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MASLD — metabolic dysfunction-associated steatotic liver disease — master index¶
Last curated: 2026-09-02 · status: built, deepened and independently audited · 22 pages · 3,570 lines · 361 records in the bibliography (360 cited by pages) · 43 open questions · 19 dots not yet connected
2026-09-02 depth pass and independent audit. Claude added 93 records to the 274-record corpus left by the preceding audit. Codex re-fetched every addition, corrected claim and provenance problems, removed eight padding-only citations, and added one corrective protocol. The audited result is 360 distinct wiki-cited records (16.36/page): a net gain of 86 over the true pre-depth baseline. Twenty pages are curated; genetics.md and clinical-trials-landscape.md remain draft because of the unresolved rapirosiran publication–registry enrolment discrepancy. See LOG.md.
The condition in five sentences. MASLD is hepatic steatosis occurring with at least one of five cardiometabolic criteria, and it acquired that name only in June 2023, when a 236-panellist multisociety Delphi process replaced "non-alcoholic fatty liver disease" — a diagnosis defined by what the patient did not do — with a positively defined one (Rinella 2023, PMID 37363821). It affects roughly 30% of the world's adults, and the clinically decisive variable is fibrosis stage, not steatohepatitis: fibrosis, and no other histological feature, tracks long-term outcomes, and adding a histological diagnosis of steatohepatitis to a model improves prediction at no fibrosis stage (Angulo 2015, PMID 25935633; Hagström 2017, PMID 28803953). After two decades in which nothing was approved, two drugs arrived in eighteen months — resmetirom in March 2024 and semaglutide in August 2025, both conditionally, both for non-cirrhotic MASH with F2–F3 fibrosis, and both on histological surrogates whose outcome confirmation is still running (Harrison 2024, PMID 38324483; Sanyal 2025, PMID 40305708). The genetic architecture is unusually tractable for a metabolic disease, anchored on PNPLA3 I148M since 2008 and now yielding antisense and siRNA therapeutics against PNPLA3 and HSD17B13 (Romeo 2008, PMID 18820647; Abul-Husn 2018, PMID 29562163). The dominant clinical problem is that most people with MASLD die of cardiovascular disease or extrahepatic cancer rather than liver disease, so a hepatology-shaped condition mis-frames the risk it is meant to describe — and a fifth fact now sits underneath the other four, that the category itself is unstable, since roughly 39% of people classified as MASLD by self-reported alcohol intake carry a phosphatidylethanol concentration in the MetALD or ALD range, unsupervised clustering splits MASLD into a liver-specific and a cardiometabolic type with opposite dominant risks, and against a metabolically matched comparator unstaged MASLD is not associated with excess mortality at all (Torp 2025, PMID 40945520; Raverdy 2024, PMID 39653777; Kwak 2025, PMID 38739848).
Start here: wiki/overview.md. Research frontier: OPEN-QUESTIONS.md. Growth history: LOG.md.
The search rule that binds this condition¶
The literature is split across three names for overlapping entities. On 2026-09-02, (MASLD OR NAFLD OR MASH OR NASH OR "steatotic liver disease") returned 78,992 PubMed records, against 50,200 for the new name alone. Every search behind every page here unions old and new vocabulary, and every asserted absence records the exact query string and date. Where a cited study enrolled under NAFLD/NASH criteria, the page says so: the 2023 statement is a reclassification of a category, not a retrospective re-diagnosis of individuals.
That rule earned itself during this build. One absence claim — that no interview-based patient-experience literature existed — was asserted from a single search formulation, and was false; a targeted re-run surfaced six interview and focus-group studies that now anchor the patient-voice layer. The correction is recorded in OPEN-QUESTIONS.md OQ-16 and literature/patient-voice/sources.md.
Borders¶
This condition owns the liver disease from steatosis through steatohepatitis and fibrosis to cirrhosis, plus its cardiometabolic context. It does not own the tumour: hepatocellular carcinoma is curated separately, and masld-related-hepatocellular-carcinoma.md covers only what is distinctive in this setting — notably that HCC arises before cirrhosis in 38.5% of cases, which breaks the surveillance rule imported from viral hepatitis. Glycaemic management belongs to type 2 diabetes; the relationship is bidirectional and each condition owns its own endpoint.
Reading paths¶
If you have twenty minutes. overview.md → natural-history-and-fibrosis-progression.md → noninvasive-assessment.md.
If you want to know why the name changed and whether it matters. nomenclature-and-definitions.md → patient-experience-and-advocacy.md → literature/patient-voice/themes.md.
If you want the therapeutic state of play. resmetirom-and-thyromimetics.md → glp1-and-incretin-therapy.md → other-pharmacotherapy.md → bariatric-and-metabolic-surgery.md → clinical-trials-landscape.md.
If you want the mechanism. pathogenesis.md → genetics.md → histology-and-biopsy.md.
If you are trying to find the patients who matter. masld-and-type-2-diabetes.md → lean-masld.md → noninvasive-assessment.md → red-flags-and-safety-concerns.md.
If you want to know how people actually die of this. cardiovascular-and-extrahepatic-outcomes.md → cirrhosis-and-decompensation.md → masld-related-hepatocellular-carcinoma.md.
If you want the argument. OPEN-QUESTIONS.md, starting with the "Dots not yet connected" table.
Pages¶
The canonical page list for this condition (CONVENTIONS.md §5). Link only to these filenames.
| # | Section | Page | Scope | Lines | Refs | Status |
|---|---|---|---|---|---|---|
| 1 | Foundations | overview.md | What MASLD is, the five organising facts, map of the condition | 178 | 45 | curated |
| 2 | Foundations | nomenclature-and-definitions.md | NAFLD → MASLD, the Delphi process, MetALD, MAFLD, what changed and what did not | 160 | 28 | curated |
| 3 | Foundations | epidemiology-and-burden.md | Global prevalence, incidence, regional variation, projections | 193 | 30 | curated |
| 4 | Mechanism | pathogenesis.md | Lipid supply and disposal, lipotoxicity, mitochondria, immunity, fibrogenesis | 126 | 26 | curated |
| 5 | Mechanism | genetics.md | Heritability, PNPLA3, TM6SF2, HSD17B13, polygenic scores, genotype as drug target | 152 | 20 | draft |
| 6 | Diagnosis | noninvasive-assessment.md | FIB-4, elastography, ELF, sequential pathways, where they fail | 166 | 25 | curated |
| 7 | Diagnosis | histology-and-biopsy.md | NAS, SAF/FLIP, reader variability, ballooning, digital pathology | 178 | 20 | curated |
| 8 | Clinical | natural-history-and-fibrosis-progression.md | Stage-specific outcomes, progression and regression rates, cause of death | 175 | 22 | curated |
| 9 | Treatment | lifestyle-and-weight-loss.md | The weight-loss dose–response, diet composition, exercise, fasting | 149 | 15 | curated |
| 10 | Treatment | resmetirom-and-thyromimetics.md | MAESTRO programme, accelerated approval, what the endpoints do and do not show | 145 | 20 | curated |
| 11 | Treatment | glp1-and-incretin-therapy.md | ESSENCE, tirzepatide, survodutide, glucagon co-agonism, the cirrhosis failure | 138 | 19 | curated |
| 12 | Treatment | bariatric-and-metabolic-surgery.md | BRAVES, five-year histology, SPLENDOR outcomes, the alcohol risk | 151 | 12 | curated |
| 13 | Treatment | other-pharmacotherapy.md | Vitamin E, pioglitazone, statins, SGLT2 inhibitors, FGF21, and the failures | 163 | 23 | curated |
| 14 | Clinical | cirrhosis-and-decompensation.md | cACLD, portal hypertension, decompensation, transplant disadvantage | 146 | 22 | curated |
| 15 | Border | masld-related-hepatocellular-carcinoma.md | Pre-cirrhotic HCC, surveillance failure, immunotherapy response; cross-links HCC | 159 | 20 | curated |
| 16 | Clinical | cardiovascular-and-extrahepatic-outcomes.md | The leading cause of death; CKD, extrahepatic cancer, sarcopenia, CKM | 156 | 32 | curated |
| 17 | Clinical | masld-and-type-2-diabetes.md | Bidirectional relationship, case-finding in diabetes clinics | 162 | 27 | curated |
| 18 | Clinical | lean-masld.md | Non-obese phenotype, distinct bile-acid biology, liver-heavy/heart-light outcomes | 145 | 16 | curated |
| 19 | Reference | guidelines.md | AASLD, EASL, APASL, ADA, ALEH, NICE and where they diverge | 172 | 39 | curated |
| 20 | Frontier | clinical-trials-landscape.md | Live NCT records, the pipeline, the surrogate-endpoint problem | 208 | 28 | draft |
| 21 | Human | red-flags-and-safety-concerns.md | Missed fibrosis, alcohol misattribution, drug safety, decompensation signals | 191 | 52 | curated |
| 22 | Human | patient-experience-and-advocacy.md | Stigma evidence vs the rename's rationale, quality of life, the qualitative literature | 163 | 20 | curated |
Reference counts are unique PMIDs cited per page and overlap between pages; the audited deduplicated total is 360.
Literature layer¶
| Layer | File | Contents |
|---|---|---|
| Bibliography | literature/BIBLIOGRAPHY.md | 361 verified records, including all 360 wiki-cited records, with tags and citing pages; retained depth-pass additions are marked within each section |
| Landmark notes | literature/notes/ | 7 deep notes: Rinella 2023 (the rename), Angulo 2015 (fibrosis only), Romeo 2008 (PNPLA3), Abul-Husn 2018 (HSD17B13), Vilar-Gomez 2015 (weight-loss dose–response), Harrison 2024 (MAESTRO-NASH), Sanyal 2025 (ESSENCE) |
| Guidelines | literature/guidelines/REGISTRY.md | 52 catalogued documents (KASL 2025, AISF 2026, INASL 2023, NICE summary and the AASLD DILI guidance added), with supersession chains, 11 disagreements, four new structural gaps and an extended watch list |
| Statistics | literature/statistics/STATISTICS.md | 13 sections of quick-reference tables (§13 holds twelve new tables from the depth pass), every figure with source, year, population and method; 21 documented conflicts |
| Patient voice | literature/patient-voice/ | README (method + ethics), organizations (13 verified, 2 unverifiable), themes (9 themes, each ≥2 sources), sources (annotated, with coverage limits) |
Anchor records — re-verified¶
All 13 anchor records resolved at scoping were re-verified against live PubMed on 2026-09-02. All 13 matched on author, year, journal, volume, pages and title.
| PMID | Year | First author | Journal | Why it anchors | Re-verified |
|---|---|---|---|---|---|
| 37363821 | 2023 | Rinella ME | Hepatology 78(6):1966-1986 | Multisociety Delphi consensus on new nomenclature | ✓ |
| 37364790 | 2023 | Rinella ME | J Hepatol 79(6):1542-1556 | Same statement, J Hepatol co-publication | ✓ |
| 38324483 | 2024 | Harrison SA | N Engl J Med 390(6):497-509 | MAESTRO-NASH phase 3, resmetirom | ✓ |
| 40305708 | 2025 | Sanyal AJ | N Engl J Med 392(21):2089-2099 | ESSENCE phase 3, semaglutide | ✓ |
| 33185364 | 2021 | Newsome PN | N Engl J Med 384(12):1113-1124 | Phase 2 semaglutide in NASH | ✓ |
| 25935633 | 2015 | Angulo P | Gastroenterology 149(2):389-97.e10 | Fibrosis, not other histology, drives outcomes | ✓ |
| 28803953 | 2017 | Hagström H | J Hepatol 67(6):1265-1273 | Fibrosis stage but not NASH predicts mortality | ✓ |
| 18820647 | 2008 | Romeo S | Nat Genet 40(12):1461-5 | PNPLA3 and hepatic fat | ✓ |
| 39798707 | 2025 | Armisen J | J Hepatol 83(1):31-42 | AZD2693 antisense — variant to drug target | ✓ |
| 26707365 | 2016 | Younossi ZM | Hepatology 64(1):73-84 | Global epidemiology, meta-analytic prevalence | ✓ |
| 36626630 | 2023 | Younossi ZM | Hepatology 77(4):1335-1347 | Updated global epidemiology | ✓ |
| 36727674 | 2023 | Rinella ME | Hepatology 77(5):1797-1835 | AASLD practice guidance | ✓ |
| 38445559 | 2024 | Kanwal F | Hepatology 79(5):1212-1219 | Impact of new nomenclature on AASLD guidance | ✓ |
Gaps flagged at scoping, all now closed with live searches: EASL guidance (PMID 38851997 and co-publications), pioglitazone and vitamin E (PIVENS PMID 20427778, Cusi PMID 27322798, TONIC PMID 21521847), FIB-4 and elastography diagnostic accuracy (PMIDs: 34001645, 33991635, 30689971), bariatric surgery histological cohorts (PMIDs: 32553765, 37088093, 34762106), lean MASLD (PMIDs: 32413340, 40087205, 38570344), transplant outcomes (PMID 37307997), the MetALD alcohol boundary (PMIDs: 39608457, 40179033), and patient-organisation material (13 organisations verified by direct retrieval).
At a glance¶
| Fact | Value | Source |
|---|---|---|
| Global adult prevalence | ~30% (published range 29.8–38%) | PMIDs: 36626630, 35798021, 34890795, 39094335 |
| Prevalence in type 2 diabetes | 65.33% (62.35–68.18) | PMID 38521116 |
| Advanced fibrosis, general population | 3.3% (2.4–4.2) | PMID 39209202 |
| Progression to cirrhosis | 3–5%, usually >20 years | PMID 39243773 |
| Spontaneous fibrosis regression, paired biopsies | 22.3% | PMID 24768810 |
| Cardiac vs liver deaths, unselected cohorts | 4.20 vs 0.92 per 1,000 person-years | PMID 36626630 |
| Liver-related mortality rate ratio, F4 vs F0 | 42.30 (3.51–510.34) | PMID 28130788 |
| MASLD-related HCC arising pre-cirrhosis | 38.5% (27.9–50.2) | PMID 35255263 |
| Median survival after first decompensation | 2.0 years | PMID 38571305 |
| Approved drugs | 2, both conditional, both F2–F3 non-cirrhotic | PMIDs: 38771485, 41201884 |
| Registered studies on ClinicalTrials.gov | 2,011 (178 interventional and recruiting; 110 phase 3) | ClinicalTrials.gov v2 API, 2026-09-02 |
Curation state¶
| Layer | State |
|---|---|
| Wiki pages | 22 of 22 built, deepened and audited; 20 curated, 2 draft |
| Literature layer | complete: bibliography, 6 landmark notes, guidelines registry, statistics, four-file patient-voice layer |
| Open questions | 23 Tier 1, 20 Tier 2, 19 dots not yet connected (OQ-31–OQ-43 and D13–D19 added in the depth pass; OQ-14 partly answered) |
| Audit | Codex independently audited Claude's 2026-09-02 depth pass; all 93 added PubMed records and all current trial IDs were live-retrieved, with corrections recorded in LOG.md |
Built and deepened by Claude on 2026-09-02; independently audited by Codex on 2026-09-02. See LOG.md.