Table 4.

Challenges of studies on therapy in DILI.

Challenges of Studies on Therapy Approaches in DILI	First Author
Some liver injury study cohorts did not provide a list of offending drug(s), while other cohorts included a mix of potential hepatotoxic compounds such as conventional drugs used at recommended doses, overdosed drugs like acetaminophen, herbal medicine, alternative medications, ethyl alcohol, and alcohol surrogates.	Benić 2022 [112]
Heterogeneity of clinical presentation, disease severity, or toxicity grades	Delire 2022 [113]
Ancillary analysis of liver injury severity	Niu 2020 [114]
Lack of DILI definition	Benić 2022 [112]
Divergent therapy efficacy results and variability of efficacy criteria	Niu 2020 [114]
Failure to consider and differentiate liver injury pattern as hepatocellular, cholestatic, or mixed	Delire 2022 [113] Niu 2020 [114]
Medications not used alone but in combination with other medications	Niu 2022 [114]
Low case number of DILI study cohorts	Benić 2022 [112] Niu 2020 [114]
Inclusion of cases with ALT values 2–5 times those of the ULN, thereby representing liver adaptation rather than real liver injury characteristics	Benić 2022 [112] Niu 2020 [114]
Low or very low grade of certainty evidence reached in most studies	Benić 2022 [112]
Retrospective rather than the preferred prospective study design	Benić 2022 [112]
Bias with respect to selection (random sequence generation and allocation concealment), performance and detection of bias (blinding of participants, personnel, and outcome assessment)	Benić 2022 [112] Niu 2020 [114]
Lack of data about causality assessment or with only limited use of RUCAM	Benić 2022 [112] Delire 2022 [113] Niu 2020 [114]
Randomized, single blind rather than double blind study protocol	Benić 2020 [112]
China as the preferred reporting country, as many treatment efficiency trials had their focus on traditional Chinese medicines (TCMs)	Benić 2022 [112] Niu 2020 [114]