Australian general practitioners' perceptions of the barriers and opportunities for community-based care of patients with viral hepatitis: a mixed methods study.

Introduction Engagement of general practitioners (GPs) is essential to improving rates of diagnosis and treatment of viral hepatitis, as traditional tertiary hospital-based models of care often face challenges. Aim We investigated Australian general practitioners' perceptions of a community-based model of care for patients with viral hepatitis. Methods We conducted a mixed methods study using survey questionnaires (23 GPs) and an open-ended interview guide (10 GPs) at primary care clinics in Brisbane, Queensland, Australia. Quantitative data were analysed using descriptive statistics in Stata 15.1 and qualitative data were analysed using thematic analysis following an inductive approach. Results Patient loss to follow up and high cost of diagnostic tests were identified as the biggest challenges to providing care for patients with viral hepatitis. Most GPs interviewed believe a more community-based model of care with support to GPs may improve uptake of care and increase both GP and patient engagement. General practitioners felt a community-based model of care could also improve viral hepatitis testing and follow-up rates. Discussion For Australian GPs, improving patient retention and diagnostics access were key pressure points in the viral hepatitis care pathway. A broader and more profound capacity-building allows community-based viral hepatitis care to be sustainable.

Visceral adipose tissue loss and 24-hour urinary profile changes post-bariatric surgery.

INTRODUCTION: The relationship between obesity and nephrolithiasis is a well-documented phenomenon. Visceral adipose tissue (VAT) has been proposed to be an accurate indicator of metabolic derangement. We present a study that investigates the relationship between computed tomography (CT) delineated VAT measurements and 24-hour urine (24 HU) profiles in the context of profound weight loss. MATERIALS AND METHODS: A total of 86 patients with a history of nephrolithiasis who underwent bariatric surgery were reviewed. All patients had pre and postoperative 24 HU analysis and CT kidney and urinary bladder performed. CT-based fat delineation program, AnalyzePro, was used to measure VAT at levels L4-L5 (VAT 1) and L1-L2 (VAT2). Univariate and multivariate analysis was utilized to examine associations between VAT measurements and comorbidities, 24 HU values, and postoperative urinary changes. RESULTS: Preoperative VAT2 was correlated with preoperative serum creatinine and all 24 HU (R2: 0.23-0.43, p = < 0.001-0.030). Only VAT1 and VAT2 had relationships with hypertension, dyslipidemia, and metabolic syndrome (R2: 0.25-0.30, p = 0.004-0.015). The percent change in VAT1 and VAT2 was a significant predictor of change in 24 HU uric acid (respectively, R2: 0.14, beta: -0.03, p = 0.002 and R2: 0.13, beta: -0.03, p = 0.003). CONCLUSIONS: This study found VAT to have strong correlations with urinary outcomes in obese patients, especially in the excretion of uric acid. These findings support a potential use of CT delineated measurements of fat as a surrogate measure for urinary metabolites, and may be used as a marker for patient counseling in stone prevention.

Fitting Health Care to People: Understanding and Adapting to the Epidemiology and Health Literacy of People Affected by Viral Hepatitis from Culturally and Linguistically Diverse Migrant Backgrounds.

This study explored the epidemiology and health literacy of people affected by viral hepatitis (VH) from migrant culturally and linguistically diverse (CALD) backgrounds attending a community-based general practitioner and specialty hepatology shared-care (HEPREACH) clinic in Brisbane, Australia. Patient-reported data on health literacy and clinical information from adult patients (n = 66) of CALD background recruited from the liver clinic were analyzed. Health literacy was assessed using a 5-question, 12-point scale. Variance weighted multiple linear regression was used to identify factors associated with knowledge about VH. About three-quarters of patients (74.2%) were diagnosed with hepatitis B. The median knowledge score was 7.8 (interquartile range [IQR] 6‒9). One in five patients did not understand the infective nature of VH, 30.3% did not understand mother-to-child transmission risk, and 30-40% of patients thought activities such as kissing, sharing food or mosquito bites could spread VH. Only 6% of patients understood the risk of liver cancer and the need for regular screening. Higher educational level (secondary, ß = 4.8, p < 0.0001 or tertiary, ß = 8.1, p < 0.0001 vs. primary) was associated with better knowledge, and transition through a refugee camp (vs. not, ß = - 1.2, p = 0.028) and country of diagnosis (overseas vs. Australia, ß = - 1.9, p = 0.016) were associated with poorer knowledge. Country of origin, refugee status and opportunities for tertiary education impact patients' understanding of VH. Ensuring delivery of culturally appropriate care and education is critical to improve knowledge, reduce misconceptions to improve care and outcomes for VH in CALD migrant communities.

Evaluation of techniques used to assess skeletal muscle quantity in patients with cirrhosis.

INTRODUCTION: Loss of skeletal muscle mass is a well-recognised complication of cirrhosis. Bedside methods to assess skeletal muscle mass including anthropometrics and bioelectrical impedance analysis (BIA) are negatively impacted by fluid overload in advanced cirrhosis and thus there is a need to identify alternatives. There is a paucity of data on the accuracy of commonly used radiological methods such as dual X-ray absorptiometry (DXA) to assess appendicular lean mass (ALM), and computed tomography (CT) skeletal muscle area in patients with cirrhosis. The aim of this study was to evaluate the relationships and agreement of several skeletal muscle mass estimation methods compared to a reference model in patients with cirrhosis. PATIENTS AND METHODS: A cross-sectional, single centre study was performed by prospectively recruiting patients with cirrhosis referred to the Queensland Liver Transplant Service. Patients underwent assessment of skeletal muscle mass using bedside techniques (mid-upper arm muscle circumference (MUAMC), bioelectrical impedance spectroscopy (BIS), ultrasound muscle thickness (USMT)) and radiological methods (DXA ALM, CT skeletal muscle area). These were compared to a reference measurement of body cell mass derived from a multi-compartment model using isotope dilution tests and DXA. RESULTS: Forty-two patients (age 56 years, interquartile range 48-60, 86% male) were recruited. Bedside skeletal muscle mass estimation techniques were strongly correlated to the body cell mass reference, with BIS estimation having the strongest correlation coefficients (r = 0.78-0.79; P < 0.01). A novel technique measuring USMT offered no advantage over traditional bedside techniques. Of the radiological methods, DXA ALM had the strongest correlation coefficient (r = 0.781; P < 0.01). Weaker correlation coefficients were observed in patients with ascites, except when using the MUAMC. Bland-Altman analysis of BIS body composition estimates demonstrated significant systematic biases and large limits of agreement compared to reference values. CONCLUSION: These results confirm the difficulties in assessing skeletal muscle mass in patients with cirrhosis, particularly in those with ascites. DXA ALM and BIS measurements provided the best correlation to body cell mass. We suggest DXA ALM for estimation of skeletal muscle mass in patients with cirrhosis as there are established thresholds for skeletal muscle mass depletion, and an accurate assessment of bone mass and density can also be provided. The use of USMT over other bedside skeletal muscle mass estimates was not supported by our results. Further studies evaluating novel bedside skeletal muscle mass estimation techniques in cirrhosis patients are required.

The inter- and intrarater reliability and feasibility of dietetic assessment of sarcopenia and frailty in potential liver transplant recipients: A mixed-methods study.

Sarcopenia and frailty are associated with poorer outcomes in potential liver transplant (LT) recipients. We examined the reliability and feasibility of dietitians assessing sarcopenia and frailty. Seventy-five adults referred for LT underwent assessments of muscle mass (abdominal CTs), physical function (handgrip strength; HGS, short physical performance battery; SPPB), and frailty (Liver Frailty Index; LFI). Inter- and intrarater reliability and agreement were assessed in subsets of patients using intraclass correlation coefficients (ICCs) and Bland-Altman plots. CTs were analyzed by a dietitian and two independent experts, two dietitians assessed function and frailty. Feasibility assessed system, patient, and profession factors (staff survey). Inter- and intrarater reliability for CT-defined low muscle were excellent (ICCs > 0.97). Reliability between dietitians was excellent for HGS (0.968, 95% CI, 0.928-0.986), SPPB (0.932, 95% CI, 0.798-0.973), and LFI (0.938, 95% CI 0.861-0.973). Bland-Altman analysis indicated excellent agreement for HGS. All transplant clinicians valued sarcopenia and frailty in LT assessments and considered the dietitian appropriate to perform them. Seven saw no barriers to implementation into practice, while five queried test standardization, learning from repeat testing, and resource cost. Dietetic assessments of sarcopenia and frailty are reliable, feasible, and valued measures in the assessment of potential LT recipients.

Efficacy and Safety of Sofosbuvir/Velpatasvir/Voxilaprevir for Hepatitis C Virus (HCV) NS5A-Inhibitor Experienced Patients With Difficult to Cure Characteristics.

BACKGROUND: In clinical trials, hepatitis C virus (HCV) salvage treatment with sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) achieved an SVR12 rate of >95% in NS5A-experienced participants. Lower SVR12 rates have been reported in real-world studies, particularly for genotype (GT)3 infection and cirrhosis. We determined the efficacy and safety of SOF/VEL/VOX in a large real-world cohort. METHODS: We assessed the efficacy of salvage SOF/VEL/VOX for HCV infection in NS5A-inhibitor experienced participants with cirrhosis and portal hypertension, prior liver transplantation (LT) or severe extra-hepatic manifestations. SOF/VEL/VOX was available via an early access program. The primary outcome was SVR12. Secondary outcome was frequency of adverse events (AE). FINDINGS: Ninety-seven participants were included. Median age was 58, 82% were male, 78% had cirrhosis, most with portal hypertension (61%, n = 46/76), and 18% had prior-LT. Of the cirrhotic participants, 96% were Child-Turcotte-Pugh class A, and 4% were class B. Of the 72% with GT3, 76% were also cirrhotic. By intention-to-treat analysis, SVR12 rate was 85% (n = 82/97). Per protocol, the SVR12 rate was 90%, including 91% in GT1 (GT1a n = 18/18, GT1b n = 2/4), 89% in GT3 (n = 59/66) and 100% in GT6 (n = 3/3). SVR12 in participants with GT3 and cirrhosis was 90%. No predictors of non-SVR12 were identified. There were 4 serious AEs including 1 death and 3 hepatic decompensation events. NS5A resistance-associated substitutions detected at baseline did not affect SVR12. CONCLUSIONS: This real-world study confirms high efficacy of SOF/VEL/VOX for the treatment of difficult-to-cure NS5A-inhibitor experienced patients, including those with GT3 and cirrhosis. Treatment was well tolerated in most; however, serious AEs can occur in those with advanced liver disease.

Is post-transplant metabolic syndrome associated with pre-liver transplant visceral adipose tissue area?

BACKGROUND: Post-liver transplant metabolic syndrome (PTMS) is a significant independent risk factor for the development of cardiovascular disease. The impact of pre-transplant body composition on the risk of developing PTMS has not been evaluated and was the aim of this study. METHODS: Seventy-five consecutive adult patients listed for liver transplant were included in the analysis. Anthropometric and metabolic data were collected pre-transplant and at three months post-transplant. Metabolic syndrome was defined in accordance with international guidelines. Skeletal muscle area (SMA), visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) areas were derived from computed tomography. RESULTS: Ten patients (13%) developed de novo PTMS by 3 months post-transplant. Patients who developed PTMS had higher pre-transplant body mass index (BMI) (P = 0.01), VAT (P = 0.001) and SAT (P = 0.008). Univariate logistic regression found that BMI, VAT and SAT were significant predictors for the development of PTMS. After stepwise multivariate analysis, only VAT remained a significant predictor (OR 1.02, 95%CI 1.01-1.04; P = 0.04). CONCLUSIONS: Higher pre-transplant VAT is independently associated with the development of metabolic syndrome three months post-transplant. Body composition analysis using cross-sectional imaging prior to liver transplant can assist with identifying patients at greatest risk for developing PTMS.

Computerised tomography skeletal muscle and adipose surface area values in a healthy Caucasian population.

BACKGROUND: The analysis of computerised tomography (CT) images to provide body composition data has grown exponentially. Despite this, there remains limited published data defining the normal range of skeletal muscle area and adipose tissue area using CT. The aim of this study was to determine age- and sex-specific body composition values using CT at the level of the third lumbar vertebrae, in a Caucasian population with a healthy body mass index (BMI). In addition, we sought to develop threshold values for low skeletal muscle mass using these data. METHODS: We included 107 healthy Caucasian patients (46 males; 61 females) with a healthy BMI (18-25 kg/m2) for analysis. Body composition data were obtained from a single transverse CT image at the mid-third lumbar vertebrae using ImageJ software. Tissue segmentation was performed using Hounsfield unit thresholds of -29 to +150 for muscle and -190 to -30 for adipose tissue. RESULTS: The mean age of the study cohort was 47.8 ± 11.0 years (range 21-73) with a median BMI of 23.7 kg/m2 (interquartile range 22.3-24.8). Patients were sub-divided into age above or below 50 years. Cut-offs for low muscle quantity, representing two standard deviations below the young healthy population mean values, were 43.5 cm2/m2 for males and 30.0 cm2/m2 for females. CONCLUSIONS: Our data provide an insight into the distribution of skeletal muscle and adipose tissue surface area values measured on CT from a healthy Caucasian population. Our CT-derived cut-offs for low muscle quantity, based on international guidelines, are much lower than those previously suggested.

Poor Cardiorespiratory Fitness Is a Risk Factor for Sepsis in Patients Awaiting Liver Transplantation.

BACKGROUND: Patients with advanced liver disease are at increased risk of infection and other complications. A significant proportion of patients also have poor fitness and low muscle mass. The primary aim of this study was to investigate if cardiorespiratory fitness and body composition are risk factors for sepsis and other complications of advanced liver disease. METHODS: Patients being listed for liver transplantation underwent cardiopulmonary exercise testing to determine ventilatory threshold (VT). Computed tomography was used to measure skeletal muscle and subcutaneous and visceral adipose tissue indexes. All unplanned hospital admissions, deaths or delistings before transplantation were recorded. RESULTS: Eighty-two patients (aged 55.1 [50.6-59.4] years, median (interquartile range); male 87%] achieved a median VT of 11.7 (9.7-13.4) mL·kg·min. Their median model of end-stage liver disease, incorporating serum sodium score was 18 (14-22); and 37 had hepatocellular carcinoma. There were 50 admissions in 31 patients; with 16 admissions for sepsis in 13 patients. Patients with sepsis had a significantly lower VT (sepsis, 9.5 [7.8-11.9]; no sepsis, 11.8 [10.5-13.8] mL·kg·min; P = 0.003]. No body composition variables correlated with sepsis, nor were there any significant associations between VT and unplanned admissions for other indications. Multivariate logistic regression demonstrated that VT was independently associated with a diagnosis of sepsis (P = 0.03). Poisson regression revealed that VT was a significant predictor for the number of septic episodes (P = 0.02); independent of age, model of end-stage liver disease, incorporating serum sodium score, hepatocellular carcinoma diagnosis, presence of ascites, and ß-blocker use. CONCLUSIONS: Poor cardiorespiratory fitness is an independent risk factor for the development of sepsis in advanced liver disease.

Characterising adrenal function using directly measured plasma free cortisol in stable severe liver disease.

BACKGROUND & AIMS: Adrenal insufficiency (AI) has been reported in patients with advanced liver disease. Diagnosing AI is problematic owing to controversies in using total serum cortisol as a measure of adrenal function. No published data exist on directly measured plasma free cortisol (PFC) in patients with liver disease. METHODS: This prospective study compared serum total and measured plasma free cortisol to evaluate adrenal function in clinically stable cirrhotic patients and healthy controls. Cortisol levels were measured at baseline and following 250 µg corticotrophin. AI was defined by total cortisol increments (delta cortisol) of less than 250 nmol/L, or a peak total cortisol under 500 nmol/L after cosyntropin. We used a peak plasma free cortisol concentration of 33 nmol/L as the threshold for AI. RESULTS: Forty-three consecutive patients and 10 healthy controls were studied. Cirrhotic patients had significantly lower peak (526 vs. 649 nmol/L, p=0.004) and delta total cortisol (264 vs. 397 nmol/L, p = 0.002) responses compared to healthy controls. However, basal plasma free cortisol was higher in patients (10.9 vs. 6.4 nmol/L, p = 0.03), and there were no differences in peak plasma free cortisol (p = 0.69) between the two groups. The prevalence of AI using total cortisol criteria was 58% compared to 12% using free cortisol (p<0.001). CONCLUSION: In patients with stable severe liver disease, a significant discrepancy exists between the rates of diagnosis of AI using the total and free cortisol criteria. We would advise caution in the interpretation of adrenal function testing using total cortisol measurements in this group.