Alcohol consumption creates reactive/toxic acrolein, a pathogenic mediator of liver injury in experimental ALD, whose adducts and metabolites are noticeable in blood and urine. 

A study evaluated 3-hydroxypropylmercapturic acid (HPMA), a major urinary acrolein metabolite, in patients with acute alcoholic hepatitis (AAH) and explored its relationship with disease severity and markers of hepatic inflammation and injury. 

And the following observations were made-

• Patients with severe [model for end-stage liver disease (MELD) ≥ 20] AAH demonstrated markedly elevated Urine HPMA than nonsevere AAH (MELD ≤ 19) or non-alcohol-consuming controls. This indicated urine HPMA to be a novel noninvasive biomarker in severe AAH. 
• Non-linear association between HPMA and MELD in patients with AAH was found.
• Patients with nonsevere AAH demonstrated a non-significant positive trend, while patients with severe AAH demonstrated a negative association, which indicated extensive injury and glutathione depletion. 
• Consistent with the multifactorial etiology of ALD, strong combined effects of HPMA and proinflammatory cytokines on hepatocyte cell death was found, thus backing the pathogenic role of acrolein in liver injury. 
• HPMA along with IL-1β demonstrated strong relation with cytokeratin 18 caspase-cleaved fragments and cytokeratin 18 full-length proteins.
• Likewise, HPMA along with IL-8, correlated with CK18-M30 and CK18-M65. 
• A robust correlation between the apoptosis index (CK18-M30:CK18-M65 ratio) and HPMA, together with IL-1β or tumor necrosis factor-α was found. 

Thus IL-1β, IL-8, and TNFα serve as the predominant proinflammatory cytokines in patients with severe AAH, which interact with HPMA and play significant mediating roles in controlling the extent/pattern of liver cell death.

SOURCE- Vatsalya V, Kong M, Gobejishvili L, Chen WY, Srivastava S, Barve S, McClain C, Joshi-Barve S. Urinary acrolein metabolite levels in severe acute alcoholic hepatitis patients, American Journal of Physiology-Gastrointestinal and Liver Physiology, 2019;316(1):G115-G122. https://doi.org/10.1152/ajpgi.00209.2018