What are the causes of liver failure? How does liver failure occur?

With the improvement of living standards, many people are under increasing work pressure and often stay up late to work overtime, which can cause great damage to the liver. So what is the pathogenesis of liver failure?

1. Pathogenesis of liver failure

In liver failure, a large number of liver cells die, accompanied by inflammatory cell infiltration and ischemic damage to the liver, which exceeds its regenerative capacity and causes liver function decompensation, thereby triggering a series of complications and ultimately multiple organ failure. Its mechanism mainly involves direct injury and immune-mediated indirect injury. Direct damage mainly refers to the direct toxic effects of various factors such as viruses, drugs, poisons and alcohol on the liver. However, immune-mediated indirect damage is crucial in the course of liver failure, especially the activation of immune cells, such as Kupffer cells, dendritic cells (DC cells), natural killer cells (NK cells), cytotoxic T cells (CTLs), regulatory T cells (Treg), Th17 cells, etc., and the production of corresponding inflammatory cytokines, resulting in an inflammatory cascade reaction. The above-mentioned activation of the immune system is mainly centered on the activation of T lymphocytes. T lymphocytes include helper T lymphocytes (Th) 1, Th2, Th17, and Treg cells. Th17 cells can express corresponding pro-inflammatory factors such as IL-17, IL-6, TNF-α, etc., and play an important role in immune activation and pro-inflammatory response, while Treg cells have the function of negative immune regulation and inhibition of inflammatory response, and express cytokines such as TGF-β and IL-10. An imbalance in the ratio of the two can lead to immune dysfunction and imbalance in pro-inflammatory and anti-inflammatory regulation, thus causing a series of diseases. Studies have suggested that patients with liver failure have a significant Treg/Th17 imbalance, which is closely related to their prognosis. Reestablishing an appropriate Treg/Th17 ratio may alleviate the disease progression.

2. Classification, evaluation and prediction of liver failure

According to the pathological histological characteristics and the speed of disease progression, liver failure can be divided into four categories: acute liver failure (ALF), subacute liver failure (SALF), acute-on-chronic liver failure (ACLF), and chronic liver failure (CLF).

Clinically, a series of scoring systems and models for predicting the risk of death from liver failure include the modified Child-Pugh score, the Model for End-Stage Liver Disease (MELD), the King's College Hospital criteria (KCH criteria), the Sequential Organ Failure Assessment (SOFA), the Patient Awareness Assessment for Chronic Disease (APACHE), the Clichy criteria, and the Severe Viral Hepatitis Scoring Standard (SMSVH), etc. However, the accuracy of these models is still controversial.