Non-alcoholic fatty liver disease (NAFLD) stands out as one of the most common contributors to chronic hepatopathy globally, affecting around a quarter of the world’s population (1). Epidemiological evidence reveals that the prevalence of NAFLD ranges from 14 to 32% across various regions worldwide, with the highest rates observed in South America and the Middle East and the lowest prevalence found in Africa (2). NAFLD commences with the accumulation of fat in the liver. In clinical practice, it is generally characterized by the presence of ≥5% hepatic fat accumulation in the absence of excessive alcohol consumption and other known causes of fatty liver, such as viral infections, medications, and autoimmune conditions. The mortality associated with NAFLD is closely tied to complications such as cirrhosis, cancer, type 2 diabetes, and cardiovascular diseases (3).

NAFLD encompasses a broad spectrum, including nonalcoholic fatty liver, nonalcoholic steatohepatitis (NASH), and cirrhosis (4). Certain NAFLD individuals exhibit advanced fibrosis, staged according to liver biopsy outcomes, where those with stage 3 or 4 liver fibrosis are diagnosed with advanced fibrosis (5, 6). Many patients with NAFLD or NASH present asymptomatically. Elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels are common findings in these patients; however, these enzyme levels show little correlation with disease severity. ALT and AST serve as markers of hepatocellular injury, with ALT being more specific to liver damage, while AST can be influenced by extrinsic factors such as muscle injury. Notably, an increased AST-to-ALT ratio is closely associated with advanced liver fibrosis and is incorporated into several composite risk scores for fibrosis assessment (7). Research indicates that advanced fibrosis serves as a robust prognostic indicator in NAFLD patients. Compared to individuals with stage 0–2 fibrosis, those with advanced fibrosis demonstrate significantly shorter survival times and an elevated risk of overall mortality (5, 8). NAFLD and advanced fibrosis pose a substantial global health burden and are acknowledged as the fastest-growing causes of liver-related mortality worldwide (9). Moreover, model projections suggest that the economic burden of these conditions on healthcare systems may escalate exponentially in the coming years (10). Given this critical situation, there is an urgent necessity to deepen our understanding of the factors contributing to the increasing incidence of NAFLD and its adverse outcomes. Strengthening public health prevention strategies and improving patient education and management are critical steps in mitigating, or even reversing, the escalating tide of these diseases.

The development of NAFLD is currently believed to be the result of complex interactions between environmental factors and genetic risk factors. Specifically, poor dietary habits, sedentary lifestyles, and socioeconomic factors are tightly linked to the occurrence and advancement of NAFLD (11, 12). Due to the absence of approved effective pharmacological treatments for NAFLD, in recent years, several studies have incorporated recommendations for lifestyle changes and dietary modifications in the management of NAFLD (13, 14). Evidence suggests that high-quality diets are associated with a reduced risk of NAFLD. However, the relationship between diet quality and mortality in NAFLD patients, especially those with advanced fibrosis, remains limited and inconsistent, necessitating further investigation (15, 16). Consequently, further exploration is imperative to investigate the connection between diet quality and mortality rates among NAFLD patients, especially those with advanced fibrosis.

Currently, an increasing number of studies are adopting a comprehensive approach to dietary patterns, recognizing the synergistic effects of food consumption on health outcomes rather than focusing solely on single foods or nutrients (17, 18). In our research, we similarly employed this strategy, utilizing various indexes to assess the overall dietary quality of participants, including the Mediterranean diet (MED) score, the Healthy Eating Index-2020 (HEI-2020), the Alternative Healthy Eating Index (AHEI), the Dietary Approaches to Stop Hypertension (DASH) diet, and the Dietary Inflammatory Index (DII) (19–22). Consequently, this observational study aimed to examine the potential impact of different dietary quality indexes on the mortality of NAFLD patients and further explore the influence of diet quality on the mortality of those with advanced fibrosis.

In this research, we explored the associations between dietary patterns and mortality rates in a population of 3,634 individuals who fulfilled the diagnostic criteria for NAFLD based on data from the NHANES 2005–2018. Furthermore, we examined the impact of diet on all-cause mortality in patients suffering from advanced liver fibrosis. We observed that the aMED, HEI-2020, DASH, and AHEI dietary scores were positively correlated with each other, indicating that healthier dietary patterns tend to overlap across different indexes. On the other hand, the DII was negatively correlated with these four previous dietary scores, suggesting that a more inflammatory diet may be inversely related to overall dietary quality. Moreover, our investigation of the relationships between five dietary quality indexes and liver enzyme and fibrosis markers revealed that the aMED, HEI-2020, AHEI, and DASH dietary scores exhibited a linear negative correlation with GGT and FLI, while the DII showed a positive correlation with GGT. GGT is a sensitive marker reflecting hepatic fat accumulation and mild hepatocellular damage, often significantly increasing during the early stages of NAFLD (47). Elevated FLI is typically associated with increased hepatic fat deposition and accelerated fibrosis progression (48, 49). These findings suggest that high-quality diets may improve NAFLD prognosis through mechanisms such as reducing liver fat accumulation, potentially slowing the progression of fibrosis. Most importantly, our study found that high-quality dietary patterns were significantly linked to reduced mortality in patients with NAFLD. This association was also evident in patients with advanced liver fibrosis, suggesting that dietary improvements may be particularly beneficial in reducing mortality risk in this high-risk subgroup. Given the growing prevalence of NAFLD and its related complications, these findings highlight the importance of dietary interventions as a modifiable factor that can complement medical management strategies in mitigating the adverse outcomes of NAFLD.

The definitions of the five dietary quality indexes (aMED, HEI-2020, AHEI, DASH, and DII) used in our study have been previously elaborated. The MED, recognized as the most recommended regimen for individuals with NAFLD, involves a plant-based, protein-rich, low-fat diet with minimal processed components. It has been proven to prevent cardiovascular disease and diabetes and to reduce mortality in patients with metabolic syndrome, all of which are highly associated with NAFLD (50–52). The HEI is a dietary index developed to evaluate compliance with the Dietary Guidelines for Americans (20). Utilizing a density-based approach, it calculates the number of foods and nutrients consumed per 1,000 calories of energy intake, emphasizing meeting nutritional requirements primarily through dietary sources rather than supplements. The HEI-2020 encompasses 13 components to evaluate a multidimensional, dynamic dietary pattern. The AHEI was developed by McCullough and colleagues in 2002 as an enhancement to the original HEI, with the aim of forecasting the chronic disease risk associated with adherence to dietary guidelines among Americans. The DASH diet was initially formulated to manage and prevent hypertension (53, 54). Numerous studies have demonstrated that the DASH diet not only addresses hypertension but also influences the occurrence and progression of various other diseases, including NAFLD (55–57). The DII was progressively developed as researchers’ comprehension of inflammation’s role in health and illness evolved (58–60). DII quantifies the inflammatory potential of participants’ diets by assessing six inflammatory biomarkers, including TNF-α and C-reactive protein. It allows for the quantification and comparison of dietary inflammation levels among individuals, enabling the exploration of the association between dietary inflammation levels and specific diseases (61–66).

Prior studies consistently validated the associations between these specific dietary patterns and NAFLD. For example, several research studies showed higher adherence to the MED, AHEI, and HEI diets was associated with a reduced likelihood of developing NAFLD (67–69). A randomized controlled trial demonstrated that the DASH diet exerted beneficial effects on liver enzymes, TGs, inflammatory markers, and insulin metabolism in NAFLD individuals, with recent reports further endorsing its potential as a management strategy for these patients (70). Likewise, the dietary inflammatory index was linked to NAFLD and an increased risk of advanced liver fibrosis, as evidenced by a study using data from the NHANES database (71). Additionally, another investigation using NHANES data highlighted significant correlations among these five dietary quality indexes and their associations with the metabolic dysfunction-associated fatty liver disease (MAFLD) phenotype (15). Collectively, these indexes reflect comprehensive dietary habits, and substantial evidence supports their close association with NAFLD development. These findings establish a foundation for our study to utilize these five validated indexes in assessing diet quality.

Previous studies emphasized the pivotal role of diet quality in influencing mortality and disease progression in NAFLD patients, providing valuable insights for interpreting our findings. A recent cross-sectional investigation identified a linear inverse relationship between diet quality and all-cause mortality among NAFLD patients, suggesting that higher dietary quality contributes to improved survival outcomes (72). Another study demonstrated that in MAFLD patients lacking regular physical activity, higher dietary quality (assessed with HEI) exerted a stronger protective effect on reducing all-cause, cardiovascular-related, and cancer-related mortality than physical activity alone (73). This underscores the potential of dietary interventions to improve outcomes in liver diseases, particularly among sedentary populations with limited physical activity. Moreover, patients with elevated DII scores face increased hospitalization rates and mortality risks, highlighting that reducing inflammatory food consumption could help mitigate liver steatosis and fibrosis progression in NAFLD patients (74, 75). Conversely, conflicting evidence exists. A cohort study utilizing NHANES data found that while higher diet quality was associated with a lower risk of all-cause mortality in individuals without NAFLD, no such association was observed in those with NAFLD (16). This discrepancy suggests that the protective effect of diet quality may diminish, possibly due to disease severity, complications, or other confounding factors. These findings highlight the complexity of dietary impacts and underscore the necessity for further research to clarify the conditions under which diet quality influences NAFLD prognosis. On the whole, these above findings reinforce the importance of dietary quality as a modifiable factor in NAFLD management, providing a basis for our study to explore the association between dietary quality and patient outcomes.

The presence of advanced fibrosis poses a risk factor for the progression of NAFLD and increased mortality rates (5, 8, 76). Our study identified that individuals with NAFLD and advanced fibrosis exhibited an independent association with a higher all-cause mortality risk. Similar findings were observed in previous research (77, 78). What’s more, our analysis demonstrated independent and inverse relationships between high-quality dietary patterns and all-cause mortality in NAFLD patients with advanced fibrosis. An previous observational study based on the American Framingham Heart Study and NHANES elucidated the negative association between a healthy diet and liver fat accumulation and fibrosis progression by correlating pre-existing dietary scores with these liver parameters in participants (79). Another investigation into the impact of dietary habits on the association between severe liver fibrosis and mortality rates in the Korean population also identified a similar influence in people with moderate and low-quality diets (80). Our findings corroborate prior research, emphasizing the potential significance of improving dietary patterns for NAFLD patients with advanced fibrosis to enhance survival outcomes and minimize adverse effects.

Our research suggests that adopting beneficial dietary practices may positively impact the mortality risks of individuals with NAFLD and advanced fibrosis. Nevertheless, the precise dietary constituents that confer this benefit and the underlying mechanisms remain elusive. Extensive research showed that certain dietary elements can influence NAFLD outcomes. Expert opinion supports the idea that reducing free sugars, trans fatty acids, saturated fatty acids (SFA), and cholesterol can mitigate fatty liver and fibrosis in NAFLD patients. Free sugars refer to refined sugars added to beverages and processed foods, predominantly sucrose, fructose, and high fructose corn syrup (81). Epidemiological data consistently link excessive added sugar consumption to an increased risk of NAFLD development and worsening liver fibrosis (82, 83). Furthermore, emerging evidence indicates that NASH patients tend to have higher intakes of SFA and cholesterol but lower levels of polyunsaturated fatty acid (PUFA) (84, 85). The recommended MED is not a low-fat diet; on the contrary, 40% of its calorie content is from fat, but it shows a preference for high-quality fats. Olive oil, nuts, and fish are rich sources of MUFA and n-3 PUFA (including eicosapentaenoic acid and docosahexaenoic acid), which can improve glucose metabolism and insulin sensitivity, reduce hepatic TG content, and alleviate fatty hepatitis (86–88). Additionally, a n-3 PUFA-rich diet demonstrated a protective effect against hepatocellular carcinoma (HCC), especially crucial given the rising incidence of HCC in individuals with NAFLD and advanced fibrosis, endorsing the significance of enhancing dietary quality in reducing mortality rates (89). What’s more, polyphenols, abundant in the MED, play a vital role in protecting NAFLD patients by reducing fat accumulation, enhancing fatty acid oxidation, and decreasing oxidative stress to prevent liver cell damage (90). In vitro studies suggested that flavonoids within polyphenols may delay the absorption of glucose by inhibiting intestinal glucosidases, thereby reducing postprandial hyperinsulinemia and hyperglycemia (91). Moreover, regardless of specific dietary components, consensus statements recognize that a high-quality, nutritious diet, coupled with caloric restriction and gradual weight loss, leads to improvements in serum liver enzymes, liver fat levels, and fibrosis (92).

The advantages of our investigation lie in the comprehensive array of dietary quality indexes. These indexes offer a superior benefit over individual dietary components and nutrients by capturing the overall diet quality and considering the synergistic interactions among diverse foods. Additionally, the data analyzed in our study was sourced from the NHANES, which provided comprehensive health data that was representative of the entire US population, ensuring the credibility and accuracy of our research. However, our research has several limitations. Firstly, our study is an observational study conducted through the NHANES database. While our findings suggest that a high-quality diet may influence the survival of individuals with NAFLD and those with NAFLD accompanied by advanced fibrosis, further exploration of the precise mechanisms is necessary. Secondly, we identified NAFLD patients using non-invasive biomarkers. Although these markers are less specific than the gold standard liver biopsy for NAFLD diagnosis, existing research substantiates the reliability and effectiveness of non-invasive diagnostic markers (93–95). Thirdly, the method of collecting nutritional status data in NHANES is confined to 24-h dietary recalls, which is susceptible to self-reporting bias and may not be sufficient to comprehensively assess long-term diet quality or reflect individual food preferences. Fourthly, the lack of pertinent information on liver-related mortality in NHANES limits our ability to conduct further analyses. Fifth, although we have controlled covariates such as diabetes and hypertension, the real situation is complex and we may not be able to completely exclude the interference of other confounding factors.

In conclusion, our observational study of the American population highlights the significant role of dietary quality in reducing mortality risk among NAFLD patients. Notably, while advanced fibrosis is an independent predictor of mortality in this population, our findings suggest that a high-quality diet can mitigate this risk. By demonstrating the beneficial effects of high-quality diets on both NAFLD and advanced fibrosis patients, our research provides theoretical support for integrating dietary improvements into the management of these conditions. We propose that nutritional strategies may serve as an effective, non-pharmacological approach to reducing mortality rates and improving outcomes in individuals with NAFLD and advanced liver fibrosis.