The maintenance of stable allograft status in the absence of immunosuppression (IS), known as operational tolerance, can be achieved in a small proportion of liver transplant recipients, but we lack reliable tools to predict its spontaneous development. We conducted a prospective, multicenter, biomarker-strategy design, IS withdrawal clinical trial to determine the utility of a predictive biomarker of operational tolerance. The biomarker test, originally identified in a patient cohort with high operational tolerance prevalence, consisted of a 5-gene transcriptional signature measured in liver tissue collected before initiating IS weaning. One hundred sixteen adult stable liver transplant recipients were randomized 1:1 to either arm A (IS withdrawal regardless of biomarker status) or arm B (IS withdrawal in biomarker-positive recipients). Immunosuppression withdrawal was initiated in 82 participants, rejection occurred in 54 (67.5%), and successful discontinuation of IS was achieved in 22 (27.5%), but only 13 (16.3%) met operational tolerance histologic criteria (10 in arm A; 3 in arm B). The biomarker test did not yield useful information in selecting patients able to successfully discontinue IS. Operational tolerance was associated with time posttransplant, recipient age, presence of circulating exhausted CD8 & thorn; T cells, and a reduced number of immune synapses within the graft.

The British Society of Gastroenterology commissioned an update on the guidelines for management of hepatocellular carcinoma (HCC) in adults at an opportune time. The incidence of and mortality from this cancer is increasing in the UK, as in other Western nations. Several clinical and scientific advances in HCC have been made in the last decade. This article, written on behalf of the HCC-UK committee, provides a commentary on the guidelines, with specific focus on areas of practice change.

Early detection of hepatocellular carcinoma (HCC) through effective surveillance is critical to improving patient outcomes. These UK national guidelines provide consensus-based standards for ultrasound (US) surveillance in individuals at risk of HCC, with the aim of enhancing diagnostic quality, consistency and service delivery. Developed by a multidisciplinary expert group, the guidelines define key components of a high-quality surveillance programme, including image acquisition protocols, structured reporting using a validated classification system, appropriate training requirements and pathways for audit and quality assurance. Emphasis is placed on equity of access, patient-centred care and improving adherence. These standards are designed to support healthcare professionals, commissioners, and service providers in delivering robust HCC surveillance across the NHS, ultimately contributing to earlier diagnosis and improved survival.

INTRODUCTION:Alpha-1 Antitrypsin Deficiency (AATD)-associated panniculitis is a rare inflammatory condition characterized by painful subcutaneous plaques or nodules, often accompanied by ulceration or oily discharge. Despite its clinical and emotional burden, limited data exist on the lived experiences of individuals with this condition. METHOD:An international online survey was conducted between April and July 2024, targeting individuals with AATD-associated panniculitis. The survey, co-designed with an affected individual and multi-disciplinary specialists, included 32 questions on demographics, diagnostic journey, life impact, and treatments. Responses were analysed using descriptive statistics and thematic analysis. RESULTS:41 responses were included in the analysis (68% female; mean age 52.3 years). Participants reported lesions at diverse sites, affecting the lower and upper limbs, followed by the trunk, buttocks, and genitalia. 41.5% experienced both ulceration and oily discharge. 61% of participants reported being misdiagnosed which negatively affected their mental health. More than half of respondents 'strongly agreed' or 'agreed' that living with alpha-1 panniculitis had made them anxious. Access to specialist care was a major concern, with 69% finding it difficult to obtain specialist advice. Treatments varied, and augmentation therapy was identified as the subjectively the most effective. Open-ended responses revealed gaps in healthcare professionals' awareness and highlighted the need for better mental health support and specialist access. CONCLUSION:AATD-associated panniculitis significantly impacts physical, emotional, and social well-being. Addressing gaps in diagnosis and treatment, increasing healthcare providers awareness, and adopting multidisciplinary approaches are essential to improve individuals' outcomes and quality of life.

Alpha-1 antitrypsin is a member of the serpin family of protease inhibitors and normally found in monomeric form at high concentration in the circulation. Certain pathogenic variants of this protein self-assemble into flexible chains (polymers) that undergo toxic accumulation in the liver, underlying the development of liver disease, and a corresponding functional deficiency in circulation results in a susceptibility to chronic damage to the lungs and thereby COPD. A proportion of these polymers are detectable in the circulation. This study aimed to provide data on the dynamics of AAT monomers and polymers in the circulation after correction of a deficiency state by liver transplantation. The evolution of the circulating AAT phenotype was characterised quantitatively over time by analysis of blood samples taken pre- and post-liver transplant from three PiZZ AAT deficiency patients, using a panel of conformer-specific monoclonal antibodies and a novel ELISA with enhanced sensitivity for AAT polymers. Circulating wild-type M AAT was found to increase with a half-time of 29-39 h, attaining a clinically-defined putative ‘protective’ threshold level within 24-50 h post-transplant. Baseline circulating polymer levels ranged from 5-35 μg/mL with a half-time clearance of 3-12 h following transplant, and levels were indistinguishable from reference wild-type plasma 22 months post-surgery. The glycosylation profile and disappearance of detectable circulating polymers of AAT were consistent with their origin in, and canonical secretion by, the liver. To our knowledge this is the first post-transplant evaluation of the hybrid conformational profile of endogenous and donor tissue-derived AAT.

Hepatocellular carcinoma (HCC) is a rapidly growing cause of cancer-related deaths in the UK, with early detection being critical for improving survival rates. Despite clear guidelines recommending 6-monthly surveillance for at-risk populations, participation remains low, with an estimated 20% of eligible patients attending regular surveillance. This guidance outlines the minimum standards for delivering effective HCC surveillance, emphasising the need for integrated patient tracking, digital call-recall systems and a multifaceted approach to engagement. Combining ultrasound with serum alpha-fetoprotein (AFP) improves detection rates, though AFP alone is insufficient due to its variability. The recommendations aim to increase surveillance adherence, enhance early diagnosis and ultimately improve outcomes for patients at risk of HCC.

Background Long-term surviving liver transplant recipients can spontaneously develop operational tolerance, which allows them to completely discontinue their immunosuppression, but we lack validated tools to predict the likelihood of rejection following immunosuppression withdrawal. A previous clinical trial showed that a logistic regression algorithm including the transcript levels of a set of five genes in a liver biopsy could predict the success of immunosuppression withdrawal with high sensitivity and specificity. Objective To determine if the use of a liver tissue transcriptional test of tolerance to stratify liver recipients prior to immunosuppression withdrawal accurately identifies operationally tolerant recipients and reduces the incidence of rejection, as compared with a control group in whom immunosuppression withdrawal is performed without stratification. Design and methods Prospective, multicentric, phase IV, biomarker-strategy design trial with a randomised control group in which adult liver transplant recipients were randomised 1 : 1 to either: (1) non-biomarker-based immunosuppression weaning (Arm A); or (2) biomarker-based immunosuppression weaning (Arm B). Setting and participants Adult liver transplant recipients ≥ 3 years post transplant (≥ 6 years if age ≤ 50 years old) with no history of autoimmunity or recent episodes of rejection, normal allograft function, and no significant histological abnormalities in a baseline screening liver biopsy, recruited from 12 transplant units in United Kingdom, Germany, Belgium and Spain. Intervention Enrolled patients underwent a screening liver biopsy to exclude the presence of subclinical allograft damage. Eligible participants randomised to Arm A underwent gradual discontinuation of immunosuppression. Among participants allocated to Arm B, only those found to be biomarker-positive were offered immunosuppression withdrawal, while biomarker-negative participants remained on their baseline immunosuppression. Patients who completely discontinued immunosuppression and maintained stable allograft function underwent protocol liver biopsies at 12 and 24 months after immunosuppression withdrawal. Main outcome measure Development of operational tolerance, defined as the successful discontinuation of immunosuppression with maintenance of normal allograft status 12 and 24 months after immunosuppression withdrawal. Results One hundred and twenty-two patients were eligible to participate in the trial, 116 were randomised (58 to Arm A and 58 to Arm B), 80 initiated immunosuppression withdrawal and 34 were maintaining on their baseline immunosuppression. Among the 80 patients who initiated withdrawal, 54 (67.5%) developed clinically apparent rejection, 22 (27.5%) successfully discontinued immunosuppression, 21 underwent a liver biopsy and 13 (16.3%) met the histological criteria of operational tolerance at 12 months after immunosuppression discontinuation. The transcriptional tolerance biomarker was not accurate at identifying patients meeting the operational tolerance criteria [odds ratio 1.466, 95% confidence interval (CI) 0.326 to 9.215; p = 0.744; Sensitivity (Sn) 54%, Specificity (Sp) 42%, positive predictive value 16%, and negative predictive value 81%, with an accuracy of 44%]. Due to the poor diagnostic performance of the test, the trial was terminated prematurely following an interim analysis of the results. No patients lost their grafts as a result of rejection during the study duration. Conclusions In selected liver transplant recipients, immunosuppression withdrawal proved to be feasible, but was successful in a much lower proportion of patients than originally estimated. A previously validated liver tissue transcriptional biomarker test was not considered accurate in predicting the success of immunosuppression withdrawal. Study registration Current Controlled Trials ISRCTN47808000 and EudraCT 2014-004557-14. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 13/94/55) and is published in full in Efficacy and Mechanism Evaluation; Vol. 12, No. 3. See the NIHR Funding and Awards website for further award information. Plain language summary After liver transplantation, the body’s immune system may reject the transplanted organ. In order to prevent rejection, the immune system has to be weakened or suppressed by administering anti-rejection medications. The majority of liver transplant patients need to take the anti-rejection drugs for life, which can be problematic due to their many side effects. However, years after transplantation, a small group of patients can stop their anti-rejection drugs without undergoing rejection. This phenomenon is known as transplantation tolerance. In a study completed in 2012, it was possible to identify liver transplant patients who had developed tolerance with high precision by conducting a genetic test in a liver biopsy. The objective of the current clinical trial was to validate this test of tolerance. This was done by enrolling patients more than 3 years after transplantation and allocating them at random to two groups. All the patients in group A had their anti-rejection medication gradually discontinued, while in group B only those patients who had a positive test result had their anti-rejection medication weaned. The expectation was that more patients would be able to stop their anti-rejection medication in group B than in group A. One hundred and twenty-two patients were enrolled in the trial, out of whom 80 patients attempted to discontinue the anti-rejection drugs, while 34 patients maintained their normal medications. Among patients who attempted to stop anti-rejection drugs, 67.5% developed rejection, 27.5% completely stopped the anti-rejection drugs, but 16% were considered as truly tolerant after having had a liver biopsy. Overall, drug discontinuation was successful in a much lower proportion of patients than originally predicted. Furthermore, the test of tolerance was not accurate enough to identify tolerant patients before initiating anti-rejection drug discontinuation. As a result of the diagnostic test not performing as expected, the trial had to be terminated prematurely. Scientific summary Background Long-term survival following liver transplantation has not significantly improved over the past 30 years, with long-term sequelae from chronic immunosuppression, including infections and cancer, being the most common causes of death. Long-term surviving liver transplant recipients can spontaneously develop operational tolerance, which allows them to completely discontinue their immunosuppression, but we lack validated tools to predict the likelihood of rejection following immunosuppression withdrawal. A previous clinical trial showed that a logistic regression algorithm including the transcript levels of a set of five genes in a liver biopsy could predict the success of immunosuppression withdrawal with high sensitivity and specificity. Objective To determine if the use of a liver tissue transcriptional test of tolerance to stratify liver recipients prior to immunosuppression withdrawal accurately identifies operationally tolerant recipients and reduces the incidence of rejection, as compared with a control group in whom immunosuppression withdrawal is performed without stratification. Methods Design The liver immunosuppression free trial (LIFT) was a prospective, multicentre, phase IV, biomarker-strategy design trial with a randomised control group in which adult liver transplant recipients were randomised 1 : 1 to either: (1) non-biomarker-based immunosuppression (IS) weaning (Arm A); or (2) biomarker-based IS weaning (Arm B). Participants: liver transplant recipients ≥ 3 years post transplant (≥ 6 years if age ≤ 50 years old) with no history of autoimmunity or recent episodes of rejection, normal allograft function, and no significant histological abnormalities in a baseline screening liver biopsy, recruited from 12 transplant units in UK, Germany, Belgium and Spain. Intervention Enrolled patients underwent a screening liver biopsy to exclude the presence of subclinical allograft damage. Eligible participants randomised to Arm A underwent gradual discontinuation of immunosuppression over a 6 to 9-month period. Among participants allocated to Arm B, only those found to be biomarker-positive were offered immunosuppression withdrawal (as in Arm A), while biomarker-negative participants remained on their baseline maintenance immunosuppression. Patients who completely discontinued immunosuppression and maintained stable allograft function underwent protocol liver biopsies at 12 and 24 months after immunosuppression withdrawal to confirm histological criteria of operational tolerance (as previously described by the Banff Liver Histopathology Group). Main outcome measure The primary end point was the development of operational tolerance, defined as the successful discontinuation of immunosuppression with maintenance of normal allograft status, as assessed by liver biopsy and liver tests 12 and 24 months after immunosuppression withdrawal. Results Of the 122 patients eligible to participate in the trial, 116 randomised (58 to Arm A and 58 to Arm B), 80 initiated immunosuppression withdrawal and 34 were maintaining on their baseline immunosuppression. Among the 80 patients who initiated immunosuppression withdrawal, 54 (67.5%) developed clinically apparent rejection, 22 (27.5%) successfully discontinued immunosuppression, 21 underwent a liver biopsy and 13 (16.3%) met the histological criteria of operational tolerance at 12 months after immunosuppression discontinuation. The remaining four patients were withdrawn from the study before developing rejection or reaching the primary end point. Ten out of the 56 (18%) of patients who initiated immunosuppression withdrawal in Arm A achieved operational tolerance at 12 months versus 3 among the 24 patients (13%) who initiated withdrawal in Arm B. The performance evaluation of the transcriptional tolerance biomarker showed that the test was not accurate at identifying patients meeting the operational tolerance criteria (odds ratio 1.466, 95% IC 0.326 to 9.215; p = 0.744; Sn 54%, Sp 42%, positive predictive value 16%, and negative predictive value 81%, with an accuracy of 44%). Due to the poor diagnostic performance of the test, the trial was terminated prematurely following an interim analysis of the results. Following the protocol liver biopsy performed 24 months after withdrawal, 16 out of the 21 who underwent a liver biopsy 12 months after IS discontinuation were considered not to require immunosuppression, 15 (18.8% of the 80 patients who initiated IS withdrawal) of whom met operational tolerance histology criteria. No patients lost their grafts as a result of rejection during the study duration. Subclinical histological abnormalities indicative of active alloimmune damage in patients considered non-eligible to participate in the trial were associated with serum transaminases, donor-specific antibodies and/or transient elastography measurements. Conclusions Immunosuppression withdrawal proved to be feasible and safe but was successful in a much lower proportion of subjects than originally estimated. A liver tissue biomarker test previously validated in a population of liver transplant recipients with a much higher prevalence of operational tolerance, was not accurate in predicting the success of immunosuppression withdrawal. As a result, the trial had to be terminated prematurely and did not meet its objectives. The use of non-invasive markers such as serum transaminases, donor-specific antibodies and transient elastography is useful to identify stable liver transplant recipients with active underlying graft alloimmunity despite receiving immunosuppression. Study registration Current Controlled Trials ISRCTN47808000 and EudraCT 2014-004557-14. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 13/94/55) and is published in full in Efficacy and Mechanism Evaluation; Vol. 12, No. 3. See the NIHR Funding and Awards website for further award information.

INTRODUCTION:Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder characterised by low circulating levels of alpha-1 antitrypsin (AAT) protein, a key inhibitor of neutrophil elastase and proteinase 3 (PR3) which is also the main autoantigen in granulomatosis with polyangiitis (GPA). This systematic review examines the association between AATD and GPA. METHODS:A systematic search of PubMed, Embase, Cochrane, EBSCO Medline and Scopus (December 2024) identified studies on AATD and GPA. Data extraction and quality assessment followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A random-effects meta-analysis was conducted to calculate pooled odds ratios and assess heterogeneity. RESULTS:23 studies (9634 individuals) met inclusion criteria. The Z-allele prevalence was 11.65% in GPA compared to 3.29% in controls and the S-allele prevalence was 10.8% in GPA compared to 5.26% in controls. Among 1755 individuals with GPA across 10 studies that provided specific genotype data, 22 (1.25%) were homozygous for the Z-allele. Meta-analysis showed that Z-allele carriers had 3.11 times higher odds of developing GPA (eight studies; 95% CI 2.43-3.9; I2: 0%). CONCLUSION:This meta-analysis reinforces the link between AATD and GPA, particularly in carriers of the Z-allele, supporting the role of PR3 dysregulation in GPA pathogenesis.

BACKGROUND:Hepatocellular carcinoma (HCC) incidence has increased rapidly, and prognosis remains poor. We aimed to explore predictors of routes to diagnosis (RtD), and outcomes, in HCC cases. METHODS:HCC cases diagnosed 2006-2017 were identified from the National Cancer Registration Dataset and linked to Hospital Episode Statistics and the RtD metric. Multivariable logistic regression was used to explore associations between RtD, diagnosis year, 365-day mortality and receipt of potentially curative treatment. RESULTS:23,555 HCC cases were identified; 36.1% via emergency presentation (EP), 30.2% GP referral (GP), 17.1% outpatient referral, 11.0% two-week wait and 4.6% other/unknown routes. Odds of 365-day mortality was >70% lower via GP or OP routes than EP, and odds of curative treatment 3-4 times higher. Further adjustment for cancer/cirrhosis stage attenuated the associations with curative treatment. People who were older, female, had alcohol-related liver disease, or were more deprived, were at increased risk of an EP. Over time, diagnoses via EP decreased, and via GP increased. CONCLUSIONS:HCC RtD is an important predictor of outcomes. Continuing to reduce EP and increase GP and OP presentations, for example by identifying and regularly monitoring patients at higher risk of HCC, may improve stage at diagnosis and survival.

Deaths from the majority of cancers are falling globally, but the incidence and mortality from hepatocellular carcinoma (HCC) is increasing in the United Kingdom and in other Western countries. HCC is a highly fatal cancer, often diagnosed late, with an incidence to mortality ratio that approaches 1. Despite there being a number of treatment options, including those associated with good medium to long-term survival, 5-year survival from HCC in the UK remains below 20%. Sex, ethnicity and deprivation are important demographics for the incidence of, and/or survival from, HCC. These clinical practice guidelines will provide evidence-based advice for the assessment and management of patients with HCC. The clinical and scientific data underpinning the recommendations we make are summarised in detail. Much of the content will have broad relevance, but the treatment algorithms are based on therapies that are available in the UK and have regulatory approval for use in the National Health Service.

Background & Aims: Liver stiffness measurement (LSM) and spleen stiffness measurement (SSM) have been shown to be useful tools for assessing the risk of fibrosis and portal hypertension, respectively. However, data on the accuracy of LSM and SSM measured by point-shear wave elastography (pSWE) in patients affected by primary sclerosing cholangitis (PSC) are still lacking. Thus, we aimed to prospectively assess their performance in a cohort of patients with PSC. Methods: We determined the correlation between LSM assessed by a pSWE technique (ElastPQ) and by FibroScan-transient elastography (F-TE). Furthermore, we used receiver-operating characteristic curves and area under the curves (AUROC) to evaluate the performance of LSM by ElastPQ for the staging of fibrosis, using F-TE as a reference standard, and the performance of LSM and SSM by ElastPQ in predicting the presence of oesophageal varices (OVs). Results: One hundred and fifty-two patients with PSC (93 males [61.2%], mean age 46 ± 16 years) were prospectively recruited. ElastPQ and F-TE LSMs were available for all patients, while ElastPQ SSM was available in 109 (72%) patients of whom 35 underwent upper gastrointestinal endoscopy within 1 year of the ultrasound assessment. ElastPQ LSM showed an excellent correlation with F-TE (p <0.001, Spearman’s 0.93; Lin’s 0.86) and a good diagnostic accuracy for fibrosis staging along all stages of liver fibrosis (AUROCs 0.96, 0.97, 0.97 and 0.99 for fibrosis stages F≥1, F≥2, F≥3 and F=4, respectively), using F-TE as a surrogate of histological fibrosis. ElastPQ SSM showed a good diagnostic performance in predicting the presence of OVs at endoscopy. Conclusions: LSM and SSM by ElastPQ can be used as accurate tools for liver fibrosis risk assessment and fibrosis staging, as well as for predicting the presence of OVs in the work-up of patients with PSC. Impact and implications: Liver and spleen stiffness measurement (LSM and SSM, respectively) by ElastPQ point-shear wave elastography in patients with primary sclerosing cholangitis represent reliable and reproducible tools for non-invasively staging the severity of liver disease and stratifying patients according to their risk of developing liver-related outcomes. In particular, LSM shows good accuracy for staging liver fibrosis and therefore detecting those patients at high risk of having compensated advanced chronic liver disease who require close monitoring. SSM seems to be promising to detect the risk of portal hypertension and therefore of oesophageal varices, enabling the triaging of patients who really need to undergo a screening endoscopy.

Introduction Cholestatic itch is challenging to manage and associated with poor quality of life. The FITCH study demonstrated efficacy for bezafibrate in the reduction of itch symptoms in primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Our cholestatic itch management algorithm employs bezafibrate after bile acid binding resins. Here we present our real world experience of BZF for itch in a tertiary liver service. Methods All patients prescribed BZF for cholestatic itch between Jan 2022 and April 2023 at a tertiary liver centre were identified from prescribing records. Demographics, clinical data and treatment responses were retrospectively recorded at the time of and 3 months after starting BZF. Differences in laboratory data before and after treatment were compared with Wilcoxon Signed-Rank tests. Results 16 patients were treated with BZF over the study period, 4 patients with PSC, 5 with PBC (one post-liver transplantation (LT)), 2 with PSC-autoimmune hepatitis (AIH) overlap, 2 with PBC-AIH, 2 with biliary stricturing post-LT and 1 with cystic fibrosis associated liver disease. Four patients had cirrhosis. Mean age was 61 years (range 24–76) and patients were started on either 400mg MR OD (10/16) or 200mg IR (6/16). At 3 month follow up 11/16 (69%) reported improvement and 5/16 (31%) unchanged itch. Prior to starting, itch was described as “severe” to “unbearable” in the majority of patients (6–10/10 severity). After three months, in those with improvement, all reported itch scores ≤ 5/10 without additional antipruritic medications. A significant decrease was observed in ALP after 3 months treatment (299 vs 203 IU/L, p = 0.005), but no significant change in ALT (70 vs 60 IU/L, p = 0.09), AST (50 vs 54 IU/L, p = 1), bilirubin (13 vs 10 μmol/L, p 0.85) or other markers of synthetic function. The smallest drop in ALP was observed in patients with PBC, likely due to UDCA treatment leading to lower baseline ALP. A rise in average serum creatinine occurred (69 μmol/L to 77 μmol/L, p = 0.03) but no individual required cessation of BZF. One patient stopped BZF due to diarrhoea and 5 due to lack of efficacy. 1 patient reported erratic blood sugar control, unlikely related to BZF. No episodes of rhabdomyolysis were reported. Conclusions This real world assessment of BZF demonstrates marked improvement in cholestatic itch in over two thirds of patients. BZF is well tolerated and associated with improvement in biochemical markers of cholestasis.

OBJECTIVE:Hepatocellular carcinoma (HCC) incidence in the UK trebled between 1997 and 2017. With increasing numbers requiring treatment, understanding the likely impact on healthcare budgets can inform service planning and commissioning. The aim of this analysis was to use existing registry data to describe the direct healthcare costs of current treatments for HCC and estimate the impact on National Health Service (NHS) budgets. DESIGN:A retrospective data analysis based on the National Cancer Registration and Analysis Service cancer registry informed a decision-analytic model for England comparing patients by cirrhosis compensation status and those on palliative or curative treatment pathways. Potential cost drivers were investigated by undertaking a series of one-way sensitivity analyses. RESULTS:Between 1 January 2010 and 31 December 2016, 15 684 patients were diagnosed with HCC. The median cost per patient over 2 years was £9065 (IQR: £1965 to £20 491), 66% did not receive active therapy. The cost of HCC treatment for England over 5 years was estimated to be £245 million. CONCLUSION:The National Cancer Registration Dataset and linked data sets have enabled a comprehensive analysis of the resource use and costs of secondary and tertiary healthcare for HCC, providing an overview of the economic impact to the NHS England of treating HCC.

Healthcare provision has been severely affected by COVID‐19, with specific challenges in organ transplantation. Here, we describe the coordinated response to, and outcomes during the first wave, across all UK liver transplant (LT) centers.