Showing papers by "Michael A. Heneghan published in 2022"

Immune checkpoint inhibitor‐related cholangiopathy: Novel clinicopathological description of a multi‐centre cohort

Abstract: 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.

Systematic review with meta‐analysis: outcomes of pregnancy in patients with autoimmune hepatitis

Abstract: Autoimmune hepatitis (AIH) is common in females of childbearing age. Although some studies have provided information about the outcomes of pregnancy, there remains uncertainty regarding conclusions.

Treatment and outcome of autoimmune hepatitis: Audit of 28 UK centres

Abstract: With few data regarding treatment and outcome of patients with AIH outside of large centres we present such a study of patients with AIH in 28 UK hospitals of varying size and facilities.

Managing hepatic complications of pregnancy: practical strategies for clinicians

Abstract: Liver disorders specific to pregnancy are rare but can have potentially serious consequences for mother and fetus. Pregnancy-related liver disorders are the most common cause of liver disease in otherwise healthy pregnant women and pose a challenge to physicians because of the need to take into account both maternal and fetal health. A good knowledge of these disorders is necessary as prompt diagnosis and appropriate management results in improved maternal and fetal outcomes. This review will focus on pregnancy-specific disorders and will aim to serve as a guide for physicians in their diagnosis, management and subsequent monitoring.

Nasobiliary drainage: an effective treatment for pruritus in cholestatic liver disease

Abstract: Introduction Nasobiliary drains (NBDs) have been successfully used to manage intrahepatic cholestasis, bile leaks and obstructive cholangitis. It allows external drainage of bile, bypassing the ileum where bile salts are reabsorbed. We assessed the utility of placement with effect on markers of cholestasis and patient symptoms. Methods Consecutive patients undergoing NBD over 12 years for the management of pruritus were retrospectively analysed. Recorded variables included patient demographics, procedural characteristics and response to therapy. Results Twenty-three patients (14, 61% male) underwent 30 episodes of NBD. The median age was 26 years old (range 2–67 years old). A single procedure was carried out in 20. One patient each had two, three and five episodes of NBD. The most common aetiologies were hereditary cholestatic disease (n=17, 74%) and drug-induced cholestasis (n=5, 22%), NBD remained in situ for a median of 8 days (range 1–45 days). Significant improvement in bilirubin was seen at 7 days post-NBD (p=0.0324), maintained at day 30 (335 μmol/L vs 302 µmol/L vs 167 µmol/L). There was symptomatic improvement in pruritus in 20 (67%, p=0.0494) episodes. One patient underwent NBD during the first trimester of pregnancy after medical therapy failure with a good symptomatic response. The catheters were well tolerated in 27 (90%) of cases. Mild pancreatitis occurred in 4 (13%) cases. Conclusion NBD can be used to provide symptomatic improvement to patients with pruritus associated with cholestasis. It is well tolerated by patients. They can be used in pregnancy where medical management has failed.

Autoimmune hepatitis and pregnancy: considerations for the clinician

Abstract: ABSTRACT Introduction Autoimmune hepatitis (AIH) is an immune-mediated inflammatory disease of the liver, which affects females of reproductive age. AIH poses unique challenges in pregnancy and historically was associated with adverse pregnancy outcomes. Areas covered This report aims to review the current evidence for AIH pregnancy outcomes and the use of medical therapies in pregnancy. The disease course of AIH in pregnancy including loss of biochemical response (LOBR) and hepatic decompensation is also reviewed. The importance of preconception counseling and continued monitoring into the post-partum phase is reinforced. Expert opinion The lack of prognostic markers and targeted immunosuppression is some of the areas for future development, as this will aid the move toward individualized risk stratification and personalized care.

Post-Transplant Immunosuppression in Autoimmune Liver Disease.

Abstract: Autoimmune liver diseases (AILDs) are a group of conditions where immune-mediated liver damage can lead to the need for transplantation. Collectively, they account for almost a quarter of all liver transplants. Outcomes in terms of graft and patient survival for all liver transplants have improved markedly over decades with improvements in patient selection, surgical techniques and longer-term care and this is also seen in patients with AILDs. The current five- and ten-year survival rates post-transplant in autoimmune disease are excellent, at 88% and 78%, respectively. A key factor in maintaining good outcomes post liver transplant for these autoimmune conditions is the immunosuppression strategy. These patients have increased the rates of rejection, and autoimmune conditions can all recur in the graft ranging from 12 to 60% depending on the population studied. Immunosuppressive regimens are centred on calcineurin inhibitors, often combined with low dose corticosteroids, with or without the addition of antimetabolite therapy. There is no clear evidence-based immunosuppressive regimen for these conditions, and a tailored approach balancing the individuals' immunological profile against the risks of immunosuppression is often used. There are disease-specific considerations to optimised graft function including the role of ursodeoxycholic acid in both primary biliary cholangitis and primary sclerosing cholangitis and the role and timing of colectomy in primary sclerosing cholangitis in inflammatory bowel disease patients. However, unmet needs still exist in the management of AILDs post liver transplantation particularly in building the evidence base for optimal immunosuppression as well as mitigating the risk of recurrent disease.

Treatment of acquired transthyretin amyloidosis in domino liver transplantation

Abstract: Domino liver transplantation (DLT) has been commonly used during the last two decades to partly meet the high need for liver transplants. However, the recipients of grafts from patients with noncirrhotic inherited metabolic disorders may ultimately develop metabolic syndrome, and management is usually intricate, being complicated by the underlying initial disorder, other comorbidities, and post‐transplantation conditions.

Development of obstetric-hepatology services: defining optimal care and impact of pregnancy counselling on patient experience

Abstract: Objective Prepregnancy counselling (PPC) is an important aspect of care for women with chronic liver disease (CLD) and liver transplantation (LT), yet its impact has not been well described. This study aims to assess the experience of women attending a joint obstetric-hepatology PPC clinic in a single-centre unit. Design/methods A retrospective questionnaire-based study in a tertiary unit within the UK where patients who attended the PPC clinic between March 2016 and July 2021 were invited to participate by filling in a questionnaire. Descriptive data and free-text content were subsequently analysed. Results 108 women attended the PPC clinic over a 5-year period. Overall, 58/108 (54%) completed the questionnaire. Principal concerns regarding pregnancy included fears around deterioration in health (66%), maternal death (24%), pregnancy loss (66%), medication effects (60%) and disease transmission (36%). 17/58 (14%) patients felt the presence of multiple doctors was intimidating, however, perceptions improved by the end of the consultation. Overall, 44/58 (76%) respondents felt the clinic helped them reach a decision about pursuing pregnancy. Almost all respondents would recommend the clinic to others. There were no major differences in pregnancy outcomes between those that received PPC and those that did not. Conclusion The PPC clinic facilitates a personalised approach to care and is well received by patients with CLD/LT. It is difficult to elucidate whether attendance alone impacts on pregnancy outcomes; registry data may be better placed at addressing this important question.

P39 Systemic inflammation associated microRNA as novel biomarkers for clinical decompensation in patients with cirrhosis

Abstract: The cardiovascular effects of topical ophthalmological preparations of 2% epinephrine (EPI), 0.1% dipivalyl epinephrine (DPE), and placebo were studied in double-blind fashion in 20 patients with glaucoma. Both drugs and placebo produced a decrease in heart rate (2 +/- 3 beats/min) which, although small, was highly significant (p less than 0.001). Neither drug not placebo produced a significant effect on mean or systolic blood pressure (BP) over the group as a whole (p greater than 0.1). However, 5 of 20 patients responded to EPI with a significant rise in mean or systolic BP (defined as a change greater than mean change +/- 2 SD), whereas there were no such responses to DPE or placebo. One patient developed marked ventricular ectopy after EPI. We conclude that EPI may cause cardiovascular side effects in a high percentage of patients (25% in this study) through individual susceptibility rather than a predictable effect. DPE, a new epinephrine analogue, appears to be devoid of these effects.

Invasive coronary angiography as a tool in cardiac evaluation for liver transplant candidates

Abstract: • Invasive coronary angiography was performed in high risk transplant candidates. • Multidisciplinary decision on listing for transplant and coronary revascularisation. • 169 patients listed underwent coronary angiography, 73 had coronary artery disease. • Coronary artery disease did not affect 5-year survival post-transplant. Cardiovascular assessment is central to evaluation of liver transplant (LT) candidates. However, there is a lack of consensus on the diagnostic algorithm for screening for coronary artery disease (CAD), and the place for invasive coronary angiography (ICA) remains undefined. We retrospectively analysed 1201 adults who underwent elective LT assessment over a 5-year period. For patients who underwent LT, survival data to 5 years post-LT was collected. ICA was performed in 259 (21.6%): 134 no CAD, 58 mild, 33 moderate, and 34 severe. Detection of CAD was associated with age (OR 1.08, P < 0.01), current smoking (OR 4.92, P < 0.01) and prior CAD (OR 8.93, P < 0.001). Poor performance on cardiopulmonary exercise test (CPET) was associated with age (OR 1.02, P < .05) and diabetes mellitus (OR 1.54, P < 0.05). 122 (10.2%) patients were declined due to severity of cardiovascular disease. 169/779 (21.7%) patients listed for LT had undergone ICA, and CAD was present in 73/169 (43.2%). The non-risk-adjusted all-cause post-LT 5-year survival was 82.6%, with no difference in survival in those with and without CAD on ICA. In patients with CAD, diabetes was associated with reduced survival (OR 3.78, P < 0.05). Multi-modality cardiac evaluation is useful in high-risk patients undergoing LT assessment. ICA can be used with non-invasive assessments and risk factors to delineate candidacy. In selected patients with CAD, LT has been undertaken with comparable post-LT survival.

P72 Management of chronic hepatitis B post liver transplantation: Is it time for a national consensus?

Abstract:

Introduction

Management of Chronic Hepatitis B (CHB) following liver transplantation includes the use of Hepatitis B Immunoglobulins (HBIG) and Nuclot(s)ides analogues (NUCs) to prevent CHB reactivation and flare. However, the duration and endpoint of HBIG remain controversial among transplant centres, and there is emerging evidence that a reduction in doses of HBIG does not adversely affect outcomes.

Methods

Retrospective data were collected for all patients identified as CHB who had a liver transplant from 2015 to 2022. Key details such as Demographics, date of transplant, the reason for transplants, type of NUCs, HBIG duration and viral serology pre-transplant, 6- and 12-months post-liver transplantation were collected and analysed.

Results

45 patients were identified as CHB patients with a liver transplants. While 29 patients (64%) had CHB mono-infection, 13 (29%) had HBV/HDV Co-infection, two had HBV/HIV Co-infection, and only one patient had CHB/HDV/HIV co-infection. The median age of our study population was 49 years (Range 29–65 years) with a Male: Female ratio of 2:1. The mean estimated survival was 79.2 months (CI 95%, Range 70–88 months). 18 patients (40%) had detectable HBV DNA prior to transplant (median= 1440 Range= 11 – 6.9 E6 IU/mL). All patients were already on NUCs prior to transplant and continued on NUCs post-liver transplantation. The average number of HBIG doses in the first-week post-liver transplant was four doses per patient (Range 0–7, SD= 2 Doses). The median duration of HBIG treatment was six months, ranging from 0 to 79 months. Most of our cohort (98%) had undetectable HBV DNA at 6- and 12- months post-liver transplant. To review practice across the UK. We reviewed six transplant centres’ local guidelines regarding HBIG for CHB post-liver transplant. There was a considerable discrepancy in approaches with variable doses at the first-week post-transplantation and duration ranging from no HBIG doses post-transplant to lifelong HBIG.

Conclusion

This quality improvement project reports good long-term outcomes for liver transplantation in CHB patients. However, whilst NUCs and HBIG effectively prevent viral reactivation and are associated with favourable long-term outcomes; there is prolonged use of HBIG post-liver transplant that burdens the service from a cost and patient perspective. A more coherent approach to HBIG is required to guarantee optimum patient care and cost-effectiveness across transplant centres in the UK.

P14 Drug induced autoimmune hepatitis from a single centre experience

Abstract:

Background

Drug induced autoimmune hepatitis (DIAIH) is poorly defined and there lacks consensus on management. Autoimmune like drug induced liver injury (AI-DILI) may be indistinguishable from DIAIH at presentation. AI-DILI can withdraw from immunosuppression without relapse whereas DIAIH require long term immunosuppression. DIAIH disease course and prognosis compared to non-drug induced AIH is not established. The aim of this study is to characterise and review long-term outcomes of DIAIH.

Methods

This retrospective cohort study reviewed patients with DIAIH (n=28) and AIH (n=39) in a single centre from 2000 to 2021. Information was gathered using patient’s notes and electronic records. DIAIH was identified based on clinical history, a temporal association with a drug and development of AIH, no previous liver disease and exclusion of other liver disease. The new consensus histology criteria for AIH from the International AIH pathology group was reviewed together with the simplified histology criteria.

Results

There were no significant difference in gender, age at presentation, presence of other autoimmune disease, duration of symptoms to presentation, liver prognostic scores and time to remission and duration of follow up between DIAIH and AIH. DIAIH were more likely to present with jaundice/pruritus (p=0.004). AIH were more likely to require immunosuppression with steroids (p=0.009) or azathioprine (p=0.0005). Five patients with DIAIH had successful immunosuppression withdrawal during study follow up compared to none in the AIH cohort. Patient information for DIAIH are shown in table 1. The commonest drugs include antibiotics (17 cases), herbal (4) and biologics (4). Six DIAIH patients did not require immunosuppression and based on the new histology criteria, 2 of these had unlikely features. One patient had atypical histology based on the simplified histology criteria but still required long-term immunosuppression. AIH patients were more likely to have fibrosis (p<0.0001) than DIAIH. Four patients required liver transplantation (LT) in both cohorts though the interval to LT was significantly shorter in DIAIH (mean 35 days DIAIH versus 1424 days in AIH, p=0.03). Of those who underwent LT, the bilirubin and INR at presentation was higher in DIAIH compared to AIH. Two deaths occurred post-LT in DIAIH.

Conclusion

DIAIH is more likely to present with acute liver failure and less fibrosis. If DIAIH progress to LT, it is more likely to occur in the acute period (<12 weeks). The new histology criteria for AIH may be more accurate for DIAIH but requires validation.

P12 Quality of life and its associated factors in autoimmune hepatitis: a cross-sectional study

Abstract: Introduction There are limited or conflicting data regarding quality of life (QoL) in patients with Autoimmune Hepatitis (AIH). We aimed to further assess QoL in AIH using three Patient Reported Outcome Measures (PROMS), seeking to compare results to those in the general population and explore associated factors. Methods We recruited outpatients with AIH from three UK sites between January 2020 and March 2022. Exclusion criteria included liver transplant, Child-Pugh C cirrhosis, malignancy within 12 months or severe co-morbidity. Participants (n=275, 78% female, median age 59 years) self-completed the EuroQol (EQ)-5D-5L; Recovering Quality of Life (ReQoL-10: a recently developed mental health-specific PROM); and Quality of life Evaluation in patients receiving Steroids (QuESt). Lower scores indicate worse QoL. EQ-5D-5L utility index (UI) and ReQoL-10 scores were compared to general population datasets using age, sex, and employment status as co-factors. Multiple linear regression analyses were performed to identify factors associated with QoL impairment. Results There were moderate-to-strong correlations between the three PROMs (r= 0.48, 0.55, 0.66, p<0.001). EQ-5D-5L UI was significantly impaired in participants with AIH compared to general population data. Following regression analyses, factors independently associated with lower EQ-5D-5L UI (worse QoL) were: BMI (β -1.79 p=0.008) and self-reported depression (β -0.229, p=0.003) or anxiety (β -0.171, p=0.047). Unexpectedly, ReQoL-10 scores were higher (p<0.001) in AIH compared to the general population. However, 50 (23%) participants with AIH had ReQoL-10 scores between 0–24, considered as falling within the clinical range for mental illness. Furthermore, ReQoL-10 scores were significantly associated with self-reported depression (β -0.304, p<0.001) and anxiety (β -0.244, p=0.001), in 10% and 9% participants with AIH, respectively. ReQoL-10 scores were also associated with BMI (β -0.172, p=0.011). QuESt scores were negatively associated with female sex (β -0.229, p=0.010), BMI (β -0.287, p=0.001) and depression (β -0.315, p<0.001). They were most impaired in the “appetite and appearance” domain. None of the PROM scores showed any association with presence of cirrhosis (n=72, 26% participants), complete biochemical remission (n=153, 64%), normal alanine aminotransferase (n=211, 78%), current use of corticosteroids (n=170, 62%), or prednisolone dose. Discussion As expected, EQ-5D-5L scores were significantly impaired in AIH compared to the general population, consistent with published data. However, unexpectedly (and in contrast to studies using other PROMs), mental health assessed by ReQoL was overall better in AIH than in controls (though not in patients with depression or anxiety). Existing PROMs may incompletely capture the experience of having AIH.

P10 Pregnancy outcomes in autoimmune hepatitis from a single tertiary centre

Abstract:

Background

Autoimmune hepatitis (AIH) affects women of reproductive age and data on pregnancy outcomes provide insight into managing this complex condition. Specifically, the effect of cirrhosis and immunosuppression use in AIH pregnancy would aid clinicians and women with pregnancy planning. This study aims to provide patient level data on pregnancy outcomes in AIH.

Method

A prospective database of self-reported pregnancies from women with liver disease was reviewed to identify AIH pregnancies. Medical records were used to gather retrospective data on demographics, preconception counselling, pregnancy outcomes, serological and biochemical markers.

Results

Between 1983 and 2022, there were 126 pregnancies from 74 women with AIH at King’s College Hospital. Mean age at conception was 28 years and women with cirrhosis were significantly younger (p=0.48). There were 64 pregnancies from 41 women with cirrhosis at conception. Women who received pre-pregnancy counselling (n=32) were more likely to have a surveillance gastroscopy (p=0.03). The majority of patients were on immunosuppression (IS) at conception with 38 pregnancies on monotherapy, 50 on dual and 7 on triple IS. During gestation, there were no changes to IS in 90 pregnancies. 25 were not on IS at conception of which 2 were started on IS during pregnancy. The IS was reduced or stopped in 4 pregnancies. Complications in pregnancy were not increased in those with cirrhosis or on IS. There were 32 post-partum loss of biochemical remission (LOBR) of which 10 were not on IS. LOBR resulted in 1 fulminant liver failure requiring liver transplantation and 1 decompensation with ascites. A total of 99 live births (LB) were reported of which 15 were preterm birth (PTB) (32- 37 weeks gestation) and 2 very preterm (<32 gestation). The rate of miscarriages, stillbirths and PTB were not increased in those with cirrhosis or IS. Preconception albumin-bilirubin score (ALBI) and AST to platelet ratio index (APRI) was predictive of LB with area under receiver operator curve of 0.7547 (p=0.0011) and 0.700 (p=0.0123) respectively. ALBI cut-off of -2.870 has sensitivity of 78.95% and specificity of 67.31% for predicting LB whereas APRI cut-off of 0.305 has sensitivity of 72.22% and specificity of 56%.

Conclusion

Women with AIH including those with cirrhosis can expect favourable pregnancy outcomes. Women with preconception counselling were more likely to receive surveillance endoscopy. The continued use of immunosuppression did not increase adverse pregnancy outcomes and may reduce post-partum LOBR. The ALBI and APRI scores may be useful as prognostic tools.

P98 Formal regional referral networks optimize patient selection for liver transplantation

Abstract:

Introduction

Unlike other conditions with high mortality (eg hepatocellular carcinoma (HCC)) chronic liver disease (CLD) patients (PTs) in the United Kingdom do not have standardised referral pathways. To improve access to liver transplantation (LT), King’s College Hospital (KCH) developed a network of satellite LT centres (SLTCs). We aimed to evaluate the impact of SLTCs in LT candidacy evaluation in CLD PTs and those within the established HCC pathway.

Methods

All PTs discussed at the KCH LT meeting between 10/2014-10/2019 were included. All second opinions from other centres and PTs without CLD or HCC were excluded. Geographic, referral (KCH, SLTC or conventional referrer (CR)), clinical, demographic and laboratory data were retrospectively recorded. HCC PTs had tumor related variables recorded. CLD and HCC PTs were analyzed separately. Univariate (UVA) and multivariate analyses (MVA) were utilized to assess the impact of SLTCs.

Results

1102 assessments from CLD PTs (CR=512 SLTC=299 KCH=291) and 240 assessments from HCC PTs (CR=110 SLTC=72 KCH=58) were included. HCC PTs were not significantly more likely to be; referred from CRs/SLTCs/KCH, listed or have a contraindication to LT than CLD PTs. 725 CLD PTs were listed and 216 had contraindications to LT. Variables significantly associated with listing included; younger age, autoimmune liver diseases (AILD), biliary atresia (BA), previous LT, higher CLD prognostic scores, shorter referral to decision time and referral from SLTCs. Variables significantly negatively associated with listing included; non-alcoholic fatty liver disease (NAFLD), alcohol related liver disease (ARLD), hepatitis C and referral from CRs. MVA was utilized to demonstrate that referrals from SLTCs remained independently associated with listing (adjusted odds ratio (aOR) 2.92 (95% confidence interval (CI) 2.07-4.17)). Variables associated with contraindication to LT included; older age, ARLD, NAFLD, higher CLD prognostic scores and referral from CRs. Variables negatively associated with contraindication to LT included; AILD, BA, previous LT or referral from SLTC. MVA was utilized to demonstrate that referrals from SLTC remained independently negatively associated with contraindications (aOR 0.33 (95%CI 0.21-0.50)). 168 HCC patients were listed and 55 had contraindications to LT. No variables were significantly associated with listing including referrals from SLTC on UVA or MVA. Older HCC PTs were significantly more likely to have a contraindication to LT but referrals from SLTC did not influence likelihood on UVA or MVA.

Conclusions

Formal referral pathways through SLTCs improve PT selection and access to LT for PTs with CLD but do not impact on the well-established HCC pathway.

LiverMultiScan as an alternative to liver biopsy to monitor autoimmune hepatitis in the National Health Service in England: an economic evaluation

Abstract: Background Autoimmune hepatitis (AIH) is a rare chronic progressive liver disease, managed with corticosteroids and immunosuppressants and monitored using a combination of liver biochemistry and histology. Liver biopsy (gold standard) is invasive, costly and has risk of complications. Non-invasive imaging using multiparametric magnetic resonance (mpMR) can detect the presence and extent of hepatic fibroinflammation in a risk-free manner. Objective To conduct early economic modelling to assess the affordability of using mpMR as an alternative to liver biopsy. Methods Medical test costs associated with following 100 patients over a 5-year time horizon were assessed from a National Health Service payor perspective using tariff costs and average biopsy-related adverse events costs. Sensitivity analyses modelling the cost consequences of increasing the frequency of mpMR monitoring within the fixed cost of liver biopsy were performed. Results Per 100 moderate/severe AIH patients receiving an annual mpMR scan (in place of biopsy), early economic modelling showed minimum cost savings of £232 333. Per 100 mild/moderate AIH patients receiving three mpMR scans over 5 years estimated minimum cost savings were £139 400. One-way sensitivity analyses showed increasing the frequency of mpMR scans from 5 to 10 over 5 years in moderate/severe AIH patients results in a cost saving of £121 926.20. In patients with mild/moderate AIH, an increase from 3 to 6 mpMR scans over 5 years could save £73 155.72. In a minimalistic approach, the use of 5 mpMR scans was still cost saving (£5770.48) if they were to replace two biopsies over the 5-year period for all patients with moderate/severe or mild/moderate AIH. Conclusions Integration of mpMR scans in AIH patient pathways leads to significant cost savings when liver biopsy frequency is either reduced or eliminated, in addition to improved patient experience and clinician acceptability as well as providing detailed phenotyping to improve patient outcomes. Trial registration NCT03979053.

Low baseline but not delta cortisol relates to 28-day transplant-free survival in acute and acute-on-chronic liver failure

Abstract:

Background and Aims

The clinical, prognostic, and therapeutic impact of adrenal insufficiency in acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) remains controversial and exact diagnostic criteria are lacking. We sought to determine the diagnostic and therapeutic value of cortisol measurement and glucocorticoid (GC) treatment in ALF and ACLF.

Methods

28-day transplant-free survival (TFS) was studied in relation to absolute cortisol concentrations and to GC treatment in ALF (n = 30) and ACLF (n = 34) patients. Cortisol concentrations and short synacthen test were assessed by chemiluminescence immunoassay and liquid chromatography-mass spectrometry. Clinicians decided independently on GC treatment. In relation, phenotypic and functional characteristics of circulating monocytes were assessed.

Results

In ALF, baseline cortisol concentrations <387 nmol/L predicted TFS (sensitivity 83%, specificity 53%). In ACLF, baseline cortisol <392 nmol/L correlated with TFS (sensitivity 80%, specificity 61%). In both, ALF and ACLF, GC treatment did not influence 28-day TFS in patients with low baseline cortisol. However, in patients with baseline cortisol exceeding 387 and 392 nmol/L, respectively, TFS was higher if they had been treated with GC. High baseline cortisol was associated with low HLA-DR expression on monocytes.

Conclusion

Our data suggest a prognostic value of baseline cortisol measurement in ALF and ACLF. Overall, strong activation of the hypothalamic–pituitary–adrenal axis indicated poor prognosis. Furthermore, baseline cortisol deserves prospective evaluation as a guide for GC treatment decision-making.