Novel Therapies for the Treatment of Drug-Induced Liver Injury: A Systematic Review
Frontiers in pharmacology. 2021;12:785790
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.
The role of apheresis in hypertriglyceridemia-induced acute pancreatitis: A systematic review
BACKGROUND Mostly published as case reports or series, the role of apheresis in hypertriglyceridemia (HTG)-related acute pancreatitis (AP) remains unclear. We performed a systematic review of available literature on this topic with specific focus on disease severity. METHODS A search of electronic databases (PubMed, EMBASE, Cochrane) and gray literature yielded 5020 articles of which 74 met criteria for inclusion (301 unique patients). Relevant data were abstracted from full manuscripts and analyzed. RESULTS Most patients were young (mean age 37.9 +/- 10.4 years) and male (71.5%). About two-thirds (69.7%) received apheresis within 48 h and most required only 1 or 2 sessions (84.4%). Apheresis resulted in an average reduction of serum TG by 85.4% (p < 0.001). There was high variability in reporting the presence of and criteria to define severe AP (reported 221/301, 73.4%; present 85/221, 38.5%) or organ failure (reported 104/301, 34.6%; present 52/104, 50.0%). Improvement was reported in the majority of patients (reported 144/301, 47.8%, present 136/144, 94.4%) mainly by clinical symptoms or laboratory tests. Overall mortality was 7.1% (21/294) which increased to 11.8% (10/85) with severe AP and 19.2% (10/52) with organ failure. CONCLUSIONS Apheresis effectively reduces serum TG levels. However, due to uncontrolled data, reporting bias and lack of a comparison group, definitive conclusions on the efficacy of apheresis in reducing AP severity cannot be made. We propose which patients may be best suitable for apheresis, type of studies needed and outcome measures to be studied in order to provide empiric data on the role of apheresis in HTG-related AP.Copyright © 2015 IAP and EPC. Published by Elsevier B.V. All rights reserved.