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Carbon tetrachloride (CCl4) is an efficient but highly toxic solvent, used in households and commercially in the industry under regulatory surveillance to ensure safety at the working place and to protect the workers’ health. However, acute unintentional or intentional intoxications by CCl4 may rarely occur and are potentially life-threatening. In this review article, therapy options are discussed that are based on a literature review of traditional poisoning cases and the clinical experience with 16 patients with acute poisoning by CCl4. Among various therapy options, the CO2-induced hyperventilation therapy will be considered in detail as the most promising approach. This special therapy was developed because only around 1% of the intoxicating CCl4 is responsible for the liver injury after conversion to toxic radicals via microsomal cytochrome P450 2E1 whereas 99% of the solvent will leave the body unchanged by exhalation. Therefore, to enhance CCl4 elimination through the lungs, CO2 is added to the inspiration air at a flow rate of 2–3 L min−1 in order to achieve hyperventilation with a respiratory volume of 25–30 L min−1. Under this therapy, the clinical course was favorable in 15/16 patients, corresponding to 93.8%. In essence, patients with acute CCl4 intoxication should be treated by forced ventilation.
The spectrum of alcoholic liver disease (ALD) is broad and includes alcoholic fatty liver, alcoholic steatohepatitis, alcoholic hepatitis, alcoholic fibrosis, alcoholic cirrhosis, and alcoholic hepatocellular carcinoma, best explained as a five-hit sequelae of injurious steps. ALD is not primarily the result of malnutrition as assumed for many decades but due to the ingested alcohol and its metabolic consequences although malnutrition may marginally contribute to disease aggravation. Ethanol is metabolized in the liver to the heavily reactive acetaldehyde via the alcohol dehydrogenase (ADH) and the cytochrome P450 isoform 2E1 of the microsomal ethanol-oxidizing system (MEOS). The resulting disturbances modify not only the liver parenchymal cells but also non-parenchymal cells such as Kupffer cells (KCs), hepatic stellate cells (HSCs), and liver sinusoidal endothelial cells (LSECs). These are activated by acetaldehyde, reactive oxygen species (ROS), and endotoxins, which are produced from bacteria in the gut and reach the liver due to gut leakage. A variety of intrahepatic signaling pathways and innate or acquired immune reactions are under discussion contributing to the pathogenesis of ALD via the five injurious hits responsible for disease aggravation. As some of the mechanistic steps are based on studies with in vitro cell systems or animal models, respective proposals for humans may be considered as tentative. However, sufficient evidence is provided for clinical risk factors that include the amount of alcohol used daily for more than a decade, gender differences with higher susceptibility of women, genetic predisposition, and preexisting liver disease. In essence, efforts within the last years were devoted to shed more light in the pathogenesis of ALD, much has been achieved but issues remain to what extent results obtained from experimental studies can be transferred to humans.