Background and aims: Cholestatic liver dysfunction is common in immune-related hepatitis (irH) during treatment with immune checkpoint inhibitors (CPI) for malignancy. We investigated the spectrum of bile duct injury and associated natural history in this cohort.Method: Clinical, laboratory, radiological and histopathological data in patients with evidence of bile duct injury during CPI treatment from 2018 to 2020 was collected in three tertiary hospitals.Results: In this study, ten patients with confirmed bile duct disease were identified.Pembrolizumab was most commonly implicated (8/10). Median CPI cycles prior to bile duct injury was 6. Median alanine aminotransferase and alkaline phosphatase were 225 U/L and 1549 U/L respectively. Clinical jaundice was seen in 6/10 and radiological evidence of bile duct pathology in 8/10. Of five patients, who had liver biopsy, three cases (including two cases with normal MRCP) showed primary sclerosing cholangitis (PSC) like changes with periductal fibrosis. All patients were treated first-line with prednisolone following cessation of CPI, three with mycophenolate mofetil and one with tacrolimus, with clinical response in four patients. Five patients died after a mean follow-up of 27 weeks; cause of death was primarily related to progression of malignancy. Conclusion:Within this heterogeneous cohort, we identified that CPI-related cholangiopathy responded poorly to immunosuppression and potentially progressed to bile duct loss. Thorough radiological and histological assessment is recommended, as identification of the cholangiopathy-associated phenotype may permit more informed advice regarding prognosis. Further data is required to determine detailed immunological characterisation in order to identify individuals at an increased risk of developing cholangiopathy.

BACKGROUND Solid organ transplantation is a life-saving intervention for end-stage organ disease. Post-transplant diabetes mellitus (PTDM) is a common complication in solid organ transplant recipients, and significantly compromises long-term survival beyond a year. AIM To perform a systematic review and meta-analysis to estimate incidence of PTDM and compare the effects of the 3 major immunosuppressants on incidence of PTDM. METHODS Two hundred and six eligible studies identified 75595 patients on Tacrolimus, 51242 on Cyclosporine and 3020 on Sirolimus. Random effects meta-analyses was used to calculate incidence. RESULTS Network meta-analysis estimated the overall risk of developing PTDM was higher with tacrolimus (OR = 1.4 95%CI: 1.0–2.0) and sirolimus (OR = 1.8; 95%CI: 1.5–2.2) than with Cyclosporine. The overall incidence of PTDM at years 2-3 was 17% for kidney, 19% for liver and 22% for heart. The risk factors for PTDM most frequently identified in the primary studies were age, body mass index, hepatitis C, and African American descent. CONCLUSION Tacrolimus tends to exhibit higher diabetogenicity in the short-term (2-3 years post-transplant), whereas sirolimus exhibits higher diabetogenicity in the long-term (5-10 years post-transplant). This study will aid clinicians in recognition of risk factors for PTDM and encourage careful evaluation of the risk/benefit of different immunosuppressant regimens in transplant recipients.

Non-alcoholic fatty liver disease presents a number of ethical dilemmas. These relate to the potential harms of diagnosing the disease in health, diagnosing a condition for which there is no effective treatment, and variability in specialists’ attitudes to discussing and managing obesity. Erroneous homogenisation of a patient group that is extremely varied in terms of risk factors such as ethnic background, socioeconomic status, and genetic predisposition may result in inappropriate uniformity of approach when counselling patients as to underlying causes. This article will explore these challenges from the perspective of the gastroenterologist or hepatologist who must navigate them. Each section starts with questions posed by patients or comments made by doctors. Caution is suggested before widespread population-based screening is established, and the need for good adherence to referral algorithms is emphasised. Physicians are urged to engage with the condition’s hidden complexities and reflect on their own communication strategies.

Chronic liver disease due to viral hepatitis continues to be a major global health concern. Timely diagnosis and treatment will prevent cirrhosis, risk of hepatocellular carcinoma (HCC), and requirement for liver transplantation. Numerous serum biomarkers are available for viral hepatitis that are helpful in diagnosis, measuring severity, progression of disease, evaluating the best therapeutic options, and monitoring antiviral treatment response. Determining the clinical use of available diagnostic tests can be challenging for the health care provider. Areas covered: This review article attempts to summarize the established and emerging serological markers for diagnosis and managing viral hepatitis. The literature search was performed in February 2018 and included MEDLINE and Embase databases for recent relevant literature on biomarkers for viral hepatitis. Expert Commentary: Despite the discovery of several candidate biomarkers, translating these to clinical practice in viral hepatitis and HCC remains challenging. While limited availability of the new biomarkers in prevalent geographic areas and significant cost remain major obstacles, there have been exciting developments in this field. Understanding the detection limits and sensitivity of these markers and translating them into clinical use is important in management of viral hepatitis and complications of liver disease such as cirrhosis and hepatocellular cancer.

Background: Emergency admissions in England for alcohol-related liver disease (ArLD) have increased steadily for decades. Statistics based on administrative data typically focus on the ArLD-specific code as the primary diagnosis and are therefore at risk of excluding ArLD admissions defined by other coding combinations. Aim: To deploy the Liverpool ArLD Algorithm (LAA), which accounts for alternative coding patterns (e.g., ArLD secondary diagnosis with alcohol/liver-related primary diagnosis), to national and local datasets in the context of studying trends in ArLD admissions before and during the COVID-19 pandemic. Methods:We applied the standard approach and LAA to Hospital Episode Statistics for England . The algorithm was also deployed at 28 hospitals to discharge coding for emergency admissions during a common 7-day period in 2019 and 2020, in which eligible patient records were reviewed manually to verify the diagnosis and extract data.Results: Nationally, LAA identified approximately 100% more monthly emergency admissions from 2013 to 2021 than the standard method. The annual number of ArLD-specific admissions increased by 30.4%. Of 39,667 admissions in 2020/21, only 19,949 were identified with standard approach, an estimated admission cost of £70 million in under-recorded cases. Within 28 local hospital datasets, 233 admissions were identified using the standard approach and a further 250 locally verified cases