Thromboelastography-guided Blood Product Transfusion in Cirrhosis Patients With Variceal Bleeding: A Randomized Controlled Trial.

GOALS: The aim of this study was to assess the use of thromboelastography (TEG)-directed blood product transfusion in cirrhotic patients with acute variceal bleeding compared with conventional transfusion for correction of coagulopathy. BACKGROUND: Coagulopathy is common in patients with cirrhosis. Recommendations for correction of conventional parameters of coagulation-platelets and the international normalized ratio before endoscopy in patients with acute variceal bleeding-need more validation. STUDY: In this randomized controlled trial, cirrhotic patients with severe coagulopathy and acute variceal bleeding were randomized to either TEG-guided blood product transfusion or conventional transfusion from March 2017 to December 2017. The primary outcome was the difference in the amount of fresh frozen plasma and platelet units transfused between the groups. Secondary outcomes were rebleeding at 5 days and 42 days, and 6-week mortality. RESULTS: Of the 60 recruited patients, 30 each were randomized to the TEG and conventional transfusion groups. There were no differences in baseline characteristic and endoscopic findings between the 2 groups. Four subjects in the TEG group received blood product transfusions versus all in the conventional transfusion group (13.3% vs. 100%; P<0.001). The control of bleeding on initial endoscopy was similar in the 2 groups. Rebleeding in the TEG and conventional transfusion groups at 5 days was similar [1 (3.3%) vs. 4 (13.3%), P=0.167], whereas it was significantly less in the TEG group at 42 days [3 (10%) vs. 11 (36.7%), P=0.012]. Mortality at 6 weeks was seen in 4 (13.3%) in the TEG group and in 8 (26.7%) patients in the conventional transfusion group (P=0.176). CONCLUSIONS: TEG-guided strategy was associated with reduced blood product transfusion to correct coagulopathy without compromising hemostasis in cirrhotic patients (Clinical trial ID: CTRI/2017/02/007864).

Dabigatran as an oral anticoagulant in patients with Budd-Chiari syndrome post-percutaneous endovascular intervention.

BACKGROUND AND AIM: Anticoagulants play an important role in the management of Budd-Chiari syndrome. There is a paucity of data on the efficacy and safety of direct-acting oral anticoagulants-dabigatran, among patients with Budd-Chiari syndrome. METHODS: In a retrospective analysis of prospectively maintained data, the stent patency rates, major bleeding episode, and a composite endpoint of major bleed and/or mortality rates were compared between Budd-Chiari syndrome patients treated with dabigatran (n = 36) or vitamin K antagonists (n = 62) following endovascular intervention. RESULTS: The baseline characteristics, including sites of block and types of interventions, were similar between the two groups. The mean duration of follow-up in the dabigatran and vitamin K antagonist groups was 10.5 ± 6.7 and 14.1 ± 6.9 months (P = 0.006), respectively. The endovascular stent patency rates were comparable between the dabigatran and vitamin K antagonist groups at 6 months (91% vs 96.5%) and 12 months (91% vs 93%), P = 0.296 (log-rank test), respectively. Major bleeding events were comparable between the dabigatran and vitamin K antagonist groups at 6 months (3.5% vs 2%) and 12 months (3.5% vs 6.5%), P = 0.895 (log-rank test), respectively. The composite endpoint of mortality and major bleed was comparable between dabigatran and vitamin K antagonists at 6 months (4% vs 5%) and 12 months (4% vs 8%), P = 0.875 (log-rank test), respectively. CONCLUSIONS: Dabigatran, as compared with vitamin K antagonists, is associated with similar stent patency rates and complications among patients with Budd-Chiari syndrome post-endovascular intervention.

A Randomized Control Trial of Thromboelastography-Guided Transfusion in Cirrhosis for High-Risk Invasive Liver-Related Procedures.

BACKGROUND AND AIM: Hemostasis in cirrhosis is dynamic and balanced. Thromboelastography (TEG) assesses global coagulation status. We aimed to assess whether TEG-guided blood product transfusions result in lower blood product requirements in patients with cirrhosis undergoing invasive liver-related procedures as compared to the conventional standard of care (SOC). METHODS: In this open-label, randomized controlled trial, cirrhosis patients with coagulopathy, undergoing invasive liver-related procedures, were randomized to either TEG-guided blood product transfusion or SOC. The primary outcome was difference in the amount of fresh frozen plasma (FFP) and platelet units transfused between the two groups. The secondary outcome was procedure-related bleeding complications within 5 days and any complications until 28 days. RESULTS: From November 2017 till June 2019, 58 patients were recruited (29: TEG and 29: SOC). Most common procedures performed were percutaneous liver biopsy (n = 48), followed by transjugular intrahepatic portosystemic shunt (n = 2), percutaneous acetic acid injection (n = 2), and transarterial chemoembolization (n = 2). There were no differences in baseline demographics, hemostatic profile, and types of procedures between the two groups. Only nine patients in TEG group received transfusions compared to all patients in SOC (31% vs 100%; P < 0.001). In TEG group, six (20.7%) received FFP (P = 0.753 vs. SOC), two (6.9%) received platelets (P < 0.001 vs. SOC), and 1(3.4%) patient received both FFP and platelet (P ≥ 0.999 vs. SOC) transfusion. None of the patients in either group developed procedure-related bleeding complications until 5 days post-procedure. The complication rates at 28-day follow-up were similar between the groups. CONCLUSION: TEG-guided blood product transfusion strategy reduces blood product transfusion without increased risk of bleeding in cirrhotic patients undergoing invasive liver-related procedures (CTRI/2017/12/010822).

Acute-on-Chronic Liver Failure in Budd-Chiari Syndrome: Profile and Predictors of Outcome.

BACKGROUND AND AIM: There is a paucity of data on the clinical presentations and outcome of Budd-Chiari syndrome (BCS) patients presenting as acute-on-chronic liver failure (BCS-ACLF). We aimed to describe the profile and outcomes of endovascular interventions in patients with BCS-ACLF. METHODS: All BCS-ACLF patients presenting between October 2007 and April 2019 satisfying the Asian Pacific Association for the Study of the Liver (APASL) definition were studied. We compared 30- , 90- and, 180-day survival among BCS-ACLF patients who underwent endovascular intervention with those who did not, and with a historical cohort of Child-C BCS patients without ACLF who underwent endovascular intervention. RESULTS: Twenty-eight (5%) of 553 BCS patients presented as ACLF as per APASL definition. The majority (60.7%) were males, and mean age was 29.6 ± 11.2 years. The most common site of the block was isolated involvement of hepatic veins-HV (68%), followed by combined inferior vena cava (IVC) and HV block (25%) and isolated IVC block (7%). The acute precipitants were stent thrombosis (17.9%), acute HV thrombosis (10.7%), acute viral hepatitis (7.1%), and antituberculosis drug with hepatitis B virus reactivation (3.6%). In 60.7% patients, no acute precipitant could be identified. The 30- , 90- , and 180-day survival in BCS-ACLF post-endovascular intervention (n = 15), BCS-ACLF without endovascular intervention (n = 13), and Child-C BCS without ACLF who underwent endovascular intervention (n = 25) were (93%, 87%, and 87%), (46%, 28%, and 0%) and (96%, 92%, and 88%), respectively (log-rank test, p value < 0.001). On multivariate Cox proportional analysis, endovascular intervention and the presence of hepatic encephalopathy were independent predictors of mortality. CONCLUSION: Budd-Chiari syndrome can present as acute-on-chronic liver failure. Endovascular intervention is associated with an improved outcome.

Development and Validation of a Novel Model for Outcomes in Patients with Cirrhosis and Acute Variceal Bleeding.

BACKGROUND: Acute variceal bleeding (AVB) in patients with cirrhosis is associated with high mortality, ranging from 12 to 20% at 6 weeks. The existing prognostic models for AVB lack precision and require further validation. AIM: In this prospective study, we aimed to develop and validate a new prognostic model for AVB, and compared it with the existing models. METHODS: We included 285 patients from March 2017 to November 2017 in the derivation cohort and 238 patients from December 2017 to June 2018 in the validation cohort. Two prognostic models were developed from derivation cohort by logistic regression analysis. Discrimination was assessed using area under the receiver operator characteristic curve (AUROC). RESULTS: The 6-week mortality was 22.1% in derivation cohort and 22.3% in validation cohort, P = 0.866. Model for end-stage liver disease (MELD) [odds ratio (OR) 1.106] and encephalopathy (E) (OR 4.658) in one analysis and Child-Pugh score (OR 1.379) and serum creatinine (OR 1.474) in another analysis were significantly associated with 6-week mortality. MELD-E model (AUROC 0.792) was superior to Child-creatinine model (AUROC) in terms of discrimination. The MELD-E model had highest AUROC; as compared to other models-MELD score (AUROC 0.751, P = 0.036), Child-Pugh score (AUROC 0.737, P = 0.037), D'Amico model (AUROC 0.716, P = 0.014) and Augustin model (AUROC 0.739, P = 0.018) in derivation cohort. In validation cohort, the discriminatory performance of MELD-E model (AUROC 0.805) was higher as compared to other models including MELD score (AUROC 0.771, P = 0.048), Child-Pugh score (AUROC 0.746, P = 0.011), Augustin model (AUROC 0.753, P = 0.039) and D'Amico model (AUROC 0.736, P = 0.021). CONCLUSION: In cirrhotic patients with AVB, the novel MELD-Encephalopathy model predicts 6 weeks mortality with higher accuracy than the existing prognostic models.

Effect of thrombocytopenia and platelet transfusion on outcomes of acute variceal bleeding in patients with chronic liver disease.

BACKGROUND: Platelet transfusion in acute variceal bleeding (AVB) is recommended by few guidelines and is common in routine clinical practice, even though the effect of thrombocytopenia and platelet transfusion on the outcomes of AVB is unclear. AIM: To determine how platelet counts, platelets transfusions, and fresh frozen plasma transfusions affect the outcomes of AVB in cirrhosis patients in terms of bleeding control, rebleeding, and mortality. METHODS: Prospectively maintained database was used to analyze the outcomes of cirrhosis patients who presented with AVB. The outcomes were assessed as the risk of rebleeding at days 5 and 42, and risk of death at day 42, considering the platelet counts and platelet transfusion. Propensity score matching (PSM) was used to compare the outcomes in those who received platelet transfusion. Statistical comparisons were done using Kaplan-Meier curves with log-rank tests and Cox-proportional hazard model for rebleeding and for 42-d mortality. RESULTS: The study included 913 patients, with 83.5% men, median age 45 years, and Model for End-stage Liver Disease score 14.7. Platelet count < 20 × 109/L, 20-50 × 109/L, and > 50 × 109/L were found in 23 (2.5%), 168 (18.4%), and 722 (79.1%) patients, respectively. Rebleeding rates were similar between the three platelet groups on days 5 and 42 (13%, 6.5%, and 4.7%, respectively, on days 5, P = 0.150; and 21.7%, 17.3%, and 14.4%, respectively, on days 42, P = 0.433). At day 42, the mortality rates for the three platelet groups were also similar (13.0%, 23.2%, and 17.2%, respectively, P = 0.153). On PSM analysis patients receiving platelets transfusions (n = 89) had significantly higher rebleeding rates on day 5 (14.6% vs 4.5%; P = 0.039) and day 42 (32.6% vs 15.7%; P = 0.014), compared to those who didn't. The mortality rates were also higher among patients receiving platelets (25.8% vs 23.6%; P = 0.862), although the difference was not significant. On multivariate analysis, platelet transfusion and not platelet count, was independently associated with 42-d rebleeding. Hepatic encephalopathy was independently associated with 42-d mortality. CONCLUSION: Thrombocytopenia had no effect on rebleeding rates or mortality in cirrhosis patients with AVB; however, platelet transfusion increased rebleeding on days 5 and 42, with a higher but non-significant effect on mortality.

Acute Liver Failure of Non-A-E Viral Hepatitis Etiology-Profile, Prognosis, and Predictors of Outcome.

BACKGROUND/OBJECTIVES: Acute liver failure (ALF) is rare and associated with poor outcomes. The outcomes of ALF and predictors of outcome may vary as per the etiology. There are limited data on the predictors of spontaneous survival among patients with ALF of non-A-E hepatitis or cryptogenic etiology. We aimed to assess clinical course, complications, and outcome of non-A-E etiology ALF. METHODS: In this prospective analysis, all consecutive ALF patients (n = 1555; January 1986-June 2018) were analyzed. Non-A-E-ALF was defined as ALF that could not be attributed to known etiologies such as drugs, viral hepatitis, autoimmune hepatitis, and Wilson's disease. Clinical course, complications, and outcomes of non-A-E-ALF patients who did not undergo liver transplantation were analyzed. Unadjusted and adjusted odds ratios (ORs) were calculated. RESULTS: Non-A-E-ALF constituted 34.6% (n = 538) of all ALF patients, whereas hepatitis E virus (HEV), hepatitis B virus (HBV), and anti-tuberculosis therapy (ATT) accounted for 29.5% (n = 459), 8.6% (n = 134), and 7.4% (n = 115), respectively. Among non-A-E-ALF patients, mean age was 28.8 ± 12.0 years, 50.9% females, majority (63.1%) had hyperacute presentation, and 79.2% had advanced encephalopathy at presentation. The frequency of cerebral edema in non-A-E-ALF (53.3%) was higher than that in HEV-ALF (41.2%) and ATT-ALF (44.2%), P < 0.001. The survival rate in non-A-E-ALF (37.5%) was poorer than HEV-ALF (54.9%) and was comparable to that in HBV (35.8%) and ATT (29.6%) induced ALF. The baseline prothrombin time prolongation (odds ratio [OR] 1.041; 95% confidence intervals [CI], 1.017-1.065) and infection (OR 2.366; 95%CI, 1.107-5.055) were independent predictors of outcome in non-A-E-ALF. The 3-days acute liver failure early dynamic model had the best value in predicting the outcome. CONCLUSIONS: Non-A-E-ALF accounts for one-third of all cases of ALF and is associated with poor spontaneous survival.

Persistent or incident hyperammonemia is associated with poor outcomes in acute decompensation and acute-on-chronic liver failure.

BACKGROUND AND AIM: The effect of elevated ammonia on organ failures (OF), apart from hepatic encephalopathy, in patients with acute decompensation (AD) of cirrhosis and acute-on-chronic liver failure (ACLF) is unclear. We aimed to assess the effect of persistent or incident hyperammonemia on OF and outcomes in patients with AD and ACLF. METHODS: A total of 229 patients with ACLF and 83 with AD were included. Arterial ammonia was measured on day 1 and day 3 of admission. Persistent or incident hyperammonemia was defined as a level of ≥79.5 µmol/L on day 3. The changes in ammonia levels during the first 3 days were analyzed with respect to the complications and outcomes. RESULTS: At admission, the median level of arterial ammonia was higher in ACLF compared to AD patients (103 vs 86 µmol/L, P < 0.001). Persistent or incident hyperammonemia was noted in 206 (66.0%) patients and was more frequent in ACLF compared to AD patients (70.7 vs 53.0%, P = 0.013). Patients with persistent or incident hyperammonemia, compared to those without it, developed a higher proportion of new-onset OF during hospitalization involving liver (P = 0.018), kidney (P = 0.001), brain (P = 0.005), coagulation (P = 0.036), circulation (P = 0.002), and respiratory (P = 0.003) issues and had higher 28-day mortality (log-rank test, P < 0.001). After adjustment for chronic liver failure consortium ACLF score, persistent or incident hyperammonemia (hazard ratio, 3.174) was independently associated with 28-day mortality. The presence of infection was an independent predictor of persistent or incident hyperammonemia. CONCLUSION: Persistent or incident hyperammonemia during first 3 days of hospitalization in patients with AD or ACLF is associated with increased risk of OF and death.

Body mass index-based controlled attenuation parameter cut-offs for assessment of hepatic steatosis in non-alcoholic fatty liver disease.

BACKGROUND AND AIM: In patients with liver disease, etiology and body mass index (BMI) affects controlled attenuation parameter (CAP) assessment using FibroScan. We aimed to assess the performance characteristics of CAP for hepatic steatosis in patients with non-alcoholic fatty liver disease (NAFLD) stratified into obese (BMI ≥ 30 kg/m2) and non-obese (BMI < 30 kg/m2) subgroups. METHODS: In this prospective study, 219 consecutive adult NAFLD patients, with an available FibroScan value (liver stiffness measurement-[LSM] and CAP) and liver biopsy, were included. Receiver operating characteristic curves were used for assessment of the CAP cut-off values predicting different stages of hepatic steatosis. RESULTS: The mean ± standard deviation age of patients was 39.7 ± 10.5 years, 116 (53%) were males, and median (interquartile range) BMI was 31.8 (25.7-43.8) kg/m2. One hundred (45.7%) and 119 (54.3%) patients were non-obese and obese, respectively. The median values of CAP and LSM were significantly higher among obese patients as compared with the non-obese ones: 333 (304-368) vs. 320 (296-345) dB/m, p = 0.002 and 8.3 (6.1-11.4) vs. 6.6 (5.7-10.3) kPa, p = 0.012, respectively. Among non-obese NAFLD, optimal CAP cut-off values for steatosis (S) ≥ S1, ≥ S2, and ≥ S3 were 275 dB/m, 319 dB/m, and 337 dB/m, respectively. The corresponding CAP values among obese patients were higher as 285 dB/m, 340 dB/m, and 355 dB/m, respectively. BMI independently predicted CAP on multivariate analysis. The discordance of 2-grades between CAP and biopsy measured steatosis was seen in 13% in non-obese and 19.3% in obese NAFLD. CAP overestimated steatosis more often than underestimating it, with a higher proportion in obese NAFLD. CONCLUSION: In patients with NAFLD, interpretation of CAP requires consideration of BMI.

Comparison of various prognostic scores in variceal and non-variceal upper gastrointestinal bleeding: A prospective cohort study.

BACKGROUND AND AIMS: Various prognostic scores like Glasgow-Blatchford bleeding score (GBS), modified Glasgow-Blatchford bleeding score (mGBS), full Rockall score (FRS) including endoscopic findings, clinical Rockall score (CRS), and albumin, international normalized ratio (INR), mental status, systolic blood pressure, age >65 (AIMS65) are used for risk stratification in patients with upper gastrointestinal bleeding (UGIB). The utility of these scores in variceal UGIB (VUGIB) is not well defined. In this prospective study, we aimed to assess the performance of these scores in patients with non-variceal (NVUGIB) and VUGIB. METHODS: We included 1011 patients (during March 2017 and August 2018) including 439 with NVUGIB and 572 VUGIB. Performance of GBS, mGBS, FRS, CRS, and AIMS65 for various outcome measures was analyzed using the area under receiver operator characteristic curve (AUROC). RESULTS: The accuracy of prognostic scores in predicting the composite outcome including the need of hospital-based intervention and 42-day mortality was higher in NVUGIB as compared with VUGIB, AUROC: CRS: 0.641 vs. 0.537; FRS: 0.669 vs. 0.625; GBS: 0.719 vs. 0.587; mGBS: 0.711 vs. 0.594; AIMS65: 0.567 vs. 0.548. GBS and mGBS at a cut-off score of 1 had the highest negative predictive value, 91.7% and 91.3%, respectively, for predicting composite outcome in NVUGIB. Similarly, these scores had better accuracy for predicting 42-day rebleeding in NVUGIB as compared to VUGIB, AUROC: CRS: 0.680 vs. 0.537; FRS: 0.698 vs. 0.565; GBS: 0.661 vs. 0.543; mGBS: 0.627 vs. 0.540; AIMS65: 0.695 vs. 0.606. CONCLUSION: The prognostic scores such as CRS, FRS, GBS, mGBS, and AIMS65 predict the need for hospital-based management, rebleeding, and mortality better among patients with NVUGIB than VUGIB.

Therapy with Oral Directly Acting Agents in Hepatitis C Infection Is Associated with Reduction in Fibrosis and Increase in Hepatic Steatosis on Transient Elastography.

BACKGROUND/AIMS: Direct-Acting Antivirals (DAAs) are now the standard of care for management of Chronic Hepatitis C (CHC) infection. The aim of this study was to evaluate change in Liver Stiffness Measurement (LSM) and Controlled Attenuation Parameter (CAP) by transient elastography (FibroScan®) after completion of DAA therapy. METHODS: LSM and CAP were measured serially (baseline pre-treatment, at 12 weeks post therapy, and one year after completion of therapy) in a prospective cohort of 372 CHC patients treated with DAAs. Patients with at least two FibroScan measurements were included. RESULTS: The mean age was 38.1 ± 12.6 years; 58.3% males. Cirrhosis as defined by biopsy or fibroscan measurement (≥12.5) kPa was found in 25.5%. On paired analysis (n = 317), LSM (IQR) decreased from a baseline value 7.1 (5.3-13.8) kPa to 6.2 (4.8-11.2) kPa 12 weeks post therapy with a median decline 0.7 (-0.6-2.6) kPa, P < 0.001. Similarly, on paired analysis (n = 160), LSM decreased from baseline 6.9 (5.1-12.7) kPa to 6.1 (4.8-9.4) kPa after one year of treatment with median decline 0.9 (-0.6-3.2) kPa, P < 0.001. In contrast, on paired analysis (n = 317), CAP increased from baseline of 213.0 (180.0-254.5) dB/m to 225.0 (190.0-269.0) dB/m at 12 weeks post therapy with median increase 7.0 (-23.5-45.5), P = 0.001. Similarly, on paired analysis (n = 160), CAP increased from baseline of 210.0 (180.3-260.8) dB/m to 234.0 (204.0-282.0) dB/m at one year post therapy with median increase 25.0 (-12.5-61.5) dB/m, P < 0.001. On multivariate linear regression analysis, low baseline CAP value and low albumin were significantly associated with increase in CAP values. CONCLUSION: Treatment with DAAs reduces liver stiffness, but is associated with increase in hepatic steatosis.

Controlled Attenuation Parameter for Assessment of Hepatic Steatosis in Indian Patients.

BACKGROUND/AIMS: The gold standard method for measurement of hepatic steatosis is liver histology. Controlled Attenuation Parameter (CAP) can measure hepatic steatosis non-invasively. We aimed to assess the accuracy of CAP for detection of hepatic steatosis. METHODS: A total of 462 patients (May 2012-January 2017)-89 non-alcoholic fatty liver disease, 182 chronic hepatitis B, 88 chronic hepatitis C and 103 patients with other etiologies who underwent simultaneous liver biopsy and CAP estimation using Transient Elastography (TE) were included. Steatosis was graded as S0: steatosis in 0-5% of hepatocytes, S1: 6-33%, S2: 34-66% and S3: 67-100%. Receiver Operating Characteristic (ROC) curves were plotted to evaluate the accuracy of CAP in detecting hepatic steatosis. Predictors of CAP were assessed by multivariate linear regression model. RESULTS: The mean age ± SD was 33.8 ± 11.6 years; 296 (64.1%) were males. On liver histology, steatosis grades S0, S1, S2 and S3 were seen in 331 (71.6%), 74 (16.0%), 39 (8.4%) and 18 (3.9%), respectively. The median CAP (IQR) values for S0, S1, S2, and S3 steatosis were 206 (176-252) dB/m, 295 (257-331) dB/m, 320 (296-356) dB/m, and 349 (306-363) dB/m, respectively. For estimation of ≥S1, ≥S2, and ≥S3 using CAP, AUROC were 0.879, 0.893, and 0.883, respectively. In multivariate analysis, only BMI (OR 1.18; CI, 1.11-1.26, P < 0.001) and grade of hepatic steatosis (grade 1, OR, 3.94; 95% CI, 1.58-9.84, P = 0.003; grade 2, OR 42.04; 95% CI, 4.97-355.31, P = 0.001 and grade 3, OR 35.83; 95% CI 4.31-297.61, P = 0.001) independently predicted CAP. CONCLUSIONS: CAP detects hepatic steatosis with good accuracy in Indian patients with various etiologies.

Alcohol-related acute-on-chronic liver failure-Comparison of various prognostic scores in predicting outcome.

BACKGROUND AND AIMS: Various prognostic scores are available for predicting outcome in acute-on-chronic liver failure (ACLF). We compared the available prognostic models as predictors of outcome in alcohol-related ACLF patients. METHODS: All consecutive patients with alcohol-related ACLF were included. At admission, prognostic indices-acute physiology and chronic health evaluation score (APACHE II), model for end-stage liver disease (MELD), MELD-Na, Maddrey's discriminant function (DF), age-bilirubin-INR-creatinine (ABIC), and Chronic Liver Failure Consortium (CLIF-C) ACLF score (CLIF-C ACLF) score were calculated. Receiver operator characteristic (ROC) curves were plotted for all prognostic scores with in-hospital, 90-day, and 1-year mortality as outcome. RESULTS: Of the 171 patients, 170 were males, and grade 1 ACLF in 20 (11.7%), grade 2 in 52 (30.4%), and grade 3 in 99 (57.9%) patients. One hundred and nineteen (69.6%) died in-hospital. The median (IQR) Maddrey's score, MELD, MELD-Na, ABIC, APACHE II, and CLIF-C ACLF were 87.8 (66.5-123.0), 33.1 (27.6-40.0), 34.4 (29.5-40.0), 8.5 (7.3-9.6), 15 (12-21), and 51.1 (44.1-56.4), respectively. On multivariate Cox regression analysis, independent predictors of in-hospital outcome were presence of hepatic encephalopathy (early HR, 2.078; 95%CI, 1.173-3.682, p = 0.012 and advanced, HR, 2.330; 95% CI, 1.270-4.276, p = 0.006), elevated serum creatinine (HR, 1.140; 95% CI, 1.023-1.270, p = 0.018), and infection at admission (HR, 1.874; 95% CI, 1.160-23.029, p = 0.010). On comparison of ROC curves, APACHE II and CLIF-C ACLF AUROC were significantly higher than MELD, MELD-Na, DF, and ABIC (p < 0.05) for predicting in-hospital, 90-day, and 1-year mortality. The AUROC was highest for APACHE II followed by CLIF-C ACLF (Hanley and McNeil, p = 0.660). CONCLUSIONS: Alcohol-related ACLF has high in-hospital mortality. Among the available prognostic scores, CLIF-C ACLF and APACHE II perform best.

Prevalence, predictors and impact of bacterial infection in acute on chronic liver failure patients.

BACKGROUND: Acute on chronic liver failure (ACLF) is associated with high short term mortality. We aimed to evaluate the prevalence, predictors and impact of bacterial infection in ACLF. METHODS: Consecutive hospitalized patients with cirrhosis and acute decompensation (AD), from January 2011-March 2017, were included. Predictors of survival and infection were assessed. RESULTS: 572 patients with cirrhosis and AD were classified into 3 groups - no infection (group 1, n = 190, 33.2%), infection at admission/within 48 h (group 2, n = 298, 52.1%) and infection after 48 h (group 3, n = 84, 14.7%). Higher frequency of organ failures - kidney, brain, circulation and respiratory failure - were seen in groups 2 and 3 as compared with group 1 (P < 0.001 for all). Most common site of infection was lungs, followed by spontaneous bacterial peritonitis and urinary tract infection. The frequency of infection increased with higher ACLF grades. Among ACLF patients, on Cox-proportional multivariate analysis, presence of infection was associated with significantly higher mortality [group 2 (HR 2.93; 95%CI, 1.97-4.38, P < 0.001) and group 3 (HR 1.84; 95%CI, 1.16-2.91, P = 0.009)], as compared with group 1. On multivariate logistic regression analysis, advanced hepatic encephalopathy and elevated total leucocyte count were independently associated with development of infection. CONCLUSIONS: Infections are common in ACLF, and associated with poor outcome.