When home is a dangerous place: the cost of falls among older people living in the community.

According to the National Institute on Alcohol Abuse and Alcoholism (NIAAA), alcohol use disorder (AUD) is a chronic, relapsing disorder defined by problematic patterns of alcohol consumption including heavy and binge drinking (NIAAA ). As of 2024, nearly 28 million Americans meet the criteria for an AUD (NIAAA ). Currently, the few pharmacotherapies approved by the US Food and Drug Administration to treat AUD have limited real‐world effectiveness, in part due to low rates of prescriptions by physicians and poor patient adherence (Hodgkin et al. ; Reus et al. ; Walker et al. ). In addition, the complex neurobiological basis of AUD further hinders the development of novel medications (Swift and Aston ). Increasing evidence suggests that AUD complexity extends beyond the central nervous system (CNS) and that peripheral pathology may contribute to AUD progression. Among peripheral organs, the liver is uniquely positioned to influence alcohol‐related behaviors, not only as the primary site of ethanol metabolism but also as a major source of metabolic and inflammatory signals capable of altering brain function (Lanquetin et al. ). However, existing evidence that liver injury can influence alcohol consumption is limited and somewhat conflicting. The most direct and well‐characterized consequence of liver damage on the CNS is hepatic encephalopathy, a serious condition marked by neurologic and cognitive impairment that occurs in up to 40% of individuals with cirrhosis (Butterworth ; Louissaint et al. ). Beyond advanced disease, inflammatory liver injury may also influence drinking behavior. This has been demonstrated in a mouse model of alcohol dependence, where the blockade of IL‐17A, a cytokine commonly upregulated in alcohol‐associated liver disease (ALD) and thought to facilitate alcohol‐associated damage, reduced alcohol‐induced liver and brain inflammation, and suppressed excessive alcohol intake (Xu et al. ). Hepatic ethanol metabolism can additionally activate pro‐inflammatory pathways, disrupting AUD‐related glutamatergic signaling in the brain and affecting communications between hepatic and neural pathways (Lee et al. ). Conversely, studies of chemically induced liver injury have shown that hepatic damage can impair ethanol metabolism, leading to acetaldehyde accumulation that correlated with reduced voluntary alcohol consumption (Ren et al. ). This conflicting evidence highlights a critical gap in understanding how alcohol‐associated liver pathology may contribute to the development or progression of AUD. Notably, as many as 95% of individuals with AUD exhibit some degree of ALD (Ramkissoon and Shah ), underscoring the close pathological interdependence of these two disorders. The earliest and most common manifestation of ALD is steatosis, characterized by the accumulation of fat in hepatocytes and accompanied by organelle dysfunction, apoptosis, and altered lipid signaling (Nguyen et al. ). Although steatosis is an initial and reversible stage of ALD, hepatic steatosis is not benign; recent data indicate an annual mortality rate of approximately 6%, driven predominantly by extrahepatic complications of alcohol consumption (Parker et al. ). Preclinical models of chronic alcohol consumption demonstrate that early liver damage is associated with increased pro‐inflammatory cytokines in the brain as well as impaired memory and sensorimotor coordination, supporting the importance of the liver–brain axis in alcohol‐induced cognitive deficits (King et al. ). Similar findings have been reported in models of metabolic dysfunction–associated steatotic liver disease (MASLD), where diet‐induced steatosis is accompanied by neuroinflammation and cognitive impairment (Kjærgaard et al. ). Several small clinical studies similarly show that MASLD is associated with impairments in verbal fluency, executive function, memory, and language (Filipović et al. ; Takahashi et al. ; Tuttolomondo et al. ). While MASLD and ALD share pathophysiological hallmarks such as lipid accumulation and inflammation, the direct contribution of ethanol metabolism and toxicity introduces unique mechanisms by which ALD‐associated steatosis may influence the CNS. Despite this, the impact of early‐stage ALD on alcohol‐seeking behavior and alcohol‐related cognition remains largely unexplored.