A multi-site, nurse-coordinated hepatitis C model of care in primary care and community services in Melbourne, Australia.

BACKGROUND: Hepatitis C virus (HCV) treatment through primary care and community-based services will be a critical component of HCV elimination. We evaluated a nurse-coordinated programme providing care across eight sites and analysed progression through the HCV care cascade. METHODS: People-accessing services from six primary care clinics, a homeless crisis accommodation provider and a mental health service were directly referred to nurses or engaged by nurses during regular clinic visits. Nurses supported HCV testing, treatment and follow-up. The prescription was provided by affiliated clinicians. Logistic regression was used to examine factors associated with treatment commencement and sustained virological response (SVR) testing. RESULTS: Of 640 people referred to and/or engaged by the nurses from January 2017 to July 2019, 518 had an HCV RNA test of whom 381 (74%) were HCV RNA positive. Treatment was commenced by 281 (74%) people of whom 161 had an SVR test, 157 (97.5%) were cured. Opioid agonist therapy was associated with treatment commencement (aOR 2.68, 95% CI 1.48-4.88). People who were homeless/unstably housed were less likely to commence treatment (aOR 0.45, 95% CI 0.23-0.87). Treatment prescription from a specialist (aOR 2.39, 95% CI 1.20-4.74) and recent injection drug use (<6 months) (aOR 2.15, 95% CI 1.07-4.31) was associated with SVR testing. CONCLUSION: A nurse-coordinated model of care led to high levels of HCV treatment uptake and cure amongst people attending primary care and community services. More tailored models of care may be beneficial for people who are homeless or have unstable housing. These results support primary care and community-based hepatitis C treatment.

Current issues in the prevalence, diagnosis and management of hepatocellular carcinoma in Australia.

Hepatocellular carcinoma (HCC) is the commonest primary liver cancer encountered in the community and a leading cause of cancer morbidity and mortality. In Australia, there are several current important issues that need to be addressed in HCC management. There is a dramatically rising incidence of HCC in Australia with comparatively poorer outcomes in remote regions and in socioeconomic disadvantaged groups. Aboriginal people have a greater incidence of HCC on a background of increased liver disease prevalence and face several barriers to delivery of better healthcare outcomes compared to other Australians. The previously adopted use of imaging alone to diagnose HCC is now being challenged with biopsy likely to become increasingly necessary with the increased uptake of personalised medicine management. Managing HCC is complex involving many disciplines with the multidisciplinary team approach being the current accepted standard of care for patients. New immunotherapy combinations promise to offer patients with advanced HCC promising novel management options. However, the Australian inequities in prevalence, diagnosis and service provision, especially in Aboriginal people, need to be redressed concurrently with the adoption of new HCC management options.

Viscoelastic Tests as Point-of-Care Tests in the Assessment and Management of Bleeding and Thrombosis in Liver Disease.

Viscoelastic point-of-care (VET POC) tests provide a global assessment of hemostasis and have an increasing role in the management of bleeding and blood component delivery across several clinical settings. VET POC tests have a rapid turnaround time, provide a better overall picture of hemostasis, predict bleeding more accurately than conventional coagulation tests, and reduce blood component usage and health care costs. Despite commonly having abnormal conventional coagulation tests, most patients with chronic liver disease have a "rebalanced" hemostasis. However, this hemostatic balance is delicate and these patients are predisposed to both bleeding and thromboembolic events. Over recent years, VET POC tests have been increasingly studied for their potential as better functional tests of hemostasis in liver disease patients. This review provides a background on the most common VET POC tests (thromboelastography and rotational thromboelastometry) and discusses the current evidence for these tests in the prediction and management of bleeding and thrombosis in patients with chronic liver disease, and in liver resection and transplant. With the recent publication of several randomized controlled trials, there is growing evidence that VET POC tests may be used to improve bleeding risk assessment and reduce blood product use in liver disease patients outside of the transplant setting. However, consensus is still lacking regarding the VET POC tests' thresholds that should be used to trigger blood product transfusion. VET POC tests also show promise in predicting thrombosis in patients with liver disease, but further research is needed before they can be used to guide anticoagulant therapy.

Nonalcoholic fatty liver disease burden: Australia, 2019-2030.

BACKGROUND AND AIM: Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) account for a large and growing proportion of liver disease burden globally. The burden of NAFLD/NASH manifests in increasing levels of advanced liver disease and primary liver cancer in Australia. A Markov model was used to forecast NAFLD burden in Australia through 2030. METHODS: A model was used to estimate fibrosis progression, primary liver cancer, and liver deaths among the Australian NAFLD population, with changes in incident NAFLD cases based on long-term trends for changes in the prevalence of obesity. Published estimates and surveillance data were applied to build and validate the model projections, including surveillance data for the incidence of liver cancer. RESULTS: Prevalent NAFLD cases were projected to increase 25% from the current burden (5 551 000 [4 748 000-6 306 000] cases in 2019) to 7 024 000 [5 838 000-7 886 000] cases in 2030. The projected increase in the number of NASH cases (40%) was greater than that of NAFLD cases. Incident cases of advanced liver disease are projected to increase up to 85% by 2030, and incident NAFLD liver deaths are estimated to increase 85% from 1900 (1100-3300) deaths in 2019 to 3500 (2100-6100) deaths in 2030. CONCLUSIONS: Restraining growth of the obese and diabetic populations, along with potential therapeutic options, will be essential for mitigating disease burden.

Nonalcoholic fatty liver disease: current concepts, epidemiology and management strategies.

Nonalcoholic fatty liver disease (NAFLD) is now the most prevalent liver disease in the world. It involves a spectrum of conditions from hepatic steatosis to nonalcoholic steatohepatitis and liver fibrosis, and is a major cause of cirrhosis and hepatocellular carcinoma. It is defined by presence of steatosis in 5% of hepatocytes or more in the absence of other causes of fatty liver. The metabolic syndrome is the major known risk factor for NAFLD. Dietary contributors such as high fructose intake and coffee consumption appear to increase and decrease the risk of disease respectively, but these links are unclear. Genetic associations have also been identified. The estimated prevalence of the disease varies according to diagnostic method and population demographics. It appears to be a major issue in Europe with population studies showing up to 50% of the individuals are affected while in the USA one in three adults are estimated to have NAFLD. Laboratory investigations and ultrasound are typically first-line investigations. Fibrosis may be assessed noninvasively through transient elastography and biomarkers but liver biopsy remains the gold standard to quantify hepatic damage. Associated comorbidities include cardiovascular disease and chronic kidney disease. Weight loss, dietary changes and exercise are recommended in management. Medications should be considered to manage underlying risk factors including insulin resistance. Surgical options include bariatric procedures and liver transplantation. The combination of rising prevalence and significant potential complications warrant further research into NAFLD, particularly in areas with research gaps including Eastern Europe.

Medical resource utilization and costs among Australian patients with genotype 1 chronic hepatitis C: results of a retrospective observational study.

OBJECTIVE: To evaluate medical resource utilization (MRU) and associated costs among Australian patients with genotype 1 chronic hepatitis C (GT1 CHC), including both untreated patients and those receiving treatment with first-generation protease inhibitor-based regimens (telaprevir, boceprevir with pegylated interferon and ribavirin). METHODS: Medical records were reviewed for a stratified random sample of GT1 CHC patients first attending two liver clinics between 2011-2013 (principal population; PP), supplemented by all GT1 CHC patients attending one transplant clinic in the same period (transplant population; TP). CHC-related MRU and associated costs are reported for the PP by treatment status (treated/not treated) stratified by baseline fibrosis grade; and for the TP for the pre-transplant, year of transplant and post-transplant periods. RESULTS: A total 1636 patients were screened and 590 patients (36.1%) were included. Comprehensive MRU data were collected for 276 PP patients (F0-1 n = 59, F2 n = 58, F3 n = 53, F4 n = 106; mean follow-up = 17.3 months). Thirty-eight (13.8%) were treatment-experienced prior to enrolment; 55 (19.9%) received triple therapy during the study. Data were collected for 112 TP patients (mean follow-up = 29.9 months), 33 (29.5%) received a transplant during the study, and 51 (45.5%) beforehand. The annual direct medical costs, excluding drug costs, were higher among treated PP vs untreated PP (AU$: $1,954 vs $1,202); and year of transplant TP vs pre-/post-transplant TP (AU$: pre-transplant $32,407, transplant $155,138, post-transplant $7,358). LIMITATIONS: To aid interpretation of results, note that only patients with GT1 CHC who are actively managed are included, and MRU data were collected specifically from liver outpatient clinics. That said, movement of patients between hospitals is rare, and any uncaptured MRU is expected to be minimal. CONCLUSIONS: CHC-related MRU increases substantially with disease severity. These real-world MRU data for GT1 CHC will be valuable in assessing the impact of new hepatitis C treatments.

Enhanced antiviral treatment efficacy and uptake in preventing the rising burden of hepatitis C-related liver disease and costs in Australia.

BACKGROUND AND AIM: Chronic hepatitis C virus (HCV) infection is an important cause of advanced liver disease and liver-related deaths in Australia. Our aim was to describe the burden of HCV infection and consider treatment strategies to reduce HCV-related morbidity and mortality. METHODS: Baseline model parameters were based upon literature review and expert consensus with a focus on Australian data. Three treatment scenarios based on anticipated introduction of improved direct-acting antiviral regimens were considered to reduce HCV disease burden. Scenario 1 evaluated the impact of increased treatment efficacy alone (to 80-90% by 2016). Scenario 2 evaluated increased efficacy and increased treatment uptake (2550 to 13,500 by 2018) without treatment restriction, while Scenario 3 considered the same increases with treatment limited to ≥ F3 during 2015-2017. RESULTS: In 2013, there were an estimated 233,490 people with chronic HCV infection: 13,850 with cirrhosis, 590 with hepatocellular carcinoma (HCC) and 530 liver-related deaths. If the current HCV treatment setting is unchanged, threefold increases in the number of people with cirrhosis, HCC, and liver disease deaths will be seen by 2030. Scenario 1 resulted in modest impacts on disease burden (4% decrease in HCC, decompensated cirrhosis, and liver deaths) and costs. Scenario 3 had the greatest impact on disease burden (approximately 50% decrease in HCC, decompensated cirrhosis, and liver deaths) and costs, while Scenario 2 had slightly lesser impact. CONCLUSIONS: Considerable increases in the burden of HCV-related advanced liver disease and its complications will be seen in Australia under current treatment levels and outcomes. Introduction of improved direct-acting antiviral regimens with enhanced efficacy at current treatment levels will lead to limited impacts on this disease burden. A combination of increased treatment efficacy and greater uptake is required to achieve major reductions in advanced liver disease and related costs.

Comprehensive clinical assessment improves the accuracy of predicting cirrhosis in chronic hepatitis C.

BACKGROUND: The diagnosis of cirrhosis in chronic hepatitis C (CHC) is important but difficult in those who are unable to undergo liver biopsy. Thus, the aims of the present study were to compare separately and in combination, clinical markers of liver disease, the discriminant score (DS) and serum hyaluronic acid (HA) for their ability to predict cirrhosis in CHC. METHODS: Two groups of consecutive patients (groups 1 and 2) with CHC were analyzed. Clinical data and routine laboratory results at the time of liver biopsy were collected, and serum HA levels were assayed. A clinical examination score (CES) was constructed using the sum of clinical markers of liver disease in group 1 and was validated in group 2, the DS was calculated, and a serum HA score (HAS) was produced. Combination scores were constructed using the sum of the CES, DS and HAS. Histological analysis of liver biopsies was performed by hepatopathologists blinded to clinical results. RESULTS: One hundred and fifty-one patients with CHC (group 1, n = 47; group 2, n = 104) including 27 with cirrhosis were assessed. Serum HA was more accurate than either CES or DS in the prediction of cirrhosis. The combination of CES, DS and HAS enabled the most accurate prediction of cirrhosis with a sensitivity and specificity of 78% and 93%, and a positive predictive value and negative predictive value of 75% and 94%, respectively. CONCLUSIONS: A comprehensive clinical assessment utilizing clinical and laboratory data more accurately predicts the presence and absence of cirrhosis in CHC than individual markers.

The direct cost of managing patients with chronic hepatitis B infection in Australia.

GOALS: To estimate the average annual cost of managing a patient with chronic hepatitis B (CHB) disease in Australia. BACKGROUND: Little is known about the prevalence or economic burden of hepatitis B viral (HBV) infection in Australia, despite it being recognized as a significant cause of morbidity and mortality. STUDY: A retrospective analysis of 149 patients with CHB disease in six disease states (noncirrhotic CHB, compensated and decompensated cirrhosis, hepatocellular carcinoma, liver transplantation in year 1, and liver transplantation in subsequent posttransplantation years) was conducted. The cost of palliative care for 53 patients with chronic hepatitis and hepatocellular carcinoma was also estimated, based on data from a palliative care unit. RESULTS: The average annual costs (year-2001 AUS$) for each disease state per patient were: noncirrhotic CHB, 1233 dollars (95% CI 939 dollars-1544 dollars); compensated cirrhosis, 1394 dollars (95% CI 975 dollars-1797 dollars); decompensated cirrhosis, 11,961 dollars (95% CI 6993 dollars-18,503 dollars); liver transplantation in year 1, 144,392 dollars (SD, 115,374 dollars); liver transplantation in year 2+, 23,160 dollars (SD, 19,289 dollars); and hepatocellular carcinoma, 11,753 dollars (95% CI 7385 dollars-17,159 dollars). Within the noncirrhotic CHB group, the cost of managing active disease was 1778 dollars (95% CI 1212 dollars-2374 dollars) compared with 758 dollars (95% CI 519 dollars-1045 dollars) for inactive disease. The average cost of palliative care for patients with chronic hepatitis and hepatocellular carcinoma was 6307 dollars (95% CI 4848 dollars-8187 dollars). Multivariate statistical analysis indicated that age, sex, marital status, country of birth, and duration of follow-up were not statistically significant in explaining variation in costs. CONCLUSIONS: The cost of managing patients with CHB disease varies significantly between the noncirrhotic CHB/compensated cirrhosis states and the other four disease states. Within the noncirrhotic CHB state, there is also a significant difference between the cost of managing active and inactive disease. These results will be useful in future cost-effectiveness analyses of prevention and treatment options.