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Multicenter Study
. 2024 Jul;59(7):586-597.
doi: 10.1007/s00535-024-02098-8. Epub 2024 Apr 15.

The biochemical pattern defines MASLD phenotypes linked to distinct histology and prognosis

Javier Ampuero  1   2   3 , Rocío Aller  4 , Rocío Gallego-Durán  5   6 , Javier Crespo  7 , Jose Luis Calleja  8 , Carmelo García-Monzón  9 , Judith Gómez-Camarero  10 , Joan Caballería  6   11 , Oreste Lo Iacono  12 , Luis Ibañez  6   13 , Javier García-Samaniego  6   14 , Agustín Albillos  6   15 , Rubén Francés  6   16 , Conrado Fernández-Rodríguez  17 , Douglas Maya-Miles  5   6 , Moisés Diago  18 , Maria Poca  6   19 , Raúl J Andrade  6   20 , Raquel Latorre  21 , Francisco Jorquera  6   22 , Rosa María Morillas  6   23 , Desamparados Escudero  24 , Manuel Hernández-Guerra  25 , María Jesús Pareja-Megia  26 , Jesús M Banales  6   27   28 , Patricia Aspichueta  29 , Salvador Benlloch  6   30 , José Miguel Rosales  31 , Juan Turnes  32 , Manuel Romero-Gómez  33   5   6 ; HEPAmet Registry
Affiliations
Multicenter Study

The biochemical pattern defines MASLD phenotypes linked to distinct histology and prognosis

Javier Ampuero et al. J Gastroenterol. 2024 Jul.

Abstract

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.

Keywords: Cholestasis; Hepatocellular; MASLD; Phenotypes; Transaminases.

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Conflict of interest statement

None.

Figures

Fig. 1
Fig. 1
A Distribution of single components of NAS, steatohepatitis, and cirrhosis depending on the biochemical pattern. B NAS score according to the biochemical pattern
Fig. 2
Fig. 2
Accuracy of FIB-4 and HFS predicting advanced fibrosis according to the biochemical pattern
Fig. 3
Fig. 3
Prediction of advanced fibrosis according to the thresholds of NITs
Fig. 4
Fig. 4
A Cumulative probability for decompensated cirrhosis. B Annual incidence rate of decompensated cirrhosis. C Cumulative probability for mortality. D Annual incidence rate of mortality
See this image and copyright information in PMC

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