Incidence and Predictors of Nonalcoholic Fatty Liver Disease by Serum Biomarkers in Patients with Inflammatory Bowel Disease.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at high risk for non-alcoholic fatty liver disease (NAFLD). Longitudinal data on incident NAFLD are lacking. We employed non-invasive methods to study incidence and predictors of NAFLD. METHODS: This was a retrospective study of IBD patients without known liver disease followed at IBD clinic of McGill University. NAFLD was defined as Hepatic Steatosis Index (HSI) ≥36 and absence of alcohol intake. Advanced liver fibrosis was diagnosed by FIB-4 ≥2.67. Active IBD was defined as partial Mayo score ≥3 for ulcerative colitis, Harvey Bradshaw Index ≥ 5 or flare during follow-up. Kaplan-Meier and Cox regression analyses were used to investigate incidence and predictors of NAFLD development. RESULTS: Three hundred twenty-one consecutive patients (median age 33.7 yr, 47% males) were observed for a median of 3.2 years (interquartile range 1.5-6). Over 1181.2 persons-year (PY), 108 (33.6%) patients developed NAFLD, accounting for an incidence rate of 9.1/100 PY (95% confidence interval [CI], 7.4-10.9). 7 (2.2%) patients developed advanced liver fibrosis, accounting for an incidence rate of 0.5/100 PY (95% CI, 0.2-1.1). Development of NAFLD was predicted by disease activity (adjusted hazard ratio [aHR] = 1.58; 95% CI, 1.08-2.33, P = 0.02), disease duration (aHR = 1.12; 95% CI, 1.03-1.23, P = 0.01), and prior surgery for IBD (aHR = 1.34; 95% CI, 1.04-1.74, P = 0.02). CONCLUSIONS: NAFLD is a frequent comorbidity in patients with IBD. These patients can also develop advanced liver fibrosis. Disease activity, duration of IBD and prior surgery are predictors of NAFLD development. This should represent one more incentive to achieve and maintain early clinical remission. Further prospective studies are of interest.

Explaining the Presence of "Heterosexual" Female Clients of a Rapid HIV Testing Site Located in the Gay Village of Montreal, Quebec.

BACKGROUND: Increasing access and uptake of HIV testing among at-risk women is needed. Examining women's motives for visiting a community-based rapid HIV testing site (Actuel sur Rue-AsR) oriented to men who have sex with men (MSM) could offer suggestions. OBJECTIVE: To compare the "heterosexual" female and male clients of AsR, located in Montreal's (Canada) gay village, to better understand the women's particular HIV prevention and sexual health service needs. METHODS: This cross-sectional pilot study analyzed questionnaire data provided by AsR clients and staff (nurse and community agent teams) between July 2012 and November 2013. Women and men reporting only opposite-sex partners were compared with chi-square, Fisher's exact, and Kruskal-Wallis tests, as appropriate, on sociodemographics, HIV-related behaviors, motives for visiting AsR, and health service provision. RESULTS: AsR received 1901 clients. Among these, 55 women and 147 men reported only opposite-sex partners. Women were significantly younger. Significantly greater proportions of women visited AsR because no appointment was necessary (67% vs. 48%), sought testing for condom failure (18% vs. 5%), and had no regular doctor (44% vs. 27%). Both groups mainly chose AsR for the rapid test results (80% and 77%), visited it to receive the rapid HIV test (71% and 76%), and sought testing due to unprotected vaginal sex (44% and 43%). Similar proportions saw the nurse (91% and 89%), received the rapid HIV test (44% and 35%), and were linked to a medical clinic (49% and 52%), especially, to receive complete sexually transmitted infection testing (50% and 44%). CONCLUSIONS: The results of this innovative study highlight the draw of rapid HIV testing for "heterosexual" users of a site mainly targeting MSM. They also suggest that further research is warranted into the importance for this group of women clients of drop-in and linkage services, particularly given their possible lesser access to regular care.

Influence of Hepatitis C Virus Sustained Virological Response on Immunosuppressive Tryptophan Catabolism in ART-Treated HIV/HCV Coinfected Patients.

BACKGROUND: We previously reported an association between tryptophan (Trp) catabolism and immune dysfunction in HIV monoinfection. Coinfection with HIV is associated with more rapid evolution of hepatitis C virus (HCV)-associated liver disease despite antiretroviral therapy (ART), possibly due to immune dysregulation. We hypothesized that liver fibrosis in HIV/HCV coinfection would be associated with immune dysfunction and alterations in Trp metabolism. METHODS: Trp catabolism and inflammatory soluble markers were assessed in plasma samples from ART-treated HIV/HCV-coinfected patients (n = 90) compared with ART-treated HIV-monoinfected patients and noninfected subjects. Furthermore, 17 additional coinfected patients with sustained virological response (SVR) were assessed longitudinally 6 months after completion of interferon-α/ribavirin treatment. RESULTS: HIV/HCV patients had higher Trp catabolism compared with HIV-monoinfected and healthy individuals. Elevated kynurenine levels in HIV/HCV patients with liver fibrosis correlated with the prognostic aspartate aminotransaminase to platelet ratio (APRI scores) and insulin levels. Furthermore, HIV/HCV patients had elevated levels of disease progression markers interleukin-6 and induced protein 10 and shared similar levels of markers of microbial translocation (intestinal fatty acid-binding protein, soluble CD14 and lipopolysaccharide-binding protein) compared with HIV-monoinfected and healthy individuals. Successful HCV treatment improved APRI score and markers of disease progression and microbial translocation although elevated Trp catabolism remained unchanged 6 months after SVR. CONCLUSION: ART-treated HIV/HCV-coinfected patients had elevated immunosuppressive Trp catabolism when compared with monoinfected HIV-treated patients, which did not normalize after SVR. These findings suggest that a necroinflammatory liver syndrome persists through inflammation by Trp catabolism after 6 month of SVR.

Ability of a rapid HIV testing site to attract and test vulnerable populations: a cross-sectional study on Actuel sur Rue.

Quebec's HIV epidemic persists, particularly among men who have sex with men (MSM) and in Montreal. Increasing access to HIV testing is necessary and community-based rapid testing offers one strategy. This paper examines the clienteles and activities of a rapid HIV testing site in Montreal, the pilot project Actuel sur Rue. Comparative analyses were conducted with 1357 MSM, 147 heterosexual men and 64 women who visited Actuel sur Rue between July 2012 and November 2013 on socio-demographics, health, drug use, sexual practices/infection and HIV testing/prevention. Significant group differences were observed in each category. Actuel sur Rue received 1901 clients, conducted 1417 rapid HIV tests and tested 77 never-tested individuals. Rapid testing produced a high reactive rate (2%). Only 1/28 of those with reactive tests had no previous HIV testing, and 36% had used post-exposure prophylaxis, suggesting missed opportunities for prevention. Findings highlight diverse client vulnerability profiles and the relevance of checkpoints and further prevention efforts.

Correlates of drug use cessation among participants in the Canadian HIV-HCV Co-infection Cohort.

BACKGROUND: Ongoing drug use remains a barrier to HIV and HCV treatment. We examined the occurrence and correlates of drug use cessation among HIV-HCV co-infected drug users participating in HIV care. METHODS: Participants from the Canadian Co-infection Cohort reporting drug use (injecting drugs and/or smoking crack) with at least two follow-up visits were included (n=521 (43%), 1832 visits). Socio-demographics, behavioural, and health information were collected at each six-month visit. Associations with cessation (no drug use since last visit) were examined using non-linear mixed effects logistic regression models with random intercepts. RESULTS: During follow-up, 361 (69%) participants ceased using drugs. Having a fixed address (aOR [adjusted odds ratio] 1.73, CI [95% confidence interval] 1.02-2.96) and smoking crack without injecting drugs (aOR 3.10, CI 2.05-4.71) were positively associated. Living alone (aOR 0.47, CI 0.35-0.63), current tobacco use (aOR 0.41, CI 0.26-0.64), hazardous alcohol drinking (aOR 0.67, CI 0.49-0.91), snorting drugs (aOR 0.52, CI 0.37-0.74), having a greater exposure to addiction programmes (aOR 0.88, CI 0.81-0.94), having been recruited in Quebec or Nova Scotia (aOR 0.41, CI 0.25-0.66), and British Columbia or Alberta (aOR 0.51, CI 0.32-0.82) were negatively associated. Various socio-demographic (age, education) and health-related (HIV duration, care adherence) factors were not associated. CONCLUSION: Drug use cessation among HIV-HCV co-infected persons is relatively common in this cohort. Stable housing and supportive living situations seem to be important facilitators for drug use cessation in this population. Greater efforts should be made to retain patients in addiction treatment programmes.

Missed opportunities for hepatocellular carcinoma screening in an HIV/hepatitis C virus-coinfected cohort.

We examined adherence to guidelines for screening of hepatocellular carcinoma in a cohort of HIV/hepatitis C virus-coinfected patients. Thirty-six percent of patients with documented cirrhosis did not have a screening ultrasound. Patients at centers with standardized systems for screening were more likely to have had an ultrasound performed.

Marijuana smoking does not accelerate progression of liver disease in HIV-hepatitis C coinfection: a longitudinal cohort analysis.

BACKGROUND: Marijuana smoking is common and believed to relieve many symptoms, but daily use has been associated with liver fibrosis in cross-sectional studies. We aimed to estimate the effect of marijuana smoking on liver disease progression in a Canadian prospective multicenter cohort of human immunodeficiency virus/hepatitis C virus (HIV/HCV) coinfected persons. METHODS: Data were analyzed for 690 HCV polymerase chain reaction positive (PCR-positive) individuals without significant fibrosis or end-stage liver disease (ESLD) at baseline. Time-updated Cox Proportional Hazards models were used to assess the association between the average number of joints smoked/week and progression to significant liver fibrosis (APRI ≥ 1.5), cirrhosis (APRI ≥ 2) or ESLD. RESULTS: At baseline, 53% had smoked marijuana in the past 6 months, consuming a median of 7 joints/week (IQR, 1-21); 40% smoked daily. There was no evidence that marijuana smoking accelerates progression to significant liver fibrosis (APRI ≥ 1.5) or cirrhosis (APRI ≥ 2; hazard ratio [HR]: 1.02 [0.93-1.12] and 0.99 [0.88-1.12], respectively). Each 10 additional joints/week smoked slightly increased the risk of progression to a clinical diagnosis of cirrhosis and ESLD combined (HR, 1.13 [1.01-1.28]). However, when exposure was lagged to 6-12 months before the diagnosis, marijuana was no longer associated with clinical disease progression (HR, 1.10 [0.95-1.26]). CONCLUSIONS: In this prospective analysis we found no evidence for an association between marijuana smoking and significant liver fibrosis progression in HIV/HCV coinfection. A slight increase in the hazard of cirrhosis and ESLD with higher intensity of marijuana smoking was attenuated after lagging marijuana exposure, suggesting that reverse causation due to self-medication could explain previous results.

Who needs direct-acting antivirals for HCV? Challenges faced in advancing HCV therapy for HIV-HCV-coinfected individuals.

BACKGROUND: The recent availability of new direct-acting antivirals (DAAs) for HCV treatment, which significantly increase sustained virological response rates for genotype 1 HCV infection, has brought new optimism with respect to curative HCV treatment for HIV-HCV-coinfected patients. We describe the characteristics of coinfected patients who could be eligible for DAAs to determine potential challenges facing clinicians and patients hoping to take advantage of these new therapies. METHODS: We evaluated the sociodemographic and clinical characteristics of the genotype 1 HCV-HIV-infected participants in a Canadian prospective multicentre cohort study at their most recent visit to assess potential eligibility for combination HCV treatment with boceprevir or telaprevir. RESULTS: Of the 1,020 coinfected participants enrolled in the cohort, 707 (85%) had evidence of chronic HCV infection (HCV-RNA-positive), of whom 497 (70%) were infected with genotype 1; 375 (75%) were naive to HCV treatment and 122 (25%) had previously received therapy and failed. Only 143 (38%) of HCV treatment-naive and 39 (32%) of treatment-experienced participants had no absolute contraindications for treatment. Alcohol abuse, active depression and decompensated liver disease were the most frequent reasons for treatment ineligibility. The majority would require alterations in antiretroviral regimens to avoid important drug-drug interactions. CONCLUSIONS: Although the need for curative HCV therapy in HIV-HCV coinfection is great, the actual number of patients who could be eligible for DAAs at the present time may be quite low. There remains an urgent need to develop safe, simple and interferon-sparing treatments for coinfected individuals.

Insulin resistance is associated with progression to hepatic fibrosis in a cohort of HIV/hepatitis C virus-coinfected patients.

OBJECTIVE: Hepatitis C virus (HCV) infection is associated with higher insulin levels and insulin resistance. We evaluated factors associated with insulin resistance in a cohort of HIV/HCV-coinfected patients and determined the effect of insulin resistance on the development of hepatic fibrosis. METHODS: Data were analysed from 158 nondiabetic participants in a prospective Canadian cohort of HIV/HCV-coinfected patients. Patients were defined as having insulin resistance using the homeostasis model for assessment of insulin resistance (HOMA-IR) index. Factors associated with a high index (HOMA-IR ≥ 2) were identified using multivariate logistic regression. Incidence rates of liver fibrosis [aspartate aminotransferase- to-platelet ratio index (APRI) ≥ 1.5] were calculated, and multivariate time-dependent Cox regression models used to assess the effect of baseline insulin resistance on the risk of developing an APRI score of at least 1.5 during follow-up. RESULTS: Overall, 56% had baseline HOMA-IR of at least 2. In the adjusted multivariate logistic analysis, only baseline BMI of more than 25 kg/m2 remained associated with insulin resistance [adjusted odds ratio 3.66, 95% confidence interval (CI) 1.70-7.92]. Rates of progression to significant hepatic fibrosis (APRI ≥ 1.5) were higher in those with HOMA-IR of at least 2 (16.32 per 100 person-years, 95% CI 6.68-25.97) compared with those with HOMA-IR less than 2 (7.95 per 100 person-years, 95% CI 0.16-15.75). Baseline HOMA-IR of at least 2 was associated with the development of significant fibrosis (adjusted hazard ratio 7.71, 95% CI 2.55-23.36).

Factors associated with discordance between absolute CD4 cell count and CD4 cell percentage in patients coinfected with HIV and hepatitis C virus.

BACKGROUND: Liver cirrhosis has been associated with decreased absolute CD4 cell counts but preserved CD4 cell percentage in human immunodeficiency virus (HIV)-negative persons. We evaluated factors associated with discordance between the absolute CD4 cell count and the CD4 cell percentage in a cohort of patients coinfected with HIV and hepatitis C virus (HCV). METHODS: Baseline data from 908 participants in a prospective, Canadian, multisite cohort of individuals with HIV-HCV coinfection were analyzed. Absolute CD4 cell count and CD4 cell percentage relationships were evaluated. We defined low and high discordance between absolute CD4 cell count/CD4 cell percentage relationships as CD4 cell percentages that differed from the expected CD4 cell percentage, given the observed absolute CD4 cell count, by ±7 percentage points; we defined very low and very high discordance as differences of ±14 percentage points. Factors associated with high or very high discordance, including either end-stage liver disease or aspartate transaminase to platelet ratio index (APRI) of >1.5, were analyzed using multivariate logistic regression models and compared to groups with concordant and low discordant results. RESULTS: High/very high discordance was seen in 31% (n = 286), while 35% (n = 321) had concordant values. Factors associated with very high discordance at baseline included history of end-stage liver disease (adjusted odds ratio [aOR], 6.52; 95% confidence interval [CI], 2.27-18.67) and APRI of >1.5 (aOR 4.69; 95% CI, 1.64-13.35). Compared with those with detectable HCV RNA, those who cleared HCV spontaneously were less likely to have very high discordance. CONCLUSIONS: Discordance between absolute CD4 cell count and CD4 cell percentage is common in an HIV/HCV-coinfected population and is associated with advanced liver disease and ongoing HCV replication.