Background In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov ( NCT04381936 ). Findings Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). Interpretation In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding UK Research and Innovation (Medical Research Council) and National Institute of Health Research.

No abstract

No abstract

No abstract

Background & Aims The incidence of primary liver cancer (PLC) is increasing in Western Europe. To understand trends over time and the current burden in the UK, a detailed analysis of the epidemiology of PLC and its subtypes was conducted. Methods Data on PLCs diagnosed during 1997–2017 were obtained from population-based, nationwide registries in the UK. European age-standardised incidence (ASR) and incidence-based mortality rates (ASMR) per 100,000 person-years were calculated overall and by sex and UK-nation. Annual percentage change in rates was estimated using Joinpoint regression. One-, 2-, and 5-year age-standardised net survival was estimated. Results A total of 82,024 PLCs were diagnosed. Both hepatocellular carcinoma (HCC) incidence and mortality rates trebled (ASR 1.8–5.5 per 100,000, ASMR 1.3–4.0). The rate of increase appeared to plateau around 2014/2015. Scottish men consistently had the highest HCC incidence rates. PLC survival increased, driven by a substantial increase in the proportion that are HCC (as prognosis is better than other PLCs) and in HCC survival (change in 1-year survival 24–47%). Intrahepatic cholangiocarcinoma was the most common PLC in women and 1-year survival improved from 22.6% to 30.5%. Conclusions PLC incidence has been increasing rapidly but, as most risk factors are modifiable, it is largely a preventable cancer. This rate of increase has slowed in recent years, possibly attributable to effective treatment for hepatitis C. As other risk factors such as obesity and diabetes remain prevalent in the UK, it is unlikely the considerable burden of this disease will abate. While improvements in survival have been made, over half of patients are not alive after 1 year, therefore further progress in prevention, early detection, and treatment innovation are needed. Lay summary Many more people are getting liver cancer, particularly the subtype hepatocellular carcinoma, than 20 years ago. Men in Scotland are most likely to get liver cancer and to die from it. Survival after liver cancer diagnosis is getting longer but still less than half are alive after 1 year.

Autoimmune hepatitis (AIH) is an immune-mediated necroinflammatory condition of the liver. Presentation can vary from the asymptomatic individual with abnormal liver function test to fulminant liver failure. The diagnosis is based on the combination of biochemical, autoimmune, and histological parameters, and exclusion of other liver diseases. Standard therapy consists of a combination of corticosteroids and azathioprine, which is efficacious in 80% of patients. Alternative therapies are increasingly being explored in patients who do not respond to the standard treatment and/or have unacceptable adverse effects. This review examines the role of alternative drugs (second-line agents) available for AIH treatment non-responders. These agents include budesonide, mycophenolate mofetil, cyclosporin, tacrolimus, 6-mercaptopurine, 6-thioguanine, rituximab, ursodeoxycholic acid, rapamycin, and methotrexate. In addition, the risk of opportunistic infections and malignancies are discussed. A treatment algorithm is proposed for the management of patients with AIH treatment non-responders.

ObjectivesOutcomes in hepatocellular carcinoma (HCC) are determined by both cancer characteristics and liver disease severity. This study aims to validate the use of inpatient electronic health records to determine liver disease severity from treatment and procedure codes.DesignRetrospective observational study.SettingTwo National Health Service (NHS) cancer centres in England.Participants339 patients with a new diagnosis of HCC between 2007 and 2016.Main outcomeUsing inpatient electronic health records, we have developed an optimised algorithm to identify cirrhosis and determine liver disease severity in a population with HCC. The diagnostic accuracy of the algorithm was optimised using clinical records from one NHS Trust and it was externally validated using anonymised data from another centre.ResultsThe optimised algorithm has a positive predictive value (PPV) of 99% for identifying cirrhosis in the derivation cohort, with a sensitivity of 86% (95% CI 82% to 90%) and a specificity of 98% (95% CI 96% to 100%). The sensitivity for detecting advanced stage cirrhosis is 80% (95% CI 75% to 87%) and specificity is 98% (95% CI 96% to 100%), with a PPV of 89%.ConclusionsOur optimised algorithm, based on inpatient electronic health records, reliably identifies and stages cirrhosis in patients with HCC. This highlights the potential of routine health data in population studies to stratify patients with HCC according to liver disease severity.

Liver transplantation (LT) is a lifesaving treatment. Because of the shortage of donor organs, some patients will not survive long enough to receive a transplant. The identification of LT candidates at increased risk of short-term mortality without transplantation may affect listing decisions. Functional capacity, determined with cardiopulmonary exercise testing (CPET), is a measure of cardiorespiratory reserve and predicts perioperative outcomes. This study examined the association between functional capacity and short-term survival before LT and the potential for CPET to predict 90-day mortality without transplantation. A total of 176 patients who were assessed for nonacute LT underwent CPET. Ninety days after the assessment, 10 of the 164 patients who had not undergone transplantation were deceased (mortality rate 5 6.1%). According to a comparison of survivors and nonsurvivors, the Model for End-Stage Liver Disease score, UK Model for End-Stage Liver Disease (UKELD) score, age, anaerobic threshold, and peak oxygen uptake (VO 2 ) were significant univariate predictors of 90-day mortality without transplantation, but only the UKELD score and peak VO 2 retained significance in a multivariate analysis. The mean peak VO 2 was significantly lower for nonsurvivors versus survivors (15.2 6 3.3 versus 21.2 6 5.3 mL/minute/kg, P < 0.001). According to a receiver operating characteristic (ROC) curve analysis, peak VO 2 performed well as a diagnostic test (area under the ROC curve 5 0.84, 95% confidence interval 5 0.76-0.92, sensitivity 5 0.90, specificity 5 0.74, P < 0.001). The optimal cutoff value for predicting mortality was 17.6 mL/minute/kg. The positive predictive value of a peak VO 2 17.6 mL/minute/kg for 90-day mortality was greatest for patients with high UKELD scores: 38% of the patients with a UKELD score 57 and a peak VO 2 17.6 mL/minute/kg died, whereas only 6% of the patients with a UKELD score 57 and a peak VO 2 > 17.6 mL/minute/kg died (P 5 0.03). In conclusion, patients assessed for LT with an impaired functional capacity have poorer short-term survival; this is particularly true for individuals with worse liver disease severity.