in two types such as intrinsic drug-induced liver injury (IN-DILI) and idiosyncratic

drug-induced liver injury (IS-DILI) (Senior 2008), whereas the third category of

liver injury consists of alcohol-induced liver cirrhosis. All these three pathologies are

briefly discussed below:

1. Intrinsic Drug-Induced liver injury (IN-DILI)

Hepatotoxicity by acetyl-para-aminophenol (APAP) is a typical example of

drug-induced liver injury. It shows a dose-dependent response in rodents and

human hepatocytes and is also reproducible (McGill et al. 2011, 2013; Xie et al.

2014). It is not feasible to conduct dose-response studies for APAP hepatotoxicity

in humans due to ethical reasons, but the available data points towards a threshold

of toxicity usually 6–10 g/day in adults (Dart et al. 2006). However, few reports

demonstrated that only a few patients taking therapeutic doses of APAP develop

temporary elevation in hepatic biomarkers, and they do not experience a signifi-

cant liver injury and never have liver failure (Watkins et al. 2006; Kuffner et al.

2006; Dart and Bailey 2007; Heard et al. 2014). In addition, rare cases of

hepatotoxicity have been reported for other drugs such as cocaine (Vitcheva

2012), amiodarone (Grecian and Ainslie 2012; Chen and Wu 2016) and metho-

trexate (Banerjee et al. 1988).

2. Idiosyncratic Drug-Induced Liver Injury (IS-DILI)

Idiosyncratic drug-induced liver injury is a severe type of liver injury which

occurs in patients who are using particular drugs at recommended doses such as

antibiotics (amoxicillin-clavulanate), cardiovascular drugs (amiodarone), CNS

drugs (phenytoin), NSAIDs (diclofenac), etc. Various dietary supplements and

herbal products may also cause idiosyncratic DILI (Björnsson et al. 2013;

Chalasani et al. 2015; Vega et al. 2017). In most of the cases, after months of

asymptomatic exposure, the injury develops suddenly which resolves quickly

upon discontinuation. However, there are some rare cases of very rapid and

extremely latent response, and this rarity and variety of causative agents make

it difficult to study idiosyncratic DILI (Uetrecht 2009).

3. Alcohol-Induced Liver Cirrhosis

Alcohol drinking resulted in about 3.8% of deaths globally and global disability

of 4.6% (Rehm et al. 2009). Alcohol use disorders (AUC) are most common

cause of liver cirrhosis, and alcoholic liver disease (ALD) is the critical cause of

death in adults due to alcohol (Rehm et al. 2013). The consumption of alcohol

when exceeds a certain amount can cause a variety of liver lesions among which

steatosis is present in almost all drinkers who consume in excess of 40 g/day

regularly. The underlying mechanisms of ALD pathogenesis are still incom-

pletely understood but seem to be related with complex interactions between

behavioural, environmental and genetic factors (Konishi and Ishii 2007). Most

recent stage of knowledge is represented by Indian authors (Namachivayam and

Gopalakrishnan 2021).

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