Sarcopenia, malnutrition, and pruritus: a cholestasis-related “Cerberus” severely impacting the quality of life in patients with Primary Biliary Cholangitis (PBC). Is the systemic oxidative stress imbalance the driver? A preliminary observation

Introduction

Sarcopenia and malnutrition are a two-faced Janus affecting prognosis in parallel with disease progression status (DPS) in various chronic liver disorders, with an unexplored role in Primary Biliary Cholangitis (PBC). Micronutrient absorption influences systemic oxidative stress imbalance (SOS-I). SOS-I impacts muscle metabolism and itch pathways, representing a leitmotif contradistinguishing PBC. Cholestasis-related malabsorption and pruritus mainly burden PBC quality of life (QoL).

Aim

In PBC, to explore the relationship between sarcopenia, malnutrition, SOS (according to DPS, compared with other CLDs-etiologies), and pruritus, estimating the impact on the QoL.

Materials and Methods

40 MASLD, 52 HBV, 50 HCV, and 41 ursodeoxycholic-acid/antioxidants-naïve receiving a first serological PBC diagnosis patients were enrolled. Clinical, biochemical, nutritional (food-intake + bioelectric-impedance-analysis), and Liver-Stiffness (LSM) data were collected after a 3-month equally prescribed dietetic-physical exercise regimen. EWGSOP2 criteria diagnosed sarcopenia. The d-ROMs/BAP test evaluated SOS: d-ROMs > 27.20 mgH₂O₂/dL+ BAPs < 2000 µmol-iron/L = SOS-I. PBC-40 questionnaire estimated pruritus and QoL (poor > 120).

Results

In PBC, sarcopenia was more prevalent even in initial-mild fibrosis (F0-F2) (PBC: 67.90% vs MASLD: 30.76%, HBV: 22.60%, HCV: 20.70%, all p<0.0001). Appendicular-skeletal-muscle-mass/height²(ASM/h²) and LSM correlated exclusively in MASLD and HBV/HCV (both p<0.0001). PBC patients with severe cholestasis and sarcopenia presented lower micronutrient levels, particularly vitamin D (PBC vs MASLD, HBV, HCV all p: 0.001). In PBC, SOS correlated with gamma-glutamyl-transferase (d-ROMs, R:0.748, p:0.002; BAP, R: -0.641, p: 0.004) and alkaline-phosphatase (d-ROMs, R:0.781, p:0.03; BAP, R: -0.702, p:0.01). Limitedly to PBC, SOS correlated with muscle mass quantity (BAP-ASM/h², R: 0.871, d-ROMs-ASM/h², both p<0.0001), and pruritus severity (d-ROMs-item3-PBC-40, R:0.835; BAP-item3-PBC-40, R: -0.775, both p<0.0001). SOS-I was more prevalent in PBC patients with sarcopenia and severe pruritus (p:0.023). A poor QoL was more represented in PBC individuals simultaneously showing sarcopenia, severe pruritus, and SOS-I (p: 0.001).

Conclusions

In PBC, cholestasis promotes sarcopenia, malnutrition, and pruritus, dramatically impacting the QoL via SOS-I.