Risk factors and therapeutic interventions for decompensated cirrhosis affecting the gut-liver-brain axis

Cirrhosis is the end-stage of chronic liver disease which manifests with increased portal pressure due to changes in liver parenchyma and vascular resistance. Patients may be in a compensated or decompensated state, the latter characterized by clinical events such as ascites, variceal bleeding, and hepatic encephalopathy (HE). Portal pressure can be reduced by placement of a transjugular intrahepatic portosystemic shunt (TIPS), though post-TIPS HE is a risk. Treatment of HE typically involves lactulose and rifaximin. However, the exact working mechanisms of rifaximin are unknown.
In part 1 we analyzed cirrhosis cohorts and outcomes after TIPS placement. We show higher mortality risk and future decompensation episodes in decompensated patients, and the benefit of hepatocellular carcinoma screening. TIPS effectively controlled bleeding and ascites, while Doppler ultrasound is unnecessary in the long-term follow-up.
Part 2 focused on HE and the working mechanisms of rifaximin. Rifaximin was studied in vitro in human small intestinal organoids. We show that rifaximin is taken up in human small intestinal organoids, where it modulates amino acid and ammonia metabolism (independent of the Pregnane-X-Receptor (PXR)). Subsequently rifaximin is excreted in the intestinal lumen via the ABCB1 transporter.
In part 3 we reviewed prognostic biomarkers for decompensated cirrhosis and studied specific neuroproteins for the diagnosis of HE. Only a few novel biomarkers were identified to be promising in predicting 28-day or 90-day mortality (e.g. urinary neutrophil gelatinase-associated lipocalin, copeptin and interleukin-6). Neurofilament light chain is a promising biomarker for HE severity, while glial fibrillary acidic protein is not.