Diabetes Core Update - Special Edition: MASH Part 2 – Diagnosis and Treatment (December 2025)

Podcast: Diabetes Core Update
Date: December 15, 2025
Host: Dr. Neil Skolnick
Guest: Dr. Alina Allen (Director of Hepatology, Mayo Clinic)
Episode Focus: Diagnosis and Treatment of Metabolic Associated Steatohepatitis (MASH)
Intended Audience: Physicians and healthcare professionals

Episode Overview

This special episode, the second in a three-part MASH (Metabolic Associated Steatohepatitis) series, centers on the diagnosis and treatment of MASH, building on Part 1's exploration of its prevalence, progression, and screening. Dr. Neil Skolnick interviews renowned hepatologist Dr. Alina Allen, providing actionable information for primary care, endocrinology, and hepatology audiences to improve the identification and management of MASH in clinical practice.

Key Discussion Points and Insights

1. Why Focus on F2 and F3 Fibrosis?

• Significance of Staging
  • Fibrosis is histologically graded 1–4, with F4 as cirrhosis.
  • Cirrhosis is linked to severe outcomes—decompensation, liver cancer, transplant. Aim is to intervene before stage 4.
  • "The risk starts at stage two, and this is where the mortality risk increases." (Dr. Allen, 03:14)
  • Screening for F2–F3 targets those where intervention impacts mortality but does not neglect earlier stages; patients with mild fibrosis (F0–F1) should still receive counseling to prevent progression.

2. Natural Progression of MASLD to Fibrosis

• Epidemiology
  • Approximately 10–14% of people with steatosis progress to F2 or higher fibrosis; cirrhosis develops in 2–3%. (05:38)
  • "A minority progress, but we want to prevent getting there for all the reasons described." (Dr. Allen, 05:52)

3. Screening and Diagnostic Modalities

• Stepwise Screening (06:06)
  • Begin with FIB4 index as recommended.
  • FIB4 Cutoffs:

    • 1.3 (general), >2.0 (age 65+) signals need for further evaluation.

• Elastography (FibroScan + MRE):
  • Elastography is the hepatologist's "stethoscope," measuring liver elasticity as a proxy for fibrosis and inflammation.
    • Fibroscan (VCTE):
      • Point-of-care test; main cutoff: 8 kPa (risk of ≥F2 fibrosis). (08:50)
    • MRI Elastography (MRE):
      • More accurate (measures greater liver volume); cutoff: 3.1 kPa; less affected by central obesity.
      • "The discordance between MRE and VCTE increases in those with BMI 35–40." (Dr. Allen, 10:47)
• ELF Test (Enhanced Liver Fibrosis):
  • Blood test assessing fibrogenesis; cutoff: ≥9–9.2 triggers further action. (13:35)
  • "ELF is convenient, especially if elastography isn't available." (Dr. Allen, 14:40)
  • Not yet standalone for treatment decisions except where elastography access is lacking.

4. When to Initiate Treatment

• Treatment Thresholds
  • FDA-approved therapies are indicated for patients with F2–F3 fibrosis.
  • No current FDA-approved therapy for cirrhosis (F4) as of 2025.
  • Always confirm staging to avoid inappropriate therapy in cirrhosis due to uncertain efficacy and safety. (15:20–16:43)

5. FDA-Approved Treatments for MASH (as of 2025)

• Resmetirom (Resdiffra):
  • Thyroid hormone receptor beta selective modulator.
  • Phase 3 data: 26% fibrosis response vs. 14% placebo; placebo-adjusted ~12%.
• Semaglutide:
  • Already familiar for diabetes/obesity—now FDA-approved for MASH with F2–F3 fibrosis.
  • Comparable placebo-adjusted fibrosis response (~14%).
  • "No GLP1 receptors in the liver; acts systemically." (Dr. Allen, 18:30)

6. Role of Primary Care and Endocrinology in MASH Treatment

• Expanding Scope:
  • Given the overlap with diabetes/obesity, primary care and endocrinology are poised to take on MASH treatment. (19:30)
  • "Absolutely, they can and should treat MASH... Awareness to screen is most important." (Dr. Allen, 19:39)
  • Always stage the liver before treatment to detect advanced fibrosis/cirrhosis and address liver cancer risks.

7. Legacy and Pipeline Treatments

• Pioglitazone, Vitamin E:
  • Former mainstays: modest benefit for steatosis/steatohepatitis, limited fibrosis impact.
  • "The bar has been raised by newly approved therapies... Vitamin E is not recommended by itself anymore." (Dr. Allen, 22:57)
• Medications in the Pipeline:
  • Tirzepatide, Retatrutide: Both are in Phase 3, with promising Phase 2 results suggesting higher response than current options.
  • Cervotide: Dual GLP1/glucagon receptor agonist; up to 65% fibrosis improvement in Phase 2.
  • "Very exciting—expect more treatment options soon." (Dr. Allen, 25:42)

8. Monitoring and Follow-Up

• Assessing Treatment Response:
  • Use elastography (FibroScan or MRE) for follow-up.
  • Look for >20% (MRE) or ~30% (VCTE) reduction as sign of histologic improvement.
  • “We shouldn’t measure earlier than a year—fibrosis improvement takes time.” (Dr. Allen, 28:18)
  • ELF: decrease of 0.5 as a supportive marker.
  • For fat/inflammation, MRI-PDFF or CAP can provide earlier indications of response.
• Guideline References:
  • Both resmetirom and semaglutide have published expert guidances (AASLD/Hepatology) for when and how to monitor.

9. Collaborative Approach

• Shared Responsibility:
  • Primary care, endocrinology, and hepatology are increasingly united in MASLD/MASH care.
  • "There's less distinction between hepatology and endocrinology now than 10 or 20 years ago." (Dr. Allen, 30:41)

Notable Quotes & Memorable Moments

• On the importance of recognizing F2 fibrosis:

  • “The most important complication is fibrosis... the only one associated with increased mortality. The risk starts at stage two.”
    — Dr. Allen (03:14)

• On the necessity of screening and intervention:

  • “We cannot really screen everybody, but mild stage 0–1 should also be counseled… to prevent further progression.”
    — Dr. Allen (04:46)

• On use of noninvasive diagnostic tools:

  • “Elastography is our stethoscope in hepatology.”
    — Dr. Allen (07:02)

  • “The FibroScan cutoff we should remember is 8 kPa for moderate-to-advanced fibrosis; 3.1 for MRE.”
    — Dr. Allen (08:50)

  • “ELF is convenient... if available it can be used as a first-line evaluation.”
    — Dr. Allen (14:40)

• On new and future therapies:

  • “The bar has risen with FDA-approved therapies; pioglitazone and vitamin E are not as potent.”
    — Dr. Allen (22:57)

  • “Very exciting—expect more agents in our toolbox soon.”
    — Dr. Allen (26:15)

• On interdisciplinary care:

  • “We are treating essentially the same disease spectrum, just focusing on different biomarkers... There’s less of a distinction now.”
    — Dr. Allen (30:41)

Timestamps for Key Segments

• [02:58] — Why screen for F2/F3 fibrosis
• [05:38] — Natural progression of MASLD to fibrosis and cirrhosis
• [06:06] — Stepwise screening: FIB4, elastography, ELF
• [08:50] — Interpreting elastography; F2 cutoff numbers
• [10:31] — Comparing MRI elastography and FibroScan
• [12:13] — The ELF blood test
• [15:20] — When to initiate (and not initiate) FDA-approved treatment
• [17:09] — Resmetirom and Semaglutide for MASH
• [19:30] — Who should treat: Primary care, endocrinologists, and hepatologists
• [22:28] — Legacy therapies: Pioglitazone and Vitamin E
• [24:05] — Pipeline therapies: Tirzepatide, Retatrutide, Cervotide
• [27:17] — How to monitor and assess treatment response
• [30:07] — Final thoughts: Interdisciplinary management and future opportunities

Conclusion

This episode offers clear, clinically relevant guidance on identifying and treating MASH, emphasizing the critical role primary care and endocrinology play alongside hepatology. New diagnostic tools and therapies are rapidly changing the landscape, and collaborative care will be central moving forward. With practical tips for staging, treating, and monitoring, this episode is an indispensable update for all providers managing patients with metabolic liver disease.