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Background Hepatocellular carcinoma (HCC) incidence and mortality rates are increasing at a greater pace than any other cancer in Australia. Cirrhosis is the major risk factor for HCC, and early detection of HCC through surveillance of people with cirrhosis can improve outcomes. However, cirrhosis is under-detected in primary care settings, with 60% of patients diagnosed with HCC having unrecognised cirrhosis and not found to be in a surveillance programme. Targeted screening of at-risk populations in primary care using noninvasive tests for liver fibrosis could lead to improved diagnosis of cirrhosis and increased participation in HCC surveillance programmes. Methods This is a prospective multicentre parallel randomised controlled trial of 2470 participants, to evaluate the impact of a cirrhosis detection and hepatocellular carcinoma surveillance pathway compared to usual care in 45–75 year olds, with risk factors for chronic liver disease, from regional and urban general practice clinics, across four Australian states. Participants will be randomised 1:1, to usual general practitioner care (control) or a cirrhosis detection pathway (intervention), stratified by clinic and potential hazardous drinking. The cirrhosis detection intervention consists of liver fibrosis blood tests (comprising the Fibrosis-4 Index and Hepascore) and a liver stiffness measurement conducted by FibroScan in those with elevated liver fibrosis blood markers. Participants with elevated FibroScan® values will be recommended for referral for hepatology assessment to determine the need for HCC surveillance. The primary outcome is the between-arm difference in proportion of participants with newly diagnosed cirrhosis in HCC surveillance at 12 months. Secondary outcomes at 12 months will include the between-arm difference in proportion of participants with a diagnosis of any stage HCC, diagnoses of advanced fibrosis and liver decompensation and mean anxiety state and mean quality of life. The cost-effectiveness of the cirrhosis detection pathway will be determined using data linkage to state and national health datasets. Process evaluation will involve assessment of the optimal cirrhosis detection pathway, along with the barriers and enablers of implementation of this pathway, assessed by participant interviews. Discussion This trial will provide evidence of the efficacy and cost-effectiveness of a cirrhosis detection pathway in Australian general practice settings. This will provide evidence to guide the early identification and appropriate placement of patients in HCC surveillance programmes, resulting in earlier HCC diagnosis and improved outcomes. Trial registration Australian and New Zealand Clinical Trial Registry ACTRN12622000185763p. Registered on 3rd February 2022.

Background and aims Liver fibrosis predicts adverse clinical outcomes, such as liver-related death (LRD) and hepatocellular carcinoma (HCC) in patients with non-alcoholic fatty liver disease (NAFLD). We aimed to investigate the accuracy of semi-automated quantification of collagen proportionate area (CPA) as an objective new method for predicting clinical outcomes. Method Liver biopsies from patients with NAFLD underwent computerized image morphometry of Sirius Red staining with CPA quantification performed by ImageScope. Clinical outcomes, including total mortality, LRD, and combined liver outcomes (liver decompensation, HCC, or LRD), were determined by medical records and population-based data-linkage. The accuracy of CPA for predicting outcomes was compared with non-invasive fibrosis tests (Hepascore, FIB-4, APRI). Results A total of 295 patients (mean age 50 years) were followed for a median (range) of 9 (0.2–25) years totalling 3253 person-years. Patients with CPA ≥ 10% had significantly higher risks for total death [hazard ratio (HR): 5.0 (1.9–13.2)], LRD [19.0 (2.0–182.0)], and combined liver outcomes [15.6 (3.1–78.6)]. CPA and pathologist fibrosis staging (FS) showed similar accuracy (AUROC) for the prediction of total death (0.68 vs. 0.70), LRD (0.72 vs. 0.77) and combined liver outcomes (0.75 vs. 0.78). Non-invasive serum markers Hepascore, APRI, and FIB-4 reached higher AUROC; however, they were not statistically significant compared to that of CPA except for Hepascore in predicting total mortality (0.86 vs. 0.68, p  = 0.009). Conclusion Liver fibrosis quantified by CPA analysis was significantly associated with clinical outcomes including total mortality, LRD, and HCC. CPA achieved similar accuracy in predicting outcomes compared to pathologist fibrosis staging and non-invasive serum markers.

Background and aim Methotrexate (MTX) is routinely used for immunological disorders, and its long‐term use is associated with hepatotoxicity. The aim of this study was to investigate whether a serum liver fibrosis test (Hepascore) predicted the risk of adverse liver‐related outcomes and mortality. Methods A total of 92 patients in Western Australia who had a long‐term MTX intake history,from 2004 to 2016, were recruited and followed up from the first Hepascore to death or end of the study. Clinical data, all deaths, and liver‐related outcomes (liver‐related death and decompensation) were obtained from hospital, PathWest, and WA Data Linkage Unit databases. Results Nine deaths and four adverse liver‐related outcomes occurred during the follow up of 354 person‐years. The 5‐year survival was 86.1%. The liver‐related outcome free survival was 95.6%. Baseline Hepascore ≥0.84 was associated with advanced fibrosis on liver biopsy (P = 0.025). A baseline Hepascore ≥0.84 was significantly associated with higher risks for adverse liver‐related outcomes (P < 0.001) and all‐cause mortality (P = 0.001). Cox regression demonstrated that only baseline Hepascore ≥0.84 was independently associated with the increased risk of all‐cause mortality (7.91 [1.52–41.29], P = 0.014). Moreover, any Hepascore ≥0.84 found during follow up was independently associated with the increased risk of all‐cause mortality (86.18 [4.03–1844.83], P = 0.007). Conclusions This study demonstrated the potential importance of Hepascore monitoring in long‐term MTX users. Patients with a Hepascore higher than 0.84 at any stage had increased mortality, but further studies are required to confirm this finding. Hepascore, a serum liver fibrosis test, predicted the risk of adverse liver‐related outcomes and mortality in long‐term MTX users. Patients with a Hepascore higher than 0.84 at any stage should be advised to stop MTX to prevent further liver decompensation or death.

Background and goals Liver fibrosis influences treatment and surveillance strategies in chronic hepatitis B (CHB). This multicenter study aimed to examine the accuracy of serum fibrosis models in CHB patients including those with low alanine aminotransferase (ALT) levels and serially in those undergoing treatment. Method We examined noninvasive fibrosis models [Hepascore, Fibrotest, APRI, hepatitis e antigen (HBeAg)-positive and -negative models] in 179 CHB patients who underwent liver biopsy and fibrosis assessment by METAVIR and image morphometry. Serial Hepascore measurements were assessed in 40 subjects for up to 8.7 years. Results Hepascore was more accurate than Fibrotest [area under the curve (AUC) 0.83 vs. 0.72, P  = 0.05] and HBeAg-positive model (AUC 0.83 vs. 72, P  = 0.03) for significant fibrosis but was not significantly different to APRI or HBeAg-negative scores. Fibrosis area assessed by morphometry was correlated with Hepascore ( r  = 0.603, P  < 0.001), Fibrotest ( r  = 0.392, P  = 0.03), and HBeAg-positive ( r  = 0.492, P  = 0.001) scores only. Among 73 patients with an ALT <60 IU/L, noninvasive models were useful to predict fibrosis (PPV 80–90%) or exclude significant fibrosis (NPV 79–100%). Hepascore increased significantly among patients monitored without treatment and reduced among patients undergoing therapy (0.05/year ± 0.03 vs. −0.04/year ± 0.02, P  = 0.007). Conclusions Serum fibrosis models are predictive of fibrosis in CHB and assist in identifying subjects with low–normal ALT levels for treatment.

An accurate assessment of the degree of fibrosis or presence of cirrhosis is critical both for the appropriate management of, and to provide prognosis for, patients with chronic hepatitis C infection. In the new era of direct acting antivirals, large numbers of patients may enter therapy, and although liver biopsy remains the gold standard, it is not practical in all settings. In recent years, a variety of noninvasive methods have been developed that may obviate the need for liver biopsy in most settings. Indirect laboratory formulas, tests, panels of biomarkers and imaging modalities may accurately stage the degree of fibrosis in hepatitis C monoinfection, hepatitis C/HIV coinfection, and post-transplant recurrent hepatitis C.