Novel Therapies for the Treatment of Drug-Induced Liver Injury: A Systematic Review

Abstract

Many drugs with different mechanisms of action and indications available on the market today are capable of inducing hepatotoxicity. Drug-induced liver injury (DILI) has been a treatment challenge nowadays as it was in the past. We searched Medline (via PubMed), CENTRAL, Science Citation Index Expanded, clinical trials registries and databases of DILI and hepatotoxicity up to 2021 for novel therapies for the management of adult patients with DILI based on the combination of three main search terms: 1) treatment, 2) novel, and 3) drug-induced liver injury. The mechanism of action of novel therapies, the potential of their benefit in clinical settings, and adverse drug reactions related to novel therapies were extracted. Cochrane Risk of bias tool and Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment approach was involved in the assessment of the certainty of the evidence for primary outcomes of included studies. One thousand three hundred seventy-two articles were identified. Twenty-eight articles were included in the final analysis. Eight randomized controlled trials (RCTs) were detected and for six the available data were sufficient for analysis. In abstract form only we found six studies which were also anaylzed. Investigated agents included: bicyclol, calmangafodipir, cytisin amidophospate, fomepizole, livina-polyherbal preparation, magnesium isoglycyrrhizinate (MgIG), picroliv, plasma exchange, radix Paeoniae Rubra, and S-adenosylmethionine. The primary outcomes of included trials mainly included laboratory markers improvement. Based on the moderate-certainty evidence, more patients treated with MgIG experienced alanine aminotransferase (ALT) normalization compared to placebo. Low-certainty evidence suggests that bicyclol treatment leads to a reduction of ALT levels compared to phosphatidylcholine. For the remaining eight interventions, the certainty of the evidence for primary outcomes was assessed as very low and we are very uncertain in any estimate of effect. More effort should be involved to investigate the novel treatment of DILI. Well-designed RCTs with appropriate sample sizes, comparable groups and precise, not only surrogate outcomes are urgently welcome.

A new nutraceutical (Livogen Plus®) improves liver steatosis in adults with non-alcoholic fatty liver disease

“…Our nutraceutical also contains the standardised fraction “Picroliv” of the root of Picrorhiza kurroa [ 20 ]. Picroliv can prevent lipid peroxidation, inhibit the production of reactive oxygen species, and neutralize free oxygen radicals [ 21 ]. Hepato-protective effects in humans have only been evaluated in one study.…”

“…Besides the bioactive components present in the diet, also endogenous substances have shown potential therapeutic effects on the liver. Glutathione (GHS) is the major endogenous hepato-protective agent, and, S -adenosyl- l -methionine (SAMe), its precursor, has an important role in the prevention of oxidative stress [ 21 , 41 ]. Administration of GHS and SAMe has been evaluated in the prevention and treatment of a variety of liver injuries [ 21 , 42 , 43 ].…”

Chemico-Pharmacological Screening of the Methanol Extract of Gynura nepalensis D.C. Deciphered Promising Antioxidant and Hepatoprotective Potentials: Evidenced from in vitro, in vivo, and Computer-Aided Studies

“…Multi-drug resistance protein (Mrp2, Mrp3, or both) excrete it into the bile, depending on the conjugated molecule. When used in large amounts, paracetamol (acetaminophen) may cause serious liver damage [ 3 ]. Furthermore, when the paracetamol become activated by the hepatic enzyme cytochrome p-45065-66 to form the very reactive metabolite, N-acetyl-P-benzoquinone imine (NAPQI), the hepatotoxicity has been induced, which is linked to the production of hazardous metabolites such as; N-acetyl-P-benzoquinone imine (NAPQI) [ 30 ].…”

“…As a consequence, interest in complementary and alternative treatments for the treatment of hepatic disorders has increased significantly. When these drugs (e.g., Bicyclol, Calmangafodipir, Cytisin amidophosphate, Fomepizole, Livina, Magnesium isoglycyrrhizinate, S-adenosylmethionine, Picroliv, Radix paeoniae rubra) [ 3 ] are used in clinical trials, generating therapeutically useful molecules from natural sources may help to reduce the risk of adverse events [ 4 ]. However, despite the fact that paracetamol is widely used as an analgesic and antipyretic, it may cause liver and kidney damage at large concentrations [ 5 ].…”

The Use of Chitosan-Coated Nanovesicles in Repairing Alcohol-Induced Damage of Liver Cells in Mice

“…Alcohol exerts toxic effects on the hepatocellular level, represented by the increased serum level of transaminases following their release into the circulation, after cell destruction. At the same time, there is an intensification of oxidative stress and lipid peroxidation as a result of the alteration of proteins and lipids by free radicals resulting from hepatocyte damage.Treatment with chitosan and chitosan vesicles resulted in a significant decrease in liver enzyme activity, which may be attributed to the antioxidant and anti-inflammatory effects of this polysaccharide [30,34,35]. The repair actions of chitosan and chitosan vesicles can be explained by a possible stabilizing effect of the hepatocyte membrane, preventing the release of transaminases into the blood.…”