Ottawa Hospital Viral Hepatitis Clinic Research Articles

Uptake and factors associated with direct-acting antiviral therapy for hepatitis C and treatment outcomes among Canadian immigrants: A retrospective cohort analysis.

We sought to compare rates and factors associated with direct acting antiviral (DAA) treatment uptake and sustained virological response (SVR) between Canadian-born and foreign-born patients. The study was conducted utilizing a retrospective cohort of hepatitis C virus (HCV)-infected patients assessed at The Ottawa Hospital Viral Hepatitis Clinic between January 2015 and October 2021. Risk factors, income, and clinical characteristics of HCV infection associated with DAA therapy uptake and SVR were compared by immigration status using logistic regression. Of 1,459 HCV-infected patients, 264 (18.1%) were born outside of the country. A median 17 years passed from immigration to first assessment at the clinic. The proportion of patients initiating DAA therapy was similar between groups (65.2% versus 69.5%, p = 0.17). Characteristics associated with DAA therapy uptake included age at first assessment (OR 1.02; 95% CI 1.01 to 1.03) and being cirrhotic (OR 3.19; 95% CI 1.99 to 2.13). Crude SVR rate was higher in immigrants than in Canadian-born patients (91.5% versus 83.7%, p = 0.01). After controlling for other variables, only advancing age was associated with the likelihood of achieving crude SVR (OR 1.04, 95% CI 1.02 to 1.05). We found that DAA therapy uptake and HCV cure rates were high in both groups suggesting equity of opportunity in those referred to our program. The older age at presentation suggests missed opportunities to diagnose and engage immigrants in HCV care. These findings emphasize the importance of early large-scale screening and engagement in care for HCV infection of immigrant populations to prevent future complications.

Hepatitis C Virus Infection Outcomes Among Immigrants to Canada: A Retrospective Cohort Analysis

Introduction and aimHCV-infected immigrants contribute to the total prevalence in Canada and other developed nations. Little is known about engagement in care, access to service, and treatment outcomes in recipients of Direct Acting Antiviral (DAA) HCV therapies among immigrants living with HCV. Material and methodsHCV patients assessed at The Ottawa Hospital Viral Hepatitis Clinic between 2000-2016 were identified. Immigration history, race, socioeconomic status, HCV work-up, treatment and outcome data were evaluated. HCV fibrosis assessment, treatment and sustained virologic response (SVR) were compared using logistic regression. Results2,335 HCV-infected patients were analyzed with 91% (2114) having data on immigration (23% immigrants). A median 16 years (Quartiles: 5, 29) passed from immigration to referral. Access to diagnostic procedures (Fibroscan/liver biopsy) was greater among immigrants compared to Canadian-born (78% vs. 68%, p = 0.001) and immigrants had an odds ratio of 1.72 (95% CI: 1.18-2.51) of receiving a FibroScan compared to Canadians after adjustment for demographic characteristics, HCV risk factors, and socioeconomic status. No differences in SVR were found between immigrants for IFN recipients. Among DAA recipients, rates of SVR were > 94% among all patients, 93% in Canadian-born and 98% among immigrants (p = 0.14). ConclusionNearly 80% of immigrants in this setting had access to fibrosis assessment which was higher than Canadian-born patients. Under half of both groups had initiated HCV therapy. Delays in accessing HCV care represent a missed opportunity to engage, treat and cure HCV patients. HCV screening and health care engagement at the time of immigration would optimize HCV care and therapeutic outcomes.

Liver enzyme normalization predicts success of Hepatitis C oral direct-acting antiviral treatment.

Monitoring of hepatitis C virus (HCV) treatment response is performed by serial HCV RNA measurements; however, this may not be useful for predicting treatment success or failure with oral direct-acting antiviral agent (DAA) therapies. Liver enzyme levels, which are elevated in chronic HCV and tend to decline on therapy, may serve as a more logistically and economically feasible alternative for monitoring treatment response. The Ottawa Hospital Viral Hepatitis Clinic patients (n=219), receiving interferon-free oral DAA treatments, were assessed for liver enzymes and HCV RNA levels at baseline, week 4 and ≥12 weeks post-treatment. Suppression cut points used for this analysis were ALT ≤ 40U L-1 and AST ≤ 30U L-1. The primary outcome was week 12 sustained virologic response (SVR). By our analysis, all indicators had strong PPV (>90%) but limited NPV (.

Improving treatment and liver fibrosis outcomes with metformin in HCV-HIV co-infected and HCV mono-infected patients with insulin resistance: study protocol for a randomized controlled trial.

BackgroundApproximately 180 million people worldwide, (3 % of the world’s population) are infected with hepatitis C (HCV). Insulin resistance (IR) and type 2 diabetes (T2DM) are common extrahepatic manifestations of chronic HCV infection and associated with poor treatment and liver-related outcomes. The presence of these metabolic complications have been associated with poor response to interferon-based HCV antiviral therapy and increased risk of liver-related outcomes. Metformin, an insulin sensitizer is known to improve HCV treatment response and has been associated with a reduced risk of developing hepatocellular carcinoma (HCC). This study will evaluate the effect of metformin on preventing progression or promoting regression of liver fibrosis, rate of virologic cure (SVR) and other metabolic measures in HCV-HIV co-infected and HCV mono-infected study participants who have IR and are planning on initiating HCV treatment.MethodsThis study is a prospective 48-week single-centre, randomized, open-label, controlled trial of HIV-HCV co-infected and HCV mono-infected patients with IR (HOMA-IR ≥ 2.0) who are planning to initiate HCV antiviral therapy. Sixty participants will be recruited from The Ottawa Hospital Viral Hepatitis Clinic. Participants will be randomized in a 1:1 ratio to either arm 1, metformin 2 g (1 g twice daily) plus lifestyle, or to arm 2, lifestyle alone. The primary outcome will be the change in FibroScan® score (kPa) from baseline to week 12 (start of HCV treatment), the end of HCV treatment (week 24) and 24 weeks post HCV treatment (week 48). Secondary outcomes include changes in liver fibrosis using AST to platelet ratio index, changes in glucose and lipid levels, anthropometric measures, changes in alpha-fetoprotein levels, patient acceptability, and changes in dietary and physical activity parameters.DiscussionThis pilot study will be the first to evaluate the role of metformin on liver fibrosis in HCV-HIV co-infected and HCV mono-infected patients with IR receiving DAA HCV treatment. If metformin is effective in reducing liver fibrosis in this patient population, this will represent a well-tolerated, easy-to-administer, inexpensive therapy that will protect against negative HCV outcomes. This study will also be an opportunity to evaluate the impact of insulin resistance and hyperglycemia on viral clearance in HCV-infected patients treated with interferon-free regimens.Trial registrationClinicalTrials.gov NCT02306070 version 4.0 (June 29, 2015)Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1454-6) contains supplementary material, which is available to authorized users.

Distribution of Hepatitis C Risk Factors and HCV Treatment Outcomes among Central Canadian Aboriginal.

Background. Aboriginal Canadians face many lifestyle risk factors for hepatitis C exposure. Methods. An analysis of Ottawa Hospital Viral Hepatitis Clinic (Ottawa, Canada) patients between January 2000 and August 2013 was performed. HCV infection risk factors and HCV treatment outcomes were assessed. Socioeconomic status markers were based on area-level indicators linked to postal codes using administrative databases. Results. 55 (2.8%) Aboriginal and 1923 (97.2%) non-Aboriginal patients were evaluated. Aboriginals were younger (45.6 versus 49.6 years, p < 0.01). The distribution of gender (63.6% versus 68.3% male), HIV coinfection (9.1% versus 8.1%), advanced fibrosis stage (29.2% versus 28.0%), and SVR (56.3% versus 58.9%) was similar between groups. Aboriginals had a higher number of HCV risk factors, (mean 4.2 versus 3.1, p < 0.001) with an odds ratio of 2.5 (95% confidence interval: 1.4–4.4) for having 4+ risk factors. This was not explained after adjustment for income, social deprivation, and poor housing. Aboriginal status was not related to SVR. Aboriginals interrupted therapy more often due to loss to follow-up, poor adherence, and substance abuse (25.0% versus 4.6%). Conclusion. Aboriginal Canadians have higher levels of HCV risk factors, even when adjusting for socioeconomic markers. Despite facing greater barriers to care, SVR rates were comparable with non-Aboriginals.

Marijuana use in hepatitis C infection does not affect liver biopsy histology or treatment outcomes.

Marijuana smoking is prevalent among hepatitis C virus-infected patients. The literature assessing the influence of marijuana on liver disease progression and hepatitis C virus antiviral treatment outcomes is conflicting. The authors evaluated hepatitis C virus RNA-positive patients followed at The Ottawa Hospital Viral Hepatitis Clinic (Ottawa, Ontario) from 2000 to 2009. Using The Ottawa Hospital Viral Hepatitis Clinic database and charts, information regarding demographics, HIV coinfection, alcohol use, liver biopsy results, treatment outcomes and self-reported marijuana use was extracted. Biopsy characteristics and hepatitis C virus antiviral treatment outcomes were assessed for association with categorized marijuana use by adjusted logistic regression; covariates were specified according to clinical relevance a priori. Information regarding marijuana use was available for 550 patients, 159 (28.9%) of whom were using marijuana at the time of first assessment. Biopsy fibrosis stage and marijuana use data were available for 377 of these 550 (F0-2 = 72.3%). Overall, marijuana use did not predict fibrosis stage, inflammation grade or steatosis. Sustained virological response and marijuana use data were available for 359 of the 550 cohort participants; a total of 211 (58.8%) achieved a sustained virological response. Marijuana use was not associated with premature interruption of therapy for side effects, the likelihood of completing a full course of therapy or sustained virological response. Marijuana use did not influence biopsy histology or alter key hard outcomes of hepatitis C virus antiviral therapy.

Evaluation of immigration status, race and language barriers on chronic hepatitis C virus infection management and treatment outcomes

Hepatitis C virus (HCV) prevalence in certain Canadian immigrant populations is higher than that of the overall population. Disparities in care related to immigration status as well as to race and language are well recognized. Identifying and understanding these disparities is vital to the provision of optimal and inclusive HCV care. HCV RNA-positive patients assessed at The Ottawa Hospital Viral Hepatitis Clinic between June 2000 and June 2007 were identified using a clinical database. As measures of access to care, liver biopsy rates, treatment initiation rates, supportive care provision (i.e. erythropoietin for treatment-related anemia) and sustained virological response (SVR) rates were assessed as a function of immigration status, race and spoken language. Nine hundred and ten patients were evaluated, of which 20% were immigrants. Biopsy rates (54 vs. 51%), HCV treatment initiation (37 vs. 38%), erythropoietin prescription (13 vs. 18%) and SVR rates (52 vs. 51%) did not differ between immigrants and Canadian-born individuals. Spoken language and race did not influence access to treatment. SVR was predicted by genotype, HIV status and race. In the context of a multidisciplinary, multilingual universal health care system, by studying the influence of barriers to HCV investigation and successful therapy can be abrogated.

Erythropoiesis‐Stimulating Agent Use for Anemia Induced by Interferon‐Ribavirin Treatment in Patients with Hepatitis C Virus Infection Is Not Associated with Increased Rates of Cardiovascular Disease, Thrombosis, Malignancy, or Death

Anemia is a complication of therapy for hepatitis C virus (HCV) infection, necessitating dose reductions or therapy abandonment. Administration of an erythropoiesis-stimulating agent (ESA) is a common strategy to manage this complication. Clinical data in other patient populations demonstrate increased rates of cardiovascular events, thrombosis, malignancy, and death among ESA recipients. Event rates in the context of HCV treatment are unknown. All recipients of interferon-ribavirin-based HCV therapy at the Ottawa Hospital Viral Hepatitis Clinic from October 2003 through October 2006 were identified. Predictors of ESA use were assessed by regression analysis. Adverse events during and after treatment were evaluated. A total of 174 courses of HCV therapy were initiated. Predictors of ESA use included older age, lower weight, lower baseline hemoglobin level, and infection with HCV genotype 1 or 4. Targeted hemoglobin levels of >110 g/L were achieved in 88% of ESA recipients. Although not statistically significant, sustained virological responses were obtained in more recipients of ESA (54%) than nonrecipients (45%). In the period after HCV treatment, no myocardial infarctions, deep vein thromboses, or pulmonary embolisms occurred; the frequency of stroke and cancer events were low; and rates of adverse events appeared to be similar between groups. ESA use is not associated with increased risk of cardiovascular events, malignancy, thrombosis, or death in HCV-infected patients during receipt of HCV therapy or in the period after completion. Given the inherent differences in patient populations, practitioners should exercise caution when extrapolating the results of studies of other diseases to HCV infection. Our efficacy and safety analysis suggests against the withholding of ESAs in the management of anemia induced by HCV treatment.

Barriers to Hepatitis C Virus Treatment in a Canadian HIV-Hepatitis C Virus Coinfection Tertiary Care Clinic

Despite demonstrated efficacy in HIV-hepatitis C virus (HCV) coinfection, not all patients initiate, complete or achieve success with HCV antiviral therapy. All HIV-HCV coinfected patient consults received at The Ottawa Hospital Viral Hepatitis Clinic (Ottawa, Ontario) between June 2000 and September 2006 were identified using a clinical database. A descriptive analysis of primary and contributing factors accounting for why patients did not initiate HCV therapy, as well as the therapeutic outcomes of treated patients, was conducted. One hundred two consults were received. Sixty-seven per cent of patients did not initiate HCV therapy. The key primary reasons included: HIV therapy was more urgently needed (22%), loss to follow-up (12%), patients were deemed unlikely to progress to advanced liver disease (18%) and patient refusal (12%). Many patients had secondary factors contributing to the decision not to treat, including substance abuse (23%) and psychiatric illness (14%). Overall, 59% of untreated patients (40 of 68) were eventually lost to follow-up. Thirty-three per cent of referred patients started HCV therapy. Twenty-seven of 42 courses (64%) were interrupted prematurely for reasons such as virological nonresponse (48%), psychiatric complications (10%) and physical side effects (7%). Of all treatment recipients, 12 of 42 full courses of therapy were completed and three remained on HCV medication. Overall, eight of the 102 coinfected patients studied (8%) achieved a sustained virological response. Not all HIV-HCV coinfected patients who are deemed to be in need of HCV treatment are initiating therapy. Only a minority of patients who do receive treatment achieve success. Implementation of HIV treatment, patient retention, attention to substance abuse and mental health care should be the focus of efforts designed to increase HCV treatment uptake and success. This can be best achieved within a multidisciplinary model of health care delivery.

Evaluation of Oral Cannabinoid-Containing Medications for the Management of Interferon and Ribavirin-Induced Anorexia, Nausea and Weight Loss in Patients Treated for Chronic Hepatitis C Virus

The systemic and cognitive side effects of hepatitis C virus (HCV) therapy may be incapacitating, necessitating dose reductions or abandonment of therapy. Oral cannabinoid-containing medications (OCs) ameliorate chemotherapy-induced nausea and vomiting, as well as AIDS wasting syndrome. The efficacy of OCs in managing HCV treatment-related side effects is unknown. All patients who initiated interferon-ribavirin therapy at The Ottawa Hospital Viral Hepatitis Clinic (Ottawa, Ontario) between August 2003 and January 2007 were identified using a computerized clinical database. The baseline characteristics of OC recipients were compared with those of nonrecipients. The treatment-related side effect response to OC was assessed by c2 analysis. The key therapeutic outcomes related to weight, interferon dose reduction and treatment outcomes were assessed by Student's t test and c2 analysis. Twenty-five of 191 patients (13%) initiated OC use. Recipients had similar characteristics to nonrecipients, aside from prior marijuana smoking history (24% versus 10%, respectively; P=0.04). The median time to OC initiation was seven weeks. The most common indications for initiation of OC were anorexia (72%) and nausea (32%). Sixty-four per cent of all patients who received OC experienced subjective improvement in symptoms. The median weight loss before OC initiation was 4.5 kg. A trend toward greater median weight loss was noted at week 4 in patients eventually initiating OC use (-1.4 kg), compared with those who did not (-1.0 kg). Weight loss stabilized one month after OC initiation (median 0.5 kg additional loss). Interferon dose reductions were rare and did not differ by OC use (8% of OC recipients versus 5% of nonrecipients). The proportions of patients completing a full course of HCV therapy and achieving a sustained virological response were greater in OC recipients. The present retrospective cohort analysis found that OC use is often effective in managing HCV treatment-related symptoms that contribute to weight loss, and may stabilize weight decline once initiated.

Rate of Infectious Complications during Interferon-Based Therapy for Hepatitis C Is Not Related to Neutropenia

The relationship between infectious complications and neutropenia was evaluated in recipients of interferon-based therapy for hepatitis C followed at The Ottawa Hospital Viral Hepatitis Clinic from June 2000 to May 2005. One hundred ninety-two patients received 211 courses of therapy (5707 person-weeks of therapy). No patients received granulocyte colony-stimulating factor. Sixty-seven infectious complications occurred in 57 patients (1.17 infections per 100 person-weeks of therapy). The median time to infection was 17 weeks after the start of therapy. Age, sex, weight, race, human immunodeficiency virus status, stage and grade of biopsy, and type of interferon were not correlated with infection rate by Cox regression analysis. The rates of total, fungal, viral, and bacterial infections did not correlate with nadir neutrophil count or magnitude of decrease from baseline. Neutrophil count is not correlated with infection rate in recipients of interferon-based therapy for hepatitis C. Reduction in interferon dose and/or dosing with granulocyte colony-stimulating factor in those with neutropenia is not supported by this analysis.

Depression and Cigarette Smoking Independently Relate to Reduced Health-Related Quality of Life among Canadians Living with Hepatitis C

Many people living with chronic viral hepatitis C (HCV) report reduced health-related quality of life. The relative contribution of behavioural, psychosocial and HCV disease factors to reduction in HCV health-related quality of life is not well understood. The objectives of the present study were to compare standardized health-related quality of life scores between Canadian HCV patients and age-matched Canadian and American norms, and to examine the relative contribution of biopsychosocial variables (ie, cigarette smoking, alcohol intake and depression) to health-related quality of life scores among Canadian HCV patients. HCV RNA-positive patients were recruited during their first visit to the Ottawa Hospital Viral Hepatitis Clinic (Ottawa, Ontario). A questionnaire assessing health behaviours, health-related quality of life and depressed mood was completed. Data on liver studies, liver biopsy findings and HIV serostatus were also collected. A total of 123 participants (71% men) ranging from 20 to 67 years of age were evaluated. All had compensated liver function. Patients reported significantly lower health-related quality of life compared with age-matched Canadian and American normative samples. In a series of hierarchical multiple regression models, depression and smoking were independently related to compromised health-related quality of life scores, even after controlling for sociodemographic variables and health behaviours. These results highlight the value of adopting a biopsychosocial model of HCV care. Depressed mood and smoking behaviour should be evaluated in HCV patients. Empirically validated psychological and pharmacological treatments for depression and smoking cessation may improve health-related quality of life in HCV infected patients.