Thyroid hormone alterations are associated with decompensated liver cirrhosis and acute-on-chronic liver failure

Thyroid hormones (TH) are important regulators of hepatic- as well as immune-metabolism and may thereby impact the pathogenesis of liver cirrhosis and acute-on-chronic liver failure (ACLF). In the present study, we therefore determined associations between TH, clinical stages of liver cirrhosis including ACLF and TH targets in immune cells.

Patients with compensated (n=163) or decompensated liver cirrhosis (n=169) or ACLF (n=36) were recruited from a prospective cohort study. TSH, FT3 and FT4 levels were determined by immunoassays. T cells were characterized for expression of TH target genes by RT-PCR.

TSH concentration in decompensated patients (2.81±0.2mU/l) was increased compared compensated patients (2.01±0.1mU/l, P=0.03) and ACLF (2.18±0.34mU/l, P=0.42). Conversely, FT3 levels were significantly lower in patients with decompensated liver cirrhosis (3.80±0.06pmol/l) compared to compensated liver cirrhosis (4.79±0.06pmol/l, P < 0.0001), and even lower in ACLF (3.24±0.15pmol/l, P < 0.01). Decreased FT3 concentrations were associated with infections in decompensated patients (3.45±0.10pmol/l vs. 3.90±0.07pmol/l, P=0.0009). Furthermore, low FT3 levels and a low FT3/FT4 ratio were associated with mortality (P < 0.001). Expression of TH targets, such as TH receptor α, were altered in T cells derived from decompensated patients or ACLF.

Decompensated cirrhosis complicated with infections and ACLF with or without infections are associated with profound alterations in the TH balance resembling low T3 syndrome. Strikingly, low FT3 level and FT3/FT4 ratio are associated with increased mortality in patients with liver cirrhosis. Decreased TH receptor α expression suggests impaired TH signaling in T cells of patients with liver cirrhosis possibly contributing to reduced survival.

Publication History

Article published online:
26 January 2022