302 - Confronting a metabolic epidemic: how to prevent, diagnose, & manage liver disease

KEYPOINTS

• 01

  The liver is the one vital organ with no temporary external support.

  Lungs have ventilators, hearts have balloon pumps and assist devices, kidneys have dialysis. For the liver, devices like the MARS machine exist but nothing really bridges acute failure. Wattacheril, a transplant hepatologist who directs Columbia's MASLD program, notes the 3.5 lb organ performs over 300 functions: macronutrient metabolism and glucose regulation, clotting proteins, immune functions, detoxification of drugs and toxins, bile acids, and lipoprotein production and clearance. Attia recalls a story from his training of baboons once used as temporary external livers.

• 02

  MASLD is the new name for NAFLD, with clearer subcategories.

  The old name defined the disease by what it wasn't, and patients who never drank were labelled alcoholics. The umbrella is now steatotic liver disease. It includes MASLD (metabolic dysfunction), MetALD (metabolic dysfunction plus moderate alcohol), alcohol-related disease, monogenic forms, drug-associated fat and cryptogenic cases. Steatosis means fat in at least 5% of hepatocytes. MASLD affects an estimated 25–35% of people, conservatively, and disproportionately children.

• 03

  A normal ultrasound doesn't rule out fatty liver.

  Standard ultrasound usually misses fat below about 30%. Vibration-controlled transient elastography (FibroScan) gives two numbers at the bedside: a CAP 'fat score' and a stiffness 'scar score' (vibrations travel differently through a 'sponge' than a 'brick'). It isn't technically feasible in about 8–10% of her patients. MRI-PDFF quantifies fat and iron precisely and is used in research. A lean person (BMI 22) with a CAP around 400 and no insulin resistance suggests a rarer export problem, such as a genetic lipid disorder.

• 04

  AST and ALT are injury markers, not 'function' tests, and lab limits have drifted up.

  These enzymes leak when stressed hepatocytes burst. True function is albumin, clotting and glucose handling. Older thresholds were about 19 for women and 30 for men; labs now flag in the 40s–50s because the population has changed. For patients already diagnosed and in treatment, she's pleased below about 30, still uses about 40 as a workup threshold, and becomes concerned at persistent 1.5–2 times the upper limit for about six months. Discussing Attia's AST 34 and ALT 21, she asks about lifting within 24 hours, CK, alcohol timing and medications such as ezetimibe, and suggests retesting after rest days without alcohol.

• 05

  Alcohol and metabolic fat injure the liver in similar ways and often coexist.

  Alcohol dehydrogenase converts ethanol to acetaldehyde. When capacity is overwhelmed, redox balance shifts, peroxidation occurs, and immune cells are recruited. Biopsies often can't distinguish alcohol from metabolic injury. A standard drink is 1.5 oz liquor, 5 oz wine or 12 oz beer (about 14 g of alcohol), and the CDC's 'moderate' is 2 a day for men and 1 for women. She asks about weekly quantity, binge patterns and context. She uses phosphatidylethanol (PEth), which reflects about 1–2 weeks of drinking, because self-report and shame often diverge. For most women who drink, she says breast cancer risk exceeds liver risk.

• 06

  Fibrosis stages progress slowly, and even early cirrhosis can reverse.

  NASH (now MASH) means fat plus inflammation plus 'ballooned' pre-death hepatocytes. Fibrosis runs from stage 1 ('chicken wire' around the central vein in adults) to stage 3 (bridging) and stage 4 (cirrhosis, with nodules). Each stage takes about 5–7 years in MASLD, based mostly on European-ancestry data. Hepatitis C cures showed some early cirrhosis regresses. Cirrhosis is 'not a death sentence' but triggers cancer screening every six months.

• 07

  For early MASLD, the bigger near-term risks are diabetes, heart disease and cancer.

  She often tells patients: your scar score is normal, your fat score is very high, and it can normalize in six weeks to six months, but unchanged you'll likely develop diabetes. Patients tend to hear that as empowering. Hepatocellular carcinoma risk in cirrhosis is about 3–5% a year. It's highest in hemochromatosis, then hepatitis C plus alcohol. Hepatitis B is the outlier, causing cancer even without advanced fibrosis. Her group is studying whether stage 3 MASLD needs earlier screening.

• 08

  Lifestyle remains first-line treatment, with specific emphasis on muscle.

  Many patients say 'I don't eat that much fat,' but she says the main issue is glucose handling and refined carbohydrates. Many of her female patients with lean fatty liver have low muscle, so she prescribes combined resistance and aerobic exercise or, for sedentary people, a walking prescription. She refers detailed, culturally appropriate nutrition planning to dietitians. On fructose, she says studies that separate it from weight loss and insulin resistance show little net difference, so she recommends avoiding processed foods rather than isolating one sugar.

• 09

  Drugs: GLP-1s for appropriate patients, and resmetirom is the first liver-directed success.

  For patients with a BMI of about 28–40, stage 2 disease and maximized lifestyle changes, she brings in GLP-1 agonists, with frank talks about muscle loss and weight regain after stopping. She raises bariatric surgery at stage 3 or early cirrhosis. The thyroid-hormone receptor agonist resmetirom showed phase 3 efficacy in a population about 90% of European ancestry. Vitamin E (from the PIVENS trial) helps steatosis but carries concerns about cardiovascular risk, prostate cancer and dose-dependent mortality.