Explore the vast range of titles available.

In this randomized trial in patients hospitalized with alcoholic hepatitis, pentoxifylline did not improve survival. The 28-day survival advantage in patients treated with prednisolone did not reach significance and was not sustained at 90 days or 1 year. Alcoholic hepatitis is a distinct manifestation of alcoholic liver disease that is characterized by jaundice and liver failure. This condition develops in persons with a history of prolonged and heavy alcohol use. 1 The severity of alcoholic hepatitis is conventionally defined by Maddrey’s discriminant function, which is calculated as 4.6×(patient’s prothrombin time in seconds−control’s prothrombin time in seconds)+patient’s serum bilirubin level in milligrams per deciliter; a value of 32 or higher indicates severe alcoholic hepatitis that carries an adverse prognosis, with mortality of 20 to 30% within 1 month after presentation and 30 to 40% within 6 months after presentation. 2 A . . .

Biochemical remission is widely considered a satisfactory treatment end point in autoimmune hepatitis (AIH). The significance of persisting histological activity despite biochemical remission is unknown. We aimed to assess the frequency and prognostic significance of persisting histological inflammation in patients with AIH who had achieved biochemical remission with treatment. We studied 120 patients (median age at diagnosis 57 years; 81% female) with AIH by International Criteria (59% definite), who received immunosuppressive treatment and underwent a follow-up liver biopsy after at least 6 months of sustained biochemical remission (defined as normal serum ALT and globulin). Fifty-five patients (46%) had persisting histological activity (Ishak histological activity index (HAI) ≥4). These patients had higher serum ALT (24 vs. 18 IU/l, P=0.003) and AST (27 vs. 23 IU/l, P=0.03) at the time of follow-up biopsy, compared with patients who achieved histological remission (HAI ≤3). They had less frequent regression of fibrosis on follow-up biopsy compared with those achieving histological remission (32 vs. 60%, P=0.004) and had excess mortality (standardized mortality ratio 1.4 vs. 0.7, P<0.05). The excess mortality was due to liver disease. On multivariate analysis, persisting histological activity was independently associated with all-cause death/transplantation (HR 3.1 (95% CI 1.2-8.1); P=0.02); an association with liver-related death/transplantation fell short of significance (HR 9.7 (95% CI 0.84-111.6; P=0.07). Persisting histological activity, despite biochemical remission, is frequent in patients with treated AIH and is associated with lower rates of fibrosis regression and reduced long-term survival.

Background Many causes of death are directly attributable to the toxic effects of alcohol and deaths from these causes are increasing in the United Kingdom. The aim of this study was to investigate variation in alcohol-related mortality in relation to socioeconomic deprivation, urban-rural location and age within a national context. Methods An ecological study design was used with data from 8797 standard table wards in England and Wales. The methodology included using the Carstairs Index as a measure of socioeconomic deprivation at the small-area level and the national harmonised classification system for urban and rural areas in England and Wales. Alcohol-related mortality was defined using the National Statistics definition, devised for tracking national trends in alcohol-related deaths. Deaths from liver cirrhosis accounted for 85% of all deaths included in this definition. Deaths from 1999-2003 were examined and 2001 census ward population estimates were used as the denominators. Results The analysis was based on 28,839 deaths. Alcohol-related mortality rates were higher in men and increased with increasing age, generally reaching peak levels in middle-aged adults. The 45-64 year age group contained a quarter of the total population but accounted for half of all alcohol-related deaths. There was a clear association between alcohol-related mortality and socioeconomic deprivation, with progressively higher rates in more deprived areas. The strength of the association varied with age. Greatest relative inequalities were seen amongst people aged 25-44 years, with relative risks of 4.73 (95% CI 4.00 to 5.59) and 4.24 (95% CI 3.50 to 5.13) for men and women respectively in the most relative to the least deprived quintiles. People living in urban areas experienced higher alcohol-related mortality relative to those living in rural areas, with differences remaining after adjustment for socioeconomic deprivation. Adjusted relative risks for urban relative to rural areas were 1.35 (95% CI 1.20 to 1.52) and 1.13 (95% CI 1.01 to 1.25) for men and women respectively. Conclusions Large inequalities in alcohol-related mortality exist between sub-groups of the population in England and Wales. These should be considered when designing public health policies to reduce alcohol-related harm.

ObjectivesUncertainty remains about many aspects of first-line treatment of autoimmune hepatitis (AIH).DesignSystemic review with meta-analysis (MA).Data sourcesBespoke AIH Endnote Library, updated to 30 June 2024.Eligibility criteriaRandomised controlled trials (RCTs) and comparative cohort studies including adult patients with AIH, reporting death/transplantation, biochemical response (BR) and/or adverse effects (AEs).Data extraction and synthesisData pooled in MA as relative risk (RR) under random effects. Risk of bias (ROB) assessed using Cochrane ROB-2 and ROBINS-1 tools.ResultsFrom seven RCTs (five with low and two with some ROB) and 18 cohort studies (12 moderate ROB, six high for death/transplant), we found lower death/transplantation rates in (a) patients receiving pred+/−aza (vs no pred): overall (RR 0.38 (95% CI 0.20 to 0.74)), in patients without symptoms (0.38 (0.19–0.75)), without cirrhosis (0.30 (0.14–0.65)), and with decompensated cirrhosis (RR 0.38 (0.23–0.61)), and (b) patients receiving pred+aza (vs pred alone) (0.38 (0.22–0.65)). Patients receiving higher (vs lower) initial pred doses had similar BR rates (RR 1.07 (0.92–1.24)) and mortality (0.71 (0.25–2.05)) but more AEs (1.73 (1.17–2.55)). Patients receiving bud (vs pred) had similar BR rates (RR 0.99 (0.71–1.39)), with fewer cosmetic AEs (0.46 (0.34–0.62)). Patients receiving mycophenolate mofetil (MMF) (vs aza) had similar BR rates (RR 1.32 (0.73–2.38)) and fewer AEs requiring drug cessation (0.20 (0.09–0.43)).ConclusionsMortality is lower in pred-treated (vs untreated) patients, overall and in several subgroups, and in those receiving pred+aza (vs pred). Higher initial pred doses confer no clear benefit and cause more AEs. Bud (vs pred) achieves similar BR rates, with fewer cosmetic AEs. MMF (vs aza) achieves similar BR rates, with fewer serious AEs.

BackgroundThe updated Shape of Training curriculum has shortened the duration of specialty training. We present the potential role of out of programme clinical fellowships.MethodAn electronic online survey was sent to all current fellows to understand their experiences, training opportunities and motivations.Data were collected on fellows’ endoscopic experiences and publications using PubMed for all previous doctors who have completed the Sheffield Fellowship Programme.ResultsSince 2004, 39 doctors have completed the Sheffield Fellowship.Endoscopic experience: current fellows completed a median average of 350 (IQR 150–500) gastroscopies and 150 (IQR 106–251) colonoscopies per year. Fellows with special interests completed either 428 hepato-pancreato-biliary procedures or 70 endoscopic mucosal resections per year.Medline publications: Median average 9 publications(IQR 4–17). They have also received multiple national or international awards and 91% achieved a doctoral degree.The seven current fellows in the new Shape of Training era (57% male, 29% Caucasian, aged 31–40 years) report high levels of enjoyment due to their research projects, supervisory teams and social aspects. The most cited reasons for undertaking the fellowship were to develop a subspecialty interest, take time off the on-call rota and develop endoscopic skills. The most reported drawback was a reduced income.All current fellows feel that the fellowship has enhanced their clinical confidence and prepared them to become consultants.ConclusionOut of programme clinical fellowships offer the opportunity to develop the required training competencies, subspecialty expertise and research skills in a supportive environment.

The formulation of guidelines are driven by a Guideline Development Group (GDG), include a writing committee, members of which are recognised authorities in the field, and others representing a range of relevant expertise, as well as patient representatives and those whose everyday practice will be influenced by the guidelines. All feedback is sent to the lead author for amendments to the guideline and if these are satisfactory, the guideline is then submitted to Gut for the usual peer review process by four to eight internationally renowned authorities.

IntroductionPrednisolone(Pred)+/-azathioprine(Aza) improves survival in patients with AIH (J.Hepatol 2010; 53:191). Uncertainty remains about (a) its efficacy in subgroups (asymptomatic, acute severe) (b) value of adding Aza, vs Pred alone (c) optimal initial Pred dose and (d) efficacy and adverse effects ((AEs) (as first-line treatment) of budesonide(Bud) vs Pred, and mycophenolate(MMF) vs Aza.We aimed to address these issues in an updated SR/MA, in adults, of randomised trials (RCTs) and cohort studies (subgroups receiving different treatments)MethodsMEDLINE and other databases were searched. Two independent authors selected and extracted data from included studies. Risk of bias (ROB) was assessed using Cochrane Risk of Bias 2 and ROBINS-I tools. Data were pooled, if >2 studies, in meta-analyses as relative risk (RR) under random effects, using R meta package.ResultsSee table 1. We found 7 RCTs (6: low, 1: some ROB) and 18 cohort studies (5: moderate, 13: high ROB)Abstract P338 Table 1 Selection (number studies) Treatment Control All-cause death/transplant RR(95%CI ) [ I2 ] Biochemical remission (BR )* 6 months 12 months Adverse Effects* General(6) (2) AcuteSevere (4)Asymptomatic(4) No cirr- hosis (2) Pred+/-Aza(n=1394) No Pred. +/-Aza(n=325) 0.38 (0.20–0.71)[66%] na na na Pred+/-Aza(n=1066) Pred alone(n=193) 0.28(0.22–0.65)[3%] na na na Pred+/- Aza(n=356) Pred+/-Aza(n=345) Pred+/-Aza(n=940) Untreated(n=55) Untreated(n=67) Untreated(n=138) 0.32(0.27–0.38)[28%] 0.43(0.21–0.86)[0%] 0.30(0.14–0.65)[0%] na na na General(3–6) High-dosePred(n=531–962) Low-dosePred(n=715–1137) 1.11(0.22–3.73)[53%] 1.10(0.94–1.28)[60%] 1.09(0.90–1.31)[63%] 1.72(1.22–2.42)[57%] General(2–5) Bud+Aza(n=163–372) Pred+Aza(n=1387–2012) na 1.07(0.80–1.43)[80%] 0.84(0.56–1.26)[90%] 0.67(0.38–1.17)[82%] General(2) MMF+Pred(n=222) Aza+Pred(n=95) na 1.32(0.73–2.38)[73%] na 0.20(0.09–0.43)[0%]** I2 =heterogeneity index, na:=not analysed, High/Low dose=>< 40mg or 1mg/kg/day. General: some specific exclusions. *Definition varied across studies. **AEs causing discontinuationConclusions(a) Pred-treated (vs untreated) patients have improved survival: overall, and in subgroups with acute severe AIH, without symptoms and without cirrhosis. Also, in those receiving Pred+Aza (vs Pred alone) (b) High (vs low) initial Pred doses confer no clear benefit and cause more AEs (c) Bud (vs Pred) achieves similar BR rates, with non-significant trend to less AEs (d) MMF(vs Aza) achieves similar BR rates, with less serious AEs. Conclusions are tentative due to ROB and heterogeneity.

IntroductionThe efficacy of CCA surveillance in PSC is not established. BSG, EASL and AASLD guideline recommendations differ significantly, and in the UK and Europe, implementation and imaging strategies vary. MRI protocol quality standards exist (Schramm Hepatology 2017 66:1675) but adherence has not been assessed in regard to CCA surveillance. We previously (Gleeson Gut 2022 71: A74) reported an audit of CCA surveillance implementation. Here, we report (in an expanded dataset), an audit of the quality of surveillance imaging for CCA in PSC.MethodsSingle-centre retrospective audit of patients with PSC attending our unit, who developed CCA from 2015–2023. We assessed quality of hepatobiliary imaging (protocols and reports) performed over 3 years prior to CCA diagnosis.Results147 patients (91 men) with PSC were seen since 2015 (diagnosed 1981–2023,140 on MRCP, 7 on liver biopsy). Age in 2018 was (median(range) 54(17–87) years, 102(70%) had IBD (78 UC 19 proctocolectomy),14 underwent transplantation and 22 died.Between 2015 and 2023, 13 patients (9 men) were diagnosed with CCA (8 intrahepatic, 4 perihilar, 1 distal), aged 57(25–88) years and 4(0–14) years after PSC diagnosis. In only three patients could the tumour be resected (2: intrahepatic, diameter 4.0–4.5 cm, 1: perihilar with spread beyond bile duct). Two patients had recurrence within 12 months. 11 patients died after 12(3–24) months, accounting for 50% of all PSC deaths.Prior to CCA diagnosis, three patients had not undergone imaging for 24–31 months, four had normal abdominal ultrasound 5–9 earlier (but no MRCP), and in five, MRCP 4(1–7) months earlier (plus ERCP with cytology in two and cholangioscopy in one) did not report CCA, despite contemporaneous raised serum Ca-19.9 in two. On imaging, CCA was visible in retrospect in three of these five patients, with suspicious abnormalities in the other two.Of 36 MR diagnostic and surveillance studies in patients developing CCA, only 28(78%) met the 2017 minimum protocol quality standard criteria. Only 39% of MRCPs performed over the 3 years prior to CCA diagnosis were of ‘acceptable’ quality.ConclusionsOutcome of CCA in PSC remains very poor. Resolving questions regarding its surveillance will require optimization of imaging quality. These data suggest that there is room for quality improvement.

Out of programme (OOP) opportunities are to be encouraged. This article gives an insightful view of the Sheffield Clinical Research Fellowship Programme. Unique trainee feedback is provided. The take home message is clear - trainees should grab OOP experiences with both hands! For consultants the logistics described are potentially transferrable to their own regions.

IntroductionDe novo cirrhosis develops on treatment in 20-30% of patients with AIH and predicts adverse outcomes (Gleeson D. Clin Liver Dis. 2019;14:24). Its prevention may be helped by effective serial monitoring of fibrosis. Transient elastography (Fibroscan, FS) is a validated marker of fibrosis in other liver diseases and evidence in AIH suggests reasonable accuracy after 6 months of treatment. (Anastasiou OE. Hepat Mon. 2016;16(11), Hartl J. J Hepatol 2018;68(4):754).MethodsThis is a retrospective single-centre review of serial FS in patients with AIH to assess changes in fibrosis and their associations, who had >2 FSs since 1/1/2017. FS validity was by criteria of Boursier, including an IQ range/median ratio of <0.30 (Boursier J. Hepatology. 2013;57(3):1182). We gathered information on liver biopsies and on serum AST, ALT and IgG values (Before 1st FS, after last FS and between). Data were analysed using SPSS.Results52 patients (10 M, age (mean±SD) 62±15 years) had >2 FSs performed, which were valid in 50 patients. First FS was performed (mean±SD) 8±6 years after diagnosis, when in 44 patients, serum ALT (mean of values before and after scan) was < twice normal. Interval between scans was 2.2±0.9 (range 0.5-4) years.Median FS score fell slightly from FS1:7.7±3.6 to FS2: 7.2±3.1 KPa (p=0.001). FS score increased in 24%, decreased in 40% and was unchanged (<1kPa change) in 36%. 1st and 2nd FS scores were highly correlated (p=0.001). However in 3 patients, FS score increased from 5.0, 7.0 and 7.0 to 12.5, 15.0 and 16.0, and in 3 others fell from 14.0, 14.0 and 11.0 to 7.0, 4.0 and 4.0.FS1 score was correlated with Ishak fibrosis stage on initial liver biopsy (n=27,p=0.003). However, neither FS1 nor FS2 scores correlated with fibrosis on subsequent biopsies. There were no associations found in the difference between FS1 and F2 scores (Δ FS score) and median serum ALT, AST, IgG values between the scans. Nor did Δ FS score differ between (a) those with and without a relapse of AIH between the scans (b) those maintaining (vs not maintaining) complete biochemical remission between the scans. These associations were also absent, regarding FS2 score considered on its own, apart from an association with median serum IgG between the scans (p=0.003).ConclusionsThe overall fall in FS score with time is reassuring. However, the marked and arguably implausible changes in some patients are of concern. The absence of associations between Δ FS score and F2 scores and several parameters of inflammatory activity in contrast to results of Hartl et al are surprising, given established associations of fibrosis progression with ongoing inflammation. Further evaluation is needed of FS as a serial marker of fibrosis in AIH.