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The first clinical case of persistent HEV infection in England was reported in 2009. We describe the demography, virology and outcomes of patients identified with persistent HEV infection in England and Wales between 2009 and 2017. A series of 94 patients with persistent HEV infection, defined by HEV viraemia of more than 12 weeks, was identified through routine reference laboratory testing. Virology, serology and clinical data were recorded through an approved PHE Enhanced Surveillance System. Sixty‐six cases (70.2%) were transplant recipients, 16 (17.0%) had an underlying haematological malignancy without stem cell transplantation, six (6.4%) had advanced HIV infection, five (5.3%) were otherwise immunosuppressed, and one patient (1.1%) had no identified immunosuppression. Retrospective analysis of 46 patients demonstrated a median 38 weeks of viraemia before diagnostic HEV testing. At initial diagnosis, 16 patients (17.0%) had no detectable anti‐HEV serological response. Of 65 patients treated with ribavirin monotherapy, 11 (16.9%) suffered virological relapse despite undetectable RNA in plasma or stool at treatment cessation. Persistent HEV infection remains a rare diagnosis, but we demonstrate that a broad range of immunocompromised patients are susceptible. Both lack of awareness and the pauci‐symptomatic nature of persistent HEV infection likely contribute to significant delays in diagnosis. Diagnosis should rely on molecular testing since anti‐HEV serology is insufficient to exclude persistent HEV infection. Finally, despite treatment with ribavirin, relapses occur even after cessation of detectable faecal shedding of HEV RNA, further emphasising the requirement to demonstrate sustained virological responses to treatment. [ABSTRACT FROM AUTHOR]

Background: The burden of non-alcoholic fatty liver disease (NAFLD) is increasing globally, and a major priority is to identify patients with non-alcoholic steatohepatitis (NASH) who are at greater risk of progression to cirrhosis, and who will be candidates for clinical trials and emerging new pharmacotherapies. We aimed to develop a score to identify patients with NASH, elevated NAFLD activity score (NAS≥4), and advanced fibrosis (stage 2 or higher [F≥2])., Methods: This prospective study included a derivation cohort before validation in multiple international cohorts. The derivation cohort was a cross-sectional, multicentre study of patients aged 18 years or older, scheduled to have a liver biopsy for suspicion of NAFLD at seven tertiary care liver centres in England. This was a prespecified secondary outcome of a study for which the primary endpoints have already been reported. Liver stiffness measurement (LSM) by vibration-controlled transient elastography and controlled attenuation parameter (CAP) measured by FibroScan device were combined with aspartate aminotransferase (AST), alanine aminotransferase (ALT), or AST:ALT ratio. To identify those patients with NASH, an elevated NAS, and significant fibrosis, the best fitting multivariable logistic regression model was identified and internally validated using boot-strapping. Score calibration and discrimination performance were determined in both the derivation dataset in England, and seven independent international (France, USA, China, Malaysia, Turkey) histologically confirmed cohorts of patients with NAFLD (external validation cohorts). This study is registered with ClinicalTrials.gov, number NCT01985009., Findings: Between March 20, 2014, and Jan 17, 2017, 350 patients with suspected NAFLD attending liver clinics in England were prospectively enrolled in the derivation cohort. The most predictive model combined LSM, CAP, and AST, and was designated FAST (FibroScan-AST). Performance was satisfactory in the derivation dataset (C-statistic 0·80, 95% CI 0·76-0·85) and was well calibrated. In external validation cohorts, calibration of the score was satisfactory and discrimination was good across the full range of validation cohorts (C-statistic range 0·74-0·95, 0·85; 95% CI 0·83-0·87 in the pooled external validation patients' cohort; n=1026). Cutoff was 0·35 for sensitivity of 0·90 or greater and 0·67 for specificity of 0·90 or greater in the derivation cohort, leading to a positive predictive value (PPV) of 0·83 (84/101) and a negative predictive value (NPV) of 0·85 (93/110). In the external validation cohorts, PPV ranged from 0·33 to 0·81 and NPV from 0·73 to 1·0., Interpretation: The FAST score provides an efficient way to non-invasively identify patients at risk of progressive NASH for clinical trials or treatments when they become available, and thereby reduce unnecessary liver biopsy in patients unlikely to have significant disease., Funding: Echosens and UK National Institute for Health Research., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)