In severe alcohol-related hepatitis, acute kidney injury is prevalent, associated with mortality independent of liver disease severity, and can be predicted using IL-8 and micro-RNAs.

BACKGROUND: The prevalence, prediction and impact of acute kidney injury (AKI) in alcohol-related hepatitis (AH) is uncertain. AIMS: We aimed to determine AKI incidence; association with mortality; evaluate serum biomarkers and the modifying effects of prednisolone and pentoxifylline in the largest AH cohort to date. METHODS: Participants in the Steroids or Pentoxifylline for Alcoholic Hepatitis trial with day zero (D0) creatinine available were included. AKI was defined by modified International Club of Ascites criteria; incident AKI as day 7 (D7) AKI without D0-AKI. Survival was compared by Kaplan-Meier; mortality associations by Cox regression; associations with AKI by binary logistic regression; biomarkers by AUROC analyses. RESULTS: D0-AKI was present in 198/1051 (19%) participants; incident AKI developed in a further 119/571 (21%) with available data. Participants with D0-AKI had higher 90-day mortality than those without (32% vs. 25%, p = 0.008), as did participants with incident AKI compared to those without D0-AKI or incident AKI (47% vs. 25%, p < 0.001). Incident AKI was associated with D90 mortality adjusted for age and discriminant function (AHR 2.15, 1.56-2.97, p < 0.001); D0-AKI was not. Prednisolone therapy reduced incident AKI (AOR 0.55, 0.36-0.85, p = 0.007) but not mortality. D0 bilirubin and IL-8 combined, miR-6826-5p, and miR-6811-3p predicted incident AKI (AUROCs 0.726, 0.821, 0.770, p < 0.01). CONCLUSIONS: Incident AKI is associated with 90-day mortality independent of liver function. Prednisolone therapy was associated with reduced incident AKI. IL-8 and several miRNAs are potential biomarkers to predict AKI. Novel therapies to prevent incident AKI should be evaluated in AH to reduce mortality.

Acamprosate may be safer than baclofen for the treatment of alcohol use disorder in patients with cirrhosis: a first description of use in real-world clinical practice.

OBJECTIVES: Patients with alcohol use disorder (AUD) and liver cirrhosis benefit from stopping alcohol intake. Baclofen has been trialled for AUD in cirrhosis and appears to be effective. However, in patients without cirrhosis acamprosate is safer and more efficacious. Acamprosate is rarely used in cirrhosis due to safety concerns: the only published report was for 24 h in a controlled setting. Our centre uses both medications off-label in cirrhotic patients. We performed an audit to pragmatically compare the safety of acamprosate to baclofen in these patients. METHODS: The electronic records of patients prescribed acamprosate or baclofen between 01/04/17 and 31/03/20 were retrospectively reviewed. Adverse events and abstinence at last follow-up were compared by Student's t-test, Mann-Whitney U or chi-square test. Confounding variables were evaluated by logistic regression. RESULTS: In total 48 cirrhotic patients taking acamprosate (median 84 days, range 2-524); 44 baclofen (247 days, 8-910) met inclusion criteria. At baseline, 41% had Childs-Pugh B or C cirrhosis. More patients taking baclofen had an unplanned hospital admission or attendance (23 vs 13; P = 0.013) and the mean number per patient was higher (1.6 vs 0.6; P = 0.032). Sub-group analysis revealed increased admissions in actively drinking patients prescribed baclofen to achieve abstinence (mean 2.4 vs 0.6; P = 0.020); acamprosate use was associated with a reduced chance of admission or attendance (OR, 0.284; 0.095-0.854; P = 0.025) independent of treatment length. No difference in efficacy was observed. CONCLUSIONS: In patients with cirrhosis, acamprosate was associated with fewer unplanned admissions than baclofen, hence may be safer despite historical concerns.

Serum keratin 19 (CYFRA21-1) is a prognostic biomarker in severe alcoholic hepatitis.

BACKGROUND AND AIMS: Up to 30% of patients with severe alcoholic hepatitis (sAH) die within 3 months of presentation. The degree of ductular reaction, characterized by accumulation of biliary and liver progenitor cells, confers a poor prognosis. Keratin fragments are established serological surrogates of liver injury and keratin 19 (K19) is a histological marker of the ductular reaction. We assessed the relationship between serum K19 levels (viz. CYFRA21-1), histology and outcome in patients with sAH. METHODS: Serum CYFRA21-1 was quantified in pre-treatment serum samples from 824 patients enrolled in the STOPAH trial. The cohort was randomly divided into two groups to test mortality associations; histological analyses were performed using the 87 cases with suitable samples. RESULTS: CYFRA21-1 levels were elevated in sAH and strongly predicted alcoholic steatohepatitis (ASH) on biopsy (area under the receiver operated characteristic [AUROC] 0.785 [95% Confidence Interval 0.602-0.967]) and 90-day survival (AUROC 0.684/0.693). The predictive ability of CYFRA21-1 was comparable with the model of end-stage liver disease (MELD) score and was independently associated with survival in multivariable analysis. CYFRA21-1 moderately correlated with hepatocellular injury markers M30/M65 but displayed a more robust predictive ability. A combination of MELD and CYFRA21-1 conferred a modest improvement in the AUROC value (0.731/0.743). CONCLUSIONS: In sAH serum, CYFRA21-1 levels associate with the presence of ASH on biopsy and independently predict 90-day survival. As a single marker performance is comparable to established scoring systems. Therefore, CYFRA21-1, which is available in many clinical laboratories, may become a useful component of prognostic models.

Development of a north-west London paracentesis simulation course for core medical trainees.

We designed, implemented and evaluated a near-peer simulation training programme teaching diagnostic and therapeutic abdominal paracentesis to core medical trainees (CMTs). We taught diagnostic and therapeutic abdominal paracentesis to 77 north-west London CMTs over 8 training days over 4 years, 2015 to 2019. The programme was optimised by use of plan, do, study, act (PDSA) cycles and the content was evaluated by anonymous pre- and post-course questionnaires. There was a need for this training; 89% of participants reported inadequate training opportunities pre-course and only 28% felt 'confident' or 'very confident' to insert an ascitic drain. Simulation training appears effective when teaching these skills. Having been low in confidence before the course, all participants reported increased confidence after completing the course. Simulation training has been highlighted as a key aspect of the new internal medicine training programme, which replaces CMT. We would recommend using PDSA cycles to implement effective simulation programmes.

How I treat alcohol-related liver disease.

Age-standardised mortality from liver disease in the United Kingdom has risen by 400% since 1970, with three-quarters of deaths from alcohol-related liver disease (ARLD). The 2013 National Confidential Enquiry into Patient Outcome and Death report found that only 47% of the patients dying in hospital from liver disease experienced 'good' care. We discuss common complications in the care of patients with ARLD and the evidence-based best practice that can improve patient outcomes, with a focus on the initial management of patients presenting acutely to the medical take.

Accurately administering oral medication to children isn't child's play.

OBJECTIVE: Parents administer oral medications with various measuring devices including metal teaspoons, calibrated spoons and oral syringes. We aimed to determine which was the most accurate. DESIGN: Self-controlled, non-randomised, experimental study. SETTING: Caregivers attending paediatric outpatient clinics. METHODOLOGY: Caregivers measured 5 ml of 120 mg/5 ml paracetamol suspension using a 5.0 ml metal teaspoon, 5.0 ml calibrated spoon and 5.0 ml oral syringe. Samples were weighed and converted to mls. MAIN OUTCOME MEASURES: The mean volume and variance of volumes were measured for each device. RESULTS: We recruited 277 caregivers (98% parents). Volumes measured ranged from 0.83-6.52 ml. Accuracy did not vary with caregivers' age, gender, instrument preference, number and age of children. The mean volumes measured with the oral syringe (95% CI 5.09 to 5.17 ml) and metal spoon (95% CI 3.90 to 4.08 ml) were significantly different to the desired 5 ml volume (p<0.0001), dissimilar to the mean volume measured using the calibrated spoon (95% CI 4.91 to 5.09 ml, p=0.99). The variance of volumes measured with the oral syringe (SD 0.348 ml) was significantly smaller (p<0.0001) than that measured using a calibrated spoon (SD 0.762 ml) or metal spoon (SD 0.749 ml). CONCLUSIONS: The calibrated spoon was the most accurate producing a mean volume of 5 ml, while the oral syringe had the smallest variance. The increased variability of calibrated or metal spoons may result in under or overdosing especially when administering drugs with a narrow therapeutic window. Health care professionals must make a case-by-case decision regarding which device is preferable depending on the medication in question. Parental education could improve measuring accuracy.

Neural crest origin of olfactory ensheathing glia.

Olfactory ensheathing cells (OECs) are a unique class of glial cells with exceptional translational potential because of their ability to support axon regeneration in the central nervous system. Although OECs are similar in many ways to immature and nonmyelinating Schwann cells, and can myelinate large-diameter axons indistinguishably from myelination by Schwann cells, current dogma holds that OECs arise from the olfactory epithelium. Here, using fate-mapping techniques in chicken embryos and genetic lineage tracing in mice, we show that OECs in fact originate from the neural crest and hence share a common developmental heritage with Schwann cells. This explains the similarities between OECs and Schwann cells and overturns the existing dogma on the developmental origin of OECs. Because neural crest stem cells persist in adult tissue, including skin and hair follicles, our results also raise the possibility that patient-derived neural crest stem cells could in the future provide an abundant and accessible source of autologous OECs for cell transplantation therapy for the injured central nervous system.