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The biochemical pattern defines MASLD phenotypes linked to distinct histology and prognosis
Javier Ampuero1,2,3, Rocío Aller4, Rocío Gallego-Durán5,6
1Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Seville, Spain. jampuero-ibis@us.es.
Background:
MASLD can manifest as hepatocellular damage, which can result in mild elevation of aminotransferases. However, in some patients, MASLD presents with cholestatic pattern.
Objective:
To assess the impact of the biochemical pattern on the natural course of MASLD, including liver damage in histology, the accuracy of non-invasive tests(NITs), and prognosis.
Methods:
Multicenter study enrolling 2156 patients with biopsy-proven MASLD, who were classified based on their[ALT/ULN)]/[(ALP/ULN)] levels at the time of biopsy: (a) hepatocellular pattern(H), > 5; (b) mixed pattern(M),2-5; (c) cholestatic pattern(C), < 2.
Outcomes:
(a) histological evaluation of the single components of NAS, MASH, and fibrosis; (b) NITs and transient elastography assessing advanced fibrosis; (c) prognosis determined by the appearance of decompensated cirrhosis and death.
Results:
Out of the 2156 patients, 22.9% exhibited the H-pattern, whilst 31.7% exhibited the C-pattern. Severe steatosis, ballooning, lobular inflammation, and MASH (56.4% H vs. 41.9% M vs. 31.9% C) were more common in H-pattern (p = 0.0001),whilst C-pattern was linked to cirrhosis (5.8% H vs. 5.6% M vs. 10.9% C; p = 0.0001). FIB-4(0.74(95% CI 0.69-0.79) vs. 0.83 (95% CI 0.80-0.85); p = 0.005) and Hepamet Fibrosis Score(0.77 (95% CI 0.69-0.85) vs. 0.84 (95% CI 0.80-0.87); p = 0.044)exhibited lower AUROCs in the H-pattern. The C-pattern[HR 2.37 (95% CI 1.12-5.02); p = 0.024], along with age, diabetes, and cirrhosis were independently associated with mortality. Most patients maintained their initial biochemical pattern during the second evaluation.
Conclusions:
The H-pattern exhibited greater necro-inflammation in the histology than the C-pattern, whereas the latter showed more cirrhosis. The accuracy of NITs in detecting fibrosis was decreased in H-pattern. The occurrence of decompensated events and mortality was predominant in C-pattern. Therefore, identifying MASLD phenotypes based on the biochemical presentation could be relevant for clinical practice.
Insights
The study found that the cholestatic pattern (C-pattern) of metabolic-associated steatotic liver disease (MASLD) is linked to more severe liver damage and higher mortality risk. Identifying MASLD phenotypes based on biochemical presentation is crucial for patient prognosis and clinical management.
Area of Science:
- Hepatology
- Biochemical markers in liver disease
- Liver disease phenotyping
Background:
- Metabolic-associated steatotic liver disease (MASLD) can present with hepatocellular damage or a cholestatic pattern.
- Understanding the clinical implications of different MASLD biochemical patterns is essential.
Purpose of the Study:
- To evaluate how biochemical patterns in MASLD influence disease progression, histological liver damage, and the accuracy of non-invasive tests (NITs).
- To determine the prognostic significance of different MASLD biochemical patterns regarding liver disease outcomes.
Main Methods:
- A multicenter study included 2156 patients with biopsy-proven MASLD.
- Patients were classified into hepatocellular (H), mixed (M), or cholestatic (C) patterns based on ALT/ALP ratios.
- Histological evaluation, NITs for fibrosis, and prognosis (decompensated cirrhosis, death) were assessed.
Main Results:
- The cholestatic (C) pattern was associated with a higher prevalence of cirrhosis (10.9%) compared to the hepatocellular (H) pattern (5.8%).
- Non-invasive tests for fibrosis showed reduced accuracy in the H-pattern group.
- The C-pattern was independently associated with increased mortality risk.
Conclusions:
- The hepatocellular pattern of MASLD shows greater necroinflammation, while the cholestatic pattern is linked to more cirrhosis.
- The accuracy of non-invasive fibrosis detection is diminished in the hepatocellular pattern.
- The cholestatic MASLD phenotype is associated with a higher risk of decompensated events and mortality, highlighting the clinical relevance of biochemical phenotyping.
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