Surveillance MRI is associated with improved survival in patients with primary sclerosing cholangitis.

BACKGROUND: The benefits of regular surveillance imaging for cholangiocarcinoma in patients with primary sclerosing cholangitis (PSC) are unclear. Hence, we aimed to evaluate the impact of regular magnetic resonance cholangiopancreatography (MRCP) on outcomes of patients with PSC in Australia, where the practice of MRCP surveillance is variable. METHODS: The relationship between MRCP surveillance and survival outcomes was assessed in a multicenter, retrospective cohort of patients with PSC from 9 tertiary liver centers in Australia. An inverse probability of treatment weighting approach was used to balance groups across potentially confounding covariates. RESULTS: A total of 298 patients with PSC with 2117 person-years of follow-up were included. Two hundred and twenty patients (73.8%) had undergone MRCP surveillance. Regular surveillance was associated with a 71% reduced risk of death on multivariate weighted Cox analysis (HR: 0.29, 95% CI: 0.14-0.59, p < 0.001) and increased likelihood of having earlier endoscopic retrograde cholangiopancreatography from the date of PSC diagnosis in patients with a dominant stricture (p < 0.001). However, survival posthepatobiliary cancer diagnosis was not significantly different between both groups (p = 0.74). Patients who had surveillance of less than 1 scan a year (n = 41) had comparable survival (HR: 0.46, 95% CI 0.16-1.35, p = 0.16) compared to patients who had surveillance at least yearly (n = 172). CONCLUSIONS: In this multicenter cohort study that employed inverse probability of treatment weighting to minimize selection bias, regular MRCP was associated with improved overall survival in patients with PSC; however, there was no difference in survival after hepatobiliary cancer diagnosis. Further prospective studies are needed to confirm the benefits of regular MRCP and optimal imaging interval in patients with PSC.

Clinical outcomes of hepatocellular carcinoma surveillance in Melbourne, Australia.

BACKGROUND: Ultrasound surveillance for hepatocellular carcinoma (HCC) may improve early tumour detection but may additionally result in surveillance-related harm through increased evaluation of non-HCC lesions. The incidence of these outcomes has not been reported outside North America. AIMS: We aimed to report the outcomes of HCC surveillance with respect to both surveillance-related benefits and harms. METHODS: We reviewed all HCC surveillance ultrasounds at a large Victorian tertiary hospital network in 2017 and followed their outcomes until 2021. Surveillance-related benefits were defined as early-stage HCC detection. Surveillance-related harm was defined as contrast imaging, biopsies or surgery performed to evaluate non-HCC liver lesions or false-positive alpha-fetoprotein levels. RESULTS: Five hundred and fifty-three patients were included (mean age 54.5 ± 12.3 years, males 67.5%, cirrhosis 50.3%). The most common liver disease aetiology was hepatitis B (53.9%). Over a median of 4.7 years follow-up, early-stage HCC was detected in 3.3% (5.4% in cirrhotic vs 1.1% in non-cirrhotic patients, P < 0.01). 75% of all HCCs were early-stage. Surveillance-related harm occurred in 12.5% (15.5% in cirrhotic vs 9.5% in non-cirrhotic patients, P < 0.04), although most harm was mild (12.1%). In subgroup analysis, the detection of early-stage HCC ranged between 0% (screened outside of guideline criteria and alcoholic cirrhotic patients) and 7.2% (hepatitis C cirrhosis). Harm occurred between 9% (non-cirrhotic hepatitis B) and 20.8% (thrombocytopenia). CONCLUSION: In our study, HCC surveillance was associated with early tumour detection, although many patients experienced mild surveillance-related harm. Novel surveillance strategies and pathways are required to improve detection in high-risk patients and minimise harm in low-risk patients.

Improved Survival Outcomes with Surgical Resection Compared to Ablative Therapy in Early-Stage HCC: A Large, Real-World, Propensity-Matched, Multi-Centre, Australian Cohort Study.

The optimal treatment approach in very-early and early-stage hepatocellular carcinoma (HCC) is not precisely defined, and there is ambiguity in the literature around the comparative efficacy of surgical resection versus ablation as curative therapies for limited disease. We performed this real-world propensity-matched, multi-centre cohort study to assess for differences in survival outcomes between those undergoing resection and those receiving ablation. Patients with Barcelona Clinic Liver Cancer (BCLC) 0/A HCC first diagnosed between 1 January 2016 and 31 December 2020 who received ablation or resection as initial treatment were included in the study. A total of 450 patients were included in the study from 10 major liver centres including two transplant centres. Following propensity score matching using key covariates, 156 patients were available for analysis with 78 in each group. Patients who underwent resection had significantly improved overall survival (log-rank test p = 0.023) and local recurrence-free survival (log rank test p = 0.027) compared to those who received ablation. Based on real-world data, our study supports the use of surgical resection in preference to ablation as first-line curative therapy in appropriately selected BCLC 0/A HCC patients.

Hepatocellular carcinoma surveillance in Australia: current and future perspectives.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, and is increasing in incidence in Australia. For most people with cirrhosis and chronic hepatitis B, HCC screening and surveillance is recommended with 6-monthly ultrasound. However, most patients with HCC are still diagnosed outside of surveillance with incurable disease. While HCC surveillance almost certainly reduces cancer-related mortality, the potential harms of surveillance are incompletely understood. Surveillance uptake remains suboptimal in many contexts, and stems from a combination of patient, clinician and system level barriers. Improved case-finding strategies may be required to identify high risk individuals in need of surveillance, as cirrhosis and viral hepatitis are often asymptomatic. HCC prediction models and novel surveillance tools such as biomarker panels, computed tomography and magnetic resonance imaging may have a future role in personalised HCC surveillance. Analyses suggest surveillance may be cost-effective, but Australian data remain limited. A centralised HCC surveillance program may ultimately have a role in delivering improved and more equitable care.

Hepatitis C virus treatment with glecaprevir and pibrentasvir in patients co-prescribed carbamazepine: Three case reports.

BACKGROUND: Highly effective and well-tolerated direct-acting antiviral (DAA) therapies have revolutionised the management of hepatitis C virus (HCV); however, niche populations face treatment barriers. DAAs co-prescribed with several first-generation anti-epileptic drugs (AEDs) are contraindicated due to drug-drug interactions. A common example is carbamazepine whereby steady-state carbamazepine reduces the maximum concentration and area under the curve of velpatasvir, glecaprevir and pibrentasvir due to potent cytochrome P450 (CYP) 3A4 induction. Carbamazepine also induces P-glycoprotein which reduces glecaprevir and pibrentasvir's area under curve to infinite time. Sofosbuvir-velpatasvir and glecaprevir-pibrentasvir are contraindicated in patients who are co-prescribed carbamazepine due to the risk of reduced DAA therapeutic effect and consequently, virological treatment failure. This presents a challenge for patients in whom carbamazepine substitution is medically unfeasible, impractical or unacceptable. However, the properties of current generation DAA therapies, including high-potency non-structural protein 5A inhibitory effect, may be sufficient to overcome reduced bioavailability arising from carbamazepine related CYP 3A4 and P-glycoprotein induction. CASE SUMMARY: We present a case series of three patients with non-cirrhotic, treatment-naïve, genotype 1a, 1b, and 3a HCV who were treated with a 12 wk course of glecaprevir-pibrentasvir, while co-prescribed carbamazepine for seizure disorders. Glecaprevir-pibrentasvir combination therapy was chosen due to its potent in vitro activity and low barrier to pan-genotypic resistance associated variants. DAA therapy was dose-separated from carbamazepine to maximise time to peak concentration, and taken with meals to improve absorption. Sustained virological response at 12 wk was achieved in each patient with no adverse outcomes. CONCLUSION: DAA therapies, including glecaprevir-pibrentasvir, warrant consideration as a therapeutic agent in people with HCV who are co-prescribed carbamazepine, particularly if AED substitution is not feasible.

Hepatocellular carcinoma surveillance in the telehealth era: A single-centre review.

BACKGROUND: Real-world hepatocellular carcinoma (HCC) surveillance uptake remains suboptimal, despite evidence that surveillance is associated with lower cancer-related mortality in patients with cirrhosis and chronic hepatitis B. We aimed to examine the impact of telehealth consultations on HCC surveillance rates within a specialist liver clinic. METHODS: We conducted a retrospective observational study within an Australian outreach liver clinic within a culturally diverse community, comparing standard consultations before the COVID-19 pandemic to telehealth consultations during the pandemic. The primary outcome was surveillance uptake defined as the percentage of time up-to-date with surveillance (PTUDS) with the 6-month interval following each scan considered up-to-date. RESULTS: Over 18 months of follow-up for each cohort, the median PTUDS was 86.5% in the standard consultation cohort and 85.5% in the telehealth consultation cohort (p = 0.12). HCC diagnoses did not differ between groups and hospitalisation and mortality rates were low. Using multivariate regression, increasing age, the need for an interpreter and being born in South-East Asia independently predicted PTUDS in the standard consultation cohort, whereas being born in Australia or New Zealand was predictive of a lower PTUDS. Current alcohol use and distance from the clinic predicted a lower PTUDS in the telehealth consultation cohort. In both groups, missed clinic attendances were strongly predictive of a lower PTUDS. CONCLUSION: Telehealth hepatology consultations effectively coordinate HCC surveillance and are associated with similar outcomes to standard consultations. Its implementation should be widely considered given its advantages with regards to accessibility for patients.

Hepatitis C virus in people with serious mental illness: an analysis of the care cascade at a tertiary health service with a pilot 'identify and treat' strategy.

BACKGROUND: People with serious mental illness (SMI) are underserved from a hepatitis C virus (HCV) screening and treatment perspective. AIMS: To examine the HCV care cascade in people with SMI and to pilot a supported HCV treatment integration programme. METHODS: HCV prevalence was retrospectively analysed from 4492 consecutive individuals admitted to a tertiary hospital mental health service between January 2017 and December 2018. Subcohort analysis of screening patterns and predictors of seropositive infection was performed. Referral pathways and community care integration were analysed for HCV-positive individuals, and a prospective community-based 'identify and treat' HCV programme was assessed. RESULTS: Screening for HCV had been performed in 18.6% (835/4492) of the cohort. Seroprevalence was 4.6% (207/4492). HCV seropositivity was associated with age >40 years (odds ratio (OR) = 9.30; confidence interval (CI) 3.69-23.45; P < 0.01), injecting drug use (OR = 24.26; CI 8.99-65.43; P < 0.01) and previous incarceration (OR = 12.26; CI 4.51-33.31; P < 0.01). In a cohort of treatment-eligible individuals, 43.3% (90/208) had neither been referred to specialist services or general practitioners for HCV management. Amongst those referred to specialist services, 64.7% (57/88) did not attend scheduled follow up, and 48.3% (15/31) of attendees were lost to follow up. Through an intensified community access programme, 10 people were successfully treated for HCV, although 22 could not be engaged. CONCLUSION: People with SMI are underserved by traditional models of HCV healthcare. Intensified community-based support can partially bolster the treatment cascade, although investment in innovative screening and management strategies are required to achieve healthcare parity.

Clinical Utility of Albumin Bilirubin Grade as a Prognostic Marker in Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization: a Systematic Review and Meta-analysis.

PURPOSE: Hepatic function is a key prognostic marker in patients with hepatocellular cancer (HCC) and central to patient selection for transarterial chemoembolization (TACE). We investigated the clinical utility of the Albumin-Bilirubin (ALBI) grade, an emerging prognostic model, in this heterogenous cohort via a meta-analysis of published studies. METHODS: Publications including full text articles and abstracts regarding ALBI grade were sourced by two independent researchers from databases including PubMed, Embase, Medline and Cochrane Library. Studies analysing patients with HCC undergoing TACE treatment were systematically screened utilising the PRISMA tool for data extraction and synthesis, after exclusion of duplicates, irrelevant studies and overlapping cohorts. The primary outcome was overall survival (OS), as determined by ALBI grade and assessed by hazard ratio (HRs) with 95% confidence intervals (CIs), with analysis of collated data using comprehensive meta-analysis, version 3.0 software. RESULTS: Eight studies were included, with a pooled population of 6538 patients with HCC that underwent TACE treatment. Higher pre-treatment grade was associated with poor OS, with median OS of 12.0 months (P < 0.001) in ALBI grade 3, compared to 33.5 months in ALBI grade 1 (P < 0.001). Significant heterogeneity within each ALBI grade was associated with age and tumour size (P < 0.001) in ALBI grades 1 and 2. In contrast, age and alcohol-related liver disease were significant in the ALBI grade 3 group (P < 0.001). CONCLUSIONS: High pre-treatment ALBI grade is associated with poorer prognosis in patients with HCC undergoing TACE therapy. The ALBI grade demonstrates clinical utility for clinical prognostication and patient selection for TACE.

Liver stiffness (Fibroscan®) is a predictor of all-cause mortality in people with non-alcoholic fatty liver disease.

BACKGROUND AND AIMS: Progressive liver fibrosis related to non-alcoholic fatty liver disease (NAFLD) is associated with all-cause and liver-related mortality. We assessed vibration-controlled transient elastography (VCTE) as a predictor of mortality. METHOD: Data from patients who underwent VCTE for NAFLD at four large health services in Victoria, Australia between the years 2008 and 2019 were linked to state-wide data registries. Cause of death (COD) and predictors of all-cause mortality were subsequently analysed using descriptive statistics and Cox-proportional regression analysis. RESULTS: Of 7079 VCTE records submitted for data linkage, 6341 were matched via data registry linkage. There were 217 deaths over a 22 653 person-year follow-up. COD included malignancies other than hepatocellular carcinoma (HCC) (18.0%, n = 39), sepsis (16.1%, n = 35), decompensated liver disease (15.2%, n = 33), cardiac disease (15.2%, n = 33) and HCC 6.0% (n = 13). Controlled attenuation parameter (CAP) was not associated with mortality in univariable analysis (HR = 1.00, CI 1.0-1.0, p = .488). Increased liver stiffness measurement (LSM) (HR 1.02 per kiloPascal, CI 1.01-1.03, p < .001), Charlson comorbidity index (CCI) (HR 1.32 for each point, CI 1.27-1.38, p < .001) and age (HR 1.05 per annum, CI 1.03-1.07, p < .001) were each associated with higher rates of all-cause mortality in multivariable analysis. LSM ≥10 kPa suggestive of compensated advanced chronic liver disease (cACLD) was associated with mortality in multivariable analysis (HR 2.31, CI 1.73-3.09, p < .001). CONCLUSION: VCTE LSM, in addition to age and CCI, is independently associated with increased all-cause mortality in a large cohort with NAFLD.

Monitoring quality of care in hepatocellular carcinoma: A modified Delphi consensus.

Although there are several established international guidelines on the management of hepatocellular carcinoma (HCC), there is limited information detailing specific indicators of good quality care. The aim of this study was to develop a core set of quality indicators (QIs) to underpin the management of HCC. We undertook a modified, two-round, Delphi consensus study comprising a working group and experts involved in the management of HCC as well as consumer representatives. QIs were derived from an extensive review of the literature. The role of the participants was to identify the most important and measurable QIs for inclusion in an HCC clinical quality registry. From an initial 94 QIs, 40 were proposed to the participants. Of these, 23 QIs ultimately met the inclusion criteria and were included in the final set. This included (a) nine related to the initial diagnosis and staging, including timing to diagnosis, required baseline clinical and laboratory assessments, prior surveillance for HCC, diagnostic imaging and pathology, tumor staging, and multidisciplinary care; (b) thirteen related to treatment and management, including role of antiviral therapy, timing to treatment, localized ablation and locoregional therapy, surgery, transplantation, systemic therapy, method of response assessment, and supportive care; and (c) one outcome assessment related to surgical mortality. Conclusion: We identified a core set of nationally agreed measurable QIs for the diagnosis, staging, and management of HCC. The adherence to these best practice QIs may lead to system-level improvement in quality of care and, ultimately, improvement in patient outcomes, including survival.

Lenvatinib for the treatment of hepatocellular carcinoma-a real-world multicenter Australian cohort study.

INTRODUCTION: Hepatocellular carcinoma (HCC) is a serious complication of chronic liver disease. Lenvatinib is an oral multikinase inhibitor registered to treat advanced HCC. This study evaluates the real-world experience with lenvatinib in Australia. METHODS: We conducted a retrospective cohort study of patients treated with lenvatinib for advanced HCC between July 2018 and November 2020 at 11 Australian tertiary care hospitals. Baseline demographic data, tumor characteristics, lenvatinib dosing, adverse events (AEs) and clinical outcomes were collected. Overall survival (OS) was the primary outcome. Progression free survival (PFS) and AEs were secondary outcomes. RESULTS: A total of 155 patients were included and were predominantly male (90.7%) with a median age of 65 years (interquartile range [IQR]: 59-75). The main causes of chronic liver disease were hepatitis C infection (40.0%) and alcohol-related liver disease (34.2). Median OS and PFS were 7.7 (95% confidence interval [CI]: 5.8-14.0) and 5.3 months (95% CI: 2.8-9.2) respectively. Multivariate predictors of mortality were the need for dose reduction due to AEs (Hazard ratio [HR] 0.41, p < 0.01), new or worsening hypertension (HR 0.42, p < 0.01), diarrhoea (HR 0.47, p = 0.04) and more advanced BCLC stage (HR 2.50, p = 0.04). Multivariable predictors of disease progression were higher Child-Pugh score (HR 1.25, p = 0.04), the need for a dose reduction (HR 0.45, p < 0.01) and age (HR 0.96, p < 0.001). AEs occurred in 83.9% of patients with most being mild (71.6%). CONCLUSIONS: Lenvatinib remains safe and effective in real-world use. Treatment emergent diarrhoea and hypertension, and the need for dose reduction appear to predict better OS.

Integrating Hepatitis C Virus Treatment Programs Within Community Mental Health.

Conventional models of health care for the hepatitis C virus (HCV) underserve people with serious mental illness. In a 6-month proof-of-concept study, colocated HCV care coordination was assessed within community mental health settings. The program, which relied on referrals to a visiting hepatologist and was augmented by a part-time nurse practitioner, received 18 referrals for HCV management. From this group, 11 individuals achieved sustained virological response at 12 weeks after direct-acting antiviral therapy. Seven individuals declined treatment or were lost to follow-up. Overall, colocated integrated services may play an important role in HCV health care parity for people with serious mental illness.

Determinants of Hepatitis C Virus Prevalence in People With Serious Mental Illness: A Systematic Review and Meta-Analysis.

Objective: To perform a meta-analysis of hepatitis C virus (HCV) prevalence in people with serious mental illness (SMI) and to systematically review barriers to care with the contention that both individual complications and HCV community transmission can be reduced with enhanced health care strategies.Data Sources: PubMed, Scopus, Embase, CINAHL, and Web of Science were searched for articles published in English between April 21, 1989, and July 1, 2020. The terms Hepatitis C Virus, HCV, HCV seroprevalence, and HCV prevalence were cross-referenced with serious mental illness, severe mental illness, psychiatric illness, mental illness, and psychiatric patients.Study Selection: We identified 230 titles after removing duplicates. The final analysis included 36 publications drawn from prospective and large retrospective cohort studies that cross-sectionally screened for HCV in people with SMI ≥ 18 years of age.Data Extraction: Pooled HCV prevalence was analyzed, with random effects modeling due to significant attributable study heterogeneity. Demographic data and HCV risk factors were subanalyzed. Qualitative and semiqualitative data relating to control cohort prevalence and the HCV care cascade were also extracted.Results: The pooled HCV prevalence was 8.0% (95% CI, 6.0%-9.0%). Subanalysis of prospective studies (n = 9,015 individuals) demonstrated a similar prevalence, 8.0% (CI, 5.0%-11.0%), to retrospective studies (n = 289,247), 8.0% (CI, 6.0%-10.0%). HCV was 3.0- to 11.3-fold higher in people with SMI relative to controls. Semiqualitative analysis of seropositive cases showed that (1) 20.0%-58.1% did not have an identified HCV risk factor; (2) 12.5%-100% of cases were not previously known to have HCV; and (3) the majority, 57.0%-96.6%, of people with SMI were receptive to HCV screening.Conclusions: People with SMI have high HCV seroprevalence and should be recognized as a priority group for HCV screening and health care access.

Clinical outcomes of patients with two small hepatocellular carcinomas.

BACKGROUND: Management of single small hepatocellular carcinoma (HCC) is straightforward with curative outcomes achieved by locoregional therapy or resection. Liver transplantation is often considered for multiple small or single large HCC. Management of two small HCC whether presenting synchronously or sequentially is less clear. AIM: To define the outcomes of patients presenting with two small HCC. METHODS: Retrospective review of HCC databases from multiple institutions of patients with either two synchronous or sequential HCC ≤ 3 cm between January 2000 and March 2018. Primary outcomes were overall survival (OS) and transplant-free survival (TFS). RESULTS: 104 patients were identified (male n = 89). Median age was 63 years (interquartile range 58-67.75) and the most common aetiology of liver disease was hepatitis C (40.4%). 59 (56.7%) had synchronous HCC and 45 (43.3%) had sequential. 36 patients died (34.6%) and 25 were transplanted (24.0%). 1, 3 and 5-year OS was 93.0%, 66.1% and 62.3% and 5-year post-transplant survival was 95.8%. 1, 3 and 5-year TFS was 82.1%, 45.85% and 37.8%. When synchronous and sequential groups were compared, OS (1,3 and 5 year synchronous 91.3%, 63.8%, 61.1%, sequential 95.3%, 69.5%, 64.6%, P = 0.41) was similar but TFS was higher in the sequential group (1,3 and 5 year synchronous 68.5%, 37.3% and 29.7%, sequential 93.2%, 56.6%, 48.5%, P = 0.02) though this difference did not remain during multivariate analysis. CONCLUSION: TFS in patients presenting with two HCC ≤ 3 cm is poor regardless of the timing of the second tumor. All patients presenting with two small HCC should be considered for transplantation.

Short-term intraperitoneal catheters: An ambulatory care intervention for refractory ascites secondary to cirrhosis during COVID-19.

BACKGROUND AND AIM: Patients with refractory ascites have frequent hospital admissions, which pose exposure risks in the context of the COVID-19 pandemic. The aim of this study was to investigate the safety and efficacy of a novel 12-week, multidisciplinary ambulatory care program allowing frequent low-volume ascitic drainage through a tunneled, intraperitoneal catheter (IPC). METHODS: Adult patients with cirrhosis complicated by refractory ascites were recruited through a liver clinic in a tertiary health service in Melbourne, Australia from April to December 2020. All patients were enrolled in a 12-week multidisciplinary program including medical, nursing, dietetics, and pharmacy support. A Rocket Medical IPC was inserted on day 1 with 1-2 L of ascitic fluid drained over 1-3 sessions per week either at the patients' homes or at the hospital day ward. Patients' demographics, death, complications, and self-reported outcomes were recorded. RESULTS: Twelve patients were enrolled with a median of 65-day (interquartile range [IQR]: 16.5-93) IPC duration between April and December 2020 across two periods of COVID-related lockdown in Melbourne, Australia. There were no IPC-related deaths. Early removal was necessitated in three patients due to leakage, nonadherence, and bacteremia. On day 30, the median self-reported health score increased from 50 (IQR: 50-70) to 78 (IQR: 50-85), attributable to a reduction in symptom burden. CONCLUSION: A multidisciplinary IPC program including the use of short-term IPC was safe and associated with a self-reported improvement in perceptions of health. In the context of the COVID-19 pandemic, the program aimed to reduce patient and clinician exposure, which is maintaining engagement and management of decompensated cirrhosis.

Management, outcomes and survival of an Australian IgG4-SC cohort: The MOSAIC study.

BACKGROUND AND AIMS: IgG4 sclerosing cholangitis (IgG4-SC) is the biliary component of the multisystem IgG4-related disease. We aimed to investigate the clinical features, demographics, treatment response and outcomes of IgG4-SC in a large Australian cohort. METHODS: We conducted nationwide retrospective cohort via the Australian Liver Association Clinical Trials Network (ALA-CRN). 39 sites were invited to participate. IgG4-SC was defined by the clinical diagnostic criteria established by the Japanese Biliary Association in 2012. Data were collected on patient demographic, clinical and laboratory information, presenting features, response to therapy and clinical outcomes. RESULTS: 67 patients meet inclusion criteria from 22 sites. 76% were male with mean age of 63.3 ± 14.5 years and a median IgG4 level of 3.6 g/L [0.09-67.1]. The most frequent presenting symptom was jaundice (62%) and abdominal pain (42%) and Type 1 biliary stricturing (52%) at the distal common bile duct was the most frequent biliary tract finding. Prednisolone was used as a primary treatment in 61 (91%) and partial or complete response occurred in 95% of subjects. Relapse was common (42%) in those who ceased medical therapy. After a median follow up of 3.9 years there was one hepatocellular carcinoma and no cholangiocarcinomas. CONCLUSIONS: Our study confirms the preponderance of IgG4-SC in males and highlights the steroid response nature of this condition although relapse is common after steroid cessation. Progression to malignancy was uncommon.

Liver disease prevalence and severity in people with serious mental illness: a cross-sectional analysis using non-invasive diagnostic tools.

BACKGROUND/PURPOSE OF THE STUDY: Little is known about all-cause liver disease in people with serious mental illness (SMI), despite heightened risk factors. We, therefore, prospectively assessed liver disease by etiology and severity in a cross-sectional cohort of people with SMI at a tertiary health service. METHODS: We recruited 255 people with SMI between August 2019 and March 2020. Liver disease data were derived from structured interview, medical records, biochemical and BBV serological analyses, and vibration-controlled transient elastography (VCTE). Steatosis was determined using a threshold of ≥ 248 db/m via the controlled attenuation parameter (CAP) on VCTE. Liver disease prevalence was assessed descriptively, and predictors of metabolic-dysfunction associated fatty liver disease (MAFLD) analyzed using linear regression and multivariable analysis. Best fit modeling of non-invasive screening tests for MAFLD was also assessed. RESULTS: Valid VCTE was obtained for 252 (98.9%) participants. Median age was 40 years (IQR 31-49) with male predominance (65.9%). Hepatitis C Virus (HCV) seroprevalence was 14.7% (37/252), with four new viremic cases identified. Hepatic steatosis was diagnosed in 61.5% (155/252) of participants, with MAFLD criteria met in 59.9% (151/252) of cases. Clozapine and paliperidone were associated with hepatic steatosis (CAP + 23.3 db/m, p 0.013 and CAP + 25.5, p 0.037, respectively). Advanced liver disease, defined by LSM ≥ 8.2 kPa, was identified in 26 individuals (10.3%). MAFLD compared to no MAFLD was associated with more advanced liver disease (5.3 kPa, 4.3-6.5 versus 4.9 kPa, 3.9-5.6, p < 0.001). CONCLUSION: Liver disease is common in people with SMI and should be screened for as part of standard physical health assessment.

Safety of rapid injection of undiluted ferric carboxymaltose to patients with iron-deficiency anaemia: a Phase II single-arm study.

BACKGROUND: Ferric carboxymaltose is increasingly utilised to treat iron deficiency and is usually diluted in saline and administered as an intravenous infusion over 15 min. Although this is highly convenient compared with older formulations, we hypothesised the drug could be administered, safely given as a rapid bolus injection. AIMS: To define the risk of serious adverse events following administration of an undiluted, rapid, high-dose ferric carboxymaltose injection. Secondary aims included all other adverse events, as well as longitudinal effects on haemoglobin, iron stores, phosphate and hepcidin. METHODS: In a single-arm, Phase II study in 121 patients with iron-deficiency anaemia, we administered up to 1000 mg of ferric carboxymaltose as a rapid undiluted bolus injection, and recorded adverse events and collected blood samples over the first hour, and again at 2 and 4 weeks post-treatment. RESULTS: No patient experienced a serious adverse event. Flushing during the injection was common, as was a transient headache in the subsequent weeks. One patient experienced Grade 3 chest tightness, necessitating emergency department assessment but not admission or treatment. Treatment produced an average 12.3 g/L improvement in haemoglobin within 2 weeks, but commonly caused reductions in serum phosphate (although none of these was clinically symptomatic). Parenteral iron caused elevations in hepcidin sustained to 4 weeks post-injection. Patients stated they would be prepared to receive the treatment again. CONCLUSION: Rapid injection of undiluted ferric carboxymaltose is well tolerated and could provide an approach to treat patients in the ambulatory setting.

SIRT Compared with DEB-TACE for Hepatocellular Carcinoma: a Real-world Study (the SITAR Study).

BACKGROUND: Hepatocellular carcinoma (HCC) is responsible for 1% of deaths worldwide, and the incidence continues to increase. Despite surveillance programs, 70% of HCC patients are not suitable for curative options at diagnosis, and therefore, non-curative treatments are essential to modern clinical practice. There are many novel treatments, though their roles are not well defined. This study aimed to contrast Selective Internal Radiation Therapy (SIRT) and Drug Eluting Bead Transarterial Chemoembolisation (DEB-TACE) to further define their roles. METHODS: This was a retrospective multicentre cohort study. Factors included for analysis were type of HCC treatment, number of lesions, lesion size, multiple disease severity scores, cirrhosis and vascular invasion. The primary endpoint was transplant-free survival. RESULTS: Transplant-free survival was similar between the two cohorts (p = 0.654), despite a variation in median lesion size, SIRT: 54.5 mm, DEB-TACE: 34 mm (p ≤ 0.001). A univariate Cox proportional hazard model utilising treatment modality as the covariate showed no significant difference in survival (DEB-TACE HR 1.4 (95%CI 0.85-2.15 p = 0.207). The size of the largest lesion was the best predictor of 3-year survival (p = 0.035). Lesion size was inversely associated with survival (HR 1.01 (95%CI 1-1.02, p = 0.025)) on multivariate analysis. CONCLUSION: This study is the first to catalogue the experience of using SIRT in HCC in a real-world Australian population. It has demonstrated no difference in survival outcomes between DEB-TACE and SIRT. Further, it has shown SIRT to be a reasonable alternative to DEB-TACE especially in larger lesions and has demonstrated that DEB-TACE has a role in select patients with advanced disease.

Adherence in chronic hepatitis B: associations between medication possession ratio and adverse viral outcomes.

BACKGROUND: Antiviral therapy for chronic hepatitis B (CHB) is effective and can substantially reduce the risk of progressive liver disease and hepatocellular carcinoma but is often administered for an indefinite duration. Adherence has been shown in clinical trials to maximize the benefit of therapy and prevent the development of resistance, however the optimal threshold for predicting clinical outcomes has not been identified. The aim of this study was to analyse adherence using the medication possession ration (MPR) and its relation to virological outcomes in a large multi-centre hospital outpatient population, and guide development of an evidence-based threshold for optimal adherence. METHODS: Pharmacy and pathology records of patients dispensed CHB antiviral therapy from 4 major hospitals in Melbourne between 2010 and 2013 were extracted and analysed to determine their MPR and identify instances of unfavourable viral outcomes. Viral outcomes were classified categorically, with unfavourable outcomes including HBV DNA remaining detectable after 2 years treatment or experiencing viral breakthrough. The association between MPR and unfavourable outcomes was assessed according to various thresholds using ROC analysis and time-to-event regression. RESULTS: Six hundred forty-two individuals were included in the analysis. Median age was 46.6 years, 68% were male, 77% were born in Asia, and the median time on treatment was 27.5 months. The majority had favourable viral outcomes (91.06%), with most having undetectable HBV DNA at the end of the study period. The most common unfavourable outcome was a rise of < 1 log in HBV DNA (6.54% of the total), while 2.49% of participants experienced viral breakthrough. Adherence was linearly associated with favourable outcomes, with increasing risk of virological breakthrough as MPR fell. Decreasing the value of MPR, at which a cut-point was taken, was associated with a progressively larger reduction in the rate of unfavourable event; from a 60% reduction under a cut-point of 1.00 to a 79% reduction when the MPR cut-point was set at 0.8. CONCLUSION: Lower adherence as measured using the MPR was strongly associated with unfavourable therapeutic outcomes, including virological failure. Optimising adherence is therefore important for preventing viral rebound and potential complications such as antiviral resistance. The evidence of dose-response highlights the need for nuanced interventions.