Albumin-bilirubin score: Monitoring hepatic function in patients with chronic hepatitis C virus infection

Abstract

Chronic hepatitis C virus (HCV) infection is a global public health concern that affects millions of people, decreasing patient quality of life and increasing health care costs. The current gold standard for assessing liver fibrosis is liver biopsy, an invasive method that can lead to various complications. However, new approaches have been introduced over the years, making diagnosis less invasive and more affordable. The albumin-bilirubin (ALBI) score, which was initially developed for hepatocellular carcinoma, has been shown to be correlated with survival, tumor relapse, and post-hepatectomy liver failure. We read with great interest the article by Ewid et al that was recently published in World Journal of Hepatology in which they reported a positive correlation between the ALBI score and inflammatory markers in patients with HCV infection after direct-acting antiviral (DAA) treatment. The ALBI score improved in patients with HCV and was useful for monitoring hepatic function during and after DAA therapy. They reported that the baseline ALBI scores were more favorable in the nonadvanced fibrosis group. Following DAA treatment, the improvement was more evident in the advanced fibrosis group. This score was significantly positively correlated with all noninvasive tests for liver fibrosis before and after DAA therapy. This editorial aimed to critically evaluate the role of the ALBI score as a biomarker in the management of chronic HCV infection, emphasizing its potential value for refining functional assessment, increasing risk stratification, and supporting long-term monitoring in patients treated with DAAs.

Key Words: Albumin-bilirubin score; Hepatitis C virus; Liver function; Liver fibrosis; Direct-acting antivirals; Child-Pugh classification

Core Tip: Chronic hepatitis C virus infection remains a significant global health challenge despite major advances in direct-acting antivirals. The albumin-bilirubin score, initially developed for hepatocellular carcinoma, has emerged as a simple, objective, and cost-effective biomarker for assessing liver function in these patients. Current evidence suggests that the albumin-bilirubin score improves following antiviral therapy, correlates well with established noninvasive tests, and captures both fibrosis and inflammatory activity. However, its full clinical utility is still being defined, and larger, more diverse studies are needed to validate its predictive value and clarify its role in precision hepatology.

This editorial refers to "Albumin-bilirubin score reflects the extent of liver fibrosis in chronic hepatitis C patients treated with direct-acting antivirals" by Ewid et al, 2025; https://dx.doi.org/10.4254/wjh.v17.i9.110049.

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INTRODUCTION

Chronic hepatitis C virus (HCV) infection is a global health challenge, pressing global public health, despite the remarkable advances and progress in antiviral therapy over the past years. It is estimated that millions of people around the world continue to deal with chronic infections, which often go undiagnosed, with progression to advanced liver disease representing a major cause of morbidity and mortality[1,2]. Chronic HCV infection is strongly associated with complications such as cirrhosis, hepatocellular carcinoma (HCC), and eventually the need for liver transplantation, outcomes that collectively become a clinical and economic hardship across both high-income and low-resource settings across the world[3,4].

The use of direct-acting antivirals (DAAs) has changed treatment paradigms with a sustained virological response (SVR) now obtainable in the majority of patients, significantly decreasing but not eliminating the long-term risk of hepatic decompensation and HCC[5]. Along with therapeutic advances, diagnostic technologies for HCV have gone through changes and transformation. Previously, the assessment for liver injury and the degree of fibrosis have relied on invasive liver biopsy, which used to be considered the gold standard but is limited by sampling error, complications, and poor patient acceptance[6]. In recent years, noninvasive tests (NITs) have emerged as more practical and efficient alternatives and include serological panels and imaging-based elastography, which have optimized monitoring approaches in both clinical practice and research[7,8]. These tools have not only improved patient stratification but also facilitated earlier detection of disease progression, complementing global elimination efforts[2].

Within this context, the albumin-bilirubin (ALBI) score has gained attention as a simple, objective, and reproducible marker of liver function. It was originally developed to improve prognostic assessment in patients with HCC, and is calculated using routinely available labs – specifically serum albumin and bilirubin – thereby avoiding the subjectivity seen in traditional systems like the Child-Pugh classification. Its interpretation is based on defined cutoff values that classify patients into different functional grades, with good predictive performance for clinical outcomes, including measures such as positive and negative predictive value and the area under the receiver operating characteristic curve. The score itself is derived from a straightforward formula using only albumin and bilirubin: ALBI score = (log10 bilirubin × 0.66) + (albumin × -0.085). Patients are then grouped into three grades, where grade 1 indicates preserved liver function and grade 3 reflects more advanced impairment (Figure 1), offering a more objective alternative to the Child-Pugh score[9,10].

Figure 1 Albumin-bilirubin score as a non-invasive marker of liver fibrosis in chronic hepatitis c virus patients treated with direct-acting antivirals. Summary of the retrospective cohort study by Ewid et al[10], including 231 patients with chronic hepatitis C virus infection treated with direct-acting antivirals (DAAs) and followed for 2 years. It shows that the albumin-bilirubin (ALBI) score improved after DAA therapy with greater changes observed in patients with advanced fibrosis (F3-F4). Positive correlations were observed between the ALBI score and standard noninvasive tests (aspartate aminotransferase-to-platelet ratio index, aspartate aminotransferase/alanine aminotransferase ratio, and fibrosis-4 index), and receiver operating characteristic analysis demonstrated its predictive value for advanced fibrosis. Together, these findings highlight the ALBI score as a feasible and cost-effective marker of liver function and fibrosis monitoring in patients with chronic hepatitis C virus during and after DAA therapy. ALBI: Albumin-bilirubin; APRI: Aspartate aminotransferase-to-platelet ratio index; AST/ALT: Aspartate aminotransferase/alanine aminotransferase; DAA: Direct-acting antiviral; FIB-4: Fibrosis-4; HCV: Hepatitis C virus; SVR: Sustained virological response.

Importantly, accumulating evidence underscores the expanding applicability of the ALBI score beyond malignant disease, extending to chronic viral hepatitis and other nonmalignant disease, extending to chronic viral hepatitis and other nonmalignant liver conditions, where it may complement existing NITs to monitor residual hepatic dysfunction even after viral clearance[4]. The study by Ewid et al[10] shows a clear association between the ALBI score and the severity of liver fibrosis in patients with chronic HCV infection, expanding its role beyond just assessing liver function to also reflecting structural liver damage. From a clinical standpoint, this suggests that the ALBI score could be a simple, low-cost, and widely available tool for monitoring treatment response and helping stratify patients during follow-up. Importantly, its performance is comparable to conventional noninvasive markers, with a significant positive correlation with established indices such as aspartate aminotransferase-to-platelet ratio index (APRI), aspartate aminotransferase/alanine aminotransferase ratio, and fibrosis-4 (FIB-4), both before and after treatment, supporting its potential as a surrogate marker of fibrosis severity. The score also improves after DAA therapy, particularly in patients with more advanced disease, highlighting its usefulness in tracking disease progression and response to treatment. In multivariate analysis, it stands out as one of the strongest predictors of fibrosis stage. However, the available studies have some limitations, including relatively small sample sizes, retrospective designs, reliance on a single baseline FibroScan measurement without post-treatment reassessment, and only moderate sensitivity, which may limit its value as a standalone diagnostic tool for staging fibrosis. In this context, the editorial aims to critically assess the role of the ALBI score in chronic HCV, focusing on its potential to refine functional assessment, improve risk stratification, and serve as a practical tool for long-term follow-up in the DAA era.

ALBI AS A RELIABLE INDICATOR OF LIVER FUNCTION AND FIBROSIS

The ALBI score was originally developed to assess the prognosis of patients with HCC, and its application has been increasingly extended to chronic liver disease and non-liver diseases in which it has been shown to be remarkably accurate in prognosis and has been successfully applied to the prediction of survival in patients with nonmalignant liver diseases of various etiologies, including chronic viral hepatitis B and C, primary biliary cholangitis, and autoimmune hepatitis[11]. The ALBI score may be used as a non-invasive tool to detect and monitor different degrees of liver fibrosis, including the assessment of fibrosis regression and its correlation with FibroScan measurements[10]. A retrospective cohort study published in World Journal of Hepatology by Ewid et al[10] conducted an analysis based on hospital records in Saudi Arabia and selected 231 eligible adult patients with a chronic HCV diagnosis. All selected patients had received one of the locally available HCV DAA regimens and completed a 2-year follow-up after the end of their treatment. The results revealed that advanced fibrosis was significantly more common in older patients with comorbidities of diabetes mellitus and hypertension than in those who did not respond to antiviral therapy. The ALBI score significantly improved for patients with nonadvanced liver fibrosis who received DAA treatment (Figure 1)[10]. The correlations between the ALBI score and NIT results for liver fibrosis were determined at baseline and after DAA therapy. Significant liver function improvement was noted following DAA treatment. The ALBI score improved the correlations with all NITs for liver fibrosis (aspartate aminotransferase-to-platelet ratio index, aspartate aminotransferase/alanine aminotransferase ratio, and FIB-4 index), both before and after antiviral therapy.

These findings are consistent with those of other reports, such as the study of Martínez Herreros et al[12], that reported similar improvements in ALBI scores among nearly 500 patients with HCV who achieved SVR with DAAs, even in those with preserved baseline function. By contrast, Hashem et al[13] demonstrated that while the ALBI score exhibited moderate performance in discriminating advanced fibrosis and cirrhosis (area under the receiver operating characteristic of 0.73-0.74), other scores, such as FIB-4, aspartate aminotransferase-to-platelet ratio index, and the Göteborg University Cirrhosis, performed better in structural staging[13]. Other noninvasive approaches, serum biomarkers, composite scores, ultrasound, and magnetic resonance elastography remain essential for the assessment of fibrosis[14].

A recent study reviewed different biomarkers for staging fibrosis and metabolic dysfunction-associated steatohepatitis and collected and compared biomarkers and liver biopsy samples from 966 participants. The results of this study revealed that none of the single biomarkers achieved the desired performance to replace liver histology in detecting metabolic dysfunction-associated steatohepatitis and clinically significant fibrosis[15]. The ALBI score provides another layer of insight by focusing on hepatic functional status rather than focusing exclusively on structural liver alterations. This difference is partially relevant in chronic HCV infection, where residual impairment in liver function can persist despite fibrosis regression and effective viral eradication with DAAs[16]. In contrast to fibrosis-oriented biomarkers-typically reflecting extracellular matrix remodeling or hepatocellular injury, the ALBI score is derived from two parameters that represent the synthetic and excretory capacity of the liver, offering a broader view of the disease evolution[17]. As a result, even if it is not the strongest standalone marker of fibrosis burden, the ALBI score provides valuable insight into dynamic functional changes and works well as a complementary tool alongside other established NITs.

CLINICAL IMPLICATIONS AND PRACTICAL APPLICATIONS OF ALBI IN HCV MANAGEMENT

The ALBI score can be used as an additional resource during the evaluation of patients with chronic HCV during and after DAA therapy. As a dynamic, noninvasive biomarker, the ALBI score can be used as a cost-effective tool because it utilizes the levels of albumin and bilirubin, two generally inexpensive and accessible serum biochemical parameters. This makes it a competent option for routine follow-up in which repeated and noninvasive monitoring is necessary to capture functional changes over time[18]. A cohort study involving 2394 patients with chronic HCV infection was conducted in the United Kingdom by Johnson et al[19]. Researchers used the ALBI score to determine liver function, and the results revealed that the achievement of SVR was possible and could be related to a major improvement in ALBI scores, indicating the restoration of liver performance over a 2-year period after initiating DAA therapy. Significantly, the most relevant improvements were evident in patients with advanced or decompensated liver disease upon enrollment. Therefore, these findings demonstrate the utility of the score as a simple yet cost-effective approach for liver function assessment without the burden of additional procedures or financial challenges[19].

The simplicity of the score makes it particularly relevant for health care systems in regions with limited resources, many of which face a greater burden of HCV infection and limited access to advanced testing modalities. In such settings the implementation of the ALBI score as a simple, low-cost, reliable tool may increase the resolution of existing gaps in patient monitoring and highlight treatment benefits beyond viral clearance[13]. In addition, the integration into clinical practice could enhance equal access in patient care by allowing healthcare facilities without advanced diagnostic tools, such as elastography or complex biomarkers panels to still perform effective monitoring and stratification of liver function[13]. Consequently, this makes the ALBI score particularly relevant in regions with a high burden of HCV infection but limited healthcare resources available, including many areas across Africa, Asia, and Latin America.

Multiple studies have attempted to apply the ALBI score across different liver diseases, suggesting both its diagnostic and prognostic versatility (Table 1)[13,20-22]. In chronic cases of HCV, the ALBI score has shown a moderate ability to distinguish fibrosis stages among Japanese patients and a moderate ability to detect advanced fibrosis among patients in Egypt[13]. For example, in patients with HCV cirrhosis, the ALBI score can be used as a predictive factor associated with portal hypertension and encephalopathy; it also serves as an indicator of long-term survival and mortality[20,23]. With respect to patients with hepatitis B virus-related acute-on-chronic liver failure, the combination of the ALBI score with the model for end-stage liver disease score improves the prediction accuracy of 3-month mortality; moreover, the ALBI score outperforms the Child-Pugh score in predicting overall survival outcomes[24,25]. In patients with metabolic dysfunction-associated steatotic liver disease, an increased ALBI score is considered an independent predictor of all-cause mortality (Table 2)[23-26]. Collectively, these results suggest the wide-ranging applicability of the ALBI score for fibrosis staging, monitoring, and prognosis evaluation in the context of viral, autoimmune, and metabolic liver diseases. This highlights it as a valuable device although the FIB-4 index and metabolic dysfunction-associated steatotic liver disease fibrosis score are more commonly used for nonviral HCC screening[21].

Table 1 Diagnostic performance of the albumin-bilirubin score across liver diseases.

Liver disease	Study type	Country	Sample size	Key findings
Chronic HCV fibrosis staging	Retrospective diagnostic accuracy	Japan	382	Cutoff of 2.125; sensitivity of 73.2%; specificity of 87.1%. ALBI differentiated fibrosis stages (F0-F4). Lower scores associated with improved HCC-free and overall survival
Chronic HCV advanced fibrosis/cirrhosis	Cross-sectional diagnostic study	Egypt	781	Area under the receiver operating characteristic of 0.73-0.74; cutoff of 2.95; sensitivity approximately 79%; specificity approximately 53%. Moderate diagnostic performance for F3-F4
HCV cirrhosis portal hypertension and encephalopathy	Retrospective correlation study	United States	61	ALBI score correlated with portal hypertension (P = 0.023) and encephalopathy (P = 0.038)
Nonviral HCC in MASLD/metabolic dysfunction-associated steatohepatitis fibrosis risk assessment	Observational study	Japan	190	Cutoff of 2.60. ALBI showed high omission rates (35.8%-62.6%). Fibrosis-4 and MASLD fibrosis score performed better for high-risk group identification

ALBI: Albumin-bilirubin; HCC: Hepatocellular carcinoma; HCV: Hepatitis C virus; MASLD: Metabolic dysfunction-associated steatotic liver disease.

Table 2 Prognostic prediction using the albumin-bilirubin score across liver diseases.

Liver disease	Study type	Country	Sample size	Key findings
HBV-related cirrhosis long-term prognosis	Prognostic comparison study	China	322	ALBI correlated with fibrosis stage and hepatocellular carcinoma-free survival. Higher scores predicted mortality, outperforming MELD and Child-Pugh in some analyses
HBV AoCLF	Prognostic study (3-month mortality)	China	84 AoCLF + 56 chronic hepatitis B	AUROC ALBI of 0.784; ALBI + MELD of 0.912. Combination improved mortality prediction
Primary biliary cholangitis	Long-term prognostic cohort	Japan	409	ALBI outperformed Child-Pugh for 3-year, 5-year, and 10-year survival (AUROC of 0.90-0.94)
Metabolic dysfunction-associated steatotic liver disease	Longitudinal cohort study	United States	5666	AUROC mortality: 1-year of 0.715, 2-year of 0.646, 3-year of 0.652. ALBI ≥ -2.69 increased mortality risk (hazard ratio = 4.86)

ALBI: Albumin-bilirubin; AoCLF: Acute-on-chronic liver failure; AUROC: Area under the receiver operating characteristic; HBV: Hepatitis B virus; MELD: Model for end-stage liver disease.

Along with its ability to reflect hepatic functional reserve, the ALBI score may also capture aspects of systemic and hepatic inflammation. Higher ALBI values have been associated with elevated inflammatory markers, including C-reactive protein and interleukin-6, supporting its potential role as an indicator of inflammatory activity within the liver[27]. Proinflammatory cytokines, particularly interleukin-6, inhibit albumin synthesis and enhance its function as a negative acute-phase reactant, resulting in reduced serum albumin concentrations during both hepatic and systemic inflammatory tests. In addition, cholestasis and compromised hepatocyte function interfere with bilirubin uptake, conjugation, and elimination, leading to an increase in circulating bilirubin levels. These combined effects reflect both decreased hepatic synthetic function and the extent of active inflammatory processes.

As mentioned by Ewid et al[10] in their article, by integrating albumin and bilirubin into a single measure, the ALBI score captures not only liver function but also elements of metabolic dysfunction and ongoing inflammatory activity. This dual capacity positions the ALBI as a versatile biomarker, not only for fibrosis staging and hepatic function status but also for guiding prognostic evaluation in patients who remain susceptible of persistent inflammatory injury despite viral clearance. More recently, the ALBI-gamma-glutamyl transferase (GGT) score was developed by Akabane et al[28], who combined the ALBI score with the GGT level, which is a known indicator of hepatic oxidative stress and inflammation. In a multicenter cohort study of 759 patients who underwent curative-intent resections for HCC, the ALBI-GGT score demonstrated superior prognostic stratification compared with the ALBI score alone. The model showed increased sensitivity to subtle alterations in liver inflammation and functional reserve. Importantly, patients with increased ALBI-GGT scores had an overall decreased 5-year survival rate, underscoring the prognostic value of incorporating inflammatory markers into liver function assessment. Overall, these findings suggest that the ALBI score, particularly when combined with markers like GGT, can serve as a more comprehensive tool, integrating fibrosis staging, functional evaluation, and both hepatic and systemic inflammatory activity.

FUTURE DIRECTIONS AND CURRENT LIMITATIONS OF ALBI RESEARCH

While the ALBI score offers practical advantages, as an objective, simple measure of hepatic function, several important limitations warrant consideration. Current evidence supporting ALBI for monitoring chronic HCV infection remains limited, as most validation studies have focused on cohorts with cirrhosis or HCC rather than patients with chronic hepatitis without cirrhosis[9,17,18]. Additionally, the ALBI is susceptible to extrahepatic confounding factors: Albumin levels may decrease due to malnutrition, chronic illness, renal loss, or systemic inflammation, while bilirubin levels may rise with hemolysis, biliary obstruction, or certain medications. Compared with established non-invasive markers such as APRI and FIB-4, which incorporate platelet count and transaminases more directly associated with fibrosis progression, ALBI may be more vulnerable to these extrahepatic influences, potentially reducing its specificity in certain clinical contexts.

Fibrosis represents structural liver alteration, whereas ALBI reflects synthetic and excretory function, these functional parameters typically become abnormal only in advanced fibrosis or cirrhosis, meaning ALBI cannot detect early or moderate fibrosis and does not correlate linearly with fibrosis stages (F0-F4). In contrast, indices such as FIB-4 and APRI have demonstrated better performance in identifying earlier stages of fibrosis, though they have limitations, particularly reduced accuracy in intermediate stages and dependence on platelet count variability. Another limitation is the absence of cross-population validation for unified ALBI cutoff values. Most existing thresholds were derived from specific cohorts (Table 1)[13,20-22], and their applicability to other populations remains uncertain. Without consistent validation across diverse groups, ALBI cutoff values may not reliably distinguish comparable degrees of liver dysfunction. These limitations can reduce the specificity of the ALBI for assessing liver-related dysfunction and limit its comparative use in broader clinical or research settings[11]. The score offers complete objectivity and improved inter-observer reproducibility; its results are simpler and more focused on hepatic function compared to model for end-stage liver disease and Child-Pugh, which include subjective variables. Additionally, unlike APRI and FIB-4, ALBI does not rely on platelet count, which may improve its reliability in patients with thrombocytopenia, a common finding in advanced liver disease. However, while ALBI enhances objectivity and simplicity, it may lack sufficient sensitivity, particularly for early-stage fibrosis, and reduced accuracy has been observed in advanced or decompensated cirrhosis. Variability in outcomes across studies likely reflects differences in patient populations and study conditions, underscoring the need for robust validation in large-scale trials[10,11].

To confirm its clinical utility, larger and longer-term studies across diverse populations are needed, ideally through multicenter prospective cohorts evaluating ALBI’s ability to predict hepatic decompensation and HCC[1-3]. Such investigations should also directly compare ALBI with established non-invasive markers to better define its relative diagnostic and prognostic value. Expanding this evidence base will be essential to validate and refine the role of the ALBI score, potentially broadening its applications beyond its current scope. Additionally, global validation presents an important challenge because a considerable amount of the current literature on the ALBI score originates from cohorts in Asia and the Middle East[10,22] that does not completely cover the diversity of global HCV populations. Given the genetic, metabolic, and environmental factors that influence disease progression, testing the reproducibility of ALBI scores in Latin America, African, and Western populations is crucial for establishing ALBI as a universally dependable biomarker in HCV management. Determining the optimal frequency and clinical thresholds for ALBI monitoring during post-DAA follow-up should be considered a priority. Long-term HCV cohorts have demonstrated that certain complications can still arise despite SVR, particularly in patients with metabolic dysfunction, alcohol abuse, or advanced fibrosis[4,5]. Determining whether dynamic changes in ALBI precede hepatic events could refine follow-up protocols and guide resource allocation in clinical practice.

ALBI scores are increasingly being incorporated into artificial intelligence-driven imaging analysis and multidimensional biomarkers integration approaches, which together may provide a more comprehensive and mechanistic understanding of liver disease biology and prognosis[29]. For instance, machine learning models that incorporate preoperative ALBI scores have demonstrated promising results, revealing strong predictive performance for severe postoperative liver complications and mortality, with ALBI measurements on postoperative days 1 and 3 emerging as key prognostic variables within these models[30]. Such integrative stratification strategies may enhance prognostic accuracy and create more individualized risk stratification models for patients with chronic HCV.

CONCLUSION

The ALBI score is shaping up to be a useful, simple, and reproducible marker for assessing liver function in patients with chronic HCV infection, especially in the era of DAAs. Its improvement after sustained virologic response, along with its correlation with established NITs, suggests that it reflects not only fibrosis but also ongoing inflammatory activity, making it a practical and cost-effective option for longitudinal follow-up. The available evidence, however, is still limited and not enough to support firm clinical recommendations.