Liver cirrhosis signifies the advanced stage of chronic liver disease, characterized by the irreversible replacement of liver parenchyma with fibrotic tissue and regenerative nodules. [1] In 2010, liver cirrhosis ranked as the eighth leading cause of death in the United States, contributing to over a million fatalities globally, with an increasing incidence over the past three decades. Hospital admissions due to liver cirrhosis carry an overall in-hospital mortality rate of around 8%, which rises to 35% in patients with decompensated liver cirrhosis [2]. Survival for individuals with decompensated cirrhosis is only 14% over five years, often necessitating transfer to an intensive care unit (ICU) for optimal management. Despite advancements in medical technology, the clinical outcomes of cirrhosis patients in the ICU are improving, but mortality rates for ICU-managed cirrhosis patients remain elevated, ranging from 34.7% to 90%. [3] The effectiveness of life support measures is currently debated, leading to increased interest in critically ill cirrhosis patients.[4-7] For those in advanced cirrhosis stages or experiencing multiple organ failure, survival is often limited, even with supportive care in the ICU.[8] Studies highlight a correlation between extensive healthcare utilization and elevated ICU mortality rates.[4, 9, 10] Therefore, identifying a reliable tool for risk stratification is crucial for pinpointing patients eligible for liver transplantation or intensive care. In the field of liver cirrhosis, various classification models are utilized. The Child-Turcotte classification, with its subsequent modification by Pugh, stands out as one of the frequently employed clinical tools for risk-stratifying patients with cirrhosis. The Acute Physiology and Chronic Health Evaluation (APACHE) III, a physiologically grounded prognostic system, is a widely utilized scale for assessing the severity of illness to predict hospital mortality across all ICU patients. The quick Sepsis-related Organ Failure Assessment (qSOFA) is a newly introduced tool for risk stratification. It has the potential to predict in-hospital mortality in patients with suspected infection at the Emergency Department (ED). In comparison to alternative prognostic scores, qSOFA demonstrates comparable or superior accuracy in screening patients with sepsis for critical illness. Identifying sepsis in Emergency Department patients, especially those with a high risk of adverse outcomes, is crucial for advancing sepsis care and enhancing patient outcomes. [11] Scores specifically tailored to liver conditions, such as the Child-Turcotte-Pugh (CTP) [12] and Model for the End-stage Liver Disease (MELD) scores, [13] offer limited insights into other organ failures that strongly indicate a poor prognosis. Consequently, general ICU scores like the APACHE III [14] and the Sequential Organ Failure Assessment (SOFA) scores might provide more accurate assessments. [3] However, these general scores are designed based on various severe illnesses beyond cirrhosis alone, and their complexity restricts their utility. Only a few prognostic scores have been specifically developed for critically ill cirrhosis patients.15-17] Therefore, the present study was undertaken to do a comparative analysis of modified QSOFA, APACHE III, and CHILD-PUGH scores in patients of critically ill liver cirrhosis to determine the better outcome predictor.

The present Comparative Observational Cross-Sectional Study was conducted at Dr. D.Y. Patil Medical College Hospital and Research Institute Kolhapur, Maharashtra for 2 years after Institutional Ethics Committee approval. A total of 105 patients satisfying the inclusion and exclusion criteria were involved in the study. Inclusion criteria All genders, Patients >18 years of age, Patients within 24 hours of hospital stay having liver cirrhosis with, Variceal bleeding, Hepatorenal Syndrome (HRS), Encephalopathy, Sepsis, Septic shock. Exclusion criteria Patients who received liver transplantation, Patients diagnosed with neuro-deficit and neurological diseases such as Acute stroke, acute seizure disorder, and Trauma injury, Patients having a known history of/ pre-existing lung pathology such as interstitial lung disease/chronic obstructive pulmonary disease/cystic fibrosis and others, Patients diagnosed with Chronic kidney disease, Acute pancreatitis, Dengue, and any Acute illness. All patients satisfying inclusion and exclusion criteria were involved in the study and written informed consent was obtained before the initiation of the study. Relevant history, clinical findings, and lab investigations were recorded. MODIFIED QSOFA, APACHE III, and CHILD-PUGH scores were applied and the outcomes were measured and compared. Investigations: Chemical- Sr. Bilirubin, Sr. albumin, PT/INR, SGOT, SGPT, Hematocrit, WBC count, Serum Creatinine, Serum Electrolytes, Blood Glucose, BUN, urine output. ABG- PaO2, FiO2, Glasgow coma scale, Heart rate, Temperature, Pulse oximeter- SpO2 Extra investigations not included in the thesis but done to confirm liver cirrhosis: USG Abdomen and Pelvis, CT Abdomen, Liver Biopsy

Age The mean age of the study subjects was 47.65±10.94 years. The majority of subjects belonged to 41-50 age group category (40.95%) followed by 31-40 years (25.71%), 51-60 years (14.29%), 61-70 years (12.38%), ≤30 years (3.81%), and >70 years (2.86%)). Gender In this study, 6.67% of the patients were female (n=7), whereas the majority, 93.33%, were male (n=98). The total number of patients evaluated was 105. The detailed distribution according to gender. Etiology The majority of patients in the study had an etiology related to alcohol consumption, accounting for 93.33% (98 out of 105 patients). Metabolic-associated fatty liver disease (MASLD) was the etiology in 5.71% (6 patients), while a viral cause was identified in only 0.95% (1 patient). The total number of patients evaluated was 105. The detailed distribution etiology is given in Table 3. Table 1. Distribution according to Etiology. Etiology Frequency (n) Percentage ALCOHOL 98 93.33% MASLD 6 5.71% VIRAL 1 0.95% Grand Total 105 100% Outcomes Among study subjects, 67.62% (n=71) of patients were discharged whereas, 32.38% (n=34) of patients died (Table 4). Child Turcotte Pugh score The mean Child Turcotte Pugh Score (CPS) at discharge for patients who survived was 10.48 ± 2.08, significantly lower than the mean Child Turcotte Pugh of 12.79 ± 1.25 for patients who died. P value was found to be 1.52E-08*. The detailed comparison of Child Turcotte Pugh between patients outcome at discharge is given in Table 2. Table 2. Comparison of Child Turcotte Pugh score according to patients CPS Outcome P value DEATH DISCHARGED Mean 12.79 10.48 1.52E-08* SD 1.25 2.08 *indicates significance (P value < 0.05) Prediction ability of Child Turcotte Pugh Score In the classification table, the observed and predicted outcomes are presented for two categories: 0.00 (discharge) and 1.00 (death). Using cut off value of .500, for the discharge category, there were 58 observations, out of which 13 were correctly predicted. In the death category, 34 observations were made, with 21 correct predictions. The sensitivity, specificity, PPV, NPV, and accuracy was found to be 81.69%, 61.76%, 81.69%, 61.76%, and 75.24%. The detailed classification results are given in Table 3. Table 3. Prediction ability of Child Turcotte Pugh Score Observed Predicted Outcome Percentage Correct Discharge Death Outcome Discharge 58 13 81.7 Death 13 21 61.8 Overall Total 71 34 75.2 a. The cut value is .500 The correlation coefficient for Child Turcotte Pugh score was 0.902 indicating a significant positive correlation with the outcome. The odds ratio for Child Turcotte Pugh score was 2.464 whereas, the AUC value was found to be 0.82 (95% CI: 1.666 to 3.644), (p < 0.001). The ROC curve is shown in Figure2. Comparison of Modified QSOFA scores according to outcomes In comparing outcomes based on Modified QSOFA scores, the mean score for patients who died was 3.29, significantly higher than the mean score of 0.77 for discharged patients (p < 0.001). Standard deviations were 1.53 for dead patients and 1.10 for discharged Prediction ability of Modified QSOFA score In the classification table, outcomes were observed and predicted based on a cut value of .500. Modified QSOFA correctly identified 88.7% of cases where the outcome was discharge (63 out of 71), and 64.7% of cases where the outcome was death (22 out of 34). The sensitivity, specificity, PPV, NPV, and accuracy was found to be 84%, 73.33%, 88.73%, 64.71%, and 80.95% respectively. The details are mentioned in Table 4. Table 4. Prediction ability of Modified QSOFA Observed Predicted Outcome Percentage Correct Discharge Death Outcome Discharge 63 8 88.7 Death 12 22 64.7 Overall Total 75 30 81.0 a. The cut value is .500 The correlation coefficient for Modified QSOFA score was 1.16 indicating a significant positive correlation with the outcome. The odds ratio for Modified QSOFA was 3.190 whereas, the AUC value was found to be 0.89 (95% CI: 2.106, 4.833) (p < 0.001) suggested that for each unit increase in Modified QSOFA score, the odds of the death increased by approximately 3.19 times Comparison of APACHE III score according to outcomes The mean APACHE III score for patients who died was 86.91 with a standard deviation of 24.59. In contrast, patients who were discharged had a mean score of 50.27 with a standard deviation of 17.32. The difference in APACHE III scores between the two groups was statistically significant (P = 1.60E-14). The detailed comparison is given in Table 5. Table 5. Comparison of APACHE III score according to outcomes APACHE III Outcome P value DEATH DISCHARGED Mean 86.91 50.27 1.60E-14* SD 24.59 17.32 *indicates significance (P value < 0.05) Prediction ability of APACHE III score Among patients who discharged (observed), 66 were correctly predicted with a percentage accuracy of 93.0%. For patients who died (observed), 24 were correctly predicted. The sensitivity, specificity, PPV, NPV, and accuracy was found to be 86.84%, 82.76%, 92.96%, 70.59% and 85.71% respectively (Table 6). Table 6. Prediction ability of APACHE III score Observed Predicted Outcome Percentage Correct Discharge Death Outcome Discharge 66 5 93.0 Death 10 24 70.6 Overall Percentage 76 29 85.7 a. The cut value is .500 The correlation coefficient for APACHE III score was 0.075 indicating a weak positive correlation with the outcome. The odds ratio for APACHE III score was 1.078 whereas, the AUC value was found to be 0.88 (95% CI: 1.048 to 1.109), (p < 0.001). The ROC curve is shown Comparison of predicting abilities of Child Turcotte Pugh, Modified QSOFA, and APACHE-III scores APACHE-III demonstrated the highest sensitivity at 86.84%, followed by Modified QSOFA at 84% and Child Turcotte Pugh at 81.69%. In terms of specificity, APACHE-III again showed superior performance with 82.76%, compared to Modified QSOFA at 73.33% and CPS at 61.76%. The PPV, which measures the proportion of positive results that are true positives, was highest for APACHE-III at 92.96%, indicating a strong ability to correctly predict positive outcomes, while Modified QSOFA and Child Turcotte Pugh had PPVs of 88.73% and 81.69%, respectively. For NPV, which assesses the proportion of negative results that are true negatives, APACHE-III led with 70.59%, while Modified QSOFA and Child Turcotte Pugh had NPVs of 64.71% and 61.76%, respectively. Finally, APACHE-III showed the highest accuracy at 85.71%, with Modified QSOFA at 80.95% and CPS at 75.24% Comparison of correlation coefficient, AUC, and odds ratio. The correlation coefficient, which measures the strength and direction of the linear relationship between the diagnostic tool's score and the actual clinical outcome, was highest for Modified QSOFA at 1.16, indicating a very strong positive relationship. Child Turcotte Pugh score followed with a correlation coefficient of 0.902, while APACHE-III had the lowest at 0.075, suggesting a weak correlation. The AUC, which measures the diagnostic tool's ability to discriminate between different outcomes, was highest for Modified QSOFA at 0.89, reflecting excellent discrimination ability. APACHE-III had a similarly high AUC of 0.88, indicating strong discriminatory power, while Child Turcotte Pugh score had an AUC of 0.82, still indicative of good performance. The odds ratio, which quantifies the odds of an outcome occurring with a unit increase in the diagnostic tool's score, was highest for Modified QSOFA at 3.190, suggesting a strong association between the Modified QSOFA score and the likelihood of the outcome. Child Turcotte Pugh score had an odds ratio of 2.464, indicating a moderate association, and APACHE-III had the lowest odds ratio at 1.078, suggesting a weak association (Table 7). Table 7. Comparison of correlation coefficient, AUC, and odds ratio Diagnostic tools Correlation coefficient AUC Odds ratio CPS 0.902 0.82 2.464 MQSOFA 1.16 0.89 3.190 APACHE-III 0.075 0.88 1.078

The present study aimed to evaluate and compare the effectiveness of three scoring systems Modified qSOFA, APACHE III, and Child-Pugh scores—in predicting outcomes in critically ill patients with liver cirrhosis. The results provide significant insights into the predictive capabilities of these scoring systems and their respective strengths and limitations. In this study a total of n=105 critically ill patients were recruited with a mean age of 47.65 years. The majority of the patients were in the 41-50years age group (40.95%), and there was a notable male predominance (93.33%). The primary etiology for liver cirrhosis in this cohort was alcohol-related (93.33%), with metabolic-associated fatty liver disease (MASLD) and viral causes being much less common. Similarly, in the study of Lan P et al. majority of patients were male whereas, more than half proportion of subjects belonged to 31-59year age category. The most common etiology for illness was alcohol abuse. [18] Among the study subjects, 67.62% were discharged while 32.38% succumbed to their illness. This distribution provides a basis for assessing the predictive validity of the three scoring systems used in this study. The Child-Pugh score, traditionally used to assess the prognosis of chronic liver disease, showed significant differentiation between patients who survived and those who did not. The mean Child Turcotte Pugh score was significantly lower for discharged patients (10.48) compared to those who died (12.79), with a P value of 1.52E-08 indicating high statistical significance. A significant correlation was seen between Child Turcotte Pugh score and outcome (0.90, P<0.001). Despite its strong performance in predicting outcomes (sensitivity 81.69%, specificity 61.76%, accuracy 75.24%), the Child Turcotte Pugh score had the lowest specificity and NPV among the three scores. Moreover, AUC of Child Turcotte Pugh score was 0.82 with an odds ratio of 2.64. This suggests that while the Child Turcotte Pugh score is useful, it may overestimate the risk of mortality in certain cases. In this study, the Modified QSOFA score demonstrated a robust ability to predict patient outcomes, with a mean score of 3.29 for patients who died compared to 0.77 for those who were discharged (P value = 2.23E-16). Its higher sensitivity (84%) and accuracy (80.95%) compared to the CPS, alongside a better specificity (73.33%), highlight its utility in a critical care setting. Moreover, the Modified QSOFA had the highest correlation coefficient (1.16) odds ratio (3.190), and AUC (0.89) indicating a strong positive relationship with patient outcomes, a significant increase in the odds of mortality with higher scores, and better discrimination ability. The APACHE III score emerged as the most effective predictor among the three. Patients who died had a significantly higher mean score (86.91) compared to those discharged (50.27), with a P value of 1.60E-14. The APACHE III score's sensitivity (86.84%) and specificity (82.76%) were the highest, and its accuracy (85.71%) was superior to both CPS and MQSOFA. These findings suggest that the APACHE III score provides a comprehensive and reliable assessment of critically ill cirrhotic patients, encompassing a broader range of physiological variables and comorbid conditions. Furthermore, based on the performance metrics of Child Turcotte Pugh score, Modified QSOFA, and APACHE-III, it is evident that APACHE-III is the most effective diagnostic tool among the three evaluated. APACHE-III demonstrated the highest sensitivity (86.84%) and specificity (82.76%), indicating it is most adept at both detecting the condition in patients and accurately identifying those who are not affected. Additionally, APACHE-III had the highest positive predictive value (92.96%) and overall accuracy (85.71%), reflecting its strong capability to correctly predict positive outcomes and its superior overall performance in clinical diagnoses. While Modified QSOFA also showed strong performance, with high sensitivity (84%) and a relatively high positive predictive value (88.73%), it fell short of APACHE-III in terms of specificity and overall accuracy. Child Turcotte Pugh score, though useful, showed the lowest sensitivity (81.69%) and specificity (61.76%), which limits its effectiveness compared to the other two tools. However, Modified QSOFA outperforms the other diagnostic tools in terms of correlation with clinical outcomes, discriminatory power, and association strength. APACHE-III, despite its high sensitivity and specificity, shows a weak correlation and association with outcomes, highlighting the complexity of its predictive capabilities. Child Turcotte Pugh score, while effective, demonstrates moderate performance across these metrics. These findings suggest that Modified QSOFA is the most robust tool for predicting clinical outcomes, providing a balance of strong correlation, excellent discrimination, and a strong association with patient outcomes. The present study suggested that while all three scoring systems are useful in predicting outcomes in critically ill cirrhotic patients, the APACHE III score demonstrates superior predictive accuracy and reliability. The Modified QSOFA score, with its simplicity and strong correlation with outcomes, also proves to be a valuable tool, particularly in resource-limited settings. The Child Turcotte Pugh score, although effective, has comparatively lower specificity and accuracy, suggesting it may be less reliable as a sole predictor of mortality in critically ill cirrhotic patients. Various studies reinforce the robustness of the SOFA score as a predictive tool. For instance, Elie-Turenne MC et al. (2021) demonstrated that qSOFA ≥2 had approximately four-fold enhanced performance in predicting hospital mortality compared to SIRS ≥2, despite qSOFA ≥2’s lower sensitivity. [19] Lan P et al. (2018) found that CLIF-SOFA, CLIF-C OF, and SAPS II had significantly higher AUROC values compared to SIRS, qSOFA, MELD, and qCLIF-SOFA, making them superior prognostic tools for critically ill cirrhotic patients with suspected infections. [18] Ebrahimi K et al. (2018) concluded that the SOFA score is more predictive of clinical outcomes in poisoning cases than APACHE 4 and PSS, reinforcing the SOFA score's reliability and effectiveness in various critical care settings. [20] Songsangjinda T et al. (2020) also supported the SOFA score’s high accuracy in predicting in-hospital mortality among septic patients admitted to the ICU, compared to other sepsis definitions. [21] These findings underscore the importance of selecting appropriate scoring systems based on the clinical context to improve prognostication and patient management in critical care settings.

The APACHE III score was identified as the most accurate and reliable predictor of outcomes in critically ill cirrhotic patients, with the highest sensitivity, specificity, and accuracy. The Modified qSOFA score also proved to be a valuable tool, especially due to its simplicity and strong correlation with outcomes. The Child Turcotte Pugh score, while effective, had lower specificity and accuracy, suggesting it might overestimate the risk of mortality in certain cases. Future studies with larger and more diverse populations are recommended to validate these findings further.

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