Smoking and Alcohol Consumption and Risk of Incident Diverticulitis in Women.

BACKGROUND & AIMS: Much of what is known about the effects of alcohol and tobacco use on diverticular disease derives from studies of asymptomatic diverticulosis or complicated diverticulitis. We examined smoking and alcohol consumption and risk of incident diverticulitis in a large cohort of women. METHODS: We conducted a prospective study of 84,232 women in the Nurses' Health Study II (NHS II) who were 39-52 years old and without known diverticulitis at baseline in 2003. Smoking was ascertained every 2 years and alcohol use every 4 years. We used Cox proportional hazards regression to estimate multivariable-adjusted hazards ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During 1,139,660 person-years of follow up, we identified 3018 incident cases of diverticulitis. After adjustment for other risk factors, current (HR, 1.20; 95% CI, 1.04-1.39) and past smoking (HR, 1.20; 95% CI, 1.11-1.30) were associated with increased risk of diverticulitis when compared with never smokers. Women who consumed ≥30 g/d of alcohol had a multivariate HR of 1.26 (95% CI, 1.05-1.50) when compared with women who did not drink. A joint analysis of smoking and alcohol found that individuals who ever smoked and consumed ≥15 g/d of alcohol were at highest risk of diverticulitis (multivariate HR, 1.60; 95% CI, 1.16-2.21), compared with participants who never smoked and reported no alcohol use. CONCLUSIONS: In this large prospective study of women, smoking and alcohol consumption were associated with an increased risk of incident diverticulitis. These data highlight additional modifiable risk factors for diverticulitis that may aid in prevention.

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. METHODS: Adults who received DAA therapy for HCV in one of 26 centers across Australia during 2016-2021 were followed up for 2 years. Data sources included the patient medical records and the national Pharmaceutical and Medicare Benefits Schemes. Linkage to Medicare provided utilization data of other health-care providers and re-treatment with DAAs. LTFU was defined as no clinic attendance for SVR testing by at least 52 weeks after DAA treatment commencement. Multivariable logistic regression assessed factors associated with LTFU. RESULTS: In 3619 patients included in the study (mean age 52.0 years; SD = 10.5), 33.6% had cirrhosis (69.4% Child-Pugh class B/C), and 19.3% had HCV treatment prior to the DAA era. Five hundred and fifteen patients (14.2%) were LTFU. HCV treatment initiation in 2017 or later (adj-OR = 2.82, 95% confidence interval [CI] 2.25-3.54), younger age (adj-OR = 2.63, 95% CI 1.80-3.84), Indigenous identification (adj-OR = 1.99, 95% CI 1.23-3.21), current injection drug use or opioid replacement therapy (adj-OR = 1.66, 95% CI 1.25-2.20), depression treatment (adj-OR = 1.49, 95% CI 1.17-1.90), and male gender (adj-OR = 1.31, 95% CI 1.04-1.66) were associated with LTFU. CONCLUSIONS: These findings stress the importance of strengthening the network of providers caring for patients with HCV. In particular, services targeting vulnerable groups of patients such as First Nations Peoples, youth health, and those with addiction and mental health disorders should be equipped to treat HCV.

Temporal change in aetiology and clinical characteristics of hepatocellular carcinoma in a large cohort of patients in New South Wales, Australia.

BACKGROUND: Viral hepatitis, alcohol-related liver disease (ARLD) and nonalcoholic fatty liver disease (NAFLD) are the main risk factors for hepatocellular carcinoma (HCC) in many countries. In Australia, given the access to hepatitis C virus (HCV) direct-acting antiviral (DAA) therapy since 2016, a temporal change in HCC aetiology was hypothesized. This study evaluated the temporal change in the aetiology and characteristics of HCC in New South Wales (NSW). METHODS: Patients diagnosed with HCC, admitted to three public hospitals in NSW between 2008 and 2021, were included in the analyses. We assessed the annual frequency of each HCC aetiology and the distribution of HCC characteristics in participants. RESULTS: Among 1370 patients, the most common HCC etiologies were HCV (n = 483, 35%), ARLD (n = 452, 33%), NAFLD (n = 347, 25%) and hepatitis B virus (n = 301, 22%). The proportion of HCV-related HCC was the highest in 2011-2016 (41%) and significantly declined to 30% in 2017-2021 (odds ratio [OR], 0.53 [95% confidence interval (CI), 0.35-0.79]; P = 0.002). The proportion of HCC diagnosed at an early stage (Barcelona Clinic Liver Cancer stage O/A) increased from 41% in 2008-2009 to 56% in 2020-2021 (OR per annum, 1.05 [95% CI, 1.02-1.08]; P = 0.002), and the proportion of patients receiving potentially curative HCC management increased from 29% in 2008-2009 to 41% in 2020-2021 (OR per annum, 1.06 [95% CI, 1.03-1.10]; P < 0.001). CONCLUSION: The contribution of HCV to HCC burden has been decreasing in the DAA era, suggesting the role of HCV elimination in decreasing HCC risk. Increasing frequency of less advanced HCC at diagnosis over time suggests improved HCC surveillance.

Predicting hepatitis B e Antigen seroconversion after pregnancy-The SydPregScore.

BACKGROUND AND AIMS: Achieving Hepatitis B e antigen seroconversion (HBeAg SC) at an earlier age confers a better prognosis. We examined baseline and post-partum factors associated with HBeAg SC after pregnancy. We developed a tool, the SydPregScore, to estimate the likelihood of HBeAg SC in the years after pregnancy. METHODS: A retrospective analysis of an HBeAg-positive pregnant cohort was conducted. Variables including baseline age, parity, alanine aminotransferase level, HBV viral load, quantitative HBsAg, use of antiviral therapy and post-partum flare were collected. Univariate and multivariate Cox regression analyses to determine predictors of HBeAg SC and develop a predictor score were performed. RESULTS: We analysed HBeAg SC rates in 220 pregnancies to 149 HBeAg-positive women from 2006 to 2019. At baseline, their median age was 33 (IQR 29-37), ALT 23 U/L (IQR 17-33) and viral load 8 log10 IU/mL (IQR 6.3-8.2 log10 IU/mL). The majority (133/198, 67.2%) received short-course antiviral therapy to prevent mother-to-child transmission, and 109/192 (56.8%) had a post-partum flare. HBeAg SC occurred in 74/220 (33.6%) after pregnancy (median follow-up 814 days, IQR 405-1531). Multivariate analysis identified baseline viral load <8 log10 IU/mL (HR 2.426 [1.224-4.809], p = .011), baseline ALT ≥2 ULN (HR 2.726 [1.299-5.721], p = .008) and age <35 (HR 2.859 [1.255-6.513], p = .012) to be positive predictors of HBeAg SC. The 'SydPreg Score' estimated the probability of HBeAg SC at 2000 days as 10%, 30%, 70% and 80% for 0, 1, 2, and 3 predictors respectively. CONCLUSION: The SydPreg Score allows the prediction of HBeAg SC in the years after pregnancy. Even in those without elevated ALT, age <35 and viral load <8 log10 IU/mL can identify women with a good chance of subsequent HBeAg SC. Those without a chance may benefit from viral suppression.

Routine screening of emergency admissions at risk of chronic hepatitis (SEARCH) identifies and links hepatitis B cases to care.

BACKGROUND AND AIMS: Significant barriers exist with hepatitis B (HBV) case detection and effective linkage to care (LTC). The emergency department (ED) is a unique healthcare interaction where hepatitis screening and LTC could be achieved. We examined the efficacy and utility of automated ED HBV screening for Overseas Born (OB) patients. METHODS: A novel-automated hepatitis screening service "SEARCH" (Screening Emergency Admissions at Risk of Chronic Hepatitis) was piloted at a metropolitan hospital. A retrospective and comparative analysis of hepatitis testing during the SEARCH pilot compared to a period of routine testing was conducted. RESULTS: During the SEARCH pilot, 4778 OB patients were tested for HBV (86% of eligible patient presentations), compared with 1.9% of eligible patients during a control period of clinician-initiated testing. SEARCH detected 108 (2.3%) hepatitis B surface antigen positive patients including 20 (19%) in whom the diagnosis was new. Among 88 patients with known HBV, 57% were receiving medical care, 33% had become lost to follow-up and 10% had never received HBV care. Overall, 30/88 (34%) patients with known HBV were receiving complete guideline-based care prior to re-engagement via SEARCH. Following SEARCH, LTC was successful achieved in 48/58 (83%) unlinked patients and 19 patients were commenced on anti-viral therapy. New diagnoses of cirrhosis and hepatocellular carcinoma were made in five and one patient(s) respectively. CONCLUSIONS: Automated ED screening of OB patients is effective in HBV diagnosis, re-diagnosis and LTC. Prior to SEARCH, the majority of patients were not receiving guideline-based care.

Frailty predicts mortality in patients with upper gastrointestinal bleed: a prospective cohort study.

BACKGROUND AND AIM: Evidence on the impact of frailty in patients with upper gastrointestinal bleed (UGIB) is limited. This study aims to define the role of frailty as defined by Canadian Study of Health and Aging clinical frailty scale (CSHA-CFS) in predicting mortality in UGIB. METHODS: A prospective single-center cohort study was conducted over 21 months on all consecutive patients with UGIB. Data on demographics, lab parameters, Glasgow Blatchford score, CSHA-CFS, Charlson Comorbidity Index, and AIMS65 score was recorded. The primary outcome was all-cause inpatient mortality. The secondary outcomes were all-cause 30-day mortality, 30-day rebleeding, 30-day readmission, hospital length of stay (LoS), intensive care unit (ICU) admission, need for repeat endoscopy, and need for blood transfusion. The data were evaluated using univariate and multivariate analysis. RESULTS: There were 298 eligible patients, of which 63% were males, median age was 68 years, 44% were from non-English-speaking background, and 72% had major comorbidities. The all-cause inpatient and 30-day mortality were 9.4% and 10.7%, respectively. In the multivariate analysis, CHSA-CFS was the independent predictor of all-cause inpatient mortality (OR 1.66; 95% CI 1.13-2.143; P = 0.010) and all-cause 30-day mortality (OR 1.83; 95% CI 1.26-2.67; P = 0.002). CHSA-CFS was not a significant predictor of 30-day rebleed, 30-day readmission, ICU admission, hospital LoS, or need for blood transfusion. CONCLUSION: Frailty is an important independent predictor of mortality in patients with UGIB. Frailty assessment can guide clinical decision making and allow targeting of health-care resource (Australia/New Zealand Clinical Trial Registry number: ACTRN12622000821796).

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. Clinical history and sustained viral response (SVR) were obtained from medical records and data linkage to the Australian Pharmaceutical Benefits Scheme. Factors associated with SVR were assessed by multivariable logistic regression (MVR). RESULTS: At recruitment, 32.2% had cirrhosis (72.9% Child Pugh class B/C), and 19.9% were treatment experienced. Of the 2,939 with data, 93.3% confirmed SVR. 137 patients received second-line therapy. Patients with cirrhosis had lower SVR rate (88.4 vs. 95.8%; p < 0.001). On MVR, failure to achieve SVR was associated with Genotype 3 (adj-OR = 0.42, 95%CI 0.29-0.61), male gender (adj-OR = 0.49, 95%CI 0.31-0.77), fair/poor adherence (adj-OR = 0.52, 95%CI 0.28-0.94), cirrhosis (adj-OR = 0.57, 95%CI 0.36-0.88), FIB-4 > 3.25 (adj-OR = 0.52, 95%CI 0.33-0.83) and MELD score ≥ 20 (adj-OR = 0.25, 95%CI 0.08-0.80). Consistent results were seen in cirrhotic sub-analysis. CONCLUSIONS: Excellent SVR rates were achieved with DAAs in this real-world cohort of patients with chronic HCV infection. More advanced liver disease and clinician impression of poor adherence were associated with HCV treatment failure. Supports to improve liver fibrosis assessment skills for non-specialist DAA prescribers in the community and to optimize patient adherence are likely to enable more effective pursuit of HCV elimination in Australia.

Hepatitis B Virus Flares After Nucleot(s)ide Analogue Cessation Are Associated With Activation of Toll-Like Receptor Signaling Pathways.

BACKGROUND: We evaluated the patterns of peripheral Toll-like receptor (TLR) signaling activity and the expression of TLRs and natural killer (NK) cell activation in a cohort of patients experiencing severe hepatitis flares after stopping nucleot(s)ide analogues (NAs) therapy. METHODS: Samples were collected longitudinally from patients with chronic hepatitis B who were enrolled in a prospective study of NA discontinuation. Patients experiencing hepatitis flares were compared with patients with normal alanine aminotransferase. Peripheral blood mononuclear cells (PBMCs) were stimulated with TLR ligands and cytokine secretion in the cell culture supernatant measured. Expression of TLR2/4, NKG2D, NKp46, and triggering receptor expressed on myeloid cells 1 (TREM-1) on monocytes, NK, and NK-T cells was measured. RESULTS: Seventeen patients with severe reactivation hepatitis flares were compared to 12 nonflare patients. Hepatitis flares were associated with increased activity of TLR2-8 and TLR9 signaling in PBMCs at the time of peak flare compared to baseline. Hepatitis flares were also associated with (1) upregulation of TLR2 and (2) TREM-1 receptor expression on NK. There were no differences at baseline between flare patients and nonflare patients. CONCLUSIONS: Hepatitis flares off NA therapy have a significant innate inflammatory response with upregulation of TLR signaling on peripheral monocytes and TLR2 and TREM-1 expression on NK cells. This implicates the innate immune system in the immunopathogenesis of hepatitis B flares.

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. 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.

Selective internal radiation therapy for hepatocellular carcinoma: A 15-year multicenter Australian cohort study.

BACKGROUND AND AIM: The exact place for selective internal radiation therapy (SIRT) in the therapeutic algorithm for hepatocellular carcinoma (HCC) is debated. There are limited data on its indications, efficacy, and safety in Australia. METHODS: We performed a multicenter retrospective cohort study of patients undergoing SIRT for HCC in all Sydney hospitals between 2005 and 2019. The primary outcome was overall survival. Secondary outcomes were progression-free survival and adverse events. RESULTS: During the study period, 156 patients underwent SIRT across 10 institutions (mean age 67 years, 81% male). SIRT use progressively increased from 2005 (n = 2), peaking in 2017 (n = 42) before declining (2019: n = 21). Barcelona Clinic Liver Cancer stages at treatment were A (13%), B (33%), C (52%), and D (2%). Forty-four (28%) patients had tumor thrombus. After a median follow-up of 13.9 months, there were 117 deaths. Median overall survival was 15 months (95% confidence interval 11-19). Independent predictors of mortality on multivariable analysis were extent of liver involvement, Barcelona Clinic Liver Cancer stage, baseline ascites, alpha fetoprotein, and model for end-stage liver disease score. Median progression-free survival was 6.0 months (95% confidence interval 5.1-6.9 months). Following SIRT, 11% of patients were downstaged to curative therapy. SIRT-related complications occurred in 17%: radioembolization-induced liver disease (11%), pneumonitis (3%), gastrointestinal ulceration, and cholecystitis (1% each). Baseline ascites predicted for radioembolization-induced liver disease. CONCLUSION: We present the largest Australian SIRT cohort for HCC. We have identified several factors associated with a poor outcome following SIRT. Patients with early-stage disease had the best survival with some being downstaged to curative therapy.

Efficacy and Safety of Sofosbuvir/Velpatasvir/Voxilaprevir for Hepatitis C Virus (HCV) NS5A-Inhibitor Experienced Patients With Difficult to Cure Characteristics.

BACKGROUND: In clinical trials, hepatitis C virus (HCV) salvage treatment with sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) achieved an SVR12 rate of >95% in NS5A-experienced participants. Lower SVR12 rates have been reported in real-world studies, particularly for genotype (GT)3 infection and cirrhosis. We determined the efficacy and safety of SOF/VEL/VOX in a large real-world cohort. METHODS: We assessed the efficacy of salvage SOF/VEL/VOX for HCV infection in NS5A-inhibitor experienced participants with cirrhosis and portal hypertension, prior liver transplantation (LT) or severe extra-hepatic manifestations. SOF/VEL/VOX was available via an early access program. The primary outcome was SVR12. Secondary outcome was frequency of adverse events (AE). FINDINGS: Ninety-seven participants were included. Median age was 58, 82% were male, 78% had cirrhosis, most with portal hypertension (61%, n = 46/76), and 18% had prior-LT. Of the cirrhotic participants, 96% were Child-Turcotte-Pugh class A, and 4% were class B. Of the 72% with GT3, 76% were also cirrhotic. By intention-to-treat analysis, SVR12 rate was 85% (n = 82/97). Per protocol, the SVR12 rate was 90%, including 91% in GT1 (GT1a n = 18/18, GT1b n = 2/4), 89% in GT3 (n = 59/66) and 100% in GT6 (n = 3/3). SVR12 in participants with GT3 and cirrhosis was 90%. No predictors of non-SVR12 were identified. There were 4 serious AEs including 1 death and 3 hepatic decompensation events. NS5A resistance-associated substitutions detected at baseline did not affect SVR12. CONCLUSIONS: This real-world study confirms high efficacy of SOF/VEL/VOX for the treatment of difficult-to-cure NS5A-inhibitor experienced patients, including those with GT3 and cirrhosis. Treatment was well tolerated in most; however, serious AEs can occur in those with advanced liver disease.

Bloodstream Infection Risk, Incidence, and Deaths for Hospitalized Patients during Coronavirus Disease Pandemic.

Hospital-acquired infections are emerging major concurrent conditions during the coronavirus disease (COVID-19) pandemic. We conducted a retrospective review of hospitalizations during March‒October 2020 of adults tested by reverse transcription PCR for severe acute respiratory syndrome coronavirus 2. We evaluated associations of COVID-19 diagnosis with risk for laboratory-confirmed bloodstream infections (LCBIs, primary outcome), time to LCBI, and risk for death by using logistic and competing risks regression with adjustment for relevant covariates. A total of 10,848 patients were included in the analysis: 918 (8.5%) were given a diagnosis of COVID-19, and 232 (2.1%) had LCBIs during their hospitalization. Of these patients, 58 (25%) were classified as having central line‒associated bloodstream infections. After adjusting for covariates, COVID-19‒positive status was associated with higher risk for LCBI and death. Reinforcement of infection control practices should be implemented in COVID-19 wards, and review of superiority and inferiority ranking methods by National Healthcare Safety Network criteria might be needed.

Hepatitis C virus cure before hepatocellular carcinoma diagnosis is associated with improved survival.

The impact of hepatitis C virus (HCV) cure on survival in patients with HCV-related hepatocellular carcinoma (HCC) has been examined, although many studies have been subject to survivor treatment selection bias. We assessed the impact of HCV cure before HCC diagnosis on overall survival. Patients with HCV-related HCC at three referral hospitals in Australia were included retrospectively (January 2008 to December 2019). The risk of death following HCC diagnosis among patients who achieved HCV cure before HCC diagnosis was compared to patients who were viraemic at diagnosis. Among 422 patients with HCV-related HCC, 101 (24%) achieved HCV cure before HCC diagnosis, 37 with interferon (IFN) and 64 with direct-acting antiviral (DAA) therapy. Patients with HCV cure were more likely to have no cirrhosis or Child-Pugh A liver disease (83% vs. 66%, p = .002), surveillance detection (71% vs. 48%, p < .001), HCC stage O or A (64% vs. 45%, p < .001) and receive curative initial HCC management (51% vs. 28%, p < .001), compared with patients who were viraemic at diagnosis. The 5-year overall survival was 51% in the HCV cure group and 22% in the viraemic group. In adjusted analysis, risk of death was lower in patients with HCV cure before HCC diagnosis compared with patients who were viraemic at diagnosis (adjusted hazard ratio: 0.63; 95% CI: 0.44-0.91; p = .013). Patients with HCV-related HCC who have achieved HCV cure before HCC diagnosis have improved overall survival compared with patients who were viraemic at diagnosis.

Screening Emergency Admissions at Risk of Chronic Hepatitis C (SEARCH) to diagnose or 're-diagnose' infections is effective in Australia.

The World Health Organization has set ambitious viral hepatitis elimination targets; however, difficulties in identifying and engaging patients remain. The emergency visit is an opportunity for enhanced linkage to care (LTC). We assessed the effectiveness of an automated Emergency Department (ED) screening service in identifying patients with hepatitis C (HCV) and achieving LTC. A retrospective evaluation was undertaken, analysing the first 5000 patients screened through an automatic Australian service termed 'Screening Emergency Admissions at Risk of Chronic Hepatitis' (SEARCH). Screening was performed for those recommended in the Australian national testing policy, specifically overseas born (OB) and Aboriginal or Torres Strait Islanders (ATSI). Healthcare worker education, patient information materials and opt-out informed consent were used to test sera already collected for biochemistry assays. 5000 of 5801 (86.2%) consecutive eligible patients were screened (OB: 4778, ATSI: 222) from 14 093 ED presentations. HCV antibody was positive in 181 patients (3.6%); 51 (1.0%) were HCV RNA positive. Of 51 HCV RNA-positive patients, 12 were new diagnoses, 32 were 're-diagnoses' (aware but lost to follow-up [LTFU]), and 7 were previously known but treatment contraindicated. LTC was successful in 38 viraemic patients (7 deceased, 4 LTFU, 1 treatment ineligible and 1 declined). Of RNA-negative patients, 75 were previously treated and 49 had presumed spontaneous clearance. Opt-out consent was acceptable to all patients and staff involved. ED screening can lead to additional diagnosing and 're-diagnosing' of HCV, with high rates of LTC. Opt-out consent and automation removed major obstacles to testing.

Australian recommendations for the management of hepatocellular carcinoma: a consensus statement.

INTRODUCTION: Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths both globally and in Australia. Surveillance for HCC in at-risk populations allows diagnosis at an early stage, when potentially curable. However, most Australians diagnosed with HCC die of the cancer or of liver disease. In the changing landscape of HCC management, unique challenges may lead to clinical practice variation. As a result, there is a need to identify best practice management of HCC in an Australian context. This consensus statement has been developed for health professionals involved in the care of adult patients with HCC in Australia. It is applicable to specialists, general medical practitioners, nurses, health coordinators and hospital administrators. METHODS AND RECOMMENDATIONS: This statement has been developed by specialists in hepatology, radiology, surgery, oncology, palliative care, and primary care, including medical practitioners and nurses. The statement addresses four main areas relevant to HCC management: epidemiology and incidence, diagnosis, treatment, and patient management. A modified Delphi process was used to reach consensus on 31 recommendations. Principal recommendations include the adoption of surveillance strategies, use of multidisciplinary meetings, diagnosis, treatment options and patient management. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: This consensus statement will simplify HCC patient management and reduce clinical variation. Ultimately, this should result in better outcomes for patients with HCC.

All-cause hepatocellular carcinoma survival in the era of direct-acting antiviral therapy.

BACKGROUND AND AIM: Hepatitis C virus (HCV) cure with direct-acting antiviral (DAA) therapy improves survival in patients with HCV-related hepatocellular carcinoma (HCC). We hypothesized that HCV-HCC survival has increased in the DAA era, more than other aetiologies of HCC. We aimed to evaluate survival following HCC diagnosis in the pre-DAA and DAA eras, across each aetiology of HCC. METHODS: Patients with HCC at three tertiary referral hospitals were included retrospectively (January 2008 to December 2019). Patients were categorized as HCV-HCC, hepatitis B virus (HBV)-HCC, or non-viral HCC. For each aetiology, the risk of death following incident HCC among patients diagnosed in the DAA era (2015-2019) was compared with patients diagnosed in the pre-DAA era (2008-2014). RESULTS: Among 1161 patients, there were 422 (36%) patients with HCV-HCC, 227 (20%) with HBV-HCC, and 512 (44%) with non-viral HCC. In adjusted analysis, the risk of death was lower in patients with HCV-HCC diagnosed in 2015-2019, compared with patients diagnosed in 2008-2014 (adjusted hazard ratio [aHR]: 0.68; 95% confidence interval [CI]: 0.52-0.89; P = 0.005). In contrast, there was no difference in the risk of death between time periods for patients with HBV-HCC (HR: 0.91; 95% CI: 0.64-1.29; P = 0.602) or non-viral HCC on adjusted analysis (aHR: 0.92; 95% CI: 0.74-1.15; P = 0.476). Although patients with HBV-HCC had better survival compared with patients with HCV-HCC in 2008-2014 (aHR: 0.74; 95% CI: 0.55-0.98; P = 0.037), this difference disappeared in 2015-2019 (aHR: 1.26; 95% CI: 0.90-1.77; P = 0.175). CONCLUSIONS: Hepatitis C virus-related HCC survival has increased in the DAA era, whereas adjusted survival remained stable for HBV-HCC and non-viral HCC.

Hepatocellular carcinoma incidence post direct-acting antivirals in hepatitis C-related advanced fibrosis/cirrhosis patients in Australia.

BACKGROUND: Despite efficacy in HCV eradication, direct-acting antiviral (DAA) therapy has raised controversies around their impact on hepatocellular carcinoma (HCC) incidence. Herein we reported the first Australian data on HCC incidence in DAA-treated HCV patients with advanced fibrosis/cirrhosis. METHODS: We conducted a retrospective single center study of DAA-treated HCV patients with advanced fibrosis/cirrhosis from April 2015 to December 2017. Patients with prior HCC were included if they had complete response to HCC treatment. RESULTS: Among 138 patients who completed DAA therapy, 133 (96.4%) achieved sustained virologic response (median follow-up 23.8 months). Ten had prior HCC and 5/10 (50.0%) developed recurrence, while de novo HCC developed in 7/128 (5.5%). Median time from DAA to HCC diagnosis was 34 weeks in recurrent HCC vs. de novo 52 weeks (P = 0.159). In patients with prior HCC, those with recurrence (vs. without) had shorter median time between last HCC treatment and DAA (12 vs. 164 weeks, P < 0.001). On bivariate analysis, failed sustained virologic response at 12 weeks (SVR12) (P = 0.011), platelets (P = 0.005), model for end-stage liver disease (MELD) score (P = 0.029), alpha fetoprotein (AFP) (P = 0.013), and prior HCC (P < 0.001) were associated with HCC post-DAA. On multivariate analysis, significant factors were prior HCC (OR = 4.80; 95% CI: 1.47-48.50; P = 0.010), failed SVR12 (OR = 2.83; 95% CI: 1.71-16.30; P = 0.016) and platelets (OR = 0.97; 95% CI: 0.95-0.99; P = 0.009). CONCLUSIONS: Our study demonstrates a high incidence of recurrent HCC in HCV patients with advanced fibrosis/cirrhosis treated with DAA. Factors associated with HCC development post-DAA were more advanced liver disease, failed SVR12 and prior HCC, with higher rates of recurrence in those who started DAA earlier.

Hepatitis C treatment for difficult to access populations: can telementoring (as distinct from telemedicine) help?

BACKGROUND: Although hepatitis C virus (HCV) infection is curable, treatment of difficult to access populations (DTAP) presents unique challenges. Project ECHO (PE) (Extension for Community Healthcare Outcomes) is a telementoring programme adopted to support clinicians treating DTAP. AIMS: To determine if the PE model supports primary care clinicians treating HCV and to compare cohort of PE patients with those in a tertiary liver clinic (TLC). METHODS: Weekly PE group video conferences were conducted. Clinical information, laboratory indices, psychosocial elements and treatment outcomes, including sustained virological response (SVR) data were recorded in the first 100 consecutive cases and retrospectively compared to 100 consecutive patients seen at a TLC from July 2016 to April 2017. RESULTS: Some patient characteristics were similar between PE and TLC: gender (72% vs 75% male; P = 0.23), median age (45 vs 50; P = 0.344) and the proportion of treatment naïve patients (95.0% vs 90.9%). Treatment for HCV was commenced in 78% of the PE patients and 81% of the TLC patients; 67/68 of the TLC patients and 60/61 PE patients with virological follow up who completed treatment and attended follow up have confirmed SVR. PE patients are more likely to have ongoing substance use (44% vs 17% P < 0.001), be active intravenous drug users (32% vs 17%; P < 0.001) and polysubstance abusers (26% vs 7%; P < 0.001) and were more likely to be taking opioid substitution therapy (74% vs 20%; P < 0.001). Indigenous patients were three times more greatly represented in PE (15% vs 5%; P = 0.018). CONCLUSION: PE is an effective model to support primary healthcare providers treating HCV in DTAP with similar rates of treatment uptake and SVR compared to patients in TLC.

Efficacy and Safety of Mycophenolate Mofetil in Patients With Autoimmune Hepatitis and Suboptimal Outcomes After Standard Therapy.

BACKGROUND & AIMS: Little is known about outcomes of patients with autoimmune hepatitis (AIH) who have a suboptimal outcome to standard therapy and are then given mycophenolate mofetil as rescue therapy. We evaluated the efficacy and safety of mycophenolate mofetil in patients failed by or intolerant to corticosteroids, with or without azathioprine. METHODS: We performed a retrospective study of 105 patients with AIH who received mycophenolate mofetil therapy after an inadequate response or intolerance to standard therapy (98% received combination therapy with corticosteroids plus thiopurines). Patients were recruited from 17 liver clinics via the Australian Liver Association Clinical Research Network. We reviewed records for baseline demographic features and characteristics of liver disease, initial therapy, mycophenolate mofetil indications, treatment outcome, and side effects. The primary outcome was biochemical remission, defined as levels of alanine and aspartate transferase and IgG level within the normal reference range, with or without normal liver histology within the first 2 years of treatment. RESULTS: The indication for mycophenolate mofetil therapy was non-response to treatment for 40% of cases and intolerance to therapy for 60%. Overall, 63 patients (60%) achieved biochemical remission following a median 12 weeks treatment with mycophenolate mofetil. The proportion of patients who achieved biochemical remission was similar between patients receiving mycophenolate mofetil for non-response to standard therapy (57%) and patients with intolerance to standard therapy (62%). However, a lower proportion of patients with cirrhosis achieved biochemical remission (47%) than patients without cirrhosis (6%) (P = .07). Serious adverse events occurred in 3 patients (2.7%) including 1 death, and 10 patients (9.2%) discontinued mycophenolate mofetil because of adverse events. CONCLUSION: In this retrospective study of patients with AIH who received mycophenolate mofetil as a rescue therapy, we found the drug to be well tolerated and moderately effective, inducing biochemical remission in 60% of subjects. Rates of response are lower and rates of infection are higher in patients with AIH and cirrhosis. Prospective studies of mycophenolate mofetil are warranted for this population.

Mother-to-child transmission of hepatitis B: Examining viral cut-offs, maternal HBsAg serology and infant testing.

BACKGROUND & AIMS: Antipartum antiviral therapy in the setting of high viral load is recommended to prevent mother-to-child transmission of hepatitis B although recommended viral load cut-offs vary. Quantitative HBsAg has been proposed as an alternative screening strategy to identify high viral load in this setting. Guidelines suggest testing all infants for vaccine response and infection. We set out to re-examine viral load cut-offs; the predictive value of quantitative HBsAg and the need for follow-up infant testing in our cohort. METHODS: A retrospective cohort study of 469 HBsAg positive mother-baby pairs from 2 tertiary hospitals in Sydney was performed. Antiviral therapy (lamivudine or tenofovir disoproxil fumarate) was offered to women with viral load ≥6 log10  IU/mL (high) from 32 weeks gestation. Transmission and vaccine response was analysed according to viral load. The utility of quantitative HBsAg in identifying high viral load was examined. RESULTS: Mother-to-child transmission only occurred in setting of high viral load, in 0.85% (1/117) of those who received antiviral therapy and in 8.66% (2/23) of those who chose not to. Quantitative HBsAg did not accurately identify high-risk mothers HBV DNA ≥6 log10  IU/mL. Successful infant vaccine response was 98.7% overall, and 99.4% when viral load was <6 log10  IU/mL. CONCLUSION: Antiviral therapy initiated at 32 weeks when maternal viral load is ≥6 log10  IU/mL almost completely abrogates transmission. Quantitative HBsAg does not reliably predict high viral load. When maternal viral load is <6 log10  IU/mL, high vaccine efficacy and zero transmission suggests testing infants is of little value.