3. DISCUSSION
There is an imperative need for novel drugs that are devoid of hepatotoxicity. Animal models have been in use for several decades for evaluating the safety, efficacy and validation of drugs. There are several animal models which can be used to examine pathogenesis and development of cirrhosis and assessment of hepatoprotective drugs. These models are developed by using drugs, diet, chemicals and surgery. Each animal model of hepatic cirrhosis has its importance in short-term or long-term studies. Various marketed drugs lead to hepatotoxicity even with long-term use or short-term exposure such as paracetamol, nimesulide, isoniazid, methotrexate, and Carbamazepine (77). Hence, to overcome the side effects like hepatotoxicity and hepatocarcinoma, there is a need to develop new drugs which can be used as safe alternatives. And animal models are necessary for assessment of these drugs. Although much work has been done in the evaluation of hepatoprotective drugs but still bioengineering and extracellular matrix studies are in limelight to evaluate their pathology, an inflammatory mediator involved, and pathway progression (104). 2D monocultures, co-cultures, 3D spheroids and organ-on-a-chip models are the advanced techniques employed in the study of cellular responses mediated via pathophysiological phenomenon in fibrosis development (105). The human stellate cells, adult stem cells, and non-parenchymal cells are used in the development of cocultures and 3D spheroids for the study of hepatic fibrosis, cirrhosis and hepatic carcinomas. (106). Ex-vivo tissue culture techniques also aid in different stage evaluation of cirrhosis (107). In future, the pathology of the individual patient could be studied by decellularisation of liver and hepatic tissue bioengineering (108).