Thromboelastography-Guided versus Standard-of-Care or On-Demand Platelet Transfusion in Patients with Cirrhosis and Thrombocytopenia Undergoing Procedures: A Randomized Controlled Trial.

PURPOSE: To determine the rate of platelet transfusion in patients with cirrhosis and severe thrombocytopenia (platelet counts <50 × 109/L) undergoing high-risk invasive procedures when prescribed by thromboelastography (TEG) compared with empirical and on-demand transfusion strategies. MATERIALS AND METHODS: This was a single-center, single-blinded, randomized controlled trial. Patients with cirrhosis and severe thrombocytopenia undergoing high-risk invasive procedures were randomized into 3 groups: TEG group, transfusions based on TEG parameters; standard of care (SOC) group, 3 units of random donor platelets before procedure; and on-demand group, transfusions based on procedural adverse events/clinician's discretion. The primary outcome was periprocedural platelet transfusion in each arm. RESULTS: Eighty-seven patients were randomized (29 in each group) with no significant differences in demographics/coagulation profile/procedures. The median platelet count was 33 × 109/L (interquartile range, 26-43 × 109/L). Percutaneous liver biopsy was the most common procedure (46, 52.9%). Significantly lower number of patients in the TEG group received platelets (4 cases, 13.8%; 95% CI, 3.9-31.7) compared with SOC group (100%; 95% CI, 88.1-100; P < .001). Four patients in the on-demand group received platelets (13.8%; 95% CI, 3.9-31.7). Minor (World Health Organization [WHO] Grade 2) procedure-related bleeding occurred in 3 (10%; 95% CI, 2.2-27.4) patients in the TEG-guided transfusion group compared with 1 (3.4%; 95% CI, 0.1-17.8) patient each in the SOC and on-demand groups (P = .43), although the study was not powered for comparison of bleeding rates. No bleeding-related mortality was observed in any of the 3 groups. CONCLUSIONS: TEG-prescribed transfusion reduced prophylactic transfusions in patients with cirrhosis and severe thrombocytopenia undergoing high-risk invasive procedures. The study was not powered for comparison of bleeding rates.

Intravenous albumin infusion does not augment the response rate to a combination of exclusive enteral nutrition and intravenous steroids in acute severe ulcerative colitis: a randomized controlled trial.

INTRODUCTION: 30-40% patients with acute severe ulcerative colitis (ASUC) fail intravenous (IV) steroids requiring medical rescue therapy/colectomy. Low baseline albumin predicts steroid non-response, and exclusive enteral nutrition (EEN) has been shown to improve steroid response and albumin levels. Albumin infusion due to its anti-inflammatory and anti-oxidant properties might further improve steroid response in ASUC, which was evaluated in present study. METHODS: In this open-label randomized controlled trial, patients with ASUC were randomized in 1:1 ratio to albumin + standard of care (SOC) + EEN vs. SOC + EEN (Jan2021 - Feb2023). Both arms received 5 days of EEN with 400 mg IV hydrocortisone/day. Patients in albumin arm were administered 5 days of 20% w/v intravenous albumin (100 ml). Primary outcome was 1) steroid failure (need for rescue medical therapy or colectomy) and 2) proportion of patients with adverse events. RESULTS: Sixty-one patients (albumin-30, SOC-31)(mean age-31.6±0.4 years, male-57.4%), were included. Baseline characteristics were comparable. There was no difference in steroid failure between albumin and SOC arm(10/30(33.33 %) vs 13/31(41.94 %), p=0.49). No adverse events were reported with albumin infusions. Colectomy rate(10% vs 9.68%, P=1), response to salvage medical therapy (88.89% vs 76.92%, P=0.62) and median duration of hospitalization (10.5(7-16) vs 10(7-20), P=0.43) were also comparable. Long-term composite outcome of colectomy and re-admission rates was numerically higher in the albumin than SOC arm (37.04% vs 17.86%, p>0.05), although it did not reach statistical significance. CONCLUSION: There was no benefit of intravenous albumin infusion as an adjunct to IV steroids and EEN in patients with ASUC.

Poor Performance of Non-invasive Tests for Advanced Fibrosis in Nonalcoholic Fatty Liver Disease: A Multicentric Asian Study.

BACKGROUND: Non-invasive tests (NITs) are useful to assess advanced fibrosis (AF) in nonalcoholic fatty liver disease (NAFLD). Data from Asian countries suggest that these tests have poor performance. We aimed to assess diagnostic accuracy of established thresholds of biomarker-based NITs and Transient Elastography (TE) in identifying AF and evaluated the utility of a two-step test approach. METHODS: Biopsy-proven 641 NAFLD patients (55.2% males, median age 42 years) were included from three different centers of Asia. AF (≥ F3) was identified as per histological staging (24.8%). RESULTS: TE had the highest area under the receiver operating characteristic curve (AUROC) 0.82 (0.79-0.86), and all other biomarker-based NITs had low AUROC (< 0.7). NITs performed poorly at established thresholds. The combination of NITs utilizing liver stiffness measurement (LSM) and biomarkers, Agile 3+ and FAST, demonstrated acceptable diagnostic accuracy (AUROC 0.82 and 0.78, respectively), but none were superior to LSM alone. LSM measured using appropriate M and XL probes remained accurate regardless of body mass index (BMI); NFS and APRI scores were less accurate at higher BMI ranges. A two-step approach using NFS rule-out criteria (< - 2.97 to rule out) followed by LSM (< 7.3 kPa to rule out and ≥ 12.7 kPa to rule in) correctly classified 62.4% of patients, with only 10.2% of patients incorrectly classified. CONCLUSION: NITs have not been validated to identify AF in the Asian NAFLD population, and internationally accepted thresholds yield high false-negative rates. LSM and LSM-based combination tests remain the most accurate.

Impact of body mass index on disease progression and outcomes in patients with nonalcoholic fatty liver disease.

BACKGROUND: The relationship between body mass index (BMI) and outcomes in patients with nonalcoholic fatty liver disease (NAFLD) is not well defined. This study aimed to assess the presentations, outcomes, and development of liver-related events (LREs) and non-LREs in patients with NAFLD stratified by BMI. METHODS: Records of NAFLD patients from 2000-2022 were reviewed. Patients were categorized as lean (18.5-22.9 kg/m2), overweight (23-24.9 kg/m2), and obese (>25 kg/m2) based on BMI. Stage of steatosis, fibrosis, and NAFLD activity score were noted in the patients undergoing liver biopsy in each group. RESULTS: Out of 1051 NAFLD patients, 127 (12.1%) had normal BMI, 177 (16.8%) and 747 (71.1%) were overweight and obese, respectively. Median [interquartile range] BMI was 21.9 [20.6-22.5], 24.2 [23.7-24.6], and 28.3 [26.6-30.6] kg/m2 in each group, respectively. Prevalence of metabolic syndrome and dyslipidemia were significantly higher in the obese. Obese patients had significantly higher median [interquartile range] liver stiffness (6.4 [4.9-9.4] kPa) than overweight and lean subjects. A higher proportion of obese patients had significant and advanced liver fibrosis. At follow-up, there were no significant differences in the progression of liver disease, new LREs, coronary artery disease, or hypertension across the BMI groups. Overweight and obese patients were more likely to develop new-onset diabetes by follow-up. The mortality rates in the three groups were comparable (0.47, 0.68, and 0.49 per 100 person-years, respectively), with similar causes of death (liver-related vs non-liver-related). CONCLUSIONS: Patients with lean NAFLD have similar disease severity and rates of progression as the obese. BMI is not a reliable determinant of outcomes in NAFLD patients.

Incidence and Predictors of Liver-Related Events in Patients With Nonalcoholic Fatty Liver Disease.

Background: Nonalcoholic fatty liver disease (NAFLD) is the commonest type of liver disease worldwide. We aimed to assess the incidence and predictors of liver-related events (LREs) and mortality in NAFLD patients. Methods: NAFLD patients (n = 957) evaluated between January 2000 and November 2021 were included. Patients were categorised as noncirrhosis (NC), compensated cirrhosis (CC) and decompensated cirrhosis (DC), and the incidence of LRE and mortality were estimated and compared. Results: The proportions of NC, CC and DC were 87.8% (n = 840), 8.8% (n = 84) and 3.4% (n = 33), respectively. The median follow-up duration was 3.9 (3.0-5.7) years, and the total cumulative duration was 4633 person-years. The incidence of LRE per 100 person-years was 0.14, 2.72 and 10.24 in patients with NC, CC and DC, respectively. The incidence of mortality was 0.12, 1.05 and 4.24 per 100 person-years, respectively, in the 3 groups. The causes of mortality in the 3 groups were liver related in 1/5 (20%), 3/4 (75%) and 6/9 (66.7%), respectively. Overall, the mortality rate was higher in those with diabetes than those without diabetes (log-rank P value = 0.005). On further analysis, diabetes was associated with poor outcomes only in NC group (log-rank P value = 0.036), and not in CC (log-rank P value = 0.353) or DC groups (log-rank P value = 0.771). On multivariate Cox proportional hazard analysis, age (hazard ratio [HR] 1.070), hypertension (HR 4.361) and DC (HR 15.036) were independent predictors of poor outcomes. Liver stiffness measurement, bilirubin, CC and DC were independent predictors of LRE. Conclusion: In our study of NAFLD from India, the incidence of LRE was found to be similar to that seen in Western studies. In NC NAFLD, diabetes was associated with poor outcomes.

Compensated Advanced Chronic Liver Disease in Nonalcoholic Fatty Liver Disease: Two-Step Strategy is Better than Baveno Criteria.

BACKGROUND: Advanced fibrosis and cirrhosis (compensated advanced chronic liver disease [cACLD]) are clinically indistinguishable and increase risk of developing clinically significant portal hypertension. Baveno VII recommends using elastography to rule out and diagnose cACLD with liver stiffness measurement (LSM) cut-offs of 10/15 kPa. METHODS: In a retrospective analysis of 330 nonalcoholic fatty liver disease (NAFLD) patients, performance of the Baveno VII cut-offs for diagnosing cACLD was compared with newly suggested lower cut-offs (8/12 kPa). A model for detecting cACLD among those with LSM between 8 and 12 kPa was developed and compared with recently published models. RESULTS: Seventy (21.2%) of the 330 NAFLD patients had biopsy-proven cACLD. The Baveno VII cut-offs (10/15 kPa) had a lower sensitivity of 72.8% (60.9-82.8%) and a specificity of 93.4% (89.7-96.1%). Sensitivity and specificity of lower cut-offs (8/12 kPa) were 91.4% (82.3-96.8%) and 88.5% (83.9-92.1%), respectively. Modeling based on the presence of diabetes (odds ratio [OR] 3.625[1.161-11.320], p = 0.027) and serum aspartate aminotransferase (AST) levels (OR 1.636[1.098-2.436], p = 0.015) correctly identified 75.7% of patients with LSM between 8 and 12 kPa. Our model performed best with an area under receiver operator curve (AUROC) of 0.725 (95%CI 0.609-0.822), compared to Papatheodoridi (AUROC 0.626, CI 0.506-.736) and Zhou (AUROC 0.523, CI 0.403-0.640) models. A two-step strategy comprising application of lower LSM cut-offs followed by the predictive model correctly identified the presence of cACLD in 83% of the patients as compared to 75% by the Baveno VII cut-offs. CONCLUSION: A two-step strategy employing lower LSM cut-offs and modeling based on diabetes and AST levels outperforms Baveno VII cut-offs for identifying cACLD in NAFLD patients.

Real-world re-treatment outcomes of direct-acting antiviral therapy failure in patients with chronic hepatitis C.

Direct-acting antiviral (DAA) drugs are associated with high (>95%) sustained virological response at 12 weeks (SVR12) in chronic hepatitis C (CHC) patients. There is a paucity of data regarding the characteristics and re-treatment outcomes of DAA treatment failure patients. In a retrospective analysis of the prospectively collected database, we assessed the outcomes of re-treatment among patients with previous DAA failure. Patients' characteristics, viral characteristics, including resistance-associated substitutions (RAS) in a subgroup of patients, SVR12, and clinical outcomes were studied. Of 40 patients with DAA failure, among whom 36 were retreated, mean age was 45.7 years, 63.9% (n = 23) were male, 63.9% (n = 23) had a genotype-3 infection and 63.9% (n = 23) were cirrhotic. The re-treatment regimens included a combination of pan-genotypic DAA, mainly sofosbuvir and velpatasvir with or without ribavirin. Three patients who declined retreatment and one who was still on treatment was excluded. For patients who completed re-treatment, SVR12 was 100% irrespective of genotypes. SVR12 among genotype 3 was 75% (15 of 20) when lost to follow-up was considered a treatment failure. Six patients died due to liver-related causes, including five (83.3%) with hepatocellular carcinoma. RAS analysis in 17 randomly selected patients did not reveal any dominant substitutions in NS5A or NS5B region affecting SVR12, though several novel mutations were observed. In conclusion, re-treatment of CHC patients with prior DAA failure using pan-genotypic DAA is associated with high SVR12 rates irrespective of genotype or the presence of RAS.

FibroScan-aspartate aminotransferase score in an Asian cohort of non-alcoholic fatty liver disease and its utility in predicting histological resolution with bariatric surgery.

BACKGROUND AND AIM: The FibroScan-aspartate aminotransferase (FAST) score was developed for identifying patients with non-alcoholic steatohepatitis, who also have an elevated non-alcoholic fatty liver disease (NAFLD) activity score (NAS) ≥ 4 and significant fibrosis (F ≥ 2). We aimed to validate it in our NAFLD cohort and assess if it correlates with the histological changes after bariatric surgery. METHODS: Patients with NAFLD, including those undergoing bariatric surgery, were included. The FAST score was calculated using liver stiffness measure, controlled attenuation parameter, and aspartate aminotransferase. Calibration and discrimination of the model were assessed by calibration plots and area under the receiver operating characteristic curve, respectively. Sensitivity and specificity were assessed at the rule-out and rule-in cutoffs (≤0.35 and ≥0.67), respectively. Changes in the NAS and FAST scores were compared in the bariatric cohort 1 year after surgery. RESULTS: The cohort composed of 309 patients, of which 48 patients underwent repeat liver biopsy at 1 year. The model showed good discrimination with area under the receiver operating characteristic curve of 0.79 (0.74-0.84); however, it was not satisfactorily calibrated (Hosmer-Lemeshow test, P = 0.008). The sensitivity and specificity at the rule-out and rule-in cutoffs were 0.90 and 0.84, respectively. A significant correlation was seen between the 1-year reduction in the NAS and FAST scores (r = 0.38, P = 0.009). A significant reduction in the median FAST score was seen in patients who had ≥2-point reduction in NAS after bariatric surgery. CONCLUSION: FibroScan-aspartate aminotransferase score demonstrated good discrimination for fibrotic non-alcoholic steatohepatitis in our cohort. However, a miscalibration resulted in overprediction. The score correlated well with the histological response to interventions for NAFLD.