Steatohepatitis, drug-induced

Chronic steatohepatitis reveals only slight elevations of IgA and IgG. A pronounced increase in IgA is usually suggestive of an alcoholic or drug-induced cause. Elevation of IgA and IgG are laboratory markers for the development of cirrhosis. 

Pessayre D, Fromenty B, Mansouri A (2001) Drug-induced steatosis and steatohepatitis. In Lemasters JJ, Niemenen AL (eds) Mitochondria in pathogenesis. Kluwer Aeademie/Plenum Publishers, New Yrak, pp 489-517... 

Raja K, Thung SN, Fiel MI, Chang C. Drug-induced steatohepatitis leading to cirrhosis long-term toxicity of amiodarone use. Semin Liver Dis 2009 29(4) 423-8. 

Berson A, De Beco V, Lettoon P, Robin MA, Moreau C, El Kahwaji J, Verthier N, Eeldmann G, Eromoity B, Pessayre D (1998) Steatohepatitis-inducing drugs cause mitochmidrial dysfunction and lipid peroxidation in rat hepatocytes. Gastroenterology 114(4) 764—774... 

Obesity can cause insulin resistance and hepatic steatosis, which can lead to nonalcoholic steatohepatitis (NASH) in some patients (Pessayre and Fromenty 2005). Patients with NASH have an impaired ability to resynthesize ATP after a fructose challenge (Cortez-Pinto et al. 1999). Their hepatic mitochondria exhibit ultrastructural lesions with paracristaUine inclusions in megamitochondria (Caldwell et al. 1999 Sanyal et al. 2001). Patients with NASH have decreased protein expression of several mtDNA-encoded polypeptides and lower activity of respiratory complexes (Perez-Carreras et al. 2003). Thus, obesity-associated NASH combined with the administration of drugs impairing mitochondrial (3-oxidation may additively damage mitochondria to aggravate steatosis and steatohepatitis. Indeed, obesity has been shown to increase the risk of tamoxifen-induced steatosis and steatohepatitis in women (Bruno et al. 2005). 

Robin MA, Albano V, Pessayre D, Berson A (2008) Steatohepatitis-inducing drugs trigg cytokeratin cross-links in hepatocytes. Possible contribution to Mallory-Denk body formation. Toxicol In Vitro 22 1511-1519... 

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