Ewid M, Sherif H, Saquib N, Alammari AM, Ismail AAM, Alkahlot MH, Ahmed ZT, Al-Zabidi FZM, Al Mutiri N. Albumin-bilirubin score reflects the extent of liver fibrosis in chronic hepatitis C patients treated with direct-acting antivirals. World J Hepatol 2025; 17(9): 110049 [DOI: 10.4254/wjh.v17.i9.110049]
Corresponding Author of This Article
Mohammed Ewid, MD, Department of Internal Medicine, College of Medicine, Sulaiman Al Rajhi University, Post Office Box 777, Al Bukayriyah 51941, Qassim, Saudi Arabia. drmohammedowid@gmail.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Retrospective Cohort Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Mohammed Ewid, Department of Internal Medicine, College of Medicine, Sulaiman Al Rajhi University, Al Bukayriyah 51941, Qassim, Saudi Arabia
Mohammed Ewid, Amro Abdelaziz Mohammed Ismail, Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo 11562, Egypt
Hossam Sherif, Department of Critical Care Medicine, College of Medicine, Sulaiman Al Rajhi University, Al Bukayriyah 51941, Qassim, Saudi Arabia
Hossam Sherif, Department of Critical Care Medicine, Cairo University, Cairo 11562, Egypt
Nazmus Saquib, Department of Epidemiology, College of Medicine, Sulaiman Al Rajhi University, Al Bukayriyah 51941, Qassim, Saudi Arabia
Ammar Mohammed Alammari, Amro Abdelaziz Mohammed Ismail, Nawaf Al Mutiri, Department of Gastroenterology, King Fahad Specialist Hospital, Buraydah 52366, Qassim, Saudi Arabia
Mohammed H Alkahlot, Ziyad T Ahmed, Faisal Zain Mohammed Al-Zabidi, College of Medicine, Sulaiman Al Rajhi University, Al Bukayriyah 51941, Qassim, Saudi Arabia
Author contributions: Ewid M, Sherif H, Saquib N, and Al-Zabidi FZM completed the statistical analysis, and interpreted the data; Ewid M and Saquib N critically revised the manuscript; Ewid M, Saquib N, Alkahlot MH, Ahmed ZT, and Al Mutiri N designed the study; Alammari AM, Ismail AAM, and Al Mutiri N provided administrative support; Alkahlot MH, Ahmed ZT, and Al-Zabidi FZM provided technical or material support.
Institutional review board statement: This study was conducted in accordance with ethical principles that have their origin in the provisions of the Declaration of Helsinki. Ethical approval was granted by the Regional Research Ethics Committee - Qassim Province, Ministry of Health, Saudi Arabia (Approval No. 1441-667587).
Informed consent statement: The requirement for participants to consent to participate was waived by the Regional Research Ethics Committee as the study was retrospective.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: The dataset supporting the conclusions of this article is available from the corresponding author upon reasonable request.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Mohammed Ewid, MD, Department of Internal Medicine, College of Medicine, Sulaiman Al Rajhi University, Post Office Box 777, Al Bukayriyah 51941, Qassim, Saudi Arabia. drmohammedowid@gmail.com
Received: May 30, 2025 Revised: June 25, 2025 Accepted: August 15, 2025 Published online: September 27, 2025 Processing time: 118 Days and 16.1 Hours
Abstract
BACKGROUND
The albumin-bilirubin (ALBI) score was developed as a prognostic tool for patients with hepatocellular carcinoma. However, its new role as an indicator of liver fibrosis in chronic hepatitis C virus (HCV) patients is under investigation.
AIM
To investigate the ALBI score as a non-invasive means of assessing the extent of liver fibrosis in chronic HCV patients.
METHODS
We evaluated hospital records of 231 eligible chronic HCV patients from King Fahad Specialist Hospital in Buraydah, Saudi Arabia. Demographic/clinical data, liver function tests, non-invasive tests for liver fibrosis, and ALBI score/grades were evaluated before and two years after direct-acting antivirals (DAA) treatment.
RESULTS
The median ALBI score improved from -2.51 to -2.62 after DAA treatment (P < 0.05). Additionally, the ALBI score improved irrespective of the level of fibrosis, with improvement more evident in patients with advanced fibrosis (-2.26 to -2.41, P < 0.05). The ALBI score showed significant positive correlation with non-invasive tests for liver fibrosis (aspartate aminotransferase/alanine aminotransferase ratio, aspartate aminotransferase to platelet ratio index, and fibrosis-4 index) at baseline and after DAA treatment (P < 0.05). Moreover, the receiver operating characteristic curve demonstrated ALBI score’s ability to predict advanced fibrosis (F3, F4) [area under the curve = 0.76, (95% confidence interval: 0.70-0.81), P < 0.001, best cut-off value = -2.38 (sensitivity 60% and specificity 83%)].
CONCLUSION
The ALBI score appears to be a useful non-invasive marker for assessing liver fibrosis in chronic HCV patients and may serve as a valuable tool for monitoring hepatic function during and after DAA treatment.
Core Tip: The albumin-bilirubin score is a simple and reproducible score that showed significant improvement following direct-acting antivirals treatment in patients with chronic hepatitis C virus infection. Moreover, it predicted advanced liver fibrosis with a sensitivity of 60% and a specificity of 83% at a cut-off value of -2.38. Accordingly, it could be utilized to monitor liver function and to determine the extent of liver fibrosis among those patients.
Citation: Ewid M, Sherif H, Saquib N, Alammari AM, Ismail AAM, Alkahlot MH, Ahmed ZT, Al-Zabidi FZM, Al Mutiri N. Albumin-bilirubin score reflects the extent of liver fibrosis in chronic hepatitis C patients treated with direct-acting antivirals. World J Hepatol 2025; 17(9): 110049
The hepatitis C virus (HCV) is a global public health issue that affects up to 57.5 million people worldwide and causes around 290000 deaths annually[1]. Unfortunately, HCV infection persists in 50%-90% of patients following acute infection, and if not treated, can lead to end-stage liver complications, including liver cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC) in up to 20%-60% of patients[2]. Furthermore, HCV induces extrahepatic disorders affecting multiple systems/organs and is the most common cause of liver transplantation from hepatic complications in developed countries. Accordingly, HCV infection has a significant morbidity and mortality burden that affects patients’ quality of life at the individual level and increases the health care costs for the public at large[3]. The treatment of HCV has evolved over the years, beginning with interferon (IFN)-based monotherapy in the late 1980s and progressing to direct-acting antivirals (DAA) in the last decade, with the use of ribavirin (RBV) monotherapy, IFN-RBV combination therapy, and pegylated IFN-RBV combination therapy during the intervening years[4]. The sustained virological response jumped from 40% with pegylated IFN-RBV to 99% with the pan-genotypic DAA[5]. HCV-induced liver fibrosis has been extensively studied, initially through liver biopsy and the METAVIR score. Due to the invasiveness and limitations of biopsy, non-invasive tests (NITs) - both biological [e.g., aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, AST to platelet ratio index (APRI), and fibrosis-4 index (FIB-4)] and radiological (e.g., liver stiffness measurement via FibroScan) - gained prominence. However, most NITs have limitations, particularly in assessing fibrosis regression after successful antiviral therapy[6-9].
Research is ongoing for a feasible and reproducible non-invasive marker of liver fibrosis. One such marker is the albumin-bilirubin (ALBI) score, calculated based on serum total bilirubin and serum albumin. It was developed as a prognostic marker for patients with HCC[10-12], but since then, ALBI has been used extensively for other hepatic conditions, such as biliary cirrhosis[13], drug-induced liver injury[14], for predicting liver outcomes in preoperative assessment[15], and estimating the prognosis following liver transplantation[16]. Moreover, research has extended into the use of the ALBI score as a prognostic tool for non-hepatic diseases like cardiovascular diseases[17-19] and extrahepatic malignancies, including gastrointestinal, lung, and central nervous system cancers[20-23]. Despite this broad utility, the role of the ALBI score in monitoring liver function in HCV patients treated with DAA remains underexplored. Specifically, its diagnostic value in tracking fibrosis regression and its correlation with FibroScan results require further investigation. Given that many chronic HCV patients are asymptomatic with preserved liver function, the ALBI score - with its objectivity and sensitivity to subtle hepatic changes - may serve as a valuable monitoring tool. Accordingly, we aimed to explore the ALBI score’s diagnostic and prognostic value in detecting degrees of liver fibrosis among patients with chronic hepatitis C who were treated with DAA.
MATERIALS AND METHODS
Study design and participants
We conducted a hospital records-based study at King Fahad Specialist Hospital in Buraydah, Qassim, Saudi Arabia, where a sample of 231 eligible adult patients (98 men, 133 women) with a chronic HCV diagnosis were selected. The study was approved by the Ministry of Health’s Regional Research Ethics Committee - Qassim Province, Ministry of Health, Saudi Arabia (Approval No. 1441-667587) and received administrative permission from the hospital to gain access to its patient records. All selected patients had received one of the locally available HCV DAA regimens and completed a two-year follow-up after the end of their treatment. Patients were excluded from the study if they had alternative documented causes of liver disease (other than HCV) such as co-infection with hepatitis B virus, human immunodeficiency virus, autoimmune hepatitis, metabolic disorders, Wilson’s disease, hemochromatosis, and/or alcohol-related liver disease, or concomitant liver or biliary cancers, end organ failure, and/or were pregnant.
Data extraction
Data for all study variables were obtained from hospital records, including demographic and clinical data such as age, gender, alcohol intake, liver cirrhosis status, presence of hepatic/portal hypertension complications, type of DAA used, achieved sustained virological response, and comorbidities. Laboratory values before and two years after DAA treatment, including serum ALT, AST, bilirubin, albumin, alkaline phosphatase, alpha fetoprotein, HCV RNA viral load, HCV genotype, complete blood count, activated partial thromboplastin time, and international normalized ratio were obtained as well.
The ALBI score was calculated using each patient’s serum levels of albumin and bilirubin with the following formula: ALBI score = [logarithm base 10 bilirubin (μmol/L) × 0.66] + [albumin (g/L) × (-0.0852)]. Then the patients were stratified into three grades based on their ALBI scores: Grade I (≤ -2.60), grade II (> -2.60 to ≤ -1.39), and grade III (> -1.39)[10]. We calculated the following NITs for liver fibrosis using their standard calculation methodology: AST/ALT ratio; APRI using the formula (AST/top normal AST)/[platelet count (109/L) × 100]; FIB-4 using the formula [age (years) × AST)]/[platelet count (109/L) × ALT square root][6]. All patients had only pre-treatment FibroScan liver stiffness measurement records and stages (Echosens, Paris, France). In the analysis of ALBI score’s predictivity for advanced liver fibrosis, we divided the FibroScan stages into two dichotomous groups with stages F3 and F4 (liver stiffness measurement ≥ 9.5 kPa) representing advanced fibrosis and the other stages considered non-advanced fibrosis[24].
Statistical analysis
The statistical analysis was conducted using SPSS version 28 (Chicago, IL, United Stated). The Kolmogorov-Smirnov test was used to test the data normality. Quantitative data is presented as mean ± SD for Gaussian distributions or median ± (interquartile range: 25th-75th percentile) for non-Gaussian distributed parameters. Qualitative data is presented as percentages. Comparisons between groups were made using the Mann-Whitney U or Wilcoxon test for continuous variables, and the χ2/Fisher’s exact/marginal homogeneity tests were used for the relevant categorical variables. The receiver operating characteristic (ROC) curve was used to test the discriminatory power of the ALBI score and its best cut-off value for detecting advanced liver fibrosis. P-values less than 0.05 were considered statistically significant.
RESULTS
Patient demographics, clinical, and laboratory characteristics
The study cohort’s baseline characteristics are represented by the degree of liver fibrosis [non-advanced (F0, F1 and F2) vs advanced (F3 and F4)] in Table 1. In terms of clinical characteristics, advanced fibrosis was significantly higher in older patients with comorbidities of diabetes mellitus and hypertension and those with no response to antiviral treatment (P < 0.05). On the other hand, patients with non-advanced liver fibrosis had significantly more favorable values on liver function tests and NITs of liver fibrosis (P < 0.05). The ALBI score was significantly lower for patients with non-advanced liver fibrosis (P < 0.05). Additionally, the distribution of ALBI grades was significantly different, with grade I being more common in patients with non-advanced fibrosis and grades II and III being more common in patients with advanced fibrosis (P < 0.05; Figure 1).
Patients’ laboratory profile before and after DAA treatment
Pre-treatment and post-treatment laboratory values are presented in Table 2. Significant liver function improvement was noted following DAA treatment. Notably, ALBI levels improved from a pre-treatment median of -2.51 ± 0.65 to -2.62 ± 0.62 after treatment (P < 0.05).
Table 2 Patients’ laboratory profile, including albumin-bilirubin score, before and after direct-acting antiviral treatment, median ± interquartile range.
ALBI score profile in relation to the degree of liver fibrosis
As shown in Table 3 and Figure 1, when we compared ALBI scores in relation to the degree of baseline liver fibrosis, we found that the baseline ALBI scores were more favorable in the non-advanced fibrosis group (-2.73 ± 0.43 vs -2.26 ± 0.65; P < 0.05). Following DAA treatment, we noted significant improvement in ALBI scores in both the non-advanced and advanced liver fibrosis groups, with the improvement more evident in the advanced fibrosis group (P < 0.05).
Table 3 Albumin-bilirubin scores before and after direct-acting antiviral treatment in relation to the degree of liver fibrosis.
Correlation of ALBI score with laboratory NITs for liver fibrosis
The correlations between the ALBI score and NITs for liver fibrosis are demonstrated in Table 4. The correlation was performed both at baseline and after DAA treatment. As shown in the table, the ALBI score had significant positive correlations with all NITs for liver fibrosis (APRI, AST/ALT ratio, and FIB-4) before and after DAA treatment.
Table 4 Correlation of albumin-bilirubin score with other non-invasive tests for liver fibrosis.
ALBI score’s discriminatory power against the degree of baseline liver fibrosis
The generated ROC curves (Figure 2; Table 5) demonstrate that the ALBI score can predict advanced fibrosis (F3, F4) with an area under the curve (AUC) = 0.76 (95% confidence interval: 0.70 to 0.81; P < 0.001) and best cut-off value = -2.38 (sensitivity 60% and specificity 83%). Moreover, the curves highlight that the ALBI score is not inferior and is comparable to the standard NITs (AST/ALT, APRI, and FIB-4) in predicting liver fibrosis as per the generated values. For more evaluation of the predictability of the ALBI score for the degree of liver fibrosis, we conducted a multivariate linear regression analysis on a model that included the ALBI score in addition to standard NITs. The results of the multivariate linear regression analysis revealed that the ALBI score had the highest significant positive correlation, in relation to the other standard NITs, for predicting the extent of liver fibrosis (Table 6).
Our study presents new data that can fill the knowledge gaps regarding the ALBI score’s predictive value for liver fibrosis severity in patients with chronic HCV infection. To our knowledge, this is the first study to give these predictive values for the ALBI score against liver fibrosis stages defined noninvasively by FibroScan. In addition, we evaluated the ALBI score’s diagnostic value against recognized biological NITs of liver fibrosis (AST/ALT ratio, APRI and FIB-4). In our study, the ALBI score had significant improvement following DAA treatment and preserved a positive correlation with biological NITs of liver fibrosis (AST/ALT ratio, APRI, and FIB-4 scores) before and after DAA treatment. Johnson et al[25] found similar results.
Taking FibroScan as a yardstick, the ALBI score successfully discriminated between advanced and non-advanced fibrosis, a finding that opens the door for using the ALBI score in the battle against liver fibrosis. This adds to recent research in this regard[26]. We further proceeded in our analysis to address the understudied sensitivity, specificity, and cut-off values of the ALBI score in relation to liver fibrosis stages assessed by FibroScan. Our generated ROC curves (Figure 2; Table 5) demonstrated that the ALBI score can detect advanced fibrosis (F3, F4), with AUC of 0.76 (95% confidence interval: 0.70-0.81; P < 0.001) and best cut-off value = -2.38 (sensitivity 60% and specificity 83%). The available comparative data in the literature for our above results are based on a retrospective study conducted by Fujita et al[27] that tested the ALBI score’s relationship to liver fibrosis identified invasively via liver biopsy (METAVIR score/grades). They found that a -2.56 ALBI score was the best cut-off value, with 79.3% sensitivity, 62.5% specificity, and a 0.78 AUC[27]. Despite the moderate sensitivity value of the ALBI score in the current study, it achieved a good specificity value with significant AUC, highlighting its validity as a discriminating test for liver fibrosis severity. We partially attribute the stringent ALBI score cut-off value (-2.38) as the reason for the good specificity and moderate sensitivity. Our generated ROC curves highlight that the ALBI score is not inferior and is comparable to the standard NITs (AST/ALT, APRI, and FIB-4) in predicting liver fibrosis, which is also supported by published data. For example, APRI had a predictive AUC of 0.77, 0.80, 0.83 for detecting ≥ F2, ≥ F3, and cirrhosis, respectively, with a collective AUC of 0.76 for advanced fibrosis. Similarly, the predictivity of FIB-4 was comparable to APRI, with a collective area under the receiver operating characteristic curve between 0.73 and 0.80[28].
Moreover, our multivariate linear regression analysis model revealed that the ALBI score has the highest positive correlation, in relation to the other standard NITs, for predicting the extent of liver fibrosis, which further supports its future value in this regard. Alongside the above, it is worth noting that most biological NITs for liver fibrosis have limitations regarding their sensitivity values, as reported in multiple studies[8,29]. An additional limitation of APRI and FIB-4 is the platelet count in their calculation. The ALBI score, however, does not include platelet count in its formula, which improves its accuracy in cases of thrombocytopenia, which is common in patients with hepatic disorders. An additional observation in our study is that when the ALBI score was categorized into its grades (I, II and III), it showed a significant statistical difference in relation to the degree of liver fibrosis. Moreover, ALBI grades showed significant improvement post-DAA treatment compared to pre-treatment status. Such research findings augment our hypothesis that the ALBI score and its generated grades are viable ways to monitor liver function, which is supported by recent research[25,27]. Our results spotlight the value of the ALBI score as a feasible, objective, and reproducible indicator of liver function and the degree of liver fibrosis among patients with chronic HCV. As it is cost-effective and reliable, the ALBI score will likely be a clinically applicable monitoring tool in the near future for patients with chronic HCV infection who are treated with DAA. However, prospective studies are required in order to validate our results before making general recommendations.
Recent studies have found a positive correlation between the ALBI score and inflammatory markers/indices, such as the peripheral inflammatory cell ratios in patients with HCC[30]. The ALBI score’s ability to reflect the cellular immune-inflammatory status could be a benefit beyond its ability to differentiate liver fibrosis severity, a point that needs further investigation in future studies. We hope that our newly generated ALBI score’s predictive values help general practitioners and experts in the follow-up of liver fibrosis in patients with chronic HCV infection and decrease the sequelae of liver fibrosis in those patients.
Study limitations
The study had a relatively small sample size, and its retrospective nature did not allow for optimum follow-up of the patients or precise prediction of the factors associated with the ALBI score’s improvement. In addition, only baseline FibroScan results were recorded in the system for the patients.
Study strength
This study is one of the few studies to provide data on the ALBI score’s predictive value in detecting the degree of liver fibrosis in relation to FibroScan. In fact, our research was generated based on researchers’ recommendations to fill the knowledge gaps related to ALBI score’s predictivity as mentioned in the limitation sections of previous studies[27,31].
CONCLUSION
The ALBI score could be used as an indicator of the degree of liver fibrosis and liver function in patients with chronic HCV infection who are treated with DAA. Future larger prospective studies are required for better assessment of the diagnostic and predictive value of the ALBI score for liver fibrosis and function.
ACKNOWLEDGEMENTS
The authors thank Erin Strotheide for her editorial contributions to this manuscript.
Footnotes
Provenance and peer review: Unsolicited article; Externally peer reviewed.
Peer-review model: Single blind
Corresponding Author's Membership in Professional Societies: Egyptian Association for the Study of Liver and Gastrointestinal Diseases.
Specialty type: Gastroenterology and hepatology
Country of origin: Saudi Arabia
Peer-review report’s classification
Scientific Quality: Grade A, Grade D
Novelty: Grade B, Grade D
Creativity or Innovation: Grade B, Grade D
Scientific Significance: Grade B, Grade D
P-Reviewer: Kayadibi H, MD, Professor, Türkiye; Liang GD, PhD, Associate Professor, China S-Editor: Zuo Q L-Editor: A P-Editor: Zhang YL
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