Albumin-bilirubin score as a practical tool for prognostication in metabolic-associated steatotic liver disease

Abstract

Metabolic-associated steatotic liver disease (MASLD) has become the leading cause of chronic liver disease worldwide, yet reliable tools for prognostication remain limited. Fibrosis-based indices such as the fibrosis-4 and nonalcoholic fatty liver disease fibrosis score are widely used but primarily reflect structural damage rather than functional decline. The albumin-bilirubin (ALBI) score, originally established to assess hepatic reserve in patients with hepatocellular carcinoma, provides a simple and objective measure of liver function derived from routine laboratory parameters. Recent validation and meta-analytic studies have shown that ALBI predicts liver-related outcomes and all-cause mortality across diverse chronic liver disease populations, including MASLD, and offers complementary prognostic information beyond fibrosis-based models. Its simplicity, cost-effectiveness, and compatibility with automated reporting systems make it feasible for integration into clinical workflows and population-level risk stratification. However, interpretation of ALBI should consider potential confounders such as renal dysfunction, inflammation, and Gilbert syndrome, and threshold calibration across ethnic groups remains necessary. The ALBI score represents a promising functional biomarker that could enhance risk prediction and care pathways in MASLD, although prospective, multiethnic, and longitudinal studies remain needed to confirm its prognostic value and define clinically meaningful cut-offs.

Key Words: Metabolic-associated steatotic liver disease; Albumin-bilirubin score; Prognosis; Risk stratification; Noninvasive biomarkers

Core Tip: The albumin-bilirubin score is a simple, objective index derived from routine laboratory tests that reflects hepatic functional reserve. In metabolic-associated steatotic liver disease, albumin-bilirubin complements fibrosis-based models by providing functional information that may improve early risk detection and guide referral or monitoring strategies. Its accessibility and cost-effectiveness make it an attractive candidate for integration into clinical workflows and public health frameworks, although further validation and threshold calibration are still needed.

INTRODUCTION

Metabolic-associated steatotic liver disease (MASLD), previously termed nonalcoholic fatty liver disease (NAFLD), affects an estimated one in three adults globally and is now the most common cause of chronic liver disease[1,2]. Its prevalence continues to increase with obesity and type 2 diabetes, making MASLD a key driver of hepatology practice and healthcare costs[3,4]. Although most individuals with MASLD will not progress to advanced liver disease, a significant minority develop cirrhosis, hepatocellular carcinoma, or experience liver-related death[5,6]. Identifying this high-risk minority early remains one of the greatest challenges in hepatology.

Although fibrosis stage remains the strongest prognostic determinant in MASLD, fibrosis-based models such as the fibrosis-4 (FIB-4), NAFLD fibrosis score, and elastography are primarily structural assessments and may not fully capture decline in hepatic function[7-9]. This gap has prompted growing interest in complementary biomarkers that reflect liver function rather than morphology. Among these, the albumin-bilirubin (ALBI) score - originally developed to quantify hepatic reserve in hepatocellular carcinoma - has emerged as a simple, objective, and easily automated index with potential prognostic value in MASLD[10,11].

In the issue of the World Journal of Gastroenterology, Sethasine et al[12] evaluated the added value of the ALBI score for predicting liver-related complications and mortality among patients with MASLD. Their findings provide important evidence that functional indices such as ALBI may enhance prognostic assessment beyond fibrosis-based tools. This review aims to summarize current evidence on the prognostic utility of ALBI in MASLD, highlight its clinical applicability in primary and secondary care, and discuss limitations and future research needs. The article is structured into sections on the evidence base, clinical implications, and remaining knowledge gaps.

LITERATURE REVIEW

A focused literature search was conducted using the PubMed and EMBASE databases for studies published between January 2019 and August 2025. The search terms included “albumin-bilirubin”, “ALBI score”, “metabolic-associated steatotic liver disease”, “nonalcoholic fatty liver disease”, and “prognosis”. Reference lists of relevant reviews and meta-analyses were also screened manually to identify additional publications.

Only English-language human studies examining the prognostic value of the ALBI score in MASLD or chronic liver disease cohorts were included. Editorials, commentaries, case reports, and studies outside the five-year window were excluded. Because of heterogeneity among study designs, a narrative synthesis rather than formal meta-analysis was adopted. Formal quality grading (e.g., Grading of Recommendations Assessment, Development and Evaluation) was not performed due to study heterogeneity, consistent with the narrative-review approach.

EVIDENCE BASE

Non-invasive fibrosis indices such as the FIB-4 index, NAFLD fibrosis score, and elastography-based assessments, are widely used to stratify risk[9,13]. These tools emphasize the fibrosis stage, which is the strongest known predictor of outcomes in MASLD. However, fibrosis-centric approaches may underestimate the risk in patients whose structural liver stiffness remains modest while their hepatic functional reserve is already declining. This gap underscores the need for complementary prognostic measures that capture liver function and structure. The principal noninvasive prognostic markers used in MASLD, and their key features are summarized in Table 1.

Table 1 Key noninvasive prognostic markers in metabolic dysfunction-associated steatotic liver disease.

Marker	Core components	Main domain assessed	Data type	Major strengths	Major limitations
FIB-4	Age, AST, ALT, platelet count	Structural (fibrosis burden)	Biochemical	Simple, widely validated; good negative predictive value	Influenced by age and inflammation; limited sensitivity for advanced fibrosis
NFS	Age, BMI, diabetes, AST/ALT ratio, platelet count, albumin	Structural + metabolic	Clinical + biochemical	Incorporates metabolic risk; widely used	Requires multiple variables; moderate specificity
ELF	Hyaluronic acid, PIIINP, TIMP-1	Structural (fibrogenesis activity)	Serum biomarkers	High diagnostic accuracy; validated vs histology	Requires specialized assays; costly
ALBI score	Albumin, bilirubin	Functional (hepatic reserve)	Biochemical	Objective, continuous, easily automated; complements fibrosis indices	Not validated in acute liver injury; limited data in early MASLD

FIB-4: Fibrosis-4; NFS: Nonalcoholic fatty liver disease fibrosis score; ELF: Enhanced liver fibrosis; ALBI: Albumin-bilirubin; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; BMI: Body mass index; PIIINP: Amino-terminal propeptide of type III procollagen; TIMP-1: Tissue inhibitor of metalloproteinases-1; MASLD: Metabolic dysfunction-associated steatotic liver disease.

Although fibrosis-based scores such as FIB-4 remain essential for identifying structural liver damage, they do not capture functional decline. The ALBI score, by contrast, quantifies hepatic reserve and therefore serves as a functional complement to fibrosis indices rather than a replacement.

These results align with prior evidence from population studies and cirrhosis cohorts, demonstrating that ALBI reflects functional liver reserve more accurately than traditional scores, such as Child-Pugh scores[14,15]. Multiple pooled analyses have confirmed the prognostic relevance of ALBI across chronic liver disease and surgical settings. In a systematic review and meta-analysis including 5377 patients undergoing hepatic resection, Marasco et al[16] reported that ALBI grades 2-3 were associated with a 2.6-fold higher risk of post-hepatectomy liver failure compared with grade 1, supporting its sensitivity to hepatic functional reserve impairment across diverse Asian and European populations.

These findings reinforce the external validity of ALBI as an objective prognostic indicator beyond single-cohort studies. By integrating albumin (a marker of synthetic capacity) and bilirubin (a marker of excretory function), ALBI condenses complex aspects of liver physiology into a single objective measure[17]. Its continuous nature avoids the subjective grading inherent to the Child-Pugh score, and requires no specialized equipment or costly assays, facilitating its broad clinical applicability across diverse practice settings. However, ALBI has not been validated in acute hepatic injury or cholestatic conditions, where transient fluctuations in albumin or bilirubin may not accurately reflect chronic hepatic reserve[18].

CLINICAL IMPLICATIONS

The ALBI and Child-Pugh scores incorporate serum albumin and bilirubin as indicators of hepatic function, yet they differ markedly in structure and interpretation. The Child-Pugh system includes additional clinical variables such as ascites and hepatic encephalopathy, introducing an element of subjectivity and categorical grading. In contrast, the ALBI score uses only continuous biochemical parameters, providing a fully objective and reproducible measure of hepatic functional reserve.

Although both tools capture aspects of liver function, ALBI’s simplicity does not reflect oversimplification but rather a focused quantification of hepatic reserve without reliance on clinical judgment. This feature makes it particularly suitable for automated use in electronic medical records and for population-level risk stratification.

An additional implication is the feasibility of incorporating ALBI into routine MASLD patient care. Unlike the FIB-4 index, which requires age, aspartate aminotransferase, alanine aminotransferase, and platelet levels, ALBI uses only albumin and bilirubin which are already performed in most liver panels. Whereas the FIB-4 index incorporates age and aminotransferases to estimate fibrosis burden, ALBI relies on functional markers (albumin and bilirubin) to assess hepatic reserve, offering a different yet complementary perspective.

Because albumin and bilirubin are part of routine liver panels, ALBI can be automatically calculated and interpreted in any healthcare setting[19]. In MASLD, an elevated ALBI can prompt early referral or closer metabolic risk management even when fibrosis-based scores suggest low risk, thereby complementing structural indices with functional assessment[20]. A recent validation study further supports the simplicity and clinical applicability of this approach. Ananchuensook et al[21] demonstrated that the easy ALBI score, a simplified derivative of the conventional ALBI model, showed excellent correlation with the original ALBI (r = 1.0, P < 0.001) and comparable prognostic accuracy for overall survival in 672 patients with intermediate-stage hepatocellular carcinoma treated with transcatheter arterial chemoembolization. These findings highlight that even simplified functional indices maintain strong predictive power, reinforcing the ALBI framework’s feasibility for routine use in clinical practice.

One practical application is embedding ALBI calculations into electronic health record systems along with FIB-4[22]. For example, in primary care, patients with obesity and diabetes could have FIB-4 and ALBI scores automatically generated from routine laboratory data to facilitate prognostic risk stratification rather than diagnosis. Abnormal ALBI, even with a low FIB-4 score, can trigger automated referral pathways or alerts for hepatology consultation. This integrated approach can streamline risk detection and reduce missed opportunities for early intervention.

The use of ALBI extends beyond hepatology. Patients with MASLD often present to diabetes, cardiology, or nephrology clinics, where liver disease is not the primary focus[23]. Because ALBI uses routine laboratory tests, it can be readily applied in these settings to flag high-risk individuals. For instance, in a cardiology clinic managing metabolic syndrome, ALBI can identify patients with MASLD at elevated hepatic risk who may otherwise remain undetected.

With pharmacotherapies for metabolic steatohepatitis advancing rapidly[9,24], clinicians will need simple and reproducible markers to guide treatment allocation and monitoring. ALBI may serve an exploratory role in capturing functional improvement during therapy, complementing imaging-based fibrosis markers[25].

Despite its prevalence, MASLD remains largely absent from national noncommunicable disease strategies. Most countries lack systematic screening or referral frameworks, leading to delayed diagnosis[26,27]. Incorporating ALBI into population-based programs could help bridge this gap. Because it requires no specialized resources, ALBI can be applied at scale, particularly in high-prevalence groups such as patients with diabetes or obesity[28].

From a policy perspective, ALBI’s greatest advantage is its cost-effectiveness. Elastography and proprietary biomarker panels are expensive and often unavailable in resource-limited settings[29]. In contrast, ALBI requires only two inexpensive laboratory values, making it feasible for inclusion in routine check-ups or health insurance packages. Widespread adoption could improve efficiency by ensuring that advanced diagnostic tests and specialty referrals are reserved for those at greatest risk.

Policy frameworks can integrate ALBI into standardized referral pathways. For instance, primary care providers may refer patients with MASLD to a hepatology department if either FIB-4 or ALBI exceeds set threshold values. Such dual-gatekeeping systems would reduce false reassurance from fibrosis-centric models and ensure earlier identification of functionally impaired patients[30].

One of the most promising research avenues is dynamic ALBI monitoring. In cirrhosis, serial ALBI changes are strongly correlated with prognosis[31]. Extending this concept to MASLD could yield valuable insights: Rising ALBI might signal impending decompensation even before fibrosis progression, whereas decreasing ALBI during therapy could validate treatment efficacy. Prospective studies are needed to test whether ALBI trajectories have additional value beyond baseline scores.

Future research should also explore the integration of ALBI with other noninvasive tools. For example, the age-male-ALBI-platelets score incorporates age, sex, albumin, and bilirubin and platelet levels, and has demonstrated excellent predictive power for hepatocellular carcinoma risk across chronic liver diseases[32,33]. Combining ALBI with elastography, magnetic resonance imaging-based biomarkers, or serum fibrosis panels could create multidimensional risk models capturing structural and functional dynamics of MASLD progression[34,35]. Rather than viewing ALBI and FIB-4 as competing tools, they can be integrated into a dual-dimension approach that combines fibrosis assessment with functional evaluation - an approach likely to improve prognostic accuracy and guide timely intervention. Although ALBI reflects changes in hepatic function over time, its use as a therapeutic endpoint or treatment-response marker has not been validated and should be considered exploratory. Future studies are warranted to determine whether dynamic changes in ALBI can reliably capture treatment-related improvements in hepatic reserve.

Beyond its practical utility, ALBI also reflects fundamental pathophysiology. Albumin is a marker of hepatic synthetic reserves and systemic inflammation, while bilirubin reflects hepatocellular function and excretory capacity[17,36]. Elevated ALBI integrates the nutritional, inflammatory, and metabolic dimensions of hepatic health[37,38]. Exploring how comorbidities such as heart failure or kidney disease influence ALBI could deepen our understanding of MASLD’s systemic nature[39,40].

With the emergence of novel therapeutic approaches, ALBI score may serve as a pragmatic endpoint in clinical trials. Although histology remains the gold standard for assessing liver status, it is invasive and impractical for repeated use[13,41]. Imaging modalities provide structural data but are costly to implement. ALBI offers an inexpensive and reproducible measure of liver reserves that can be incorporated into trial designs, particularly in long-term outcome studies[10]. Its responsiveness to changes in hepatic function renders it a promising surrogate marker to complement fibrosis regression endpoints[10].

The ALBI score, once developed for hepatocellular carcinoma, has proven to be a practical, inexpensive, and powerful prognostic tool for MASLD. Clinically, ALBI provides an accessible means to triage patients, guide referrals, and monitor responses to therapy. At the policy level, its scalability and cost-effectiveness make it ideal for inclusion in population health strategies. From a research perspective, ALBI opens avenues for dynamic monitoring, biomarker integration, and surrogate endpoints in MASLD trials.

LIMITATIONS AND FUTURE DIRECTIONS

Although the ALBI score provides an accessible reflection of hepatic functional reserve, its interpretation can be influenced by several non-hepatic factors. Renal dysfunction, systemic inflammation, and nutritional status may lower serum albumin or raise bilirubin independently of hepatic impairment, whereas Gilbert syndrome and benign hyperbilirubinemia can lead to spuriously elevated ALBI values. These confounders should therefore be considered when interpreting ALBI in metabolic liver disease populations.

Furthermore, ethnic and regional differences in baseline albumin and bilirubin distributions suggest that threshold calibration may be required for MASLD cohorts outside East Asia and Europe. The risk of false-positive classification in acute or transient hepatic injury and false negatives in compensated disease also warrants caution. Prospective multiethnic validation and serial monitoring studies are needed to determine clinically meaningful ALBI changes and optimal cut-off points.

CONCLUSION

As the prevalence of MASLD continues to increase worldwide, the need for simple, reliable, and broadly applicable prognostic tools has increased. The ALBI score, grounded in everyday laboratory practice yet rich in prognostic value, stands out as such a tool. Integrating ALBI into MASLD care represents a timely step toward more proactive, equitable, and effective hepatology.