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Summary: Background: Sequential use of non‐invasive fibrosis tests (NITs) to identify patients with advanced hepatic fibrosis is recommended. However, it remains unclear how reliable clinicians are staging liver fibrosis using combinations of NITs. Aim: Our aim was to assess concordance between NIT‐based 'clinician fibrosis assessment (CFA)' and histology in patients with metabolic dysfunction‐associated steatotic liver disease (MASLD) and compare this with established algorithmic approaches. Methods: Six experienced hepatologists independently staged 230 MASLD patients for advanced fibrosis (F0‐2 vs F3‐4) using FIB‐4, FIB‐4+ELF, FIB‐4+ vibration controlled transient elastography (VCTE; Fibroscan™) and FIB‐4+ELF+VTCE. Concordance between histology and CFA or algorithmic approaches were assessed. Results: A total of 230 patients were included (median age 54 [22–78] years; 55% female; median FIB‐4 1.21 [IQR: 0.78–1.91]; ELF 9.3 [IQR: 8.6–10.2]; VCTE 9.4 [IQR: 6.3–14.3]; 41% F0‐1, 22% F2, 21% F3 and 16% F4). Overall, area under the receiver operator curves for histologic F3‐4 for the raw tests were 0.84 for FIB‐4, 0.86 for ELF and 0.86 for VCTE. Concordance between the hepatologists was good (FIB4, κ = 0.64; FIB‐4+ELF, κ = 0.70; FIB‐4+VCTE, κ = 0.69; FIB‐4+ELF+VCTE, κ = 0.70). Concordance between individual CFA and histology was variable, which was reflected in variability in sensitivity (44%–84%) and specificity (76%–94%). Concordance with histology was better when clinicians used NIT combinations. Purely algorithmic approaches, particularly sequential use of FIB‐4 then VCTE, tended to perform better than the CFA. Conclusions: Adhering to the recommended algorithmic approaches using NITs to stage fibrosis tended to perform more accurately than less‐structured clinician NIT‐based assessments conducted by experienced hepatologists. [ABSTRACT FROM AUTHOR]

Primary Sclerosing Cholangitis (PSC) is a progressive cholestatic liver disease with no licensed therapies. Previous Genome Wide Association Studies (GWAS) have identified genes that correlate significantly with PSC, and these were identified by systematic review. Here we use novel Network Proximity Analysis (NPA) methods to identify already licensed candidate drugs that may have an effect on the genetically coded aspects of PSC pathophysiology. Over 2000 agents were identified as significantly linked to genes implicated in PSC by this method. The most significant results include previously researched agents such as metronidazole, as well as biological agents such as basiliximab, abatacept and belatacept. This in silico analysis could potentially serve as a basis for developing novel clinical trials in this rare disease. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to McPherson et al papers. To view these articles, visit https://doi.org/10.1111/apt.18061 and https://doi.org/10.1111/apt.18176 [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to McPherson et al papers. To view these articles, visit https://doi.org/10.1111/apt.18061 and https://doi.org/10.1111/apt.18171. [ABSTRACT FROM AUTHOR]

Background: Data show that patients with autoimmune hepatitis have significantly reduced quality-of-life and that corticosteroids carry marked side effects. Aims: This study explored patients' experiences of autoimmune hepatitis and its treatments; key aspects for developing safe and effective new approaches to therapy. Methods: An anonymised, internet-based survey collected data including patient demographics, treatments, side-effects, impact on day-to-day life, sources of support and attitudes towards autoimmune hepatitis between December 2019–January 2020. Semi-structured interviews were conducted with 13 patients to further explore their support networks, treatment experiences and health priorities. Descriptive and quantitative analyses were undertaken using R and free text responses were subject to thematic analysis. Results: In total, 270 survey responses were received (median age 55 years and 94% female). Perceived medication side-effects were reported by 66% (169/257) and 73% responded negatively about their experience of corticosteroids. The majority (62·3% [(109/175]) would 'definitely' or 'probably' consider clinical trial participation to improve their care. Only 18·7% (31/166) reported access to a specialist liver nurse and nearly half were involved in support groups. Interview and survey data suggested that major issues were stigma, loss of control and fatigue. Conclusions: This study provides insights into the realities of living with autoimmune hepatitis with clear issues around lack of support networks, need for patient empowerment and stigma surrounding liver disease. Patient priorities are better therapies to slow disease progression, avoiding corticosteroids and minimising side-effects. Patient willingness to participate in trials suggests that they are achievable provided they have the right design and clinical endpoints. [ABSTRACT FROM AUTHOR]

SUMMARY: Background: Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that results in substantial morbidity and mortality with many unanswered clinical and research questions. Improved understanding of disease pathogenesis, including the extra‐hepatic manifestations of AIH, may allow targeted treatments with greater efficacy and fewer associated adverse events. Aim: To identify the spectrum of unanswered clinical and research questions facing care providers in the management of patients with autoimmune hepatitis (AIH). Methods: The International Autoimmune Hepatitis Group initiated a series of research workshops to start to address these questions. Key issues were discussed in small group sessions with collation of all discussions to be summarised in this manuscript. Results: Key issues were identified as: the need for better understanding of disease pathogenesis, standardisation of the methods and assays used to evaluate autoantibodies in AIH, refinement of the histopathological criteria for "typical" or "compatible" AIH, focus on the interaction with non‐alcohol related fatty liver disease, how to treat acute severe AIH, better assessment of quality of life in adults and paediatrics, standardising use of standard, third‐line and experimental therapies in AIH and search for biomarkers early in the disease course that predict outcome. Conclusion: This workshop has outlined the key unanswered clinical and research questions to help to define the research agenda in AIH. [ABSTRACT FROM AUTHOR]

Summary: Background: Treatment paradigms in autoimmune hepatitis (AIH) have remained largely unchanged for decades. Studies report ≤20% of patients have sub‐optimal treatment response with most requiring long‐term therapy. Aim: The United Kingdom Autoimmune Hepatitis (UK‐AIH) study was established to evaluate current treatment practice and outcomes, determine the unmet needs of patients, and develop and implement improved treatment approaches. Methods: The United Kingdom Autoimmune Hepatitis study is a cross‐sectional cohort study examining secondary care management of prevalent adult patients with a clinical diagnosis of autoimmune hepatitis. Enrolment began in March 2014. Prevalent cases were defined as having been diagnosed and treated for >1 year. Demographic data, biochemistry, treatment history and response, and care location were collected. Results: In total, 1249 patients were recruited; 635 were cared for in transplant units and 614 in non‐transplant centres (81% female with median age at diagnosis 50 years). Overall, 29 treatment regimens were reported and biochemical remission rate was 59%. Remission rates were significantly higher in transplant compared to non‐transplant centres (62 vs 55%, P = 0.028). 55% have ongoing corticosteroid exposure; 9% are receiving prednisolone monotherapy. Those aged ≤20 years at diagnosis were more likely to develop cirrhosis and place of care was associated with an aggressive disease phenotype. Conclusions: There are significant discrepancies in the care received by patients with autoimmune hepatitis in the UK. A high proportion remains on corticosteroids and there is significant treatment variability. Patients receiving care in transplant centres were more likely to achieve and maintain remission. Overall poor remission rates suggest that there are significant unmet therapeutic needs for patients with autoimmune hepatitis. [ABSTRACT FROM AUTHOR]

Objectives: Parenteral nutrition (PN) is widely used to provide nutritional support to patients with inaccessible or inadequate length of gut or non-functioning gut. The objective was to compare practice in PN administration to results of the National Confidential Enquiry into Patient Outcome and Death (NCEPOD) report, 'A Mixed Bag', and to establish whether good practice was being followed within this part of the UK. Setting: Using the Northern Nutrition Network (NNN), we examined the care of adult patients receiving PN in all 10 secondary care hospitals in our region. Participants: All patients receiving PN were included with no exclusions. Data were collected on 192 patients (51% females, median age 65 years (range 18-96)). Outcome measures: A data collection tool was designed based on the recommendations of the NCEPOD report. Results: PN was used for a median of 7 days with a 30-day mortality rate of 8%. Metabolic complications occurred in 34%, of which only 13% were avoidable. The catheter sepsis rate was 1.5 per 1000 PN days. The audit suggests that nutrition team input improves patient assessment prior to starting PN and review once PN is established. Risk of refeeding syndrome was identified in 75%. Areas for improvement are documentation of treatment goal (39%), review of PN constitution (38%), ensuring patients are weighed regularly (56%) and documentation of line-tip position (52%). Conclusions: This region-wide prospective audit suggests improved practice within the UK compared to the NCEPOD audit with lower mortality and line sepsis rates. However, documentation remains suboptimal. This work strengthens the case for introducing nutrition teams in hospitals without this service. These findings are likely to be reproduced across the UK and in other healthcare settings. We provide a template for similar audits of clinical practice. [ABSTRACT FROM AUTHOR]

Background: Fenofibrate (FF) has been suggested as a second-line agent in primary biliary cholangitis (PBC) patients who do not achieve adequate biochemical response to ursodeoxycholic acid (UDCA) monotherapy. Limited data exist on FF use beyond 12 months, and its long-term effects are unclear.Aim: To study the biochemical outcome of long-term (>12 months) FF treatment in combination with UDCA (FF + UDCA) in PBC patients and to determine the effect on predicted prognosis using the UK-PBC Risk Score.Methods: This was a retrospective cohort study of all PBC patients treated in a specialist center with FF + UDCA therapy after failure to achieve biochemical response. Liver and renal biochemical indices and the UK-PBC Risk Score at baseline and at 12, 24, 36, 48, and 60 months of FF + UDCA treatment were compared. Biochemical response was assessed using the POISE trial criteria at the end of FF + UDCA treatment.Results: Data from 23 patients treated with FF + UDCA combination were analyzed. The median dose of fenofibrate was 200 mg/day, and median treatment duration was 21 months (range 1-123 months). Six (26 %) patients discontinued FF within 1 year. In patients who completed 12 months (n = 17) and long-term therapy, significant decrease in ALP was seen at 12 (p = 0.0002), 24 (p = 0.002), and 36 (p = 0.03) months. More than 75 % patients met the POISE criteria of ALP response at all study time points. There was no significant improvement in the 5-, 10-, and 15-year UK-PBC Risk Scores after FF + UDCA treatment. No significant renal impairment or adverse events were reported.Conclusion: The long-term treatment of PBC patients with fenofibrate as an adjunct to UDCA is safe and effective in improving ALP, but the treatment did not significantly reduce the estimated probability of liver-related death or need for liver transplantation. [ABSTRACT FROM AUTHOR]

Background & Aims Patients with primary sclerosing cholangitis ( PSC) frequently highlight the impact of fatigue on their life quality. The study aims were to evaluate fatigue and its associations in PSC and investigate whether overt autonomic dysfunction contributes to the expression of fatigue. Methods All PSC patients under active follow-up at a regional liver centre were sent disease- and symptom-assessment tools. Three control groups were utilized; unselected community controls, patients with inflammatory bowel disease ( IBD) without PSC, and cholestatic controls with primary biliary cirrhosis ( PBC). A representative subgroup of PSC patients and normal controls underwent formal autonomic assessment. Results Symptom-assessment tools were returned by 40 non-transplanted patients. PSC patients had significantly worse fatigue than population controls ( P = 0.005). Fatigue was significant compared to population controls whether or not patients had accompanying IBD, although was more marked in those with both PSC and IBD. In patients with PSC and IBD, fatigue severity and autonomic symptoms were significantly increased in those with prior significant surgical intervention. Clinically significant autonomic dysfunction was seen in 22.5% of PSC patients, and of those, 78% had significant fatigue. Neurally mediated hypotension was found in 60% of PSC patients compared to 8% in the control group. The PSC group had increased sympathetic activity and reduced parasympathetic activity. Conclusion Fatigue is a significant problem in a minority of PSC patients and appears to be associated with autonomic dysfunction. Fatigued PSC patients should be screened for autonomic dysfunction and targeting such dysfunction represents a potential approach to treatment which warrants further exploration. [ABSTRACT FROM AUTHOR]

Primary biliary cirrhosis (PBC) is an autoimmune cholestatic liver disease. Susceptibility to PBC probably arises from a combination of genetic and environmental factors. The prevalence of PBC varies both on an international and a regional level. This can be explained, in part, by differences in clinical practice and case-finding activity. It is likely, however, that substantive geographical differences exist both in terms of genetic susceptibility and environmental factors that potentially trigger the disease in genetically susceptible individuals. The study of the epidemiology of PBC has strongly supported the concept of an environmental triggering factor, but as yet no specific agent has been identified. Ongoing work to discover the environmental agent, as well as the mechanism that causes the disease will answer key questions as to the epidemiology of this complex autoimmune disease as well as providing useful information for other autoimmune conditions. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is now the commonest cause of abnormal liver function tests (LFTs) in the UK with approximately a third of the population being affected. The exact prevalence is not known, but population studies from the USA and China using magnetic resonance spectroscopy estimate that approximately 30% of the general population have steatosis. It is a spectrum of disease ranging from simple steatosis, to non-alcoholic steatohepatitis (NASH), through to advanced fibrosis and cirrhosis. The majority have simple steatosis, but approximately 10-30% develop NASH and the development of NASH cirrhosis is associated with a poor long-term prognosis. Patients with NASH have increased liver-related and cardiovascular mortality. Many patients with NAFLD remain undiagnosed, and recognising those at risk is the first step. Clinicians overly rely on abnormal liver enzymes to identify patients with NAFLD, so patients with significant liver disease can be overlooked, potentially missing opportunities for intervention. Although liver biopsy is the gold standard method for diagnosing and staging NAFLD, the majority of patients can be effectively diagnosed noninvasively with tests that are routinely available in the clinic today. This review discusses a pragmatic approach to diagnosis and staging of NAFLD so that patients at the highest risk of liver-related complications can be identified. [ABSTRACT FROM AUTHOR]

Background and study aims: Discomfort during colonoscopymay affect acceptability of the procedure. The study aim was to determine factors, including prior hysterectomy and gender, associated with higher levels of patient discomfort during colonoscopy to help with procedural planning such as choice of instrument and sedation. Methods: A retrospective cohort study of colonoscopies (n=1098) performed between February 2007 and March 2012at the Tees Bowel Cancer Screening Centre within the English Bowel Cancer Screening Programme (BCSP). Determinants of moderate/severe discomfort assessed using the Gloucester Scale were explored, using logistic regression with a range of participant and procedural variables. Results: Rates of moderate/severe discomfort varied significantly among men, women without hysterectomy, and women with hysterectomy (5.8 %, 10.4 %, and 17.8 %, respectively; P<0.001). In an unadjusted model, women with hysterectomy were significantly more likely to experience moderate/severe discomfort than those without (odds ratio [OR]1.87, 95% confidence interval [95 %CI] 1.05-3.32, P=0.005). The very strong influence of sedation on discomfort level precluded an adjusted model. In subgroup analysis of participants receiving sedation, adjusted comparison again showed increased odds for moderate/severe discomfort for women with hysterectomy, compared with women without (OR 1.70, 95%CI 1.03-2.80, P=0.036). Conclusions: Prior hysterectomy is associated with greater levels ofmoderate/severe discomfort in women undergoing colonoscopy. Minimizing participant discomfort is desirable in any screening or surveillance program. This should be considered in preprocedural counseling and in selecting equipment, sedation, and analgesia. Further studies should examine methods to minimize discomfort in those with prior hysterectomy. [ABSTRACT FROM AUTHOR]