Dysgeusia in MASLD-related advanced chronic liver disease (ACLD): a silent driver towards the "Bermuda" triangle of malnutrition-sarcopenia-frailty severely affecting prognosis

Abstract

Background: Dysgeusia is a distortion of the sense of taste whose prevalence and relationship with nutritional status in Metabolic dysfunction-associated Steatotic Liver Disease (MASLD)-related advanced chronic liver disease (ACLD) have never been systematically explored.

Methods: 200 MASLD patients [60 ≤ F3 fibrosis, 70 compensated ACLD (cACLD), and 70 decompensated (dACLD)] were enrolled. At baseline, the Child-Pugh (CP) score was determined. Dietary habits, body composition, and frailty were evaluated. The European Working Group (EWGSOP2) criteria defined sarcopenia. Dysgeusia was assessed by the Dysgeusia-Total-Score (DTS). A visual analog scale identified appetite impairment (VASAI). During a 6-month follow-up, liver-related decompensation events (LRDEs) were recorded.

Results: The prevalence of dysgeusia increased with the liver disease progression, appearing significantly higher in ACLD compared with ≤ F3 (65.7% vs 5%, p:0.003), as well as in dACLD compared to cACLD patients (58.5 vs 7.1% p < 0.0001). On 41 dACLD patients presenting dysgeusia, 37 (90.2%) showed a significant impairment of appetite levels. In dACLD, the CP score was positively correlated with both DTS (R:0.742) and VASAI (R:0.704), as well as DTS was directly correlated with VASAI (R:0.765) (all p < 0.0001). Compared with dACLD patients without dysgeusia, dysgeusia-affected dACLD patients presented a lower daily protein intake (g/kg/die) (1.55 ± 0.192 vs 1.34 ± 0.15, p < 0.0001). Sarcopenia (70.7 vs 41.3%) and frailty (69.29 vs 37.9%) were significantly more prevalent in dysgeusia-affected dACLD individuals (both p < 0.0001). These patients showed a higher risk of LRDEs occurrence during the follow-up [HR:2.205; C.I. 95%:1.186-4.099; p:0.01]. Logistic regression analysis revealed dysgeusia (aOR: 3.32), appetite impairment (aOR:1.32), sarcopenia (aOR: 3.75), and frailty (aOR:3.03) significantly associated with this outcome (all p < 0.0001).

Conclusions: Dysgeusia appears predominant in MASLD-dACLD and, via appetite impairment, in a close relationship with malnutrition, sarcopenia, and frailty, negatively influencing patients' outcomes.

Keywords: Frailty; Liver cirrhosis; Nutrition; Sarcopenia; Translational Medicine.

Fig. 1

Experimental flow-chart. LSM was adopted to discriminate ≤ F3 patients and ACLD individuals, whereas the evaluation of LRDEs’ occurrence (ongoing and in the previous 12 months) distinguished cACLD and dACLD patients. In particular, LRDEs were: (a) progressive jaundice in not-cholestatic disease, (b) ascites, (c) HE, (d) variceal bleeding, or (e) any acute bacterial infections. The evidence of esophageal varices defined CSPH. Anthropometric parameters included Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Body Mass Index (BMI), and Waist-hip ratio (Whr) determination. Biochemical variables included platelet count (PLT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TB), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), Fasting Plasma Glucose (FPG), total cholesterol, High-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides (TG), serum albumin (SA), International-Normalized Ratio (INR), and creatinine. For ACLD, the Child-Pugh-Turcotte score was determined. Nutritional counseling was offered to all the patients: for this purpose, dietary and physical exercise habits were assessed, as well as the presence of dysgeusia (see the main text) and appetite levels. Nutritional status, including the evaluation for sarcopenia and frailty, was opportunely defined by using bioelectrical impedance analysis (BIA) and Liver Frailty Index (LFI) calculation. During a 6-month follow-up period, further LRDEs were recorded for dACLD.  At the baseline, as well as during the follow-up, LRDEs considered were (a) progressive jaundice in not-cholestatic disease, (b) ascites, (c) HE, (d) variceal bleeding, or (e) any acute bacterial infections. Jan: January; Dec: December; MASLD: Metabolic dysfunction-associated Steatotic Liver Disease; LSM: Liver stiffness measurement; ACLD: advanced chronic liver disease; cACLD: compensated advanced chronic liver disease; dACLD: decompensated advanced chronic liver disease. LRDEs: liver-related decompensation events; CSPH: Clinically Significant Portal Hypertension

Fig. 2

The prevalence of dysgeusia in the study population.The frequency distribution of dysgeusia in mild-advanced fibrosis (≤ F3) compared with ACLD, and in cACLD compared with dACLD patients. ACLD: advanced chronic liver disease; cACLD: compensated advanced chronic liver disease; dACLD: decompensated advanced chronic liver disease. Chi-square test analysis. Statistically significant differences (p < 0.05)

Fig. 3

Daily food intake according to the presence of dysgeusia in decompensated patients. A Daily protein intake (g/kg/die) in dACLD patients presenting and not presenting dysgeusia dACLD: decompensated advanced chronic liver disease. Mann–Whitney test. Statistically significant differences (p < 0.05). B The prevalence of individuals presenting a daily protein intake under the CPGs-recommended cut-off (1.5 g/kg/die) in dACLD patients presenting and not presenting dysgeusia CPGs: clinical practice guidelines; dACLD: decompensated advanced chronic liver disease. Chi-square test analysis. Statistically significant differences (p < 0.05). C Total energy intake (kcal/kg/die) in dACLD patients presenting and not presenting dysgeusia dACLD: decompensated advanced chronic liver disease. Mann–Whitney test. Statistically significant differences (p < 0.05). D The prevalence of individuals presenting a total energy intake under the CPGs-recommended cut-off (35 kcal/kg/die) in dACLD patients presenting and not presenting dysgeusia. CPGs: clinical practice guidelines; dACLD: decompensated advanced chronic liver disease. Chi-square test analysis. Statistically significant differences (p < 0.05)

Fig. 4

Sarcopenia and frailty according to the presence of dysgeusia and disease progression status. A Appendicula Skeletal Muscle Mass (ASM)/square of the height (ASM/h.²) values comparison in mild-advanced fibrosis (≤ F3), cACLD, dACLD without dysgeusia, and dACLD presenting dysgeusia. cACLD: compensated advanced chronic liver disease; dACLD: decompensated advanced chronic liver disease. Kruskal–Wallis test analysis. Statistically significant differences (p < 0.05). B Liver Frailty Index (LFI) values in mild-advanced fibrosis (≤ F3), cACLD, dACLD without dysgeusia, and dACLD presenting dysgeusia. cACLD: compensated advanced chronic liver disease; dACLD: decompensated advanced chronic liver disease. Kruskal–Wallis test analysis. Statistically significant differences (p < 0.05). C The prevalence of sarcopenia and D frailty mild-advanced fibrosis (≤ F3), cACLD, dACLD without dysgeusia, and dACLD with dysgeusia. Chi-square test analysis. Statistically significant differences (p < 0.05)

Fig. 5

Liver-related decompensation events in dACLD according to the presence of dysgeusia. The occurrence of further liver-related decompensation events in dACLD patients presenting (blue) and not-presenting (black) dysgeusia. LRDEs: Liver-related decompensation events; HR: Hazard Ratio; Log-rank test analysis with Kaplan–Meier curve comparison; time-to-event (TTE) analysis; Statistically significant differences (p < 0.05)

Fig. 6

Adjusted Odds Ratios for clinical and nutritional variables associated with LRDEs occurrence in dACLD patients. LFI: Liver Frailty Index; LSM: Liver Stiffness Measurement; OR: Odds ratio; C.I.: Confidence Interval; Logistic regression model (adjusted for sex, age, diabetes, BMI, baseline CSPH, administration of NSBB, and human albumin); Statistically significant differences are reported in bold (p < 0.05)