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Liver and systemic inflammatory factors influence monocyte phenotype and function, which has implications for hepatic recruitment and subsequent inflammatory and fibrogenic responses, as well as host defence. Peripheral blood monocyte surface marker (CD14, CD16, CD163, CSF1R, CCR2, CCR4, CCR5, CXCR3, CXCR4, CX3CR1, HLA-DR, CD62L, SIGLEC-1) expression and capacity for phagocytosis, oxidative burst and LPS-stimulated TNF production were assessed in patients with hepatitis C (HCV) (n = 39) or non-alcoholic fatty liver disease (NAFLD) (n = 34) (classified as non-advanced disease, compensated cirrhosis and decompensated cirrhosis) and healthy controls (n = 11) by flow cytometry. The selected markers exhibited similar monocyte-subset-specific expression patterns between patients and controls. Monocyte phenotypic signatures differed between NAFLD and HCV patients, with an increased proportion of CD16+ non-classical monocytes in NAFLD, but increased expression of CXCR3 and CXCR4 in HCV. In both cohorts, monocyte CCR2 expression was reduced and CCR4 elevated over controls. CD62L expression was specifically elevated in patients with decompensated cirrhosis and positively correlated with the model-for-end-stage-liver-disease score. Functionally, monocytes from patients with decompensated cirrhosis had equal phagocytic capacity, but displayed features of dysfunction, characterised by lower HLA-DR expression and blunted oxidative responses. Lower monocyte TNF production in response to LPS stimulation correlated with time to death in 7 (46%) of the decompensated patients who died within 8 months of recruitment. Chronic HCV and NAFLD differentially affect circulating monocyte phenotype, suggesting specific injury-induced signals may contribute to hepatic monocyte recruitment and systemic activation state. Monocyte function, however, was similarly impaired in patients with both HCV and NAFLD, particularly in advanced disease, which likely contributes to the increased susceptibility to infection in these patients.

Non-alcoholic fatty liver disease (NAFLD) affects 25% of the adult population globally. Since liver fibrosis is the most important predictor of liver-related complications in patients with NAFLD, identification of patients with advanced fibrosis among at-risk individuals is an important issue in clinical practice. Transient elastography is the best evaluated non-invasive method used in referral centres to assess liver fibrosis, however serum-based tests, such as the Enhanced Liver Fibrosis (ELF) score, have a practical advantage as first-line tests due to their wider availability and lower cost. We previously identified matrix metalloproteinase 7 (MMP7) as a serum biomarker of histological advanced fibrosis in a mixed-etiology patient cohort. In this study we aimed to determine the association between MMP7 and fibrosis, assessed by transient elastography, in patients with NAFLD. Serum MMP7 levels were measured in a cohort of 228 patients with NAFLD. Associations between MMP7, liver stiffness measurement (LSM), ELF score and clinical parameters were determined using logistic regression modelling. Serum MMP7 was associated with clinically significant fibrosis (LSM ≥ 8.2), independent of age, gender, BMI and diabetes. The addition of MMP7 significantly improved the diagnostic performance of the ELF test, particularly in patients over the age of 60. Combinations of serum biomarkers have the potential to improve the sensitivity and specificity of detection of advanced fibrosis in at-risk patients with NAFLD. We have demonstrated that serum MMP7 is independently associated with clinically significant fibrosis and improves the diagnostic performance of currently available tests in older patients.

Non-alcoholic fatty liver disease (NAFLD) and depression are common disorders and have bidirectional contributing relationships to metabolic syndrome. We aimed to determine whether a fasting serum signature of recent, self-reported depressive symptoms could be identified in a heterogeneous NAFLD cohort using nuclear magnetic resonance (NMR)-based metabolomics integrated with clinical chemistry. Serum nuclear magnetic resonance (NMR) metabolite profiles and corresponding clinical chemistry were compared between patients with depressive symptoms in the last 12-months (n = 81) and patients without recent depressive symptoms (n = 137 controls) using multivariate statistics. Orthogonal partial least squares discriminant analysis (OPLS-DA) of the biochemical and metabolomic data identified NAFLD patients with recent depression with a cross-validated accuracy of 61.5%, independent of age, sex, medication, and other comorbidities. This led to the development of a diagnostic algorithm with AUC 0.83 for future testing in larger clinical cohorts. Serum triglycerides, VLDL cholesterol, and the inflammatory biomarker GlycA were key metabolites increased in patients with recent depressive symptoms, while serum glutamine level was reduced. Here, serum NMR metabolite analysis provides a link between disturbed lipid metabolism, inflammation, and active mental health issues in NAFLD, irrespective of disease severity.

Non-alcoholic fatty liver disease (NAFLD) accounts for 10–15% of orthotopic liver transplants (OLTs) in the UK. Index presentations with cirrhotic decompensation represent missed opportunities for preventive treatment leaving OLT or palliation as the only options. We retrospectively reviewed patient records for all NAFLD patients undergoing assessment for OLT between January 2003 and December 2017. Data were available for 81 patients with NAFLD as the primary diagnosis. Fifty-two patients had decompensated cirrhosis at first presentation; 91.7% presented to secondary care compared to 52.7% referred from primary care (p=0.001). Cirrhosis was not suspected at the time of referral to hospital in 24.7% of patients subsequently assessed for OLT. Most patients undergoing assessment for OLT for NAFLD had decompensated cirrhosis at their first diagnosis of chronic liver disease. These data highlight the plight of patients with NAFLD cirrhosis in whom chronic liver disease is diagnosed late.

Discrepancies between the medicines consumed by patients and those documented in the medical record can affect medication safety. We aimed to characterize medication discrepancies and medication regimen complexity over time in a cohort of outpatients with decompensated cirrhosis, and evaluate the impact of pharmacist-led intervention on discrepancies and patient outcomes. In a randomized-controlled trial (n = 57 intervention and n = 57 usual care participants), medication reconciliation and patient-oriented education delivered over a six-month period was associated with a 45% reduction in the incidence rate of ‘high’ risk discrepancies (IRR = 0.55, 95%CI = 0.31–0.96) compared to usual care. For each additional ‘high’ risk discrepancy at baseline, the odds of having ≥ 1 unplanned medication-related admission during a 12-month follow-up period increased by 25% (adj-OR = 1.25, 95%CI = 0.97–1.63) independently of the Child–Pugh score and a history of variceal bleeding. Among participants with complete follow-up, intervention patients were 3-fold less likely to have an unplanned medication-related admission (adj-OR = 0.27, 95%CI = 0.07–0.97) compared to usual care. There was no association between medication discrepancies and mortality. Medication regimen complexity, frequent changes to the regimen and hepatic encephalopathy were associated with discrepancies. Medication reconciliation may improve medication safety by facilitating communication between patients and clinicians about ‘current’ therapies and identifying potentially inappropriate medicines that may lead to harm.

Aim. To examine the association between lifetime alcohol consumption and significant liver disease in type 2 diabetic patients with NAFLD. Methods. A cross-sectional study assessing 151 patients with NAFLD at risk of clinically significant liver disease. NAFLD fibrosis severity was classified by transient elastography; liver stiffness measurements ≥8.2 kPa defined significant fibrosis. Lifetime drinking history classified patients into nondrinkers, light drinkers (always ≤20 g/day), and moderate drinkers (any period with intake >20 g/day). Result. Compared with lifetime nondrinkers, light and moderate drinkers were more likely to be male (p=0.008) and to be Caucasian (p=0.007) and to have a history of cigarette smoking (p=0.000), obstructive sleep apnea (p=0.003), and self-reported depression (p=0.003). Moderate drinkers required ≥3 hypoglycemic agents to maintain diabetic control (p=0.041) and fibrate medication to lower blood triglyceride levels (p=0.044). Compared to lifetime nondrinkers, light drinkers had 1.79 (95% CI: 0.67–4.82; p=0.247) and moderate drinkers had 0.91 (95% CI: 0.27–3.10; p=0.881) times the odds of having liver stiffness measurements ≥8.2 kPa (adjusted for age, gender, and body mass index). Conclusions. In diabetic patients with NAFLD, light or moderate lifetime alcohol consumption was not significantly associated with liver fibrosis. The impact of lifetime alcohol intake on fibrosis progression and diabetic comorbidities, in particular obstructive sleep apnea and hypertriglyceridemia, requires further investigation.

Background People with decompensated cirrhosis require complex medical care and are often prescribed an intricate and frequently changing medication and lifestyle regimen. However, many patients mismanage their medications or have poor comprehension of their disease and self-management tasks. This can lead to harm, hospitalization, and death. Methods/design A patient-oriented education and medication management intervention has been developed for implementation at a tertiary hospital hepatology outpatient center in Queensland, Australia. Consenting patients with decompensated cirrhosis will be randomly allocated to education intervention or usual care treatment arms when they attend routine follow-up appointments. In the usual care arm, participants will be reviewed by their hepatologist according to the current model of care in the hepatology clinic. In the intervention arm, participants will be reviewed by a clinical pharmacist to receive the education and medication management intervention at baseline in addition to review by their hepatologist. Intervention participants will also receive three further educational contacts from the clinical pharmacist within the following 6-month period, in addition to routine hepatologist review that is scheduled within this time frame. All participants will be surveyed at baseline and follow-up (approximately 6 months post-enrollment). Validated questionnaire tools will be used to determine participant adherence, medication beliefs, illness perceptions, and quality of life. Patients’ knowledge of dietary and lifestyle modifications, their current medications, and other clinical data will be obtained from the survey, patient interview, and medical records. Patient outcome data will be collected at 52 weeks. Discussion The intervention described within this protocol is ready to adapt and implement in hepatology ambulatory care centers globally. Investigation of potentially modifiable variables that may impact medication management, in addition to the effect of a clinical pharmacist-driven education and medication management intervention on modifying these variables, will provide valuable information for future management of these patients. Trial registration Australian and New Zealand Clinical Trial Registry identifier: ACTRN12616000780459 . Registered on 15 June 2016.

People with decompensated cirrhosis are often prescribed a complex regimen of therapeutic and prophylactic medications. In other chronic diseases, polypharmacy increases the risk of medication misadventure and medication‐related problems (MRPs), with associated increased morbidity, mortality, and health care costs. This study examined MRPs in a cohort of ambulatory patients with a history of decompensated cirrhosis who were enrolled in a randomized controlled trial of a pharmacist‐led, patient‐oriented medication education intervention and assessed the association between MRPs and patient outcomes. A total of 375 MRPs were identified among 57 intervention patients (median, 6.0; interquartile range, 3.5‐8.0 per patient; maximum 17). Nonadherence (31.5%) and indication issues (29.1%) were the most prevalent MRP types. The risk of potential harm associated with MRPs was low in 18.9% of instances, medium in 33.1%, and high in 48.0%, as categorized by a clinician panel using a risk matrix tool. Patients had a greater incidence rate of high‐risk MRPs if they had a higher Child‐Pugh score (incidence rate ratio [IRR], 1.31; 95% confidence interval [CI], 1.09‐1.56); greater comorbidity burden (IRR, 1.15; 95% CI, 1.02‐1.29); and were taking more medications (IRR, 1.12; 95% CI, 1.04‐1.22). A total of 221 MRPs (58.9%) were resolved following pharmacist intervention. A greater proportion of high‐risk MRPs were resolved compared to those of low and medium risk (68.9% versus 49.7%; P < 0.001). During the 12‐month follow‐up period, intervention patients had a lower incidence rate of unplanned admissions compared to usual care (IRR, 0.52; 95% CI, 0.30‐0.92). Conclusion: High‐risk MRPs are prevalent among adults with decompensated cirrhosis. Pharmacist intervention facilitated identification and resolution of high‐risk MRPs and was associated with reduced incidence rate of unplanned hospital admissions in this group. People with decompensated cirrhosis are often prescribed a complex medication regimen to manage liver disease and comorbidities. ‘High’ risk medication‐related problems are present in approximately half of patients, with greater incidence in patients with a higher Child‐Pugh score (IRR = 1.31, 95%CI 1.09–1.56), greater comorbidity burden (IRR = 1.15, 95%CI 1.02–1.29) and those taking more medications (IRR = 1.12, 95%CI 1.04–1.22). Pharmacist‐led intervention in a collaborative model of hepatology ambulatory care aided the resolution of ‘High’ risk medication‐related problems and reduced the incidence of hospitalization in outpatients with decompensated cirrhosis.

IntroductionHepatitis C virus infection (HCV) is associated with an increased risk of cardiovascular disease (CVD) and reduced health-related quality of life (HRQoL). Although physical activity (PA)/exercise has been shown to reduce CVD risk and improve HRQoL in patients with liver disease, there is limited data in HCV. We aimed to explore the association between PA/exercise levels, CVD risk and HRQoL in patients with HCV and assess individuals’ attitudes to PA/exercise.MethodsCross-sectional observational study recruiting consecutive patients with HCV from viral hepatitis clinics. Data was collected on CVD risk factors, anthropometry, HRQoL, and the exercise benefits and barriers scale (EBBS).Results86 patients were recruited (71% male, 94% white, age 52 ±13 years); 49% of the cohort self-reported to be currently active. Although HRQoL was reduced across the cohort, patients that were regularly ‘active’ reported significantly higher HRQoL scores across SF36v2 domains compared to their inactive counterparts (p<0.05). Metabolic and cardiovascular characteristics were no different between groups stratified by PA/exercise status (p>0.05). EBBS scores were similar in the ‘active’ vs ‘inactive’ groups, however, patients categorised as ‘active’ scored significantly higher on the psychological outlook and social interaction sub-scales (p<0.05) than those that were ‘inactive’. There were significant associations between EBBS scores and HRQoL (p<0.05).ConclusionsPA/exercise is associated with increased HRQoL in patients with HCV irrespective of clinical parameters. Addressing specific motivators/barriers to exercise for patients will be key to designing effective PA/exercise interventions in this patient population to ensure maximum uptake and adherence.

Spinal involvement may be the first manifestation of tuberculosis. 1 Have a high index of suspicion of tuberculosis in patients from endemic countries, who have had contact with someone from an endemic country, the immunocompromised, intravenous drug users, the homeless 2 and those who present with any of; fever, cough malaise, back pain, neurological symptoms or weight loss.