Patient perspectives about treatment preferences for obesity with complications.

Objective: Obesity and many of its comorbidities can be improved by nutritional therapy, lifestyle modification, pharmacotherapy, and surgical intervention. Relatively little is known about patients' preferences for the range of obesity treatments. The present study was undertaken to identify factors that may influence these preferences. By evaluating patient-preferred treatment options and factors influencing patients, treatment adherence and efficacy may be improved. Our objective was to identify factors that influence patient preferences and subsequent choice of obesity treatment among those seeking treatment for obesity-related complications. Methods: Participatory action research, using purposeful sampling, was used to recruit 33 patients with obesity complications. Recruitment took place in specialist clinics for non-alcoholic fatty liver disease, diabetes, hypertension, and chronic kidney disease. Sixteen males and 17 females aged 18-70 years with a BMI>35 kg/m2 were recruited. Prior to the interview, participants watched a 60-min video explaining nutritional therapies, pharmacotherapies, and surgical therapies in equipoise. Data were collected in one-to-one semi-structured interviews using zoom or the telephone; reflective thematic analysis was used. Results: Four themes emerged: 1) structural factors, 2) autonomy, 3) interaction with formal care, and 4) the emotional and physical consequences of obesity. 39% of participants preferred nutritional therapy with support from medical professionals. 27% chose bariatric surgery. 24% chose pharmacotherapy alone, while 6% chose pharmacotherapy combined with nutritional therapy, 3% of participants wanted no intervention. Conclusion: The challenges can be addressed by increasing support for healthcare professionals toward enhancing both their knowledge and the health literacy of patients. Future research should focus on improving access to treatment pathways for patients as well as developing health literacy programs and educational programs for healthcare professionals.

Incidence and Impact of Non-alcoholic Fatty Liver Disease (NAFLD) in Patients with Adenocarcinoma of the Esophagus Treated with Curative Intent.

BACKGROUND AND AIMS: Esophageal adenocarcinoma (EAC) is associated with visceral obesity (VO). Non-alcoholic fatty liver disease (NAFLD) is common within this phenotype; however, its incidence and clinical significance in EAC have not been studied. STUDY DESIGN: A total of 559 patients with hepatic stetatosis (HS) defined by unenhanced CT were enrolled. In a sub-study, in 140 consecutive patients a liver biopsy was taken intraoperatively to study HS and non-alcoholic steatohepatitis (NASH). Postoperative complications were defined as per the Esophageal Complications Consensus Group (ECCG). Liver biochemistry was measured peri-operatively, with an ALT > 5 defined as acute liver injury (ALI). Mann-Whitney U test or Fisher's exact test was utilized and the Kaplan-Meier method for survival. RESULTS: 42% (n = 234/559) of patients had CT-defined HS. HS was associated with VO in 56% of cases, metabolic syndrome (Met S) in 37% and type 2 diabetes in 25%, compared with 44, 21, and 15% in non-HS patients (p < 0.01). Pathologic HS was present in 32% (45/140) and graded as mild, moderate, and severe in 73, 24, and 3%, respectively, with NASH reported in 16% and indefinite/borderline NASH in 42% of HS cases. Postoperative ALI was similar (p = 0.88) in both HS (10%) and non-HS cohorts (11%). Operative complication severity was similar in both cohorts. 5-yr survival was 53% (HS) vs 50% (p = 0.890). CONCLUSION: This study establishes for the first time the incidence and clinical impact of NAFLD in EAC patients undergoing surgery and highlights no major impact on oncologic outcomes, nor in the severity of complications.

Differential Effects of Dietary versus Exercise Intervention on Intrahepatic MAIT Cells and Histological Features of NAFLD.

BACKGROUND: Mucosal-associated invariant T (MAIT) cells promote inflammation in obesity and are implicated in the progression of non-alcoholic fatty liver disease (NAFLD). However, as the intrahepatic MAIT cell response to lifestyle intervention in NAFLD has not been investigated, this work aimed to examine circulating and intrahepatic MAIT cell populations in patients with NAFLD, after either 12 weeks of dietary intervention (DI) or aerobic exercise intervention (EI). METHODS: Multicolour flow cytometry was used to immunophenotype circulating and intrahepatic MAIT cells and measure MAIT cell expression (median fluorescence intensity, MFI) of the activation marker CD69 and apoptotic marker CD95. Liver histology, clinical parameters, and MAIT cell populations were assessed at baseline (T0) and following completion (T1) of DI or EI. RESULTS: Forty-five patients completed the study. DI participants showed decreased median (interquartile range) expression of the activation marker CD69 on circulating MAIT cells (T0: 104 (134) versus T1 27 (114) MFI; p = 0.0353) and improvements in histological steatosis grade post-intervention. EI participants showed increased expression of the apoptotic marker CD95, both in circulating (T0: 1549 (888) versus T1: 2563 (1371) MFI; p = 0.0043) and intrahepatic MAIT cells (T0: 2724 (862) versus T1: 3117 (1622) MFI; p = 0.0269). Moreover, the percentage of intrahepatic MAIT cells significantly decreased after EI (T0: 11.1 (14.4) versus T1: 5.3 (9.3)%; p = 0.0029), in conjunction with significant improvements in fibrosis stage and hepatocyte ballooning. CONCLUSIONS: These data demonstrate independent benefits from dietary and exercise intervention and suggest a role for intrahepatic MAIT cells in the observed histological improvements in NAFLD.

Prevalence of frailty in patients with non-cirrhotic non-alcoholic fatty liver disease.

OBJECTIVE: End-stage chronic liver disease is associated with accelerated ageing and increased frailty. Frailty measures have provided clinical utility in identifying patients at increased risk of poor health outcomes, including those awaiting liver transplantation. However, there is limited data on the prevalence and severity of frailty in patients with non-cirrhotic non-alcoholic fatty liver disease (NAFLD). The aim of this study was to evaluate the prevalence of frailty and prefrailty in patients with non-cirrhotic NAFLD and correlate with severity of liver disease. DESIGN: A cross-sectional analysis of functional and laboratory frailty assessments, including the Fried frailty index (FFI), a self-reported frailty index (SRFI) and a lab-based frailty index (FI-LAB), was performed in a cohort of 109 patients with NAFLD, and results compared with fibrosis staging based on transient elastography. RESULTS: Patients with NAFLD had a high prevalence of prefrailty and frailty, with a median SRFI score of 0.18 (IQR: 0.18), FFI of 1 (IQR: 1) and FI-LAB of 0.18 (IQR: 0.12). Using the SRFI, 45% of F0/F1 patients were classified as prefrail and 20% were classified as frail, while in F2/F3 patients this increased to 36% and 41%, respectively. SRFI, 30 s sit-to-stand and FI-LAB scores increased with increasing liver fibrosis stages (p=0.001, 0.006 and <0.001, respectively). On multivariate linear regression, female gender was identified as a significant predictor of elevated frailty scores. CONCLUSION: This study identifies a high prevalence of frailty in individuals with non-cirrhotic NAFLD. Addressing frailty through early rehabilitation interventions may reduce overall morbidity and mortality in this population.

Cardiac Magnetic Resonance at 3.0 T in Patients With C282Y Homozygous Hereditary Hemochromatosis: Superiority of Radial and Circumferential Strain Over Cardiac T2* Measurements at Baseline and at Post Venesection Follow-up.

BACKGROUND: Iron-overload cardiomyopathy initially manifests with diastolic dysfunction and can progress to dilated cardiomyopathy if untreated. Previous studies have shown that patients with primary and secondary hemochromatosis can have subclinical left ventricle dysfunction with abnormalities on strain imaging. This study aimed to evaluate the relationship between cardiac T2* values and myocardial-wall strain in patients with hereditary hemochromatosis (HH) at the time of diagnosis and after a course of venesection treatment. MATERIALS AND METHODS: Baseline cardiac magnetic resonance (CMR) at 3 T was performed in 19 patients with newly diagnosed HH with elevated serum ferritin levels and repeated after a course of treatment with venesection. Quantitative T2* mapping and strain analysis were performed offline using dedicated relaxometry fitting and feature-tracking software. RESULTS: The majority (84%) of patients had normal baseline myocardial T2* values (mean 19.3 ms, range 8.9 to 31.2 ms), which improved significantly after venesection (mean 24.1 ms, range 11 to 38.1 ms) ( P =0.021). Mean global radial strain significantly improved from 25.0 (range: 15.6 to 32.9) to 28.3 (range: 19.8 to 35.8) ( P =0.001) and mean global circumferential strain improved, decreasing from -15.7 (range: -11.1 to -19.2) to -17.1 (range: -13.0 to -20.1) ( P =0.001). CONCLUSION: Patients with HH may have normal T2* values in the presence of subclinical left ventricle dysfunction, which can be detected by abnormal radial and circumferential strain. As strain imaging improves following venesection in HH, it may serve as a useful biomarker to guide treatment.

Exercising in the COVID-19 era: implications in non-alcoholic fatty liver disease (NAFLD).

COVID-19 is a major public health pandemic. Risk factors for severe infection and poorer outcomes include cardiovascular disease, obesity, type 2 diabetes mellitus and non-alcoholic fatty liver disease (NAFLD). Lifestyle interventions, including diet and physical activity modifications, are the current recommended treatment for NAFLD. In this communication, the authors discuss the crossover link between NAFLD and severe COVID-19 infection and the impact of essential public health measures to suppress the spread of COVID-19 on exercise and physical activity participation in patients with NAFLD. The future of exercise prescription and the potential use of digital technology in addressing NAFLD healthcare needs in the COVID-19 era are also explored.

Improvement in cognitive impairment following a 12-week aerobic exercise intervention in individuals with non-cirrhotic chronic hepatitis C.

Cognitive impairment occurs in 30%-50% of patients with non-cirrhotic chronic hepatitis C virus (HCV) infection. Exercise is beneficial in preventing and treating cognitive impairment and cardiometabolic abnormalities in many chronic inflammatory diseases, but there are few studies investigating the impact of exercise in HCV infection. The study aimed to assess the effect of a 12-week aerobic exercise intervention on cognition and extrahepatic manifestations in individuals with HCV. In this nonrandomized controlled pilot study, individuals with HCV participated in a 12-week aerobic exercise intervention. Outcome measures included cognition (Montreal Cognitive Assessment [MOCA], Trail Making Test A & B [TMT-A; TMT-B], Digit Symbol Test [DST]), cardiorespiratory fitness (estimated V˙O2max ), physical activity (accelerometry), anthropometry, quality of life (depression; fatigue; sleep quality) and biochemical markers. Outcomes were assessed at baseline (T0), intervention completion (T1) and 12 weeks after intervention completion (T2). Thirty-one patients completed the study (exercise group n = 13, control group n = 18). In the exercise group, cognition improved at T1 in the TMT-A (31% mean improvement, p = 0.019), TMT-B (15% mean improvement, p = 0.012) time and MOCA (14% mean improvement, p ≤ 0.001). These improvements were not maintained at T2. Depression (p = 0.038), sleep quality (p = 0.002), fatigue (p = 0.037) and estimated V˙O2max (7.8 mL kg-1  min-1 [22%] mean increase, p = 0.004) also improved at T1. In conclusion, this study demonstrates the benefits of a 12-week aerobic exercise intervention in improving cognition, quality of life and cardiorespiratory fitness in individuals with HCV. Larger studies are needed to confirm these findings and strategies for continued exercise engagement in individuals with HCV are warranted for sustained benefits.

Determinants of Physical Activity Engagement in Patients With Nonalcoholic Fatty Liver Disease: The Need for an Individualized Approach to Lifestyle Interventions.

OBJECTIVES: Physical activity (PA) is an important non-pharmacological treatment for non-alcoholic fatty liver disease (NAFLD). This study investigated the determinants of PA engagement and awareness of the World Health Organization (WHO) PA guidelines in patients with NAFLD. METHODS: Study participants were 101 patients with NAFLD (median age: 54 [IQR = 15] y; 53 men and 48 women) who completed 4 questionnaires: (1) a PA guideline awareness questionnaire; (2) a PA questionnaire assessing PA levels; and (3) 2 questionnaires assessing perceived barriers and motivators for engaging in PA. Binary logistic regression was performed to assess predictors of PA levels. RESULTS: Twenty-four percent of participants correctly identified the recommended WHO weekly PA guidelines, and 39% adhered to the guidelines. Lack of willpower, time, and energy were the most frequently cited barrier domains. Scores for lack of willpower (odds ratio [OR] = 1.445, 95% CI = 1.088-1.919) and lack of resources (OR = 1.378, 95% CI = 1.003-1.893), and reporting 3 or more "significant" barrier domains (OR = 5.348, 95% CI = 1.792-15.873) were significant predictors of PA levels. Maintaining health and fitness was the most cited motivator domain and was a significant predictor (OR = 2.551, 95% CI = 1.253-5.208) of PA levels. CONCLUSIONS: This study highlights the lack of awareness of the WHO PA guidelines and the key determinants of PA participation in patients with NAFLD. Determinants of PA should be identified at the individual level to create a personalized approach for PA maintenance for people with NAFLD to promote lifelong participation in PA. IMPACT: This study closes a gap in the published data on the determinants of PA engagement in patients with NAFLD. LAY SUMMARY: Physical inactivity is the fourth leading cause of global mortality and contributes to many chronic inflammatory diseases, including obesity, type 2 diabetes, cardiovascular disease, and nonalcoholic fatty liver disease (NAFLD). People with NAFLD engage in less physical activity compared with people who are healthy, and this study provides new information that clinicians can use to help these patients increase their physical activity participation.

Improvement in histological endpoints of MAFLD following a 12-week aerobic exercise intervention.

BACKGROUND: Lifestyle interventions are the primary treatment for metabolic (dysfunction) associated fatty liver disease (MAFLD). However, the histological and cardiometabolic effects of aerobic exercise in MAFLD remain unclear. AIMS: To assess the effects of a 12-week aerobic exercise intervention on histological and cardiometabolic endpoints in MAFLD. METHODS: Patients with biopsy-confirmed MAFLD participated in a 12-week aerobic exercise intervention. Liver histology, cardiorespiratory fitness (estimated V̇O2max ), physical activity, anthropometry and biochemical markers were assessed at baseline, intervention completion, and 12 and 52 weeks after intervention completion. RESULTS: Twenty-four patients completed the exercise intervention (exercise group n = 16, control group n = 8). In the exercise group, 12 weeks of aerobic exercise reduced fibrosis and hepatocyte ballooning by one stage in 58% (P = 0.034) and 67% (P = 0.020) of patients, with no changes in steatosis (P = 1.000), lobular inflammation (P = 0.739) or NAFLD activity score (P = 0.172). Estimated V̇O2max increased by 17% compared to the control group (P = 0.027) but this level of improvement was not maintained at 12 or 52 weeks after the intervention. Patients with fibrosis and ballooning improvement increased estimated V̇O2max by 25% (P = 0.020) and 26% (P = 0.010), respectively. Anthropometric reductions including body mass (P = 0.038), waist circumference (P = 0.015) and fat mass (P = 0.007) were also observed, but no patient achieved 7%-10% weight loss. CONCLUSION: This study highlights the potential benefits of a 12-week aerobic exercise intervention in improving histological endpoints of MAFLD. The development of strategies to ensure continued engagement in aerobic exercise in MAFLD are needed.

Development and relative validation of a short food frequency questionnaire for assessing dietary intakes of non-alcoholic fatty liver disease patients.

PURPOSE: This work aimed to design and validate a novel short food frequency questionnaire (SFFQ) to assess habitual intakes of food items related to non-alcoholic fatty liver disease (NAFLD) in a cohort of European patients. METHODS: A 48-item SFFQ was created, with questions from existing FFQs and expert knowledge, emphasizing foods and nutrients implicated in NAFLD pathogenesis. Consenting, fibroscan-diagnosed, NAFLD patients completed the SFFQ during a short interview and were asked to complete a 4-day diet diary (4DDD) at home for return by mail. Nutritional intakes were assessed utilizing the myfood24™ food composition dataset and estimated energy requirements (EER) were calculated using sex-, age- and weight-specific equations. Agreement between the dietary instruments was assessed by Spearman correlations and Bland Altman analysis. RESULTS: Fifty-five patients completed both the SFFQ and the 4DDD within 30 weeks; 42 (76%) were diagnosed with simple steatosis, whereas 13 (24%) had biopsy-proven steatohepatitis; the majority were overweight or obese, with a median (25th; 75th percentile) BMI of 33.2 kg/m2 (29.3; 36.0). Reported energy intakes were well below EER with a median intake of 73% of requirements, suggesting widespread under-reporting. Significant correlations were observed between sugar (r = 0.408, P = 0.002), fat (r = 0.44, P = 0.001), fruits (r = 0.51, P = 0.0001) and vegetables (r = 0.40, P = 0.0024) measurements by the SFFQ and 4DDD. Bland Altman plots with regression analysis demonstrated broad comparability with the 4DDD for intakes of fat (bias - 13.8 g/day) and sugar (bias + 12.9 g/day). CONCLUSIONS: A novel SFFQ designed to be minimally burdensome to participants was effective at assessing dietary intakes in NAFLD patients.

Opt-out screening for HIV, hepatitis B and hepatitis C: observational study of screening acceptance, yield and treatment outcomes.

BACKGROUND: We initiated an emergency department (ED) opt-out screening programme for HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) at our hospital in Dublin, Ireland. The objective of this study was to determine screening acceptance, yield and the impact on follow-up care. METHODS: From July 2015 through June 2018, ED patients who underwent phlebotomy and could consent to testing were tested for HIV, HBV and HCV using an opt-out approach. We examined acceptance of screening, linkage to care, treatment and viral suppression using screening programme data and electronic health records. The duration of follow-up ranged from 1 to 36 months. RESULTS: Over the 36-month study period, there were 140 550 ED patient visits, of whom 88 854 (63.2%, 95% CI 63.0% to 63.5%) underwent phlebotomy and 54 817 (61.7%, 95% CI 61.4% to 62.0%) accepted screening for HIV, HBV and HCV, representing 41 535 individual patients. 2202 of these patients had a positive test result. Of these, 267 (12.1%, 95% CI 10.8% to 13.6%) were newly diagnosed with an infection and 1762 (80.0%, 95% CI 78.3% to 81.7%) had known diagnoses. There were 38 new HIV, 47 new HBV and 182 new HCV diagnoses. 81.5% (95% CI 74.9% to 87.0%) of known patients who were not linked were relinked to care after screening. Of the new diagnoses, 86.2% (95% CI 80.4 to 90.8%) were linked to care. CONCLUSION: Although high proportions of patients had known diagnoses, our programme was able to identify many new infected patients and link them to care, as well as relink patients with known diagnoses who had been lost to follow-up.

Improvements in cardiac function detected using echocardiography in patients with hereditary haemochromatosis.

BACKGROUND: Hereditary haemochromatosis is often not diagnosed until adulthood. Iron overload cardiomyopathy initially results in diastolic dysfunction and can result in arrhythmias and irreversible cardiac failure if untreated. The aim of this study was to investigate whether patients with newly diagnosed hereditary haemochromatosis without signs of heart failure exhibit subclinical alterations of cardiac function and to determine if cardiac function improved after 1 year of venesection. METHODS: Baseline echocardiography was performed on 25 patients with newly diagnosed hereditary haemochromatosis with elevated serum ferritin levels. The test was repeated after 1 year of treatment with venesection. Tissue Doppler imaging (TDI) and deformation (strain) imaging using speckle tracking were performed. Left atrial force was measured according to the Newtonian principle, in which force (dynes) = mass × acceleration. Left atrial force was calculated by the Manning method expressed as ρ × 0.53 × mitral annular orifice area × (peak A velocity)2. RESULTS: Radial strain showed a significant improvement after 1 year of venesection (increase from 38.8 to 52.6). The LAF showed a significant decrease after 1 year of venesection (median decrease = 0.6 (IQR 0, 1.60), p = 0.0004). Iso-volumetric relaxation time (IVRT) decreased significantly in patients after 1 year of venesection (decrease from 107.4 ± 16.2 to 97.68 ± 15.4 ms, p (0.0187)). CONCLUSION: Among all measurements, radial strain, IVRT and left atrial force were shown to significantly improve following a 1-year course of venesection, suggesting that these parameters could be used to identify subclinical cardiac dysfunction in patients with iron overload secondary to hereditary haemochromatosis and to guide intensification of venesection therapy.

Pharmacist-led pre-treatment assessment, management and outcomes in a Hepatitis C treatment patient cohort.

Background Medication reconciliation and drug-drug interaction management represent important patient safety processes completed by pharmacists as part of Hepatitis C patient care. Objectives To describe the pharmacist-led interventions of medication reconciliation and drug-drug interaction assessment, grading and management in a real-world Hepatitis C treatment cohort and to assesses the impact on patient outcomes. Setting Two Hepatitis C hospital outpatient clinics at St. James's Hospital, Dublin. Method Patients treated with Hepatitis C direct acting anti-viral agents between December 2014 and February 2017 were included in this retrospective cohort study. The study employed a standardised medication reconciliation proforma and drug-drug interaction reference list. Main outcome measures Analyse medication variances identified during pharmacist-led medication reconciliation. Assess the prevalence, type and severity of drug-drug interactions between direct acting anti-virals and co-medications. Assess the rate of prescriber acceptance of the pharmacist-developed drug-drug interaction management strategies. Results Among the 300 patients in this study, medication reconciliation identified 1543 co-medications, with 71% of patients prescribed co-medications which were subject to a potential drug-drug interaction. Drug-drug interaction assessments assigned a rating of severe to 68 interaction episodes. At least one co-medication was stopped during treatment in 25% of patients to facilitate drug-drug interaction management. Pharmacist proposed management recommendations were accepted by prescribers in 96.9% of cases. The sustained virological response rate among the cohort was 92.7%. Conclusions In this Hepatitis C pre-treatment pharmacist assessment analysis, a significant number of medication reconciliation variances and clinically significant drug-drug interactions were identified which present unique and important patient safety risks. Pharmacist-led management strategies aided the achievement of optimum treatment response while promoting patient safety and antiviral stewardship.

Real-world safety and effectiveness of ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin in hepatitis C virus genotype 1- and 4-infected patients with diverse comorbidities and comedications: A pooled analysis of post-marketing observational studies from 13 countries.

Ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin (OBV/PTV/r ± DSV ± RBV) regimens show high efficacy and good tolerability in clinical trials for chronic hepatitis C virus (HCV) genotypes (GT) 1 or 4. To evaluate whether these results translate to clinical practice, data were pooled from observational studies across 13 countries. Treatment-naïve or -experienced patients, with or without cirrhosis, received OBV/PTV/r ± DSV ± RBV according to approved local labels and clinical practice. Sustained virologic response at post-treatment Week 12 (SVR12), adverse events (AEs) and comedication management were assessed for patients initiating treatment before 1 June 2017. The safety population included 3850 patients who received ≥1 dose of study drug. The core population (N = 3808) further excluded patients with unknown GT or cirrhosis status, or who received off-label treatment. Patients had HCV GT1a (n = 732; 19%), GT1b (n = 2619; 69%) or GT4 (n = 457; 12%). In 3546 patients with sufficient follow-up data at post-treatment Week 12, the SVR12 rate was 96% (n/N = 3401/3546 [95% CI 95.2-96.5]). In patients with or without cirrhosis, SVR12 was comparable (96%). In patients with HCV GT1a, GT1b or GT4, SVR12 rates were 93%, 97% and 94%. In GT1b-infected patients with planned treatment for 8 weeks, SVR12 was 96%. In patients with ≥1 comorbidity (67%), SVR12 was 95%. 58% of patients received ≥1 comedication, and there was minimal impact on SVR12 rates using comedications for peptic ulcers and gastro-esophageal reflux disease, statins, antipsychotics or antiepileptics. Most comedications were maintained during treatment although 58% of patients changed their statin medication. AEs and serious AEs occurred in 26% and 3% of patients. Post-baseline Grade 3-4 laboratory abnormalities were rare (<3%), and discontinuation rates were low (<4%). Real-world evidence confirms the effectiveness of OBV/PTV/r ± DSV ± RBV in patients with HCV GT1 or GT4, regardless of common comorbidities or comedications, and is consistent with clinical trial results. Adverse safety outcomes may be limited by underreporting in the real-world setting.

Restrictions for reimbursement of interferon-free direct-acting antiviral drugs for HCV infection in Europe.

All-oral direct-acting antiviral drugs (DAAs) for hepatitis C virus, which have response rates of 95% or more, represent a major clinical advance. However, the high list price of DAAs has led many governments to restrict their reimbursement. We reviewed the availability of, and national criteria for, interferon-free DAA reimbursement among countries in the European Union and European Economic Area, and Switzerland. Reimbursement documentation was reviewed between Nov 18, 2016, and Aug 1, 2017. Primary outcomes were fibrosis stage, drug or alcohol use, prescriber type, and HIV co-infection restrictions. Among the 35 European countries and jurisdictions included, the most commonly reimbursed DAA was ombitasvir, paritaprevir, and ritonavir, with dasabuvir, and with or without ribavirin (33 [94%] countries and jurisdictions). 16 (46%) countries and jurisdictions required patients to have fibrosis at stage F2 or higher, 29 (83%) had no listed restrictions based on drug or alcohol use, 33 (94%) required a specialist prescriber, and 34 (97%) had no additional restrictions for people co-infected with HIV and hepatitis C virus. These findings have implications for meeting WHO targets, with evidence of some countries not following the 2016 hepatitis C virus treatment guidelines by the European Association for the Study of Liver.

Disease outcomes in a cohort of women in Ireland infected by hepatitis C-contaminated anti-D immunoglobulin during 1970s.

BACKGROUND & AIM: In the mid-1990s, a group of Rh negative women was diagnosed with hepatitis C virus (HCV) genotype 1b infection, following administration of contaminated anti-D immunoglobulin in 1977-79. We aimed to describe their disease history and estimate the effect of selected host and treatment factors on disease progression. METHODS: We conducted a cohort study on the women infected with HCV. Information was collected from records at seven HCV treatment centres on demographics, treatment and health outcomes up to the 31st December 2013. We calculated cumulative incidence, case fatality, and sub hazard ratios (SHR) for disease progression using competing risks regression. RESULTS: Six hundred and eighty-two patients were included in the study. Among the chronically infected patients (n=374), 35% completed interferon-based antiviral treatment; 42% of whom had a sustained virological response. At the end of 2013, 19%, 1.9%, and 4.9% of chronically infected patients had developed cirrhosis, hepatocellular carcinoma, and liver-related death, respectively, compared with 10%, 0.8%, and 2.4% at the end of 2008. At the end of 2013, 321 (86%) of the chronically infected patients remained alive, 247 (77%) of whom were still chronically infected. Factors associated with increased cirrhosis rates included high alcohol intake (aSHR=4.9 [2.5-9.5]) and diabetes mellitus (aSHR=5.0 [2.9-8.8]). CONCLUSIONS: Development of liver-related outcomes accelerated with time, with the risk of cirrhosis, hepatocellular carcinoma, and liver-related death doubling in the last five years of follow-up, particularly in women with high alcohol consumption and diabetes mellitus. We recommend that patients with chronic HCV infection be advised of the additive harmful effect of alcohol, and that data be collected on this cohort after a further five years to analyse the effect of subsequent antiviral treatment during this rapidly evolving period in HCV treatment history. LAY SUMMARY: In the mid-1990s, a group of women were diagnosed with chronic hepatitis C virus (HCV) infection following receipt of contaminated anti-D immunoglobulin between 1977 and 1979 in Ireland. Seventy-two (19%) developed cirrhosis and 18 had died from liver-related causes (5%) after 36years of infection. Disease progression accelerated in the last five years of follow-up, particularly in women with diabetes mellitus and high alcohol consumption. We recommend that patients with chronic HCV infection be advised of the additive harmful effect of high alcohol consumption.

Outcomes from a large 10 year hepatitis C treatment programme in people who inject drugs: No effect of recent or former injecting drug use on treatment adherence or therapeutic response.

BACKGROUND AND AIMS: People who inject drugs (PWID) are historically viewed as having "difficult to treat" hepatitis C disease, with perceived inferior treatment adherence and outcomes, and concerns regarding reinfection risk. We evaluated for differences in treatment adherence and response to Peginterferon-alfa-2a/Ribavirin (Peg-IFNα/RBV) in a large urban cohort with and without a history of remote or recent injection drug use. METHODS: Patient data was retrospectively reviewed for 1000 consecutive patients-608 former (no injecting drug use for 6 months of therapy), 85 recent (injecting drug use within 6 months) PWID, and 307 non-drug users who were treated for chronic hepatitis C with Peg-IFNα/RBV. The groups were compared for baseline characteristics, treatment adherence, and outcome. RESULTS: There was no significant difference in treatment non-adherence between the groups (8.4% in PWID vs 6.8% in non-PWIDs; RR = 1.23, CI 0.76-1.99). The overall SVR rate in PWID (64.2%) was not different from non-PWIDs (60.9%) [RR = 1.05, 95% CI 0.95-1.17]. There was no significant difference in SVR rates between the groups controlling for genotype (48.4% vs 48.4% for genotype 1; 74.9 vs 73.3% for genotype 3). Former and recent PWID had similar adherence rates. CONCLUSIONS: PWID have comparable treatment adherence and SVR rates when compared to non-drug users treated with Peg-IFNα/RBV. These data support a public health strategy of HCV treatment and eradication in PWID in the DAA era.

Effectiveness of triple therapy with direct-acting antivirals for hepatitis C genotype 1 infection: application of propensity score matching in a national HCV treatment registry.

BACKGROUND: Observational studies are used to measure the effectiveness of an intervention in non-experimental, real world scenarios at the population level and are recognised as an important component of the evidence pyramid. Such data can be accrued through prospective cohort studies and a patient registry is a proven method for this type of study. The national hepatitis C (HCV) registry was established in Ireland in 2012 with the aim of monitoring the clinical and economic outcomes from new, high cost regimens for the treatment of HCV infection. A sustained virological response (SVR) 24 weeks following completion of therapy with interferon-containing regimens is considered a cure. Non-randomisation in these studies can result in confounding or selection bias. Propensity score (PS) matching is one of a number of statistical tools that can be used to mitigate the effects of confounding in observational studies. METHODS: We analysed the data of 309 patients who underwent triple therapy treatment with telaprevir (TPV) in combination with pegylated-interferon and ribavirin (PR) or boceprevir (BOC)/PR between June 2012 and December 2014. The decision to initiate treatment and the selection of the treatment regimen was at the discretion of the physician. To adjust for confounding, three approaches to propensity score matching were assessed Adjusted sustained-virological response rates (SVR), odds ratios, p-values and 95% confidence intervals were calculated from the three PS matched dataset. RESULTS: Prior to matching, the unadjusted sustained virological response rates 24 weeks after treatment complete (SVR24) were 74% (n = 158/215) and 61% (n = 57/94) for telaprevir/PR and boceprevir/PR, respectively. After matching, adjusted SVR24 rates were between 73-74% and 60-61% for telaprevir/PR and boceprevir/PR, respectively. CONCLUSION: Efficacy rates were comparable with those reported in pivotal clinical trials and real world studies. After adjusting for confounding, we conclude that there was no difference in treatment effect after PS matching. The small sample size limits the conclusions that can be made about the effect of PS matching. Propensity score adjustment remains a tool that can be applied to future analysis, however, we suggest, where possible, using a larger sample size in order to reduce the uncertainty around the outcomes.

Do disparities between populations in randomized controlled trials and the real world lead to differences in outcomes?

AIM: To conduct a systematic review investigating reasons for the disparity between the efficacy and effectiveness rates reported in randomized controlled trials (RCTs) and observational studies of direct-acting antiviral treatment regimens licensed for use in genotype1 hepatitis C virus-infected individuals. METHODS: This systematic review was conducted in accordance with the criteria of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses group. RESULTS: Statistically significant (p < 0.05) differences in the baseline demographics and sustained virological response rates were observed between RCT and observational studies. CONCLUSION: In order for outcomes from RCTs to be generalizable to the real world, greater consideration needs to be taken to include patient populations that are more representative of those awaiting treatment in the clinical setting.