A cholestatic pattern predicts major liver-related outcomes in patients with non-alcoholic fatty liver disease

Daniela Cabibi, Grazia Pennisi, Vito Di Marco, Antonio Craxi, Antonino Giulio Giannone, Giulia Lupo, Calogero Camma', Rossana Porcasi, Francesca Di Salvo, Federica Vernuccio, Stefania Grimaudo, Marco Enea, Rossella Zito, Salvatore Petta, Rosaria Maria Pipitone, Giada Sebastiani, Antonino Giulio Giannone, Annalisa Berzigotti, Vincent Wai-Sun Wong, Rossella ZitoManuel Romero-Gomez, Rossana Porcasi, Daniela Cabibi, Marco Enea, Elisabetta Bugianesi, Anna Ludovica Fracanzani, Manuel Romero-Gomez, Victor De Ledinghen, Mauro Viganò, Claudia La Mantia

Risultato della ricerca: Articlepeer review


Background & aims: NAFLD patients usually have an increase in AST/ALT levels, but cholestasis can also be observed. We aimed to assess in subjects with NAFLD the impact of the (cholestatic) C pattern on the likelihood of developing major liver-related outcomes (MALO).Methods: Five hundred and eighty-two consecutive patients with biopsy-proven NAFLD or a clinical diagnosis of NAFLD-related compensated cirrhosis were classified as hepatocellular (H), C and mixed (M) patterns, by using the formula (ALT/ALT Upper Limit of Normal-ULN)/(ALP/ALP ULN). MALO were recorded during follow-up. An external cohort of 1281 biopsy-proven NAFLD patients was enrolled as validation set.Results: H, M and C patterns were found in 153 (26.3%), 272 (46.7%) and 157 (27%) patients respectively. During a median follow-up of 78 months, only 1 (0.6%) patient with H pattern experienced MALO, whilst 15 (5.5%) and 38 (24.2%) patients in M and C groups had MALO. At multivariate Cox regression analysis, age >55 years (HR 2.55, 95% CI 1.17-5.54; p = .01), platelets <150 000/mmc (HR 0.14, 95% CI 0.06-0.32; p < .001), albumin <4 g/L(HR 0.62, 95% CI 0.35-1.08; p = .09), C versus M pattern (HR 7.86, 95% CI 1.03-60.1; p = .04), C versus H pattern(HR 12.1, 95% CI 1.61-90.9; p = .01) and fibrosis F3-F4(HR 35.8, 95% CI 4.65-275.2; p < .001) were independent risk factors for MALO occurrence. C versus M pattern(HR 14.3, 95% CI 1.90-105.6; p = .008) and C versus H pattern (HR 15.6, 95% CI 2.10-115.1; p = .0068) were confirmed independently associated with MALO occurrence in the validation set. The immunohistochemical analysis found a significantly higher prevalence of moderate-high-grade ductular metaplasia combined with low-grade ductular proliferation in C pattern when compared with the biochemical H pattern. Gene expression analysis showed a lower expression of NR1H3, RXRα and VCAM1 in patients with the C pattern.Conclusions: The presence of a cholestatic pattern in patients with NAFLD predicts a higher risk of MALO independently from other features of liver disease.
Lingua originaleEnglish
Numero di pagine20
RivistaLiver International
Stato di pubblicazionePublished - 2022

All Science Journal Classification (ASJC) codes

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