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Aims: Autoimmune liver diseases (AILD) represent a spectrum of related yet distinct immune-mediated disorders. The literature on the prevalence of these AILDs in Indian population is scarce. This study aims to assess the prevalence and clinicopathological spectrum of various AILDs especially the overlap syndrome. Materials and Methods: A 10-year (2011–2020) cross-sectional, retrospective observational study of histological proven cases of AILD was conducted. Clinical, demographic, and laboratory parameters were retrieved. Two pathologists independently reviewed the liver biopsies and reassessed 18 histopathological parameters. Results: During the study period, 17664 liver biopsies were received, out of which 1060 (6%) biopsies of AILD were identified. After exclusion, we had 721 cases which revealed a distribution of autoimmune hepatitis (AIH)-64.7%, primary biliary cholangitis (PBC)-14.8%, primary sclerosing cholangitis (PSC)-7.6%, overlap AIH-PBC 11%, and overlap AIH-PSC 1.7%. AIH patients had significantly higher prevalence for severe lobular inflammation (27%, P ≤ 0.001), several lobular plasma cells (37%, P ≤ 0.001), central perivenulitis (30%, P ≤ 0.001), hepatic rosettes (51%, P ≤ 0.001), and necrosis (35.5%, P ≤ 0.001), while PBC patients had significantly higher frequency of florid duct lesions (11.2%, P ≤ 0.001), duct loss (83.17%, P ≤ 0.001), bile duct damage (76.6%, P ≤ 0.001), and periportal copper deposits (19.6%, P ≤ 0.001). Overlap AIH-PBC group had the highest proportion of severe portal inflammation (27.5%, P ≤ 0.001), prominent portal plasma cells (75%, P ≤ 0.001), moderate interface activity (53.7%, P ≤ 0.001), Mallory-Denk bodies (27.5%, P ≤ 0.001), and periportal cholate stasis (25%, P ≤ 0.001). Conclusion: Prevalence of biopsy-proven AILDs in our study cohort is 6%. AIH (64.7%) is the most common AILD followed by PBC (14.8%). Overlap syndrome (AIH-PBC) showed prevalence of 11%.

Objectives Direct intrahepatic portosystemic shunt (DIPS) stent placement is an effective treatment for patients with Budd-Chiari syndrome (BCS); however, thrombotic occlusion of DIPS stent remains a cause of concern. The purpose of this study is to describe a novel technique of balloon-occluded-thrombolysis (BOT) for occluded DIPS stent, and compare it with the conventional catheter-directed-thrombolysis (CDT).

Background & Aims: Model for End-Stage Liver Disease (MELD) score better predicts mortality in alcohol-associated hepatitis (AH) but could underestimate severity in women and malnourished patients. Using a global cohort, we assessed the ability of the MELD 3.0 score to predict short-term mortality in AH. Methods: This was a retrospective cohort study of patients admitted to hospital with AH from 2009 to 2019. The main outcome was all-cause 30-day mortality. We compared the AUC using DeLong's method and also performed a time-dependent AUC with competing risks analysis. Results: A total of 2,124 patients were included from 28 centres from 10 countries on three continents (median age 47.2 ± 11.2 years, 29.9% women, 71.3% with underlying cirrhosis). The median MELD 3.0 score at admission was 25 (20–33), with an estimated survival of 73.7% at 30 days. The MELD 3.0 score had a better performance in predicting 30-day mortality (AUC:0.761, 95%CI:0.732–0.791) compared with MELD sodium (MELD-Na; AUC: 0.744, 95% CI: 0.713–0.775; p = 0.042) and Maddrey’s discriminant function (mDF) (AUC: 0.724, 95% CI: 0.691–0.757; p = 0.013). However, MELD 3.0 did not perform better than traditional MELD (AUC: 0.753, 95% CI: 0.723–0.783; p = 0.300) and Age-Bilirubin-International Normalised Ratio-Creatinine (ABIC) (AUC:0.757, 95% CI: 0.727–0.788; p = 0.765). These results were consistent in competing-risk analysis, where MELD 3.0 (AUC: 0.757, 95% CI: 0.724–0.790) predicted better 30-day mortality compared with MELD-Na (AUC: 0.739, 95% CI: 0.708–0.770; p = 0.028) and mDF (AUC:0.717, 95% CI: 0.687–0.748; p = 0.042). The MELD 3.0 score was significantly better in predicting renal replacement therapy requirements during admission compared with the other scores (AUC: 0.844, 95% CI: 0.805–0.883). Conclusions: MELD 3.0 demonstrated better performance compared with MELD-Na and mDF in predicting 30-day and 90-day mortality, and was the best predictor of renal replacement therapy requirements during admission for AH. However, further prospective studies are needed to validate its extensive use in AH. Impact and implications: Severe AH has high short-term mortality. The establishment of treatments and liver transplantation depends on mortality prediction. We evaluated the performance of the new MELD 3.0 score to predict short-term mortality in AH in a large global cohort. MELD 3.0 performed better in predicting 30- and 90-day mortality compared with MELD-Na and mDF, but was similar to MELD and ABIC scores. MELD 3.0 was the best predictor of renal replacement therapy requirements. Thus, further prospective studies are needed to support the wide use of MELD 3.0 in AH.

Hepatic arterioportal fistula (APF) in the setting of cirrhosis may aggravate the preexisting portal hypertension and its complications. Cirrhotic patients undergo various percutaneous invasive procedures and are at risk of developing an APF. These should be diagnosed early and should be treated accordingly at the earliest when indicated. Presently embolization is the treatment of choice with coil embolization as the most commonly used method. We describe four cases from our institute with a history of liver parenchymal disease and were found to have acquired APF on imaging. These were successfully managed with transarterial embolization with resolution or improvement in their clinical symptoms on follow-up. The present case series and review emphasize the importance of APF in the setting of liver parenchymal disease and the role of early diagnosis and therapeutic intravascular interventions.

Introduction and Objectives: Alcohol-associated hepatitis (AH) is a severe entity associated with high mortality. Corticosteroids might be used in cases with severe disease and several dynamic models can predict mortality and response to corticosteroids in AH patients. However, there is no consensus on the best of them. This study aimed to evaluate dynamic models to predict response to corticosteroid treatment based on short-term mortality in patients with severe AH based on a worldwide cohort. Materials and Methods: A retrospective cohort study of patients with severe AH (between 2009 – 2019). We included patients who received corticosteroid treatment and calculated the Lille model of day 4 (Lille-4), day 7 (Lille-7) (cut-off value ≥0.45), and the Trajectory of Serum Bilirubin (TSB)(cut-off value ≥0.8 of the ratio between bilirubin at admission and day 7) to predict mortality. We estimated up to 30-day survival using Kaplan-Meier curves, and we performed multivariable analyzes using Cox regression. Specifically, we constructed two models to compare Lille-4 vs. TSB and Lille-7 vs. TSB, adjusting by well-known clinical variables associated with higher mortality in AH (age, sex, and creatinine at admission). Results: 1,066 patients were included (30 centers, 10 countries), age 47.7 ± 10.9 years, 30% women. The MELD score on admission was 25 [21-30]. Responders were considered by Lille-4 49.1%, Lille-7 46.6%, and TSB 55.4%. In the first Cox regression, we observed that Lille-4 and TSB predicted 30-day mortality (HR 3.0, 95%CI: 1.7-5.1; p

Background: Cytomegalovirus (CMV) reactivation is known to occur among intensive care unit (ICU) patients. CMV-reactivation is not well-evaluated among critically ill cirrhotic adults who are not overtly immunocompromised. Objectives: Primary objective was to estimate the CMV-reactivation incidence rate among seropositive/latently infected critically ill cirrhotic adults. The secondary objective was to study the risk factors, host-related cytokine responses, and ICU outcomes associated with CMV-reactivation. Methods: In this longitudinal study conducted between November 2018 and June 2019, all consecutive anti-CMV-IgG-positive cirrhotic Liver-ICU patients were assessed at day 0/ICU-admission, day 7, 14, and 21 for CMV-reactivation/plasma-DNAemia (≥500 IU/ml), cytokines, clinical, laboratory and outcome parameters. Results: Fifty-five (48 male) cirrhosis patients consecutively admitted to liver-ICU were prospectively studied. Twenty (36%) adults developed CMV-reactivation. Majority (n=17/55, 30.9%; 95% CI: 19.1 - 44.8) showed CMV- reactivation on ICU-day 7. CMV-reactivation incidence rate during 21-day follow-up was 2.75% per person-day (95% CI: 1.68-4.26% per person-day). None of the risk factors studied was independently associated with CMV-reactivation. Acute respiratory distress syndrome (p=0.04), systemic inflammatory response syndrome (p=0.01), secondary (bacterial and/or fungal) infections (p=0.009), and raised pro-inflammatory cytokines (IFN γ, p=0.012; TNFα, p=0.052) were observed concomitantly to CMV-reactivation on ICU-day 7. ICU-Mortality (n=34/55, 61.8%) did not vary with a presence or absence of CMV-reactivation (55% versus 65.7%; p=0.43). Length of stay (LOS) in liver-ICU did not differ concerning CMV-reactivation (5 days versus 4.5 days; p=0.17) Conclusions: CMV-reactivation incidence rate was considerable among seropositive non-immunosuppressed critically ill cirrhotic adults. Mortality and LOS in Liver-ICU were not significantly influenced by CMV-reactivation.

ObjectiveThe monocyte–macrophage system is central to the host’s innate immune defense and in resolving injury. It is reported to be dysfunctional in acute-on-chronic liver failure (ACLF). The disease-associated alterations in ACLF monocytes are not fully understood. We investigated the mechanism of monocytes’ functional exhaustion and the role of umbilical cord mesenchymal stem cells (ucMSCs) in re-energizing monocytes in ACLF.DesignMonocytes were isolated from the peripheral blood of ACLF patients (n = 34) and matched healthy controls (n = 7) and patients with compensated cirrhosis (n = 7); phagocytic function, oxidative burst, and bioenergetics were analyzed. In the ACLF mouse model, ucMSCs were infused intravenously, and animals were sacrificed at 24 h and day 11 to assess changes in monocyte function, liver injury, and regeneration.ResultsPatients with ACLF (alcohol 64%) compared with healthy controls and those with compensated cirrhosis had an increased number of peripheral blood monocytes (p < 0.0001) which displayed significant defects in phagocytic (p < 0.0001) and oxidative burst capacity (p < 0.0001). ACLF patients also showed a significant increase in the number of liver macrophages as compared with healthy controls (p < 0.001). Bioenergetic analysis showed markedly reduced oxidative phosphorylation (p < 0.0001) and glycolysis (p < 0.001) in ACLF monocytes. Patients with monocytes having maximum mitochondrial respiration of

A complication of transjugular and direct intrahepatic portosystemic stent (TIPS and DIPS) graft is stent blockage. Routinely described procedures for shunt revision include angioplasty, deployment of endoprosthesis, catheter-directed thrombolysis, or rarely performing a second parallel TIPS/DIPS. We describe a case of hepatic vein outflow tract obstruction who presented with DIPS blockage. We performed a revision where a new stent was placed by a lateral puncture through the fenestration of the existing dysfunctioning DIPS stent graft. In our opinion, this alternate technique has theoretical advantages over the conventionally described parallel TIPS/DIPS as it prevents the creation of a completely new long hepatic parenchymal tract.

Hyperoxidized albumin promotes inflammation and modulates several immune cells in severe alcoholic hepatitis (SAH). Platelets mediate inflammation by interacting with immune cells, endothelium, and other cells. The role of hyperoxidized albumin in platelet activation and alteration of platelet phenotype/functions is not known. Quantitative platelet proteomics performed in 10 patients with SAH was compared with 10 patients with alcoholic cirrhosis and 10 healthy controls, respectively. Dysregulated pathways were identified and validated in a separate cohort (n = 40). Healthy platelets were exposed to patient plasma or purified albumin or ex vivo modified albumin (human‐mercaptalbumin, humannonmercaptalbumin‐1, and human nonmercaptalbumin 2) in the presence or absence of CD36 blockade, and platelet secretome was analyzed. Two hundred and two up‐regulated proteins linked to platelet activation, complement regulation, lipid transportation, and 321 down‐regulated proteins related to platelet hemostasis and coagulation (fold change ± 1.5, P 0.3, P

Purpose: To study the prevalence of back pain in patients of Budd–Chiari syndrome (BCS) with inferior vena cava (IVC) obstruction, and to evaluate the role of IVC recanalization in resolution of back pain. Methods: All patients with BCS and IVC obstruction who underwent IVC recanalization between January 2018 and October 2022 were included. Patients with degenerative spine disease or other identifiable causes for back pain were excluded; remaining patients were assessed for the presence of back pain. In patients with back pain, pain relief was assessed at 24 h following IVC recanalization. Results: Fifty-eight patients with BCS and IVC occlusion were identified, of which six with degenerative spine diseases were excluded. Of the remaining 52 patients, 34 (65.4%) had back pain, with pain score between 3 and 9. Engorged epidural venous plexus on preprocedural imaging (p = 0.002), and degree of luminal narrowing (p = 0.021) had a significant association with back pain. Twenty-nine of thirty-four patients (85.3%) with back pain had pain relief immediately following IVC recanalization, more so in patients with engorged epidural venous plexus on preprocedural imaging (p < 0.001). Conclusion: Back pain is one of the under-reported symptoms of IVC obstruction in BCS. IVC recanalization by IVC angioplasty with or without stenting relieves back pain due to the decompression of engorged epidural veins.

Background Mechanical ventilation in cirrhosis with acute respiratory distress syndrome (ARDS) is not widely studied. We aimed to study the effect of the staircase recruitment manoeuvre followed by two different modes of ventilation. Methods Thirty patients with cirrhosis with moderate ARDS underwent the staircase recruitment manoeuvre followed by randomisation to volume control or pressure control group. Results The PaO~2~/FiO~2~ ratio showed a significant improvement in both the groups after recruitment. The improvement was significantly higher in the pressure control ventilation (PCV) group at the end of the first hour as compared to the volume control ventilation (VCV) group. However, this difference was not significant at the end of 6 and 12 h. In the PCV group it improved from 118.47 ± 10.21 at baseline to 189.87 ± 55.18 12 h post-recruitment. In the VCV group it improved from 113.79 ± 13.22 at baseline to 180.93 ± 81.971. Static lung compliance also improved in both the groups significantly (P \< 0.001). The PCV group showed an improvement from 25.42 ± 11.94 mL/cm H~2~O at baseline to 29.51 ± 14.58 mL/cm H~2~O. In the VCV group the lung compliance improved from 24.78 ± 4.87 mL/cm H~2~O to 31.31 ± 10.88 mL/cm H~2~O. Conclusion This study shows that stepwise recruitment manoeuvre is an effective rescue therapy to improve oxygenation in cirrhosis with moderate ARDS. PCV may have an advantage over VCV in terms of better oxygenation.

BACKGROUND: Clinical significance of respiratory viruses (RVs) as an etiology of pneumonia in liver disease patients with cirrhosis is usually underestimated. Therefore, the aim of this study was to evaluate the spectrum of RVs in cirrhotic patients with pneumonia admitted in critical care units (CCUs) and its impact on the clinical outcome of cirrhotic patients. MATERIAL AND METHOD: A prospective study was conducted in a tertiary care CCU, and consecutive cirrhotic patients with pneumonia were included. Bronchoalveolar lavage or throat swab/nasal swab was collected in viral transport medium for analysis of RVs by multiplex real-time polymerase chain reaction. A total of 135 cirrhotic patients were included, viral and bacterial etiology of pneumonia was identified, and analysis was done with the clinical outcome. RESULTS: Overall, RVs were detected in 30 (22.2%) cirrhotic patients and viral–bacterial coinfection in 16 (11.8%) cirrhotic patients. The most common virus detected was rhinovirus in 9 (30%) patients. Mortality in cirrhotic patients with RV infection was significantly higher in comparison to cirrhotic patients with no RV infection (25 [83.3%] and 11 [12.3%], respectively, P < 0.001). CONCLUSION: Respiratory viruses in cirrhotic patients with pneumonia are associated with poor clinical outcome.

Background/Aims The aim of this study was to study the efficacy and safety of zolpidem for sleep disturbances in patients with cirrhosis. Methods Fifty-two Child-Turcotte-Pugh (CTP) class A or B cirrhotics with Pittsburgh Sleep Quality Index >5 were randomized to either zolpidem 5 mg daily (n=26) or placebo (n=26) for 4 weeks. Results The therapy of 4 weeks was completed by 23 patients receiving zolpidem (3 stopped treatment due to excessive daytime drowsiness) and 24 receiving placebo (2 refused to continue the study). In the zolpidem group, after 4 weeks of therapy, there was significant increase in total sleep time (TST) and sleep efficiency compared to baseline and improvement in polysomnographic parameters of sleep initiation and maintenance (i.e., decrease in sleep latency time, decrease in wake time, and decreases in number of arousals and periodic limbs movements per hour of sleep), without any significant change in sleep architecture. Conclusions Four weeks of 5 mg daily zolpidem in CTP class A or B cirrhosis patients with insomnia led to significant increases in TST and sleep efficiency and improvement in polysomnographic parameters of sleep initiation and maintenance without any significant change in sleep architecture.

Hepatic hydrothorax (HH) is an infrequent but a well-known complication of portal hypertension. Medical management of this condition often fails, and there are no large randomized-controlled trials establishing the best treatment strategies. HH thus represents a formidable entity in the management of end-stage liver disease, and the only definitive treatment is liver transplantation. Despite documented ominous outcome, tube thoracostomy (TT) is still a widely practiced approach to HH mostly by the unaware primary care physician. This communication reports the occurrence of pleurosubcutaneous fistula as a presenting complication of TT in a patient with HH. TT should thus be avoided at all costs in this subset of patients because it is fraught with multiple complications. This report reinforces the importance of clinical education and awareness of these complications and outcomes of TT in a cirrhotic patient with HH.

Extrahepatic portal vein obstruction is a vascular disorder of liver, which results in obstruction and cavernomatous transformation of portal vein with or without the involvement of intrahepatic portal vein, splenic vein, or superior mesenteric vein. Portal vein obstruction due to chronic liver disease, neoplasm, or postsurgery is a separate entity and is not the same as extrahepatic portal vein obstruction. Patients with extrahepatic portal vein obstruction are generally young and belong mostly to Asian countries. It is therefore very important to define portal vein thrombosis as acute or chronic from management point of view. Portal vein thrombosis in certain situations such as liver transplant and postsurgical/liver transplant period is an evolving area and needs extensive research. There is a need for a new classification, which includes all areas of the entity. In the current review, the most recent literature of extrahepatic portal vein obstruction is reviewed and summarized.

Gastric varices (GV) are responsible for 10-30% of all variceal hemorrhage. However, they tend to bleed more severely with higher mortality. Around 35-90% rebleed after spontaneous hemostasis. Approximately 50% of patients with cirrhosis of liver harbor gastroesophageal varices. In this review, new treatment modalities in the form of endoscopic treatment options and interventional radiological procedures have been discussed besides discussion on classification and pathophysiology of GV.

Background/Aims: Literature regarding safe doses of carvedilol is limited, and safe doses across different Child classes of chronic liver disease are not clear. Patients and Methods: A total of 102 consecutive cirrhotic patients with significant portal hypertension were included in this study. Hepatic venous pressure gradient was measured at baseline and 3 months after dose optimization. Results: A total of 102 patients (63 males, 39 females) with a mean age of 58.3 ± 6.6 years were included. Among these patients, 42.2% had Child Class A, 31.9% had Class B, and 26.6% had Child Class C liver disease. The mean baseline hepatic venous pressure gradient was 16.75 ± 2.12 mmHg, and after dose optimization and reassessment of hepatic venous pressure gradient at 3 months, the mean reduction in the hepatic venous pressure gradient was 5.5 ± 1.7 mmHg and 2.8 ± 1.6 mmHg among responders and nonresponders respectively. The mean dose of carvedilol was higher in nonresponders (19.2 ± 5.7 mg) than responders (18.75 ± 5.1 mg). However, this difference was not statistically significant (P > 0.05). The univariate analysis determined that the absence of adverse events, the absence of ascites, and low baseline cardiac output were significantly associated with chronic response, whereas, the etiology, Child class, variceal size (large vs small), and gender were not. On multivariate analysis, the absence of any adverse event was determined to be an independent predictor of chronic response (OR 11.3, 95% CI; 1.9–67.8). Conclusion: The proper optimization of the dose of carvedilol, when administered chronically, may enable carvedilol treatment to achieve a greater response with minimum side effects among different Child classes of liver disease.

Background: Acute viral hepatitis E (AVH-E) can often result in acute liver failure (ALF) during pregnancy. microRNAs serve as mediators in drug induced liver failure. We investigated their role as a biomarker in predicting ALF due to HEV (ALF-E). Methods: We performed next generation sequencing and subsequent validation studies in PBMCs of pregnant (P) self limiting AVH-E, ALF due to HEV (ALF-E) and compared with AVH-E in non-pregnant (NP) females and healthy controls. Findings: Eleven microRNAs were significantly expressed in response to HEV infection; importantly, miR- 431, 654, 1468 and 4435, were distinctly expressed in pregnant self-limiting AVH-E and healthy females (p = 0.0005), but not in ALF-E. Sixteen exclusive microRNAs differentiated ALF-E from self limiting AVH-E in pregnant females. miR-450b which affects cellular proliferation and metabolic processes through RNF20 and SECB was predominanlty upregulated and correlated with poor outcome (ROC 0.958, p = 0.001). Interpretation: Our results reveal that a specific microRNA profile can predict fatality in ALF-E in pregnancy. These microRNAs could be exploited as prognostic biomarkers and help in the development of new therapeutic interventions.

Background: Liver biopsy plays a crucial role in evaluating allograft dysfunction. Comprehensive analysis of the histological spectrum of complications, particularly rejection, in different time zones is lacking. Aim: To evaluate the histological spectrum of rejection, in four time zones, in a large Living donor liver transplant series. Patients and Methods: Retrospective analysis of 313 biopsies for the last 10 years of living donor liver transplantation (LDLT) recipients. 123 of which had rejection as diagnosis, were redistributed in four time zones [1-early ( 12) months] and were assessed for sixteen histological parameters. Results: Biopsies in time zone 1 (26.5%), 2 (20.7%), 3 (24.6%), and 4 (28.1%)] were nearly equal. Multiple coexistent complications existed in 12% of the cases. Rejection diagnosed in time zone groups: 1 = 22 (17.9%), 2 = 27 (22%), 3 = 36 (29.3%), and 4 = 38 (30.9%). Portal inflammation mixed type (P < 0.000), portal vein (P = 0.001) and hepatic vein endothelialitis (P < 0.000), portal eosinophils (P = 0.001), and lymphocytic bile duct damage (P = 0.01) were most pronounced in group 1. Perivenulitis without hepatic vein endothelialitis was observed (P = 0.03) in groups 3, whereas bile duct atypia (P = 0.01) and duct loss (P < 0.000) were observed in group 4. Multiple episodes of rejection displayed significant association with central perivenulitis (P = 0.002) and bile duct loss (P < 0.001). Conclusions: Histological analysis in large series of LDLT recipients highlights the spectrum of complications in different time zones. Late acute and chronic rejection occurred as early as 3 months posttransplant. Central perivenulitis and bile duct atrophy were associated with repeated episodes of rejection and deterioration.

Abstract Patients with acute‐on‐chronic liver failure (ACLF) have a high probability of developing systemic inflammation and sepsis due to immune dysregulation. Fifty‐nine patients with ACLF (12 without and 19 with systemic inflammation, and 28 with sepsis) were serially monitored for clinical and immunological changes at baseline, 6 hours, 24 hours, day 3, and day 7 following hospitalization. Ten healthy controls were also included. At all time points, soluble plasma factors and monocyte functions were studied. Patients with ACLF and systemic inflammation showed higher interleukin (IL)–6, vascular endothelial growth factor‐a, monocyte chemoattractant protein 1, and macrophage inflammatory protein 1β than patients with no systemic inflammation. Patients with ACLF with sepsis had raised (p

Introduction: Transfusion in cirrhotic patients remains a challenge due to the absence of evidence-based guidelines. Our study aimed to determine the indication of transfusion and the associated transfusion thresholds in cirrhotic patients. Methods: This retrospective observational study was conducted in the Department of Transfusion Medicine at a tertiary care liver center from October 2018 to March 2019. The blood bank and patient records of cirrhotic patients admitted during the study period were retrieved and analyzed to determine the current transfusion practice. Results: A total of 992 cirrhotic patients were included in the study. Blood components were transfused to 402 (40.5%) patients. Sixty-nine (17.2%) patients were transfused to control/treat active bleeding, while 333 (82.8%) were transfused prophylactically. Packed red blood cells (65.4%) was the most commonly transfused blood component, followed by fresh frozen plasma (35.6%), among patients receiving transfusions (therapeutic & prophylactic). The mean pre-transfusion thresholds for: (i) packed red blood cell transfusion: hemoglobin less than 7 g/dL; (ii) fresh frozen plasma transfusion: international normalized ratio over 2.6; (iii) platelet concentrate transfusion: platelet count less than 40,700/μL, and; (iv) cryoprecipitate transfusion: fibrinogen less than 110 mg/dL. The average length of stay of the study population was 5 days (3–9). Conclusion: To conclude, 40.5% of our hospitalized cirrhotic patients were transfused, with the majority of the transfusions being prophylactic (82.8%). Separate guidelines are required for this patient population, as these patients have an altered hemostasis which responds differently to the transfusion of blood components.

The relevance of hemodynamic derangements on the incidence of recurrent acute kidney injury (AKI) and chronic kidney disease (CKD) in patients with cirrhosis is largely unknown. Consecutive patients with cirrhosis with a complete record of baseline hemodynamics were followed for identifying risk factors for the development of recurrent AKI and CKD by using negative binomial regression and competing risk analysis, respectively. Consecutive patients with cirrhosis (n = 2013, age 50.1 ± 11.8 years, 80% male, Child A:B:C percentage 13.7:52.9:33.4, and mean Child‐Turcotte‐Pugh score 8.6 ± 1.8) were enrolled, 893 (44.3%) of whom received beta‐blockers, with 44.2% responders. Prior AKI was noted in 12.4% at enrollment. At a median follow‐up of 379 (interquartile range: 68‐869) days, AKI developed at a rate of 0.37 episodes per person‐year, and 26% patients developed CKD. A lower mean number of AKI episodes (0.05 ± 0.25 vs. 0.42 ± 0.868; P

Background/Aims Liver cirrhosis is an important cause of morbidity and mortality globally. Every episode of decompensation and hospitalization reduces survival. We studied the clinical profile and long-term outcomes comparing alcohol-related cirrhosis (ALC) and non-ALC. Methods Cirrhosis patients at index hospitalisation (from January 2010 to June 2017), with ≥1 year follow-up were included. Results Five thousand and one hundred thirty-eight cirrhosis patients (age, 49.8±14.6 years; male, 79.5%; alcohol, 39.5%; Child-A:B:C, 11.7%:41.6%:46.8%) from their index hospitalization were analysed. The median time from diagnosis of cirrhosis to index hospitalization was 2 years (0.2–10). One thousand and seven hundred seven patients (33.2%) died within a year; 1,248 (24.3%) during index hospitalization. 59.5% (2,316/3,890) of the survivors, required at least one readmission, with additional mortality of 19.8% (459/2,316). ALC compared to non-ALC were more often (P

BackgroundDecompensated cirrhosis patients are more prone to bacterial infections. Myeloid-derived suppressor cells (MDSCs) expand in sepsis patients and disrupt immune cell functions. Granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy helps in restoring immune cell functions and resolving infections. Its role in MDSC modulation in cirrhosis with sepsis is not well understood.MethodsA total of 164 decompensated cirrhotic—62 without (w/o), 72 with sepsis, and 30 with sepsis treated with GM-CSF—and 15 healthy were studied. High-dimensional flow cytometry was performed to analyze MDSCs, monocytes, neutrophils, CD4 T cells, and Tregs at admission and on days 3 and day 7. Ex vivo co-cultured MDSCs with T cells were assessed for proliferation and apoptosis of T cells and differentiation to Tregs. Plasma factors and mRNA levels were analyzed by cytokine-bead assay and qRT-PCR.ResultsFrequencies of MDSCs and Tregs were significantly increased (p = 0.011 and p = 0.02) with decreased CD4 T cells (p = 0.01) in sepsis than w/o sepsis and healthy controls (HCs) (p = 0.000, p = 0.07, and p = 0.01) at day 0 and day 7. In sepsis patients, MDSCs had increased IL-10, Arg1, and iNOS mRNA levels (p = 0.016, p = 0.043, and p = 0.045). Ex vivo co-cultured MDSCs with T cells drove T-cell apoptosis (p = 0.03, p = 0.03) with decreased T-cell proliferation and enhanced FOXP3+ expression (p = 0.044 and p = 0.043) in sepsis compared to w/o sepsis at day 0. Moreover, blocking the MDSCs with inhibitors suppressed FOXP3 expression. GM-CSF treatment in sepsis patients significantly decreased MDSCs and FOXP3+ Tregs but increased CD4 T-cell functionality and improved survival.ConclusionMDSCs have an immunosuppressive function by expanding FOXP3+ Tregs and inhibiting CD4+ T-cell proliferation in sepsis. GM-CSF treatment suppressed MDSCs, improved T-cell functionality, and reduced Tregs in circulation.

Background & Aims: Endothelial injury and dysfunction play a detrimental role in the pathogenesis of infections. Endothelium-related molecules have been reported as potential diagnostic and/or prognostic biomarkers of infection. The prognostic value of these biomarkers in patients with cirrhosis and infections remains elusive. Methods: In this study, we investigated the performance of key soluble endothelial injury biomarkers, including intercellular adhesion molecule 1 (ICAM1), von Willebrand factor (vWF), vascular endothelial growth factor receptor 1 (VEGFR1), and angiopoietin 1 and 2 (Ang1, 2) as mortality predictors in patients with cirrhosis and severe COVID-19 or bacterial sepsis. Results: A total of 66 hospitalized patients (admitted to the COVID-19 ward or liver intensive care unit [ICU]) were included. Twenty-two patients had COVID-19 alone, while 20 patients had cirrhosis plus COVID-19. Twenty-four patients had cirrhosis plus bacterial sepsis. Among patients with cirrhosis, the most common aetiology of liver disease was alcohol. ICAM1 was increased (p = 0.003) while VEGFR1 (p

Decompensated cirrhosis (DC) is susceptible to infections and sepsis. Neutrophils and monocytes provide the first line of defense to encounter infection. We aimed to evaluate proteins related to neutrophils functionality in sepsis. 70 (DC), 40 with sepsis, 30 without (w/o) sepsis and 15 healthy controls (HC) plasma was analyzed for proteomic analysis, cytokine bead array, endotoxin, cell free DNA and whole blood cells were analyzed for nCD64-mHLADR index, neutrophils-monocytes, functionality and QRT-PCR. nCD64-mHLADR index was significantly increased (p < 0.0001) with decreased HLA-DR expression on total monocytes in sepsis (p = 0.045). Phagocytic activity of both neutrophils and monocytes were significantly decreased in sepsis (p = 0.002 and p = 0.0003). Sepsis plasma stimulated healthy neutrophils, showed significant increase in NETs (neutrophil extracellular traps) and cell free DNA (p = 0.049 and p = 0.04) compared to w/o sepsis and HC. Proteomic analysis revealed upregulated- DNAJC13, TMSB4X, GPI, GSTP1, PNP, ANPEP, COTL1, GCA, APOA1 and PGAM1 while downregulated- AHSG, DEFA1,SERPINA3, MPO, MMRN1and PROS1 proteins (FC > 1.5; p < 0.05) associated to neutrophil activation and autophagy in sepsis. Proteins such as DNAJC13, GPI, GSTP1, PNP, ANPEP, COTL1, PGAM1, PROS1, MPO, SERPINA3 and MMRN1 showed positive correlation with neutrophils activity and number, oxidative burst activity and clinical parameters such as MELD, MELD Na and Bilirubin. Proteomic analysis revealed that faulty functionality of neutrophils may be due to the autophagy proteins i.e., DNAJC13, AHSG, TMSB4X, PROS1 and SERPINA3, which can be used as therapeutic targets in decompensated cirrhosis patients with sepsis.