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.

Prior hospital attendances in deceased Australian patients with alcohol-related liver disease: a multicentre project.

BACKGROUND AND AIMS: To establish the hospital visit history of patients who die with alcohol-related liver disease (ArLD). To determine if patients with ArLD present to hospital early or in the terminal phase of their disease. METHODS: Retrospective cohort study of patients with a history of ArLD who died as an inpatient at three tertiary Western Australian hospitals from February 2015 to February 2017. Hospital records were reviewed to identify the number and cause of emergency department (ED), inpatient and outpatient attendances in all Western Australian public hospitals in the 10 years prior to death. RESULTS: One hundred fifty-nine patients (23% female) had a total of 753 ED, 3535 outpatient appointments, 1602 hospital admissions and 10 755 admission days. Twelve months prior to death, 82% of patients had a public hospital contact and 74% an admission. Patients who had their first hospital contact within 12 months prior to death were significantly more likely to have a liver-related cause of death (P < 0.01). Aboriginal and Torres Strait Islander patients (15% of cohort) died at a significantly younger age (M = 49.2, SD = 10.5 years) than non-Aboriginal and Torres Strait Islander patients (M = 59.9, SD = 10.2 years, P < 0.01). Despite having more ED attendances and hospital admissions, Aboriginal and Torres Strait Islander patients had significantly less (P = 0.04) outpatient appointments (Mdn = 5.5, interquartile range [IQR] = 1-18 vs Mdn = 11, IQR = 3-33). CONCLUSIONS: Most patients with ArLD have multiple early attendances, which present an opportunity for early interventions. There are missed opportunities for Aboriginal and Torres Strait Islander patients for outpatient hospital engagement.

Critical Role of General Practitioners in Preventing Readmission Following Emergency Department Alcohol Screening and Brief Intervention Management of Alcohol-Related Problems.

INTRODUCTION/OBJECTIVES: Alcohol screening and brief intervention (ASBI) strategies are useful in general practice (GP) but their effectiveness in the emergency department (ED) is unclear. We evaluated the effect of ED-based ASBI on re-admissions. METHODS: 453 ED subjects exceeding the threshold score on the three-item Alcohol Use Disorders Identification Test-Consumption (females 3+: males 4+) were randomized. We conducted telephone follow-up at 1 and 3 months and recorded hospital events 6 months pre- and post-enrolment. RESULTS: Median weekly alcohol use was 20 standard drinks (interquartile range (IQR) 9-45) on enrolment. After 3 months, 247 (55%) were able to be re-interviewed. Median alcohol use was 10 drinks (IQR 4-26). Six months later, subjects receiving ED-ASBI without GP follow-up had significantly greater risk of re-admission compared with those having GP follow-up (OR 1.68, 95%CI 1.06-2.65; P = .028). CONCLUSIONS: ASBI reduces the likelihood of ED re-presentation only in subjects who have GP follow-up. The study has been registered as a clinical trial (Australian and New Zealand Clinical Trial Registry ACTRN12617001254381).

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.

Detection of HFE Haemochromatosis in the clinic and community using standard erythrocyte tests.

Detection of HFE Haemochromatosis (HH) is challenging in the absence of clinical features. HH subjects have elevated erythrocyte parameters compared to those without HH, but it remains unclear how this could be applied in clinical practice. Thus, we determined the sensitivity, specificity and clinical utility of erythrocyte parameters in 144 HH subjects with (n = 122) or without (n = 22) clinical and/or biochemical expression of iron overload, 1844 general population controls, and 700 chronic disease subjects. For both expressing and non-expressing HH subjects, the mean pre- and post-phlebotomy values of mean cell volume (MCV) and mean cell haemoglobin (MCH) were always significantly higher when compared to all other groups and demonstrated excellent diagnostic utility for detection of HH in men and women (AUROC 0.83-0.9; maximal sensitivity and specificity 82% and 78%) using cut-off values for MCV >91 fL or MCH >31 pg, respectively. Between 34 and 62% of all HH subjects would be detected, and <4% of all non-HH subjects would undergo unnecessary testing, if those with MCV or MCH values >94 fL or 32.2 pg, respectively, were evaluated.

Alcoholic liver disease - the extent of the problem and what you can do about it.

It takes upwards of ten years for alcohol-related liver disease to progress from fatty liver through fibrosis to cirrhosis to acute on chronic liver failure. This process is silent and symptom free and can easily be missed in primary care, usually presenting with advanced cirrhosis. At this late stage, management consists of expert supportive care, with prompt identification and treatment of bleeding, sepsis and renal problems, as well as support to change behaviour and stop harmful alcohol consumption. There are opportunities to improve care by bringing liver care everywhere up to the standards of the best liver units, as detailed in the Lancet Commission report. We also need a fundamental rethink of the technologies and approaches used in primary care to detect and intervene in liver disease at a much earlier stage. However, the most effective and cost-effective measure would be a proper evidence-based alcohol strategy.

Current treatment options for alcohol-related liver disease.

PURPOSE OF REVIEW: The burden of alcohol on global health is increasing, and there is a strong relationship between population alcohol consumption and liver-related deaths. As alcohol-related liver disease (ArLD) often develops with no signs or symptoms, the prevention of liver disease relies on the recognition of harmful drinking and screening of those patients at risk for early markers of liver disease. RECENT FINDINGS: A robust method of screening patients at risk of ArLD is essential. Once a patient develops ArLD, abstinence and early recognition of its complications are keys to improving outcomes. Corticosteroids remain the mainstay treatment in alcoholic hepatitis pending the results from large multicentre trials. More recently, there has been an increased interest in the use of rifaximin and albumin in various settings of ArLD. SUMMARY: Advances in the treatment of ArLD and its complications, such as alcoholic hepatitis, will allow a greater proportion of patients chance for their liver to recover. However, new strategies to detect and intervene in those patients at higher risk of ArLD are likely to have the greatest overall impact.

Elevated serum ferritin - what should GPs know?

BACKGROUND: Elevated serum ferritin is commonly encountered in general practice. Ninety percent of elevated serum ferritin is due to noniron overload conditions, where venesection therapy is not the treatment of choice. OBJECTIVE: This article aims to outline the role of the Australian Red Cross Blood Service Therapeutic Venesection program, to clarify the interpretation of the HFE gene test and iron studies, and to describe the steps in evaluating a patient with elevated serum ferritin. DISCUSSION: After exclusion of hereditary haemochromatosis, investigation of elevated serum ferritin involves identifying alcohol consumption, metabolic syndrome, obesity, diabetes, liver disease, malignancy, infection or inflammation as causative factors. Referral to a gastroenterologist, haematologist or physician with an interest in iron overload is appropriate if serum ferritin is >1000 µg/L or if the cause of elevated serum ferritin is still unclear.

Predicting patient tolerance of endoscopy with conscious sedation.

OBJECTIVE: To evaluate the adequacy of benzodiazepine/opiate sedation for endoscopic procedures and to identify patient and procedure characteristics that may predict poor procedural tolerance. MATERIALS AND METHODS: A total of 2155 patients who underwent sedated gastroscopy, colonoscopy or flexible sigmoidoscopy between January and December 2007, participated in the prospective evaluation of procedural tolerance and the procedures were evaluated using three questionnaires completed by the patient, endoscopist and assisting nurse. Perception of procedural tolerance was scored using a 100-point visual analog scale (VAS), 0: very good to 100: very poorly. In order to identify patient and procedure characteristics predictive of poor procedural tolerance, we compared 10% of patients who tolerated the procedure least well with the remaining patients. RESULTS: About 216 (10%) of 2155 patients gave a VAS score of >30, and were compared with the 1939 patients with a VAS <30. Patients who tolerated the procedure least well (VAS ≥30) were more likely female [odds ratio (OR) 2.8, 95% confidence interval 1.9-4.1], had colonoscopy (OR 2.9, 1.8-4.5) or had a training endoscopist perform the procedure (OR 3.2, 2.2-4.8). Patients with BMI ≥35 were also more likely to have a VAS ≥30 (p < 0.01). Sedation type and American Society of Anesthesiologists grade had no significant effect on patient tolerance. CONCLUSIONS: A majority of patients tolerate endoscopic procedures well when benzodiazepine/opiate sedation is used. Accurately identifying the minority who tolerate these procedures less well remains difficult.

Autochthonous hepatitis E in Southwest England: natural history, complications and seasonal variation, and hepatitis E virus IgG seroprevalence in blood donors, the elderly and patients with chronic liver disease.

AIMS: To report the natural history of autochthonous hepatitis E and hepatitis E virus (HEV) IgG seroprevalence in Southwest England. METHODS: Patients with unexplained hepatitis were tested for hepatitis E and cases followed until recovery or death. Five hundred blood donors, 336 individuals over the age of 60 years and 126 patients with chronic liver disease were tested for HEV IgG. RESULTS: Forty cases of autochthonous hepatitis E (genotype 3) were identified. Hepatitis E was anicteric in 25% of cases and usually caused a self-limiting hepatitis predominantly in elderly Caucasian males. Six of 40 had a significant complication and three patients died, two of who had previously undiagnosed cirrhosis. Hepatitis E shows a seasonal variation with peaks in the spring and summer and no cases in November and December. HEV IgG prevalence increases with age, is more common in men and is 16% in blood donors, 13% in patients with chronic liver disease and 25% in individuals over 60 years. CONCLUSION: Autochthonous hepatitis E is more common than previously recognized, and should be considered in the differential diagnosis in patients with hepatitis, whatever their age or travel history. It carries a significant morbidity and when seen in the context of chronic liver disease carries an adverse prognosis.