Shift in disparities in hepatitis C treatment from interferon to DAA era: A population-based cohort study.

We evaluated the shift in the characteristics of people who received interferon-based hepatitis C virus (HCV) treatments and those who received recently introduced direct-acting antivirals (DAAs) in British Columbia (BC), Canada. The BC Hepatitis Testers Cohort includes 1.5 million individuals tested for HCV or HIV, or reported cases of hepatitis B and active tuberculosis in BC from 1990 to 2013 linked to medical visits, hospitalization, cancer, prescription drugs and mortality data. This analysis included all patients who filled at least one prescription for HCV treatment until 31 July 2015. HCV treatments were classified as older interferon-based treatments including pegylated interferon/ribavirin (PegIFN/RBV) with/without boceprevir or telaprevir, DAAs with RBV or PegIFN/RBV, and newer interferon-free DAAs. Of 11 886 people treated for HCV between 2000 and 2015, 1164 (9.8%) received interferon-free DAAs (ledipasvir/sofosbuvir: n=1075; 92.4%), while 452 (3.8%) received a combination of DAAs and RBV or PegIFN/RBV. Compared to those receiving interferon-based treatment, people with HIV co-infection (adjusted odds ratio [aOR]: 2.96, 95% CI: 2.31-3.81), cirrhosis (aOR: 1.77, 95% CI: 1.45-2.15), decompensated cirrhosis (aOR: 1.72, 95% CI: 1.31-2.28), diabetes (aOR: 1.30, 95% CI: 1.10-1.54), a history of injection drug use (aOR: 1.34, 95% CI: 1.09-1.65) and opioid substitution therapy (aOR: 1.30, 95% CI: 1.01-1.67) were more likely to receive interferon-free DAAs. Socio-economically marginalized individuals were significantly less likely (most deprived vs most privileged: aOR: 0.71, 95% CI: 0.58-0.87) to receive DAAs. In conclusion, there is a shift in prescription of new HCV treatments to previously excluded groups (eg HIV-co-infected), although gaps remain for the socio-economically marginalized populations.

Open-label study of faldaprevir plus peginterferon and ribavirin in hepatitis C virus genotype 1-infected patients who failed placebo plus peginterferon and ribavirin.

Faldaprevir, a hepatitis C virus (HCV) NS3/4A protease inhibitor, was evaluated in HCV genotype 1-infected patients who failed peginterferon and ribavirin (PegIFN/RBV) treatment during one of three prior faldaprevir trials. Patients who received placebo plus PegIFN/RBV and had virological failure during a prior trial were enrolled and treated in two cohorts: prior relapsers (n = 43) and prior nonresponders (null responders, partial responders and patients with breakthrough; n = 75). Both cohorts received faldaprevir 240 mg once daily plus PegIFN/RBV for 24 weeks. Prior relapsers with early treatment success (ETS; HCV RNA <25 IU/mL detectable or undetectable at week 4 and <25 IU/mL undetectable at week 8) stopped treatment at week 24. Others received PegIFN/RBV through week 48. The primary efficacy endpoint was sustained virological response (HCV RNA <25 IU/mL undetectable) 12 weeks post treatment (SVR12). More prior nonresponders than prior relapsers had baseline HCV RNA ≥ 800,000 IU/mL (80% vs 58%) and a non-CC IL28B genotype (91% vs 70%). Rates of SVR12 (95% CI) were 95.3% (89.1, 100.0) among prior relapsers and 54.7% (43.4, 65.9) among prior nonresponders; corresponding ETS rates were 97.7% and 65.3%. Adverse events led to faldaprevir discontinuations in 3% of patients. The most common Division of AIDS Grade ≥ 2 adverse events were anaemia (13%), nausea (10%) and hyperbilirubinaemia (9%). In conclusion, faldaprevir plus PegIFN/RBV achieved clinically meaningful SVR12 rates in patients who failed PegIFN/RBV in a prior trial, with response rates higher among prior relapsers than among prior nonresponders. The adverse event profile was consistent with the known safety profile of faldaprevir.

Trends in health care utilization and costs attributable to hepatocellular carcinoma, 2002-2009: a population-based cohort study.

BACKGROUND: The incidence of hepatocellular carcinoma (hcc) and the complexity of its diagnosis and treatment are increasing. We estimated trends in net health care utilization, costs of care attributable to hcc in Ontario, and rate ratios of resource use at various stages of care. METHODS: This population-based retrospective cohort study identified hcc patients and non-cancer control subjects, and health care resource utilization between 2002 and 2009. Generalized estimating equations were then used to estimate net health care utilization (hcc patients vs. the matched control subjects) and net costs of care attributable to hcc. Generalized linear models were used to analyze rate ratios of resource use. RESULTS: We identified 2832 hcc patients and 2808 matched control subjects. In comparison with the control subjects, hcc patients generally used a greater number of health care services. Overall, the mean net cost of care per 30 patient-days (2013 Canadian dollars) attributable to outpatient visits and hospitalizations was highest in the pre-diagnosis (1 year before diagnosis), initial (1st year after diagnosis), and end-of-life (last 6 months before death, short-term survivors) phases. Mean net homecare costs were highest in the end-of-life phase (long-term survivors). In the end-of-life phase (short-term survivors), mean net costs attributable to outpatient visits and total services significantly increased to $14,220 from $1,547 and to $33,121 from $14,450 (2008-2009 and 2002-2003 respectively). CONCLUSIONS: In hcc, our study found increasing resource use and net costs of care, particularly in the end-of-life phase among short-term survivors. Our findings offer a basis for resource allocation decisions in the area of cancer prevention and control.

Solid organ transplant recipients: clinical considerations in the application of exercise.

Over 100 000 solid organ transplants are performed worldwide each year and this has a significant impact on physical function and quality of life. However, the capacity for exercise in solid-organ recipients is reduced. Regular physical activity improves most of the indices of fitness in these patients but, with few exceptions, they do not reach the values seen in healthy controls. The reason for the 40-60% reduction in maximal exercise capacity is not clear; the disease process, need for life long immunosuppression and sedentary lifestyle all contribute. The interaction between exercise and immunosuppressing medication merits research as does the specifics of the exercise prescription for these patients. This paper reviews important features of this rapidly expanding group of patients and suggests clinical considerations in the application of exercise in this population.

Influence of intra-oral sensory impairment by anaesthesia on food comminution and mixing in dentate subjects.

Sensory input from sensory receptors regarding food morsels can affect jaw motor behaviours during mastication. The aim was to clarify the effects of intra-oral sensory input on the food-comminuting and food-mixing capacities of dentate subjects. Eleven dentate subjects without sensory dysfunction in their oro-facial region participated in this study. Local anaesthesia was achieved on the periodontal structures and on the oral mucosa of the subjects' preferred chewing side by injecting a lidocaine solution with adrenalin. At baseline (control) and after anaesthesia, data on the subjects' food-comminuting and food-mixing capacities were gathered. The food-comminuting capacity was quantified by measuring the degree of pulverisation of peanuts (objective hardness; 45.3 [Newton, N]) after a prescribed 20 chewing strokes. The food-mixing capacity was measured as the degree of immixture of a two-coloured paraffin wax cube after 10 chewing strokes. Wax cubes of three different hardness levels were used (soft, medium and hard: 20.3, 32.6 and 75.5 [N], respectively) and were chewed in random order. After anaesthesia, the subjects' food-comminuting capacity significantly decreased (P < 0.001), as did the food-mixing capacity for each hardness level of the wax cubes (P < 0.01). A significant correlation was observed between the objective hardness values and the anaesthesia effects for the food-mixing capacity (P < 0.05), indicating that after anaesthesia, deterioration of the mixing capacity increased as the hardness increased. In conclusion, intra-oral sensory input can affect both food-comminuting and food-mixing capacities.

Compact 100Gb/s DP-QPSK integrated receiver module employing three-dimensional assembly technology.

We demonstrate a compact 100 Gbit/s DP-QPSK receiver module that is only 18 mm (W) x 16 mm (D) x 2.8 mm (H). The module size is reduced by using a ball grid array (BGA) package with three-dimensional assembly technology and by applying a heterogeneous integrated PLC. Error-free DP-QPSK signal demodulation is successfully demonstrated.

Hepatic embolotherapy in interventional oncology: technology, techniques, and applications.

Embolotherapy continues to play a growing role in the management of primary and secondary hepatic malignancies. In this review article, we examine the basis of therapy with a focus on neovascularization, which makes treatments via the hepatic artery possible. An overview of the three generations of embolic and therapeutic agents follows. The techniques, technologies, and complications of bland embolization, transarterial chemoembolization, drug-eluting beads, and selective internal radiotherapy are covered to give the reader an overview of this exciting field in interventional radiology.

Two-colour chewing gum mixing ability: digitalisation and spatial heterogeneity analysis.

Many techniques are available to assess masticatory performance, but not all are appropriate for every population. A proxy suitable for elderly persons suffering from dementia was lacking, and a two-colour chewing gum mixing ability test was investigated for this purpose. A fully automated digital analysis algorithm was applied to a mixing ability test using two-coloured gum samples in a stepwise increased number of chewing cycles protocol (Experiment 1: n = 14; seven men, 19-63 years), a test-retest assessment (Experiment 2: n = 10; four men, 20-49 years) and compared to an established wax cubes mixing ability test (Experiment 3: n = 13; 0 men, 21-31 years). Data were analysed with repeated measures anova (Experiment 1), the calculation of the intraclass correlation coefficient (ICC; Experiment 2) and Spearman's rho correlation coefficient (Experiment 3). The method was sensitive to increasing numbers of chewing cycles (F5,65 = 57·270, P = 0·000) and reliable in the test-retest (ICC value of 0·714, P = 0·004). There was no significant correlation between the two-coloured gum test and the wax cubes test. The two-coloured gum mixing ability test was able to adequately assess masticatory function and is recommended for use in a population of elderly persons with dementia.

Pneumocystis pneumonia in solid organ transplant recipients: not yet an infection of the past.

BACKGROUND: Solid organ transplant (SOT) recipients are at risk for Pneumocystis pneumonia (PCP), especially in the first year post transplant. Although trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis substantially decreases this risk, there is little data or consensus on optimal duration of prophylaxis. Consequently, there is lack of standardization of prophylaxis duration (3 months to lifelong, depending on organ group) in SOT programs. METHODS: We performed a retrospective chart review of all cases of confirmed PCP, in adult kidney, pancreas, liver, and lung transplant recipients from 2001 to 2011 in our SOT program. RESULTS: Of 1241 patients followed in our clinic (657 kidney, 44 kidney/pancreas, 436 liver, and 104 lung or heart/lung), a total of 14 PCP cases were identified in 2 kidney, 1 kidney/pancreas, 5 liver, 5 single lung, and 1 heart/lung transplant recipient. At the time of PCP diagnosis, immunosuppression in most cases consisted of prednisone, tacrolimus, and mycophenolate mofetil (79% of patients), and 53% had previously received TMP-SMX for prophylaxis. None were on PCP prophylaxis at the time of illness onset. PCP occurred early in all 5 liver transplant recipients and in 1 kidney transplant recipient, none of whom had ever received prophylaxis (17-204 days post transplant). Of those who had received 6 months of prophylaxis (1 kidney, 1 kidney/pancreas), PCP occurred at 846 and 4778 days, respectively. Late onset PCP occurred in lung recipients who had received 12 months of prophylaxis (lung 645-1414 days, heart/lung 1583 days post transplant). Five patients had experienced acute rejection and 6 patients had cytomegalovirus (CMV) viremia on average 59 and 204 days preceding PCP, respectively. Three deaths (1 liver, 2 lung) were thought to be directly related to complications of PCP. CONCLUSION: Our experience with late PCP cases in lung transplant recipients receiving only 1 year of prophylaxis lends support to prolonged PCP prophylaxis in this group. Given the number of patients who had experienced an acute rejection episode or CMV disease preceding PCP in non-lung SOT recipients, consideration should be given to re-institution of PCP prophylaxis for a period of time after these events in kidney, kidney/pancreas, and liver transplant recipients.

High-dose frequency beta-interferons increase the risk of liver test abnormalities in multiple sclerosis: a longitudinal study.

BACKGROUND: Post-marketing studies and case reports have linked beta-interferon (IFNß) treatment with liver enzyme abnormalities and liver injuries in patients with multiple sclerosis (MS). Few predictors of risk exist. OBJECTIVE: We investigated the effect of IFNß and other patient characteristics on levels of the liver enzyme, alanine aminotransferase (ALT). METHOD: Repeated ALT test results were reviewed retrospectively for 1064 MS patients prescribed an IFNß as their first immunomodulatory drug. Liver enzyme abnormality was defined as an ALT elevation twice the upper limit of normal (≥ 2 ULN). The Generalized Estimating Equation (GEE) was used to analyze the effect of age (≤ 35, >35-40, >40-45, >45 years), gender, disease duration, IFNß product, and duration of treatment (≤ 5, >5-15, >15-40, >40 months) on de novo liver enzyme abnormality. RESULTS: Over a mean treatment period of 38.7 months (SD=34.9), 12.4% (95/766) of MS patients developed de novo liver enzyme abnormality. Multivariable GEE results showed a dose frequency response effect of IFNßs on liver enzyme abnormality: OR=3.8(95% CI: 1.6-9.2) for IFNß-1a 44 µg SC, and OR=3.4 (95% CI: 1.5-7.9) for IFNß-1b 250 µg SC compared with the lower frequency IFNß-1a 30 µg IM. Younger age (≤ 40 years), male gender, and ≤ 15 months of IFNß exposure were also independent predictors. CONCLUSION: A dose frequency response effect was observed, with high-frequency IFNßs having the greatest risk. The first 15 months of treatment, men, and younger patients were also associated with elevated risk. Regular ALT monitoring in MS patients appears prudent; long-term consequences of ALT elevations should be further investigated.

Spectrophotometer and ultrasound evaluation of late toxicity following breast-cancer radiotherapy.

PURPOSE: Radiation-induced normal-tissue toxicities are common, complex, and distressing side effects that affect 90% of patients receiving breast-cancer radiotherapy and 40% of patients post radiotherapy. In this study, the authors investigated the use of spectrophotometry and ultrasound to quantitatively measure radiation-induced skin discoloration and subcutaneous-tissue fibrosis. The study's purpose is to determine whether skin discoloration correlates with the development of fibrosis in breast-cancer radiotherapy. METHODS: Eighteen breast-cancer patients were enrolled in our initial study. All patients were previously treated with a standard course of radiation, and the median follow-up time was 22 months. The treated and untreated breasts were scanned with a spectrophotometer and an ultrasound. Two spectrophotometer parameters-melanin and erythema indices-were used to quantitatively assess skin discoloration. Two ultrasound parameters-skin thickness and Pearson coefficient of the hypodermis-were used to quantitatively assess severity of fibrosis. These measurements were correlated with clinical assessments (RTOG late morbidity scores). RESULTS: Significant measurement differences between the treated and contralateral breasts were observed among all patients: 27.3% mean increase in skin thickness (p < 0.001), 34.1% mean decrease in Pearson coefficient (p < 0.001), 27.3% mean increase in melanin (p < 0.001), and 22.6% mean increase in erythema (p < 0.001). All parameters except skin thickness correlated with RTOG scores. A moderate correlation exists between melanin and erythema; however, spectrophotometer parameters do not correlate with ultrasound parameters. CONCLUSIONS: Spectrophotometry and quantitative ultrasound are objective tools that assess radiation-induced tissue injury. Spectrophotometer parameters did not correlate with those of quantitative ultrasound suggesting that skin discoloration cannot be used as a marker for subcutaneous fibrosis. These tools may prove useful for the reduction of radiation morbidities and improvement of patient quality of life.

A structural equation model to investigate the impact of missing occlusal units on objective masticatory function in patients with shortened dental arches.

The aim of this study was to investigate the impact of missing occlusal units (MOUs) on objective masticatory function with respect to food comminuting and mixing ability. Sixty partially dentate patients (mean age, 64·1 years) with shortened dental arches participated in the study. Food comminuting ability was assessed using a masticatory performance test with peanuts as a test food. Food mixing ability was assessed using a mixing ability test with a two-coloured wax cube. Maximum bite force (MBF) was measured using a pressure-sensitive film as a mediator for food comminuting and mixing ability. A structural equation model was constructed based on a hypothesis that MOUs would be associated with reduced MBF and impairment of food comminuting and mixing ability. Structural equation modelling analysis found significant direct effects of MOU on median particle size and mixing ability index (MAI) (P < 0·001). In addition, MOU had significant indirect effects on median particle size and MAI with MBF as a mediator (P < 0·05). These results suggest that decrease in occlusal platform area and reduced MBF because of MOUs are associated with the impairment of food comminution and mixing in patients with shortened dental arches.

A structural equation model relating objective and subjective masticatory function and oral health-related quality of life in patients with removable partial dentures.

The aim of this study was to investigate the relationships between objective masticatory function with respect to masticatory performance and food mixing ability, patients' perception of chewing ability and oral health-related quality of life (OHRQoL). Partially dentate patients with removable partial dentures (n = 131, mean age 67·1 year) participated in the study. Four tests were performed to evaluate objective and subjective masticatory function and OHRQoL. Masticatory performance and food mixing ability were assessed using peanuts or a two-coloured wax cube as test items. Patients' perception of chewing ability was rated using a food intake questionnaire. OHRQoL was measured using the Japanese version of the oral health impact profile. A structural equation model was constructed based on hypothesis in which objective masticatory function would be related to OHRQoL via perceived chewing ability as a mediator. Structural equation modelling analysis found a statistically significant medium effect of perceived chewing ability on OHRQoL and statistically significant medium or small effects of masticatory performance on perceived chewing ability and OHRQoL (P < 0·05); however, the effect of food mixing ability on perceived chewing ability or OHRQoL was not statistically significant (P > 0·05). A fit index indicated that the model fitted well to the data (Goodness-of-fit index = 0·99). These results suggest that perceived chewing ability is a critical factor for OHRQoL and that masticatory performance rather than food mixing ability is important for perceived chewing ability and OHRQoL in patients with removable partial dentures.

Stereotactic Body Radiotherapy for Large Unresectable Hepatocellular Carcinomas - A Single Institution Phase II Study.

AIMS: To evaluate the safety and efficacy of liver stereotactic body radiotherapy (SBRT) in the treatment of unresectable hepatocellular carcinomas (HCC) measuring >5 cm. MATERIALS AND METHODS: Between November 2013 and February 2016, 13 patients with unresectable HCC (>5 cm), ineligible for other local treatments, with a Child-Pugh score (CPS) ≤ B7, were enrolled into a single-institution phase II study. SBRT was delivered by volumetric-modulated arc radiotherapy. Radiological response was reported using modified Response Evaluation Criteria in Solid Tumours criteria and toxicities graded by Common Terminology Criteria for Adverse Events v4 criteria. RESULTS: Sixteen hepatomas (median size 7.5 cm, range 5.1-9.7 cm) were treated in 13 patients. The baseline CPS was A5/6 in nine patients (69%) and B7 in four patients (31%). Five patients (38%) received previous liver-directed treatment. The median prescribed dose was 45 Gy (range 40-45 Gy) in five fractions. The median follow-up was 17.7 months. The 1-year local control rate was 92%. The median overall survival was 17.7 months and the 1-year overall survival was 62%. The median time to local progression was not reached. Five patients (39%) had an increase in CPS by two or more points at 3 months. Overall, there were 10 grade 3 acute toxicities occurring in seven patients, of which six were haematological. Quality of life remained clinically stable or improved at 3 months in 61.5% and 53.8% of patients based on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 Global Health Score and Functional Assessment of Cancer Therapy - Hepatobiliary version 4 score, respectively. CONCLUSIONS: In our cohort, SBRT to unresectable large HCC tumours provided excellent local control with acceptable toxicities. Regional recurrence remained the major cause of failure. Further studies are warranted to examine the role for SBRT in combination with other modalities to maximise disease control in the liver.

An independent and prospective comparison of two commercial fibrosis marker panels (HCV FibroSURE and FIBROSpect II) during albinterferon alfa-2b combination therapy for chronic hepatitis C.

SUMMARY: Noninvasive markers that accurately follow changes in fibrosis may provide alternatives to liver biopsy for assessment of histological endpoints of antiviral therapy in chronic hepatitis C (CHC). This study compared two commercially available serum marker panels (HCV FibroSURE and FIBROSpect II) during interferon-based therapy. Ninety-five interferon-naïve patients with genotype 1 CHC were enrolled in a phase 2b, active-controlled study of albinterferon alfa-2b/ribavirin for 48 weeks. Proprietary and simple biochemical marker panels were independently evaluated in serum before and during the study. Baseline liver biopsies were evaluated for METAVIR fibrosis by a single pathologist. Index scores were obtained for HCV FibroSURE (n = 84) and FIBROSpect II (n = 95); mean biopsy length: 17.8 +/- 8.0 mm. For detecting fibrosis stages 2-4 (prevalence 23% [22/95] and 21% [18/84]), HCV FibroSURE and FIBROSpect II indicated high sensitivity (1.00 and 0.95, respectively), lower but comparable specificity (0.61 and 0.66, respectively), and a good area under the receiver operating characteristic curve (0.89 and 0.90, respectively). Simple indices had high indeterminate rates (31-40%) at baseline. Patients with a sustained virological response had lower baseline scores than nonresponders, and reduced median percent changes in index scores for HCV FibroSURE (-20.0%vs 2.9%; P = 0.14) and FIBROS Spect II (-6.8%vs 18.4%; P = 0.05). The panels demonstrated comparable performance characteristics for differentiating mild from moderate-severe stage disease in CHC. Lower index scores at baseline that continue to decline likely reflect reduced fibrogenesis activity in patients with successful antiviral responses to therapy.

Induction of inflammatory arthropathy resembling rheumatoid arthritis in mice transgenic for HTLV-I.

Human T cell leukemia virus type-I (HTLV-I) is the etiologic agent of adult T cell leukemia and has also been suggested to be involved in other diseases such as chronic arthritis or myelopathy. To elucidate pathological roles of the virus in disease, transgenic mice were produced that carry the HTLV-I genome. At 2 to 3 months of age, many of the mice developed chronic arthritis resembling rheumatoid arthritis. Synovial and periarticular inflammation with articular erosion caused by invasion of granulation tissues were marked. These observations suggest a possibility that HTLV-I is one of the etiologic agents of chronic arthritis in humans.

Chylous ascites: a late complication of intra-abdominal Mycobacterium avium complex immune reconstitution syndrome in HIV-infected patients.

Chylous ascites related to Mycobacterium avium complex (MAC) in HIV-infected patients is rare, with only six cases reported in the English literature. We report a series of six cases from a single institution. During the past six years, chylous ascites was diagnosed in six (35%) of 17 AIDS patients, all of whom had previously been diagnosed with intra-abdominal MAC immune reconstitution syndrome (MAC-IRS). A review of medical records identified no other cases of chylous ascites among HIV-positive patients over the past 13 years (1994-2007), and the incidence was estimated at one in 2248 HIV-positive admissions. The ascitic fluid had a milky appearance and a median triglyceride level of 4.07 mmol/L (range 3.19-29.6 mmol/L) (360 mg/dL, range 282-2620 mg/dL). After a median follow-up of 20 months, five (83%) of six patients survived. Chylous ascites is a late complication of intra-abdominal MAC-IRS, and is usually associated with a favourable prognosis.

All that bleeds is not infliximab-refractory ulcerative colitis.

The role of biological agents in moderate to severe ulcerative colitis has been shown to be effective in the induction of clinical remission. However, the role of infliximab therapy for induction of remission in patients with fulminant colitis is debatable. A case of a hospitalized patient with a new diagnosis of severe ulcerative colitis refractory to intravenous steroids is presented. The patient was treated with infliximab and discharged with clinical remission, but subsequently presented back to hospital with a lower gastrointestinal hemorrhage.

Re-treatment with peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have relapsed or not responded to a first course of pegylated interferon-based therapy.

BACKGROUND: Pegylated interferon (pegIFN) and ribavirin combination therapy remains the first-line treatment for chronic hepatitis C virus (HCV) infection. In contrast to the wealth of studies in treatment-naive patients, the effectiveness of retreatment in patients who have previously failed pegIFN-based therapy is largely unreported. AIM: To assess the effectiveness of the retreatment of patients who have previously failed an initial course of pegIFN-based therapy with pegIFNalpha-2a and ribavirin. METHODS: A post-hoc analysis of a multicentre open-label study was performed. Patients received pegIFNalpha-2a and ribavirin at a dose of 800 mg/day and later 1000 mg/day to 1200 mg/day for 24 to 48 weeks at the discretion of the investigator. Outcomes at week 12 (early virological response [EVR]) and week 24 (sustained virological response [SVR]) were analyzed. RESULTS: Eighty-seven patients who had relapsed after previous pegIFN-based therapy (n=28; 78% genotype 1) or were nonresponders (n=59; 71% genotype 1) were analyzed. Of the relapsers, 86% achieved an EVR and 68% achieved an SVR. In relapsers to pegIFN monotherapy (n=15) or pegIFN plus ribavirin (n=13), 60% and 77% achieved an SVR, respectively. Fibrosis and genotype did not affect the likelihood of SVR in relapsers although this may be the result of the relatively small number of patients. In previous nonresponders, an EVR was achieved in 53% but an SVR occurred in only 17%. In nonresponders to pegIFN monotherapy (n=9) and pegIFN plus ribavirin (n=50), 33% and 14% achieved an SVR, respectively. Genotype did not affect SVR in nonresponders. Only 10% with a METAVIR score of F3 or F4 on liver biopsy achieved an SVR. CONCLUSIONS: Relapse after previous pegIFN-based therapy is associated with a strong probability of treatment success whereas retreatment of those with previous nonresponse does not.

"Another thing to live for": Supporting HCV treatment and cure among Indigenous people impacted by substance use in Canadian cities.

BACKGROUND: Colonization and colonial systems have led to the overrepresentation of Indigenous people impacted by substance use and HCV infection in Canada. It is critical to ensure Indigenous people's equitable access to new direct acting antiviral HCV treatments (DAAs). Identifying culturally-safe, healing-centered approaches that support the wellbeing of Indigenous people living with HCV is an essential step toward this goal. We listened to the stories and perspectives of HCV-affected Indigenous people and HCV treatment providers with the aim of providing pragmatic recommendations for decolonizing HCV care. METHODS: Forty-five semi-structured interviews were carried out with Indigenous participants affected by HCV from the Cedar Project (n = 20, British Columbia (BC)) and the Canadian Coinfection Cohort (n = 25, BC; Ontario (ON); Saskatchewan (SK)). In addition, 10 HCV treatment providers were interviewed (n = 4 BC, n = 4 ON, n = 2 SK). Interpretive description identified themes to inform clinical approaches and public health HCV care. Themes and related recommendations were validated by Indigenous health experts and Indigenous participants prior to coding and re-contextualization. RESULTS: Taken together, participants' stories and perceptions were interpreted to coalesce into three overarching and interdependent themes representing their recommendations. First: treatment providers must understand and accept colonization as a determinant of health and wellness among HCV-affected Indigenous people, including ongoing cycles of child apprehension and discrimination within the healthcare system. Second: consistently safe attitudes and actions create trust within HCV treatment provider-patient relationships and open opportunities for engagement into care. Third: treatment providers who identify, build, and strengthen circles of care will have greater success engaging HCV-affected Indigenous people who have used drugs into care. CONCLUSION: There are several pragmatic ways to integrate Truth and Reconciliation as well as Indigenous concepts of whole-person wellness into the HCV cascade of care. By doing so, HCV treatment providers have an opportunity to create greater equity and support long-term wellness of Indigenous patients.