Eat more carrots? Dampening cell death in ethanol-induced liver fibrosis by β-carotene

Alcoholic liver disease (ALD) represents one of the principal causes of liver damage in humans. Long-term ethanol abuse leads to progressive liver injury and tissue remodeling, including steatosis, inflammation, fibrosis, cirrhosis and increased risk for hepatocellular carcinoma (HCC) development. Oxidative stress and subsequent liver cell death has long been identified as one of the key mechanisms during ALD progression, therefore antioxidants may display promising treatment options. In this issue of Hepatobiliary Surgery and Nutrition (HBSN), Peng et al. demonstrate that oral supplementation with β-carotene during chronic ethanol feeding in rats reduces oxidative stress, apoptotic cell death and inflammation. Reducing hepatocyte apoptosis, a major trigger for fibrogenesis and tumorigenesis, would make β-carotene a prospective target for treatment. However, before translating the promising findings of Peng and colleagues into clinical scenarios, it needs to be determined which cell death pathways, including necrosis and necroptosis, are affected by β-carotene, which liver cell populations are targeted by this vitamin A precursor, how specific the effects are for ALD in comparison to non-alcoholic steatohepatitis (NASH) or other chronic liver diseases, and whether reduced hepatic oxidative stress and apoptosis upon β-carotene supplementation truly relate to beneficial long-term consequences with respect to fibrosis, cirrhosis or HCC development.