# Influence of a Zombie-like State of the Liver on Drugs and Its Medico-Legal Implications: A Scoping Review

## TL;DR

This review explores how 'zombie-like' liver cells affect drug responses and their implications in legal and medical contexts.

## Contribution

The paper introduces the medico-legal relevance of hepatocyte senescence and its secretory phenotype in drug administration.

## Key findings

- Hepatocyte senescence impacts drug metabolism and clinical interpretations.
- Senescent cells release SASP, which influences surrounding tissues and drug effects.
- The review highlights the importance of senescence in medico-legal and insurance assessments.

## Abstract

When cells remain permanently trapped in a particular cell cycle stage, they are in senescence. This also occurs in the liver. Such cells are often referred to as “zombie cells”, and an entire organ filled with these “zombie cells” is said to be in a “zombie-like” state, characterized by a lack of function. The senescence-associated secretory phenotype (SASP) encompasses the substances these “zombie cells” release, which can significantly affect nearby cells and tissues. While cellular senescence and SASP are related concepts, they are distinct. This scoping review aims to clarify the role of hepatocyte senescence and hepatocyte SASP in the administration of pharmaceuticals, as well as their relevance to medico-legal practice, disability claims, and insurance coverage. In this context, the effects of pharmaceuticals on senescent hepatocytes are discussed, particularly regarding the medico-legal implications of substances likely to be abused. In conclusion, hepatocyte senescence may be relevant in clinical or medico-legal work because it sheds a new light on interpreting clinical findings and expert witness statements.