Serum CC-Chemokine Ligand 2 Is Associated with Visceral Adiposity but Not Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is caused by ectopic fat accumulation in the liver as a consequence of metabolic perturbations associated with obesity, type 2 diabetes, dyslipidemia, and insulin resistance. People with NAFLD may develop metabolic and cardiovascular complications and/or liver-related complications, especially fibrosis and hepatocellular carcinoma, associated with high morbidity and mortality. Due to the high and increasing prevalence of NAFLD, there is an urgent need to identify people at risk of developing liver fibrosis and complications. CC-chemokine ligand 2 (CCL2) is chemokine that attracts inflammatory monocytes to stressed or injured tissues. Infiltrating inflammatory monocytes and CCL2 are strongly implicated in the pathogenesis of liver disease in animal models; however, evidence in patient cohorts is conflicting. METHODS: We investigated associations between circulating CCL2 and clinical parameters, including fibrosis assessed by liver stiffness measurement, in a cohort of 250 NAFLD patients. We also measured fatty acid binding protein 2 (FABP2), a putative biomarker of intestinal permeability in patients with liver disease, since pro-inflammatory gut-derived microbial products may induce inflammatory chemokines such as CCL2. RESULTS: Serum CCL2 levels were weakly associated with liver stiffness, but the association was no longer significant after accounting for age, diabetes, and BMI in a multivariable model. Consistent with this, girth and BMI were the strongest predictors of elevated circulating CCL2. Serum FABP2 was weakly, but significantly, correlated with CCL2, and negatively correlated with estimated glomerular filtration rate. CONCLUSION: Circulating CCL2 and FABP2 are associated with NAFLD comorbidities but not liver disease progression in patients with NAFLD.

Towards collaborative management of non-alcoholic fatty liver disease: a 'real-world' pathway for fibrosis risk assessment in primary care.

BACKGROUND: The optimal strategy to support primary care practitioners (PCP) to assess fibrosis severity in non-alcoholic fatty liver disease (NAFLD) and thereby make appropriate management decisions remains unclear. AIMS: To examine the feasibility of using a two-step pathway that combined simple scores (NAFLD Fibrosis Score and Fibrosis-4 Index) with transient elastography (FibroScan) to streamline NAFLD referrals from a 'routine' primary care population to specialist hepatology management clinics (HMC). METHODS: The two-step 'Towards Collaborative Management of NAFLD' (TCM-NAFLD) fibrosis risk assessment pathway was implemented at two outer metropolitan primary healthcare practices in Brisbane. Patients aged ≥18 years with a new or established PCP-diagnosis of NAFLD were eligible for assessment. The pathway triaged patients at 'high risk' of clinically significant fibrosis to HMC for specialist review, and 'low risk' patients to receive ongoing management and longitudinal follow up in primary care. RESULTS: A total of 162 patient assessments between June 2019 and December 2020 were included. Mean age was 58.7 ± 11.7 years, 30.9% were male, 54.3% had type 2 diabetes or impaired fasting glucose, and mean body mass index was 34.2 ± 6.9 kg/m2 . A total 122 patients was considered 'low risk' for clinically significant fibrosis, two patients had incomplete assessments and 38 (23.5%) were triaged to HMC. Among 31 completed HMC assessments to date, 45.2% were considered to have clinically significant (or more advanced) fibrosis, representing 9.2% of 153 completed assessments. CONCLUSION: Implementation of the two-step TCM-NAFLD pathway streamlined hepatology referrals for NAFLD and may facilitate a more cost-effective and targeted use of specialist hepatology resources.

Clinically Significant Fibrosis Is Associated With Longitudinal Increases in Fibrosis-4 and Nonalcoholic Fatty Liver Disease Fibrosis Scores.

BACKGROUND & AIMS: There is limited knowledge regarding the longitudinal utility of biomarkers of fibrosis, such as the nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) or the fibrosis-4 score (FIB-4) score. We examined longitudinal changes in the NFS and the FIB-4 score in patients with NAFLD, with and without clinically significant fibrosis (CSF). METHODS: We performed a retrospective study of 230 patients with NAFLD, collecting clinical and laboratory records to calculate NFS and FIB-4 scores at 6 monthly intervals for 5 years before hepatology assessment of fibrosis. Linear mixed models with random intercept and slope and adjusted for age at baseline were used to assess the progression of NFS and log-transformed FIB-4 scores over time in subjects with and without CSF, determined by liver stiffness measurements of 8.2 kPa or greater. RESULTS: Patients had a median of 11 (minimum, 10; maximum, 11) retrospective observations over a median time period of 5 years (minimum, 4.5 y; maximum, 5 y). Of patients with low baseline NFS and FIB-4 scores, 31.11% and 37.76%, respectively, had CSF at the time of hepatology assessment. There was a correlation between NFS and log10 FIB-4 over time (repeated measure r = 0.55; 95% CI, 0.52-0.59). The rate of increase in NFS and log10 FIB-4 was significantly higher in patients with than without CSF (both P < .001). Predicted NFS increased by 0.17 and 0.06 units per year in subjects with and without CSF, respectively. Predicted log10 FIB-4 score increased by 0.032 and 0.0003 units per year in subjects with and without CSF, respectively. CONCLUSIONS: Noninvasively measured fibrosis scores increase progressively in patients with NAFLD and CSF. Further studies are needed to determine whether repeated measurements can identify patients at risk for CSF.

Effectiveness of patient-oriented education and medication management intervention in people with decompensated cirrhosis.

People with chronic disease often have poor comprehension of their disease and medications, which can negatively affect health outcomes. In a randomised-controlled trial, we found that patients with decompensated cirrhosis who received a pharmacist-led, patient-oriented education and medication management intervention (n = 57) had greater knowledge of cirrhosis and key self-care tasks compared with usual care (n = 59). Intervention patients also experienced improved quality of life. Dedicated resources are needed to support implementation of evidence-based measures at local centres to improve outcomes.

Protocol for a randomised trial testing a community fibrosis assessment service for patients with suspected non-alcoholic fatty liver disease: LOCal assessment and triage evaluation of non-alcoholic fatty liver disease (LOCATE-NAFLD).

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common type of chronic liver disease in Australia and its recent increase mirrors the obesity and type 2 diabetes epidemics. Currently, many patients who present to primary care with abnormal liver function tests or steatosis on liver ultrasound are referred for assessment in secondary care. Due to the large number of patients with NAFLD, this results in long waits for clinical and fibrosis assessment, placing unnecessary burden on the public hospital system. METHODS: We will conduct a 1:1 parallel randomised trial to compare two alternative models of care for NAFLD. Participants will be randomised to usual care or the LOCal Assessment and Triage Evaluation (LOCATE) model of care and followed for 1 year. We will recruit patients from the non-neighbouring Sunshine Coast and Metro South Hospital and Health Services (HHSs) in Queensland, Australia. Our primary outcome of interest is time to diagnosis of high-risk NAFLD, based on the number of participants in each arm of the study who receive a diagnosis of clinically significant fibrosis. Two hundred and 34 participants will give us a 95% power to detect a 50% reduction in the primary outcome of time to diagnosis of high-risk disease. We will also conduct an economic evaluation, evaluating the cost-effectiveness of the new model of care. We will also evaluate the implementation of the new model of care. DISCUSSION: It is anticipated that the results of this study will provide valuable new information regarding the management of NAFLD in the Australian setting. A relatively simple change to care could result in earlier identification of patients with significant liver disease and lower overall costs for the health system. Results will be directly disseminated to key staff for further distribution to consumers, policy- and decision-makers in the form of evidence briefs, plain language summaries and policy recommendations. TRIAL REGISTRATION: The trial was registered on 30 January, 2020 and can be found via ANZCTR - number ACTRN12620000158965.

Underappreciation of non-alcoholic fatty liver disease by primary care clinicians: limited awareness of surrogate markers of fibrosis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a common cause of incidental liver test abnormalities. General practitioners (GP) have a key role in identifying people with NAFLD at risk of significant liver disease. Recent specialist guidelines emphasise the use of fibrosis algorithms or serum biomarkers rather than routine liver tests, to assess advanced fibrosis. AIM: To evaluate primary care clinicians' current approach to diagnosis, management and referral of NAFLD. METHODS: A cross-sectional survey of primary care clinicians was undertaken through a structured questionnaire about NAFLD. A convenience sample of general practice clinics and general practice conferences in Metropolitan Brisbane and regional south east Queensland was selected. RESULTS: A total of 108 primary care clinicians completed the survey (participation rate 100%). Fifty-one percent of respondents considered the prevalence of NAFLD in the general population to be ≤10%. Twenty-four percent of respondents felt that liver enzymes were sufficiently sensitive to detect underlying NAFLD. Most respondents were unsure whether the Fibrosis 4 score (62.7% unsure) or Enhanced Liver Fibrosis score (63.7% unsure) could help to identify advanced fibrosis or cirrhosis. Although 47% of respondents said they would refer a patient to a Gastroenterologist/Hepatologist if they suspect the patient has NAFLD, 44.1% do not make any referrals. Of concern, 70.6% of clinicians said they were unlikely to refer a patient to Hepatology unless liver function tests are abnormal. CONCLUSION: Our findings demonstrate that many primary care clinicians underestimate the prevalence of NAFLD and under-recognise the clinical spectrum of NAFLD and how this is assessed.

Exploratory study into the unmet supportive needs of people diagnosed with cirrhosis in Queensland, Australia.

BACKGROUND: Many patients with cirrhosis follow complex medication and dietary regimens, and those with decompensated cirrhosis suffer debilitating complications. These factors impact activities of daily living and quality of life. AIMS: To explore the concerns and challenges of people with cirrhosis and their use of support services and to also describe health professionals' (HP) perspectives of patients' concerns. METHODS: This is a cross-sectional study at a tertiary liver clinic involving 50 patients and 54 HP. Data were collected using structured questionnaires. The study includes patients' report of their challenges/problems now that they have cirrhosis ('patient-volunteered concerns') and HP' report of patients' concerns. Both also ranked a list of 10 potential concerns. RESULTS: Patients were, on average, 58 years old (SD = 10.2), mostly male (78%), Caucasian (86%) and with compensated cirrhosis (60%). The patients' most common volunteered concerns related to managing symptoms, emotional issues and disease. Most ranked 'developing liver cancer' (79%), 'losing ability to do daily tasks for yourself' (76%), 'fear of dying' (64%) and 'fear of the unknown' (64%) as priority concerns. Regarding the use of support services, 24% of patients had accessed a dietician, 20% a pharmacist and 18% a psychologist. From the HP' perspective, the patients' most significant challenges related to managing disease (65%) and symptoms (48%), access to healthcare (56%) and information/knowledge (48%). CONCLUSIONS: Our findings demonstrate that cirrhosis (its symptoms, complications and treatment) is associated with significant concerns for patients. The discrepancies between the views of HP and patients suggest that we may not be measuring or addressing patients' needs appropriately.

Optimising care of patients with chronic disease: patient-oriented education may improve disease knowledge and self-management.

Many patients with chronic disease do not possess the knowledge and skills required to access and interpret appropriate health information. A pilot study in people with liver cirrhosis (n = 50) identified that only 54% of patients could recall being given written information by a clinician and 64% had self-sought information, most commonly using the Internet. Many patients reported difficulties understanding the material and the majority wanted more accessible information. A pilot chronic disease educational booklet was well received by the study participants with 85% reporting it was helpful and 78% using it in between clinic appointments.

Identifying areas of need relative to liver disease: geographic clustering within a health service district.

Background Many people with chronic liver disease (CLD) are not detected until they present to hospital with advanced disease, when opportunities for intervention are reduced and morbidity is high. In order to build capacity and liver expertise in the community, it is important to focus liver healthcare resources in high-prevalence disease areas and specific populations with an identified need. The aim of the present study was to examine the geographic location of people seen in a tertiary hospital hepatology clinic, as well as ethnic and sociodemographic characteristics of these geographic areas. Methods The geographic locations of hepatology out-patients were identified via the out-patient scheduling database and grouped into statistical area (SA) regions for demographic analysis using data compiled by the Australian Bureau of Statistics. Results During the 3-month study period, 943 individuals from 71 SA Level 3 regions attended clinic. Nine SA Level 3 regions accounted for 55% of the entire patient cohort. Geographic clustering was seen especially for people living with chronic hepatitis B virus. There was a wide spectrum of socioeconomic advantage and disadvantage in areas with high liver disease prevalence. Conclusions The geographic area from which people living with CLD travel to access liver health care is extensive. However, the greatest demand for tertiary liver disease speciality care is clustered within specific geographic areas. Outreach programs targeted to these areas may enhance liver disease-specific health service resourcing. What is known about the topic? The demand for tertiary hospital clinical services in CLD is rising. However, there is limited knowledge about the geographic areas from which people living with CLD travel to access liver services, or the ethnic, socioeconomic and education characteristics of these areas. What does this paper add? The present study demonstrates that a substantial proportion of people living with CLD and accessing tertiary hospital liver services are clustered within specific geographic areas. The most striking geographic clustering was seen for people living with chronic hepatitis B, in regions with a relatively high proportion of people born in Vietnam and China. In addition to ethnicity, the data show an apparent ecological association between liver disease and both socioeconomic and educational and/or occupational disadvantage. What are the implications for practitioners? Identifying where demand for clinical services arises is an important step for service planning and preparing for potential outreach programs to optimise community-based care. It is likely that outreach programs to engage and enhance primary care services in geographic areas from which the greatest demand for tertiary liver disease speciality care arises would yield greater relative return on investment than non-targeted outreach programs.

The Enhanced liver fibrosis score is associated with clinical outcomes and disease progression in patients with chronic liver disease.

BACKGROUND AND AIMS: Current tools for risk stratification of chronic liver disease subjects are limited. We aimed to determine whether the serum-based ELF (Enhanced Liver Fibrosis) test predicted liver-related clinical outcomes, or progression to advanced liver disease, and to compare the performance of ELF to liver biopsy and non-invasive algorithms. METHODS: Three hundred patients with ELF scores assayed at the time of liver biopsy were followed up (median 6.1 years) for liver-related clinical outcomes (n = 16) and clear evidence of progression to advanced fibrosis (n = 18), by review of medical records and clinical data. RESULTS: Fourteen of 73 (19.2%) patients with ELF score indicative of advanced fibrosis (≥9.8, the manufacturer's cut-off) had a liver-related clinical outcome, compared to only two of 227 (<1%) patients with ELF score <9.8. In contrast, the simple scores APRI and FIB-4 would only have predicted subsequent decompensation in six and four patients respectively. A unit increase in ELF score was associated with a 2.53-fold increased risk of a liver-related event (adjusted for age and stage of fibrosis). In patients without advanced fibrosis on biopsy at recruitment, 55% (10/18) with an ELF score ≥9.8 showed clear evidence of progression to advanced fibrosis (after an average 6 years), whereas only 3.5% of those with an ELF score <9.8 (8/207) progressed (average 14 years). In these subjects, a unit increase in ELF score was associated with a 4.34-fold increased risk of progression. CONCLUSIONS: The ELF score is a valuable tool for risk stratification of patients with chronic liver disease.

Prevalence of medication discrepancies in patients with cirrhosis: a pilot study.

BACKGROUND: Cirrhosis patients are prescribed multiple medications for their liver disease and comorbidities. Discrepancies between medicines consumed by patients and those documented in the medical record may contribute to patient harm and impair disease management. The aim of the present study was to assess the magnitude and types of discrepancies among patient-reported and medical record-documented medications in patients with cirrhosis, and examine factors associated with such discrepancies. METHODS: Fifty patients who attended a hospital hepatology outpatient clinic were interviewed using a questionnaire composed of mixed short-response and multiple-choice questions. Patients' reported medication use was compared with documentation in the hospital medical records and pharmacy database. Medication adherence was assessed using the 8-question ©Morisky Medication Adherence Scale (MMAS-8). The multivariate logistic regression model was constructed using clinically relevant and/or statistically significant variables as determined by univariate analysis. All p-values were 2-sided (α = 0.05). RESULTS: Twenty-seven patients (54.0 %) had ≥1 discrepancy between reported and documented medicines. Patients with ≥1 discrepancy were older (p = 0.04) and multivariate analysis identified taking ≥5 conventional medicines or having a 'low' or 'medium' adherence ranking as independent predictors of discrepancy (adjusted OR 11.0 (95 % CI 1.8-67.4), 20.7 (95 % CI 1.3-337.7) and 49.0 (95 % CI 3.3-718.5) respectively). Concordance was highest for liver disease medicines (71.9 %) and lowest for complementary and alternative medicines (14.5 %) and respiratory medicines (0 %). CONCLUSION: There is significant discrepancy between sources of patient medication information within the hepatology clinic. Medication reconciliation and medicines-management intervention may address the complex relationship between medication discrepancies, number of medications and patient adherence identified in this study.

The portal inflammatory infiltrate and ductular reaction in human nonalcoholic fatty liver disease.

UNLABELLED: Although nonalcoholic fatty liver disease (NAFLD) is conventionally assessed histologically for lobular features of inflammation, development of portal fibrosis appears to be associated with disease progression. We investigated the composition of the portal inflammatory infiltrate and its relationship to the ductular reaction (DR), a second portal phenomenon implicated in fibrogenesis. The portal inflammatory infiltrate may contribute directly to fibrogenesis as well as influence the fate of the DR hepatic progenitor cells (HPCs), regulating the balance between liver repair and fibrosis. The presence of portal inflammation in NAFLD was strongly correlated with disease severity (fibrosis stage) and the DR. The portal infiltrate was characterized by immunostaining NAFLD liver biopsy sections (n = 33) for broad leukocyte subset markers (CD68, CD3, CD8, CD4, CD20, and neutrophil elastase) and selected inflammatory markers (matrix metalloproteinase 9 and interleukin [IL]-17). Cells expressing all markers examined were identified throughout the liver lobules and in portal tracts, although portal tracts were more densely populated (P < 0.01), and dominated by CD68(+) macrophages and CD8(+) lymphocytes, at all stages of disease. An increase in portal macrophages in NAFLD patients with steatosis alone (P < 0.01) was the earliest change detected, even before elevated expression of the proinflammatory cytokines, IL1B and TNF, in patients with early NASH (P < 0.05). Portal and periductal accumulation of all other cell types examined occurred in progressed NASH (all P < 0.05). CONCLUSION: Knowledge of the complex cellular composition of the portal inflammatory infiltrate and HPC/DR niche in NAFLD will shape future functional studies to elucidate the contribution of portal inflammation to HPC differentiation and NAFLD pathogenesis.

ELF score ≥9.8 indicates advanced hepatic fibrosis and is influenced by age, steatosis and histological activity.

BACKGROUND & AIMS: There is increasing need to identify individuals with advanced liver fibrosis, who are at risk of complications such as hepatocellular carcinoma. The commercially available enhanced liver fibrosis (ELF) test provides a non-invasive assessment of fibrosis severity. This study was designed to determine the diagnostic accuracy of the manufacturer's cut-off value (≥9.8) in identifying advanced fibrosis. METHODS: The relationship between ELF score and fibrosis was examined using serum collected at time of liver biopsy for investigation of liver disease, particularly viral hepatitis. Fibrosis was staged using a modified METAVIR score. If available, liver tissue was recut and stained with Sirius red to determine collagen proportional area (CPA) and subsinusoidal fibrosis (SSF). RESULTS: Enhanced liver fibrosis score ≥9.8 had a sensitivity of 74.4% and specificity 92.4% for detecting advanced fibrosis. In the whole cohort (n = 329), ELF score was more likely to incorrectly classify individuals if age was ≥45 years and METAVIR inflammatory grade was 2 or 3 (adjusted OR, odds ratio 3.71 and 2.62 respectively). In contrast, ELF score was less likely to misclassify individuals in the presence of steatosis (OR 0.37). Neither SSF nor CPA explained the discordance in ELF score for patients with or without advanced fibrosis. CONCLUSION: Although ELF score ≥9.8 reliably identifies advanced fibrosis in patients with chronic liver disease, both age and inflammatory activity need to be considered when interpreting the result. Importantly, ELF score performed well in the presence of steatosis and could thus be helpful in the assessment of fatty liver disease.

Diagnostic sensitivity of carbohydrate deficient transferrin in heavy drinkers.

BACKGROUND AND AIM: Carbohydrate deficient transferrin (CDT) is the most specific serum biomarker of heavy alcohol consumption, defined as ≥ 350-420 g alcohol/week. Despite introduction of a standardized reference measurement technique, widespread use of CDT remains limited due to low sensitivity. The aim of this study was to determine the factors that affect diagnostic sensitivity in patients with sustained heavy alcohol intake. METHODS: Patients with a self-reported history of sustained heavy alcohol consumption were recruited from the hepatology outpatient department or medical wards. Each patient was interviewed with a validated structured questionnaire of alcohol consumption and CDT analysis using the standardized reference measurement technique with high performance liquid chromatography was performed on serum collected at time of interview. RESULTS: 52 patients were recruited: 19 from the hepatology outpatient department and 33 from general medical wards. Median alcohol intake was 1013 (range 366-5880) g/week over the preceding two week period. 26 patients had a diagnostic CDT based on a threshold value of %CDT > 1.7 indicating heavy alcohol consumption, yielding a sensitivity of 50%. Overweight/obesity (defined as body mass index (BMI) ≥ 25 kg/m2 in Caucasians and ≥ 23.0 kg/m2 in Asians), female gender and presence of cirrhosis were independently associated with non-diagnostic %CDT (≤ 1.7). CONCLUSIONS: CDT has limited sensitivity as a biomarker of heavy alcohol consumption. Caution should be applied when ordering and interpreting %CDT results, particularly in women, patients with cirrhosis and those with an elevated BMI.

Portal, but not lobular, macrophages express matrix metalloproteinase-9: association with the ductular reaction and fibrosis in chronic hepatitis C.

BACKGROUND: Liver macrophages are a heterogeneous cell population that produces factors involved in fibrogenesis and matrix turnover, including matrix metalloproteinase (MMP) -9. During liver injury, their close proximity to hepatic progenitor cells and the ductular reaction may enable them to regulate liver repair and fibrosis. AIMS: To enumerate and characterise liver macrophages in patients with chronic hepatitis C, to determine whether a distinct population of macrophages is associated with the ductular reaction and portal fibrosis. METHODS: Immunostaining for macrophage markers (CD68, CD163, CCR2), the ductular reaction (keratin-7) and MMP-9 was performed in liver biopsy sections from patients with chronic hepatitis C virus (HCV) (n = 85). RESULTS: Portal tracts were more densely populated with macrophages (10.5 ± 0.36 macrophages/HPF) than lobules (7.2 ± 0.16 macrophages/HPF, P < 0.001) and macrophages were found in close proximity to the ductular reaction. ≥30% of portal and periductal macrophages expressed MMP-9 and these were significantly associated with increasing stage of fibrosis (rs  = 0.58, 0.68, respectively, both P < 0.001). In contrast, MMP-9(+) macrophages were largely absent in lobular regions and non-diseased liver. Hepatic MMP-9 mRNA levels and gelatinolytic activity were significantly associated with stage of fibrosis (rs  = 0.47, rs  = 0.89, respectively, both P < 0.001). Furthermore, a second distinct CCR2(+) macrophage population was localised to the centrilobular regions and was predominantly absent from portal and periductal areas. CONCLUSIONS: These findings demonstrate significant regional differences in macrophage phenotypes, suggesting that there are at least two populations of liver macrophages. We propose that these populations have distinct contributions to the pathogenesis of chronic HCV-related liver disease.

BMI but not stage or etiology of nonalcoholic liver disease affects the diagnostic utility of carbohydrate-deficient transferrin.

BACKGROUND: A reliable biomarker is required in hepatology clinics for detection and follow-up of heavy alcohol consumption. Carbohydrate-deficient transferrin (CDT) increases with sustained heavy alcohol consumption and is the most specific biomarker of ethanol (EtOH) consumption. Recent introduction of a standardized method for measuring CDT has improved its clinical application. This study was designed to determine whether alcohol-independent factors influence CDT levels in patients with chronic liver disease (CLD). METHODS: The relationship between serum %CDT and self-reported history of alcohol consumption was examined in 254 patients referred for evaluation of liver disease. CDT analysis was performed on serum collected at time of liver biopsy. RESULTS: CDT levels were not affected by severity or etiology of nonalcoholic liver disease. Thirteen of 254 subjects had a %CDT >1.7, predictive of heavy alcohol intake, 6 of whom did not acknowledge heavy drinking. Twelve of these 13 subjects were suspected heavy drinkers on review of their medical records and clinical results. Conversely, not all acknowledged heavy drinkers had %CDT >1.7. Heavy drinkers with a body mass index (BMI) in the overweight or obese range had significantly lower %CDT than lean heavy drinkers. This persisted even when lean body weight was used as an approximation of the EtOH volume of distribution. CONCLUSIONS: An elevated BMI reduces the diagnostic utility of CDT at higher alcohol intake in subjects with CLD using the standardized method. In a hepatology outpatient setting, this assay is likely to be useful to confirm suspicion of heavy drinking in subjects who are not overweight, but cannot reliably identify moderate drinkers or heavy drinkers who are overweight.

Use of standardised assessment forms in referrals to hepatology outpatient services: implications for accurate triaging of patients with chronic hepatitis C.

OBJECTIVES: To determine the spectrum of disease among non-urgent referrals to a tertiary hospital hepatology outpatient clinic, assess the adequacy of referral information in terms of risk stratification and determine whether a specifically designed referral template altered urgency for specialist assessment. METHODS: A snapshot of the waiting list of a hepatology clinic at a tertiary hospital was taken from the scheduling database. Information was retrieved from referrals and attached investigations. Updated information was requested from subjects and their current general practitioner. RESULTS: Hepatitis C virus accounted for 68.7% of the 1223 reviewed referrals. Clinical information provided by referring clinicians was often incomplete. Provision of updated information identified the presence of comorbidities (obesity, 'heavy' alcohol consumption, mental health issues) and altered the need or urgency for specialist assessment in 22% of cases. CONCLUSIONS: Hepatitis C virus accounts for the majority of non-urgent referrals waiting to access hepatology outpatient consultations. Using a standardised assessment form as part of the referral process provides more information on comorbidities and risk factors and facilitates more accurate triaging of clinical urgency. Wider adoption of this strategy may increase appropriate access to hepatology services and reduce the future burden of cirrhosis and hepatocellular cancer. WHAT IS KNOWN ABOUT THE TOPIC? Little published data are available that describe the content and standard of hepatology referrals, or the urgency with which these patients need to be reviewed. Inadequate clinical information impairs the ability to accurately triage referrals and may lead to delays in access. WHAT DOES THE PAPER ADD? Almost 70% of reviewed referrals were for management of patients with hepatitis C virus infection, confirming this condition remains a major priority area in liver disease. Clinical information provided by referring clinicians was often incomplete, impairing the ability to accurately triage referrals. Only a minority of referrals provided information about relevant comorbidities (alcohol intake, injecting drug use, mental health issues and obesity) that negatively impact on the progression of liver disease or the response to antiviral treatment. WHAT ARE THE IMPLICATIONS FOR PRACTITIONERS? Hepatitis C virus remains a major health priority area in liver disease, increasing the future burden of cirrhosis and hepatocellular cancer. Many referred patients have comorbidities that increase their risk of progressive liver disease and related complications. Strategies to increase recognition and management of liver disease and its comorbidities in the community are required. The use of a standardised assessment form in referrals to hepatology outpatient services may assist with triaging of patients and improve access to appropriate care.

Triage of referrals to outpatient hepatology services: an ineffective tool to prioritise patients?

BACKGROUND: Appropriate and uniform prioritisation ('triaging') of outpatient referrals is critical to good patient outcomes, equity of access to services and efficient use of resources. OBJECTIVE: To determine whether there is uniformity in the allocation of triage categories for hepatology outpatient referrals at public hospitals in Queensland. METHODS: A series of 10 recent hepatology referrals were de-identified for both patient and referring clinician details and sent to nine gastroenterology or hepatology centres throughout Queensland. Consultant gastroenterologists and hepatologists (n=25) were asked to triage the referrals using the process in place in their centre. Responses were de-identified and analysed. Each case was reviewed and allocated an 'agreed triage category' based upon the majority view of respondents. RESULTS: Nineteen responses were received. There was substantial variation amongst consultants in the allocation of triage categories. Although almost two-thirds of respondents agreed with the majority view in 60-80% of cases, none agreed with the majority for every case and some agreed in as few as 50% cases. Disagreement with the majority view of an appropriate triage category was not associated with geography or specialist experience. CONCLUSIONS: Variability in triage categorisation suggests that similar cases may be allocated different priorities by those responsible for determining the urgency of outpatient review. This has implications for equity of access to treatment. The development of triage guidelines and formal training in their implementation, along with periodic audits of triage practices in different centres, may reduce variability.

Predicting Liver-Related Outcomes in People With Nonalcoholic Fatty Liver Disease: The Prognostic Value of Noninvasive Fibrosis Tests.

It remains unclear whether screening for advanced fibrosis in the community can identify the subgroup of people with nonalcoholic fatty liver disease (NAFLD) at higher risk for development of liver-related complications. We aimed to determine the prognostic value of baseline noninvasive fibrosis tests for predicting liver-related outcomes and mortality in patients with NAFLD from type 2 diabetes (T2D) clinics or primary care. Patients (n = 243) who were screened for NAFLD with advanced fibrosis by using NAFLD fibrosis score (NFS), fibrosis 4 score (FIB-4), enhanced liver fibrosis (ELF) test, and liver stiffness measurements (LSMs) were followed up for clinical outcomes by review of electronic medical records. During a median follow-up of 50 months, decompensated liver disease or primary liver cancer occurred in 6 of 35 (17.1%) patients with baseline LSM > 13 kPa, 1 of 17 (5.9%) patients with LSM 9.5-13 kPa, and in no patients with LSM < 9.5 kPa. No patient with low-risk NFS developed liver decompensation or liver-related mortality. Following repeat NFSs at the end of follow-up, all patients with a liver-related complication were in the high-risk NFS category. Patients who developed liver-related complications were also more likely to have baseline high-risk FIB-4 scores or ELF test ≥9.8 compared to patients who did not develop liver outcomes. Conclusion: Liver fibrosis risk stratification in non-hepatology settings can identify the subset of patients at risk of liver-related complications. Although the rate of development of a decompensation event or hepatocellular carcinoma was low (2.1% per year) in our patients with compensated cirrhosis (LSM > 13 kPa), these events are projected to lead to a substantial increase in NAFLD-related disease burden over the next decade due to the high prevalence of NAFLD in people with obesity and T2D.