This study aimed to investigate the relationship among alcohol consumption, metabolic disorder, and liver dysfunction in the elderly population of Zhejiang province, China. To our knowledge, this is the first study to comprehensively assess the combined impact of alcohol consumption and metabolic disorder on liver dysfunction in an Asian population, particularly among Chinese elderly individuals. The current study suggests that the risk of liver dysfunction is associated with numerous factors, including gender, age, residence, education level, marital status, alcohol consumption behavior, and the presence of MetS. Our findings underscore the importance of avoiding excessive alcohol consumption, maintaining a healthy lifestyle, and effectively controlling various components of MetS, especially triglyceride levels, for the prevention of liver dysfunction. In addition, our research provides a comprehensive perspective on the impact of alcohol consumption and metabolic disorder on liver dysfunction.

MetS has been identified as an independent driver of cirrhosis and liver-related diseases. In a recent US study, MetS was the largest contributor to population-level HCC (attributable fraction: 32%) [21]. Additionally, the presence of MetS can predict liver-related mortality in various chronic liver diseases [22]. A recent large study in the US involving 271,906 NAFLD patients and an average 9-year follow-up reported that each additional metabolic feature (diabetes, obesity, hypertension, dyslipidemia) was associated with a stepwise increase in the risk of liver-related outcomes (cirrhosis or HCC). All four metabolic features independently influenced the risk, but diabetes had the strongest correlation with HCC events (hazard ratio [HR]: 2.8) [23]. Metabolic disorder, particularly MetS, is also considered a significant factor leading to liver dysfunction [24]. MetS includes characteristics such as obesity, hypertension, hyperglycemia, elevated triglyceride levels, and low high-density lipoprotein cholesterol levels, all of which have been proven to be associated with the progression of liver disease [25]. Compared to the group with normal liver function, participants in the group with abnormal liver function demonstrated adverse performances on multiple metabolic indicators. They exhibited significantly elevated levels of BMI, WC, SBP, DBP, FBG, TG, and HDL-C. Furthermore, participants in the group with abnormal liver function also had a higher prevalence and quantity of MetS. These results suggest a clear positive correlation relationship between the number of MetS and the risk of liver dysfunction, i.e., the more MetS, the higher the risk of liver dysfunction. Abnormal liver function may be a significant component of MetS, or one of the outcomes of MetS. Therefore, improving the management of MetS, such as weight loss, dietary improvement, and increased physical activity, may help in the prevention and management of liver dysfunction. Additionally, high-density lipoprotein cholesterol (HDL-C) is a beneficial lipid with antioxidative, anti-inflammatory, and anticoagulant effects [26]. A reduction in HDL-C levels may be associated with metabolic abnormalities and the occurrence of liver dysfunction [27]. Thus, improving lipid metabolism, especially by increasing HDL-C levels, may help protect liver function. Therefore, the higher level of HDL-C found in patients with liver dysfunction in this study may be a feedback mechanism. Interestingly, in the univariate analysis, low levels of HDL-C were a risk factor for abnormal liver function, while in the multivariate analysis, low levels of HDL-C exhibited a weak but positive protective effect on liver function. Nevertheless, the presence of other MetS remains still remains a risk factor, especially elevated triglyceride (TG) levels. Our research also found that in populations with MetS, particularly those with higher TG levels, the risk of liver dysfunction significantly increased (adjusted OR 1.52; 95% CI 1.51–1.54). These results suggest that improving lipid metabolism can have a positive impact on liver function. However, while the presence and quantity of MetS seem to be associated with an increased risk of liver dysfunction, we also found that female participants, younger individuals, people living in rural areas, individuals with lower education levels, single individuals, and those with MetS had a significantly increased risk of liver dysfunction. This might be related to lifestyle, socioeconomic status, and differences in access to and understanding of health information in these groups. This further enhances the understanding of the relationship between abnormal liver function and specific populations and metabolic disorders.

It is estimated that fatty degeneration occurs in drinkers who consume 4–5 standard drinks daily. Persistent drinking leads to approximately 25% of individuals developing alcohol-related fatty hepatitis or cirrhosis, eventually progressing to portal hypertension and liver cancer [28, 29]. Most patients remain asymptomatic until late stages of chronic liver disease unless they develop alcohol-related hepatitis [30]. This latter condition is a severe form of ALD characterized by rapid jaundice, discomfort, decompensated liver disease, and coagulation dysfunction, with a high mortality rate (up to 50% at 3 months) [31]. Cross-sectional data from the United States indicate that the co-occurrence of high levels of alcohol consumption and obesity increases the risk of abnormal liver enzyme activity more than either risk factor alone [32]. Recently, these results were confirmed by a data from a prospective population-based cohort, indicating that an average daily alcohol intake of at least 40 g, in conjunction with obesity, is associated with liver enzyme abnormalities seven years later [33]. A longitudinal cohort study involving 52,066 type 2 diabetes patients found that the majority of the liver burden may be attributed to alcohol consumption rather than obesity [34]. Model studies confirmed that excessive alcohol consumption contributes more to liver disease relative to metabolic factors [35]. Alcohol can cause direct toxic damage to the liver, leading to hepatitis, cirrhosis, and even liver cancer [36]. In the multivariate analysis, we corrected for the effects of other covariates and found a significant correlation between alcohol consumption and the risk of liver dysfunction. The higher the frequency of alcohol consumption, the greater the risk of liver dysfunction. This is consistent with previous research findings, where alcohol consumption is one of the important risk factors leading to liver disease. Moreover, our study also shows that the impact of years of abstaining from alcohol on liver dysfunction is non-linear. People who have abstained from alcohol for less than five years are still more likely to have liver dysfunction than those who drink occasionally, but once the abstinence period exceeds five years, the risk remains relatively constant. This may suggest that the liver's ability to self-repair and recover is effective within a certain time frame, but the risk of liver dysfunction does not further decrease after prolonged abstinence, possibly due to other factors such as age, genetics or lifestyle, and the liver's repair ability may weaken over time [37, 38]. This indicates that abstaining from alcohol has a positive impact on liver function recovery and underscores the importance of long-term abstinence.

Alcohol consumption and MetS are very common among the population and often coexist, indicating a complex relationship between alcohol and the components of MetS [4]. Both alcohol consumption and metabolic disorder are considered important factors leading to liver dysfunction, but their synergistic impact is more complex to analyze. Our results indicate that MetS increases the risk of liver-related outcomes regardless of the level of alcohol consumption. Metabolic components appear to alter the positive correlation relationship between alcohol intake and the risk of liver disease. On the other hand, we have divided the sample into distinct categories based on the frequency of alcohol intake (either occasional or usual/daily) and the presence of MetS disorder (either absent or present), aiming to delve into the combined impact of alcohol consumption and metabolic disorder on liver dysfunction. The results of this statistical analysis showed a significant sub-multiplicative interaction between alcohol consumption and metabolic disorder concerning liver dysfunction, without a clear additive interaction, indicating that the observed relationship between alcohol consumption, metabolic disorder, and liver dysfunction does not appear to be additive. Although the multiplicative interaction between alcohol consumption and metabolic disorder is significant and suggests a compounded, albeit less than expected, impact on liver dysfunction, the lack of an additive interaction highlights the nuanced ways in which these factors work together. These results contribute to the understanding of the complex interplay between lifestyle factors and disease, and they reinforce the need for personalized approaches in the prevention and management of liver dysfunction. Considering the risk stratification of both alcohol consumption and metabolic abnormalities may help identify individuals at risk of liver-related outcomes at an early stage. When both alcohol consumption and metabolic disorder are present, they may interact synergistically, accelerating liver damage. For instance, alcohol consumption could exacerbate symptoms of MetS and the syndrome could reduce the liver's tolerance to alcohol, thereby increasing the risk of liver dysfunction [1]. Hence, alcohol consumption and metabolic disorder could create a vicious cycle, aggravating liver damage. Recently, the utilization of a non-invasive liver fibrosis scoring method, FIB-4, has revealed a positive correlation relationship between alcohol intake and the progression of SLD (Steatotic Liver Disease), providing essential insights for the clinical management of SLD [39]. These findings underscore the importance of avoiding excessive alcohol consumption and managing metabolic diseases in maintaining liver health. Intervention strategies targeting these two factors could help reduce the risk of liver dysfunction, including limiting alcohol intake, improving dietary habits, increasing physical activity, and controlling weight. Meanwhile, those with existing alcohol consumption habits or metabolic diseases may require more aggressive and proactive interventions to prevent the occurrence and progression of liver dysfunction.

It's important to note that the study has several limitations. Firstly, it is cross-sectional and cannot establish causality. Further long-term follow-up studies are necessary. Secondly, the study was conducted in one region of China, potentially introducing regional bias. Lastly, this study did not include testing for gamma-GTP. In future research, consideration will be given to including this indicator and to further explore any potential associations with the components of MetS, providing additional valuable information.