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Summary: Background: Seladelpar is a potent and selective peroxisome proliferator‐activated receptor‐δ agonist that targets multiple cell types involved in primary biliary cholangitis (PBC), leading to anti‐cholestatic, anti‐inflammatory and anti‐pruritic effects. Aims: To evaluate the long‐term safety and efficacy of seladelpar in patients with PBC. Methods: In an open‐label, international, long‐term extension study, patients with PBC completing seladelpar lead‐in studies continued treatment. Seladelpar was taken orally once daily at doses of 5 or 10 mg with dose adjustment permitted for safety or tolerability. The primary analysis was for safety and the secondary efficacy analysis examined biochemical markers of cholestasis and liver injury. The study was terminated early due to the unexpected histological findings in a concurrent study for non‐alcoholic steatohepatitis, which were subsequently found to predate treatment. Safety and efficacy data were analysed through 2 years. Results: There were no serious treatment‐related adverse events observed among 106 patients treated with seladelpar for up to 2 years. There were four discontinuations for safety, one possibly related to seladelpar. Among 53 patients who completed 2 years of seladelpar, response rates increased from years 1 to 2 for the composite endpoint (alkaline phosphatase [ALP] <1.67 × ULN, ≥15% decrease in ALP, and total bilirubin ≤ULN) and ALP normalisation from 66% to 79% and from 26% to 42%, respectively. In those with elevated bilirubin at baseline, 43% achieved normalisation at year 2. Conclusions: Seladelpar was safe, and markedly improved biochemical markers of cholestasis and liver injury in patients with PBC. These effects were maintained or improved throughout the second year. Clinicaltrials.gov: NCT03301506; Clinicaltrialsregister.eu: 2017‐003910‐16. [ABSTRACT FROM AUTHOR]

Foaming of rigid polyvinyl chloride (PVC) is studied as a function of high molecular weight acrylic processing aids. The industrial process to evaluate quality of foam is discussed in detail. The role of acrylic processing aids to improve melt strength and hence foaming of PVC is explained. It is demonstrated that increase in molecular weight of acrylic processing aids increases its effectiveness. It is found that ultra‐high molecular weight processing aids is 25%–30% more efficient than relatively lower, but still high, molecular weight acrylic processing aids. The higher molecular weight processing aids provided comparable foaming performance at lower loading levels. Foaming reduced the density of PVC compounds to 0.32–0.34 g/cm3. More than 1000% expansion is achieved in the melt extrusion process using a chemical blowing agent. Fusion characteristics are also studied. Fusion times for initial fusion peaks are in the range of 42–44 s while the fusion times of the second fusion peaks are in the range of 74–94 s. The higher molecular weight processing aids maintained fusion characteristics of PVC compounds, warranting no significant changes in commercial process. [ABSTRACT FROM AUTHOR]

Objective: The rationale for this study was based on reports that valosin‐containing protein (VCP) mutations are found in hereditary inclusion body myositis (IBM) and VCP was detected in rimmed vacuoles of sporadic IBM (sIBM) muscle biopsies. Autoantibodies to VCP have not been reported in sIBM or other inflammatory myopathies (IIMs). The aim of this study was to determine the frequency and clinical significance of anti‐VCP antibodies in sIBM and other IIMs. Methods: Sera were collected from 73 patients with sIBM and 383 comparators or controls, including patients with IIM (n = 69), those with juvenile dermatomyositis (JDM) (n = 67), those with juvenile idiopathic arthritis (JIA) (n = 47), those with primary biliary cholangitis (PBC) (n = 105), controls that were age matched to patients with sIBM (similarly aged controls [SACs]) (n = 63), and healthy controls (HCs) (n = 32). Immunoglobulin G antibodies to VCP were detected by addressable laser bead immunoassay using a full‐length recombinant human protein. Results: Among patients with sIBM, 26.0% (19/73) were positive for anti‐VCP. The frequency in disease controls was 15.0% (48/320). Among SACs, the frequency was 1.6% (1/63), and in HCs 0% (0/32). Frequencies were 17.5% (11/63) for IIM, 25.7% (27/105) for PBC, 3.0% (2/67) for JDM, and 17.0% (8/47) for JIA. The sensitivity, specificity, positive predictive value, and negative predictive value of anti‐VCP for sIBM were 26.0%, 87.2%, 28.4%, and 85.9%, respectively. Of patients with sIBM, 15.1% (11/73) were positive for both anti‐VCP and anti–cytosolic 5′‐nucleotidase 1A (NT5c1A). Eleven percent of patients (8/73) were positive for anti‐VCP, but negative for anti‐NT5c1A. Conclusion: Anti‐VCP has low sensitivity and moderate specificity for sIBM but may help fill the seronegative gap in sIBM. Further studies are needed to determine whether anti‐VCP is a biomarker for a clinical phenotype that may have clinical value. [ABSTRACT FROM AUTHOR]

Background and Aims: The effect of major depression and antidepressant use on patient survival in chronic liver disease is unknown. We evaluated the impact of major depressive disorder (MDD) and antidepressants on survival among patients with alcoholic liver disease (ALD) and non‐alcoholic fatty liver disease (NAFLD). Methods: The Health Improvement Network database, the largest medical database in the United Kingdom, was used to identify incident ALD (n = 4148) and NAFLD (n = 19 053) in patients between 1986 and 2017. Our primary outcome was development of decompensated cirrhosis or death. MDD and each class of antidepressants were assessed in multivariate Cox proportional hazards models as time‐varying covariates. Models were adjusted for age, sex, socio‐economic status and comorbidities. Results: MDD rate was higher among patients with ALD (22.8%) compared to those with NAFLD (16.1%), P <.01. Antidepressant usage was common in patients with ALD (47.4%) and NAFLD (40.8%). After adjusting for covariates, MDD (adjusted hazard ratio [AHR]: 0.80, 95% CI: 0.63‐1.02 for NAFLD; and AHR 1.01, 0.88‐1.15 for ALD) was not associated with improved decompensated cirrhosis‐free survival. The antidepressant mirtazapine was associated with worse decompensated cirrhosis‐free survival among NAFLD (AHR 2.16, 95% CI: 1.32‐3.52) and ALD (AHR 1.53, 1.09‐2.15) cohorts. Similarly, mirtazapine was associated with mortality in both cohorts. Conclusions: MDD was not associated with worse outcomes for ALD or NAFLD. Mirtazapine was associated with an increased risk of decompensated cirrhosis or death, which was not observed with other antidepressants. Prospective studies are warranted to confirm these findings. [ABSTRACT FROM AUTHOR]

Summary: Background: There are limited long‐term data on outcomes of chronic hepatitis B (CHB) in untreated and tenofovir disoproxil fumarate (TDF)‐treated women during pregnancy. Aims: To assess clinical outcomes in a multiethnic cohort of patients during pregnancy and post‐partum in a low HBV endemic region. Methods: Retrospective real‐world study of women with CHB (treated or untreated with TDF) from 2011 to 2019; data including ALT, HBV DNA, HBeAg and liver stiffness measurement were collected during pregnancy and post‐partum. Results: In 341 women (446 pregnancies) followed for a median of 33 months (IQR: 26.7‐39.5) post‐partum, 19% (65/341) received TDF (11 initiated pre‐pregnancy, 53 for mother‐to‐child transmission (MTCT) prevention). During follow‐up, 72/341 had subsequent pregnancy, including 18/53 on TDF for MTCT risk, of whom 7/18 were re‐treated. In all TDF‐treated women, HBV DNA declined but rebounded after TDF withdrawal (median baseline, near birth and early follow‐up levels were 7.2, 3.0 and 5.5 log IU/mL respectively [P < 0.01]). In HBeAg+ patients (65/341) ALT flares were more common (P = 0.03), especially for those who stopped TDF post‐partum, requiring re‐treatment in 21% (11/53). In comparison, 54% (116/215) of untreated women had a post‐partum ALT flare; one with fulminant hepatitis underwent transplant 13 months post‐partum. HBsAg clearance occurred in 2.6% (9/341, 3/9 HBeAg+, 2/9 TDF treated) at median 30 months (IQR: 23‐40) and 37% (24/65) of HBeAg+ patients had HBeAg loss at median 17 months (IQR: 12‐26) post‐partum. Conclusions: Post‐partum ALT flares were common, especially after TDF withdrawal. Overall, 37% achieved HBeAg clearance and 2.9% had HBsAg loss during long‐term follow‐up. [ABSTRACT FROM AUTHOR]

Background: The burden of cirrhosis on the healthcare system is substantial and growing. Our objectives were to estimate the readmission rates and hospitalization costs as well as to identify risk factors for 90‐day readmission in patients with cirrhosis. Methods: We conducted a weighted analysis of the 2014 Nationwide Readmission Database to identify adult patients with cirrhosis‐related complications in the United States and assessed readmission rates at 30, 60 and 90 days post‐index hospitalization. Predictors of 90‐day readmissions were identified using weighted regression models adjusting for patient and hospital characteristics; the national estimate of hospitalization costs was also calculated. Results: Of the 58 954 patients admitted with cirrhosis‐related complications in 2014, 14 910 (25%) were readmitted within 90 days because of cirrhosis‐related complications. The main causes of readmission were ascites (56%), hepatic encephalopathy (47%) and bleeding oesophageal varices (9%). Independent predictors of 90‐day readmissions were male sex (adjusted OR [aOR]: 1.08, 95% CI, 1.04‐1.13), age <60 (aOR: 1.27, 95% CI, 1.22‐1.32), privately insured (aOR: 0.74, 95% CI, 0.70‐0.77), having ≥3 comorbid conditions (aOR: 1.27, 95% CI, 1.14‐1.42) and being discharged against medical advice (aOR: 1.41, 95% CI, 1.25‐1.59). The weighted cumulative national cost estimate of the index admission was $1.8 billion, compared to $0.5 billion for readmission. Conclusions: A quarter of patients admitted with cirrhosis‐related complications were readmitted within 90 days, representing a significant economic burden related to readmission of this population. Interventions and resource allocations to reduce readmission rates among cirrhotic patients is critical. [ABSTRACT FROM AUTHOR]

This document is a featured cover image for the journal Alimentary Pharmacology & Therapeutics. The image is based on a clinical trial extension study on the safety and efficacy of seladelpar in patients with primary biliary cholangitis. The study was conducted by a team of authors and provides two-year results. The document does not provide any specific details or findings from the study, but it serves as a visual representation of the research. [Extracted from the article]

The management of fatigue associated with chronic liver disease is a complex and major clinical challenge. Although fatigue can complicate many chronic diseases, it is particularly common in diseases with an inflammatory component. Fatigue can have both peripheral (i.e., neuromuscular) and central (i.e., resulting from changes in neurotransmission within the brain) causes. However, fatigue in chronic liver disease has strong social/contextual components and is often associated with behavioural alterations including depression and anxiety. Given the increasing awareness of patient‐reported outcomes as important components of treatment outcomes and clinical research, there is a growing need to better understand and manage this poorly understood yet debilitating symptom. Although several pathophysiological mechanisms for explaining the development of fatigue have been generated, our understanding of fatigue in patients with chronic liver disease remains incomplete. A better understanding of the pathways and neurotransmitter systems involved may provide specific directed therapies. Currently, the management of fatigue in chronic liver disease can involve a combined use of methods to beneficially alter behavioural components and pharmacological interventions, of which several treatments have potential for the improved management of fatigue in chronic liver disease. However, evidence and consensus are lacking on the best approach and the most appropriate biochemical target(s) whilst clinical trials to address this issue have been few and limited by small sample size. In this review, we outline current understanding of the impact of fatigue and related symptoms in chronic liver disease, discuss theories of pathogenesis, and examine current and emerging approaches to its treatment. [ABSTRACT FROM AUTHOR]

Problem In chronic hepatitis B ( CHB) carriers, alanine transaminase ( ALT) flares are common in the peripartum period. There are limited data on immunological changes of pregnancy in CHB. We hypothesize that in pregnant CHB carriers, the Th1/Th2 cytokine ratio is altered resulting in changes in biochemical/virological and liver fibrosis markers. Study methods Serum from 38 pregnant/post-partum CHB carriers (median age 32 years, 53% Asian, 8 HBeAg+) was tested for HBV DNA, quantitative HBV surface antigen, ALT and liver fibrosis by transient elastography ( TE). Serum cytokines were analyzed using a Luminex assay. Results Untreated CHB cases had mild ALT flares post-partum, but showed normal TE, and no change in viral markers despite increased Th1 cytokines compared to healthy controls ( P<.05). Conclusion CHB carriers show increased Th1 cytokines in the peripartum period albeit with no effect on viral load or liver disease suggesting an aborted antiviral immune response. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article related to the treatment of telaprevir-based therapy for HIV/hepatitis C coinfected patients.

A test procedure has been developed and used to characterise the performance of domestic microwave ovens in relation to the heating of chilled ready meals. The procedure uses reproducible test loads, which simulate the heating and weight loss characteristics of a chilled ready meal under consumer use. The temperature distribution after heating from 5 °C to a defined minimum temperature of 70 °C is measured in the food simulant using a purpose designed multipoint thermocouple ‘hedgehog’ probe. The temperature, weight loss and heating time data from the test are entered into a spreadsheet analysis program, which provides a simple oven performance ‘score’ and/or comprehensive heating performance data. [ABSTRACT FROM AUTHOR]

Background: Currently, the approved dosage of ribavirin has not been studied in patients with ‘normal’ alanine aminotransferase (ALT) levels. Methods: Modelling and simulations were performed using generalised additive models (GAMs) to predict the incidence of anaemia and rate of sustained virological response (SVR) in patients with hepatitis C virus (HCV) genotype 1 and persistently ‘normal’ ALT levels treated with peginterferon α-2a (40KD) 180 μg/week plus ribavirin 1000/1200 mg/day for 48 weeks. Results: Model-based simulations predicted that SVR rates would increase from 39 to 48% if patients with genotype 1 and persistently ‘normal’ ALT levels had received the standard weight-adjusted dose of ribavirin. This was similar to the predicted 49% SVR rate for genotype 1 patients with elevated ALT levels. The incidence of anaemia was predicted to increase from 13% to 23% in patients with persistently ‘normal’ ALT activity and was higher than that predicted for patients with elevated ALT levels; however, the difference appeared to be largely explained by the higher proportion of women in the former group. Conclusions: Simulations based on GAM suggest that regimens for patients with HCV genotype 1 should include the standard weight-adjusted dose of ribavirin, as similar SVR rates are predicted to be achieved, regardless of patients' ALT status at baseline. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) and hepatitis C virus (HCV) share similar transmission routes; thus, coinfection is frequent. The consequences of acute HBV infection in patients with chronic hepatitis C are unknown. Methods: We describe a 47-year-old male with chronic hepatitis C who acquired HBV and then spontaneously and apparently completely cleared HCV but developed chronic hepatitis B. Five serum samples collected over 14 months and lymphoid cells obtained after acquiring HBV were tested for HCV and HBV by both standard assays and ultra-sensitive polymerase chain reaction/nucleic acid hybridization (PCR/NAH) (sensitivity ∼2 IU/ml). Results: After superinfection with HBV, HBV surface antigen-positive chronic hepatitis developed with readily detectable HBV DNA. All sera collected after acquisition of HBV, which tested negative for HCV RNA by standard laboratory assay, were positive for HCV genomes when analysed by PCR/NAH. Peripheral lymphoid cells carried HBV DNA and covalently closed circular DNA, but were negative for HCV. Conclusions: This is the first reported case of profound suppression of chronic hepatitis C after superinfection with HBV and establishment of chronic hepatitis B. It is hypothesized that HBV infection precipitated generalized and/or virus-specific cellular immune responses that profoundly suppressed HCV replication and yet failed to inhibit progression to chronic hepatitis B. [ABSTRACT FROM AUTHOR]

Abstract: Albumin-interferon alfa (alb-IFN) is a novel recombinant protein derived from IFNα-2b genetically fused to human albumin, which combines in a single polypeptide the antiviral properties of IFNα with the long serum half-life of albumin. Interferon alfa (IFNα) mediated biological responses stem from the engagement of IFNα with its target receptor and subsequent modulation of interferon-specific gene (ISG) expression. The dynamics of ISG expression were evaluated in a Phase 2a study conducted in IFNα naïve patients with genotype 1 chronic hepatitis C (CHC) treated with alb-IFN. Whole blood was obtained pre-dose and on days 7 and 28 from 47 patients enrolled to receive two subcutaneous injections of alb-IFN 14 days apart in five dose cohorts ranging from 200 to1200μg. Gene expression of nine candidate genes including four ISGs was determined by a TaqMan Real-time PCR assay. There was sustained >5-fold median induction on days 7 and 28 of the ISG''s- OAS1, IRF7, IFI44 and IFI27. While all subjects showed a molecular response to alb-IFN, individual variability in pre-treatment gene expression levels and fold of modulation during treatment was observed. At days 7 and 28, induction of OAS1, IFI44 and IRF7 showed significant pair-wise correlation in individual patients (r >0.7 and P <0.001). There was no correlation of baseline expression or induction of gene expression with antiviral response. In conclusion, alb-IFN demonstrated robust induction of ISG that was consistent with the molecular response associated with an IFNα. [Copyright &y& Elsevier]

The power output of five recent domestic microwave ovens (on the market 2003/2004) was measured using a standard 1000 g water load during 30 min of continuous use. The power output of the ovens declined significantly ( P ≤ 0.05) in the first 5 min of use, ranging from a minimum of 7.0% to a maximum of 19.7%. Further but not always significant declines ( P ≤ 0.05) were measured after 20 min of continuous use. No significant reductions were measured between 20 and 30 min. Overall, the mean reduction in power output after 30 min of continuous use was 17.3% for these five ovens compared with 13.5% for five ovens in a previous study. Based on trials carried out approximately a decade apart, there has not been any improvement in the performance of domestic microwave ovens in terms of the decline in power output after continuous or prolonged use. The authors believe that many users, including consumers, caterers and those using domestic microwave ovens for research purposes, would benefit from a greater awareness and understanding of how the rapid reduction in power output in the first 5–20 min of use is likely to affect the expected heating performance. [ABSTRACT FROM AUTHOR]

T cell-mediated hepatitis is associated with significant morbidity and mortality worldwide. Levels of C-C chemokine ligand 3/macrophage inflammatory protein-1α (CCL3/MIP-1α) are elevated in the serum of patients with T cell-mediated liver diseases, but its role is not fully understood. Con A-induced hepatitis is a murine liver-specific inflammation mediated by activated T cells and is driven by an up-regulation of the hepatic expression of IFN-γ. In this study, we have used CCL3/MIP-1α gene-deficient mice to examine the role of CCL3/MIP-1α in the pathogenesis of Con A-induced hepatitis. We demonstrate a novel pro-inflammatory role for CCL3/MIP-1α since CCL3/MIP-1α deficiency significantly attenuated hepatic injury, both biochemically and histologically. Moreover, the recruitment of CCR1-expressing CD4 T cells to the liver after Con A treatment was strikingly attenuated by CCL3/MIP-1α deficiency. Correspondingly, hepatic IFN-γ produced by the recruited CD4 T cells was significantly reduced by CCL3/MIP-1α deficiency during Con A-induced hepatitis. Furthermore, treatment of mice with a dual CCR1/CCR5 peptide antagonist, methionylated RANTES, also markedly reduced hepatic injury and decreased the numbers of CD4 T cells within the liver producing IFN-γ during Con A-induced hepatitis. These findings demonstrate that blockade of the CCL3/MIP-1α-CCR1 pathway may represent a novel therapeutic target for treating T cell-mediated liver diseases. [ABSTRACT FROM AUTHOR]

The microwave heating characteristics of foods vary with temperature, chemical composition, physical state and geometry. The purpose of the food simulates reported in this paper is to provide heating loads that will enable reliable and reproducible characterization of the heating performance of microwave ovens (2.45 GHz), specifically when heating chilled convenience meals. An extensive literature search was done to identify food simulants that had been used to mimic the heating responses of foods when heated both conventionally and in microwave fields. Each prospective food simulant was initially assessed against a set of criteria that included ease of manufacture, stability and formability. Four meals were chosen to represent the range of chilled convenience meals available in the UK. Tests, using continuous fibre-optic temperature measurement during heating, indicated that the meals could be separated into two broad categories according to heating times, i.e. ‘slow’ and ‘fast’ responders. Food simulants were developed for the two food categories. A good match between food simulant and meal was achieved for the main indicators, i.e. temperatures at central and intermediate locations and weight loss. A close match (a difference of 2% between food simulant and meal) was achieved for the centre location, which is important, as this is often the coolest area in the meal after heating in domestic microwave ovens. [ABSTRACT FROM AUTHOR]

Summary The pathological association between leucocytes and gastrointestinal diseases has long been recognized. Chemokines are a large family of chemotactic cytokines whose fundamental role is the recruitment of leucocytes to tissues. Although chemokines and their receptors are considered to be mediators of inflammation and tissue injury in several inflammatory diseases, their precise role in the pathophysiology of gastrointestinal diseases remains incompletely understood. Nonetheless, by virtue of their expression and localization at sites of gastrointestinal tissue injury and inflammation, a number of investigators have suggested a vital role for chemokines and their receptors in the pathophysiology of gastrointestinal diseases. This short review examines the role of chemokines and their receptors in the gastrointestinal tract with an emphasis on their involvement in the regulation of intestinal and hepatic inflammation. [ABSTRACT FROM AUTHOR]

The liver of adult rats with cholestasis secondary to bile duct resection has been shown to express the proenkephalin gene and, by immunohistochemical stains, to contain met-enkephalin. To further study hepatic opioids in cholestasis, concentrations of proenkephalin-derived endogenous opioids were measured in a rat model of cholestasis by the use of radioimmunoassays. The specificity of the immunoreactivity detected by the assays was confirmed by high performance liquid chromatography (HPLC). In adult male rats with cholestasis due to BDR, the concentrations of three proenkephalin-derived opioid peptides were increased. Specifically, the mean hepatic concentrations of met-enkephalin, Met-Enk-Arg6-Phe7 and leu-enkephalin were 2.5 ( p<0.005), 2.1 ( p<0.005) and 2.5 ( p<0.01) fold higher than the corresponding mean for controls. These findings provide further independent evidence that opioid peptides accumulate in the liver in a model of cholestasis and are consistent with de novo synthesis of opioid peptides occurring in the cholestatic liver. This phenomenon may have relevance to the altered function of the opioid system in cholestasis and to the role of the liver as a neuroendocrine organ. [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Kang et al and Jun and Nguyen papers. To view these articles, visit https://doi.org/10.1111/apt.15626 and https://doi.org/10.1111/apt.15651 [ABSTRACT FROM AUTHOR]

Front cover: The cover image, by Shivali S. Joshi et al., is based on the Original Article Peripartum cytokine flares in a multiethnic cohort of chronic hepatitis B carriers does not correlate with hepatitis B virus suppression or increased risk of liver disease, DOI: 10.1111/aji.12707. [ABSTRACT FROM AUTHOR]

Introduction: Patient, clinician, and system-related barriers may affect adherence to hepatocellular carcinoma (HCC) surveillance programmes. The impact of a dedicated automated recall HCC surveillance programme on retention rates in patients eligible for screening is unknown. We aimed to describe and evaluate a large HCC surveillance programme in a publicly funded healthcare system., Methods: Data were collected from January 1, 2013, to December 31, 2022, from a retrospective cohort of subjects enrolled in a publicly funded automated recall semi-annual surveillance programme as per the American Association for the Study of Liver Disease HCC guidance in the Calgary Health Zone (~1.6 million), Canada. Patients were excluded if there was incomplete data or did not meet indications for surveillance. Cox regression was used to identify predictors of non-retention to surveillance., Results: A total of 7269 patients were included. The median was age 55.5 years (IQR: 45.5-63.8), 60% were male, 46% were of Asian descent, 51% had HBV infection, and 36% had cirrhosis (35% alcohol-related). Median follow-up was 4.9 years (IQR: 1.5-7.2). Overall, 52% (n = 3768) of patients were retained in the surveillance programme, while 8.3% (n = 603) left for potential medical reasons, and 40% (n = 2898) were lost in follow-up. The median time in the programme for those lost in follow-up was 0.81 years (IQR: 0.0-2.8) compared to 6.75 years if retained (IQR: 5.6-8.6; p < 0.001). In multivariable Cox regression analysis, HCV aetiology (HR 1.41; CI 1.23-1.62, p < 0.01), African ethnicity (HR 1.20, CI 1.02-1.42, p = 0.03), and cirrhosis (HR 1.16, CI 1.05-1.28, p < 0.01) increased risk of dropout. On interaction analysis, Hepatitis B amongst cirrhotic patients also increased risk of dropout (HR 1.48, CI 1.05-2.07, p = 0.02)., Conclusion: A dedicated automated recall HCC surveillance programme has a high retention rate in a large multi-ethnic cohort of patients while identifying certain marginalised patient populations, such as those with viral liver disease, cirrhosis, or African ethnicity, as particularly vulnerable to loss to follow-up., (© 2025 The Author(s). Liver International published by John Wiley & Sons Ltd.)

Prior to the introduction of virally inactivated clotting factor concentrates, the majority of individuals with congenital bleeding disorders became infected with the hepatitis C virus. Although liver biopsy is valuable in prognosis and guiding antiviral therapy, there is a reluctance to perform biopsies in this population because of the risk of hemorrhage. The purpose of this study was to evaluate the safety of transjugular liver biopsy, and the usefulness of evaluating liver histology in this patient population. Liver histopathology was assessed by the METAVIR index and compared with corrected sinusoidal pressures, platelet counts, and abdominal ultrasonography. Liver biopsy was performed at seven Canadian centers in 65 patients with hemophilia or von Willebrand's disease. Biopsies were done on an outpatient basis, followed by a 4-hr observation period in hospital. Normal hemostasis was maintained during the peribiopsy period, with follow-up doses of factor concentrate self administered by the patient at home. One patient (1.4%) had significant bleeding leading to readmission and red cell transfusion. Liver histology showed 14 patients (22%) had cirrhosis. Ten patients had elevated corrected sinusoidal pressures; 7 of these (70%) had cirrhosis on biopsy, and the other 3 (30%) likely had cirrhosis although histology showed stage 3 fibrosis. This series represents the largest reported experience of transjugular biopsy in individuals with congenital bleeding disorders. We conclude that this procedure can be safely performed on an outpatient basis. The diagnosis of cirrhosis and/or portal hypertension was made in a substantial proportion of individuals (26%), all of whom had asymptomatic liver disease., (Copyright 2005 Wiley-Liss, Inc.)