, and semaglutide followed. Pioglitazone and vitamin E are older off-label options with biopsy evidence in defined groups.

22:59Semaglutide suits him best. It's a GLP-1 receptor agonist that drives weight loss through central appetite suppression and delayed gastric emptying, and it improves insulin sensitivity. At two point four milligrams weekly in biopsy-proven MASH with stage two to three fibrosis, it resolved MASH without worsening fibrosis in about sixty-three percent at seventy-two weeks, roughly twice the placebo rate. It received FDA accelerated approval on August fifteenth, twenty twenty-five, for MASH without cirrhosis and with stage two to three fibrosis, as an adjunct to diet and activity, the first GLP-1 drug approved for MASH. Tirzepatide, a dual GLP-1 and glucose-dependent insulinotropic polypeptide, GIP, agonist, produces even larger weight loss and has shown MASH resolution. With obesity and diabetes, one drug treats all three problems.

23:52Its side effects are mostly early. Nausea, vomiting, and gastroparesis-like symptoms dominate the first weeks, with rare pancreatitis and a thyroid C-cell concern that hasn't been confirmed in clinical use, so it's titrated slowly. He meets the label and starts semaglutide, titrated to two point four milligrams weekly.

24:12His primary care doctor's worry has a clear answer: keep the statin. Statins don't treat MASH, but they're safe to start and continue in MASLD, even with stable raised aminotransferases, and they reduce cardiovascular death in a population that dies mostly of cardiovascular disease. Stopping his atorvastatin would trade a liver risk that's been dismissed for a cardiac risk that's real, and semaglutide doesn't change his statin dose.

24:37The other approved drug is resmetirom, an oral thyroid hormone receptor beta-selective agonist that acts in the liver. The beta receptor dominates in the liver and drives mitochondrial fatty acid oxidation and bile acid metabolism, while the alpha receptor carries the effects on the heart and bone, so beta selectivity activates liver metabolism without thyroid toxicity. In biopsy-proven MASH with stage one-B to three fibrosis, it resolved MASH in about a quarter to thirty percent at fifty-two weeks, roughly three times the placebo rate, and improved fibrosis by a stage in about a quarter. It has accelerated approval for MASH without cirrhosis and with stage two to three fibrosis, alongside diet and exercise, without a biopsy requirement.

25:20Its dosing and limits matter. The dose is eighty milligrams daily under one hundred kilograms and one hundred milligrams at or above one hundred, given for a year, after which fibrosis is reassessed and the drug is stopped if fibrosis has worsened. It isn't approved in compensated cirrhosis, which its trial excluded. It's a CYP2C8 substrate and a strong inhibitor of OATP1B1 and OATP1B3, so statin doses are capped, atorvastatin and pravastatin at forty milligrams and rosuvastatin and simvastatin at twenty, the resmetirom dose is lowered with clopidogrel, and gemfibrozil is avoided. On resmetirom, his atorvastatin would have to drop to forty, another reason semaglutide suits him.

26:06A different patient shows where resmetirom fits. A forty-eight-year-old woman with MASH and stage two fibrosis has a normal BMI and no diabetes, takes simvastatin forty milligrams, and weighs seventy kilograms. Both labels fit, but semaglutide's weight and diabetes benefits matter little for her, so resmetirom fits better: eighty milligrams daily, her simvastatin reduced to twenty, and her fibrosis reassessed at a year.

26:34The older options need a biopsy. Pioglitazone is a thiazolidinedione that targets peroxisome proliferator-activated receptor gamma, PPAR gamma, improving insulin sensitivity, liver fat, and MASH histology. A trial in patients without diabetes missed its primary endpoint but resolved MASH significantly more often than placebo, and later trials in diabetes confirmed the benefit. The twenty twenty-three AASLD guidance recommends it for biopsy-proven MASH with type two diabetes, so a patient staged by MR elastography would need a biopsy to follow the guidance, unlike with the approved drugs.

27:14Pioglitazone has real costs. It causes weight gain of about two and a half to nearly five kilograms over one to three years, worsens heart failure, so it's avoided in class three or four heart failure, raises fractures in postmenopausal women, causes fluid retention, and carries a debated bladder cancer signal. Against that, it lowers major adverse cardiovascular events in diabetes. For a man with obesity trying to lose weight, the weight gain is a real cost.

27:41Vitamin E fits a different patient. A thirty-six-year-old woman has biopsy-proven MASH without diabetes or cirrhosis. Natural alpha-tocopherol, eight hundred international units a day, improves histology in about forty percent of such patients, as an antioxidant that quenches the reactive oxygen species of lipotoxicity, and the twenty twenty-three AASLD guidance recommends it for biopsy-proven MASH without diabetes. Its cautions are a prostate cancer signal from a large prevention trial, hemorrhagic stroke at high doses, and a controversial signal for all-cause mortality above eight hundred units. It isn't recommended with diabetes, in MASH or cryptogenic cirrhosis, or without biopsy-proven MASH. She meets every requirement.

28:25Several drugs didn't work. Obeticholic acid improved fibrosis, but the FDA declined to approve it for MASH, with itching in about half of patients and an adverse lipid profile. Pentoxifylline, fibrates, ursodeoxycholic acid, omega-three fatty acids, and vitamin C showed no histologic benefit.

28:45Here are the traps the boards set in these patients. MASLD needs one metabolic criterion, not three. Drinks a day have to be converted to grams a week. A moderate drinker with metabolic risk has MetALD, not pure MASLD. Prognosis comes from fibrosis stage, not the ALT or the amount of fat. A normal lipid panel in a TM6SF2 carrier, or a normal BMI in a lean patient, isn't reassuring. And cirrhosis in a patient with diabetes and obesity isn't cryptogenic.

29:18The staging traps follow. Staging doesn't start with a biopsy. The cutoff of one point three doesn't apply over sixty-five. An indeterminate FIB-4 isn't reassuring. A FibroScan after a meal, or in severe obesity, congestion, obstruction, or acute hepatitis, overcalls fibrosis. CAP measures fat, not stiffness. Cutoffs from another liver disease don't apply. Patients whose two tests agree don't need a biopsy, while discordant results need a third test.

29:50The lifestyle and surgery traps come next. A vague weight target doesn't work, and less than five percent isn't enough. Added fructose matters. Exercise is prescribed from the first visit, not after weight loss. Alcohol stops with significant fibrosis. The old BMI threshold of forty no longer applies to surgery. Cirrhosis alone doesn't rule out surgery, but a gradient over fifteen does.

30:14The drug traps close the list. Resmetirom and semaglutide aren't used in cirrhosis. Resmetirom needs capped statin doses, a lower dose with clopidogrel, and no gemfibrozil. Vitamin E isn't given with diabetes or cirrhosis, and neither pioglitazone nor vitamin E is given without biopsy-proven MASH. Pioglitazone is avoided in advanced heart failure. Pentoxifylline and ursodeoxycholic acid don't work. And a statin is never withheld because of MASLD.

30:47So, start to finish. Diagnose MASLD positively: steatosis plus at least one cardiometabolic criterion. Classify by alcohol in grams a week: under one hundred forty for women or two hundred ten for men is MASLD, up to three hundred fifty or four hundred twenty is MetALD, and above that is alcohol-associated disease. PNPLA3 raises risk, TM6SF2 raises liver fat while lowering LDL, and HSD17B13 loss of function protects. Lean MASLD carries similar risk, and cryptogenic cirrhosis with metabolic risk is burned-out MASH. Judge prognosis by fibrosis stage.

31:31Stage with FIB-4 first: under one point three, or two point zero over sixty-five, is low risk and is repeated in one to three years. Then use VCTE, where under eight kilopascals rules out advanced fibrosis and twelve to fourteen or more suggests cirrhosis, read in light of meals, obesity, congestion, obstruction, and inflammation. Twenty-five or more rules in clinically significant portal hypertension, and under twenty with platelets over one hundred fifty thousand means no screening endoscopy. Send discordant or unreliable results to MR elastography.

32:09Treat with weight loss as a dose: five percent reduces fat, seven to ten resolves MASH, and ten or more can regress fibrosis, or three to five in lean MASLD. Use a Mediterranean diet without added fructose, one hundred fifty to three hundred minutes of exercise a week, coffee, and no alcohol with significant fibrosis. Offer bariatric surgery at a BMI of thirty-five, or thirty with metabolic disease, including in compensated cirrhosis with a gradient under ten at an experienced center.

32:39For MASH without cirrhosis and with stage two to three fibrosis, use semaglutide with obesity or diabetes, or weight-dosed resmetirom with capped statins. Pioglitazone suits biopsy-proven MASH with diabetes, and vitamin E suits biopsy-proven MASH without diabetes or cirrhosis. Never withhold a statin.

33:00Episode two is alcohol-associated liver disease: the spectrum, severe alcoholic hepatitis and its scores, steroids and what doesn't work, and early transplant.

33:13For the full chapter, the practice vignettes, and the topic-tagged question bank, head to board pearls dot com. You'll find the rest of the series on Apple Podcasts, Spotify, or wherever you listen to podcasts. That brings us to the end of episode one of two of chapter twenty-one, and I'll see you in the next one.