*1.3. Overview of the Current Treatment Options for Chronic Liver Disease and Liver Fibrosis*

Current therapeutic interventions targeting CLD are etiology-dependent. Whereas in the last years, a quantum leap has been made in the therapy of hepatitis-induced CLD thanks to the development of novel and effective anti-viral drugs [25,26], therapeutic interventions in the case of ALD remain abstinence, treating the alcohol withdrawal syndrome, nutritional support, glucocorticosteroids or Pentoxifylline, anti-TNF therapy, antioxidants, or liver transplantation. On the other hand, treatment options for NAFLD and NASH are mainly directed toward lifestyle changes and weight loss, in combination with drugs such as insulin sensitizers, lipid lowering agents, hepatoprotective agents, antioxidants, incretin analogues, and anti-inflammatory agents (reviewed by [7]). First-line treatment for PBC involves the ursodeoxycholic acid (UDCA), which is able to prevent the progression of the disease in approximately two thirds of the patients [27–29]. For those PBC patients with insufficient response or intolerance to UDCA, second-line therapy is obeticholic acid [30,31]. There is currently no effective pharmacological therapy for PSC being liver transplantation the most definitive treatment [32].

Importantly, current clinical guidelines reinforce that, independently of the etiology of CLD, liver fibrosis should be the pharmaceutical target stage, once liver fibrosis reversibility is a reality. Taking into consideration that liver fibrosis is a multi-step disease characterized by pan-cellular and pan-pathway mechanisms, post-translational modifications (PTMs) of proteins can provide a better understanding of the liver fibrosis pathology as well as novel and more effective therapeutic approaches.
