Liver cirrhosis is the advanced stage of chronic liver disease, characterized by diffuse hepatic fibrosis, regenerative nodules, and distortion of normal liver architecture, resulting in progressive hepatic dysfunction and portal hypertension.¹ Persistent hepatocellular injury caused by alcohol consumption, viral hepatitis, metabolic disorders, or autoimmune diseases activates hepatic stellate cells and promotes excessive extracellular matrix deposition. This progressive fibrogenesis impairs hepatic synthetic function and contributes to complications such as ascites, hepatic encephalopathy, and variceal bleeding.¹˒² Assessment of disease severity is essential for clinical management and is commonly performed using the Child–Turcotte–Pugh (CTP) and Model for End-Stage Liver Disease (MELD) scoring systems.³ Serum cholinesterase, also known as butyrylcholinesterase or pseudocholinesterase, is an enzyme predominantly synthesized by hepatocytes. Its circulating activity decreases with impaired hepatic protein synthesis, making it a potentially useful biochemical indicator of hepatic functional reserve. Unlike aminotransferases, which primarily reflect hepatocellular injury, serum cholinesterase may provide information regarding hepatic synthetic capacity. Previous studies have demonstrated significantly reduced serum cholinesterase activity in patients with cirrhosis, with progressively lower levels across Child–Pugh classes and inverse correlations with CTP and MELD scores.⁴˒⁵ Although conventional biochemical parameters and established scoring systems remain central to cirrhosis assessment, additional inexpensive and readily measurable biomarkers may improve the characterization of hepatic functional impairment. Serum cholinesterase is a promising candidate; however, its clinical utility for distinguishing different grades of cirrhosis severity requires further evaluation across patient populations. Therefore, the present cross-sectional study was undertaken to assess serum cholinesterase activity in patients with liver cirrhosis and determine its correlation with CTP and MELD scores, conventional biochemical parameters, and clinical manifestations of hepatic decompensation.

This hospital-based, observational, cross-sectional study was conducted in the Department of General Medicine over a period of 18 months. A total of 80 adult patients aged 18 years and above with an established diagnosis of liver cirrhosis were included. The diagnosis was based on clinical features, biochemical investigations, and radiological findings. Patients with acute liver failure, organophosphorus poisoning, pregnancy, known inherited cholinesterase deficiency, or exposure to medications known to significantly affect cholinesterase activity were excluded. The study was conducted after obtaining approval from the Institutional Ethics Committee, and written informed consent was obtained from all participants. Detailed demographic and clinical information, including age, sex, etiology of cirrhosis, relevant medical history, and manifestations of hepatic decompensation, was recorded using a structured data collection form. All patients underwent comprehensive clinical examination, particularly for ascites, hepatic encephalopathy, jaundice, splenomegaly, and pedal edema. Laboratory investigations included complete blood count, serum bilirubin, albumin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, prothrombin time, international normalized ratio (INR), and serum creatinine. Serum cholinesterase activity was measured using a standardized enzymatic assay in the hospital's clinical biochemistry laboratory and expressed in international units per litre (IU/L). The severity of liver cirrhosis was assessed using the Child–Turcotte–Pugh (CTP) and Model for End-Stage Liver Disease (MELD) scores. Patients were classified into Child–Pugh classes A, B, and C according to established scoring criteria. Data were analyzed using 25. Continuous variables were expressed as mean ± standard deviation or median with interquartile range, as appropriate, while categorical variables were presented as frequencies and percentages. Serum cholinesterase activity was compared across Child–Pugh classes using one-way analysis of variance or the Kruskal–Wallis test, depending on data distribution. Spearman's rank correlation coefficient was used to assess the association of serum cholinesterase activity with CTP and MELD scores and biochemical parameters, including serum albumin, bilirubin, INR, liver enzymes, and creatinine. Receiver operating characteristic (ROC) curve analysis was used to evaluate the discriminatory ability of serum cholinesterase activity in identifying severe cirrhosis, defined as Child–Pugh class C, compared with classes A and B. The area under the ROC curve (AUC), sensitivity, specificity, and optimal cut-off value were assessed. A two-sided p-value of less than 0.05 was considered statistically significant.

Table 1: Baseline demographic, etiological, and clinical characteristics of patients with liver cirrhosis (N = 80) Characteristic n (%) Age group (years) 18–30 6 (7.5) 31–40 14 (17.5) 41–50 22 (27.5) 51–60 24 (30.0) >60 14 (17.5) Sex Male 58 (72.5) Female 22 (27.5) Etiology of cirrhosis Alcohol-related liver disease 36 (45.0) Chronic hepatitis B 12 (15.0) Chronic hepatitis C 10 (12.5) Metabolic dysfunction-associated steatotic liver disease (previously NAFLD/NASH) 9 (11.3) Autoimmune hepatitis 5 (6.3) Cryptogenic cirrhosis 8 (10.0) Clinical manifestations Ascites 52 (65.0) Hepatic encephalopathy 26 (32.5) Pedal edema 44 (55.0) Splenomegaly 48 (60.0) Icterus 50 (62.5) A total of 80 patients with liver cirrhosis were included in the study. The largest proportion of patients belonged to the 51–60-year age group (30.0%), followed by 41–50 years (27.5%). Males predominated, accounting for 58 (72.5%) patients. Alcohol-related liver disease was the most common etiology (45.0%), followed by chronic hepatitis B (15.0%) and hepatitis C (12.5%). Ascites was the most frequent clinical manifestation (65.0%), followed by icterus (62.5%), splenomegaly (60.0%), pedal edema (55.0%), and hepatic encephalopathy (32.5%). Table 2: Biochemical profile and distribution of cirrhosis severity among study participants (N = 80) A. Biochemical parameters Parameter Mean ± SD Median (IQR) Serum cholinesterase (IU/L) 3,610 ± 1,740 3,420 (2,150–5,180) Serum albumin (g/dL) 2.9 ± 0.6 2.8 (2.3–3.4) Total bilirubin (mg/dL) 4.4 ± 3.2 3.6 (1.8–6.9) Direct bilirubin (mg/dL) 2.2 ± 1.7 1.8 (0.9–3.8) AST (IU/L) 104 ± 76 86 (52–142) ALT (IU/L) 78 ± 59 64 (38–112) Alkaline phosphatase (IU/L) 210 ± 104 186 (128–284) Prothrombin time (seconds) 19.1 ± 4.5 18.4 (15.6–22.8) INR 1.81 ± 0.54 1.72 (1.38–2.14) Serum creatinine (mg/dL) 1.3 ± 0.7 1.1 (0.8–1.6) B. Distribution according to cirrhosis severity Severity classification n (%) Child–Pugh class Class A (score 5–6) 18 (22.5) Class B (score 7–9) 34 (42.5) Class C (score 10–15) 28 (35.0) MELD score category <10 14 (17.5) 10–19 38 (47.5) 20–29 20 (25.0) ≥30 8 (10.0) The mean serum cholinesterase activity was 3,610 ± 1,740 IU/L, with a median of 3,420 IU/L (IQR: 2,150–5,180). Mean serum albumin was 2.9 ± 0.6 g/dL, total bilirubin was 4.4 ± 3.2 mg/dL, and INR was 1.81 ± 0.54. According to the Child–Pugh classification, 18 (22.5%) patients belonged to class A, 34 (42.5%) to class B, and 28 (35.0%) to class C. The most common MELD score category was 10–19 (47.5%), followed by 20–29 (25.0%), indicating that a substantial proportion of the study population had moderate-to-advanced cirrhosis. Table 3: Comparison of serum cholinesterase activity across Child–Turcotte–Pugh classes (N = 80) Child–Pugh class n Mean ± SD (IU/L) Median (IQR), IU/L Class A 18 5,910 ± 1,120 5,820 (4,950–6,740) Class B 34 3,620 ± 1,030 3,480 (2,640–4,420) Class C 28 1,860 ± 620 1,780 (1,240–2,420) Overall (as reported) 80 3,610 ± 1,740 3,420 (2,150–5,180) Serum cholinesterase activity showed a progressive decline with increasing Child–Pugh class. The mean cholinesterase activity was highest in class A (5,910 ± 1,120 IU/L), decreased in class B (3,620 ± 1,030 IU/L), and was lowest in class C (1,860 ± 620 IU/L). Corresponding median values were 5,820, 3,480, and 1,780 IU/L, respectively. These findings demonstrated a marked inverse gradient between serum cholinesterase activity and the severity of liver cirrhosis. Table 4: Correlation of serum cholinesterase activity with cirrhosis severity scores and biochemical parameters (N = 80) Variable Spearman's ρ 95% CI p-value Disease severity scores Child–Turcotte–Pugh score −0.76 −0.85 to −0.63 <0.001 MELD score −0.72 −0.82 to −0.58 <0.001 Biochemical parameters Serum albumin +0.68 — <0.001 Total bilirubin −0.59 — <0.001 INR −0.64 — <0.001 AST −0.41 — 0.001 ALT −0.29 — 0.009 Alkaline phosphatase −0.36 — 0.003 Serum creatinine −0.48 — <0.001 Serum cholinesterase activity demonstrated strong negative correlations with the Child–Pugh score (ρ = −0.76, p < 0.001) and MELD score (ρ = −0.72, p < 0.001). A significant positive correlation was observed with serum albumin (ρ = 0.68, p < 0.001), whereas significant negative correlations were noted with INR (ρ = −0.64, p < 0.001), total bilirubin (ρ = −0.59, p < 0.001), and serum creatinine (ρ = −0.48, p < 0.001). Negative correlations were also observed with AST (ρ = −0.41), alkaline phosphatase (ρ = −0.36), and ALT (ρ = −0.29). These observations indicated that lower serum cholinesterase activity was associated with greater biochemical and clinical severity of cirrhosis. Table 5: Discriminatory performance of serum cholinesterase activity for identifying severe cirrhosis (Child–Pugh class C versus classes A/B) Performance measure Reported result Patients with Child–Pugh class C 28 Patients with Child–Pugh classes A/B 52 Area under the ROC curve (AUC) 0.91 95% confidence interval for AUC 0.85–0.97 Standard error 0.031 Reported optimal cut-off ≤2,350 IU/L Sensitivity 85.7% Specificity 82.7% Positive predictive value 72.7% Negative predictive value 91.3% Overall classification accuracy 83.8% Reported ROC p-value <0.001 Receiver operating characteristic analysis demonstrated an area under the curve of 0.91 (95% CI: 0.85–0.97; p < 0.001) for distinguishing Child–Pugh class C from classes A and B. At a reported serum cholinesterase cut-off of ≤2,350 IU/L, sensitivity was 85.7% and specificity was 82.7%. The positive predictive value was 72.7%, while the reported negative predictive value and overall accuracy were 91.3% and 83.8%, respectively. These findings suggested good discriminatory performance of serum cholinesterase activity for identifying patients with advanced cirrhosis.

The present cross-sectional study evaluated serum cholinesterase activity in 80 patients with liver cirrhosis and its relationship with disease severity. Alcohol-related liver disease was the leading etiology (45%), while ascites (65%) and hepatic encephalopathy (32.5%) were common manifestations. Comparable findings were reported by Ramanathan et al., who studied 100 patients and observed alcohol-related cirrhosis in 68%, ascites in 83%, and hepatic encephalopathy in 31%.⁶ These findings highlight the substantial burden of advanced liver disease in hospital-based populations. The principal finding was a progressive reduction in mean serum cholinesterase activity from Child–Pugh class A (5,910 ± 1,120 IU/L) to class B (3,620 ± 1,030 IU/L) and class C (1,860 ± 620 IU/L). Similar results were reported by Meng et al. in 866 patients, with corresponding values of 5,368 ± 1,657, 2,943 ± 1,213, and 1,833 ± 711 U/L (p < 0.001).⁷ Rashid et al. also observed a comparable decline among 50 cirrhotic patients, from 4,740 ± 1,046 U/L in class A to 3,157 ± 1,161 U/L in class B and 1,493 ± 500 U/L in class C.⁴ These consistent trends support the relationship between reduced cholinesterase synthesis and increasing hepatic functional impairment. Serum cholinesterase demonstrated strong inverse correlations with Child–Pugh (ρ = −0.76) and MELD (ρ = −0.72) scores, alongside a positive correlation with albumin (ρ = 0.68) and negative correlations with INR (ρ = −0.64) and bilirubin (ρ = −0.59), all with p < 0.001. Abbas and Abbas, in a study involving 233 patients with chronic hepatitis D, similarly demonstrated significant associations of cholinesterase with albumin, INR, CTP, and MELD scores (all p < 0.001).⁵ These findings suggest that serum cholinesterase reflects hepatic synthetic impairment and is closely associated with established indicators of cirrhosis severity. In the present study, serum cholinesterase demonstrated an area under the ROC curve of 0.91 (95% CI: 0.85–0.97) for distinguishing Child–Pugh class C from classes A and B. At a cut-off of ≤2,350 IU/L, sensitivity and specificity were 85.7% and 82.7%, respectively. Ramachandran et al., studying 178 patients with cirrhosis and 154 healthy controls, reported that a cholinesterase threshold below 2,385 IU/L distinguished decompensated from compensated cirrhosis with 80.1% sensitivity and 88.2% specificity.⁸ Abbas and Abbas reported an AUC of 0.966 for identifying CTP scores ≥10, with a cut-off below 2,853 IU/L providing 100% sensitivity and 84.79% specificity.⁵ Although these studies used different patient populations and severity definitions, their findings support the discriminatory potential of serum cholinesterase. Interpretation: The findings indicate that serum cholinesterase activity decreases progressively with increasing cirrhosis severity and shows strong associations with established clinical scores and biochemical markers of hepatic synthetic function. Its relatively simple measurement may make it a useful adjunct to conventional severity assessment. However, the single-centre, cross-sectional design, modest sample size, and absence of longitudinal follow-up limit generalizability and prevent conclusions regarding future clinical outcomes. Larger prospective studies are needed to validate clinically useful cut-offs and determine whether cholinesterase adds information beyond established scoring systems.

The present study demonstrated that serum cholinesterase activity decreases progressively with increasing severity of liver cirrhosis and exhibits strong negative correlations with Child–Turcotte–Pugh and MELD scores. Its association with conventional biochemical markers and good discriminatory performance for Child–Pugh class C suggest that serum cholinesterase may serve as a useful, inexpensive, and readily available adjunctive marker for assessing hepatic synthetic function and cirrhosis severity. Recommendations: Serum cholinesterase estimation may be considered alongside conventional liver function tests and established severity scoring systems, rather than as a replacement. Larger multicentre prospective studies are recommended to validate clinically relevant cut-off values and evaluate its additional prognostic utility. Limitations: The study was limited by its single-centre, cross-sectional design, relatively small sample size (80 patients), absence of a healthy control group, and lack of longitudinal follow-up. Consequently, its findings cannot establish causality, diagnostic accuracy for detecting cirrhosis, or prediction of long-term clinical outcomes.

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