Alcohol does not impact chronic hepatitis C treatment outcomes but increases risk for progressive liver disease: Findings from a prospective multicentre Australian study (OPERA-C).

Introduction: Alcohol use is common in patients with chronic hepatitis C virus (HCV) infection. We examined the impact of alcohol use on direct-acting antiviral (DAA) therapy outcome and the clinical course of liver disease and 2-year survival for patients receiving HCV DAA therapy.

Methods: Adults (n = 2624) recruited from 26 Australian hospital liver clinics during 2016-2021 were followed up for 2 years.

Australians with metabolic dysfunction-associated steatotic liver disease have a twofold increase in the incidence of cancer.

Background And Aim: Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with an increased risk of extrahepatic morbidity. We compared the incidence of cancers in adults admitted to Queensland hospitals with MASLD with that for the Queensland population and examined the association between cirrhosis and type 2 diabetes and the development of extrahepatic cancers.

Methods: In this retrospective study, we identified all cancers (Queensland Cancer Registry) after the first hospitalization with MASLD during Jul-2007 to Dec-2019, estimated age-standardized incidence (ASI) of cancers, and compared that with the ASI in the Queensland population (incidence rate ratios [IRR]).

Spontaneous remission of Cronkhite-Canada syndrome without immunosuppressive medication in the context of decompensated cirrhosis: A case report.

We present a case of Cronkhite-Canada syndrome in a patient with decompensated cirrhosis who had successful induction of remission with nutritional supplementation alone. We propose that early institution of high-protein, high-energy enteral supplementation should be offered to all patients, especially those with compelling contraindications to immunosuppression.

High prevalence of diabetes among young First Nations Peoples with metabolic dysfunction-associated steatotic liver disease: a population-based study in Australia.

Background: Liver disease is an important contributor to the mortality gap between First Nations Peoples and non-Indigenous Australian adults. Despite a high burden of metabolic comorbidities among First Nations Peoples, data about the epidemiology of metabolic dysfunction-associated steatotic liver disease (MASLD) in this population is scarce.

Methods: A retrospective analysis of all adults hospitalized with MASLD or metabolic dysfunction-associated steatohepatitis (MASH) with/without cirrhosis during 2007-2019 in the state of Queensland was performed.

Efficacy, safety, and pharmacokinetics of capsid assembly modulator linvencorvir plus standard of care in chronic hepatitis B patients.

Background/aims: Four-week treatment of linvencorvir (RO7049389) was generally safe and well tolerated, and showed anti-viral activity in chronic hepatitis B (CHB) patients. This study evaluated the efficacy, safety, and pharmacokinetics of 48-week treatment with linvencorvir plus standard of care (SoC) in CHB patients.

Methods: This was a multicentre, non-randomized, non-controlled, open-label phase 2 study enrolling three cohorts: nucleos(t)ide analogue (NUC)-suppressed patients received linvencorvir plus NUC (Cohort A, n=32); treatment-naïve patients received linvencorvir plus NUC without (Cohort B, n=10) or with (Cohort C, n=30) pegylated interferon-α (Peg-IFN-α).

Broadening and strengthening the health providers caring for patients with chronic hepatitis C may improve continuity of care.

Background: Direct-acting antiviral (DAA) therapies for hepatitis C virus infection (HCV) lead to excellent rates of sustained virological response (SVR). However, loss to follow-up (LTFU) for SVR testing remains a challenge. We examine factors associated with LTFU in a real-world setting.

Diabetes mellitus and the progression of non-alcoholic fatty liver disease to decompensated cirrhosis: a retrospective cohort study.

Objective: To determine the incidence of decompensated cirrhosis and associated risk factors in people hospitalised with non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) with or without cirrhosis.

Design: Retrospective cohort study; analysis of linked Queensland Hospital Admitted Patient Data Collection, Queensland Registry of Births, Deaths and Marriages, and Queensland Cancer Register data.

Setting, Participants: Queensland residents aged 20 years or older admitted to Queensland hospitals with NAFLD/NASH during 1 July 2009 - 31 December 2018.

Relapsed nodular lymphocyte-predominant Hodgkin lymphoma presenting as severe paraneoplastic hepatitis: a case report.

Background: Hematological malignancies are an infrequent but important cause of liver dysfunction. There are several mechanisms by which this can occur, including direct malignant infiltration of the hepatic parenchyma and/or vasculature, vanishing bile duct syndrome, and paraneoplastic hepatitis. Paraneoplastic hepatitis is an extremely rare mechanism by which a hematological malignancy can cause liver dysfunction, and we present the first case, to our knowledge, of paraneoplastic hepatitis caused by nodular lymphocyte-predominant Hodgkin lymphoma in the literature.

Comparative analysis of Illumina Mouse Methylation BeadChip and reduced-representation bisulfite sequencing for routine DNA methylation analysis.

Researching the murine epigenome in disease models has been hampered by the lack of appropriate and cost-effective DNA methylation arrays. Here we perform a comprehensive, comparative analysis between the Mouse Methylation BeadChip (MMB) and reduced-representation bisulfite sequencing (RRBS) in two murine models of colorectal carcinogenesis. We evaluate the coverage, variability, and ability to identify differential DNA methylation of RRBS and MMB.

Post-colonoscopy cancer rate at a tertiary referral hospital in Australia: A data linkage analysis.

Background And Aim: Colorectal cancer (CRC) diagnosed following a cancer-negative colonoscopy is termed as post-colonoscopy CRC (PCCRC). The World Endoscopy Organization has recently standardized the definition of PCCRC-3Y (CRC developing within 3 years of a cancer-negative colonoscopy). In the present study, we sought to assess PCCRC-3Y rate, perform root-cause analyses, and identify factors associated with development of PCCRC at a tertiary referral hospital in Australia.

Hepatitis C treatment outcomes for Australian First Nations Peoples: equivalent SVR rate but higher rates of loss to follow-up.

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.

Liver Disease and Poor Adherence Limit Hepatitis C Cure: A Real-World Australian Treatment Cohort.

Background And Aims: In 2016, direct-acting antiviral (DAA) treatment for hepatitis C (HCV) became available through Australia's universal health care system, with the aim of HCV elimination. We report real-world effectiveness of DAA HCV treatment in Australia from a clinically well-informed cohort, enriched for cirrhosis and prior HCV treatment.

Methods: 3413 patients were recruited from 26 hospital liver clinics across Australia from February 2016 to June 2020.

Clinicopathological Correlates of Dysplastic Sessile Serrated Lesion: A Prospective Cohort Study With a High Detection Rate.

Background And Aims: Sessile serrated lesions (SSLs) develop colorectal cancer (CRC), through a critical intermediary stage of SSL with dysplasia (SSLd). In this prospective observational study, we aimed to assess clinicopathological correlates of SSLd in the setting of a high lesion-detection rate.

Methods: Patients diagnosed with SSL and SSLd from February 2018 until January 2020 were prospectively recruited, and SSLd specimens were re-evaluated by 2 expert pathologists in a blinded manner.

mutation induces rapid neoplastic transformation in the aged and aberrantly methylated intestinal epithelium.

Objective: Sessile serrated lesions (SSLs) are common across the age spectrum, but the mutant cancers arising occur predominantly in the elderly. Aberrant DNA methylation is uncommon in SSL from young patients. Here, we interrogate the role of ageing and DNA methylation in SSL initiation and progression.

Aspirin reduces the incidence of metastasis in a pre-clinical study of Braf mutant serrated colorectal neoplasia.

Background: Aspirin reduces the incidence of conventional adenomas driven by APC mutation and thus colorectal cancer. The effect of aspirin on the ~20% of colorectal cancers arising via BRAF mutation is yet to be established.

Methods: Braf;Villin-Cre mice were allocated to a control (n = 86) or aspirin-supplemented (n = 83) diet.

Association of with Specific T-cell Subsets in the Colorectal Carcinoma Microenvironment.

Purpose: While evidence indicates that () may promote colorectal carcinogenesis through its suppressive effect on T-cell-mediated antitumor immunity, the specific T-cell subsets involved remain uncertain.

Experimental Design: We measured DNA within tumor tissue by quantitative PCR on 933 cases (including 128 -positive cases) among 4,465 incident colorectal carcinoma cases in two prospective cohorts. Multiplex immunofluorescence combined with digital image analysis and machine learning algorithms for CD3, CD4, CD8, CD45RO (PTPRC isoform), and FOXP3 measured various T-cell subsets.

Curcumin Chemoprevention Reduces the Incidence of Braf Mutant Colorectal Cancer in a Preclinical Study.

Background: Colorectal cancer is a leading cause of cancer-related death worldwide and approximately 20% of cases can be attributed to a mutation in the BRAF oncogene. Curcumin is a promising chemopreventive agent with various anti-cancer benefits. Although curcumin has been reported to have poor bioavailability, this limitation has been overcome by the formulation of nano-carriers.

Pathways to a cancer-free future: a protocol for modelled evaluations to minimise the future burden of colorectal cancer in Australia.

Introduction: With almost 50% of cases preventable and the Australian National Bowel Cancer Screening Program in place, colorectal cancer (CRC) is a prime candidate for investment to reduce the cancer burden. The challenge is determining effective ways to reduce morbidity and mortality and their implementation through policy and practice. -Bowel is a multistage programme that aims to identify best-value investment in CRC control by integrating expert and end-user engagement; relevant evidence; modelled interventions to guide future investment; and policy-driven implementation of interventions using evidence-based methods.

Mutation Marks an Aggressive Subtype of Mutant Colorectal Cancers.

Background: WNT activation is a hallmark of colorectal cancer. mutation is present in 15% of colorectal cancers, and the role of mutations in WNT signaling regulators in this context is unclear. Here, we evaluate the mutational landscape of WNT signaling regulators in mutant cancers.

Alterations in signaling pathways that accompany spontaneous transition to malignancy in a mouse model of BRAF mutant microsatellite stable colorectal cancer.

The serrated neoplasia pathway gives rise to a distinct subgroup of colorectal cancers distinguished by the presence of mutant BRAF and the CpG Island Methylator Phenotype (CIMP). BRAF mutant CRC are commonly associated with microsatellite instability, which have an excellent clinical outcome. However, a proportion of BRAF mutant CRC retain microsatellite stability and have a dismal prognosis.

Traditional serrated adenoma-like lesions in patients with inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) have an increased risk of colorectal carcinoma. The significance of serrated lesions resembling traditional serrated adenoma (TSA) in IBD patients is unclear. In this retrospective study, we analyzed 52 TSA-like lesions arising in 30 IBD patients and diagnosed in colectomy or endoscopic specimens.

DNA methylation changes that precede onset of dysplasia in advanced sessile serrated adenomas.

Background: Sessile serrated adenomas (SSAs) are common polyps which give rise to 20-30% of colorectal cancer (CRC). SSAs display clinicopathologic features which present challenges in surveillance, including overrepresentation in young patients, proclivity for the proximal colon and rarity of histologic dysplasia (referred to then as SSAs with dysplasia, SSADs). Once dysplasia develops, there is rapid progression to CRC, even at a small size.

Integrative Genome-Scale DNA Methylation Analysis of a Large and Unselected Cohort Reveals 5 Distinct Subtypes of Colorectal Adenocarcinomas.

Background & Aims: Colorectal cancer is an epigenetically heterogeneous disease, however, the extent and spectrum of the CpG island methylator phenotype (CIMP) is not clear.

Methods: Genome-scale methylation and transcript expression were measured by DNA Methylation and RNA expression microarray in 216 unselected colorectal cancers, and findings were validated using The Cancer Genome Atlas 450K and RNA sequencing data. Mutations in epigenetic regulators were assessed using CIMP-subtyped Cancer Genome Atlas exomes.