Prognostic value of non-invasive scores based on liver stiffness measurement, spleen diameter and platelets in HIV-infected patients.

BACKGROUND AND AIMS People living with HIV (PLWH) are at high risk for advanced chronic liver disease and related adverse outcomes. We aimed to validate the prognostic value of non-invasive scores based on liver stiffness measurement (LSM) and on markers of portal hypertension (PH), namely platelets and spleen diameter, in PLWH. METHODS We combined data from eight international cohorts of PLWH with available non-invasive scores, including LSM and the composite biomarkers liver stiffness-spleen size-to-platelet ratio score (LSPS), LSM-to-Platelet ratio (LPR) and PH risk score. Incidence and predictors of all-cause mortality, any liver-related event and classical hepatic decompensation were determined by survival analysis, controlling for competing risks for the latter two. Non-invasive scores were assessed and compared using area under the receiver operating curve (AUROC). RESULTS We included 1695 PLWH (66.8% coinfected with hepatitis C virus). During a median follow-up of 4.7 (interquartile range 2.8-7.7) years, the incidence rates of any liver-related event, all-cause mortality and hepatic decompensation were 13.7 per 1000 persons-year (PY) (95% confidence interval [CI], 11.4-16.3), 13.8 per 1000 PY (95% CI, 11.6-16.4) and 9.9 per 1000 PY (95% CI, 8.1-12.2), respectively. The AUROC of LSM was similar to that of the composite biomarkers, ranging between 0.83 and 0.86 for any liver-related event, 0.79-0.85 for all-cause mortality and 0.87-0.88 for classical hepatic decompensation. All individual non-invasive scores remained independent predictors of clinical outcomes in multivariable analysis. CONCLUSIONS Non-invasive scores based on LSM, spleen diameter and platelets predict clinical outcomes in PLWH. Composite biomarkers do not achieve higher prognostic performance compared to LSM alone

Prognostic value of non-invasive scores based on liver stiffness measurement, spleen diameter and platelets in HIV-infected patients

BACKGROUND AND AIMS: People living with HIV (PLWH) are at high risk for advanced chronic liver disease and related adverse outcomes. We aimed to validate the prognostic value of non-invasive scores based on liver stiffness measurement (LSM) and on markers of portal hypertension (PH), namely platelets and spleen diameter, in PLWH. METHODS: We combined data from eight international cohorts of PLWH with available non-invasive scores, including LSM and the composite biomarkers liver stiffness-spleen size-to-platelet ratio score (LSPS), LSM-to-Platelet ratio (LPR) and PH risk score. Incidence and predictors of all-cause mortality, any liver-related event and classical hepatic decompensation were determined by survival analysis, controlling for competing risks for the latter two. Non-invasive scores were assessed and compared using area under the receiver operating curve (AUROC). RESULTS: We included 1695 PLWH (66.8% coinfected with hepatitis C virus). During a median follow-up of 4.7 (interquartile range 2.8-7.7) years, the incidence rates of any liver-related event, all-cause mortality and hepatic decompensation were 13.7 per 1000 persons-year (PY) (95% confidence interval [CI], 11.4-16.3), 13.8 per 1000 PY (95% CI, 11.6-16.4) and 9.9 per 1000 PY (95% CI, 8.1-12.2), respectively. The AUROC of LSM was similar to that of the composite biomarkers, ranging between 0.83 and 0.86 for any liver-related event, 0.79-0.85 for all-cause mortality and 0.87-0.88 for classical hepatic decompensation. All individual non-invasive scores remained independent predictors of clinical outcomes in multivariable analysis. CONCLUSIONS: Non-invasive scores based on LSM, spleen diameter and platelets predict clinical outcomes in PLWH. Composite biomarkers do not achieve higher prognostic performance compared to LSM alone

PERDUS DE VUE (MOTIFS D'ARRET DE SUIVI DES PORTEURS DU VIH : ETUDE CAS-TEMOINS ET RECHERCHE EN ETHIQUE CLINIQUE)

LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUM (751062103) / SudocLYON-Université catholique (693822301) / SudocSudocFranceF

Developing a patient-reported outcome measure for HIV care on perceived barriers to antiretroviral adherence: assessing the needs of HIV clinicians through qualitative analysis

To identify HIV clinicians' needs for the clinical use of a new patient-reported outcome measure (PRO) on barriers to antiretroviral therapy (ART) adherence. In 2015, five focus groups with 31 clinicians from France were transcribed, coded with Atlas.ti, and submitted to a typological analysis. The analysis identified seven patient profiles, each tied to distinct barriers to adherence and to specific needs for the PRO's content, data collection and transmission. Clinicians preferred, for the patient who is: (1) `passive,' that the PRO collect information on ART knowledge, to ensure that the prescription's instructions are being respected; (2) `misleading,' that it be able to detect adherence to ART and socially desirable responses; (3) `stoic,' that questions challenge the patient to recognize treatment-specific side effects; (4) `hedonistic,' that the PRO contains content on lifestyle and risk-taking; (5) `obsessive,' that the PRO captures quality of life and stressful life events; (6) `overburdened,' that the PRO provides information on the person's home environment, socioeconomic status and cultural constraints. For all or most patient profiles, the clinicians wished that the PRO be completed, minimally, prior to the medical consultation and to receive alerts, under varying conditions, when problematic scores were detected. Depending on the profile, there was preference for the inclusion of open-ended questions and transmission of cross-sectional, periodic or longitudinal PRO data. Overall, this study's findings suggest that to support the clinical management of ART adherence, our PRO must meet the needs of a wide variety of patients and must perform multiple functions

Patient profiles as organizing HIV clinicians' ART adherence management: a qualitative analysis

The effectiveness of antiretroviral therapy (ART) depends on optimal clinical management and patient adherence. Little is known about patient characteristics that clinicians consider in the management of ART adherence. Exploring this issue, five focus groups were conducted with 31 HIV-clinicians from across France. A qualitative typological analysis suggests that clinician management of patient adherence is based on characteristics that coalesce into seven patient profiles. For the passive patient, described as taking ART exactly as prescribed without questioning their doctor's expertise, a directive and simple management style was preferred. The misleading patient is characterized as concerned with social desirability and as reporting no adherence difficulties for fear of displeasing their doctor. If clinical outcomes are suboptimal, the clinicians' strategy is to remind them of the importance of open patient-clinician communication. The stoic patient is described as requesting and adequately taking the most potent ART available. Here, clinicians emphasize assessment of side effects, which the patient may minimize. The hedonistic patient's festive lifestyle and sexual risk-taking are seen as compromising adherence; with them, clinicians stress the patient's responsibility for their own health and that of their sexual partners. The obsessive patient is portrayed as having an irrational fear of ART failure and an inability to distinguish illusory from genuine adherence barriers. With this patient, clinicians seek to identify the latter. The overburdened patient is recognized as coping with life priorities that interfere with adherence and, with them, a forgiving ART is favored. The underprivileged patient is presented as having limited education, income and housing. In this case, clinicians seek to improve the patient's living conditions and access to care. These results shed light on HIV clinicians' ART adherence management. The value of these profiles for HIV care and patients should be investigated

Prevalence, Predictors, and Severity of Lean Nonalcoholic Fatty Liver Disease in Patients Living With Human Immunodeficiency Virus

The burden of non-alcoholic fatty liver disease (NAFLD) is growing in people with HIV. NAFLD is associated with obesity, however it can occur in normoweight (lean) patients. We aimed to investigate lean NAFLD in HIV-infected patients

Screening for nonalcoholic steatohepatitis by using cytokeratin 18 and transient elastography in HIV mono-infection.

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.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.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<0.001) were independent predictors of NASH.NASH, diagnosed by a non-invasive diagnostic approach employing CK-18 and TE with CAP, is common in unselected HIV mono-infected individuals, particularly in the presence of insulin resistance and elevated ALT

Diagnosis of liver fibrosis in ageing patients with HIV at risk for non-alcoholic fatty liver disease in Italy and Canada: assessment of a two-tier pathway

Background: Since the introduction of effective antiretroviral therapy, liver-related mortality has increased ten-fold in ageing people with HIV. This trend is driven by ageing-related metabolic conditions that cause non-alcoholic fatty liver disease (NAFLD), which affects 35-65% of people with HIV. Clinically significant (stage 2-4) liver fibrosis develops in over 15% of people with HIV who have NAFLD. Strategies are needed to identify people with HIV at risk for significant liver fibrosis and reduce cirrhosis-related complications. Non-invasive tests to diagnose liver fibrosis include ultrasound-based transient elastography and serum biomarkers. Transient elastography is a feasible tool to assess liver fibrosis, but it is not largely accessible in HIV clinics. We aimed to determine whether a two-tier care pathway with assessment of simple serum biomarkers for fibrosis as first tier could reduce the need for the specialist transient elastography test (second tier). Methods: Patients were consecutively identified through a clinical programme for liver disease in people with HIV in Canada and Italy. We applied a two-tier care pathway to three prospective cohorts of people with HIV at risk for NAFLD, defined as those with elevated liver transaminases, body mass index (BMI) of 25 or greater, or diabetes. Patients with alcohol abuse or coinfection with hepatitis B or C viruses were excluded. Five simple serum biomarkers of fibrosis, based on liver transaminases, platelets, and BMI (fibrosis-4 index [FIB-4], BARD [BMI, AST to ALT ratio, diabetes] score, NAFLD fibrosis score, AST to ALT ratio, and AST-to-platelet ratio index [APRI]) were applied as a first-tier assessment to exclude significant liver fibrosis. All patients then received transient elastography. We assessed the decrease in referral for transient elastography that would have occurred based on biomarker assessment and discordance between high transient elastography (≥7·1 kPa), indicating significant liver fibrosis, and low serum fibrosis biomarkers (FIB-4 &lt;1·3, BARD score 0-1, NAFLD fibrosis score less than -1·455, AST to ALT ratio &lt;0·8, and APRI &lt;0·5). We also assessed independent factors associated with that discordance by multivariable logistic regression analysis. Findings: We included 1202 people with HIV at risk for NAFLD (mean age 51·2 years [SD 10·1], 914 [76%] male and 288 [24%] female, mean HIV duration 16·3 years [SE 9·7], mean BMI 26·5 Kg/m2 [SD 4·5]; prevalence of diabetes 49·5%). 222 (18·5%) of these participants had significant liver fibrosis according to transient elastography. Assessment of simple fibrosis biomarkers would have decreased transient elastography referrals between 22·5% (BARD score) and 82·4% (APRI). Discordance rate ranged from 3·9% (NAFLD fibrosis score) to 11·1% (APRI). After adjustment for age, sex, presence of diabetes, level of HDL cholesterol, and CD4 cell count, BMI (odds ratio 1·12, 95% CI 1·07-1·17) and triglyceride level (1·25, 1·08-1·46) were independent predictors of discordance for low APRI and high transient elastography. Interpretation: Use of a two-tier pathway to identify liver fibrosis in ageing people with HIV at risk for NAFLD could reduce transient elastography examinations by a substantial proportion, reducing costs and helping to optimise use of resources in HIV care