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Coxsackievirus A6 (CVA6) has become increasingly clinically relevant as a cause of Hand, Foot and Mouth Disease (HFMD) globally since 2008. However, most laboratories do not routinely determine the enteroviral type of positive samples. The non-pharmaceutical measures introduced to curb transmission during the COVID-19 pandemic may also have perturbed CVA6 epidemiology. We thus aimed to determine the prevalence, clinical presentation and genetic relationship of CVA6 across three complete epidemic seasons: one pre-SARS-CoV-2 emergence and two post-SARS-CoV-2 emergence in our regional healthcare setting. Surplus diagnostic nucleic acid from diagnosed enteroviral positives diagnosed between September and December of 2018 and between May 2021 and April of 2023 was subject to VP1 gene sequencing to determine the CVA6 cases and interrogate their phylogenetic relationship. The confirmed CVA6 cases were also retrospectively clinically audited. CVA6 infections were identified in 33 and 69 individuals pre- and post-pandemic, respectively, with cases peaking in November of 2018 and 2022, but in October of 2021. HFMD was the primary diagnosis in 85.5% of the post-pandemic cases, but only 69.7% of the pre-pandemic cases, where respiratory and neurological symptoms (45.5% and 12.1%, respectively) were significantly elevated. A complete VP1 sequence was retrieved for 94% of the CVA6 cases, revealing that studied infections were genetically diverse and suggestive of multiple local and international transmission chains. CVA6 presented a significant clinical burden in our regional U.K. hospital setting both pre- and post-pandemic and was subject to dynamic clinical and genetic epidemiology.

We report the retrospective identification and subsequent recovery of a near-complete West Nile Virus lineage 2 genomes from a hospitalized patient with acute febrile illness in Uganda, using a combination of degenerate primer polymerase chain reaction screening and a novel 1200bp nanopore-based whole-genome amplicon sequencing scheme. This represents the first West Nile virus genome to be recovered from a human in Uganda since its discovery in 1937. Basic molecular rather than serological surveillance methods could be more widely deployed in the region to better diagnose febrile infections., Competing Interests: The authors have no competing interests to declare., (© 2024 The Author(s).)

Background: The addition of vancomycin to beta-lactam prophylaxis in arthroplasty may reduce surgical-site infections; however, the efficacy and safety are unclear., Methods: In this multicenter, double-blind, superiority, placebo-controlled trial, we randomly assigned adult patients without known methicillin-resistant Staphylococcus aureus (MRSA) colonization who were undergoing arthroplasty to receive 1.5 g of vancomycin or normal saline placebo, in addition to cefazolin prophylaxis. The primary outcome was surgical-site infection within 90 days after surgery., Results: A total of 4239 patients underwent randomization. Among 4113 patients in the modified intention-to-treat population (2233 undergoing knee arthroplasty, 1850 undergoing hip arthroplasty, and 30 undergoing shoulder arthroplasty), surgical-site infections occurred in 91 of 2044 patients (4.5%) in the vancomycin group and in 72 of 2069 patients (3.5%) in the placebo group (relative risk, 1.28; 95% confidence interval [CI], 0.94 to 1.73; P = 0.11). Among patients undergoing knee arthroplasty, surgical-site infections occurred in 63 of 1109 patients (5.7%) in the vancomyin group and in 42 of 1124 patients (3.7%) in the placebo group (relative risk, 1.52; 95% CI, 1.04 to 2.23). Among patients undergoing hip arthroplasty, surgical-site infections occurred in 28 of 920 patients (3.0%) in the vancomyin group and in 29 of 930 patients (3.1%) in the placebo group (relative risk, 0.98; 95% CI, 0.59 to 1.63). Adverse events occurred in 35 of 2010 patients (1.7%) in the vancomycin group and in 35 of 2030 patients (1.7%) in the placebo group, including hypersensitivity reactions in 24 of 2010 patients (1.2%) and 11 of 2030 patients (0.5%), respectively (relative risk, 2.20; 95% CI, 1.08 to 4.49), and acute kidney injury in 42 of 2010 patients (2.1%) and 74 of 2030 patients (3.6%), respectively (relative risk, 0.57; 95% CI, 0.39 to 0.83)., Conclusions: The addition of vancomycin to cefazolin prophylaxis was not superior to placebo for the prevention of surgical-site infections in arthroplasty among patients without known MRSA colonization. (Funded by the Australian National Health and Medical Research Council; Australian New Zealand Clinical Trials Registry number, ACTRN12618000642280.)., (Copyright © 2023 Massachusetts Medical Society.)

The gut microbiome is a significant contributor to mental health, with growing evidence linking its composition to anxiety and depressive disorders. Gut microbiome composition is associated with signs of anxiety and depression both in clinically diagnosed mood disorders and subclinically in the general population and may be influenced by dietary fibre intake and the presence of chronic pain. We provide an update of current evidence on the role of gut microbiome composition in depressive and anxiety disorders or symptoms by reviewing available studies. Analysing data from three independent cohorts (osteoarthritis 1 (OA1); n = 46, osteoarthritis 2 (OA2); n = 58, and healthy controls (CON); n = 67), we identified microbial composition signatures of anxiety and depressive symptoms at genus level and cross-validated our findings performing meta-analyses of our results with results from previously published studies. The genera Bifidobacterium (fixed-effect beta (95% CI) = -0.22 (-0.34, -0.10), p = 3.90e-04) and Lachnospiraceae NK4A136 group (fixed-effect beta (95% CI) = -0.09 (-0.13, -0.05), p = 2.53e-06) were found to be the best predictors of anxiety and depressive symptoms, respectively, across our three cohorts and published literature taking into account demographic and lifestyle covariates, such as fibre intake. The association with anxiety was robust in accounting for heterogeneity between cohorts and supports previous observations of the potential prophylactic effect of Bifidobacterium against anxiety symptoms., Competing Interests: AMV and AV are members of the Chuckling Goat (a nutrition company) Scientific Advisory Board. AMV is a member of the CP Kelco SAB. AMV and CM are consultants for Zoe Ltd. DAW has undertaken consultancy through University of Nottingham for Contura International A/S, Glaxo SmithKline, AKL Research and Development Ltd, Pfizer Ltd, Abbvie Ltd, Ely Lilly & Co.Ltd, Galapagos Ltd., and Reckitt Benckiser Health Ltd and is responsible for research grants paid to University of Nottingham from Versus Arthritis, UKRI, NIHR, Pfizer Ltd, Ely Lilly & Co Ltd, UCB Pharma, and Orion Pharma (all non-personal pecuniary interests)., (© 2023 The Authors.)

Background and study aims Pancreatic cysts are common incidental findings, with an estimated prevalence of 13% to 15% in imaging done for other reasons. Diagnosis often relies on collection of cyst fluid, but tissue sampling using micro-forceps may allow for a more reliable diagnosis and higher yield of DNA for next-generation sequencing (NGS). The primary aim was to assess the performance of NGS in identifying mucinous cyst. The secondary aims were to assess DNA yield between the cyst fluid and cyst wall tissue, complication rate and performance of conventional investigations. Patients and methods Twenty-four patients referred for endoscopic ultrasound were recruited. Biopsies were taken using micro-forceps and the AmpliSeq Cancer Hotspot panel was used for NGS, a polymerase chain reaction assay targeting several hotspots within 50 genes, including GNAS , KRAS and VHL . Results The concentration of DNA extracted from 24 cyst wall samples was significantly higher than in the nine of 24 available matched cyst fluid samples. The sensitivity, specificity, and diagnostic accuracy of NGS for diagnosing mucinous cyst were 93%, 50% and 84%; for standard of care, they were -66.6%, 50% and 63.1%; and for standard of care with NGS, they were 100%, 50%, and 89.4% respectively. Cyst wall biopsy was able to diagnose 19 of 24 cysts (4 high risk, 7 intraductal papillary mucinous neoplasms, 4 cysts of mucinous origin, and 4 benign). Conclusions NGS data correlate well with histology and may aid in diagnosis and risk stratification of pancreatic cysts. Cyst wall biopsy performs well in diagnosing cysts but was inadequate in five of 24 patients., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Hepatocyte senescence is associated with liver fibrosis. However, the possibility of a direct, causal relation between hepatocyte senescence and hepatic stellate cell (HSC) activation was the subject of this study. Liver biopsy specimens obtained from 50 patients with non-alcoholic fatty liver disease and a spectrum of liver fibrosis stages were stained for p16, αSMA, and picrosirius red (PSR). Primary human HSCs were cultured in conditioned media derived from senescent or control HepG2 cells. Expression of inflammatory and fibrogenic genes in HSCs cultured in conditioned media were studied using RT-PCR. ELISAs were undertaken to measure factors known to activate HSCs in the conditioned media from senescent and control HepG2 cells and serum samples from healthy volunteers or patients with biopsy-proven cirrhosis. There was a strong association between proportion of senescent hepatocytes and hepatic stellate cell activation. Both proportion of hepatocyte senescence and hepatic stellate cell activation were closely associated with fibrosis stage. Inflammatory and fibrogenic genes were up-regulated significantly in HSCs cultured in conditioned media from senescent HepG2 cells compared with control HepG2 cells. PDGF levels were significantly higher in the conditioned media from senescent hepatocytes than control HepG2-conditioned media, and in serum samples from patients with cirrhosis than healthy volunteers. In conclusion, this 'proof of concept' study revealed activation of human HSCs by media from senescent HepG2 cells, indicating direct involvement of factors secreted by senescent hepatocytes in liver fibrosis.

SARS-CoV-2 infection results in different outcomes ranging from asymptomatic infection to mild or severe disease and death. Reasons for this diversity of outcome include differences in challenge dose, age, gender, comorbidity and host genomic variation. Human leukocyte antigen (HLA) polymorphisms may influence immune response and disease outcome. We investigated the association of HLAII alleles with case definition symptomatic COVID-19, virus-specific antibody and T-cell immunity. A total of 1364 UK healthcare workers (HCWs) were recruited during the first UK SARS-CoV-2 wave and analysed longitudinally, encompassing regular PCR screening for infection, symptom reporting, imputation of HLAII genotype and analysis for antibody and T-cell responses to nucleoprotein (N) and spike (S). Of 272 (20%) HCW who seroconverted, the presence of HLA-DRB1*13:02 was associated with a 6·7-fold increased risk of case definition symptomatic COVID-19. In terms of immune responsiveness, HLA-DRB1*15:02 was associated with lower nucleocapsid T-cell responses. There was no association between DRB1 alleles and anti-spike antibody titres after two COVID vaccine doses. However, HLA DRB1*15:01 was associated with increased spike T-cell responses following both first and second dose vaccination. Trial registration: NCT04318314 and ISRCTN15677965., (© 2022 The Authors. Immunology published by John Wiley & Sons Ltd.)

Background/aims: Community-based assessment and management of chronic liver disease (CLD) in people who are homeless (PWAH) remain poorly described. We aimed to determine prevalence/predictors of CLD in PWAH and assess the performance of non-invasive liver fibrosis and injury markers., Methods: The Vulnerable Adult LIver Disease (VALID) study provided a "one-stop" liver service based at homeless hostels. Our primary outcome was the prevalence of clinically significant hepatic fibrosis (CSHF; liver stiffness measurement (LSM) ≥8 kPa)., Results: Total individuals recruited were 127, mean ± SD age 47 ± 9.4 years, 50% (95% CI 41%-59%) and 39% (95% CI 31%-48%) having alcohol dependence and a positive HCV RNA respectively. CSHF was detected in 26% (95% CI 17%-35%), independent predictors being total alcohol unit/week (OR 1.01, 95% CI 1.00-1.02, P = .002) and HCV RNA positivity (OR 2.93, 95% CI 1.12-7.66, P = .029). There was moderate agreement between LSM and Enhanced Liver Fibrosis (ELF) score (kappa 0.536, P < .001) for CSHF as assessed by LSM ≥8 kPa. Those with CSHF had significantly higher levels of IFN-γ (P = .002), IL-6 (P = .001), MMP-2 (P = .006), ccCK-18 (P < .001) and ELF biomarkers (P < .001), compared to those without CSHF. Service uptake was ≥95%. Direct acting antiviral (DAA) treatment completion was 93% (95% CI 77%-99%), sustained virological response (SVR) being 83% (95% CI 64%-94%)., Conclusion: There is a significant liver disease burden from HCV and alcohol in PWAH. Non-invasive liver fibrosis and injury markers can help in identifying such individuals in the community. Despite a challenging cohort, excellent service uptake and high DAA-based SVRs can be achieved., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Biopsy remains the gold-standard measure for staging liver disease, both to inform prognosis and to assess the response to a given treatment. Semiquantitative scores such as the Ishak fibrosis score are used for evaluation. These scores are utilised in clinical trials, with the US Food and Drug Administration mandating particular scores as inclusion criteria for participants and using the change in score as evidence of treatment efficacy. There is an urgent need for improved, quantitative assessment of liver biopsies to detect small incremental changes in liver architecture over the course of a clinical trial. Artificial intelligence (AI) methods have been proposed as a way to increase the amount of information extracted from a biopsy and to potentially remove bias introduced by manual scoring. We have trained and evaluated an AI tool for measuring the amount of scarring in sections of picrosirius red-stained liver. The AI methodology was compared with both manual scoring and widely available colour space thresholding. Four sequential sections from each case were stained on two separate occasions by two independent clinical laboratories using routine protocols to study the effect of inter- and intra-laboratory staining variation on these tools. Finally, we compared these methods to second harmonic generation (SHG) imaging, a stain-free quantitative measure of collagen. Although AI methods provided a modest improvement over simpler computer-assisted measures, staining variation both within and between laboratories had a dramatic effect on quantitation, with manual assignment of scar proportion being the most consistent. Manual assessment also most strongly correlated with collagen measured by SHG. In conclusion, results suggest that computational measures of liver scarring from stained sections are compromised by inter- and intra-laboratory staining. Stain-free quantitative measurement using SHG avoids staining-related variation and may prove more accurate in detecting small changes in scarring that may occur in therapeutic trials., (© 2021 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland & John Wiley & Sons, Ltd.)

Purpose: To determine the potential effectiveness of a novel 10-week manualised Practical Body Image therapy (PBI) with mirror exposure (ME), when used as an adjuvant to an intensive treatment package (TAU) in adolescent inpatients with Anorexia Nervosa (AN). To evaluate the effectiveness of ME in an adolescent population., Methods: Using a randomised control design, 40 girls aged 11-17 years with AN were assigned to PBI with TAU (n = 20) and TAU alone (n = 20). Both groups completed self-report measures of body image at week 1 and week 10 of the study to measure the potential effectiveness of PBI. The PBI group completed measures at week 7 to evaluate the ME component., Results: 31 participants completed the study; 16 TAU, 15 PBI. PBI participants had greater improvement in all outcomes than TAU participants. Medium effect sizes were seen for self-reported weight concern, body image avoidance in terms of clothing and body image anxiety. ME produced effect sizes in self-reported body image avoidance in terms of clothing and grooming that were greater than 0.40, n = 14., Conclusion: The findings demonstrate that PBI supports an intensive inpatient treatment package and addresses elements of negative body image. PBI was beneficial for addressing body image dissatisfaction with improvements in weight concerns, body image avoidance and physical appearance trait anxiety following the ME component. The magnitude of the effect sizes is comparable to previous studies. Positive qualitative feedback indicated the intervention was acceptable to users. PBI is a promising new adjuvant treatment for AN., Emb Rating: Level I: randomized controlled trial., (© 2020. The Author(s).)

Aims: The current study investigates the role of diet in mediating the gut microbiome-cardiovascular association which has not yet been explored in humans. Methods and Results: Using a two-arm dietary intervention study in healthy participants ( N = 70), we assessed the effects of omega-3 and fibre supplementation on gut microbiome composition and short-chain fatty acid (SCFA) production. We then investigated how changes in gut microbiome composition correlated with changes in traditional cardiovascular risk factors (cholesterol, triglycerides, blood pressure), cytokines, and novel validated markers such as GlycA and ceramides, previously linked to CVD incidence and mortality. Both interventions resulted in significant drops in blood pressure, cholesterol, proinflammatory cytokines, GlycA and ceramides (all P < 0.05). Decreases in the atherogenic low-density lipoprotein triglyceride fraction, in total serum cholesterol were correlated with increases in butyric acid-production [β(SE) = -0.58 (0.06), P < 0.001; -0.53 (0.04), P < 0.001] and nominally associated with increases in some butyrogenic bacteria. Drops in GlycA were linked to increases in Bifidobacterium [β(SE) = -0.32 (0.04), P = 0.02] and other SCFAs including acetic acid [β(SE) = -0.28 (0.04), P = 0.02] and propionic acid [β(SE) = -0.3 (0.04), P = 0.02]. Additionally, we report for the first-time reductions in specific ceramide ratios that have been shown to predict CVD mortality and major adverse cardiovascular events such as d18:1/16:0, d18:0/24:0, and d18:1/24:1 which were associated with the reduction in the abundance in Colinsella and increases in Bifidobacteriuim and Coprococcus 3 and SCFAs (all P < 0.05). Conclusion: Overall, these findings support the potential of using simple dietary interventions to alter validated biomarkers linked to cardiovascular risk via the gut microbiome composition and its metabolic functions., Competing Interests: TS is co-founder of Zoe Global Ltd. AMV is a consultant for Zoe Global Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Vijay, Astbury, Panayiotis, Marques, Spector, Menni and Valdes.)

Undernutrition is a leading contributor to disease and disability in people of all ages. Several studies have reported significant association between nutritional status and gut microbiome composition but other factors such as demographic settings may also influence the adult microbiome. The relationship between undernourishment and gut microbiome in adults has not been described to date. In this study, we compared the gut microbiome in fecal samples of 48 individuals, from two demographic settings (rural and urban slum) in Karnataka, India using 16S rRNA sequencing. Nutritional status was assessed based on BMI, with a BMI of < 18.5 kg/m 2 classified as undernourished, and a BMI in the range 18.5-25 kg/m 2 as nourished. We analyzed 25 individuals from rural settings (12 undernourished and 13 nourished) and 23 individuals from urban slum settings (11 undernourished and 12 nourished). We found no significant difference in overall gut microbial diversity (Shannon and Unweighted UniFrac) between undernourished and nourished individuals in either geographical settings, however, microbial taxa at the phylum level (i.e., Firmicutes and Proteobacteria) and beta diversity (unweighted UniFrac) differed significantly between the rural and urban slum settings. By predicting microbial function from 16S data profiling we found significant differences in metabolic pathways present in the gut microbiota from people residing in different settings; specifically, those related to carbohydrate and lipid metabolism. The weighted sum of the KEGG Orthologs associated with carbohydrate metabolism (Spearman's correlation coefficient, ρ = -0.707, p < 0.001), lipid metabolism (Spearman's correlation coefficient, ρ = -0.330, p < 0.022) and biosynthesis of secondary metabolites (Spearman's correlation coefficient, ρ = -0.507, p < 0.001) were decreased in the urban slum group compared to the rural group. In conclusion, we report that the geographical location of residence is associated with differences in gut microbiome composition in adults. We found no significant differences in microbiome composition between nourished and undernourished adults from urban slum or rural settings in India., Competing Interests: AMV is a consultant for Zoe Global Ltd., and a member of the scientific advisory board of CPKelco. GA has served as a consultant and an advisory board member for Pfizer and Glaxo SmithKline; he has been a consultant to Amryt Pharmaceuticals and Astra Zeneca. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mehta, Inbaraj, Astbury, Grove, Norman, Aithal, Valdes and Vijay.)

Background: Chronic inflammation, which can be modulated by diet, is linked to high white blood cell counts and correlates with higher cardiometabolic risk and risk of more severe infections, as in the case of COVID-19., Methods: Here, we assessed the association between white blood cell profile (lymphocytes, basophils, eosinophils, neutrophils, monocytes and total white blood cells) as markers of chronic inflammation, habitual diet and gut microbiome composition (determined by sequencing of the 16S RNA) in 986 healthy individuals from the PREDICT-1 nutritional intervention study. We then investigated whether the gut microbiome mediates part of the benefits of vegetable intake on lymphocyte counts., Results: Higher levels of white blood cells, lymphocytes and basophils were all significantly correlated with lower habitual intake of vegetables, with vegetable intake explaining between 3.59 and 6.58% of variation in white blood cells after adjusting for covariates and multiple testing using false discovery rate (q < 0.1). No such association was seen with fruit intake. A mediation analysis found that 20.00% of the effect of vegetable intake on lymphocyte counts was mediated by one bacterial genus, Collinsella, known to increase with the intake of processed foods and previously associated with fatty liver disease. We further correlated white blood cells to other inflammatory markers including IL6 and GlycA, fasting and post-prandial glucose levels and found a significant relationship between inflammation and diet., Conclusion: A habitual diet high in vegetables, but not fruits, is linked to a lower inflammatory profile for white blood cells, and a fifth of the effect is mediated by the genus Collinsella., Trial Registration: The ClinicalTrials.gov registration identifier is NCT03479866 .

Prebiotics are compounds in food that benefit health via affecting the gut microbiome. Omega-3 fatty acids have been associated with differences in gut microbiome composition and are widely accepted to have health benefits, although recent large trials have been inconclusive. We carried out a 6-week dietary intervention comparing the effects of daily supplementation with 500 mg of omega-3 versus 20 g of a well-characterized prebiotic, inulin. Inulin supplementation resulted in large increases in Bifidobacterium and Lachnospiraceae. In contrast, omega-3 supplementation resulted in significant increases in Coprococcus spp . and Bacteroides spp , and significant decreases in the fatty-liver associated Collinsella spp . On the other hand, similar to the results with inulin supplementation which resulted in significant increases in butyrate, iso-valerate, and iso-butyrate ( p < .004), omega-3 supplementation resulted in significant increases in iso-butyrate and isovalerate ( p < .002) and nearly significant increases in butyrate ( p < .053). Coprococcus , which was significantly increased post-supplementation with omega-3, was found to be positively associated with iso-butyric acid (Beta (SE) = 0.69 (0.02), P = 1.4 x 10 -3 ) and negatively associated with triglyceride-rich lipoproteins such as VLDL (Beta (SE) = -0.381 (0.01), P = .001) and VLDL-TG (Beta (SE) = -0.372 (0.04), P = .001) after adjusting for confounders. Dietary omega-3 alters gut microbiome composition and some of its cardiovascular effects appear to be potentially mediated by its effect on gut microbial fermentation products indicating that it may be a prebiotic nutrient.

Introduction: Up to 40% of patients with severe alcoholic hepatitis (AH) die within 6 months of presentation, making prompt diagnosis and appropriate treatment essential. We determined the associations between serum keratin-18 (K18) and histological features, prognosis, and differential response to prednisolone in patients with severe AH., Methods: Total (K18-M65) and caspase-cleaved K18 (K18-M30) were quantified in pretreatment sera from 824 patients enrolled in the Steroids or Pentoxifylline for Alcoholic Hepatitis trial (87 with suitable histological samples) and disease controls., Results: K18 fragments were markedly elevated in severe AH and strongly predicted steatohepatitis (alcoholic steatohepatitis) on biopsy (area under receiver operating characteristics: 0.787 and 0.807). Application of published thresholds to predict alcoholic steatohepatitis would have rendered biopsy unnecessary in 84% of all AH cases. K18-M30 and M65 were associated with 90-day mortality, independent of age and Model for End-stage Liver Disease score in untreated patients. The association for K18-M65 was independent of both age and Model for End-stage Liver Disease in prednisolone-treated patients. Modelling of the effect of prednisolone on 90-day mortality as a function of pretreatment serum K18 levels indicated benefit in those with high serum levels of K18-M30. At low pretreatment serum K18 levels, prednisolone was potentially harmful. A threshold of K18-M30 5 kIU/L predicted therapeutic benefit from prednisolone above this level (odds ratio: 0.433, 95% confidence interval: 0.19-0.95, P = 0.0398), but not below (odds ratio: 1.271, 95% confidence interval: 0.88-1.84, P = 0.199). Restricting prednisolone usage to the former group would have reduced exposure by 87%., Discussion: In a large cohort of patients with severe AH, serum K18 strongly correlated with histological severity, independently associated with 90-day mortality, and predicted response to prednisolone therapy. Quantification of serum K18 levels could assist in clinical decision-making.