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Background and Aims: Inappropriate treatment of infections fuels drug-resistance, organ failures, and costs in cirrhosis. We explored proteomics to improve infection diagnosis and management in acutely decompensated (AD) cirrhosis., Methods: We enrolled 391 patients with AD(92% males, median-age: 41 years), 84 in discovery-cohort(54 infected, 30 non-infected), 147 in validation-cohort-I(106 infected, 41 non-infected), and 160 in validation-cohort-II(108 infected, 52 non-infected). High-throughput proteomics identified biomarkers in discovery cohort, validated through ELISA in subsequent cohorts. A model for infection was evaluated through discrimination, calibration, and decision curves, and was externally validated., Results: Infected patients exhibited higher leucocyte-counts, procalcitonin, organ failures, MELD, and 30-day mortality(p<0.001 each). Proteomics identified 516 proteins, 27 upregulated and 38 downregulated in infections. LGALS3BP, PLTP, CFP, and GPX3 were independently linked to infections (adjusting for severity and SIRS), with composite-AUC of 0.854(0.787-0.922) in validation-cohort-I. A PACIFY model(LGALS3BP+procalcitonin+CLIF-COF+lactate) predicted infections with AUC of 0.965;0.933-0.997 and 0.906;0.860-0.952 in validation-cohorts-I and II, outperforming procalcitonin, SIRS, WBC, NLR, neutrophil%, and composite models(p<0.001). Model demonstrated fair calibration, with decision curves indicating net benefit of model in treating infections, and reducing unnecessary antimicrobials use. Consistent findings were observed on external validation(AUC: 0.949; 0.916-0.982) re-enforcing the accuracy and clinical utility of model. A deployable app was developed for infection risk estimation, enhancing practical applicability. Impaired phagocytosis, complement functions, hypocoagulation, hypofibrinolysis, dysregulated carbohydrate metabolism, autophagy, heightened cell death, and proteolysis were key perturbed pathways in infections., Conclusion: The study identifies novel protein signatures and pathways linked with infections in AD. A biomarker guided treatment of infections can limit unnecessary antimicrobials use and the burden of drug-resistance in cirrhosis., (Copyright © 2025. Published by Elsevier Inc.)

Background: The growth hormone-insulin-like growth factor (GH-IGF-1) axis and its impairment with sarcopenia, frailty, bone health, complications, and prognosis are not well characterized in cirrhosis., Methods: We investigated the adult decompensated cirrhosis out-patients at a tertiary care institute between 2021 and 2023 for serum GH and IGF-1 levels, and associated them with sarcopenia (CT-SMI in cm 2 /m 2 ), liver frailty index (LFI), osteodystrophy (DEXA), clinical decompensations (overall, ascites, encephalopathy, infection, and bleed), and survival up to 180 days., Results: One-hundred-seventy-two patients, 95% males, aged 46.5 years (median). log IGF-1 levels were negatively associated with sarcopenia, osteodystrophy, LFI, CTP, and MELD-Na score ( P  < 0.05 each). Patients with low IGF-1 levels had a higher incidence of complications (overall, ascites and encephalopathy) than those with intermediate, and high IGF-1 levels ( P  < 0.05 each). Both log IGF-1 (AUC: 0.686) and MELD (AUC: 0.690) could predict 180-day mortality ( P  < 0.05, each). Adding log IGF-1 with MELDNa further improved discriminative accuracy of MELDNa (AUC: 0.729) P  < 0.001. The increase in IGF-1 on follow-up was associated with better survival and fewer complications., Conclusion: Reduced IGF-1 levels reflect sarcopenia, frailty, and osteodystrophy in cirrhosis. Low IGF-1 are associated with severity, development of decompensations, and mortality., (© 2024 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Introduction: Hospitalized patients with acute decompensation (AD) of cirrhosis are at risk of progressing to acute-on-chronic liver failure (ACLF), significantly increasing their mortality. The aim of this study was to identify key predictors and patient trajectories predisposing to ACLF., Methods: In this multicenter, prospective study spanning 2 years, clinical, biochemical, and 90-day survival data were collected from 625 patients with AD (European Association for the Study of the Liver criteria) across North, South, and East India. We divided the cohort into a Derivation cohort (DC: 318 patients) and a Validation cohort (VC: 307 patients). Predictive models for pre-ACLF were derived, validated, and compared with established scores such as model for end-stage liver disease (MELD) 3.0 and chronic liver failure Consortium acute decompensation., Results: Of 625 patients (mean age 49 years, 83% male, 77.5% with alcohol-related liver disease), 32.2% progressed to ACLF. Patients progressing to ACLF showed significantly higher bilirubin (10.9 vs 8.1 mg/dL), leukocyte counts (9,400 vs 8,000 per mm 3 ), international normalized ratio (1.9 vs 1.8), and MELD 3.0 (28 vs 25) but lower sodium (131 vs 134 mEq/L) and survival (62% vs 86%) compared with those without progression ( P < 0.05) in the DC. Consistent results were noted with alcohol-associated hepatitis, infection and hepatic encephalopathy as additional risk factors in VC. Liver failure at presentation (odds ratio: 2.4 [in DC], 6.9 [in VC]) and the 7-day trajectories of bilirubin, international normalized ratio, and MELD 3.0 significantly predicted ACLF progression ( P < 0.001). A new pre-ACLF model showed superior predictive capability (area under the curve of 0.71 in DC and 0.82 in VC) compared with MELD 3.0 and chronic liver failure Consortium acute decompensation scores ( P < 0.05)., Discussion: Approximately one-third of AD patients in this Indian cohort rapidly progressed to ACLF, resulting in high mortality. Early identification of patients at risk can guide targeted interventions to prevent ACLF., (Copyright © 2024 by The American College of Gastroenterology.)

Background and Aims: Myokines are the muscle-derived hormones orchestrating muscle and systemic health. Their role in the progression of alcohol-associated liver disease (ALD) remains elusive., Methods: Three-hundred-one patients across the spectrum of ALD including fatty liver (FL, N = 13), compensated cirrhosis (CC, N = 17), non-acute decompensation (NAD, N = 95), acute decompensation (AD, N = 51) and acute-on-chronic liver failure (ACLF, N = 125) were recruited between 2021 and 2023. Plasma myostatin, decorin levels, nutritional status, handgrip strength (HGS), systemic inflammation, infection, ammonia, disease course and 30-day mortality were recorded., Results: Patients aged 48 years (IQR: 38-52) and 97.7% of males were enrolled. Myostatin was elevated while decorin was reduced in cirrhosis compared to without cirrhosis, and further in DC compared to CC (p < 0.001). A step-wise increase in myostatin and reduction in decorin was observed transitioning from NAD to AD to ACLF (p < 0.001). Myostatin was further increased and decorin was reduced along with the grades and organ failures in AD and ACLF (p < 0.001, each). Baseline decorin (AUC: 0.797) and its combination with MELD (AUC: 0.814) predicted disease resolution in AD and ACLF. Although, both myostatin (aOR: 18.96) and decorin (aOR: 0.02) could predict mortality, decorin was independent (aOR: 0.04) and additive to MELD (AUC of MELD+ log Decorin +  log TLC + HE-grade:0.815); p < 0.05 each. Myostatin increased and decorin reduced with inflammation, hyperammonaemia, malnutrition and HGS in AD and ACLF (p < 0.05, each)., Conclusion: Myokines are linked with malnutrition, fibrosis, systemic inflammation, organ failures, disease course and mortality in ALD. Decorin enhances the risk estimation of mortality of MELD in AD and ACLF. Therapeutic modulation of myokines is a potentially disease-modifying target in ALD., (© 2024 John Wiley & Sons Ltd.)