**1. Introduction**

Chronic liver disease (CLD) is a major global health problem [1, 2]. Recent studies have shown a global increase in the morbidity and mortality of chronic liver diseases during the past decade [3, 4]. CLD was the cause of an estimated 1.32 million deaths in 2017. Around 1.5 billion people globally are thought to suffer from at least one CLD. The main problem with CLDs is that diagnosis takes place once the disease is already advanced and therapy is no longer as effective [5]. Their treatment also continues to lag behind despite available drug therapies because of three key issues: (1) costly treatments are not accessible to all sectors of the population; (2) the presence of

comorbidities such as obesity, hyperlipidemias, or the increase of intravenous drug use and nosocomial spread, just to mention a few, can promote and accelerate the disease, and (3) lack of treatment continuity by either the patient or the health system once the diagnosis has been made. All of these factors play a role in the increase of morbidity and mortality.

Liver cirrhosis is largely due to (1) chronic infection with the hepatitis B virus (HBV) and hepatitis C virus (HCV), (2) alcohol-related liver disease (ALD), and (3) metabolic-associated fatty liver disease (MAFLD) [6–9]. The development of chronic liver disease occurs in different stages: acute hepatic decompensation, multiorgan failure, and compensated and decompensated cirrhosis resulting in higher mortality risks. Decompensated chronic liver disease is associated with the development of hepatocellular carcinoma [10]. Patients with end-stage chronic liver disease or in the hepatocellular carcinoma stage are admitted to hospitals more often, stay in there longer, and are readmitted more often compared with patients suffering from other serious chronic diseases [11]. CLD is a serious illness that entails high medical costs and impacts global public health [12]. It is characterized by extensive production of inflammatory mediators that include cytokines, chemokines, growth factors, bioactive lipid mediators, and immune-mediated tissue damage, all leading to subsequent liver failure [13–17]. The histopathological common denominator, independently of the CLD's origin, is liver inflammation as a mechanism of immune response to hepatocyte injury. Progressive destruction and regeneration of the hepatic parenchyma can lead to the development of fibrosis, cirrhosis, and hepatocellular carcinoma, causing both morbidity and mortality (**Figure 1**) [18–20]. Knowing each of these processes in detail is critical to our understanding of the disease and its therapeutic approaches. Animal models have played an important role in the study of the molecular mechanisms leading to the disease, data collection for early diagnosis, and the evaluation of most of the drugs currently employed in the clinic. Furthermore, they enable the study of new therapeutic alternatives for the prevention and treatment of this group of diseases. This chapter will review the different models employed for the study of the main histopathological and functional alterations that characterize the chronic liver disease. We also include some examples of drugs that have been evaluated using these models.

#### **Figure 1.**

*Progressive necrosis, inflammation, and steatosis of the hepatic parenchyma can lead to the development of fibrosis, cirrhosis, and hepatocellular carcinoma.*
