The clinical and pathological features and prognostic analysis of progressive liver fibrosis in metabolic dysfunction associated steatotic liver disease

Abstract

Abstract: Objective To comparatively study on the similarities and differences in clinical, pathological characteristics, and clinical outcomes between advanced liver fibrosis (F3) and cirrhosis (F4) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Methods A retrospective analysis was conducted on 65 patients with MASLD diagnosed with advanced liver fibrosis via liver biopsy. The patients were divided into two groups: F3 and F4. The clinical, pathological characteristics, and clinical outcomes of the two groups of patients were compared. Cox regression models were used to analyze the factors influencing the progression of patients with advanced liver fibrosis to decompensated cirrhosis. Results Among the 65 patients analyzed, 28 were in the F3 stage and 37 were in the F4 stage. There were no statistically significant differences between the two groups in terms of gender, age, body mass index (BMI), or comorbidities (P>0.05). Laboratory tests showed that, compared to the F3 group, the F4 group had lower prothrombin activity and ferritin levels (81.30% vs 93.45%, P<0.05; 135.60 ng/mL vs 261.45 ng/mL, P<0.05), and higher international normalized ratio and liver stiffness measurement values (1.11 vs 1.06, P<0.05; 20.80 kPa vs 16.30 kPa, P<0.05). In terms of pathological features, there were no significant differences in the extent of steatosis or ballooning degeneration between the two groups (P>0.05). However, compared to the F3 group, the F4 group exhibited more irregular distribution of steatosis, significantly reduced lobular inflammation, significantly increased portal inflammation and interface hepatitis, as well as ductular reaction (P<0.05). Regarding clinical outcomes, there were no significant differences between the two groups in the occurrence of decompensated cirrhosis, hepatocellular carcinoma, or death/transplantation (P>0.05). Univariate Cox regression analysis of factors influencing the progression of patients with advanced liver fibrosis to decompensated cirrhosis identified that age, BMI, fasting blood glucose, gamma-glutamyl transferase, and controlled attenuation parameter (CAP) were the significant factors. Multivariate Cox regression analysis revealed that age and fasting blood glucose were independent risk factors for the progression of patients with advanced liver fibrosis to decompensated cirrhosis (HR=0.859, 95%CI:0.754~0.977, P<0.05; HR=1.343, 95%CI:1.004~1.796, P<0.05). Conclusion There are certain differences in clinical and pathological characteristics between F3 and F4 stages of advanced liver fibrosis in MASLD patients, but there is no significant difference in clinical outcomes.

Key words: Metabolic dysfunction-associated steatotic liver disease, Advanced liver fibrosis, Clinical features, Pathological features, Clinical prognosis, Risk factors

CHANG Liu-yi, SHAO Mo-li, TENG Guo-xin, MA Zi-kun, LI Min, ZHAO Xin-yan. The clinical and pathological features and prognostic analysis of progressive liver fibrosis in metabolic dysfunction associated steatotic liver disease[J]. Chinese Hepatolgy, 2025, 30(9): 1186-1191.

References

[1] Sanyal A J, Van Natta M L, Clark J, et al. Prospective study of outcomes in adults with nonalcoholic fatty liver disease[J]. N Engl J Med,2021,385(17): 1559-1569.
[2] 中华医学会肝病学分会, 中华医学会消化病学分会, 中华医学会感染病学分会. 肝纤维化诊断及治疗共识(2019年)[J]. 中华肝脏病杂志, 2019, 27(9): 657-667.
[3] Kleiner D E. Histopathology, grading and staging of nonalcoholic fatty liver disease[J]. Minerva Gastroenterol Dietol, 2018, 64(1): 28-38.
[4] Kleiner D E, Brunt E M, Van Natta M, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease[J]. Hepatology, 2005, 41(6): 1313-21.
[5] Zhu J Z, Zhou Q Y, Wang Y M, et al. Prevalence of fatty liver disease and the economy in China: a systematic review[J]. World J Gastroenterol, 2015,21(18): 5695-706.
[6] Angulo P, Keach J C, Batts K P, et al. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis[J]. Hepatology, 1999,30(6):1356-1362.
[7] Lembo E, Russo M F, Verrastro O, et al. Prevalence and predictors of non-alcoholic steatohepatitis in subjects with morbid obesity and with or without type 2 diabetes[J]. Diabetes Metab, 2022,48(5):101363.
[8] Patel Y A, Gifford E J, Glass L M, et al. Risk factors for biopsy-proven advanced non-alcoholic fatty liver disease in the Veterans Health Administration[J]. Aliment Pharmacol Ther, 2018,47(2):268-278.
[9] Younossi Z M, Koenig A B, Abdelatif D, et al. Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes[J]. Hepatology,2016,64(1): 73-84.
[10] Ciardullo S, Muraca E, Zerbini F, et al. Liver stiffness is associated with all-cause mortality in patients with NAFLD: a systematic review and meta-analysis[J]. Liver Int, 2023,43(12):2604-2610.
[11] Loomba R, Huang D Q, Sanyal A J, et al. Liver stiffness thresholds to predict disease progression and clinical outcomes in bridging fibrosis and cirrhosis[J]. Gut, 2023,72(3):581-589.
[12] Van der Poorten D, Samer CF, Ramezani-Moghadam M, et al. Hepatic fat loss in advanced nonalcoholic steatohepatitis: are alterations in serum adiponectin the cause[J]. Hepatology, 2013, 57(6): 2180-2188.
[13] Gadd V L, Skoien R, Powell E E, et al. The portal inflammatory infiltrate and ductular reaction in human nonalcoholic fatty liver disease[J]. Hepatology, 2014,59(4): 1393-1405.
[14] Ng C H, Lim W H, Hui Lim G E, et al. Mortality outcomes by fibrosis stage in nonalcoholic fatty liver disease: a systematic review and meta-analysis[J]. Clin Gastroenterol Hepatol, 2023,21(4):931-939.e5.
[15] Vilar-Gomez E, Calzadilla-Bertot L, Wai-Sun Wong V, et al. Fibrosis severity as a determinant of cause-specific mortality in patients with advanced nonalcoholic fatty liver disease: a multi-national cohort study[J]. Gastroenterology, 2018,155(2):443-457.e17.
[16] Kanwal F, Kramer J R, Li L, et al. Effect of metabolic traits on the risk of cirrhosis and hepatocellular cancer in nonalcoholic fatty liver disease[J]. Hepatology, 2020,71(3):808-819.
[17] Jarvis H, Craig D, Barker R, et al. Metabolic risk factors and incident advanced liver disease in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of population-based observational studies[J]. PLoS Med, 2020,17(4):e1003100.