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Background: Hepatocellular cancer (HCC) typically arises in the background of cirrhosis. Its epidemiology has been changing due to availability of antivirals, changing life-styles and early detection. We undertook a multicentric national sentinel surveillance for liver cirrhosis and HCC to assess the attributable risk factors for development of HCC, both with and without a background of cirrhosis. Methods: Data from January 2017 till August 2022 from hospital-based records of eleven participating centres was included. Diagnosed cases of cirrhosis [radiological (multiphase and/or histopathological] and HCC [as per AASLD 2018] were included. History of significant alcohol intake was elicited by AUDIT-C questionnaire. Results: Altogether 5798 enrolled patients were assessed, of which 2664 patients had HCC. The mean age was 58.2±11.7 years and 84.3% (n=2247) were males. Diabetes was found in over a third of those with HCC (n=1032;39.5%). The most common etiology of HCC was NAFLD (n=927;35.5%) followed by viral hepatitis B and C and harmful levels of alcohol. Among those with HCC, 27.9% (n=744) had no cirrhosis. Higher proportion of cirrhotic HCC patients had alcohol as an etiological factor as compared to non-cirrhotic (17.5% Vs 4.7%, p= 60 years, 1.372 times for males and 3.472 times for harmful alcohol consumption. Those with NAFLD were 1.553 times more likely to develop non-cirrhotic HCC. Conclusion: This large multi-centric study demonstrates that NAFLD is the most important risk factor for development of both cirrhotic and non-cirrhotic HCC in India and has overtaken viral hepatitis. Awareness campaigns and large-scale screening are required to reduce the high burden of NAFLD related HCC in India.

Acute-on-chronic liver failure (ACLF) is a severe form of alcoholic hepatitis (SAH). We aimed to study the natural course, response to corticosteroids (CS), and the role of the Asian Pacific Association for the Study of Liver (APASL) research consortium (AARC) score in determining clinical outcomes in AH patients.Prospectively collected data from the AARC database were analyzed.Of the 1249 AH patients, (aged 43.8 ± 10.6 years, 96.9% male, AARC score 9.2 ± 1.9), 38.8% died on a 90 day follow-up. Of these, 150 (12.0%) had mild-moderate AH (MAH), 65 (5.2%) had SAH and 1034 (82.8%) had ACLF. Two hundred and eleven (16.9%) patients received CS, of which 101 (47.87%) were steroid responders by day 7 of Lille's model, which was associated with improved survival [Hazard ratio (HR) 0.15, 95% CI 0.12-0.19]. AARC-ACLF grade 3 [OR 0.28, 0.14-0.55] was an independent predictor of steroid non-response and mortality [HR 3.29, 2.63-4.11]. Complications increased with degree of liver failure [AARC grade III vs. II vs I], bacterial infections [48.6% vs. 37% vs. 34.7%; p 0.001); extrahepatic organ failure [66.9% vs. 41.8% vs. 35.4%; p 0.001] respectively. The AARC score better discriminated 90-day mortality. Harrell's C-index was 0.72 compared to other scores.Nearly 4 of 5 patients with AH present with ACLF. Such patients have a higher risk of infections, organ failures, lower response to CS, and higher mortality. Patients with AH and ACLF with AARC grade 3 should be considered for an early liver transplant.

Continuous infusion of terlipressin is better tolerated, and equally effective at lower doses than intravenous boluses in type 1 hepatorenal syndrome. This approach in cirrhosis patients with acute esophageal variceal bleed was investigated by comparing the efficacy and adverse events of continuous versus bolus administration of terlipressin.One hundred ten consecutive cirrhosis patients with acute esophageal variceal bleed (AEVB) were randomized to receive either terlipressin as bolus (BOL, n = 55), 2 mg every 4 h, or, continuous infusion (CONI, n = 55), 4 mg/24 h for 5 days. Hepatic venous pressure gradient (HVPG) was measured at baseline, 12 and 24 h and response to terlipressin was defined as 10% decline from baseline.Baseline demographics, model for end-stage liver disease (MELD) and HVPG were comparable between groups. The primary objective of HVPG response at 24 h was achieved in significantly more patients in CONI than BOL group {47/55(85.4%) vs. 32/55(58.2%), p = 0.002}. Early HVPG response at 12 h was also higher in CONI group (71.5 vs. 49.1%, p 0.01). Median dose of terlipressin was significantly lower {4.25 ± 1.26 mg vs. 7.42 ± 1.42 mg/24 h, p 0.001)} and adverse events were fewer {20/55(36.3%) vs. 31/55(56.4%), p = 0.03} in the CONI than BOL group. Significantly higher incidence of very early rebleed was noted in BOL group {8/55 (14.5%) vs. 1/55, (1.8%), p = 0.03}. Baseline HVPG (OR 1.90, 95% CI = 1.25-2.89, p = 0.002) and MELD (OR 1.18, 95% CI = 0.99-1.41, p = 0.05) were predictors of rebleed."HVPG-tailored" continuous terlipressin infusion is more effective than bolus administration in reducing HVPG at a lower dose with fewer adverse events in cirrhotic patients.NCT02695862.

Hepatitis B surface antigen (HBsAg) seroconversion is sometimes observed in hepatitis B reactivation (rHBV), probably due to immune resetting and differentiation.To investigate sequential immune differentiation and abrogation of tolerance in patients with rHBV who achieved HBsAg seroconversion.We included 19 patients with chronic hepatitis B (CHBV; HBV DNA log10At 24 weeks, 81% rHBV (n = 67) lost HBV DNA and HBeAg (41%), and 12 (19%) lost HBsAg and made anti-HBs titers10 IU/ml. rHBV patients had higher Th1/17, TNon-seroconverters have increased inhibitory markers on CD4/CD8 T cells. There is a critical play of CD8, Tfh and B cells and subsets in seroclearance, along with checkpoint molecules as a potential therapy for non-seroconverters in HBV infection.

Dynamic assessment of critically ill patients with cirrhosis (CICs) is required for accurate prognostication.Development of a dynamic model for prediction of mortality and decision on futility of care in CICs.In a prospective cohort study, we developed the PIRO-CIC model (predisposition, injury, response, organ failure for critically ill cirrhotics)] in a derivative cohort (n = 360) and validated it (n = 240) for patients admitted to the Liver ICU.Decompensated cirrhosis admitted to ICU. The model was developed using Cox-regression analysis, and futility was performed by decision-curve analysis.CICs aged 48 ± 11.5 years, 87% males, majority being alcoholics, were enrolled, of which 73.5% were alive at one month. Factors significant for P component were INR [hazard ratio 1.12, 95% confidence interval 1.07-1.18] and CystatinC [2.25, 1.70-2.97]; for I component were sepsis [4.69, 1.90-11.57], arterial lactate[1.40, 1.02-1.93] and alcohol as etiology [2.78, 1.85-4.18]; for R component-systemic inflammatory response syndrome [1.97, 1.14-3.42] and urine neutrophil-gelatinase-associated lipocalin [HR 2.37, 1.59-3.53]; for O component-low PaO2/FiO2 ratio and need of mechanical ventilation [7.41, 4.63-11.86]. The PIRO-CIC model predicted one-month mortality with a C-index of 0.83 in the derivation and 0.80 in the validation cohorts. It predicted futility of care better than other prognostic scores. The immediate risk of mortality increased by 39% with each unit increase in PIRO-CIC score.Not applicable for acute-on-chronic liver failure and patients requiring emergency liver transplant.Assessment and stratification of CICs with the dynamic PIRO-CIC model could determine one-month mortality and futility in the first week. Targeted and aggressive management of coagulation, kidneys, sepsis, and severe systemic inflammation may improve outcomes of CICs.

Whether non-selective β-blockers can prevent decompensation of cirrhosis needs clarification. Carvedilol might be particularly effective since its intrinsic vasodilatory activity may ameliorate hepatic vascular resistance, a major mechanism of portal-hypertension in early cirrhosis. We assessed whether carvedilol may prevent decompensation and improve survival in compensated cirrhosis with clinically significant portal hypertension (CSPH). METHODS By systematic review we identified RCTs comparing carvedilol vs control therapy (no-active treatment or EVL) in patients with cirrhosis and CSPH without previous bleeding. We performed a competing-risk time-to-event meta-analysis using individual patient data (IPD) obtained from principal investigators of RCTs. Only compensated patients were included. Primary outcomes were prevention of decompensation (OLT and death were competing-events) and death (OLT, competing-event). Models were adjusted using propensity score for baseline covariates with the IPTW approach. RESULTS Among 125 full-text studies evaluated, 4 RCTs were eligible. The four provided IPD and were included, comprising 352 patients with compensated cirrhosis, 181 treated with carvedilol and 171 controls (79 received EVL and 92 placebo). Baseline characteristics were similar between groups. Standardized differences were

To evaluate role of perfluorobutane in guiding microwave ablation of HCC and to compare treatment response at 3 h of ablation using contrast-enhanced US (CEUS) with Sonazoid with 1-month follow-up contrast-enhanced CT/MRI.This was a single center prospective study and consecutive patients planned for microwave ablation of HCC from October to November 2021 were enrolled. Pre-procedure CEUS were performed using Sonazoid in both vascular and Kupffer phase and number of Kupffer defects compared with gray scale US. Precise needle placement of microwave applicator was done in the Kupffer phase. 3 hours post ablation CEUS was repeated to evaluate response assessment using Liver Imaging Reporting and Data System Treatment Response criteria (LR TR). One-month follow-up imaging was done using multiphasic CECT/dynamic CEMRI and comparison was done with post procedure CEUS.Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 5 Given name: [Manoj Kumar] Last name [Sharma]. Author 6 Given name: [Shiv Kumar] Last name [Sarin]. Also, kindly confirm the details in the metadata are correct. all the names and affiliations are correct RESULTS: A total of 26 patients (24 males and 2 females, mean age 61.38 ± 9.76 years) having 40 lesions, of mean tumor diameter 21.4 ± 7.7 mm, underwent CEUS and ablation. Most common etiology for cirrhosis was viral hepatitis, followed by non-alcoholic steatohepatitis (NASH). Four (10%) additional lesions (which were seen on pre-procedure imaging) were detected in Kupffer phase over gray scale US. All lesions showed complete response in the immediate post procedure CEUS. Technique efficacy at 1-month was 95% according to the LR TR criteria.Please check the edit made in article title and amend if necessary.The edit is correct and appropriatePlease check and confirm that the authors and their respective affiliations have been correctly identified and amend if necessary.All the names and their respective affiliations are correct CONCLUSION: CEUS with Sonazoid is an excellent modality for precise needle placement for ablation due to stable nature and excellent lesion visibility of Kupffer phase.

Objective: To assess the efficacy and outcomes of percutaneous ablative therapies for hepatocellular carcinoma (HCC) in the caudate lobe. Methods: Patients within Milan criteria, who underwent thermal ablation (RFA/MWA) for HCC were analyzed. Based on the inclusion-criteria, patients were categorized in two groups. Group-1 (caudate-lobe HCC) and Group-2 (non-caudate-lobe HCC). Both the groups were analyzed for technical success (TS), local tumor progression (LTP), disease-free survival (DFS), and overall survival (OS) were compared between both the groups. Predictive factors for LTP, DFS, or OS in the study cohort were analyzed using appropriate statistical analyses. Results: Twenty-one patients qualified to be in Group-1 while 130 patients fulfilled the criteria for Group-2. TS of 90.5 and 97.7% was seen after the first session of ablation for Group-1 and group-2 respectively, while a TS of 95.2% (Group-1) and 100% (Group-2) was achieved after second session. The right-intercostal-approach was used in 66.7% (n = 14) and the anterior-epigastric-approach was used in 33.3% (n = 7) of patients having caudate-lobe HCC. Procedure-related complications in both the groups were comparable. Although, statistically insignificant, LTP in the Group-1 (19.5%, n = 4) was twice that of non-caudate lobe HCC (8.5%, n = 11). The cumulative DFS rate was better in Group-2 while OS in both groups were comparable. Multivariate analysis showed: tumor size and ablative margin of 5 mm being independent predictors of LTP after percutaneous-ablation of caudate-lobe HCC. Conclusion: Ablative therapies for HCC in caudate lobe is feasible and safe with comparable LTP and OS to non-caudate lobe HCC. Tumor size >2 cm and lack of 5 mm ablative margin are independent predictors of LTP. Advances in knowledge: 1. Percutaneous ablation of caudate lobe HCC is feasible using anterior epigastric approach or right intercostal approach. 2. These approaches may allow a safe and effective ablation of caudate lobe HCC with results comparable to non-caudate HCC ablation.

BackgroundPregnancy being immune compromised state, COVID-19 disease poses high risk of premature delivery and threat to fetus. Plasma metabolome regulates immune cellular responses and we aimed to analyze the plasma secretome, metabolome and immune cells in COVID-19 positive pregnant mother and cord blood.MethodsCOVID-19 RT-PCR positive pregnant females (n=112) asymptomatic (n=82), or with mild (n=21) or moderate (n=9) disease and control healthy pregnant (n=10) females were included. Mother’s blood and cord blood (n=80) was analysed for untargeted metabolome profiling and plasma cytokines by high-resolution mass spectrometry (MS) and multiplex cytokine bead array. Immune scan in mothers was done using flow cytometry.ResultsIn asymptomatic SARS-CoV-2 infection, --the amino acid metabolic pathways such as glycine, serine, L-lactate and threonine metabolism was upregulated, riboflavin and tyrosine metabolism, downregulated. In mild to moderate disease, the pyruvate and NAD+metabolism (energy metabolic pathways) were mostly altered. In addition to raised TNF-α, IFN-α, IFN-γ, IL-6 cytokine storm, IL-9 was increased in both mothers and neonates. Pyruvate and NAD+metabolic pathways along with IL-9 and IFN-γ had impact on non-classical monocytes, increased CD4 T cells and B cells but depleted CD8+T cells. Cord blood mimicked the mother’s metabolomic profiles by showing altered valine, leucine, isoleucine, glycine, serine, threonine in asymptomatic and NAD+and riboflavin metabolism in mild and moderate disease subjects.ConclusionsOur results demonstrate a graduated immune-metabolomic interplay in mother and fetus in pregnant females with different degrees of severity of COVID-19 disease. IL-9 and IFN- γ regulated pyruvate, lactate TCA metabolism and riboflavin metabolism with context to disease severity are hall marks of this materno-fetal metabolome.HighlightsSARS-CoV-2 infection alters energy consumption metabolic pathways during pregnancy.Pregnant women with mild to moderate COVID-19 show increased energy demands, and consume stored glucose by upregulating pyruvate and NAD+metabolism.Increased TNF-α and IL-9 in mild COVID-19 disease involve TCA cycle to produce lactate and consume stored glucose by up regulating pyruvate and nicotinamide and nicotinate metabolism.With mild to moderate disease, raised IL-9 and TNF-α, decreased riboflavin pathway, exhaustion of T and B cells cause pathogenesis.Cord blood mimics the metabolic profile of mother’s peripheral blood, SARS- CoV-2 infection reshapes immune-metabolic profiles of mother-infant dyad.Graphical Abstract

Background and AimsSevere alcoholic hepatitis (SAH) has a high mortality and corticosteroid therapy is effective in 60% patients. Reliable indicators of response to therapy and mortality in SAH are needed. A total of 223 SAH patients, 70 in derivative [50 responders (R) and 20 non-responders (NR)] and 153 in validation cohort [136R, 17NR] were subjected to plasma metabolic/meta-proteomic analysis using UHPLC-HRMS and validated using Machine-Learning (ML). Temporal metabolic changes were assessed using Weighted Metabolome Correlation Network Analysis (WMCNA). Functionality (inflammatory-nature, effect on membrane integrity and glucocorticoid receptor) of non-response indicator was assessedin-vitroon primary healthy neutrophils or mice enterocytes. Baseline plasma metabolomics and meta-proteomics clearly discriminated NR and showed significant increase in urobilinogen (3.6-fold), cholesterol sulfate (6.9-fold), Adenosine monophosphate (4.7-fold) and others (p1.5, FDR0.07mg/ml segregated non-survivors (p98% accuracy using ML. Plasma urobilinogen directly correlated with circulating bacterial peptides linked to bilirubin to urobilinogen metabolising bacteria (r2>0.7;pneutrophil activation,oxidative-stressandpro-inflammatory cytokines (CXCR1, NGAL, NOXO1, NOX4, IL15, TNFα and others, pcorticosteroid resistanceby increasing the expression of GR-Beta and trans-repression genes under GR-alpha (inflammatory-NFkB, MAPK-MAP) and reducing GR-alpha, and transactivation (anti-inflammatory) gene levels. Urobilinogen also promoted leaky gut by deregulating intestinal membrane junction proteins.ConclusionPlasma metabolome/meta-proteome can stratify pre-therapy steroid response. Increase in plasma Urobilinogen pedals a vicious cycle of bacterial translocation and increase in inflammation and corticosteroid non-response in SAH patients.

BACKGROUND AND AIMS: Noninvasive tools (NITs) reliably categorise patients with compensated advanced chronic liver disease (cACLD) into high-risk and low-risk group for harbouring varices needing treatment. Here, we assess the ability of these NITs to predict the need for nonselective beta-blockers at baseline based on risk of variceal bleeding (VB) on follow-up. METHODS: This was a retrospective multicentre analysis of patients with cACLD categorised at baseline into different risk groups by NITs (Baveno-VI, expanded Baveno-VI, platelet-albumin, platelet-model for end-stage liver disease (MELD) and anticipate study platelet criteria) and by endoscopy (high risk vs low risk/no varices). VB event rates on follow-up were estimated in different risk strata. Decision curve analysis (DCA) was used to estimate the benefit of administering nonselective beta-blockers (NSBB) using NITs over endoscopic classification at different threshold probabilities of VB event rates and estimating the number needed to treat (NNT) to identify one additional bleeder over endoscopy. RESULTS: A total of 1284 patients (mean age: 44.7 ± 13.5 years, 72.4% males) of hepatitis B (29.2%), nonalcoholic fatty liver disease (24.9%), hepatitis C (20.1%), and alcohol (17.5%)-related cACLD were included with 323 (25.2%) having high-risk varices. Ninety-eight (7.6%) patients developed VB over a median follow-up of 20 (9–35) months. The 1-year and 3-year rate of VB with all NITs was 5.7–7.4% and 13.2–16.4% among high-risk and 0–2.3% and 0–5% among low-risk subgroups, respectively (P

Purpose To evaluate the clinical outcomes of transcatheter arterial embolization (TAE) with n-butyl-2-cyanoacrylate (NBCA) for treatment of bleeding in cirrhotic patients. Materials and methods A total of 35 cirrhotic patients (26 men, 9 women; mean age, 48.4 ± 11.1) who underwent TAE with NBCA for bleeding from January 2011 to December 2020 were retrospectively analysed. Only cirrhotic patients with active arterial bleeding confirmed on computed tomography (CT) were included. Fifteen patients were hemodynamically unstable before embolization procedure, and coagulopathy was observed in 32 patients. The mean MELD score and Child Pugh score were 24 ± 9.9 and 9.9 ± 2.2, respectively. The mean haemoglobin level and mean number of RBC units transfused before embolization were 7.4 ± 1.4 g/dL and 10.2 ± 4, respectively. The technical, clinical success rate and 30-day mortality rate were evaluated. Results Technical success and clinical success rates were achieved in 100% and 82.8% of patients, respectively. Overall 30-day mortality rate was 48%. No major complications related to the embolization procedure was seen. Only the greater number of RBC units transfused before the embolization procedure (OR = 1.81, 95% CI = 1.17–2.80, P = 0.007) was significantly associated with clinical failure. Greater number of RBC units transfused (OR = 1.53, 95% CI: 1.00–2.34, P = 0.004) and higher Child Pugh score (OR 2.44, 95% CI 1.26–4.71, P = 0.008) were significantly associated with higher 30-day mortality rate. Conclusion Transcatheter arterial embolization using NBCA can be used as the effective treatment option for bleeding in cirrhotic patients which has a high technical and clinical success despite the grave prognosis associated with cirrhosis.

Cirrhosis patients exhibit cytopenia, and, at times refractory neutropenia to granulocyte colony-stimulating factor (G-CSF), which acts through the CSF3-receptor (CSF3R), and changes in CSF3R can affect the response. We conducted this study to assess the CSF3R status and its relevance in cirrhotic patients.Cirrhotic patients (The mean age was 48.6±13.4 years, and 80.3% were men. Circulatory CSF3R reduction was noted with the advancement of cirrhosis, and confirmed by qRT-PCR and IHC in BM. CSF3R decline was related to decreased hematopoietic stem cells (HSCs) and downregulation of CSF3R in the remaining HSCs. Cocultures confirmed that CEACAM1 led to CSF3R downregulation in BM cells by possible lysosomal degradation. Baseline low peripheral blood-(PB)-CSF3R also predisposed development of infections on follow-up. Decreased CSF3R was also associated with nonresponse to exogenous G-CSF treatment of neutropenia.Advanced liver cirrhosis was associated with low CSF3R and high CEACAM1 levels in the BM and circulation, making patients prone to infection and inadequate response to exogenous G-CSF.

Liver diseases are responsible for over 2 million deaths each year and the number is rapidly increasing. There is a strong link between edibles, gut microbiota, liver fat and the liver damage. There are very limited therapeutic options for treatment specifically for Alcoholic liver disease (ALD) and Non-Alcoholic liver disease (NAFLD). Recently, identified Edible Exosomes-like nanoparticles (ELNs) are plant derived membrane bound particles, released by microvesicular bodies for cellular communication and regulate immune responses against many pathogens. Many studies have identified their role as hepatoprotective agent as they carry bioactive material as cargoes which are transferred to recipient cells and affect various biological functions in liver. They are also known to carry specific miRNA, which increases the copy number of beneficial bacteria and the production of lactic acid metabolites in gut and hence restrains from liver injury through portal vein. Few in-vitro studies also have been reported about the anti-inflammatory, anti-oxidant and detoxification properties of ELNs which again protects the liver. The properties such as small size, biocompatibility, stability, low toxicity and non-immunogenicity make ELNs as a better therapeutic option. But, till now, studies on the effect of ELNs as therapeutics are still at its infancy yet promising. Here we discuss about the isolation, characterization, their role in maintaining the gut microbiome and liver homeostasis. Also, we give an outline about the latest advances in ELNs modifications, its biological effects, limitations and we propose the future prospective of ELNs as therapeutics.

BackgroundSevere Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2), is a causative agent of current global pandemic of Coronavirus disease-19 (COVID-19). Due to propagated outbreak and global vaccination drive an immense immunological selection pressure has been exerted on SARS CoV-2 leading to evolution of new variants. This study was performed to compare the mutational and clinical profile of liver disease patients infected with different variants of SARS CoV-2.MethodologyThis was a single-centre, retrospective, cohort study in which clinicogenomic analysis of liver disease (LD) patients infected with SARS CoV-2 was performed. Complete demographic and clinical details were retrieved from Hospital Information System (HIS). QC-threshold passed FASTA files containing sequences from COVID-19 patients (n=174) were compared with a reference genome of SARS-CoV-2 isolate named Wuhan-Hu-1 (NCBI Reference Sequence: NC_045512.2) for mutational analysis.ResultsOut of 232 finally analysed patients 137 (59.1%) were LD-CoV (+) and 95 (40.9%) were LD-CoV(-). LD patients with comorbidities were affected more with COVID-19 (p=0.002). On comparing the outcome in the terms of mortality, LD-CoV (+) had 2.29 times (OR 2.29, CI 95%, 1.25-4.29) higher of odds of succumbing to COVID-19 (p=0.006). Multivariate regression analysis revealed, abdominal distention (p=0.05), severe COVID-19 pneumonia (p=0.046) and the change in serum bilirubin levels (p=0.005) as well as Alkaline phosphatase (ALP) levels (p=0.003) to have an association with adverse outcome in LD patients with COVID-19. In Delta (22%) and Omicron (48%) groups, Spike gene harboured maximum mutations. On comparing the mutations between LD-CoV(+/D) and LD-CoV(+/O) a total of nine genes had more mutations in LD-CoV(+/O) whereas three genes had more mutations in LD-CoV(+/D).ConclusionWe concluded that LD patients are more susceptible to COVID-19 as compared to a healthy adult with associated adverse clinical outcomes in terms of mortality and morbidity. Therefore this special group should be given priority while devising and introducing new vaccination and vaccination policies. The infection with different variants did not result in different outcome in our group of patients.

Introduction: Non-cirrhotic portal hypertension (NCPH) usually has lower liver stiffness (LS) and hepatic pressure gradient (HPVG), than cirrhosis. At times, it can have elevated LS and HVPG and be confused with liver cirrhosis. In this study we aimed to categorize those entities of NCPH with higher values of LS and HVPG for the prognostic relevance. Patients & Methods: This study included liver biopsy cases diagnosed as NCPH (2015-2021). Age and gender-matched controls of cryptogenic cirrhosis (n=127) were included. Parameters were obtained from the electronic records. The histological categories were- Obliterative portal venopathy (OPV), OPV with bridges (OPV-F), incomplete septal cirrhosis (ISC), nodular regenerative hyperplasia (NRH), mega sinusoids with fibrosis (MSF) and unclassified. Results: Mean age of study participants (n=173) was 39 (27.5-50) years. LS and HVPG were significantly lower than the cirrhosis {8 (6-12) vs 16 (14-17) Kpa; and 8 (6.9-11.7) vs. 27 (23-36), p10 mmHg was: OPV (0/45, 0%), OPV-F (29/37, 78.3%), ISC (13/20, 65%), NRH (8/19, 42%), MSF (1/19, 5.2%), and unclassified (1/33, 3%) with pConclusions: OPV-F and ISC have more fibrosis contents and higher HVPG values than the other categories of NCPH. Whereas, MSF and NRH have spuriously high liver stiffness.

Introduction Intense monocyte activation and infiltration into the target tissues are the main mechanisms of lung injury in severe acute respiratory syndrome coronavirus 2 infection. A reduction in the degree and nature of such cellular responses is expected following recovery. We aimed to investigate the immune responses in moderate coronavirus disease 2019 (COVID‐19) patients and recovered patients. Methods Moderate COVID‐19 patients (n = 34) at Lok Nayak Hospital, New Delhi, and COVID‐19 recovered patients (n = 15) from the mild disease who were considered for convalescent plasma (COPLA) donation at the Institute of Liver and Biliary Sciences, New Delhi and healthy individuals (n = 10), were recruited. We have assessed 21 plasma cytokines using cytokine bead array, performed proteomics on serum proteins, and analyzed immune cells using a detailed multicolor flow cytometry. Results A significant increase in inflammatory markers such as macrophage inflammatory protein (MIP)1‐α, monocyte chemotactic protein‐1, macrophage migration inhibitory factor, vascular endothelial growth factor‐A, and Leptin was observed in the moderate patients. Nonsurvivors additionally showed increased interleukin (IL)‐6 levels. Consistently, the proteomics analysis showed the signatures of cytokine production and interferon‐γ response, and increased level of acute‐phase protein SAA1 in the serum of COVID‐19 patients. Despite the sustained expression of MIPs, the recovered COPLA donors showed a surge in MCSF and IL‐18 levels. Both the groups had increased CCR2, CX3CR1 positive monocytes, low CD8+ T cells, A proliferation‐inducing ligand, and B‐cell activating factor receptor+ B cells compared with healthy subjects. Conclusions Patients who have recovered and considered for COPLA donations still have compromised immunity with sustained expression of inflammatory monocytes and activated T cells., Graphical abstract Covid patients who have recovered and considered for considered for convalescent plasma donations still have compromised immunity with sustained expression of inflammatory monocytes and activated T cells

This study elucidated the clinical, humoral immune response and genomic analysis of vaccine breakthrough (VBT) infections after ChAdOx1 nCoV-19/Covishield vaccine in healthcare workers (HCWs). Amongst 1858 HCWs, 1639 had received either two doses (1346) or a single dose (293) of ChAdOx1 nCoV-19 vaccine. SARS-CoV-2 IgG antibodies and neutralizing antibodies were measured in the vaccinated group and the development of SARS-CoV-2 infection was monitored.Forty-six RT-PCR positive samples from the 203 positive samples were subjected to whole genome sequencing (WGS). Of the 203 (10.92%) infected HCWs, 21.46% (47/219) were non-vaccinated, which was significantly more than 9.52% (156/1639) who were vaccinated and infection was higher in doctors and nurses. Unvaccinated HCWs had 1.57 times higher risk compared to partially vaccinated HCWs and 2.49 times higher risk than those who were fully vaccinated.The partially vaccinated were at higher risk than the fully vaccinated (RR 1.58). Antibody non-response was seen in 3.44% (4/116), low antibody levels in 15.51% (18/116) and medium levels were found in 81.03% (94/116). Fully vaccinated HCWs had a higher antibody response at day 42 than those who were partially vaccinated (8.96 + 4.00 vs. 7.17 + 3.82). Whole genome sequencing of 46 samples revealed that the Delta variant (B.1.617.2) was predominant (69.5%). HCWs who had received two doses of vaccine showed better protection from mild, moderate, or severe infection, with a higher humoral immune response than those who had received a single dose. The genomic analysis revealed the predominance of the Delta variant (B.1.617.2) in the VBT infections.

BACKGROUND AND AIMS India has a significant burden of hepatitis C virus (HCV) infection and has committed to achieving national elimination by 2030. This will require a substantial scale-up in testing and treatment. The "HEAD-Start Project Delhi" aimed to enhance HCV diagnosis and treatment pathways among the general population. METHODS A prospective study was conducted at 5 district hospitals (Arm 1: one-stop shop), 15 polyclinics (Arm 2: referral for viral load (VL) testing and treatment) and 62 screening camps (Arm 3: referral for treatment). HCV prevalence, retention in the HCV care cascade, and turn-around time were measured. RESULTS Between January and September 2019, 37 425 participants were screened for HCV. The median (IQR) age of participants was 35 (26-48) years, with 50.4% male and 49.6% female. A significantly higher proportion of participants in Arm 1 (93.7%) and Arm 3 (90.3%) received a VL test compared with Arm 2 (52.5%, P