Explore the vast range of titles available.

Robust biomarkers for population-level hepatocellular carcinoma (HCC) surveillance are lacking. We compared serum midkine (MDK), dickkopf-1 (DKK1), osteopontin (OPN) and AFP for HCC diagnosis in 86 HCC patients matched to 86 cirrhotics, 86 with chronic liver disease (CLD) and 86 healthy controls (HC). Based on the performance of each biomarker, we assessed a separate longitudinal cohort of 28 HCC patients, at and before cancer diagnosis. Serum levels of MDK and OPN were higher in HCC patients compared to cirrhosis, CLD and HC groups. DKK1 was not different between cases and controls. More than half of HCC patients had normal AFP. In this AFP-negative HCC cohort, 59.18% (n = 29/49) had elevated MDK, applying the optimal cut-off of 0.44 ng/ml. Using AFP ≥ 20 IU/ml or MDK ≥ 0.44 ng/ml, a significantly greater number (76.7%; n = 66/86) of HCC cases were detected. The area under the receiver operating curve for MDK was superior to AFP and OPN in NASH-HCC diagnosis. In the longitudinal cohort, MDK was elevated in 15/28 (54%) of HCC patients at diagnosis, of whom 67% had elevated MDK 6 months prior. AFP and MDK have a complementary role in HCC detection. MDK increases the diagnostic yield in AFP-negative HCC and has greater diagnostic performance than AFP, OPN and DKK-1 in the diagnosis of NASH-HCC. Additionally, MDK has a promising role in the pre-clinical diagnosis of HCC.

ObjectivesPalliative care (PC) service involvement for hepatocellular carcinoma (HCC) patients is suboptimal and little is known about the underlying reasons for this. We aimed to study clinicians’ experience and attitudes towards PC in HCC.MethodsA nationwide survey was conducted of consultants/trainees recruited from the Gastroenterological Society of Australia membership directory. Clinician demographics, experience and attitudes towards PC use for HCC patients were collected.ResultsThere were 160 participants. Most attended weekly multidisciplinary team meetings (MDTM, 60%) and had no formal PC training (71%). MDTM with PC attendance was reported by 12%. Rates of PC referral increased incrementally from BCLC 0/A to D patients but were not universal even in advanced (46%) or terminal (87%) stages. Most acknowledged PC patient discussions occurred too late (61%). Those with prior PC training were more likely to refer BCLC 0/A and B patients for early PC. Referral rates for outpatient PC were higher in respondents who attended MDTM with PC present across all BCLC stages. PC service was rated good/very good by 70%/81% for outpatients/inpatients. Barriers to PC referral included clinician-perceived negative patient associations with PC (83%), clinician-perceived patient/caregiver lack of acceptance (81%/77%) and insufficient time (70%).ConclusionsPC referral for HCC patients is not universal and occurs late even in late-stage disease. Prior PC training and/or PC presence at MDTM positively influences referral practices. Barriers to PC referral are not related to quality of PC services but rather to clinician-perceived patients’ negative reactions to or lack of acceptance of PC.

Background/Aims: The global proportion of hepatocellular carcinoma (HCC) attributable to metabolic dysfunction-associated fatty liver disease (MAFLD) is unclear. The MAFLD diagnostic criteria allows objective diagnosis in the presence of steatosis plus defined markers of metabolic dysfunction, irrespective of concurrent liver disease. We aimed to determine the total global prevalence of MAFLD in HCC cohorts (total-MAFLD), including the proportion with MAFLD as their sole liver disease (single-MAFLD), and the proportion of those with concurrent liver disease where MAFLD was a contributary factor (mixed-MAFLD).Methods: This systematic review and meta-analysis included studies systematically ascertaining MAFLD in HCC cohorts, defined using international expert panel criteria including ethnicity-specific BMI cut-offs. A comparison of clinical and tumour characteristics was performed between single-MAFLD, mixed-MAFLD, and non-MAFLD HCC.Results: 22 studies (56,565 individuals with HCC) were included. Total and single-MAFLD HCC prevalence was 48.7% (95% confidence interval [CI] 34.5–63.0%) and 12.4% (95% CI 8.3–17.3%), respectively. In HCC due to chronic hepatitis B, C, and alcohol-related liver disease, mixed-MAFLD prevalence was 40.0% (95% CI 30.2–50.3%), 54.1% (95% CI 40.4–67.6%) and 64.3% (95% CI 52.7–75.0%), respectively. Mixed-MAFLD HCC had significantly higher likelihood of cirrhosis and lower likelihood of metastatic spread compared to single-MAFLD HCC, and a higher platelet count and lower likelihood of macrovascular invasion compared to non-MAFLD HCC.Conclusions: MAFLD is common as a sole aetiology, but more so as a co-factor in mixed-aetiology HCC, supporting the use of positive diagnostic criteria.

Abstract Introduction: Hepatocellular carcinoma (HCC) is the sixth most commonly diagnosed cancer and the third leading cause of cancer death worldwide. While there has been rapid evolution in the treatment paradigm of HCC across the past decade, the extent to which these newly approved therapies are utilized in clinical practice in the real world is, however, unknown. The INSIGHT study was an investigator-initiated, multi-site longitudinal cohort study conducted to reflect real-world epidemiology and clinical practice in Asia-Pacific in the immediate 7-year period after the conclusion of the BRIDGE study. Methods: Data were collected both retrospectively (planned 30% of the total cohort size) and prospectively (planned 70%) from January 2013 to December 2019 from eligible patients newly diagnosed with HCC from 33 participating sites across 9 Asia-Pacific countries. Results: A total of 2,533 newly diagnosed HCC patients (1,052 in retrospective cohort and 1,481 in prospective cohort) were enrolled. The most common risk factor was hepatitis B in all countries except Japan, Australia, and New Zealand, where the prevalence of hepatitis C and diabetes were more common. The top three comorbidities reported in the INSIGHT study include cirrhosis, hypertension, and diabetes. We observe high heterogeneity in the first-line treatment recorded across countries and across disease stages, which significantly affects survival outcomes. Stratification by factors such as etiologies, tumor characteristics, the presence of extrahepatic metastases or macrovascular invasion, and the use of subsequent lines of treatment were performed. Conclusion: The INSIGHT study describes a wide spectrum of clinical management practices in HCC, where patient demographics, differential costs, and patient access to therapies may lead to wide geographical variations through the patient’s treatment cycle, from diagnosis to clinical outcome. The high heterogeneity in patient outcomes demonstrates the need for more robust and clinical management strategies to be designed and adopted to bring about better patient outcomes.

Introduction: Hepatic encephalopathy (HE) is common in patients with cirrhosis and is characterised by reduced hepatic ammonia clearance. This is accompanied by alterations in gut bacteria that may be ameliorated with synbiotics (pro- and prebiotics). Branched chain amino acids (BCAAs) are thought to have a role in the detoxification of ammonia. We investigated the effects of the administration of synbiotics and/or BCAAs in treating HE. Methods: Participants with overt HE were randomised in a blinded placebo-controlled study to receive synbiotics, BCAAs, or a combination of BCAAs and Synbiotics. Relevant biochemical and nutritional data and depression and anxiety scores (DASS-21) were collected at entry, 4 weeks, and on completion, at 8 weeks. The Trail Making Test (TMT) and Inhibitory Control Test (ICT) were used to assess cognitive function in patients withHE. Results were analysed using linear mixed effects regression analyses. Results: Sixty-one participants were enrolled and 49 who returned for at least 1 follow-up review were included in the intention to treat analysis. The mean age was 55.8 ± 6.1 years and 86% were males. Despite evidence of a placebo effect, there was significant improvement in TMT B and ICT weighted lures in participants who received combined synbiotics/BCAAs treatment compared to placebo at study completion (p ≤ 0.05). Cognitive improvement occurred without a significant change in ammonia levels. Conclusion: To our knowledge, this is the first study reporting that combined synbiotics and BCAAs improve HE, and that may be beneficial in the management of HE. A larger study is needed to confirm these results.

Background First Nations Peoples of Australia are disproportionally affected by hepatitis C (HCV) infection. Through a prospective study we evaluated the outcome of direct-acting antiviral (DAA) therapy among First Nations Peoples with HCV infection. Methods Adults who initiated DAA therapy at one of 26 hospitals across Australia, 2016–2019 were included in the study. Clinical data were obtained from medical records and the Pharmaceutical and Medicare Benefits Schemes. Outcomes included sustained virologic response (SVR) and loss to follow-up (LTFU). A multivariable analysis assessed factors associated with LTFU. Results Compared to non-Indigenous Australians (n = 3206), First Nations Peoples (n = 89) were younger ( p  < 0.001), morel likely to reside in most disadvantaged ( p  = 0.002) and in regional/remote areas ( p  < 0.001), and had similar liver disease severity. Medicines for mental health conditions were most commonly dispensed among First Nations Peoples (55.2% vs. 42.8%; p  = 0.022). Of 2910 patients with follow-up data, both groups had high SVR rates (95.3% of First Nations Peoples vs. 93.2% of non-Indigenous patients; p  = 0.51) and ‘good’ adherence (90.0% vs. 86.9%, respectively; p  = 0.43). However, 28.1% of First Nations Peoples were LTFU vs. 11.2% of non-Indigenous patients ( p  < 0.001). Among First Nations Peoples, younger age (adj-OR = 0.93, 95% CI 0.87–0.99) and treatment initiation in 2018–2019 vs. 2016 (adj-OR = 5.14, 95% CI 1.23–21.36) predicted LTFU, while higher fibrosis score was associated with better engagement in HCV care (adj-OR = 0.71, 95% CI 0.50–0.99). Conclusions Our data showed that First Nations Peoples have an equivalent HCV cure rate, but higher rates of LTFU. Better strategies to increase engagement of First Nations Peoples with HCV care are needed.

Background While anaemia following liver transplant is common, anaemia in the context of BK viraemia is not a commonly recognised phenomenon. Case presentation We present the case of 59-year old gentleman with severe anaemia in the context of BK viraemia and nephropathy following ABO incompatible liver transplant. Severity of anaemia appeared to correlate with high titres of BK virus in the serum. Bone marrow biopsy revealed hypocellular marrow with normal cytogenetics. Anaemia improved with treatment with cidofovir, intravenous immunoglobulin, reduction in immunosuppression and erythropoietin stimulating agent. Conclusion To our knowledge, this is the first case of anaemia post liver transplant contributed to by BK viraemia.

Background: Malnutrition is common in cirrhosis but is challenging to identify, grade, and manage during liver transplantation (LT) assessment. The resting energy expenditure informs nutritional needs and can be measured with indirect calorimetry (IC); however, it is not routinely used in this context. We aimed to assess the prognostic value of the measured resting energy expenditure (mREE) and its associations in patients with cirrhosis referred for LT assessment. Methods: We performed a single-center, retrospective cohort study of adult patients with cirrhosis who underwent IC between 2002 and 2019 at a statewide LT center. The predicted REE (pREE) was estimated using the Harris–Benedict equation. Patients were classified as normo-, hypo-, and hypermetabolic based on the difference between the mREE and pREE. Malnutrition was determined prospectively using the Subjective Global Assessment. The primary outcome was LT-free survival. Results: A total 203 patients were recruited (74% male, median age 55 [IQR 49–60], median MELD score 14 [IQR 11–17]). The most common cause of cirrhosis was alcohol (40%). The median pREE and mREE were 1652 (IQR 1459–1873) and 1708 (IQR 1490–1907) kcal/day, respectively. The mREE was lower in females and those with older age and malnutrition, significantly correlating with body composition measures (p < 0.01 for all). Most patients were normometabolic (88.6%), with others being hypometabolic (3.5%) or hypermetabolic (8.0%). After a median follow-up of 104 months (IQR 28–175), there were 107 LT and 49 deaths without LT. Hypermetabolism was independently associated with a worse LT-free survival (HR 2.11, 95%CI 1.161–3.845, p = 0.014) but, along with mREE, had no impact on post-LT graft survival. Conclusions: Patients with cirrhosis and hypermetabolism identified with IC had a two-fold increased risk of LT or death, independent of the MELD score and nutritional status. These findings suggest that IC provides valuable prognostic information for pre-LT assessment and may support individualized nutritional and risk stratification strategies in cirrhosis.

Viral hepatitis remains one of the most significant health issues globally, directly responsible for over 1 million deaths each year and affecting almost 300 million people around the world. Scientific research in recent decades has brought about improvements in the lives of people living with chronic viral hepatitis. On the 29 July 2021, the Australian Centre for Hepatitis Virology (ACHV) for the first time held a public educational forum for the general public. The main aim of this event was to inform the affected community about the importance of scientific research and give an overview of upcoming developments in the field. Here, we provide a detailed report of the panel discussion (including its organisation, execution, and lessons learned to incorporate into future events) and provide strategies that can be used by other scientific societies to hold similar events in their own communities.

Background Integration of symptom and palliative care for people with advanced cancer is established in many tumour types, but its role in people with hepatocellular carcinoma (HCC) has not been clearly defined. This study aims to evaluate the clinical and cost effectiveness of an intervention involving a suite of strategies designed to assess and treat palliative care symptoms and needs in adult outpatients with HCC attending four New South Wales (NSW) metropolitan tertiary hospitals. Methods This trial will use a pragmatic cluster-based randomised-controlled design, with ambulatory HCC services as the clusters. HCC patients will be recruited if they have Barcelona Clinical Liver Cancer (BCLC) stage A disease with active tumour or a current or prior diagnosis of BCLC stage B or C disease regardless of tumour activity. Patients with BCLC stage D disease will be excluded as palliative care is the standard of care (SOC) in this group. Cluster sites will be randomised to the study intervention or control where patients are managed according to SOC. All participants will complete the liver-specific Edmonton Symptom Assessment Scale (ESAS) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire at regular ambulatory clinic appointments. At intervention sites, patients scoring ≥ 5 on any liver-specific ESAS symptom will be referred to palliative care physicians for consultation. The primary clinical outcome will be improvement in all symptoms scored ≥ 5 on the liver-specific ESAS by 50% within 3 months and the primary implementation outcome will recording the liver-specific ESAS in ≥ 80% of all participants attending clinic appointments. Caregivers of patients enrolled in the trial will be invited to perform Carer Support Needs Assessment Tool at each appointment. Discussion This trial will inform if earlier palliative care involvement significantly reduces the symptom burden associated with HCC. If found to be effective, earlier implementation of palliative care consultation should be included in HCC treatment guidelines. Trial registration ACTRN12623000010695. Registered on September 1, 2023.