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BACKGROUND Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) seem common after liver transplantation. AIM To investigate incidence and predictors of NAFLD and NASH by employing noninvasive testing in liver transplant recipients, namely controlled attenuation parameter (CAP) and the serum biomarker cytokeratin 18 (CK-18). We also evaluated the diagnostic accuracy of CK-18 and CAP compared to liver histology. METHODS We prospectively recruited consecutive adult patients who received liver transplant at the McGill University Health Centre between 2015-2018. Serial measurements of CK-18 and CAP were recorded. NAFLD and NASH were diagnosed by CAP ≥ 270 dB/m, and a combination of CAP ≥ 270 dB/m with CK-18 > 130.5 U/L, respectively. Incidences and predictors of NAFLD and NASH were investigated using survival analysis and Cox proportional hazards. RESULTS Overall, 40 liver transplant recipients (mean age 57 years; 70% males) were included. During a median follow-up of 16.8 mo (interquartile range 15.6-18.0), 63.0% and 48.5% of patients developed NAFLD and NASH, respectively. On multivariable analysis, after adjusting for sex and alanine aminotransferase, body mass index was an independent predictor of development of NAFLD [adjusted hazard ratio (aHR): 1.21, 95% confidence interval (CI): 1.04-1.41; P = 0.01] and NASH (aHR: 1.26, 95%CI: 1.06-1.49; P < 0.01). Compared to liver histology, CAP had a 76% accuracy to diagnose NAFLD, while the accuracy of CAP plus CK-18 to diagnose NASH was 82%. CONCLUSION NAFLD and NASH diagnosed non-invasively are frequent in liver transplant recipients within the first 18 mo. Close follow-up and nutritional counselling should be planned in overweight patients.

Hepatorenal syndrome (HRS) is a functional renal failure that develops in patients with advanced hepatic cirrhosis with ascites and in those with fulminant hepatic failure. The prevalence of HRS varies among studies but in general it is the third most common cause of acute kidney injury (AKI) in cirrhotic patients after pre-renal azotemia and acute tubular necrosis. HRS carries a grim prognosis with a mortality rate approaching 90% three months after disease diagnosis. Fortunately, different strategies have been proven to be successful in preventing HRS. Although treatment options are available, they are not universally effective in restoring renal function but they might prolong survival long enough for liver transplantation, which is the ultimate treatment. Much has been learned in the last two decades regarding the pathophysiology and management of this disease which lead to notable evolution in the HRS definition and better understanding on how best to manage HRS patients. In the current review, we will summarize the recent advancement in epidemiology, pathophysiology, and management of HRS.

Background and Aim Non‐alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) are prevalent conditions sharing common pathogenic factors. We performed a systematic literature review and meta‐analysis aiming to investigate the association between NAFLD and PCOS among premenopausal PCOS patients. Methods Relevant studies were systematically identified from scientific databases until 2019. We calculated pooled odds ratio (OR) using a random‐effect model, and heterogeneity was addressed through I 2. Subgroup analyses and meta‐regression for various covariates were performed. Results Of the 1833 studies retrieved, 23 studies with 7148 participants qualified for quantitative synthesis. The pooled result showed that women with PCOS had a 2.5‐fold increase in the risk of NAFLD compared to controls (pooled OR 2.49, 95% confidence interval [CI] 2.20–2.82). In subgroup analyses comparing PCOS to controls, South American/Middle East PCOS patients had a greater risk of NAFLD (OR 3.55, 95% CI 2.27–5.55) compared to their counterpart from Europe (OR 2.22, 95% CI 1.85–2.67) and Asia (OR 2.63, 95% CI 2.20–3.15). Insulin resistance and metabolic syndrome were more frequent in the PCOS group (OR 1.97, 95% CI 1.44–2.71 and OR 3.39, 95% CI 2.42–4.76, respectively). Study quality and body mass index (BMI) were the only covariates that showed a relationship with the outcome in the meta‐regression, with a regression coefficient of −2.219 (95% CI −3.927 to −0.511) and −1.929 (95% CI −3.776 to −0.0826), respectively. Conclusions This meta‐analysis indicates that premenopausal PCOS patients are associated with 2.5‐fold increase in the risk of NAFLD, and BMI seems to be the main cofactor., We performed a systematic literature review and meta‐analysis to investigate the association between NAFLD and PCOS among premenopausal PCOS patients. Of 1833 studies, 23 studies with 7148 participants were included. Women with PCOS had a 2.5‐fold increase in the risk of NAFLD compared to controls (Pooled OR 2.49, 95% CI 2.20‐2.82; I2=55.2%, p=0.001). South American/Middle East populations had a greater risk of NAFLD (OR 3.55, 95% CI 2.27‐5.55).

Background Cardiovascular and liver disease are main causes of death in people with human immunodeficiency virus (HIV) (PWH). In HIV-uninfected patients, nonalcoholic fatty liver disease (NAFLD) is associated with incident metabolic complications. We investigated the effect of NAFLD on development of metabolic comorbid conditions in PWH. Methods We included PWH undergoing a screening program for NAFLD using transient elastography. NAFLD was defined as a controlled attenuation parameter ≥248 dB/m with exclusion of other liver diseases. Incident diabetes, hypertension, dyslipidemia, and chronic kidney disease were investigated using survival analysis and Cox proportional hazards. Results The study included 485 HIV-monoinfected patients. During a median follow-up of 40.1 months (interquartile range, 26.5–50.7 months), patients with NAFLD had higher incidences of diabetes (4.74 [95% confidence interval, 3.09–7.27] vs 0.87 [.42–1.83] per 100 person-years) and dyslipidemia (8.16 [5.42–12.27] vs 3.99 [2.67–5.95] per 100 person-years) than those without NAFLD. With multivariable analysis, NAFLD was an independent predictor of diabetes (adjusted hazard ratio, 5.13; 95% confidence interval, 2.14–12.31) and dyslipidemia (2.35; 1.34–4.14) development. Conclusions HIV-monoinfected patients with NAFLD are at higher risk of incident diabetes and dyslipidemia. Early referral strategies and timely management of metabolic risk may improve outcomes.

HIV-infected patients are at increased risk of nonalcoholic steatohepatitis (NASH). Vitamin E is recommended for treatment of NASH in the general population. However, its safety and efficacy among HIV-infected patients remain unknown.Single-centre, phase IV, open-label, single arm clinical trial.HIV mono-infected patients without significant alcohol intake or viral hepatitis coinfection were included. The diagnosis of NASH was based on the co-existence of fatty liver, diagnosed by controlled attenuation parameter (CAP) at least 248 dB/m and significant hepatocyte apoptosis, defined by the serum biomarker cytokeratin 18 (CK-18) greater than 130.5 U/L. Participants were treated with 800 IU daily of oral vitamin E (alpha-tocopherol) for 24 weeks, and followed for an additional 24 weeks postdiscontinuation. Generalized linear mixed effects models were used to evaluate changes in alanine aminotransferase (ALT), CAP and CK-18 at the completion of treatment and end of follow-up, controlling for pretreatment trends.A total of 27 patients were included. Four (15%) had a pretreatment liver biopsy, which confirmed the diagnosis of NASH in all cases. Compared with baseline, 24 weeks of vitamin E treatment improved ALT [-27 units/l; 95% confidence interval (CI) -37 to -17], CAP scores (-22 dB/m; 95% CI -42 to -1) and CK-18 (-123 units/l; 95% CI -201 to -46). Conversely, there was no change in BMI. No serious adverse event was reported and no patient was lost to follow-up.In this first clinical trial, we showed that vitamin E is an effective and well tolerated treatment for NASH in HIV-infected patients.

Non-alcoholic fatty liver disease (NAFLD) affects approximately 8 million Canadians. NAFLD refers to a disease spectrum ranging from bland steatosis to non-alcoholic steatohepatitis (NASH). Nearly 25% of patients with NAFLD develop NASH, which can progress to liver cirrhosis and related end-stage complications. Type 2 diabetes and obesity represent the main risk factors for the disease. The Canadian NASH Network is a national collaborative organization of health care professionals and researchers with a primary interest in enhancing understanding, care, education, and research around NAFLD, with a vision of best practices for this disease state. At the 1st International Workshop of the CanNASH network in April 2021, a joint event with the single topic conference of the Canadian Association for the Study of the Liver (CASL), clinicians, epidemiologists, basic scientists, and community members came together to share their work under the theme of NASH. This symposium also marked the initiation of collaborations between Canadian and other key opinion leaders in the field representative of international liver associations. The main objective is to develop a policy framework that outlines specific targets, suggested activities, and evidence-based best practices to guide provincial, territorial, and federal organizations in developing multidisciplinary models of care and strategies to address this epidemic.

Background Human immunodeficiency virus (HIV)–infected patients are at increased risk of liver-related mortality. The effect of occult cirrhosis (OcC), defined as preclinical compensated cirrhosis without any clinical findings, on liver-related events is unknown. Methods HIV-infected patients from 2 Canadian cohorts underwent transient elastography (TE) examination and were classified as (1) OcC (TE ≥13 kPa with no sign of cirrhosis, including absence of thrombocytopenia and signs of advanced liver disease on ultrasound or gastroscopy); (2) overt cirrhosis (OvC) (TE ≥13 kPa with signs of cirrhosis); or (3) noncirrhotic patients (TE Results A total of 1092 HIV-infected patients (51% coinfected with hepatitis C virus) were included. Prevalence of OcC and OvC at baseline was 2.7% and 10.7%, respectively. During a median follow-up of 1.8 (interquartile range, 1.5–2.8) years, the incidence of liver-related events in noncirrhosis, OcC, and OvC was 3.4 (95% confidence interval [CI], 1.2–7.3), 34.0 (95% CI, 6.0–104.0), and 37.0 (95% CI, 17.0–69.1) per 1000 person-years, respectively. Baseline OcC (adjusted hazard ratio [aHR], 7.1 [95% CI, 1.3–38.0]) and OvC (aHR, 8.5 [95% CI, 2.8–26.0]) were independently associated with liver-related events. Monitoring rates for HCC were lower in patients with OcC (24%) compared to those with OvC (40%). Conclusions HIV-infected patients with OcC have a high incidence of liver-related events. Greater surveillance and earlier recognition with appropriate screening strategies are necessary for improved outcomes.

Background: Chronic inflammation and residual HIV transcription persist in people living with HIV (PLWH) receiving antiretroviral therapy (ART), thus increasing the risk of developing non-AIDS co-morbidities. The mechanistic target of rapamycin (mTOR) is a key regulator of cellular metabolism and HIV transcription, and therefore represents an interesting novel therapeutic target. Methods: The LILAC pilot clinical trial, performed on non-diabetic ART-treated PLWH with CD4+/CD8+ T-cell ratios

Background: Canada was the first country to approve elbasvir/grazoprevir (EBR/GZR) for the treatment of chronic HCV infection for genotypes 1 and 4 with or without ribavirin and genotype 3 with sofosbuvir, with no recommendation for baseline resistance testing. The aim of this study was to describe the effectiveness of EBR/GZR and the profile of patients selected for treatment in a Canadian real-world setting. Methods: This multicenter retrospective study of HCV-infected patients treated with EBR/GZR took place among selected Canadian health care providers, with no exclusion criteria. Primary outcome measures included parameters associated with patient profile and sustained virologic response at 12 weeks (SVR12) and 24 weeks after treatment. Results: A total of 408 patients were included; 244 had available SVR12 information (per-protocol population [PP]). Genotype distribution included 1a (54.7%), 1b (17.2%), 3 (11.8%), 4 (10.0%), and other (6.4%). The majority (88.7%) of participants were treated for 12 weeks without ribavirin. Fifty-nine (14.5%) participants, predominantly with genotype 1a (49/59) infection, were tested for baseline resistance-associated substitutions (bRAS). SVR12 was achieved by 95.9% of the PP. In an exploratory analysis assessing potential predictors of SVR12, participants who had undergone bRAS testing (OR 0.14, 95% CI 0.03–0.64) and participants who had undergone liver transplant (OR 0.05, 95% CI 0.00–0.68) had significantly lower odds of achieving SVR12. Conclusions: This study supports the real-world effectiveness of EBR/GZR—including a broad range of genotypes and diverse fibrosis stages—in the absence of bRAS testing and in special populations.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries. Non-alcoholic steatohepatitis (NASH), which is the progressive counterpart of the disease, is becoming the leading indication for liver transplantation in North America. Owing to the lack of symptoms, NASH is often an incidental diagnosis, resulting in a significant proportion of patients being diagnosed when advanced liver disease has already developed. NAFLD has recently been characterized as the hepatic manifestation of metabolic syndrome. Consequently, it is a multisystem disease that often co-exists with several other conditions, such as obesity, diabetes, cardiovascular diseases, and extra-hepatic malignancy, which have an impact on selection of transplant recipients. The complexity of diagnostic approach, need for multidisciplinary clinical management, and lack of a specific treatment further complicate the picture of this extremely prevalent liver condition. NAFLD patients with advanced liver disease should be considered for early referral to liver transplant clinics for careful metabolic and cardiovascular risk stratification because they have worse survival rates after liver transplantation than other patients with chronic liver disease. Early referral will also facilitate optimization of metabolic comorbidities before proceeding with transplantation. This review provides an overview of strategies to identify patients with advanced NAFLD, with an emphasis on the management of associated comorbidities and optimal timing of pre-transplant evaluation. Other topics that have been shown to affect recipient optimization, such as the role of lifestyle changes and bariatric surgery in the management of obesity, as well as sarcopenia in decompensated NASH-related cirrhosis, are addressed.

Background & Aims: Polycystic ovary disease (PCOS) may be a risk factor for nonalcoholic fatty liver disease (NAFLD) due to common pathogenetic pathways, including insulin resistance and obesity. Both PCOS and NAFLD are more severe in South Asian women. Data on NAFLD in South Asian women with PCOS are lacking.Methods: We investigated prevalence and predictors of NAFLD and liver fibrosis by transient elastography (TE) with associated controlled attenuation parameter (CAP) in PCOS patients from South Asia, through a routine screening program. NAFLD was defined as CAP >288 dB/m. Significant liver fibrosis (stage 2 and higher out of 4) was defined as TE measurement >8.0 kPa. Elevated ALT was defined as ALT >24 IU/L, as per upper limit of normal reported in South Asian women. Hyperandrogenism was defined as free androgen index >5. Predictors of NAFLD were determined by logistic regression analysis.Results: 101 PCOS patients (mean age 36.3 years) with no significant alcohol intake or viral hepatitis were included. Prevalence of NAFLD and significant liver fibrosis was 39.6% and 6.9%, respectively. Elevated ALT was observed in 40.0% and 11.5% of patients with and without NAFLD, respectively. After adjusting for duration of PCOS and insulin resistance measured by HOMA-IR, independent predictors of NAFLD were higher BMI (adjusted odds ratio [aOR] 1.30, 95% CI 1.13-1.52), hyperandrogenism (aOR 5.32, 95% CI 1.56-18.17) and elevated ALT (aOR 3.54, 95% CI 1.10-11.47). Lifetime cardiovascular risk was higher in patients with NAFLD compared to those without NAFLD (0.31+0.11 vs. 0.26+0.13).Conclusions: Despite their young age, NAFLD diagnosed by TE with CAP is a frequent comorbidity in South Asian women with PCOS and is strongly associated with higher BMI and hyperandrogenism. Non-invasive screening strategies could help early diagnosis and initiation of interventions, including counselling on weight loss, cardiovascular risk stratification and linkage to hepatology care where appropriate.

Objectives: Current guidelines recommend use of a diagnostic algorithm to assess disease severity in cases of suspected nonalcoholic fatty liver disease (NAFLD). We applied this algorithm to HIV-monoinfected patients. Methods: We analysed three prospective screening programmes for NAFLD carried out in the following cohorts: the Liver Disease in HIV (LIVEHIV) cohort in Montreal, the Modena HIV Metabolic Clinic (MHMC) cohort and the Liver Pathologies in HIV in Palermo (LHivPa) cohort. In the LIVEHIV and LHivPa cohorts, NAFLD was diagnosed if the controlled attenuation parameter (CAP) was ≥248dB/m; in the MHMC cohort, it was diagnosed if the liver/spleen Hounsfield unit (HU) ratio on abdominal computerized tomography scan was

Background Inflammatory bowel disease (IBD) patients may be at risk for nonalcoholic fatty liver disease (NAFLD) due to chronic inflammation, hepatotoxic drugs, and alteration of the gut microbiota. Prospective data using accurate diagnostic methods are lacking. Methods We prospectively investigated prevalence and predictors of NAFLD and liver fibrosis by transient elastography (TE) with associated controlled attenuation parameter (CAP) in IBD patients as part of a routine screening program. NAFLD was defined as CAP ≥248 dB/m. Significant liver fibrosis (stage 2 or higher out of 4) was defined as TE measurement ≥7.0 kPa. Predictors of NAFLD and significant liver fibrosis were determined by logistic regression analysis. Results A total of 384 patients (mean age 42.4 years, 45.0% male, 64.6% with Crohn's disease) with no significant alcohol intake were included. Prevalence of NAFLD and significant liver fibrosis was 32.8% and 12.2%, respectively. Independent predictors of NAFLD were older age (adjusted odds ratio [aOR], 1.45; 95% confidence interval [CI], 1.15-1.82), higher body mass index (BMI; aOR, 1.31; 95% CI, 1.20-1.42) and higher triglycerides (aOR, 1.45; 95% CI, 1.01-2.09). Significant liver fibrosis was independently predicted by older age (aOR, 1.38; 95% CI, 1.12-1.64) and higher BMI (aOR, 1.14; 95% CI, 1.07-1.23). Extrahepatic diseases were more common in IBD patients with NAFLD compared with those without, namely chronic kidney disease (10.3 vs 2.3%; P < 0.001) and cardiovascular diseases (11.3 vs 4.7%; P = 0.02). Conclusions NAFLD diagnosed by TE with CAP is a frequent comorbidity in IBD patients and is associated with extrahepatic diseases. Noninvasive screening strategies could help early diagnosis and initiation of interventions, including weight loss, correction of dyslipidemia, and linkage to care. 10.1093/ibd/izy200_video1izy200.video15794817619001.

Author(s): Tam, Edward; Luetkemeyer, Anne F; Mantry, Parvez S; Satapathy, Sanjaya K; Ghali, Peter; Kang, Minhee; Haubrich, Richard; Shen, Xianlin; Ni, Liyun; Camus, Gregory; Copans, Amanda; Rossaro, Lorenzo; Guyer, Bill; Brown, Robert S; RESCUE and ACTG A5348 study investigators | Abstract: Background a aimsWe report data from two similarly designed studies that evaluated the efficacy, safety, and optimal duration of ledipasvir/sofosbuvir (LDV/SOF)n±nribavirin (RBV) for retreatment of chronic hepatitis C virus (HCV) in individuals who failed to achieve sustained virological response (SVR) with prior SOF-based, non-NS5A inhibitor-containing regimens.MethodsThe RESCUE study enrolled HCV mono-infected adults with genotype (GT) 1 or 4. Non-cirrhotic participants were randomized to 12nweeks of LDV/SOF or LDV/SOFn+nRBV. Compensated cirrhotic participants were randomized to LDV/SOFn+nRBV (12nweeks) or LDV/SOF (24nweeks). The AIDS Clinical Trials Group A5348 study randomized genotype 1 adults with HCV/HIV co-infection to LDV/SOFn+nRBV (12nweeks) or LDV/SOF (24nweeks). Both studies used SVR at 12nweeks post-treatment (SVR12) as the primary endpoint.ResultsIn the RESCUE study, 82 participants were randomized and treated, and all completed treatment. Overall, SVR12 was 88% (72/82); 81-100% in non-cirrhotic participants treated with LDV/SOF or LDV/SOFn+nRBV for 12nweeks and 80-92% in cirrhotic participants treated with LDV/SOFn+nRBV for 12nweeks or LDV/SOF for 24nweeks. Adverse events (AEs), mostly mild-to-moderate in severity, were experienced by 78% of participants, with headache and fatigue most frequently reported. One serious AE, not related to treatment, was observed. No premature discontinuations of study drug, or deaths occurred. In the A5348 study, seven participants were randomized (cirrhotic nn=n1; GT1a nn=n5) and all attained SVR12, with no serious AEs or premature discontinuations.ConclusionsIn this SOF-experienced, NS5A inhibitor-naive population, which included participants with cirrhosis or HCV/HIV co-infection, high SVR12 rates were achieved.

Introduction Antiretroviral therapy (ART) does not cure HIV infection due to the persistence of HIV reservoirs in long-lived memory CD4 T cells present in the blood, lymph nodes, intestinal tract, and other tissues. Interest grows in obtaining gut-tissue samples for HIV persistence studies, which poses an ethical challenge to provide study volunteers with adequate information on risks and benefits. Herein we assess the risks and benefits of undergoing gut biopsy procedures for HIV pathogenesis and reservoir studies. Methods A group discussion was organised with physicians and community representatives on performing either a flexible sigmoidoscopy or a colonoscopy. Consensus was reached on conducting colonoscopy in persons ≥50 years. Thirty HIV-infected, ART-treated and nine uninfected participants were recruited. Colonoscopy was performed to collect 30 gut mucosal biopsies. When present, polyps were removed and abnormal mucosal findings were biopsied for pathological analysis. Participants were interviewed on potential discomfort following colonoscopic examination. Results The HIV-infected and uninfected groups were comparable in terms of age and gender with more men who have sex with men (MSM) in the former group. Abnormal colonoscopic findings were observed in 43.6% of all the participants and did not differ by HIV status. In total, 24 polyps were removed with a higher mean number of polyps removed in HIV-infected versus uninfected participants (1.7 vs 1.0, P=0.013). The number of polyps marginally correlated with inverted CD4:CD8 ratio. Based on our findings, colonoscopic examination was safe to use for gut biopsy procedures where almost half of the participants had polyps removed. Conclusion Participation in the study provided colon cancer screening as an ancillary benefit that participants could have received in standard medical care, thus mitigating burdens of invasive procedures. Dialogue between community representatives and clinical researchers can increase participation and advance HIV cure research.

Background Non-alcoholic fatty liver disease (NAFLD) is the main cause of liver disease in Western countries and is a frequently reported comorbidity in inflammatory bowel disease (IBD). A complex interaction among polygenic predisposition, IBD-specific risk factors, microbiome, multiple environmental and patients’ factors could explain the development of NAFLD in IBD. Gut dysbiosis is increasingly recognised as an important player in NAFLD, as well as in IBD pathogenesis. So far, no study has examined the gut microbiota composition in IBD patients with NAFLD. We aimed to characterise faecal microbiota according to NAFLD status in a pilot cohort of ulcerative colitis (UC) pancolitis in clinical remission. Methods This was a cross-sectional pilot study using transient elastography (TE) with controlled attenuation parameter (CAP) to diagnose NAFLD in UC pancolitis patients in clinical remission, defined as partial Mayo score ≤1. NAFLD was diagnosed non-invasively as CAP ≥248 dB/m. Exclusion criteria included: use of corticosteroids in the last year and antibiotics or probiotics/prebiotics in the last 2 months prior to inclusion; significant alcohol intake (AUDIT-C Results A total of 11 UC pancolitis patients in clinical remission were included (mean age 53 years, 36.4% male, time since IBD diagnosis 16 years). NAFLD was diagnosed in 7 cases (63.6%, mean CAP 291 dB/m). Patients with pancolitis and NAFLD had higher BMI (mean 31 vs. 22 kg/m2, p = 0.006) as well as waist circumference (mean 100 vs. 81 cm, p = 0.006) compared with those without NAFLD, but no other differences in demographic, clinical or pharmacological parameters were found between pancolitis with or without NAFLD. Patients with pancolitis and NAFLD clustered separately from those without NAFLD, when computing Bray Curtis dissimilarities (tested with Adonis, p = 0.006). In addition, patients with pancolitis and NAFLD presented with decreased bacterial richness (p = 0.017) but not diversity. This was accompanied by a significant increase of Bacteroides spp. relative abundance in faecal samples of patients with pancolitis and NAFLD (q = 0.017). Conclusion This pilot study demonstrates, for the first time, that, in UC pancolitis patients, NAFLD associates with altered gut microbiota composition. Further studies are needed to understand the exact role of gut microbiota in UC pancolitis with NAFLD and to evaluate the use of microbiota-directed approaches for the treatment of NAFLD in these patients.

BACKGROUND: Most recent major treatment guidelines recommend considering the patient profile and baseline prognostic factors (genotype, fibrosis level, treatment history) in the management of chronic hepatitis C virus (HCV) infections (CHC). There is, therefore, a need to better characterize clinician decision-making in real-life CHC management in Canada. AIMS: To describe the patient profile, prognostic factors and treatment strategies used in Canadian real-life CHC management. METHODS: Multicenter chart review of CHC patients diagnosed from 2005 to 2012. Patient data were extracted for a minimum of 2 years after CHC diagnosis. RESULTS: 250 patients were included with a mean (SD) follow-up after diagnosis of 5.9 (2.3) years. Table1 summarizes the patient/disease characteristics at CHC diagnosis and the mode of management. A majority of patients (70.4%) received some antiviral treatment, with a lower proportion of treated G1 patients vs. non-G1 patients (64% vs. 76.7%). The most common initial treatments were IFN/RBV dual therapy (68.4%) and NS3/4-containing IFN/RBV therapy (19.3%); Among non-G1 patients, 92.4% were treated with IFN/RBV dual therapy. SVR was achieved by 51.5% of patients (G1: 44.7%; non-G1: 62.2%), 19.3% relapsed and 11.1% were non-responders with initial treatment. The majority of treated patients (72.2%) experienced AEs, the most common ones being fatigue (33%), anemia (27.3%), insomnia (21.6%), neutropenia (18.8%). Two deaths were reported. CONCLUSIONS: Despite the majority of HCV patients having mild fibrosis and being treated, most frequently with dual IFN/RBV therapy, SVR rates were low prior to the all-oral DAA era, highlighting the need for more efficacious treatments and suggesting that recommendations to still use IFN are not justifiable. FUNDING AGENCIES: Abbvie corporation

BACKGROUND The preparation for colonoscopy is elaborate and complex. In the context of colorectal cancer screening, up to 11% of patients do not keep their colonoscopy appointments and up to 33% of those attending their appointments have inadequately cleansed bowels that can delay cancer diagnosis and treatment. A smartphone app may be an acceptable and wide-reaching tool to improve patient adherence to colonoscopy. OBJECTIVE The aim of this qualitative study was to employ a user-centered approach to design the content and features of a smartphone app called colonAPPscopy to support individuals preparing for their colonoscopy appointments. METHODS We conducted 2 focus group discussions (FGDs) with gastroenterology patients treated at the McGill University Health Centre in Montreal, Canada. Patients were aged 50 to 75 years, were English- or French-speaking, and had undergone outpatient colonoscopy in the previous 3 months; they did not have inflammatory bowel disease or colorectal cancer. FGDs were 75 to 90 min, conducted by a trained facilitator, and audiotaped. Participants discussed the electronic health support tools they might use to help them prepare for the colonoscopy, the content needed for colonoscopy preparation, and the features that would make the smartphone app useful. Recordings of FGDs were transcribed and analyzed using thematic analysis to identify key user-defined content and features to inform the design of colonAPPscopy. RESULTS A total of 9 patients (7 male and 2 female) participated in one of 2 FGDs. Main content areas focused on bowel preparation instructions, medication restrictions, appointment logistics, communication, and postcolonoscopy expectations. Design features to make the app useful and engaging included minimization of data input, reminders and alerts for up to 7 days precolonoscopy, and visual aids. Participants wanted a smartphone app that comes from a trusted source, sends timely and tailored messages, provides reassurance, provides clear instructions, and is simple to use. CONCLUSIONS Participants identified the need for postcolonoscopy information as well as reminders and alerts in the week before colonoscopy, novel content, and features that had not been included in previous smartphone-based strategies for colonoscopy preparation. The ability to tailor instructions made the smartphone app preferable to other modes of delivery. Study findings recognize the importance of including potential users in the development phase of building a smartphone app.

Background & Aims Diagnosis of preclinical compensated cirrhosis (occult cirrhosis, OC) is challenging due to lack of clinical findings. We evaluated prevalence and outcomes of OC by transient elastography (TE, Fibroscan®). Methods Eight hundred and seventy-one patients with compensated chronic liver disease (CLD) and TE examination were divided into: (i) OC (TE ≥ 13 kPa and no sign of cirrhosis, including absence of thrombocytopenia and signs of advanced liver disease on ultrasound or gastroscopy); (ii) clinically evident cirrhosis (TE ≥ 13 kPa with signs of cirrhosis); (iii) non-cirrhotic CLD (TE

Background and aim HIV-infected individuals are at high risk of developing nonalcoholic steatohepatitis (NASH), a leading cause of end-stage liver disease in Western countries. Nonetheless, due to the invasiveness of liver biopsy, NASH remains poorly understood in HIV mono-infection. We aimed to characterize the prevalence and predictors of NASH in unselected HIV mono-infected patients by means of non-invasive diagnostic tools. Methods HIV-infected adults without significant alcohol intake or co-infection with hepatitis B or C underwent a routine screening program employing transient elastography (TE) with controlled attenuation parameter (CAP) and the serum biomarker cytokeratin-18 (CK-18). NASH was diagnosed non-invasively as the coexistence of fatty liver (CAP ≥248 dB/m) and CK-18 >246 U/L. Identified cases of NASH were offered a diagnostic liver biopsy. Predictors of NASH were determined by multivariate logistic regression analysis. Results 202 consecutive HIV mono-infected patients were included. NASH was non-invasively diagnosed in 23 cases (11.4%). Among them, 17 underwent a liver biopsy, and histology confirmed NASH in all cases. The prevalence of NASH was higher in patients with hypertriglyceridemia (17.1%), insulin resistance defined by homeostasis model for assessment of insulin resistance (HOMA-IR) (25%), those with detectable HIV viral load (42.9%) and those with elevated ALT (53.6%). After adjustment, higher HOMA-IR (adjusted odds ratio [aOR] = 1.20, 95% CI 1.01–1.43; p = 0.03) and ALT (aOR = 2.39, 95% CI 1.50–3.79; p

Background and Aims. Serum fibrosis biomarkers have shown good accuracy in the liver transplant (LT) population. We employed a simple serum biomarker to elucidate incidence and predictors of advanced fibrosis after LT over a long follow-up period.Methods. We included 440 consecutive patients who underwent LT between 1991 and 2013. Advanced liver fibrosis was defined as FIB-4 > 3.25 beyond 12 months after LT.Results. Over 2030.5 person-years (PY) of follow-up, 189 (43%) developed FIB-4 > 3.25, accounting for an incidence of 9.3/100 PY (95% confidence interval [CI], 8.1–10.7). Advanced fibrosis was predicted by chronic HCV infection (adjusted hazard ratio (aHR) = 3.96, 95% CI 2.92–5.36,p< 0.001), hypoalbuminemia (aHR = 2.31, 95% CI 1.72–3.09;p< 0.001), and hyponatremia (aHR = 1.48, 95% CI 1.09–2.01;p= 0.01). LT recipients with more than 1 predictor had a higher incidence of advanced fibrosis, the highest being when all 3 predictors coexisted (log-rank:p< 0.001).Conclusions. Chronic HCV infection, hypoalbuminemia, and hyponatremia predict progression to advanced liver fibrosis following LT. Patients with these risk factors should be serially monitored using noninvasive fibrosis biomarkers and prioritized for interventions.

Hepatic steatosis (HS) seems common in patients infected with human immunodeficiency virus (HIV). However, the relative effect of HIV, as well as hepatitis C virus (HCV) in those co-infected, and the influence of HS on liver fibrosis progression are unclear.The LIVEr disease in HIV (LIVEHIV) is a Canadian prospective cohort study using transient elastography and associated controlled attenuation parameter (CAP) to screen for HS and liver fibrosis, in unselected HIV-infected adults. HS progression was defined as development of any grade HS (CAP ⩾248dB/m), or transition to severe HS (CAP292dB/m), for those with any grade HS at baseline. Fibrosis progression was defined as development of significant liver fibrosis (liver stiffness measurement [LSM]7.1kPa), or transition to cirrhosis (LSM12.5kPa) for those with significant liver fibrosis at baseline. Cox regression analysis was used to assess predictors of HS and fibrosis progression.A prospective cohort study was conducted, which included 726 HIV-infected patients (22.7% HCV co-infected). Prevalence of any grade HS did not differ between HIV mono-infected and HIV/HCV co-infected patients (36.1% vs. 38.6%, respectively). 313 patients were followed for a median of 15.4 (interquartile range 8.5-23.0) months. The rate of HS progression was 37.8 (95% confidence interval [CI] 29.2-49.0) and 21.9 (95% CI 15.6-30.7) per 100 person-years in HIV mono-infection and HIV/HCV co-infection, respectively. HCV co-infection was an independent negative predictor of HS progression (adjusted hazard ratio [aHR] 0.50, 95% CI 0.28-0.89). HS predicted liver fibrosis progression in HIV mono-infection (aHR 4.18, 95% CI 1.21-14.5), but not in HIV/HCV co-infection.HS progresses faster and is associated with liver fibrosis progression in HIV mono-infection but not in HIV/HCV co-infection. Lay summary: Fatty liver is the most frequent liver disease in Western countries. People living with HIV seem at high risk of fatty liver due to frequent metabolic disorders and the long-term effects of antiretroviral therapy. However, due to the invasiveness of liver biopsy, the traditional method of diagnosing fatty liver, there are few data regarding its frequency in people living with HIV. In this study, we used a non-invasive diagnostic tool to analyze the epidemiology of fatty liver in 726 HIV+ patients. We found that fatty liver affects over one-third of people living with HIV. When followed over time, we found that HIV+ patients without HCV co-infection develop fatty liver more frequently than those co-infected with HCV.

Chylous ascites refers to the accumulation of lipid-rich lymph in the peritoneal cavity due to disruption of the lymphatic system secondary to traumatic injury or obstruction. Worldwide, abdominal malignancy, cirrhosis, and tuberculosis are the commonest causes of CA in adults, the latter being most prevalent in developing countries, whereas congenital abnormalities of the lymphatic system and trauma are commonest in children. The presence of a milky, creamy appearing ascitic fluid with triglyceride content above 200 mg/dL is diagnostic, and, in the majority of cases, unless there is a strong suspicion of malignancy, further investigations are not required in patients with cirrhosis. If an underlying cause is identified, targeted therapy is possible, but most cases will be treated conservatively, with dietary support including high-protein and low-fat diets supplemented with medium-chain triglycerides, therapeutic paracentesis, total parenteral nutrition, and somatostatins. Rarely, resistant cases have been treated by transjugular intrahepatic portosystemic shunt, surgical exploration, or peritoneovenous shunt.

OBJECTIVE: To provide an approach to the care of liver transplant (LT) patients, a growing patient population with unique needs.METHODS: A literature search of PubMed for guidelines and review articles using the keywords “liver transplantation”, “long term complications” and “medical management” was conducted, resulting in 77 articles.RESULTS: As a result of being on immunosuppression, LT recipients are at increased risk of infections and must be screened regularly for metabolic complications and malignancies.DISCUSSION: Although immunosuppression is key to maintaining allograft health after transplantation, it comes with its own set of medical issues to follow. Physicians following LT recipients must be aware of the greater risk for hypertension, diabetes, dyslipidemia, renal failure, metabolic bone disease and malignancies in these patients, all of whom require regular monitoring and screening. Vaccination, quality of life, sexual function and pregnancy must be specifically addressed in transplant patients.