Liver Diseases from Lab to Clinic

Abstract

Liver diseases are most common health problems in our country and even in the Middle East. After 10 years working on the pharmacotherapy of the liver diseases, I think that there is still gap between the lab research and the management of patients at clinics. In this review, I will try to summarize the different rat models of liver diseases, the common pathways that most therapeutic approaches working on and the application of these approaches on the patients based on the recent valid international publications. The Most Common Type of Benign Hepatic Lesions that are Induced in our Lab Fatty liver diseaseBased on recent epidemiological studies, fatty liver disease is the 2 nd most common cause of liver cirrhosis in Egypt and even in the Alcoholic Liver Disease (ALD)The pathological feature of ALD in human include; steatosis begins in zone 3 (perivenular/centrilobular) which can be classified into microvesicular (small-droplet) or macrovesicular (large-droplet) types. Inflammation in Alcoholic Steato Hepatitis (ASH) is typically neutrophil-rich which has been attributed to the increase of chemokines, such as IL-8 and IL-17, in both the serum and the liver parenchyma. Histologic cholestasis is more often seen in ASH than Non Alcoholic ASH (NASH) and can be a key feature when distinguishing between these entities. Alcoholic foamy degeneration, is an uncommon pattern of microvesicular steatosis, which has been described as classically centrilobular and at times diffuse. An iron stain (i.e., Prussian blue) reveals an increase in parenchymal iron in later stage of ALD, particularly within Kupffer cells. Alcohol increases iron absorption in the gut. Significant siderosis, including significant iron staining within hepatocytes, should prompt consideration of a concurrent process such as hereditary hemochromatosis. Clinically, the patient may present with acute hepatotoxicity and markedly elevated serum gamma-glutamyl transaminase levels, with or without elevation of the transaminases. The pathogenesis is related to mitochondrial dysfunction and an identical histologic pattern can be seen in Reye's syndrome, tetracycline toxicity and fatty liver of pregnancy [1].According to Brandon-Warner et al., no inclusive rodent model has been developed to date that accurately reflects the complete human pathology of ALD [2]. Several explanations as to why rodents do not develop ALD parallel to the human disease have been suggested; 1. Rodents (generally) have a natural dislike to alcohol consumption, but will consume alcohol partially for its caloric value. However, unlike humans, consumption does not increase over time.2. The rate of alcohol catabolism is up to 5 times faster in rodents than humans, and rodents will stop consuming alcohol when blood acetaldehyde levels increase. However, differences in alcohol catabolism between humans and rodents must also be considered within the context of higher basal metabolic rates in rodents (in general) as compared to humans.3. Alcohol avoidance is most likely favored as a result of survi...