{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:13:03Z","timestamp":1790885583458,"version":"4.1.0"},"reference-count":222,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Liver disease encompasses a wide range of conditions, each requiring tailored therapeutic approaches. This review describes and critically discusses treatments with robust evidence for improving liver health. Ursodeoxycholic acid (UDCA) is a drug approved by the Food and Drug Administration of the USA to treat primary biliary cholangitis (PBC). In addition, UDCA has been demonstrated to protect against metabolic dysfunction-associated steatohepatitis, fibrosis, and drug-induced liver injury (DILI). The mechanism of action of UDCA has been attributed not only to decreasing the effects of toxic bile acids but also to protecting mitochondrial integrity and function, as well as to antioxidant, anti-inflammatory, and anti-apoptotic activities. UDCA can scavenge reactive oxygen species (ROS) and activate the nuclear factor-E2-related factor-2 (Nrf2) pathway, thereby exerting antioxidant activity. The anti-inflammatory activity of UDCA is associated with its ability to inhibit the nuclear factor-\u03baB pathway. Pirfenidone is a well-recognized antifibrotic drug for the treatment of idiopathic pulmonary fibrosis; its effects on liver fibrosis have also been demonstrated. Pirfenidone exerts anti-inflammatory effects by attenuating the nucleotide-binding oligomerization domain-like receptor 3 inflammasome signaling pathway. The antioxidant actions of pirfenidone are associated with its ability to upregulate the Nrf2 pathway. Both the anti-inflammatory and antioxidant properties of pirfenidone act together to attenuate lung and liver fibrosis, decreasing transforming growth factor-\u03b2 levels, inhibiting profibrogenic hepatic stellate cell activation, and increasing extracellular matrix degradation. Methyltransferases utilize S-adenosyl-L-methionine (SAM) as a methyl donor for most transmethylation reactions in the body. SAM increases reduced glutathione (GSH) levels, exerting important antioxidant effects. Evidence indicates that SAM prevents fibrosis and attenuates hepatocellular carcinoma development, improving patient survival. N-acetylcysteine (NAC) is a precursor to L-cysteine and GSH and is used in clinical settings to treat cancer, nephropathy, heart disease, pulmonary fibrosis, polycystic ovary syndrome, and influenza. Regarding the liver, NAC is the most accepted treatment for DILI, especially after paracetamol overdose. Owing to its antioxidant and anti-inflammatory actions, NAC has been successfully used to treat chronic liver injuries, including hepatosteatosis and fibrosis. Therefore, ursodeoxycholic acid, pirfenidone, S-adenosyl-L-methionine, and N-acetylcysteine could represent therapeutic strategies for the treatment of liver pathologies.<\/jats:p>","DOI":"10.3390\/ijms27062546","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T14:45:39Z","timestamp":1773153939000},"page":"2546","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Potential Therapeutic Strategies for Steatosis, Oxidative Stress, Inflammation, and Fibrosis in Liver Disease"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2236-6631","authenticated-orcid":false,"given":"Pablo","family":"Muriel","sequence":"first","affiliation":[{"name":"Departamento de Farmacolog\u00eda, CINVESTAV, Av. Instituto Polit\u00e9cnico Nacional 2508, Col. San Pedro Zacatenco, Alcald\u00eda Gustavo A. Madero, Ciudad de M\u00e9xico 07360, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo E.","family":"Vargas-Pozada","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, CINVESTAV, Av. Instituto Polit\u00e9cnico Nacional 2508, Col. San Pedro Zacatenco, Alcald\u00eda Gustavo A. Madero, Ciudad de M\u00e9xico 07360, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda Vanessa","family":"M\u00e1rquez-Quiroga","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, CINVESTAV, Av. Instituto Polit\u00e9cnico Nacional 2508, Col. San Pedro Zacatenco, Alcald\u00eda Gustavo A. Madero, Ciudad de M\u00e9xico 07360, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6616-9760","authenticated-orcid":false,"given":"Erika","family":"Ramos-Tovar","sequence":"additional","affiliation":[{"name":"Secci\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Escuela Superior de Medicina-Instituto Polit\u00e9cnico Nacional, Plan de San Luis Esq. D\u00edaz Mir\u00f3n s\/n, Casco de Santo Tom\u00e1s, Miguel Hidalgo, Ciudad de M\u00e9xico 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1007\/s12072-009-9158-6","article-title":"Role of Free Radicals in Liver Diseases","volume":"3","author":"Muriel","year":"2009","journal-title":"Hepatol. 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