Hepatitis C Virus Antiviral Drug Resistance and Salvage Therapy Outcomes Across Australia.

Background: Hepatitis C virus (HCV) infection can now be cured with well-tolerated direct-acting antiviral (DAA) therapy. However, a potential barrier to HCV elimination is the emergence of resistance-associated substitutions (RASs) that reduce the efficacy of antiviral drugs, but real-world studies assessing the clinical impact of RASs are limited. Here, an analysis of the impact of RASs on retreatment outcomes for different salvage regimens in patients nationally who failed first-line DAA therapy is reported. Methods: We collected data from 363 Australian patients who failed first-line DAA therapy, including: age, sex, fibrosis stage, HCV genotype, NS3/NS5A/NS5B RASs, details of failed first-line regimen, subsequent salvage regimens, and treatment outcome. Results: Of 240 patients who were initially retreated as per protocol, 210 (87.5%) achieved sustained virologic response (SVR) and 30 (12.5%) relapsed or did not respond. The SVR rate for salvage regimens that included sofosbuvir/velpatasvir/voxilaprevir was 94.3% (n = 140), sofosbuvir/velpatasvir 75.0% (n = 52), elbasvir/grazoprevir 81.6% (n = 38), and glecaprevir/pibrentasvir 84.6% (n = 13). NS5A RASs were present in 71.0% (n = 210) of patients who achieved SVR and in 66.7% (n = 30) of patients who subsequently relapsed. NS3 RASs were detected in 20 patients (20%) in the SVR group and 1 patient in the relapse group. NS5B RASs were observed in only 3 patients. Cirrhosis was a predictor of relapse after retreatment, as was previous treatment with sofosbuvir/velpatasvir. Conclusions: In our cohort, the SVR rate for sofosbuvir/velpatasvir/voxilaprevir was higher than with other salvage regimens. The presence of NS5A, NS5B, or NS3 RASs did not appear to negatively influence retreatment outcomes.

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.

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 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.

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.

The MOWER (middle of the week everyone gets a re-chart) pilot study: reducing in-hospital charting error with a multi-intervention.

BACKGROUND: Medication charting errors occur often and can be harmful for patients. Interventions to improve charting errors have demonstrated some success particularly if the intervention uses multiple approaches including an education component. The aim of this pilot study was to determine whether a multi-faceted intervention, including education of junior doctors and weekday re-charting could reduce in-hospital charting error. METHODS: Medication charts (n = 579) of all patients admitted to the medical ward of a medium sized regionally-based hospital in Australia over nine months (baseline and during intervention) were inspected for errors. The intervention ran for three months and involved implementation of a National Inpatient Medication Chart targeted error tool with eight targeted charting requirements which was used for visual reminders in the ward and training of junior doctors. In addition, mid-weekly re-charting (MOWER) was performed by a senior and junior doctor team. RESULTS: The mean number of charting requirement errors significantly reduced during the intervention by 26% from 4.6 ± 1.3 to 3.4 ± 1.7 per chart (p < 0.001). Re-chart errors reduced on average by 50% (4.4 ± 1.4 to 2.2 ± 1.7 per chart, p < 0.001) and primary (initial) charts by 20% (4.6 ± 1.3 to 3.7 ± 1.5 per chart, p < 0.001) during the intervention. Failing to provide indication information for a drug, prescriber name, and failing to use generic rather than brand names were the categories with the most errors at baseline and also showed the largest error reductions during the intervention. CONCLUSIONS: A multi-intervention including education of junior doctors, visual reminders and midweek re-charting are effective in reducing the rate of charting errors. We advise that a larger study is now conducted using the same multi-intervention strategy in different ward settings to evaluate feasibility and sustainability of this intervention.

Management and outcomes following an acute coronary event in patients with chronic heart failure 1999-2007.

AIM: The outcome of patients with chronic heart failure (CHF) following an ischaemic event is poorly understood. We evaluated the management and outcomes of CHF patients presenting with an acute coronary syndrome (ACS) and explored changes in outcomes over time. METHOD AND RESULTS: A total of 5556 patients enrolled in the Australia-New Zealand population of the Global Registry of Acute Coronary Events (GRACE) between 1999 and 2007 were included. Patients with CHF (n = 609) were compared with those without CHF (n = 4947). Patients with CHF were on average 10 years older, were more likely to be female, had more co-morbidities and cardiac risk factors, and were more likely to have a prior history of angina, myocardial infarction, and revascularization by coronary artery bypass graft (CABG) when compared with those without CHF. CHF was associated with a substantial increase in in-hospital renal failure [odds ratio (OR) 1.76, 95% confidence interval (CI) 1.15-2.71], readmission post-discharge (OR 1.47, 95% CI 1.17-1.90), and 6-month mortality (OR 2.25, 95% CI 1.55-3.27). Over the 9 year study period, in-hospital and 6 month mortality in those with CHF declined by absolute rates of 7.5% and 14%, respectively. This was temporally associated with an increase in prescription of thienopyridines, beta-blockers, statins, and angiotensin II receptor blockers, increased rates of coronary angiography, and 31.8% absolute increase in referral rates for cardiac rehabilitation. CONCLUSIONS: Acute coronary syndrome patients with pre-existing CHF are a very high risk group and carry a disproportionate mortality burden. Encouragingly, there was a marked temporal improvement in outcomes over a 9 year period with an increase in evidence-based treatments and secondary preventative measures.

Autoimmune hepatitis following infliximab therapy for ankylosing spondylitis.

Autoimmune hepatitis is a rare but increasingly recognised serious complication of treatment with the tumour necrosis factor-alpha (TNF-alpha) blocking agent, infliximab. This report adds to the small but growing number of articles describing this significant adverse effect. Baseline liver function should be routinely tested in all patients receiving anti-TNF-alpha agents, and periodic monitoring for the development of hepatitis is important.

The length of superficial temporal artery biopsies.

BACKGROUND: To compare temporal artery biopsy specimen lengths from a tertiary care and a community hospital in New South Wales to recommended clinical guidelines in suspected giant cell arteritis. DESIGN: A retrospective observational study of all patients who underwent temporal artery biopsy at Bathurst Base Hospital (BBH) and Royal Prince Alfred Hospital (RPAH) over a 5-year period. METHODS: Patients who underwent temporal artery biopsy during the 5-year period were identified using computerized hospital databases. A retrospective chart review was carried out on all cases. Data were collected regarding patient age, patient sex, length of biopsy specimen, histopathological results and surgical team carrying out the biopsy. RESULTS: During the 5-year period, 157 temporal artery biopsies were carried out at both hospitals, with 38/157(24%) at BBH and 119/157 (76%) at RPAH. There was no significant difference in biopsy length at the two hospitals. The mean specimen length at BBH was 12.1 mm compared with 11.7 mm at RPAH (t=0.35; P=0.73). At RPAH, there was no significant difference in specimen length between the surgical specialties carrying out the biopsy (ANOVA F=1.37; P=0.26). Specimens of length 20 mm or greater were 2.8 times more likely to show features of giant cell arteritis than those less than 20 mm. CONCLUSION: The mean length of temporal artery biopsy specimens at both hospitals was substantially shorter than recommended guidelines of a minimum 20 mm. We recommend all surgeons carrying out temporal artery biopsies ensure a specimen of sufficient length is obtained.