It is safe to assume that most of us are aware of the short-term and long-term effects of alcohol consumption on our bodies. After all, a lot of us have gone through the intensive AlcoholEdu course prior to our freshman year at Muhlenberg. The course was effective in that it informed the general audience of the dangers of chronic alcohol consumption, but left the biochemists in us thirsty (haha) for more.
In my quest to learn more about how ethanol can cause so many health problems, more often than not, I find myself asking questions that begin with “why…”. I mean seriously, it is a simple two-carbon molecule! Thankfully the biochemical literature was packed with possible answers to how Alcoholic Liver Damage (ALD) begins, and how it progresses. I decided to organize my findings into six categories: General Background, Clinical Trials, Oxidative Stress, Immune Responses, Microbiota, and Nonalcoholic Liver Damage (NALD). ALD is a short term for a wide spectrum of injury. Starting with deposition of fat in hepatocytes (steatosis), these injuries can quickly progress to Steatohepatitis, Progressive fibrosis, Cirrhosis, and even hepatocellular carcinoma.
Steatohepatitis is characterized by an inflammation of the liver caused by an immune response. This immune response is promoted by pro-inflammatory cytokines such as acetaldehyde, a metabolite of ethanol. Important players, such as natural killer (NK) cells are suppressed in high ethanol conditions, and therefore are unable to degrade pro-inflammatory cytokines such as Acetaldehyde, LPS, TNF-α, and palmitic acid. As researchers are looking for a clearer understanding of the mechanisms of such reactions, they are hoping to find targets for treatment options. Ezquer F., et all explored the feasibility of managing ALD associated ateatohepatitis and its progression by using mesenchymal stromal cells.
Progressive fibrosis is also related to innate immune responses and NK cells. When NK cells are suppressed, they cannot deactivate hepatic stellate cells (HSCs). When HSCs are activated, acetaldehyde can increase collagen expression in them, which leads to the accumulation of extracellular collagen and other matrix proteins, or fibrosis. To my surprise, however, recent studies have show other ways, such as reactive oxygen species (ROS), in which HSCs can be activated in liver cells. Using this knowledge, researchers are on a mission to find ways to relieve oxidative stress in patients with ALD in hopes of reversing the damage.
Since the only surefire way of treating ALD is by liver transplantation, many fields of research are working simultaneously to find novel therapeutic treatments. Studies show that we are close to putting together a safe and effective treatment, but we are not quite there yet. In order to get there, researchers suggest that we 1) work on developing novel antioxidant compounds with well-characterized pharmacokinetic and pharmacodynamic profiles, 2) and characterizing interactions between different molecules to obtain a clearer understanding of the underlying reactions in affected cells.
You can find my complete list of references here.
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