Table 1.
Studies reporting the characteristics of systemic inflammation in acute liver failure and chronic liver disease.
| Study | Experimental setting | Experimental results | Clinical results |
|---|---|---|---|
| Yaiza et al. 2024 [17] | rats with hyperammonemia and MHE | Increased levels of IL-17 and membrane expression of its receptor were observed in the rat cerebellum, along with enhanced activation of the IL-17 receptor in microglia and elevated levels of both IL-17 and TNFα. | |
| Elina Manzhalii et al. 2019 [7] | Wistar rats with CCL4-induced cirrhosis and HE | ↑ IFN-γ, IL-1β, IL-6 | The degree of HE and depression correlated with a proinflammatory cytokine pattern. |
| Patients with cirrhosis and HE | ↑ IFN-γ, IL-1β, IL-6 correlated to the degree of HE and depression,↑ anti-inflammatory IL-4 as a physiologic counterbalance mechanism | ||
| Mangas-Losada et al. 2017 [18] | Patients with liver cirrhosis (125 without and 62 with MHE) | ↑Levels of IL-6, IL-21, IL-17, IL-10, IL-18, CCL20, TNFα, CXCL13, IL-15, and CX3CL1 (fractalkine) in patients with MHE compared to those without; ↑IL-12, IL-1β, and IL-22 only in the MHE group. | These changes may promote immune cell infiltration into the brain and neuroinflammation, contributing to cognitive impairment in MHE. |
| Simon Johannes Gairing et al. 2022 [19] | Liver cirrhosis patients | IL-6 levels ≥ 8 pg/mL discriminated best between patients with and without MHE. | Higher IL‐6 levels remained independently associated with the presence of MHE. |
| Shawcross et al. 2011 [20] | 100 patients with cirrhosis and HE (59% Grade 3; 41% Grade 4) | ↑ SIRS score and SOFA score in patients with Grade 4 HE | The severity of HE (grades 3–4) and patient prognosis are linked to infection and systemic inflammation, rather than serum ammonia levels. |
| Nishi et al. 2025 [21] | Patients with HBV-ALF | TFS patients: ↑ IL-12p70, TNF-α, IFN-γ, G-CSF, RANTES, IL-6, IL-8, and fractalkine,↑IL-10 levels | A persistent inflammatory storm in non-TFS patients; reduced hepatic inflammation and improved survival in TFS patients; anti-inflammatory response in both groups. |
| TFS Acute HBV-ALF: ↓IL-1α, IL-2, IL-6, and IL-8,↑IL-10 levels | |||
| Shuyao Li et al. 2025 [22] | 18 cirrhotic patients (divided into HPA and LPA groups) and 3 healthy individuals | ↑In the abundance of the phylum Proteobacteria (especially aerobic Enterobacteriaceae) in the HPA group, ↑SCFA-producing bacteria (e.g. Roseburia, Blautia, Coprococcus) in the LPA group | Longer reaction times in the Stroop test and more severe cognitive impairment in the HPA group |
HE: hepatic encephalopathy; SIRS: systemic inflammatory response syndrome; SOFA: sequential organ failure assessment; MHE: minimal hepatic encephalopathy; IL: interleukin; TNF: tumor necrosis factor; CXCL13: C-X-C motif chemokine ligand 13; CX3CL1: C-X3-C motif chemokine ligand 1; CCl4: carbon tetrachloride; IFN: interferon; HBV-ALF: hepatitis B virus-related acute liver failure; TFS: non transplant-free survival; HPA: high plasma ammonia; LPA: low plasma ammonia; SCFA: short-chain fatty acid.