Clinical Profile, Short-term Prognostic Accuracies of CLIF-C ACLF Score and Serial CLIF-C OF Scores in Acute-on-chronic Liver Failure Patients: A Prospective Observational Study.

Background: Acute-on-chronic liver failure (ACLF) is a recently defined entity that carries high short-term mortality. The European Association for Study of Liver (EASL) has given a different definition for ACLF and derived two scores called Chronic Liver Failure-Consortium Organ Failure (CLIF-C OF) and CLIF-C ACLF to diagnose and predict the short-term outcome, respectively. Materials and methods: This was the prospective observational study, included 40 ACLF patients diagnosed as per the EASL definition and calculated CLIF-C ACLF as well as other scores (CTP, MELD, MELD-Na, CLIF-C OF) on admission. Serial CLIF-C OF scores were also calculated (Day 3 and Day 7). The 28-day and 90-day mortality was recorded. Results: Alcohol was the predominant etiology of cirrhosis (32 patients-80%). Infection was the chief precipitating factor in 19 patients (47.5%). The 28-day and 90-day mortality was 45% and 52.5%. Mean (SD) of CLIF-C ACLF scores of survivors and non-survivors on Day-90 were 44.11(6.62) and 53.86 (7.83). The prognostic accuracy of the CLIF-C ACLF score (Area Under Receiver Operating Characteristic Curve-AUROC) to predict 28-day and 90-day mortality was 0.86 and 0.84, respectively. MELD-Na and CLIF-C ACLF scores had higher AUROC for predicting 28-day and 90-day mortality, respectively. The AUROC of the CLIF-C OF score on Day 3 was found to be higher than the values of Day 1 and Day 7, but it was not statistically significant. Conclusion: CLIF-C ACLF has good short-term prognostic accuracy and it is as good as other available scores. Serial CLIF-C OF scores were equally good in predicting in short-term mortality. How to cite this article: Hareesh GJ, Ramadoss R. Clinical Profile, Short-term Prognostic Accuracies of CLIF-C ACLF Score and Serial CLIF-C OF Scores in Acute-on-chronic Liver Failure Patients: A Prospective Observational Study. Indian J Crit Care Med 2024;28(2):126-133.

Acute on Chronic Liver Failure: Lessons from a Decade of EASL-CLIF Definition and Scoring Systems.

How to cite this article: Solao V. Acute on Chronic Liver Failure: Lessons from a Decade of EASL-CLIF Definition and Scoring Systems. Indian J Crit Care Med 2024;28(2):100-102.

Liver Severity Score-Based Modeling to Predict Six-Week Mortality Risk Among Hospitalized Cirrhosis Patients With Upper Gastrointestinal Bleeding.

Background: Patients with cirrhosis who have gastrointestinal bleeding have high short-term mortality, but the best modality for risk calculation remains in debate. Liver severity indices, such as Child-Turcotte-Pugh (CTP) and Model-for-End-Stage-Liver Disease (MELD) score, are well-studied in portal hypertensive bleeding, but there is a paucity of data confirming their accuracy in non-portal hypertensive bleeding and overall acute upper gastrointestinal bleeding (UGIB), unrelated to portal hypertension. Aims: This study aims to better understand the accuracy of current mortality risk calculators in predicting mortality for patients with any type of UGIB, which could allow for earlier risk stratification and targeted intervention prior to endoscopy to identify the bleeding source. Methods: In a large US single-center cohort, we investigated and recalibrated the model performance of CTP and MELD scores to predict six-week mortality risk for both sources of UGIB (portal hypertensive and non-portal hypertensive). Results: Both CTP- and MELD-based models have excellent discrimination in predicting six-week mortality for all types of bleeding sources. However, only a CTP-based model demonstrates calibration for all bleeding, regardless of bleeding etiology. Median predicted 6-week mortality by CTP class A, B, and C estimates a risk of 1%, 7%, and 35% respectively. Conclusions: Our study corroborates findings in the literature that CTP- and MELD-based models have similar discriminative abilities for predicting 6-week mortality in hospitalized cirrhosis patients presenting with either portal hypertensive or non-portal hypertensive UGIB. CTP class is an effective clinical decision tool that can be used, even prior to endoscopy, to accurately risk stratify a patient with known cirrhosis presenting with any UGIB into low, moderate, and severe risk groupings.

Derivation and Validation of a Prognostic Model for Acute Decompensated Cirrhosis Patients.

Background: Acute decompensated cirrhosis (AD) is related to high medical costs and high mortality. We recently proposed a new score model to predict the outcome of AD patients and compared it with the common score model (CTP, MELD and CLIF-C AD score) in the training and validation sets. Materials and Methods: A total of 703 patients with AD were enrolled from The First Affiliated Hospital of Nanchang University between December 2018 and May 2021. These patients were randomly assigned to the training set (n=528) and validation set (n=175). Risk factors affecting prognosis were identified by Cox regression analysis and then used to establish a new score model. The prognostic value was determined by the area under the receiver operating characteristic curve (AUROC). Results: A total of 192 (36.3%) patients in the training cohort and 51 (29.1%) patients in the validation cohort died over the course of 6 months. A new score model was developed with predictors including age, bilirubin, INR, WBC, albumin, ALT and BUN. The new prognostic score (0.022×Age + 0.003×TBil + 0.397×INR + 0.023×WBC- 0.07×albumin + 0.001×ALT + 0.038×BUN) for long-term mortality was superior to three other scores based on both training and internal validation studies. Conclusion: This new score model appears to be a valid tool for assessing the long-term survival of AD patients, improving the prognostic value compared with the CTP, MELD and CLIF-C AD scores.

Serum IGF-1 Scores and Clinical Outcomes in the Phase III IMbrave150 Study of Atezolizumab Plus Bevacizumab versus Sorafenib in Patients with Unresectable Hepatocellular Carcinoma.

Purpose: Child-Turcotte-Pugh class A (CTP-A) in unresectable hepatocellular carcinoma (HCC) is the standard criterion for active therapy and clinical trial enrollment. We hypothesized that insulin-like growth factor-1 (IGF-1) derived scores may provide improved survival prediction over CTP classification. This study aimed to evaluate the potential prognostic and predictive effects of IGF-1 derived scores in the phase III IMbrave150 study. Patients and Methods: Baseline and on-treatment serum IGF-1 levels from 371 patients were subjected to central analysis. Patients' IGF-1 score (1/2/3) and IGF-CTP score (A/B/C) were determined based on pre-specified cutoffs. Outcomes were analyzed by baseline and by on-treatment changes of the IGF-1 and IGF-CTP scores within and between the two treatment arms. The interaction between these scores and outcomes was assessed using univariate and multivariate analyses. Results: Baseline IGF-CTP score (A vs B/C) showed prognostic significance for OS in both the atezolizumab-bevacizumab (hazard ratio [HR], 0.33; 95% confidence interval [CI], 0.20-0.56; P<0.001) and sorafenib (HR, 0.32; 95% CI, 0.16-0.65; P=0.002) arms. Baseline IGF-1 score (1 vs 2/3) also showed prognostic significance for OS in both the atezolizumab-bevacizumab (HR, 0.33; 95% CI, 0.20-0.55; P<0.001) and sorafenib (HR, 0.48; 95% CI, 0.26-0.89; P=0.02) arms. HRs for PFS were consistent with those for OS. No significant predictive effects were observed for either score between the two arms. Kinetic analysis revealed that patients with increased IGF-1 score (1-> 2/3) at 3 weeks post treatment had shorter OS than patients with stable IGF-1 score of 1 in both the atezolizumab-bevacizumab (HR, 3.70; 95% CI, 1.56-8.77; P=0.003) and sorafenib (HR, 5.83; 95% CI, 1.88-18.12; P=0.0023) arms. Conclusion: Baseline and kinetic change of IGF-CTP and IGF-1 scores are independent prognostic factors for patients with unresectable HCC treated with atezolizumab-bevacizumab or sorafenib. These novel scores may provide improved patient stratification in future HCC clinical trials. IMbrave150 ClincialTrials.gov number, NCT03434379.

Predictors of Outcome of Cirrhotic Patients Requiring Invasive Mechanical Ventilation: Experience From a Non-Transplant Tertiary Care Hospital in Pakistan.

Background Patients with known liver cirrhosis, irrespective of the etiology, have poor outcomes when put on invasive mechanical ventilation in an intensive care unit (ICU) setting. The clinical situation becomes even more complicated when such patients are managed in a non-transplant center. Various factors are associated with poor outcomes, and hence, various scoring systems are available to help determine the prognosis in patients with liver cirrhosis. These scoring systems are broadly classified into two categories, namely, ICU-specific scoring systems and liver disease-specific scoring systems. There is a dearth of data from Pakistan regarding which score better determines the prognosis of patients with liver cirrhosis admitted to the ICU. In this study, we aimed to determine the outcome of cirrhotic patients requiring invasive mechanical ventilation in a non-transplant tertiary care hospital in Pakistan using ICU-specific and liver disease-specific scoring systems. Methodology A retrospective study design was applied to a record of 88 cirrhotic patients admitted to the medical ICU of a tertiary care teaching hospital in Karachi, Pakistan, from January 2016 to November 2016. Patients with acute hepatitis were excluded. Data on patients' characteristics, the reason for intubation, hepatic encephalopathy, the need for vasopressor support, and the duration of ICU and hospital stay were collected. Moreover, the first-day Acute Physiology and Chronic Health Evaluation (APACHE) II, Sequential Organ Failure Assessment (SOFA), Child-Turcotte-Pugh (CTP), and Model for End-Stage Liver Disease (MELD) scores were calculated, with mortality being the primary outcome measure. Results The most common etiology was hepatitis C (52.3%, 46/88). The most common reason for intubation was airway protection (57.9%, 51/88). Overall mortality was 71.6% (63/88). On univariate analysis, CTP score >10, MELD score >18, hepatic encephalopathy, bilirubin, prothrombin time, presence of tense ascites, and APACHE II were significantly associated with mortality. On multivariate analysis, CTP score >10 (odd ratio = 21; 95% confidence interval (CI): 4-104; p < 0.001) was an independent predictor of mortality. Area under curve was 0.89 (95% CI = 0.82-0.96) for CTP, 0.86 (95% CI = 0.77-0.95) for MELD, 0.81 (95% CI = 0.69-0.92) for APACHE II, and 0.81 (95% CI = 0.71-0.91) for SOFA in predicting mortality. Conclusions CTP and MELD scores are better predictors of short-term mortality in patients with liver cirrhosis requiring invasive mechanical ventilation compared to APACHE II and SOFA scores. CTP score >10 was an independent predictor of mortality.

Low high-density lipoprotein cholesterol levels predicting poor outcomes in patients with hepatitis B virus-related acute-on-chronic liver failure.

Background: Lipid profile disorders frequently occur in patients with advanced liver diseases. High-density lipoprotein cholesterol (HDL-C) levels decrease rapidly during acute conditions of some diseases, and HDL-C levels may be related to mortality in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). Materials and methods: A retrospective cohort study was conducted on 200 subjects with HBV-ACLF. The patients were separated into non-survivors and survivors according to their 28-day outcome. Univariate and multivariate Cox regression analyses were performed to identify predictors of mortality, and the performance of these predictors was evaluated by receiver operating characteristic (ROC) curve analysis. Kaplan-Meier analysis was performed to draw survival curves of HDL-C. Results: The 28-day mortality in the cohort was 27.0%. HDL-C levels differed markedly between non-survivors and survivors. In the multivariate analysis, HDL-C, the Child-Turcotte-Pugh (CTP), model for end-stage liver disease (MELD), and Chinese Group on the Study of Severe Hepatitis B-ACLF II (COSSH-ACLF II) scores were identified as independent predictors for mortality (HR = 0.806, 95% CI: 0.724-0.898; HR = 1.424, 95% CI: 1.143-1.775; HR = 1.006, 95% CI: 1.002-1.007; and HR = 1.609, 95% CI: 1.005-2.575, respectively). Patients with lower HDL-C levels had a worse prognosis than those with higher HDL-C levels. In ROC analysis, the prognostic accuracy for mortality was similar between HDL-C (AUROC: 0.733) and the CTP, MELD, and COSSH-ACLF II scores (AUROC: 0.753; 0.674 and 0.770, respectively). Conclusion: The HDL-C level may serve as a potential indicator for the prognosis of HBV-ACLF and can be used as a simple marker for risk assessment and selection of therapeutic options.

Impact of sarcopenia on post-liver transplant morbidity and mortality in cirrhotic patients.

BACKGROUND: Modalities available for severity assessment and prediction of complications after liver transplant (LT) in cirrhotic patients are model for end-stage liver disease-sodium (MELD-Na) and Child-Turcotte-Pugh (CTP) scores. The limitation of these scores is the lack of assessment of nutritional and functional status. Sarcopenia is a newer modality, which is developed for objective assessment of nutritional status. The aim of this study is to analyze the significance of sarcopenia in predicting 1-year mortality and morbidity in post-LT patients. METHODS: In this retrospective study, patients who underwent LT for cirrhosis between January 2013 and December 2018 were included. A computerized tomography (CT) image was used to analyze the psoas muscle index at the L3 vertebra (L3-PMI), and sarcopenia was defined as the values belonging to the lowest quartile of L3-PMI. The effect of sarcopenia on mortality and morbidity in terms of requirement for mechanical ventilation, duration of hospital stay, and occurrence of infections was studied. RESULTS: Among the study population (n = 74), 71 were men and the mean age was 51 years. Sarcopenia was observed in 27% (n = 20). Fifteen recipients had mortality within 1 year after transplant. In our analysis, sarcopenia was significantly associated with 1-year mortality (sensitivity 60%, specificity 81%; positive predictive value [PPV] 45%; negative predictive value [NPV] 88%; and p-value 0.001). Duration of mechanical ventilation, total hospital stay, and occurrence of infection were not significantly associated with sarcopenia. Sarcopenia was found as an independent predictor of mortality on binary logistic regression. CONCLUSION: The preoperative sarcopenia index in cirrhotic patients can predict the risk of mortality in post-liver transplant patients.

Bleeding Stomal Varices and Their Interventional Management- A Series of Three Cases.

Although stomal and parastomal varices are uncommon causes of variceal bleeding, the mortality rate might be as high as 40%. Timely intervention is essential for the management of these ectopic bleeding varices. Due to the rarity of such varices, no standard treatment guideline is available. We present three cases of bleeding stomal varices managed with an endovascular approach, one through percutaneous transhepatic and the other two through transjugular intrahepatic portosystemic shunt approach.

Hepatogenous Diabetes - A Report from Central India.

Background/Objectives: Cirrhosis of liver is associated with loss of liver function, portal hypertension, and pancreatic ß-cell dysfunction leading to hepatogenous diabetes (HD). Often HD is an underestimated and understudied problem, particularly in the Indian subcontinent, where the prevalence of both Chronic liver disease (CLD) and diabetes is high. Hence this study was planned to highlight the prevalence of HD and its association with the severity of cirrhosis. Methods: A total of 121 cirrhotic patients without a history of diabetes were included in this prospective cross-sectional study. Seventy five g oral glucose tolerance test (OGTT) was done in all patients. Fasting serum insulin levels were done to calculate insulin resistance (IR) using homeostatic model assessment-insulin resistance (HOMA-IR). Upper gastrointestinal endoscopy was done to detect varices. Patients were divided into HD group and non-HD group for comparison of results. Results: HD was seen in 52 (42.98%) patients; among them, 63.4% did not show evidence of HD by fasting plasma glucose (FPG) levels. Impaired glucose tolerance (IGT) was seen in 58 (47.93%) patients. Compared with the non-HD group, the HD group had significantly higher model for end-stage liver disease (MELD) score (P = 0.038), HOMA-IR (P < 0.001), incidence of large varices (P < 0.001) and variceal bleeding (P < 0.001). A statistically significant association was noted between HD and Hepatocellular carcinoma (HCC) (P < 0.001). Conclusion: Patients with cirrhosis had a high prevalence of IGT, IR, and HD. The presence of HD is well associated with the severity of cirrhosis in the form of higher MELD score (>15), CTP score (>10), higher bilirubin levels, large varices, bleeding varices, and HCC. FPG levels and glycated hemoglobin (HbA1c) cannot be relied upon, and OGTT aids in the unmasking of HD in these patients.

Spectrum of Neuroimaging Abnormalities in Brain in Patients of Acute-on-Chronic Liver Failure.

Background and aims: Acute-on-chronic liver failure (ACLF) is associated with high short-term mortality. There is a paucity of data about the spectrum of neuroimaging abnormalities in the brain in ACLF patients. The present study was aimed to study the prevalence of cerebral edema and other parenchymal changes in MR imaging of the brain in patients with ACLF. Methods: In this prospective observational study, MR imaging was done in patients with ACLF (n = 41), and findings were compared with age and sex-matched patients with acute decompensation (AD) (n = 13) and those with cirrhosis but without any decompensation at recruitment (n = 21). Results: Forty-one patients with ACLF (24.4% Grade 1 and Grade 2, 51.2% Grade 3) with 14 (34.1%) having cerebral failure were included in the study. T2-weighted (T2W) diffuse white matter hyperintensities (WMHs) and focal WMHs were seen in 17 (41.4%) and 7 (17%) patients, respectively. T1W basal ganglia hyperintensities in 20 (48.7%), cerebral microbleeds (CMBs) in 6 (14.6%), and 2 (4.8%) patients had cerebral edema. In patients with AD, T2W diffuse WMHs were seen in 3 (23%), T2W focal WMHs in 3 (23%) patients. None of the patients with AD had cerebral edema or CMBs. In compensated cirrhosis patients, T2W diffuse WMHs were present in 7 (33.3%), T2W focal WMHs in 5 (23.8%), while 3 (14.2%) patients had CMBs. T1 weighted hyperintensities in basal ganglia were more common in AD [9 (69.2%)] and compensated cirrhosis [15 (71.4%)] as compared to ACLF patients [20 (48.7%)], P = 0.174. The survival time of 30 and 90 days for patients with diffuse T2W WMHs was significantly lesser than patients without T2W WMHs (P = 0.007). Conclusion: Cerebral edema is uncommon in ACLF patients, and T2-weighted diffuse white matter hyperintensities may be associated with worse outcomes. However, due to the limited scope of the present study, the same needs to be explored further in larger cohorts.

Soluble CD163 Is a Predictor of Mortality in Patients With Decompensated Cirrhosis.

Background: Soluble CD163 (sCD163) is a scavenger receptor membrane protein expressed almost exclusively on Kupffer cells and other macrophages. It was found to be associated with the severity of liver cirrhosis. The aim of the present study was to determine whether the novel biomarker sCD163 predicts outcomes in patients with decompensated cirrhosis. Materials and Methods: A single-center, observational, prospective study with 345 decompensated cirrhosis patients was conducted in the Gastroenterology Department between January 2017 and December 2020. Their plasma samples were tested by enzyme-linked immunosorbent assay (ELISA) for sCD163 within 24 hours of admission. These patients were followed up at 28 days, 3 months and 6 months. The independent risk factors were identified with uni- and multivariate logistic regression analyses. We evaluated the predictive performance of the new scoring system (including sCD163) and the original scoring system. Results: The sCD163 level was significantly higher in non-surviving patients than in surviving patients. Positive associations were found between sCD163 levels and the Child-Turcotte-Pugh (CTP), Model for End-Stage Liver Disease (MELD) and albumin-bilirubin (ALBI) scores. Logistic regression confirmed that sCD163 was an independent risk factor for 28-day, 3-month, and 6-month mortality. The areas under the receiver operating characteristic curves (AUROCs) of the use of sCD163 for the prediction of 28-day, 3-month, and 6-month mortality were relatively higher (AUROCs: 0.856; 0.823 and 0.811, respectively). The AUROCs of the new scores obtained by adding sCD163 to the original scoring systems (CTP + sCD163, MELD + sCD163 and ALBI + sCD163) showed that the new scoring systems had better predictive performance than the original scoring systems at all time points (P < 0.001). Conclusion: sCD163 is a prognostic predictor of short-term and long-term outcomes in decompensated cirrhosis patients. Accordingly, the addition of sCD163 to the original clinical scoring systems improved their prognostic performance.

Restructuring Living-Donor Liver Transplantation at a High-Volume Center During the COVID-19 Pandemic.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic has led to deferral of elective transplants and proactive pretransplant testing of the donor/recipient. The impact of these on living-donor liver transplantation (LDLT) activity and outcome is not known. We performed LDLT only for sick patients or patients with advanced hepatocellular carcinoma in this period, with special COVID protocols. METHODS: Patients undergoing LDLT counseling, evaluation, and transplant in the period March to June 2020 (group A) under COVID-19 restrictions and special protocols were included. LDLT activity and outcomes among these patients were compared with those in the same period in 2019 (group B). RESULTS: In the period March 15-June 10, we performed 39 and 23 (59%) LDLTs in 2019 and 2020, respectively. The adult patients with cirrhosis in group A (n = 20) had a significantly higher MELD score, 19.8 ± 7.0 versus 16.1 ± 5.6 in group B (n = 36), p = 0.034. Early recipient mortality was similar in 2019 (2/39) and 2020 (2/23). One of 23 post-transplant recipients, 3/71 recipients and donors during evaluation, and 8/125 healthcare workers (HCWs) developed COVID-19, all of whom recovered uneventfully. CONCLUSION: LDLT activity substantially reduced during the COVID era. The incidence and outcome of COVID-19 among the waiting or transplanted patients and HCWs were similar to those of the general population. The outcome after LDLT in the COVID era was similar to that in non-COVID times. These data suggest that LDLT may be extended to more stable patients with strict protocols.

Differential blood transcriptome modules predict response to corticosteroid therapy in alcoholic hepatitis.

BACKGROUND & AIMS: In patients with severe alcoholic hepatitis (SAH), little is known about the profile of peripheral blood mononuclear cells (PBMCs) at baseline and during corticosteroid therapy, among those who can be treated successfully with steroids (steroid-responders [R] and those who cannot (steroid-non-responders [NR]); 2 groups with different outcomes. METHODS: We performed RNA-seq analysis in PBMCs from 32 patients with definite SAH, at baseline and after 7 days of corticosteroids. The data were sorted into R and NR (n = 16, each group) using the Lille model and 346 blood transcription modules (BTMs) were identified. BTMs are predefined modules of highly co-expressed PBMC genes, which can determine specific immune cell types and cellular functions. The activity of each BTM was taken as the mean value of its member genes. RESULTS: At baseline, 345 BTMs had higher activity (i.e. were upregulated) in NR relative to R. The 100 most upregulated BTMs in NR, included several modules related to lymphoid lineage (T, B, and natural killer [NK] cells), modules for cell division and mitochondrial respiratory electron transport chain (ETC, relating to energy production), but only a few modules of myeloid cells. Correlation studies of BTM activities found features of significantly greater activation/proliferation and differentiation for T and B cells in NR relative to R. After 7 days of corticosteroids, NR had no significant changes in BTM activities relative to baseline, whereas R had downregulation of BTMs related to innate and adaptive immunity. CONCLUSIONS: At baseline and during corticosteroid therapy, increased activity in the PBMCs of gene modules related to activation/proliferation and differentiation of T and B cells, NK cells, and mitochondrial ETC, is a hallmark of SAH patients who are steroid-non-responders. LAY SUMMARY: Patients with severe alcoholic hepatitis receive steroid therapy as the main line of treatment; however, this treatment is ineffective in some patients. This only becomes apparent after 7 days of steroid therapy. We have developed an approach where it can be estimated if a patient is going to respond or not to steroid therapy using the gene expression information of blood cells. This method will allow clinicians to assess the response of patients to steroids earlier, and will help them in adopting alternate strategies if the treatment is found to be ineffective in a particular patient.

Admission Serum Urea is a Better Predictor of Mortality than Creatinine in Patients With Acute-On-Chronic Liver Failure and Acute Kidney Injury.

BACKGROUND: The occurrence of acute kidney injury (AKI) in acute-on-chronic liver failure (ACLF) negatively impacts the survival of patients. There are scant data on the impact of serum urea on outcomes in these patients. We performed this study to evaluate the relationship between admission serum urea and the survival in patients with ACLF and AKI. METHODS: A prospective study was conducted on patients with ACLF (as per Asian Pacific Association for the Study of the Liver criteria) and AKI (as per Acute Kidney Injury Network criteria) hospitalized in the gastroenterology ward between October 2016 and May 2018. Demographic, clinical and laboratory parameters were recorded, and outcomes were compared in patients with respect to the admission serum urea level. RESULTS: A total of 103 of 143 hospitalized patients with ACLF had AKI and were included as study subjects. The discrimination ability between survivors and the deceased was similar for serum urea levels (area under the receiver operating characteristic curve [AUROC] [95% confidence interval {CI}]: 28 days survival, 0.76 [0.67-0.85]; 90 days survival, 0.81 [0.72-0.91]) and serum creatinine levels (AUROC [95% CI]: 28 days survival, 0.75 [0.66-0.84]; 90 days survival: 0.77 [0.67-0.88]) in patients with ACLF and AKI. However, on multivariate analysis, admission serum urea (not serum creatinine) was an independent predictor of mortality in these patients both at 28 days (p = 0.001, adjusted hazard ratio [AHR]: 1.013 [1.005-1.021]) and 90 days (p = 0.001, AHR: 1.014 [1.006-1.022]). CONCLUSION: Over two-thirds of patients with ACLF had AKI. The discrimination ability between survivors and the deceased was similar for both serum urea and serum creatinine levels. However admission serum urea was found to be a better predictor of mortality than serum creatinine in patients with ACLF and AKI.

Granulocyte Colony-Stimulating Factor Use in Decompensated Cirrhosis: Lack of Survival Benefit.

BACKGROUND: Granulocyte colony-stimulating factor (GCSF) has been utilized in decompensated cirrhosis (DC) for improving transplant-free survival (TFS). Data from multiple centers are conflicting with regard to patient outcomes. In this retrospective study, we present our 'real-world experience' of GCSF use in a large group of DC. METHODS: From September 2016 to September 2018, 1231 patients with cirrhosis were screened, of which 754 were found to have decompensation(s). Seventy-three patients with active ascites, jaundice, or both completed GCSF treatment (10 mcg/kg per day for 5 days, followed by 5 mcg/kg/day once every third day for total 12 doses). Per-protocol analysis (n = 56) was performed to study clinical events, liver disease severity, and outcomes at 3, 6, and 12 months after treatment. Modified intention-to-treat (mITT, n = 100) analysis was performed to study overall survival at 180 days. Outcomes were compared with a matched historical control (HC) group (n = 24). RESULTS: Nine (16%, n = 56), 24 (43%, n = 56), and 36 (75%, n = 48) patients died at 3, 6, and 12-month follow-up after GCSF. The commonest cause of death was sepsis (53%) followed by progressive liver failure (33%). Nine percent of patients developed hepatocellular carcinoma on follow-up at the end of 1 year. Acute variceal bleeds, overt hepatic encephalopathy, intensive unit admissions, and liver disease severity scores were higher after treatment at the end of 1 year. The Child-Pugh score >11 and model for end-stage liver disease-sodium score >25 and > 20 predicted worse outcomes at all time points and at 6 and 12 months after GCSF, respectively. Compared to a matched HC group, patients receiving GCSF had higher mortality (75% vs 46%, P = 0.04) at one year. mITT analysis revealed poor overall survival at 6 months compared to HCs (48% vs 75%, P = 0.04). CONCLUSION: Survival in DC was shorter than what was expected in the natural history of the disease after GCSF use.

To determine the prognostic value of the albumin-bilirubin grade (ALBI) in patients underwent transarterial chemoembolization for unresectable hepatocellular carcinoma.

AIM: We aimed at determining the prognostic value of the albumin-bilirubin grade (ALBI) in patients undergoing transarterial Chemoembolization for unresectable Hepatocellular carcinoma. BACKGROUND: Various noninvasive liver reserve markers are used to predict the severity of liver injury. The role and probability of these markers in predicting the prognosis of patients with hepatocellular carcinoma (HCC) is still unknown. METHODS: Patients who underwent TACE from 2013 to 2017 were included. Patient's age, gender, cause of cirrhosis, ALBI Grade along with the site, size and number of tumors were recorded. Radiological response to TACE was assessed by CT scan at 1 and 3 months after the procedure, respectively. Survival assessment was performed and all patients were assessed for survival until the last follow-up. RESULTS: A total of 71 patients were included. Majority of them were male (80.3 %). The mean tumor size of 6 ± 3.9 cm. Majority of patients (54.9 %) had a single lesion and it was mostly localized to the right lobe (60.5 %). The most common cause of chronic liver disease was HCV (65.3%). Median Child class score (CTP) and MELD score were 7 and 10, respectively. Ascites was treated prior to TACE in 12 patients (16.9 %).Mean ALBI score in the study population was -1.59 ± 0.69, with the majority (49. 2 %) falling in grade 2. The mean duration of survival at the last follow up was of 12.1 ± 12.14 months (1- 49).Univariate analysis showed serum albumin (p = 0.003), serum bilirubin (p = 0.018), CTP score (p = 0.019), ALBI grade (p = 0.001) and presence of varices (p = 0.04) to be the main predictors of 6 months survival after TACE. On Cox analysis, only ALBI score (p = 0.038) showed statistical significant association. CONCLUSION: ALBI grade may serve as a surrogate marker in predicting the prognosis of HCC patients undergoing Transarterial Chemoembolization.

Patients with Cirrhosis of Liver Operated for Non-transplant Surgery: A Retrospective Analysis.

Background and Aims: Patients with cirrhosis of the liver have high mortality after surgery. We investigated the mortality in patients with cirrhosis of the liver who underwent surgery other than liver transplant and applied the Mayo clinic model to predict mortality and compare with the observed mortality. We also studied the association of the observed mortality with the Child-Turcotte-Pugh (CTP) class and the model for end-stage liver disease (MELD) and model for end-stage liver disease-sodium (MELD-Na) scores. Methods: The electronic records database of our hospital was accessed to analyze the data of 133 cirrhotic patients who underwent various surgeries under general anesthesia from October 2009 to June 2017. The Mayo risk score was applied to each and used to calculate predicted mortality; the MELD and MELD-Na scores were also calculated. Telephonic interview was performed with the patients and or their relative to ascertain survival or time of death after surgery, when the information was not available from the hospital records. Results: The all-cause observed mortality rates at postoperative days 30 and 90 and at 1 year were 12%, 20.3% and 26.3% respectively. The area under the receiver operating characteristic curve values for the Mayo model as a predictor of 30-day, 90-day and 1-year mortality were 0.836, 0.828 and 0.744 respectively. Good correlation was seen for observed mortality with CTP class and with MELD and MELD-Na scores. Conclusions: The Mayo model for predicting postoperative mortality in patients with cirrhosis of the liver demonstrated good correlation in this study. The strength of prediction of mortality by Mayo risk score calculation was similar at postoperative days 30 and 90 but decreased at 1-year after the surgery. Good correlation was seen for the observed mortality with MELD, MELD-Na and CTP scores.

Impact of Vitamin D Status in Chronic Liver Disease.

BACKGROUND: Vitamin D deficiency is extremely common in chronic liver disease (CLD) patients. Up to 93% of these patients have some degree of vitamin D insufficiency. Liver plays an important role in the metabolism and pleiotropic functions of vitamin D. Vitamin D deficiency has been associated with increased mortality, bacterial infections, portal hypertension complications, and fibrosis severity. We aimed to determine the impact of vitamin D level in CLD. METHODS: One hundred fifty individuals consisting of 75 cirrhotic patients (cases) and 75 respective attendants (controls) were enrolled between July 2015 and July 2017. A detailed clinical and laboratory evaluation was done along with estimation of vitamin D level. Unpaired t-test and analysis of variance was used to compare difference in the level of continuous variables between different groups. Linear regression analysis was performed to analyze the correlation between vitamin D deficiency and severity of liver disease. RESULTS: The age of patients ranged from 18 years to 69 years with mean of 48.85 ± 13.6 years in the case group and 46.57 ± 17.24 years in the control group. Out of 75 CLD patients, vitamin D deficiency (<20 ng/dl) was found in 31 (41.4%) patients, out of which 14(18.7%) suffered from severe vitamin D deficiency (<10 ng/ml). On applying analysis of variance test, there was significant difference in vitamin D level and serum albumin and serum bilirubin (P < 0.05). On linear regression, vitamin D level showed significant negative correlation with Child-Pugh score (r = -0.7379, P < 0.0001) and Model For End-Stage Liver Disease score (r = -0.6671, P < 0.0001). CONCLUSION: Our study concluded that CLD is associated with a significantly low level of vitamin D, which was independent to patient's gender, body mass index, residence, and education level. The findings of our study suggest that awareness of serum vitamin D level in patients with CLD is important. Further studies are required to validate the importance of vitamin D levels and impact of vitamin D supplementation on CLD.

Noradrenaline versus terlipressin in the management of type 1 hepatorenal syndrome: A randomized controlled study.

BACKGROUND: Hepatorenal syndrome (HRS) occurs in decompensated liver disease and carries high mortality. Vasoconstrictors are the drug of choice. Terlipressin is widely used and is expensive. In this study, we compared noradrenaline and terlipressin in the management of type 1 HRS. METHODS: Sixty consecutive patients with type 1 HRS were managed with noradrenaline (Group A, n = 30) or terlipressin (Group B, n = 30) with albumin in a randomized controlled trial at a tertiary center. RESULTS: Reversal of type 1 HRS was achieved in 16 (53%) patients in group A and 17 (57%) in group B. There was statistically insignificant difference between the two groups in decreasing serum creatinine and increasing urine output (p > 0.05). On univariate analysis, Child-Turcotte-Pugh (CTP) score, serum sodium, serum urea, serum albumin, prothrombin time, International normalized ratio (INR), serum alanine aminotransferase (ALT), ascitic fluid protein, and history of bleeding were associated with response to treatment (noradrenaline/terlipressin). However, on multivariate analysis, only baseline CTP score, serum urea, serum albumin, and prothrombin time were independent predictors of response. All patients who responded were discharged alive with no mortality within 30 days. CONCLUSIONS: There is no difference in outcome of patients with type 1 HRS treated with noradrenaline or terlipressin. Thus, noradrenaline, which is cheaper, can be used instead of terlipressin (Clinical Trials Registry-India [CTRI] No. CTRI/2011/09/002032).