Chen YF, Lin YX, Chi MM, Li DQ, Chen LT, Zhang Y, Wu RQ, Du ZQ. Preoperative serum total bilirubin-albumin ratio as a prognostic indicator in patients with hepatitis-related cirrhosis after splenectomy. World J Gastrointest Surg 2025; 17(1): 96512 [DOI: 10.4240/wjgs.v17.i1.96512]
Corresponding Author of This Article
Zhao-Qing Du, PhD, Academic Editor, Researcher, Department of Hepatobiliary Surgery, Shaanxi Provincial People’s Hospital, No. 256 Youyi West Road, Xi’an 710068, Shaanxi Province, China. duzhaoqing2007@126.com
Research Domain of This Article
Surgery
Article-Type of This Article
Retrospective 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/
Yi-Fan Chen, Yu-Xin Lin, Miao-Miao Chi, Da-Qing Li, Lin-Tao Chen, Yu Zhang, Zhao-Qing Du, Department of Hepatobiliary Surgery, Shaanxi Provincial People’s Hospital, Xi’an 710068, Shaanxi Province, China
Yi-Fan Chen, Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
Yu-Xin Lin, Shanghai Institute of Hematology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
Miao-Miao Chi, Department of Ophthalmology, Peking University Third Hospital, Beijing 100191, China
Rong-Qian Wu, National Local Joint Engineering Research Center for Precision Surgery and Regenerative Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
Zhao-Qing Du, National Engineering Research Center for Miniaturized Detection Systems, College of Life Sciences, Northwest University of Xi’an, Xi’an 710069, Shaanxi Province, China
Author contributions: Du ZQ conceived and designed the overall research framework; Chen YF, Lin YX, Chi MM, Li DQ, and Chen LT did the data analysis; Lin YX, Chi MM, and Zhang Y provided the resources and supervision; Chen YF, Wu RQ, and Du ZQ wrote the draft; all authors contributed to the study, and read and approved the final manuscript.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of the Shaanxi Provincial People’s Hospital (Approval Number: SPPH-LLBG-17-3.2).
Informed consent statement: Written informed consent from the patients was waived due to the retrospective nature of this study.
Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose.
Data sharing statement: No additional data are available.
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: Zhao-Qing Du, PhD, Academic Editor, Researcher, Department of Hepatobiliary Surgery, Shaanxi Provincial People’s Hospital, No. 256 Youyi West Road, Xi’an 710068, Shaanxi Province, China. duzhaoqing2007@126.com
Received: May 8, 2024 Revised: September 6, 2024 Accepted: October 28, 2024 Published online: January 27, 2025 Processing time: 232 Days and 23.4 Hours
Abstract
BACKGROUND
Splenectomy is an effective yet invasive intervention for alleviating portal pressure in patients with hepatitis cirrhosis. However, the current prognostic indicators for predicting long-term overall survival of these patients have several limitations.
AIM
To assess the potential of preoperative total bilirubin-albumin (B/A) ratio as a prognostic indicator for patients with hepatitis cirrhosis undergoing splenectomy.
METHODS
A total of 257 patients diagnosed with hepatitis cirrhosis were retrospectively enrolled in the study. Normality test, t-test, Wilcoxon test, χ2 test, or Fisher’s exact test was employed to analyze the intraoperative and postoperative conditions of the patients. Receiver operating characteristic (ROC) curve analysis was utilized to depict the 10-year overall survival rate.
RESULTS
During the follow-up period, 85.99% of the patients survived, with a median survival time of 64.6 months. Multivariate analysis revealed that total serum B/A ratio was an independent risk factor for overall survival (P = 0.037). ROC curve analysis demonstrated that a B/A ratio of 0.87 was the optimal cut-off value. Consequently, the patients were categorized into two groups: High B/A group (n = 64) and low B/A group (n = 193). The median follow-up time for the high B/A group and low B/A group was 56.8 months and 67.2 months, respectively (P = 0.045). Notably, the high B/A group exhibited a significantly lower 10-year overall survival compared to the low B/A group (P < 0.001). Patients with hepatocellular carcinoma (HCC) had lower overall survival rates. Patients with a high B/A ratio exhibited a lower overall survival than those with a low B/A rate in the overall cohort and the subgroups of patients with HCC or not, early Child-Pugh grade, low albumin-bilirubin grade, and model for end-stage liver disease score ≥ 10 (log-rank test, P < 0.001 for all).
CONCLUSION
The B/A ratio can serve as an effective prognostic indicator for overall survival in patients with hepatitis B virus-related cirrhosis following splenectomy, and a higher B/A ratio may suggest a poorer prognosis.
Core Tip: High serum total bilirubin-albumin (B/A) ratio shows distinct specificities in hepatitis-related cirrhosis patients. In this study, we investigated the B/A ratio as a predictor of overall survival (OS) of hepatitis-related cirrhosis patients after splenectomy. Based on the cutoff point, patients with a high B/A ratio showed a worse long-term survival in the overall cohort and in the subgroups of patients with hepatpcellular carcinoma (HCC), without HCC, early Child-Pugh stage, low albumin-bilirubin grade, and model for end-stage liver disease score ≥ 10. B/A ratio was the only independent risk factor for OS. Because its convenience and effectiveness, the B/A ratio may be used to predict the prognosis of such patients.
Citation: Chen YF, Lin YX, Chi MM, Li DQ, Chen LT, Zhang Y, Wu RQ, Du ZQ. Preoperative serum total bilirubin-albumin ratio as a prognostic indicator in patients with hepatitis-related cirrhosis after splenectomy. World J Gastrointest Surg 2025; 17(1): 96512
Hepatitis cirrhosis is the primary etiology of portal hypertension in China and frequently results in hepatic dysfunction and hepatocellular carcinoma (HCC)[1,2]. It is estimated that around 130 million individuals are carriers of hepatitis B virus (HBV), with 30 million suffering from chronic infection and having a significantly increased risk of developing cirrhosis and subsequent portal hypertension[3]. Common manifestations associated with portal hypertension include hypersplenism and esophagogastric varices, which have an incidence rate ranging from 24% to 80% and are often accompanied by high mortality rates[4-7]. The accessibility of splenectomy has made it the primary surgical approach for portal hypertension in China[8,9]. However, its invasive nature has been associated with postoperative complications such as thrombosis and liver failure, which can be serious or even life-threatening[9-12]. Therefore, it is imperative and advantageous to explore novel prognostic indicators for patient outcomes.
However, the current albumin-bilirubin (ALBI) grade, platelet-ALBI (PALBI) classification, Child-Hugh stage, model for end-stage liver disease (MELD) score, and other prognostic indicators for patients with hepatitis cirrhosis are suboptimal[13,14]. The convenience of these indicators is compromised by complex calculation procedures, while variables such as ascites and encephalopathy introduce subjectivity[15]. Therefore, it is highly valuable to explore alternative predictors that encompass both accessibility and accuracy. Bilirubin, a key biochemical marker for liver function assessment[15,16], is primarily synthesized in the liver. Low levels of serum albumin may indicate disease progression within the liver[16]. Hulzebos et al[17] discovered that the bilirubin-albumin (B/A) ratio serves as an effective predictor of bilirubin-induced neonatal neurological dysfunction[17]. Combined with serum total bilirubin levels, the prediction of bilirubin toxicity can be enhanced by the B/A ratio [18]. Khairy et al[19] confirmed that the B/A ratio serves as an early predictor of neonatal hyperbilirubinemia[19]. This retrospective study examined the role of B/A ratio in predicting overall survival (OS) in cirrhotic patients following splenectomy.
MATERIALS AND METHODS
Patients
The clinical data of 423 patients diagnosed with hepatitis cirrhosis at Shaanxi Provincial People’s Hospital between 2010 and 2020 were collected. A total of 257 patients who underwent splenectomy and were diagnosed with hepatitis cirrhosis and portal hypertension were included in this study. Data collection took place from August 2021 to April 2022, and the collected data were analyzed in October 2022. Hepatitis-related viruses, including HBV and hepatitis C virus (HCV), were considered. Portal hypertension was defined as a portal pressure gradient of ≥ 25 mmH2O. Patient details were obtained from the hospital’s electronic health system. Patients with the following conditions were excluded from this study: (1) Multiple malignancies; (2) Severe cardiovascular disorders; (3) Incomplete medical records or inadequate follow-up; (4) Prior hepatectomy procedure; and (5) Concurrent autoimmune diseases or other comorbidities impacting serum total bilirubin or albumin levels. HCC, closely associated with cirrhosis, was not excluded from the study. Ultimately, a total of 257 patients were included in this retrospective investigation. The research protocol received approval from the Ethics Committee of Shaanxi Provincial People’s Hospital (Approval No. SPPH-LLBG-17-3.2) and adhered strictly to the principles outlined in the Helsinki Treaty. Due to the retrospective nature of this study, obtaining written informed consent was unfeasible; however, all collected information was anonymized and de-identified prior to analysis.
Data collection
The electronic health system was utilized to collect the following data: Age, gender, comorbidities (alcohol consumption, smoking, hypertension, diabetes, HBV infection, esophageal and gastric varices), laboratory test results [white blood cells, platelets, hemoglobin, alanine aminotransferase (ALT), aspartate transaminase (AST), albumin (ALB), total bilirubin (TBIL), blood urea nitrogen (BUN), creatinine, prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, international normalized ratio (INR), alpha fetoprotein (AFP), and HBV/HCV-DNA/RNA status], and surgical procedures performed during hospitalization, as well as associated costs and length of hospital stay. Blood samples were collected from patients on admission day with only the earliest set of measurements extracted for one patient. Histological evidence was collected to determine the presence of cirrhosis and the occurrence of HCC. Intraoperative data were gathered, including intraoperative blood loss, intraoperative blood transfusion, spleen volume, spleen size, etc. Postoperative data were collected on intensive care unit admission, bleeding events, portal vein thrombosis, ascites development, hepatic encephalopathy occurrence, surgical site infection incidence, pneumonia cases, and systemic inflammatory response syndrome (SIRS) episodes. The B/A ratio was calculated using the following formula: B/A ratio = total bilirubin/albumin ratio.
Follow-up
The patients were followed for a minimum of 10 years post-discharge, with the follow-up period extending until April 2022. The primary focus of the follow-up encompassed monitoring disease progression and patient mortality. OS was calculated from the time of splenectomy. To mitigate bias, two investigators independently conducted the follow-up process.
Statistical analysis
Continuous variables are presented as the mean ± SD or medians (min-max), while categorical variables are reported as frequencies or percentages. The t-test or Wilcoxon test was employed for measurement data, and the χ2 test or Fisher’s exact test was utilized for count data. Additionally, a receiver operating characteristic (ROC) curve was constructed to determine the optimal cut-off point with respect to OS. The Kaplan-Meier method was employed to construct the survival curve, while the log-rank test was utilized for statistical analysis. Risk factors for OS that exhibited a P value of less than 0.10 in the univariate analysis were further assessed through multivariate analysis. Statistical analyses were conducted using statistical product and service solutions 23.0 software (IBM Corporation, Armonk, NY, United States). GraphPad Prism 8.0 software (GraphPad Software Inc., La Jolla, CA, United States) was employed for enhancing the visual presentation of the survival curves. A significance level of P < 0.05 denoted statistical significance.
RESULTS
Patient characteristics
A total of 257 patients diagnosed with liver cirrhosis were enrolled in the study. As depicted in Table 1, the male population accounted for 73.15%, while individuals aged over 50 years constituted 33.07%. Moreover, HBV infection was observed in 93.77% of the patients, and severe esophageal and gastric varices (> 6 mm) were present in 46.69% of them. The distribution according to Child-Pugh classification revealed that grade B encompassed 61.09%, grade A comprised 31.52%, and grade C represented a smaller proportion at 7.39%.
Table 1 Clinical characteristics of 257 cirrhosis patients with high and low serum total bilirubin-albumin ratio, n (%).
Variable
Median (range) (n = 257)
High B/A group (> 0.87) (n = 64)
Low B/A group (≤ 0.87) (n = 193)
P value
Gender (male)
188 (73.15)
47 (73.44)
141 (73.06)
0.953
Age (≥ 50 years)
85 (33.07)
22 (34.38)
63 (32.64)
0.798
Coexisting conditions
Drinking
30 (11.67)
5 (7.81)
25 (12.95)
0.267
Smoking
60 (23.35)
16 (25.00)
44 (22.80)
0.718
Hypertension
4 (1.56)
0 (0.00)
4 (2.07)
0.575
Diabetes
18 (7.00)
3 (4.69)
15 (7.77)
0.574
Hepatitis B virus infection
241 (93.77)
63 (98.44)
178 (92.23)
0.130
Severe gastro-esophageal varices (> 6 mm)
120 (46.69)
33 (51.56)
87 (45.08)
0.368
Laboratory tests
Leucocytes (109/L)
2.66 (0.60-59.00)
2.67 (0.97-12.30)
2.66 (0.60-59.00)
0.992
Platelet count (< 30 × 109/L)
71 (27.63)
30 (46.88)
41 (21.24)
< 0.001
Hemoglobin (< 120 g/L)
196 (76.26)
42 (65.63)
154 (79.79)
0.021
ALT (> 40 U/L)
89 (34.63)
26 (40.63)
63 (32.64)
0.245
AST (> 40 U/L)
122 (47.47)
39 (60.94)
83 (43.01)
0.013
Albumin (< 35 g/L)
123 (47.86)
42 (65.63)
81 (41.97)
0.001
Total bilirubin (> 17 μmol/L)
181 (70.43)
64 (100.00)
117 (60.62)
< 0.001
BUN (mmol/L)
4.93 (2.08-11.51)
4.81 (2.08-10.40)
4.96 (2.09-11.51)
0.545
Creatinine (μmol/L)
65.98 (15.00-187.60)
61.94 (15.00-114.54)
67.36 (32.00-187.60)
0.033
PT (> 17 s)
77 (29.96)
38 (59.38)
39 (20.21)
< 0.001
APTT (> 45 s)
75 (29.18)
33 (51.56)
42 (21.76)
< 0.001
Fibrinogen (mg/dL)
1.89 (0.60-5.36)
1.69 (0.60-3.56)
1.96 (0.76-5.36)
0.001
INR (> 1.2)
173 (67.32)
55 (85.94)
118 (61.14)
< 0.001
AFP (mg/L)
10.95 (0.76-69.31)
17.95 (1.12-69.31)
8.76 (0.76-125.8)
0.007
HB/CV-DNA/RNA (104 IU/mL)
1267.2 (0.1-149100.0)
84.0 (0.1-729)
1632.8 (0.1-149100.0)
0.484
Child-Pugh score
Child A
81 (31.52)
2 (3.13)
79 (40.93)
< 0.001
Child B
157 (61.09)
45 (70.31)
112 (58.03)
Child C
19 (7.39)
17 (26.56)
2 (1.04)
ALBI grade
1 (≤ -2.60)
40 (15.56)
1 (1.56)
39 (20.21)
< 0.001
2 (-2.60 to -1.39)
202 (78.60)
51 (79.69)
151 (78.24)
3 (> -1.39)
15 (5.84)
12 (18.75)
3 (1.55)
MELD score (≥ 10)
48 (18.68)
27 (42.19)
21 (10.88)
< 0.001
Additionally, an assessment based on ALBI grading was conducted. The ALBI grade distribution among patients was as follows: Grade 2 (78.60%), grade 1 (15.56%), and grade 3 (5.84%). A total of 48 patients (18.68%) had a MELD score ≥ 10. Open splenectomy was performed in the majority of cases (86.38%). The most prevalent surgical complications observed were ascites (55.25%) and SIRS (51.75%). The comprehensive complication index (CCI) was calculated, revealing that 29.96% of patients had a CCI exceeding 30. Meanwhile, 15.56% of the patients were diagnosed with HCC. The average median survival time for this cohort was 64.6 months (range: 0.3-185.0 months), and 85.99% survived after completion of the follow-up period.
ROC curve analysis
ROC curve analysis was utilized to determine the optimal cut-off value of B/A ratio corresponding to the maximum Youden index. As depicted in Figure 1A, the optimal cut-off value for the B/A ratio were found to be 0.871 [with a sensitivity of 50.0% and specificity of 79.6%, area under curve = 0.668, 95% confidence interval (CI): 0.566-0.770, P = 0.001). Based on this cut-off point, the 257 patients were divided into two groups: High B/A group (n = 64) and low B/A group (n = 193). The median time for patients in the high B/A group was significantly lower than that in the low B/A group [56.8 months (range: 0.3-166.8 months) vs 67.2 months (range: 2.4-185.0 months), P = 0 .045], as shown in Table 2.
Figure 1 Receiver operating characteristic curve analysis and overall survival.
A: Receiver operating characteristic curve analysis was conducted to determine the optimal cutoff values for total bilirubin-albumin ratio (B/A), total bilirubin (TBIL), and albumin (ALB). The calculated optimal cutoff values for B/A ratio, TBIL, and ALB were 0.8714, 23.9, and 52.4 respectively; B: The Kaplan-Meier curves were compared between high B/A ratio and low B/A ratio groups for overall survival. The P values were calculated by the log-rank test. ROC: Receiver operating characteristic; B/A: Bilirubin-albumin ratio; TBIL: Total bilirubin; ALB: Albumin.
Table 2 Intraoperative and postoperative characteristics of patients with high and low serum total bilirubin-albumin ratio, n (%).
Variable
Median (range)
High B/A group (> 0.87)
Low B/A group (≤ 0.87)
P value
Intraoperative data
Estimated blood loss (mL)
403 (50-2000)
420 (50-1500)
397 (50-2000)
0.792
Intraoperative transfusion (mL)
446 (0-1400)
637 (400-1400)
381 (200-1200)
< 0.001
Spleen volume (mm3)
1291 (157-4896)
1389 (270-3864)
1256 (156-4896)
0.278
Spleen size (mL)
159 (12-230)
168 (106-230)
155 (12-224)
0.063
Surgical methods
Laparoscopic surgery
35 (13.62)
6 (9.38)
29 (15.03)
0.253
Laparotomy
222 (86.38)
58 (90.63)
164 (84.97)
Postoperative complications
ICU stay
2 (0.78)
1 (1.56)
1 (0.52)
0.437
Hemorrhage
4 (1.56)
3 (4.69)
1 (0.52)
0.049
Portal vein thrombosis
45 (17.51)
7 (10.94)
38 (19.69)
0.110
Ascites
142 (55.25)
47 (73.44)
95 (49.22)
0.001
Hepatic encephalopathy
2 (0.78)
1 (1.56)
1 (0.52)
0.437
Surgical site infection
14 (5.45)
6 (9.38)
8 (4.15)
0.110
Pneumonia
7 (2.72)
2 (3.13)
5 (2.59)
1.000
SIRS
133 (51.75)
30 (46.88)
103 (53.37)
0.368
CCI > 30
77 (29.96)
26 (40.63)
51 (26.42)
0.032
Length of hospital stay (d)
27 (11-88)
30 (14-88)
26 (11-86)
0.030
Survival time (months)
64.6 (0.3-185.0)
56.8 (0.3-166.8)
67.2 (2.4-185.0)
0.045
Survival (yes/no)
221 (85.99)/36 (14.01)
46 (71.88)/18 (28.12)
175 (90.67)/18 (9.33)
< 0.001
HCC occurrence (yes/no)
40 (15.56)/217 (84.44)
10 (15.63)/54 (84.37)
30 (15.54)/163 (84.46)
0.988
B/A ratio is an independent risk factor for OS
To investigate the risk factors associated with the 10-year OS of the cohort, both univariable and multivariable analyses were conducted. Gender, ALT, B/A ratio, albumin, PT (> 17 s), Child-Pugh score (Child B vs Child A), ALBI grade (ALBI 3/2 vs ALBI 1), and portal vein thrombosis were identified as risk factors through the univariate analysis. However, in terms of multivariable analysis alone, the B/A ratio emerged as the sole independent risk factor for OS (odds ratio = 5.350, 95%CI: 1.109-25.807, P = 0.037) (Table 3).
Table 3 Univariable and multivariable analyses of risk factors for overall survival.
Variable
Univariate analysis
Multivariate analysis
OR (95%CI)
P value
OR (95%CI)
P value
Age > 50 years
0.571 (0.277-1.177)
0.129
Gender (male/female)
2.209 (1.064-4.585)
0.033
2.464 (0.668-9.097)
0.176
Smoking (yes/no)
0.712 (0.294-1.726)
0.453
Drinking (yes/no)
0.377 (0.086-1.658)
0.197
Ascites (yes/no)
1.681 (0.505-5.593)
0.397
Hepatitis B infection (yes/no)
1.150 (0.250-5.285)
0.858
Platelet count (< 30 × 109/L)
1.181 (0.547-2.546)
0.672
Hemoglobin (< 120 g/L)
1.340 (0.555-3.231)
0.515
ALT (> 40 U/L)
0.473 (0.232-0.964)
0.039
0.687 (0.168-2.803)
0.600
AST (> 40 U/L)
0.526 (0.256-1.081)
0.080
0.284 (0.043-1.886)
0.193
B/A ratio (high/low)
3.804 (1.834-7.891)
< 0.001
5.350 (1.109-25.807)
0.037
Albumin (< 35 g/L)
2.141 (1.032-4.442)
0.041
1.133 (0.252-5.093)
0.871
Total bilirubin (> 17 μmol/L)
0.489 (0.205-1.170)
0.108
PT (> 17 s)
0.453 (0.212-0.967)
0.041
0.615 (0.129-2.941)
0.542
APTT (> 45 s)
1.016 (0.461-2.238)
0.968
Fibrinogen (< 2 mg/dL)
0.627 (0.305-1.290)
0.205
INR (> 1.2)
0.675 (0.264-1.728)
0.413
AFP (> 20 mg/L)
1.462 (0.314-6.912)
0.629
Child-Pugh score (C vs A)
0.340 (0.125-0.924)
0.297
Child-Pugh score (B vs A)
0.189 (0.048-0.741)
0.017
0.579 (0.042-8.022)
0.684
ALBI 3 vs ALBI 1
3.241 (1.029-10.209)
0.045
1.023 (0.023-45.884)
0.991
ALBI 2 vs ALBI 1
4.500 (1.014-19.963)
0.048
2.386 (0.246-23.142)
0.453
MELD score (≥ 10)
1.577 (0.679-3.660)
0.289
Estimated blood loss ≥ 470 mL
0.369 (0.099-1.372)
0.137
Intraoperative transfusion (yes/no)
0.141 (0.018-1.112)
0.063
0.758 (0.070-8.175)
0.819
Spleen volume ≥ 1426 mm3
0.891 (0.415-1.913)
0.768
Spleen size ≥ 158 mm
0.933 (0.375-2.318)
0.881
Portal vein thrombosis (yes/no)
8.701 (1.160-65.261)
0.035
1.177 (0.106-13.095)
0.894
CCI > 30
0.965 (0.444-2.096)
0.928
Characteristics in different B/A groups
There were no significant differences in terms of gender, age, coexisting conditions such as HBV infection, gastro-esophageal varices, and laboratory results including leucocytes, ALT, BUN, and HBV/HCV-DNA/RNA between the two groups. The study revealed that a higher B/A ratio was associated with the worse levels of platelets, hemoglobin, aspartate transaminase, albumin, total bilirubin, creatinine, PT, APTT, fibrinogen, INR, and AFP. Based on multiple grading systems, the higher B/A ratio consistently corresponded to more severe liver dysfunction (Child-Pugh score: P < 0.001; ALBI: P < 0.001) (Table 1). The high B/A group exhibited more pronounced intraoperative and postoperative complications, including intraoperative transfusion, hemorrhage, ascites, CCI, and prolonged hospital stay. However, no significant differences were observed in terms of surgical methods, HCC occurrence, and certain partial postoperative complications such as portal vein thrombosis, hepatic encephalopathy, and surgical site infection.
OS between patients with high and low B/A ratio
The high B/A group exhibited a significantly lower 10-year OS rate (log-rank test, P < 0.001), resulting in a mortality rate of 28.12% compared to the low B/A ratio group (9.33%, P < 0.001). The median survival time for the high and low B/A groups was 56.8 months (range: 0.3-166.8 months) and 67.2 months (range: 2.4-185 months), respectively (P = 0.045) (Figure 1B and Table 2). There was no statistically significant difference in HCC occurrence between the two groups (P = 0.988). Regardless of whether they had HCC or not, compared with patients with a low B/A ratio, those with a high B/A ratio had a lower 10-year OS (log-rank test, P = 0.067 and P < 0.001, respectively). However, HCC did have a negative impact on the 10-year OS (Figure 2A-C). As shown in Figure 2D-F, the OS of patients with early Child-Pugh stage, low ALBI grade and MELD score ≥ 10 was analyzed using the Kaplan-Meier curve. It was found that patients with a high B/A ratio had a lower 10-year OS in both the overall cohort and in all the three subgroups (log-rank test, P < 0.001 for all).
Figure 2 Survival analysis in different groups.
A: Kaplan-Meier curves were generated to compare overall survival (OS) between patients with and without hepatocellular carcinoma (HCC); B and C: Kaplan-Meier curves of patients in HCC groups and non-HCC groups stratified by high total bilirubin-albumin ratio (B/A) vs low B/A ratio; D-F: Kaplan-Meier curves for OS in patients with early Child-Pugh stage, low albumin-bilirubin grade, and model for end-stage liver disease score ≥ 10 were compared between high B/A ratio and low B/A ratio groups. The P values were calculated using the log-rank test. B/A: Bilirubin-albumin ratio; HCC: Hepatocellular carcinoma.
DISCUSSION
Since 1950, splenectomy has been routinely performed in patients with cirrhosis, portal hypertension, and secondary hypersplenism[4,11]. However, due to the invasiveness of splenectomy, significant intraoperative blood loss is often inevitable[15,20]. Additionally, postoperative pain, infection risk, decreased peripheral blood cell count recovery, and other complications also significantly impact patient survival following splenectomy[15,21,22]. Undoubtedly, the prognosis after splenectomy is frequently influenced by the preoperative liver function of patients[23]. In some cases where patients have poor liver function along with hypersplenism, the procedure itself carries a considerable mortality rate[20]. Therefore, preoperative evaluation of the prognostic factors for patients with hepatitis-related cirrhosis holds great importance.
Previously, the B/A ratio has demonstrated significant clinical utility as a prognostic factor for various diseases. For instance, the B/A ratio serves as a predictive marker for neonatal neurologic dysfunction induced by bilirubin[17]. Additionally, it has been observed that the B/A ratio, along with serum bilirubin and albumin levels, can serve as early indicators of hyperbilirubinemia in term neonates[19]. Wang et al[24] also established a correlation between the B/A ratio and bilirubin encephalopathy in newborns. Moreover, the B/A ratio has been employed to predict bilirubin reduction during in vitro albumin dialysis using a molecular adsorbent recirculator. Building upon these findings, our study is pioneering in utilizing preoperative serum total B/A ratio for assessing patients with hepatitis-related cirrhosis after splenectomy.
Beforehand, Child-Pugh score, ALBI grade, and platelet-albumin-bilirubin (PALBI) grade were commonly utilized as indicators for grading liver function, while tumor-node-metastasis stage, MELD score, and other markers were primarily employed for prognostic prediction in the fields of liver-related cancers, liver transplantation, donor liver allocation, and other related areas[25-27]. In comparison to the B/A ratio, the Child-Pugh score incorporates serum albumin, serum bilirubin, PT, ascites, and hepatic encephalopathy[14]. Albumin and ascites exhibit a correlation with each other while scores for ascites and hepatic encephalopathy are subjectively influenced by the assessor. Therefore, the prognosis outcomes of the disease may vary due to the aforementioned factors. Furthermore, Wang et al[25] discovered that ALBI grading exhibited superior performance compared to Child-Pugh score in determining the OS of HCC patients[25,28]. ALBI grading, similar to B/A ratio, encompasses two laboratory parameters, albumin and bilirubin, which are simpler and more objective[14]. In a study conducted by Liu et al[29], involving 8445 individuals, PALBI grading was validated as being more accurate than ALBI grading[29]. The PALBI grading system incorporates platelet count into the ALBI grading system to account for the impact of portal hypertension[14]. However, despite further optimization, the limited clinical application of ALBI and PALBI is primarily attributed to the complexity involved in their score calculation[29,30]. Therefore, utilizing the B/A ratio based on the two well-established laboratory indicators albumin and bilirubin offers a simpler approach that facilitates widespread adoption among clinicians.
In addition to its convenient use, the preoperative B/A ratio demonstrates both accuracy and uniqueness in predicting survival among patients with hepatitis-related cirrhosis after splenectomy. Our analysis of 11 variables involving 257 cirrhosis patients revealed that the B/A ratio was the sole independent risk factor. When compared to the optimal cut-off values of total bilirubin and albumin in the ROC curve, the optimal cut-off value of the B/A ratio exhibited higher sensitivity and specificity, thus indicating superior predictive value. From the perspective of cut-off point analysis, patients with a higher B/A ratio exhibited a tendency towards diminished OS. Simultaneously, the prognostic evaluation encompassed Child-Pugh score, ALBI score, and MELD score for all participants in this study. This further substantiated the association between elevated B/A ratio and reduced survival rates. These findings validate the applicability of B/A ratio across diverse subcategories.
Although our study demonstrated the validity and enforceability of B/A ratios in predicting OS in patients with hepatitis-related cirrhosis after splenectomy, their role in clinical decision-making has not been fully established. Additionally, due to the limited number of cases included, further verification by multiple research teams is necessary to determine its prognostic effect on a broader range of patients with hepatitis-related cirrhosis or across different countries and regions. In summary, the B/A ratio is anticipated to become a future prognostic indicator for patients with hepatitis-related cirrhosis after splenectomy due to its advantages such as simple calculation and consistency under various classifications. However, given the limitations of existing research, more evidence is required for its practical application in the future.
CONCLUSION
The B/A ratio exhibits distinct specificities in patients with hepatitis-related cirrhosis. In this study, we investigated the predictive value of the B/A ratio for OS in patients with hepatitis-related cirrhosis following splenectomy. Based on a predefined cutoff point, patients with a high B/A ratio demonstrated significantly poorer long-term survival outcomes across all subgroups, including those with HCC, without HCC, early Child-Pugh stage, low ALBI grade, and MELD score ≥ 10. Furthermore, the high B/A ratio emerged as the sole independent risk factor for OS. Given its convenience and effectiveness, the B/A ratio may serve as a valuable prognostic indicator for these patients.
ACKNOWLEDGEMENTS
We thank the Department of Hepatobiliary Surgery of Shaanxi Provincial People’s Hospital for its support to this study.
Footnotes
Provenance and peer review: Unsolicited article; Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Gastroenterology and hepatology
Country of origin: China
Peer-review report’s classification
Scientific Quality: Grade B
Novelty: Grade C
Creativity or Innovation: Grade B
Scientific Significance: Grade B
P-Reviewer: Huang KP S-Editor: Fan M L-Editor: Wang TQ P-Editor: Zhao YQ
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