Altered peripheral blood monocyte phenotype and function in chronic liver disease:Implications for hepatic recruitment and systemic inflammation

Background and Aim

Controlled attenuation parameter in NAFLD identifies risk of suboptimal glycaemic and metabolic control

To examine the relationship between steatosis quantified by controlled attenuation parameter (CAP) values and glycaemic/metabolic control. 230 patients, recruited from an Endocrine clinic or primary care underwent routine Hepatology assessment, with liver stiffness measurements and simultaneous CAP. Multivariable logistic regression was performed to identify potential predictors of Metabolic Syndrome (MetS), HbA1c ≥ 7%, use of insulin, hypertriglyceridaemia and CAP ≥ 300 dB/m. Patients were 56.7 ± 12.3 years of age with a high prevalence of MetS (83.5%), T2DM (81.3%), and BMI ≥ 40 kg/m (18%). Median CAP score was 344 dB/m, ranging from 128 to 400 dB/m. BMI (aOR 1.140 95% CI 1.068-1.216), requirement for insulin (aOR 2.599 95% CI 1.212-5.575), and serum ALT (aOR 1.018 95% CI 1.004-1.033) were independently associated with CAP ≥ 300 dB/m. Patients with CAP interquartile range

Is there scope to improve the selection of patients with alcohol-related liver disease for referral to secondary care? A retrospective analysis of primary care referrals to a UK liver centre, incorporating simple blood tests

Objectives Twenty per cent of people with alcohol use disorders develop advanced fibrosis and warrant referral to secondary care. Improving outcomes in alcohol-related liver disease (ArLD) relies on its earlier detection in primary care with non-invasive tests (NIT). We aimed to determine the proportion of alcohol-related referrals who were diagnosed with advanced fibrosis in secondary care, the prevalence of both alcohol and fatty liver disease (‘BAFLD’) and the potential impact of NIT on referral stratification.Design/setting Retrospective analysis of all general practitioner-referrals with suspected ArLD/non-alcoholic fatty liver disease (NAFLD) to a UK hepatology-centre between January 2015 and January 2018.Participants Of 2944 new referrals, 762 (mean age 55.5±13.53 years) met inclusion criteria: 531 NAFLD and 231 ArLD, of which 147 (64%) could be reclassified as ‘BAFLD’.Primary outcome measure Proportion of referrals with suspected ArLD/NAFLD with advanced fibrosis as assessed by tertiary centre hepatologists using combinations of FibroScan, imaging, examination and blood tests and liver histology, where indicated.Secondary outcome measures Included impact of body mass index/alcohol consumption on the odds of a diagnosis of advanced fibrosis, and performance of NIT in predicting advanced fibrosis in planned post-hoc analysis of referrals.Results Among ArLD referrals 147/229 (64.2%) had no evidence of advanced fibrosis and were judged ‘unnecessary’. Advanced fibrosis was observed in men drinking ≥50 units per week (U/w) (OR 2.74, 95% CI 1.51 to 5, p=0.001) and ≥35 U/w in women (OR 5.11, 95% CI 1.31 to 20.03, p=0.019). Drinking >14 U/w doubled the likelihood of advanced fibrosis in overweight/obesity (OR 2.11; 95% CI 1.44 to 3.09; p<0.001). Use of fibrosis 4 score could halve unnecessary referrals (OR 0.50; 95% CI 0.32 to 0.79, p=0.003) with false-negative rate of 22%, but was rarely used.Conclusions The majority of referrals with suspected ArLD were deemed unnecessary. NIT could improve identification of liver damage in ArLD, BAFLD and NAFLD in primary care. Anecdotal thresholds for harmful drinking (35 U/w in women and 50 U/w in men) were validated. The impact of alcohol on NAFLD highlights the importance of multi-causality in chronic liver disease

Derivation and performance of standardized enhanced liver fibrosis (ELF) test thresholds for the detection and prognosis of liver fibrosis

Introduction Noninvasive tests are increasingly used to assess liver fibrosis and determine prognosis but suggested test thresholds vary. We describe the selection of standardized thresholds for the Enhanced Liver Fibrosis (ELF) test for the detection of liver fibrosis and for prognostication in chronic liver disease. Methods A Delphi method was used to identify thresholds for the ELF test to predict histological liver fibrosis stages, including cirrhosis, using data derived from 921 patients in the EUROGOLF cohort. These thresholds were then used to determine the prognostic performance of ELF in a subset of 457 patients followed for a mean of 5 years. Results The Delphi panel selected sensitivity of 85% for the detection of fibrosis and >95% specificity for cirrhosis. The corresponding thresholds were 7.7, 9.8, and 11.3. Eighty-five percent of patients with mild or worse fibrosis had an ELF score ≥7.7. The sensitivity for cirrhosis of ELF ≥9.8 was 76%. ELF ≥11.3 was 97% specific for cirrhosis. ELF scores show a near-linear relationship with Ishak fibrosis stages. Relative to the <7.7 group, the hazard ratios for a liver-related outcome at 5 years were 21.00 (95% CI, 2.68–164.65) and 71.04 (95% CI, 9.4–536.7) in the 9.8 to <11.3 and ≥11.3 subgroups, respectively. Conclusion The selection of standard thresholds for detection and prognosis of liver fibrosis is described and their performance reported. These thresholds should prove useful in both interpreting and explaining test results and when considering the relationship of ELF score to Ishak stage in the context of monitoring

Bilateral Cranial Nerve VI Palsies in Cryptococcal Meningitis, HIV, and Syphilis: A Case Report

Introduction: Cranial nerve (CN) VI palsy is a common complaint seen in the emergency department (ED) and has a wide range of causes. Bilateral CN VI palsies are uncommon and appear to be associated with more severe complications.Case Report: A 29-year-old male presented to the ED from an ophthalmology office for diplopia, headache, and strabismus. He was found to have bilateral CN VI palsies and new-onset seizure in the ED. A lumbar puncture revealed cryptococcal meningitis. Additional tests revealed a new diagnosis of human immunodeficiency virus (HIV), acquired immunodeficiency syndrome (AIDS), and syphilis.Conclusion: Cryptococcal meningitis remains a life-threatening complication of HIV/AIDS. Coinfections with HIV, particularly syphilis, further complicate a patient’s prognosis as both can lead to devastating neurological sequelae. In cryptococcal meningitis, elevated intracranial pressure is a complication that can manifest as seizures, altered mental status, and cranial nerve palsies

Association of exercise participation levels with cardiometabolic health and quality of life in individuals with hepatitis C

Objective Hepatitis C virus (HCV) infection 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.Design Cross-sectional observational study recruiting consecutive patients with HCV from viral hepatitis clinics. Data were collected on CVD risk factors, anthropometry, HRQoL and the Exercise Benefits and Barriers Scale (EBBS).Results 86 patients were recruited (71% men, 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 Short-Form 36v2 domains compared with 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’ versus ‘inactive’ groups, however, patients categorised as ‘active’ scored significantly higher on the psychological outlook and social interaction subscales (p<0.05) than those that were ‘inactive’. There were significant associations between EBBS scores and HRQoL (p<0.05).Conclusions PA/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

Increased cardiovascular risk and reduced quality of life are highly prevalent among individuals with hepatitis C

Objective Hepatitis C virus (HCV) infection is common. Although treatment is effective, with oral antivirals curing >95% of patients, most individuals have comorbidities that persist long term. Therefore, our aim was to determine the prevalence of potentially modifiable health problems in patients with HCV and develop an HCV care bundle to identify and target comorbidities. Design Cross-sectional, observational single-centre study that recruited consecutive patients with HCV from our viral hepatitis clinics. Data were collected on cardiovascular (CV) risk factors, lifestyle behaviours, anthropometry and health-related quality of life (HRQoL). QRISK 3 was used to predict 10-year CV event risk. Results 100 patients were recruited (67% male, 93% white, median age 52 years (range 24–80); 71% were treated for HCV; 34% had cirrhosis; 14% had diabetes; 61% had hypertension; 31% had metabolic syndrome; and 54% were smokers). The median 10-year CV event risk was 8.3% (range 0.3%–63%). 45% had a predicted 10-year CV event risk of >10%. Only 10% of individuals were treated with statins and 27% with antihypertensives. 92% had a predicted ‘heart age’ greater than their chronological age (median difference +7 (−4 to +26) years). HRQoL was reduced in all SF36v2 domains in the cohort. Factors independently associated with HRQoL included cirrhosis, metabolic syndrome, history of mental health disorder, sedentary behaviour and HCV viraemia. Conclusion A large proportion of patients with HCV presented with increased risk of CV events, and rates of smoking and sedentary behaviour were high, while prescribing of primary prophylaxis was infrequent. HRQoL was also reduced in the cohort. A ‘care bundle’ was developed to provide a structured approach to treating potentially modifiable health problems

Association of exercise participation levels with cardiometabolic health and quality of life in individuals with hepatitis C

Objective Hepatitis C virus (HCV) infection 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. Design Cross-sectional observational study recruiting consecutive patients with HCV from viral hepatitis clinics. Data were collected on CVD risk factors, anthropometry, HRQoL and the Exercise Benefits and Barriers Scale (EBBS). Results 86 patients were recruited (71% men, 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 Short-Form 36v2 domains compared with their inactive counterparts (p0.05). EBBS scores were similar in the ‘active’ versus ‘inactive’ groups, however, patients categorised as ‘active’ scored significantly higher on the psychological outlook and social interaction subscales (p<0.05) than those that were ‘inactive’. There were significant associations between EBBS scores and HRQoL (p<0.05). Conclusions PA/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

Peripheral blood monocyte subset distribution in chronic liver disease (CLD).

<p>(A) Representative flow cytometry plot of the 3 main monocyte subsets, i—CD14^highCD16^- “Classical”, ii—CD14^highCD16⁺ “intermediate”, iii—CD14⁺CD16⁺ “non-classical” monocytes. (B) Distribution of peripheral leukocyte lineages obtained from patient haematology full blood counts. (C) Proportion of monocytes in isolated peripheral blood mononuclear cell (PBMC) in control subjects and CLD patients with no-advanced fibrosis (No adv.), cirrhosis or decompensated cirrhosis (Decomp). (D) Distribution of monocyte subsets in the PBMC fraction of control subjects and CLD patients. (Data represented as mean +SEM, ** ^{++ ## ψψ} P<0.01; D, significance shown vs corresponding control subset; Neut, neutrophils; Lymph, lymphocytes; Mono, monocytes; Eosin, eosinophils; Baso, basophils)</p