Increased case-finding and uptake of direct-acting antiviral treatment essential for micro-elimination of hepatitis C among people living with HIV: a national record linkage study.

OBJECTIVES: Micro-elimination of hepatitis C virus (HCV) in people living with HIV (PLHIV) and co-infected with HCV has been proposed as a key contribution to the overall goal of HCV elimination. While other studies have examined micro-elimination in HIV-treated cohorts, few have considered HCV micro-elimination among those not treated for HIV or at a national level. METHODS: Through data linkage of national and sentinel surveillance data, we examined the extent of HCV testing, diagnosis and treatment among a cohort of PLHIV in Scotland identified through the national database of HIV-diagnosed individuals, up to the end of 2017. RESULTS: Of 5018 PLHIV, an estimated 797 (15%) had never been tested for HCV and 70 (9%) of these had undiagnosed chronic HCV. The odds of never having been tested for HCV were the highest in those not on HIV treatment [adjusted odds ratio (aOR) = 7.21, 95% confidence interval (CI): 5.15-10.10). Overall HCV antibody positivity was 11%, and it was at its highest among people who inject drugs (49%). Most of those with chronic HCV (91%) had attended an HCV treatment clinic but only half had been successfully treated (54% for those on HIV treatment, 12% for those not) by the end of 2017. The odds of never having been treated for HCV were the highest in those not on HIV treatment (aOR = 3.60, 95% CI: 1.59-8.15). CONCLUSIONS: Our data demonstrate that micro-elimination of HCV in PLHIV is achievable but progress will require increased effort to engage and treat those co-infected, including those not being treated for their HIV.

Index serum hyaluronic acid independently and accurately predicts mortality in patients with liver disease.

BACKGROUND: Hyaluronic acid is a recognised noninvasive marker of liver fibrosis. However, its prognostic ability has not been extensively studied. AIMS: To investigate the ability of an index serum hyaluronic acid measurement to independently predict transplant-free survival in patients with liver disease of varying aetiology and severity. METHODS: This was a retrospective single-centre cohort study. Serum hyaluronic acid was measured at the discretion of the attending clinicians, in patients attending the liver clinic, to assess disease severity. Patients with a hyaluronic acid measurement between 1995 and 2010 were identified. Patient characteristics at the point of hyaluronic acid measurement were recorded from medical records. Follow-up was from date of index hyaluronic acid measurement to date of death, date of transplant or censor date (July 01, 2015). Primary outcomes were all-cause and liver-related mortality. Kaplan-Meier analysis was used to compare survival in 3 patient groups with hyaluronic acid levels of <100 µg/L, 100-300 µg/L and >300 µg/L. Survival models were constructed using Cox proportional hazard and prediction accuracy was assessed by Harrell's C-statistic. RESULTS: Five hundred and eighty nine patients fulfilled inclusion criteria. Median follow-up was 5.6 years (range 0.1-19.7). Transplant-free survival was significantly different between patients with hyaluronic acid <100 µg/L, 100-300 µg/L and >300 µg/L for liver-related as well as all-cause mortality (P < 0.001). Hyaluronic acid level was an independent predictor of survival (liver-related: HR 1.39, 95% CI 1.20-1.60, P < 0.001; all-cause: HR 1.04, 95% CI 1.02-1.06, P = 0.001). The liver-related prediction accuracy of hyaluronic acid was 0.74 (Standard error 0.03). CONCLUSION: Index hyaluronic acid measurement can accurately and independently predict liver-related and all-cause mortality in patients with liver disease.

Impact of previous hepatitis B infection on the clinical outcomes from chronic hepatitis C? A population-level analysis.

Chronic coinfection with hepatitis C virus (HCV) and hepatitis B virus (HBV) is associated with adverse liver outcomes. The clinical impact of previous HBV infection on liver disease in HCV infection is unknown. We aimed at determining any association of previous HBV infection with liver outcomes using antibodies to the hepatitis B core antigen (HBcAb) positivity as a marker of exposure. The Scottish Hepatitis C Clinical Database containing data for all patients attending HCV clinics in participating health boards was linked to the HBV diagnostic registry and mortality data from Information Services Division, Scotland. Survival analyses with competing risks were constructed for time from the first appointment to decompensated cirrhosis, hepatocellular carcinoma (HCC) and liver-related mortality. Records of 8513 chronic HCV patients were included in the analyses (87 HBcAb positive and HBV surface antigen [HBsAg] positive, 1577 HBcAb positive and HBsAg negative, and 6849 HBcAb negative). Multivariate cause-specific proportional hazards models showed previous HBV infection (HBcAb positive and HBsAg negative) significantly increased the risks of decompensated cirrhosis (hazard ratio [HR]: 1.29, 95% CI: 1.01-1.65) and HCC (HR: 1.64, 95% CI: 1.09-2.49), but not liver-related death (HR: 1.02, 95% CI: 0.80-1.30). This is the largest study to date showing an association between previous HBV infection and certain adverse liver outcomes in HCV infection. Our analyses add significantly to evidence which suggests that HBV infection adversely affects liver health despite apparent clearance. This has important implications for HBV vaccination policy and indications for prioritization of HCV therapy.

Trends in hepatocellular carcinoma incidence and survival among people with hepatitis C: An international study.

This study evaluates trends in hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) incidence and survival in three settings, prior to introduction of direct-acting antiviral (DAA) therapies. HCV notifications from British Columbia (BC), Canada; New South Wales (NSW), Australia; and Scotland (1995-2011/2012/2013, respectively) were linked to HCC diagnosis data via hospital admissions (2001-2012/2013/2014, respectively) and mortality (1995-2013/2014/2015, respectively). Age-standardized HCC incidence rates were evaluated, associated factors were assessed using Cox regression, and median survival time after HCC diagnosis was calculated. Among 58 487, 84 529 and 31 924 people with HCV in BC, NSW and Scotland, 734 (1.3%), 1045 (1.2%) and 345 (1.1%) had an HCC diagnosis. Since mid-2000s, HCC diagnosis numbers increased in all jurisdictions. Age-standardized HCC incidence rates remained stable in BC and Scotland and increased in NSW. The strongest predictor of HCC diagnosis was older age [birth <1945, aHR in BC 5.74, 95% CI 4.84, 6.82; NSW 9.26, 95% CI 7.93, 10.82; Scotland 12.55, 95% CI 9.19, 17.15]. Median survival after HCC diagnosis remained stable in BC (0.8 years in 2001-2006 and 2007-2011) and NSW (0.9 years in 2001-2006 and 2007-2013) and improved in Scotland (0.7 years in 2001-2006 to 1.5 years in 2007-2014). Across the settings, HCC burden increased, individual-level risk of HCC remained stable or increased, and HCC survival remained extremely low. These findings highlight the minimal impact of HCC prevention and management strategies during the interferon-based HCV treatment era and form the basis for evaluating the impact of DAA therapy in the coming years.

Review article: hepatitis E-a concise review of virology, epidemiology, clinical presentation and therapy.

BACKGROUND: Hepatitis E virus (HEV) is a leading cause of acute icteric hepatitis and acute liver failure in the developing world. During the last decade, there has been increasing recognition of autochthonous (locally acquired) HEV infection in developed countries. Chronic HEV infection is now recognised, and in transplant recipients this may lead to cirrhosis and organ failure. AIM: To detail current understanding of the molecular biology of HEV, diagnostic and therapeutic strategies and propose future directions for basic science and clinical research. METHODS: PubMed was searched for English language articles using the key words "hepatitis E", "viral hepatitis", "autochthonous infection", "antiviral therapy", "liver transplantation", "acute", "chronic", "HEV", "genotype", "transmission" "food-borne", "transfusion". Additional relevant publications were identified from article reference lists. RESULTS: There has been increasing recognition of autochthonous HEV infection in Western countries, mainly associated with genotype 3. Chronic HEV infection has been recognised since 2008, and in transplant recipients this may lead to cirrhosis and organ failure. Modes of transmission include food-borne transmission, transfusion of blood products and solid organ transplantation. Ribavirin therapy is used to treat patients with chronic HEV infection, but new therapies are required as there have been reports of treatment failure with ribavirin. CONCLUSIONS: Autochthonous HEV infection is a clinical issue with increasing burden. Future work should focus on increasing awareness of HEV infection in the developed world, emphasising the need for clinicians to have a low threshold for HEV testing, particularly in immunosuppressed patients. Patients at potential risk of chronic HEV infection must also be educated and given advice regarding prevention of infection.

Acute liver failure in Scotland: changes in aetiology and outcomes over time (the Scottish Look-Back Study).

BACKGROUND: Acute liver failure is a rare and devastating clinical condition resulting from sudden loss of hepatic parenchyma and metabolic function. The Scottish Liver Transplant Unit (SLTU) offers specialist management and emergency liver transplantation to patients with acute liver failure from across Scotland. AIM: To describe temporal changes in number of admissions, aetiology of acute liver failure, severity of disease at presentation and outcomes over a 22-year period. METHODS: Retrospective analysis of the SLTU database, including all patients admitted with acute liver injury or acute liver failure between November 1992 and March 2014. RESULTS: There has been no change in the number of patients presenting with acute liver injury or failure secondary to paracetamol overdose, but a reduction in the number of admissions with acute liver injury or failure secondary to non paracetamol causes. Over time, disease severity at presentation has not changed in the paracetamol cohort; those with a non paracetamol aetiology have latterly presented with milder hepatic encephalopathy. Spontaneous survival rates improved significantly over time for those patients with acute liver failure due to paracetamol and non paracetamol aetiologies. The most marked improvement in survival is observed in the sickest patients meeting Kings College Hospital poor prognostic criteria. CONCLUSIONS: The number of admissions to the SLTU with acute liver failure is decreasing, due to reduced numbers of non paracetamol cases. Outcomes in this condition are improving, due to improvements in intensive care management and use of liver transplantation, and the increase in survival is most marked in patients meeting Kings College Hospital poor prognostic criteria.

Prognosis of 1169 hepatitis C chronically infected patients with decompensated cirrhosis in the predirect-acting antiviral era.

At a population level, little is known regarding the risk of liver- and nonliver-related mortality and hospitalization and the development of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-infected patients with decompensated cirrhosis (DC). This large-scale national record-linkage study estimates these outcomes following first hospital admission for DC. Record-linkages between national HCV diagnosis and clinical databases and the national inpatient hospital episode database and mortality register were conducted to follow-up the disease course of all identified HCV-diagnosed and chronically infected persons. The study population consisted of 1169 HCV chronically infected persons who had a first hospital admission for DC within the period 1994-2013. We observed an overall average annual percentage change of 12.6% in new DC patients (from 63 in 1994-1999 to 541 in 2009-2013), with no evidence for any improvement in the relative risks of liver-related or all-cause death over time. Between 1 January 1994 and 31 May 2014, 722 and 95 DC patients had died of a liver- and a nonliver-related cause, respectively, and 106 patients had a subsequent first admission for HCC. The 5-year cumulative incidence of liver-related mortality, nonliver-related mortality and first subsequent HCC admission was 61.3%, 8.2% and 8.8%, respectively. The health burden in HCV-infected patients associated with development of decompensated cirrhosis has increased dramatically over the last 20 years. Our findings establish the baseline mortality and HCC progression rates in DC patients against which the impact of new antiviral therapies can be measured.

The impact of proton pump inhibitor therapy on patients with liver disease.

BACKGROUND: Proton pump inhibitor (PPI) therapy has been reported to be an independent mortality risk factor in patients with cirrhosis. AIM: To identify the prevalence of PPI prescription, the appropriateness of this therapy and to investigate the relationship between PPI therapy and overall survival in patients with liver disease. METHODS: This retrospective cohort study used patient data for 2012 to 2014 collected from the Scottish Liver Transplant Unit and the Hepatology Ward at the New Royal Infirmary of Edinburgh. RESULTS: A total of 64% of the 198 patients discharged from the Hepatology ward were prescribed a PPI. Of the 206 patients assessed and listed for orthotopic liver transplant (OLT), 55% were prescribed a PPI. These percentages are significant, particularly as the majority had no recorded appropriate indication for this therapy. For patients listed for OLT, a logistic regression model revealed significant associations between PPI treatment and male sex, higher model of end-stage liver disease (MELD) scores and patient encephalopathy. A multivariate Cox regression model showed that MELD and UK model for end-stage liver disease scores were independent predictors of patient mortality, while alcoholic liver disease aetiology was a protective factor. There was no statistically significant difference in survival between patients who were prescribed a PPI at assessment and those who were not. CONCLUSION: Associations between PPI use, encephalopathy and higher MELD scores imply caution should be exercised in prescribing gastric acid suppressants to patients with cirrhosis, particularly in the absence of clear indications.

Differential visceral blood flow in the hyperdynamic circulation of patients with liver cirrhosis.

BACKGROUND: With advancing liver disease and the development of portal hypertension, there are major alterations in somatic and visceral blood flow. Using phase-contrast magnetic resonance angiography, we characterised alterations in blood flow within the hepatic, splanchnic and extra-splanchnic circulations of patients with established liver cirrhosis. AIM: To compare blood flow in splanchnic and extra-splanchnic circulations in patients with varying degrees of cirrhosis and healthy controls. METHODS: In a single-centre prospective study, 21 healthy volunteers and 19 patients with established liver disease (Child's stage B and C) underwent electrocardiogram-gated phase-contrast-enhanced 3T magnetic resonance angiography of the aorta, hepatic artery, portal vein, superior mesenteric artery, and the renal and common carotid arteries. RESULTS: In comparison to healthy volunteers, resting blood flow in the descending thoracic aorta was increased by 43% in patients with liver disease (4.31 ± 1.47 vs. 3.31 ± 0.80 L/min, P = 0.011). While portal vein flow was similar (0.83 ± 0.38 vs. 0.77 ± 0.35 L/min, P = 0.649), hepatic artery flow doubled (0.50 ± 0.46 vs. 0.25 ± 0.15 L/min, P = 0.021) and consequently total liver blood flow increased by 30% (1.33 ± 0.84 vs. 1.027 ± 0.5 L/min, P = 0.043). In patients with liver disease, superior mesenteric artery flow was threefold higher (0.65 ± 0.35 vs. 0.22 ± 0.13 L/min, P < 0.001), while total renal blood flow was reduced by 40% (0.37 ± 0.14 vs. 0.62 ± 0.22 L/min, P < 0.001) and total carotid blood flow unchanged (0.62 ± 0.20 vs. 0.65 ± 0.13 L/min, P = 0.315). CONCLUSIONS: Rather than a generalised systemic hyperdynamic circulation, liver disease is associated with dysregulated splanchnic vasodilatation and portosystemic shunting that, while inducing a high cardiac output, causes compensatory extra-splanchnic vasoconstriction - the 'splanchnic steal' phenomenon. These circulatory disturbances may underlie many of the manifestations of advanced liver disease.

Systematic review with meta-analysis: coffee consumption and the risk of cirrhosis.

BACKGROUND: Liver cirrhosis is a large burden on global health, causing over one million deaths per year. Observational studies have reported an inverse association between coffee and cirrhosis. AIMS: To perform a systematic review and meta-analysis to characterise the relationship between coffee consumption and cirrhosis. METHODS: We searched for studies published until July 2015 that reported odds ratios, relative risks (RR) or hazard ratios for cirrhosis stratified by coffee consumption. We calculated RRs of cirrhosis for an increase in daily coffee consumption of two cups for each study and overall. We performed analyses by study design, type of cirrhosis and mortality. We assessed the risk of bias in each study and the overall quality of evidence for the effect of coffee on cirrhosis. RESULTS: We identified five cohort studies and four case-control studies involving 1990 cases and 432 133 participants. We observed a dose-response in most studies and overall. The pooled RR of cirrhosis for a daily increase in coffee consumption of two cups was 0.56 (95% CI 0.44-0.68; I(2) 83.3%). The RR pooled from cohort studies for a daily increase of two cups was 0.58 (95% CI 0.41-0.76; I(2) 91.1%) and from case-control studies it was 0.52 (95% CI 0.40-0.63; I(2) 0.0%). The pooled RR of alcoholic cirrhosis for a daily increase of two cups was 0.62 (95% CI 0.51-0.73; I(2) 0%) and of death from cirrhosis it was 0.55 (95% CI 0.35-0.74; I(2) 90.3%). CONCLUSION: This meta-analysis suggests that increasing coffee consumption may substantially reduce the risk of cirrhosis.

Fulminant hepatic failure in autoimmune polyendocrine syndrome type-1.

Fulminant hepatic failure is liver disease that causes encephalopathy within 8 weeks of onset of symptoms or within 2 weeks of onset of jaundice in a patient without prior evidence of liver disease. Autoimmune polyendocrine syndrome type-1 is an autoimmune autosomal-recessive condition causing parathyroid and adrenal insufficiency, alopecia, chronic mucocutaneous candidiasis, ectodermal dystrophy and, rarely, hepatitis. Although the liver can be affected as a consequence of the autoimmune process, the spectrum of disease activity is varied. Autoimmune hepatitis develops in 10-20% of patients and successful liver transplantation has been reported in pediatric patients who failed immunosuppressive treatment. We report fulminant hepatic failure in an adult patient with autoimmune polyendocrine syndrome type-1 who responded to medical treatment and did not require liver transplantation. We highlight the diagnostic scoring system for autoimmune hepatitis and the referral criteria for liver transplantation in fulminant hepatic failure.

Randomised clinical study: comparison of acceptability, patient tolerance, cardiac stress and endoscopic views in transnasal and transoral endoscopy under local anaesthetic.

BACKGROUND: Transnasal endoscopy (TNE) with ultrathin endoscopes has been advocated as an attractive alternative, for diagnostic upper endoscopy. AIM: To assess tolerability, acceptability and quality of TNE, in comparison with standard upper endoscopy (SOGD, standard oesophago-gastro-duodenoscopy) under local anaesthetic. METHODS: We prospectively recruited 157 patients (83 females/74 males) mean age 57 years. The Fujinon EG530N (5.9 mm) and EG530WR (9.4 mm) endoscopes were used. The endoscopist and all patients completed detailed questionnaires regarding tolerability, acceptance and quality of endoscopy using standard visual analogue scales (VAS). Oxygen saturation (SaO2 ), heart rate (HR) and systolic blood pressure (SBP) were recorded. Quality of biopsies was evaluated. RESULTS: Analysis included 161 procedures (TNE:79, SOGD:82) with duodenal intubation achieved in all patients. VAS scores for patient comfort were significantly better in the TNE group (7.3 vs. 5.3 respectively, P < 0.001). Twenty patients with previous experience of standard endoscopy were randomised to TNE and 19 of them (95.5%) preferred the TNE. Gagging was significantly less in the TNE group (0.12 vs. 3.41 respectively, P < 0.001). Cardiovascular stress was significantly less in the TNE group irrespective of the degree of gagging or comfort. TNE biopsies were smaller, but adequate for definitive diagnosis, similarly to standard endoscopy. CONCLUSIONS: Transnasal endoscopy is superior to SOGD in terms of comfort and patient acceptance with significantly less cardiovascular stress. TNE can routinely be used as alternative to SOGD under local anaesthetic, for diagnosis and should be preferentially offered in cardiorespiratory compromised patients.

Review article: 2014 UK consensus guidelines - hepatitis C management and direct-acting anti-viral therapy.

BACKGROUND: Therapeutic options for the management of hepatitis C virus (HCV) infection have evolved rapidly over the past two decades, with a consequent improvement in cure rates. Novel therapeutic agents are an area of great interest in the research community, with a number of these agents showing promise in the clinical setting. AIMS: To assess and present the available evidence for the use of novel therapeutic agents for the treatment of HCV, updating previous guidelines. METHODS: All Phase 2 and 3 studies, as well as abstract presentations from international Hepatology meetings were identified and reviewed for suitable inclusion, based on studies of new therapies in HCV. Treatment-naïve and experienced individuals, as well as cirrhotic and co-infected individuals were included. RESULTS: Sofosbuvir, simeprevir and faldaprevir, along with pegylated interferon and ribavirin, have a role in the treatment of chronic HCV infection. The precise regimens are largely dependent on the patient characteristics, patient and physician preferences, and cost implication. CONCLUSIONS: Therapies for chronic HCV have evolved dramatically in recent years. Interferon-free regimens are now possible without compromise in the rate of sustained viral response. The decision as to which regimen is most appropriate is multifactorial, and based on efficacy, safety and cost.

Attendance at specialist hepatitis clinics and initiation of antiviral treatment among persons chronically infected with hepatitis C: examining the early impact of Scotland's Hepatitis C Action Plan.

Primary goals of the Hepatitis C Action Plan for Scotland Phase II (May 2008-March 2011) were to increase, among persons chronically infected with the hepatitis C (HCV) virus, attendance at specialist outpatient clinics and initiation on antiviral therapy. We evaluated progress towards these goals by comparing the odds, across time, of (a) first clinic attendance within 12 months of HCV diagnosis (n = 9747) and (b) initiation on antiviral treatment within 12 months of first attendance (n = 5736). Record linkage between the national HCV diagnosis (1996-2009) and HCV clinical (1996-2010) databases and logistic regression analyses were conducted for both outcomes. For outcome (a), 32% and 45% in the respective pre-Phase II (before 1 May 2008) and Phase II periods attended a specialist clinic within 12 months of diagnosis; the odds of attendance within 12 months increased over time (OR = 1.05 per year, 95% CI: 1.04-1.07), but was not significantly greater for persons diagnosed with HCV in the Phase II era, compared with the pre-Phase II era (OR = 1.1, 95% CI: 0.9-1.3), after adjustment for temporal trend. For outcome (b), 13% and 28% were initiated on treatment within 12 months of their first clinic attendance in the pre-Phase II and Phase II periods, respectively. Higher odds of treatment initiation were associated with first clinic attendance in the Phase II (OR = 1.9, 95% CI: 1.5-2.4), compared with the pre-Phase II era. Results were consistent with a positive impact of the Hepatitis C Action Plan on the treatment of chronically infected individuals, but further monitoring is required to confirm a sustained effect.

Review article: advances in the management of patients with cirrhosis and portal hypertension-related renal dysfunction.

BACKGROUND: In cirrhosis, portal hypertension is associated with a spectrum of renal dysfunction that has significant implications for morbidity and mortality. AIM: To discuss recent progress in the patho-physiological mechanisms and therapeutic options for portal hypertension-related renal dysfunction. METHODS: A literature search using Pubmed was performed. RESULTS: Portal hypertension-related renal dysfunction occurs in the setting of marked neuro-humoral and circulatory derangement. A systemic inflammatory response is a pathogenetic factor in advanced disease. Such physiological changes render the individual vulnerable to further deterioration of renal function. Patients are primed to develop acute kidney injury when exposed to additional 'hits', such as sepsis. Recent progress has been made regarding our understanding of the aetiopathogenesis. However, treatment options once hepatorenal syndrome develops are limited, and prognosis remains poor. Various strategies to prevent acute kidney injury are suggested. CONCLUSION: Prevention of acute kidney injury in high risk patients with cirrhosis and portal hypertension-related renal dysfunction should be a clinical priority.

An epidemiological study of the association of coffee with chronic liver disease.

BACKGROUND AND AIMS: Chronic liver disease affects 855 people per million in the UK. Previous studies have reported that coffee appears protective against the development of abnormal liver enzymes, hepatic fibrosis and cirrhosis. The aim of this study, the first in a Scottish population, was to compare coffee consumption in patients with liver disease and that of control populations to determine correlations between coffee intake and the incidence of non-cancerous liver disease and with Child's-Pugh and model for end-stage liver disease (MELD) scores. METHODS AND RESULTS: Two hundred and eighty-six patients attending the liver outpatient department at the Royal Infirmary of Edinburgh completed a questionnaire regarding coffee consumption and lifestyle factors. Control questionnaires were also completed by 100 orthopaedic outpatients and 120 medical students. Patients with cirrhosis (n = 95) drank significantly less coffee than those without cirrhosis (p = <0.001). There was no correlation between Child's-Pugh (-0.018) and MELD scores (-0.132) with coffee consumption. CONCLUSION: Coffee drinking is associated with a reduced prevalence of cirrhosis in patients with chronic liver disease. However, there was no significant difference in the amount of coffee drunk by liver patients and the control groups. It is possible that by changing the amount of coffee drunk, the development of cirrhosis in liver disease could be postponed.

Serum neopterin and soluble CD163 as markers of macrophage activation in paracetamol (acetaminophen)-induced human acute liver injury.

BACKGROUND: Macrophage activation is implicated in the pathogenesis of the systemic inflammatory response syndrome (SIRS) following paracetamol (acetaminophen) overdose (POD). Neopterin is synthesised from macrophages and reflects the intensity of monocyte/macrophage activation. Soluble CD163 (sCD163) is a marker of alternatively activated M2 macrophages. AIM: To examine neopterin and sCD163 levels in a cohort of acute liver injury patients. METHODS: Consecutive patients (n = 41, (18 (43.9%) male) with acute liver injury were enrolled. Neopterin and sCD163 levels were measured by ELISA. RESULTS: A total of 24/33 (72.7%) POD patients developed hepatic encephalopathy (HE), and therefore acute liver failure. Both neopterin and sCD163 levels were significantly higher in PODs compared with chronic liver disease (neopterin P < 0.001, sCD163 P = 0.038) and healthy (both P < 0.001) controls. Admission neopterin levels were significantly higher in PODs: with HE (P = 0.001); with the SIRS (P = 0.005); who required renal replacement therapy (P = 0.003); who died or required liver transplantation (P = 0.006; AUROC 78.6% (95% CI 62.2-94.9%). Serum sCD163 levels were significantly higher in those PODs with the SIRS (P = 0.033) on admission, and were higher in those PODs who died or required OLT (P = 0.024). Both admission neopterin and sCD163 levels in PODs correlated with organ failure scores but not with serum ALT. There was no significant correlation between neopterin and sCD163 values. CONCLUSIONS: Both serum neopterin and sCD163 levels are significantly elevated following paracetamol overdose, and reflect the degree of macrophage activation in this condition. Serum neopterin in particular may have value as an early proxy marker of macrophage activation following paracetamol overdose.

Persistently elevated troponin I in paracetamol hepatotoxicity: association with liver injury, organ failure, and outcome.

CONTEXT: An elevated troponin I (TnI) is associated with a poorer prognosis during critical illness. OBJECTIVE: Our aims were to determine whether significant paracetamol-induced hepatotoxicity was associated with an elevated TnI; if this elevation was persistent and was associated with worse clinical outcomes. MATERIALS AND METHODS: In this retrospective cohort study, the requirement for orthotopic liver transplantation (OLT) or death and/or the development of multiorgan failure (MOF) was evaluated for 48 consecutive patients admitted to the Royal Infirmary of Edinburgh (a university tertiary referral centre) with acute liver injury or acute liver failure secondary to paracetamol overdose. RESULTS: TnI was elevated (≥ 0.05 ng/L) in 13/48 patients (27%). This appeared to be sustained for at least 6 days which has not been shown previously in the context of Acute Liver Injury (ALI). Elevated TnI was strongly associated with MOF, with the requirement for inotropic support being the strongest predictor (p = 0.003, OR 9.00, 95% CI 2.13-37.98). TnI elevations also correlated strongly with Acute Physiology and Chronic Health Evaluation (APACHE) II scores (p = 0.0006, r = 0.482, 95% CI 0.22-0.68) and with interleukin 6 (IL-6) levels (p = 0.0001, r = 0.55, 95% CI 0.29-0.73). Although a raised TnI was associated with a markedly increased risk of death or orthotopic liver transplant (p = 0.005, OR 7.73, 95% CI 1.87-32.05) on univariate analysis, this was primarily seen in the context of MOF (SOFA score p = 0.003, OR 1.23, 95% CI 1.07-1.41) and was not an independent predictor of death. There was no correlation between TnI or outcome with other cardiac biomarkers and markers of cardiovascular risk. DISCUSSION AND CONCLUSION: An elevated TnI in the context of acute liver injury or liver failure following paracetamol overdose is associated with a significantly worse patient outcome but it is not an independent prognostic factor. Further studies should be undertaken to investigate the mechanism behind this elevated troponin association.