Alcohol Consumption Is Associated With the Severity and Outcome of Acute Liver Injury/Failure

Puneet Puri; William M. Lee; Robert J. Fontana; Nak-Kyeong Kim; Valerie Durkalski; Brendan M. McGuire; Iris Liou; Carla Pezzia; R. Todd Stravitz


Liver International. 2020;40(2):360-367. 

In This Article

Abstract and Introduction


Background & Aims: Non-medical factors which contribute to the severity of acute liver failure (ALF) remain poorly defined. The association of alcohol consumption on the severity of presentation and outcome were determined in patients with ALF and acute liver injury (ALI) in a large, multicentre registry.

Methods: Alcohol consumption during the 6 months prior to study entry was analysed in 1170 patients enrolled in the ALF Study Group Registry. Consumption was categorized as none/minimal (<3 alcoholic beverages/week) or at least moderate (≥3/week). Clinical characteristics, the severity of liver injury at presentation (ALI or ALF) and outcome were compared.

Results: In patients with acetaminophen (APAP) overdose, at least moderate alcohol consumption was associated with higher peak aminotransferases, bilirubin, creatinine and INR on admission, compared to no/minimal consumption. In patients with non-APAP ALI/ALF, at least moderate alcohol consumption was associated with higher peak aminotransferases and creatinine. In APAP, non-APAP or all aetiologies, at least moderate alcohol consumption was associated with a 75%, 89% and 82% higher odds, respectively, of presenting as ALF rather than ALI (all P < .005). At least moderate alcohol consumption increased the odds of death by 45% (P = .01) across all aetiologies. In multivariate analysis, older age, non-Caucasian race, peak INR, peak bilirubin and at least moderate alcohol consumption were significantly associated with death. Finally, in Kaplan-Meier analysis of patients with all aetiologies, at least moderate alcohol consumption was associated with decreased time-dependent survival (P = .002).

Conclusion: Alcohol consumption adversely affects the presentation and outcome of both APAP- and non-APAP-induced ALI/ALF.


Acute liver failure (ALF) is a clinical syndrome consisting of a primary liver injury followed by secondary multi-organ system failure (MOSF), culminating in death or the need for liver transplantation (LT) in more than half of affected individuals.[1] The aetiology of the primary liver injury may be a toxin or drug, or less commonly, a viral, vascular or metabolic injury. In the United States and parts of Western Europe, acetaminophen (APAP) is the most common toxin incriminated in ALF, accounting for nearly half of cases.[1,2] Clinical features of patients with ALI/ALF which increase the susceptibility to, or severity of, primary liver injury have not been well-defined.

Although alcohol consumption has been reported to decrease the threshold of APAP hepatotoxicity,[3] the interaction is complex, and studies have not universally agreed that alcohol increases the hepatotoxicity of APAP. In experimental animals (highly controlled conditions), alcohol increases hepatotoxicity of APAP by induction of specific cytochrome P-450's (both P-450 3a and 1a[4]), thereby shunting more APAP into the metabolic pathway to produce the toxic metabolite, N-acetyl-p-benzoquinoneimine (NAPQI) and away from the non-toxic production of glucuronides or sulphates.[5] In humans (highly variable conditions), the timing, chronicity and quantity of both the alcohol and the APAP exposure determine the degree of liver injury. Other poorly defined cofactors modulate this interaction, such as fasting and/or the nutritional state of the patient, which determine glutathione reserves.[6,7] A less well-documented interaction between alcohol and APAP-induced liver injury has been hypothesized to occur with the co-ingestion of alcohol and APAP, in which experimental animals and humans appear to be more resistant to liver injury because of competition of alcohol and APAP for metabolism by the same cytochrome P450's, resulting in decreased NAPQI formation.[8,9]

The independent contribution of regular alcohol consumption (not abuse) to the severity of presentation and outcome of ALI/ALF has not been well-established in patients with APAP overdose partly because study populations have not been large enough to account for the heterogeneity of alcohol and APAP ingestion. Furthermore, the association of alcohol consumption on the severity on ALI/ALF of non-APAP-induced liver injury has not been explored. The ALF Study Group Registry has prospectively collected alcohol consumption data on participants with ALF and ALI (a less severe liver injury without hepatic encephalopathy) since its inception in 1998. The work presented herein attempts to quantify the association of alcohol consumption on the severity of liver injury in patients with ALI/ALF of diverse aetiologies, and to determine whether alcohol consumption adversely affects the clinical course of patients with non-APAP liver injury.