Therapeutic mechanisms and beneficial effects of non-antidiabetic drugs in chronic liver diseases

Abstract

The global burden of chronic liver disease (CLD) is substantial. Due to the limited indication of and accessibility to antiviral therapy in viral hepatitis and lack of effective pharmacological treatment in nonalcoholic fatty liver disease, the beneficial effects of antidiabetics and non–antidiabetics in clinical practice have been continuously investigated in patients with CLD. In this narrative review, we focused on non-antidiabetic drugs, including ursodeoxycholic acid, silymarin, dimethyl4,4’-dimethoxy-5,6,5’,6’-dimethylenedixoybiphenyl-2,2’-dicarboxylate, L-ornithine L-aspartate, branched chain amino acids, statin, probiotics, vitamin E, and aspirin, and summarized their beneficial effects in CLD. Based on the antioxidant, anti-inflammatory properties, and regulatory functions in glucose or lipid metabolism, several non–antidiabetic drugs have shown beneficial effects in improving liver histology, aminotransferase level, and metabolic parameters and reducing risks of hepatocellular carcinoma and mortality, without significant safety concerns, in patients with CLD. Although the effect as the centerpiece management in patients with CLD is not robust, the use of these non-antidiabetic drugs might be potentially beneficial as an adjuvant or combined treatment strategy.

Forecasted 2040 global prevalence of nonalcoholic fatty liver disease using hierarchical bayesian approach

“…This is particularly relevant as increasingly NAFLD is recognized as a metabolic liver disease with a proposed name change to metabolic fatty liver disease (MAFLD), [41] and therapeutic strategies should include not only liver specific agents such as anti-fibrotics but also systemic metabolic modifying agents such as antidiabetic and antilipid medications. [42,43]…”

“…However, the information provided in our analysis provides a worst-case scenario which may help policy makers in developing policies to raise awareness of NAFLD, while simultaneously providing direction and funding for reversing the upward trajectory for both obesity and type 2 diabetes mellitus. This is particularly relevant as NAFLD is increasingly being recognized as a metabolic liver disease with a proposed name change to metabolic fatty liver disease (MAFLD) [ 41 ], and therapeutic strategies should include not only liver specific agents, such as anti-fibrotics, but also systemic metabolic modifying agents, such as antidiabetic and antilipid medications [ 42 , 43 ].…”

Genotype–Phenotype Association in ABCC2 Exon 18 Missense Mutation Leading to Dubin–Johnson Syndrome: A Case Report

“…However, no significant treatment has been established for DJS. Therefore, hepatotonics to minimize liver injury and regular follow-ups were planned for this patient [15].…”

Case 9: A 62-Year-Old Woman With Jaundice and General Weakness

“…In some clinics, hepatotonics with antioxidizing properties may be used. 9 Corticosteroid therapy for DILI has a limited role and is reserved for patients with immune-mediated DILI or ‘drug-induced’ AIH. 6 With the withdrawal of the causative drug, liver injury improves without any additional treatment, which confirms a diagnosis of DILI.…”