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Purpose: Hepatic steatosis (fatty liver disease) affects 25% of the world's population, particularly people with HIV (PWH). Pharmacoepidemiologic studies to identify medications associated with steatosis have not been conducted because methods to evaluate liver fat within digitized images have not been developed. We determined the accuracy of a deep learning algorithm (automatic liver attenuation region‐of‐interest‐based measurement [ALARM]) to identify steatosis within clinically obtained noncontrast abdominal CT images compared to manual radiologist review and evaluated its performance by HIV status. Methods: We performed a cross‐sectional study to evaluate the performance of ALARM within noncontrast abdominal CT images from a sample of patients with and without HIV in the US Veterans Health Administration. We evaluated the ability of ALARM to identify moderate‐to‐severe hepatic steatosis, defined by mean absolute liver attenuation <40 Hounsfield units (HU), compared to manual radiologist assessment. Results: Among 120 patients (51 PWH) who underwent noncontrast abdominal CT, moderate‐to‐severe hepatic steatosis was identified in 15 (12.5%) persons via ALARM and 12 (10%) by radiologist assessment. Percent agreement between ALARM and radiologist assessment of absolute liver attenuation <40 HU was 95.8%. Sensitivity, specificity, positive predictive value, and negative predictive value of ALARM were 91.7% (95%CI, 51.5%–99.8%), 96.3% (95%CI, 90.8%–99.0%), 73.3% (95%CI, 44.9%–92.2%), and 99.0% (95%CI, 94.8%–100%), respectively. No differences in performance were observed by HIV status. Conclusions: ALARM demonstrated excellent accuracy for moderate‐to‐severe hepatic steatosis regardless of HIV status. Application of ALARM to radiographic repositories could facilitate real‐world studies to evaluate medications associated with steatosis and assess differences by HIV status. [ABSTRACT FROM AUTHOR]

Objectives: To perform a systematic review and meta‐analysis of the techniques and outcomes associated with percutaneous decannulation of venoarterial extracorporeal membrane oxygenation (VA–ECMO) using the Manta vascular closure device. Background: Peripheral VA–ECMO can be used to treat critically ill patients with conditions such as refractory cardiogenic shock. After percutaneous implantation of VA–ECMO, VA–ECMO can also be decannulated completely percutaneously by using a vascular closure device. The Manta vascular closure device is a dedicated device used in the closure of large‐bore arteriotomies by sandwiching the arteriotomy with an intra‐arterial toggle and an extraluminal collagen plug. Methods: We performed a thorough literature search using various electronic databases. We included studies that reported outcomes after peripheral femorofemoral VA–ECMO decannulation with the Manta vascular closure device. We performed a meta‐analysis of proportions on outcome measures, including technical success, bleeding complications, vascular complications, wound complications, major amputation, and procedural‐related deaths. Results: We included seven studies with a total of 116 patients. The overall technical success of percutaneous decannulation of VA–ECMO with the Manta vascular closure device was 93.7%. The overall incidence of bleeding, vascular and wound complications was 1.7%, 13.8%, and 3.4%, respectively. No patient required lower limb amputation or died due to VA–ECMO decannulation. Conclusion: Percutaneous decannulation with the Manta vascular closure device is an effective and safe procedure that should be considered in suitable patients on VA–ECMO. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Tan et al paper. To view this article, visit https://doi.org/10.1111/apt.17914 [ABSTRACT FROM AUTHOR]

Background and Aim: Chronic hepatitis C virus (HCV) infection, long‐term alcohol use, cigarette smoking, and obesity are the major risk factors for hepatocellular carcinoma (HCC) in the United States, but the disease risk varies substantially among individuals with these factors, suggesting host susceptibility to and gene–environment interactions in HCC. To address genetic susceptibility to HCC, we conducted a genome‐wide association study (GWAS). Methods: Two case‐control studies on HCC were conducted in the United States. DNA samples were genotyped using the Illumian microarray chip with over 710 000 single nucleotide polymorphisms (SNPs). We compared these SNPs between 705 HCC cases and 1455 population controls for their associations with HCC and verified our findings in additional studies. Results: In this GWAS, we found that two SNPs were associated with HCC at P < 5E‐8 and six SNPs at P < 5E‐6 after adjusting for age, sex, and the top three principal components (PCs). Five of the SNPs in chromosome 22q13.31, three in PNPLA3 (rs2281135, rs2896019, and rs4823173) and two in SAMM50 (rs3761472, rs3827385), were replicated in a small US case‐control study and a cohort study in Singapore. The associations remained significant after adjusting for body mass index and HCV infection. Meta‐analysis of multiple datasets indicated that these SNPs were significantly associated with HCC. Conclusions: SNPs in PNPLA3 and SAMM50 are known risk loci for nonalcoholic fatty liver disease (NAFLD) and are suspected to be associated with HCC. Our GWAS demonstrated the associations of these SNPs with HCC in a US population. Biological mechanisms underlying the relationship remain to be elucidated. [ABSTRACT FROM AUTHOR]

Background: Inflammation and the immune system significantly impact the development, progression, and treatment response of hepatocellular carcinoma (HCC). This retrospective study investigated the neutrophil-to-lymphocyte ratio (NLR) as a prognostic biomarker in Western patients with HCC in the setting of chronic viral hepatitis. Methods: Patients diagnosed with HCC from 2005 to 2016 were selected from a tertiary care institution. NLR was calculated within 30 days prior to treatment and dichotomized at the median. Kaplan–Meier overall survival (OS) curves and Cox hazard proportional models were utilized. Tumor and liver reserve parameters were included in multivariable analyses (MVA). Results: A total of 581 patients met inclusion criteria (median age 61.0 yr; 78.3% male; 66.3% Caucasian) with median OS = 34.9 mo. 371 patients (63.9%) had viral hepatitis, of which 350 had hepatitis C (94.3%). The low-NLR group (

In the United States, Black people are disproportionately diagnosed with hepatitis C virus (HCV) compared with White people but are under‐represented in HCV studies. In this US‐based cross‐sectional telephone survey study, we assessed willingness to participate (WTP) in health/medical research and attitudes and beliefs that may influence WTP among Black patients with HCV. Two hundred participants who had current or prior HCV diagnosis and self‐identified as Black or African American were recruited from a national HCV cohort study and an outpatient hepatology clinic. WTP responses ranged from 1 (not at all willing) to 5 (very willing). Multivariable models were used to identify factors associated with the overall mean WTP score. In addition, an open‐ended question solicited strategies to help increase research participation from the Black community. Overall, participants reported moderate WTP in research (Mean [95% Confidence Interval (CI)] = 3.78 [3.68, 3.88]). Of 13 types of research presented, participants reported lowest WTP for randomized controlled trials of medications (Mean [95% CI] = 2.31 [2.11, 2.50]). The initial multivariable model identified higher subjective knowledge of research as positively associated with WTP (Parameter estimate [95% CI] = 0.15 [0.02, 0.27]). Sensitivity analyses also identified higher perceived benefits of research as an additional factor associated with WTP. Qualitative findings indicate that greater community‐based outreach efforts would increase accessibility of research opportunities. When given the opportunity to participate, Black participants with HCV reported moderate WTP in health/medical research. Research sponsors and investigators should employ community‐based outreach to expand access and awareness of research opportunities. [ABSTRACT FROM AUTHOR]

Background & Aims: The long‐term impact of hepatitis C virus (HCV) therapy with all‐oral direct‐acting antivirals (DAAs) on patient‐reported outcomes (PROs) has not been well‐described. We characterized changes in PROs from pre‐treatment to 12 months post‐treatment in a real‐world cohort. Methods: PROP UP was a multi‐centre observational cohort study of 1601 patients treated with DAAs at 11 US gastroenterology/hepatology practices from 2015 to 2017. PROs were evaluated pre‐treatment (T1) and 12 months post‐treatment (T5). A minimally important change (MIC) threshold was prespecified as >5% change in PRO scores from T1 to T5. Multivariable analyses identified predictors of change. Results: Three‐quarters of patients were 55 or older; 45% were female, 60% were white, 33% were black, nearly half had cirrhosis. The most commonly‐prescribed DAA regimens were sofosbuvir‐based (83%) and grazoprevir/elbasvir (11%). Study retention was >95%. On average, small improvements were observed at 3 months post‐treatment in all PROs and sustained at 12 months post‐treatment among patients with sustained virologic response (SVR). Clinically meaningful improvements were achieved in fatigue (mean change score: −3.7 [−4.2, −3.1]), sleep (mean change score: −3.1 [−3.7, −2.5]), abdominal pain (mean change score: −2.6 [−3.3, −1.9]) and functional well‐being (mean change score: −7.0 [−6.0, −8.0]). Symptom improvements were generally not sustained with no SVR (n = 52). Patients with cirrhosis and MELD ≥12 had the greatest improvements in functional well‐being (−12.9 [−17.6, −8.1]). Conclusions: The improvements in patient‐reported outcomes reported by patients who achieved SVR following HCV DAA therapy were durable at 12 months post‐treatment. [ABSTRACT FROM AUTHOR]

Background: To investigate the impact of insurance status on outcomes in patients with hepatocellular carcinoma (HCC). Methods: Patients diagnosed with HCC in the cancer registry from 2005 to 2016 were retrospectively stratified by insurance group. Overall survival was assessed via Kaplan‐Meier curves and Cox proportional hazard models including potential confounders in multivariable analyses. Results: Seven hundred and sixty‐nine patients met inclusion criteria (median age 63 years, 78.8% male, 65.9% Caucasian). 44.5% had private insurance (n = 342), 29.1% had Medicare (n = 224), and 26.4% had Medicaid (n = 203). At diagnosis, Medicaid patients had higher rates of Child‐Pugh B (32.0%) and C disease (23.6%) vs Medicare (28.6% and 9.8%) and private insurance (26.9% and 6.7%, P < 0.0001) and higher MELD scores (median 11.0) vs Medicare (9.0) and private insurance (9.0, P = 0.0266). Across insurance groups, patients had similar distribution of American Joint Committee on Cancer stage, tumor size, and multifocal tumor burden. Patients with private insurance had the highest survival (median OS 21.9 months) vs Medicare (17.7 months) and Medicaid (13.0 months, overall P = 0.0061). On univariate analysis, Medicaid patients demonstrated decreased survival vs private insurance (HR 1.40, 95% CI: 1.146‐1.715, P = 0.0011). After adjustment for liver disease factors, this survival difference lost statistical significance (Medicaid vs private insurance, HR 1.02, 95% CI: 0.819‐1.266, P = 0.8596). Conclusion: Medicaid was associated with advanced liver disease at HCC diagnosis; however, insurance status is not an independent predictor of HCC survival. [ABSTRACT FROM AUTHOR]

Alterations in parietal and temporal white matter microstructure derived from diffusion tensor imaging occur in preclinical and clinical Alzheimer's disease. Amyloid beta (Aβ) deposition and such white matter alterations are two pathological hallmarks of Alzheimer's disease. However, the relationship between these pathologies is not yet understood, partly since conventional diffusion MRI methods cannot distinguish between cellular and extracellular processes. Thus, we studied Aβ‐associated longitudinal diffusion MRI changes in Aβ‐positive (N = 21) and Aβ‐negative (N = 51) cognitively normal elderly obtained from the Alzheimer's Disease Neuroimaging Initiative dataset using linear mixed models. Aβ‐positivity was based on Alzheimer's Disease Neuroimaging Initiative amyloid‐PET recommendations using a standardized uptake value ratio cut‐off of 1.11. We used free‐water imaging to distinguish cellular and extracellular changes. We found that Aβ‐positive subjects had increased baseline right uncinate fasciculus free‐water fraction (FW), associated with worse baseline Alzheimer's disease assessment scale scores. Furthermore, Aβ‐positive subjects showed faster decrease in fractional anisotropy (FW‐corrected) in the right uncinate fasciculus and faster age‐dependent right inferior longitudinal fasciculus FW increases over time. Right inferior longitudinal fasciculus FW increases were associated with greater memory decline. Importantly, these results remained significant after controlling for gray and white matter volume and hippocampal volume. This is the first study to illustrate the influence of Aβ burden on early longitudinal (in addition to baseline) white matter changes in cognitively normal elderly individuals at‐risk of Alzheimer's disease, thus underscoring the importance of longitudinal studies in assessing microstructural alterations in individuals at risk of Alzheimer's disease prior to symptoms onset. [ABSTRACT FROM AUTHOR]

Purpose Among patients dually infected with human immunodeficiency virus (HIV) and chronic hepatitis C virus (HCV), use of antiretroviral therapy (ART) containing mitochondrial toxic nucleoside reverse transcriptase inhibitors (mtNRTIs) might induce chronic hepatic injury, which could accelerate HCV-associated liver fibrosis and increase the risk of hepatic decompensation and death. Methods We conducted a cohort study among 1747 HIV/HCV patients initiating NRTI-containing ART within the Veterans Aging Cohort Study (2002-2009) to determine if cumulative mtNRTI use increased the risk of hepatic decompensation and death among HIV-/HCV-coinfected patients. Separate marginal structural models were used to estimate hazard ratios (HRs) of each outcome associated with cumulative exposure to ART regimens that contain mtNRTIs versus regimens that contain other NRTIs. Results Over 7033 person-years, we observed 97 (5.6%) decompensation events (incidence rate, 13.8/1000 person-years) and 125 (7.2%) deaths (incidence rate, 17.8 events/1000 person-years). The risk of hepatic decompensation increased with cumulative mtNRTI use (1-11 mo: HR, 1.79 [95% confidence interval (CI), 0.74-4.31]; 12-35 mo: HR, 1.39 [95% CI, 0.68-2.87]; 36-71 mo: HR, 2.27 [95% CI, 0.92-5.60]; >71 mo: HR, 4.66 [95% CI, 1.04-20.83]; P = .045) versus nonuse. Cumulative mtNRTI use also increased risk of death (1-11 mo: HR, 2.24 [95% CI, 1.04-4.81]; 12-35 mo: HR, 2.05 [95% CI, 0.68-6.20]; 36-71 mo: HR, 3.04 [95% CI, 1.12-8.26]; >71 mo: HR, 3.93 [95% CI, 0.75-20.50]; P = .030). Conclusions These findings suggest that cumulative mtNRTI use may increase the risk of hepatic decompensation and death in HIV/HCV coinfection. These drugs should be avoided when alternatives exist for HIV/HCV patients. [ABSTRACT FROM AUTHOR]

Background and Aim Patients with HIV-hepatitis C virus (HCV) coinfection progress towards liver fibrosis and cirrhosis more rapidly compared with HCV mono-infected individuals. This necessitates an accurate assessment of liver stiffness with transient elastography to guide treatment. Methods Searches of PubMed, EMBASE, Web of Science, and the Cochrane Library databases were performed through January 2016 to assess the diagnostic accuracy of transient elastography for liver stiffness in the HIV-HCV population. Included studies were analyzed according to the Cochrane DTA Working Group methodology. Bivariate and hierarchical models were used to compute pooled sensitivity and specificity. Positive and negative likelihood ratios were also determined. A Fagan nomogram was constructed. Meta-regression analysis was performed with assessment of publication bias using Deeks' funnel plot asymmetry testing. Results A total of six studies ( n = 756) met the inclusion criteria. The diagnostic accuracy of elastography for the diagnosis of moderate (≥F2) fibrosis was 88% (95% confidence interval [CI], 0.85-0.90). The pooled sensitivity and specificity of moderate fibrosis was 97% (95% CI, 0.82-0.91) and 64% (95% CI, 0.45-0.79), respectively. The diagnostic accuracy of elastography for the assessment of cirrhosis was 94% (95% CI, 0.91-0.95). The pooled sensitivity and specificity for cirrhosis was 90% (95% CI, 0.74-0.97) and 87% (95% CI, 0.80-0.92), respectively. Meta-regression analysis demonstrated that CD4 cell count did not impact diagnostic accuracy of elastography. Conclusions Transient elastography is a noninvasive imaging modality with excellent ability to assess for cirrhosis in patients with HIV-HCV coinfection. [ABSTRACT FROM AUTHOR]

Background & Aims Renal clearance is the major elimination pathway for sofosbuvir ( SOF). We assessed the safety and efficacy of SOF-containing regimens in patients with varying baseline estimated glomerular filtration rate ( eGFR). Methods HCV- TARGET database is a multicentre, longitudinal 'real-world' treatment cohort. Results A total of 1789 patients [genotypes 1 (72%), 2 (17%) 3 (9%), 4-6 (2%)] had baseline eGFR determination: 73 with eGFR≤45 (18 with eGFR≤30, 5 on dialysis) were compared to 1716 with eGFR>45 ml/min/1.73 m2. Patients with baseline eGFR≤45 vs. >45 differed in being female (55% vs. 36%), age ≥65 years (24% vs. 16%), Black race (22% vs. 12%), having cirrhosis with decompensation (73% vs. 24%) and being post-transplant (49% vs. 10%), all P < 0.05. All patients with eGFR≤45 were treated with SOF 400 mg/day (including those on haemodialysis) and had median starting ribavirin ( RBV) dose of 800 mg ( IQR: 400-1200). Sustained virologic response ( SVR) frequencies were similar across eGFR groups, ranging from 82-83%. Patients with eGFR ≤45 more frequently experienced anaemia, worsening renal function and serious AEs (all P < 0.05), and these associations persisted when limiting analysis to RBV-free regimens. Patients with baseline eGFR≤30 and eGFR 31-45 had similar frequencies of efficacy and safety outcomes. Conclusions Sustained viral clearance was achieved in 83% of patients with renal impairment ( eGFR ≤45 ml/min/1.73 m2) treated with SOF-containing regimens. However, these patients had higher rates of anaemia, worsening renal dysfunction and serious adverse events regardless of use of RBV. Patient with renal impairment require close monitoring and should be treated by providers extensively experienced with SOF-containing regimens. [ABSTRACT FROM AUTHOR]

Background & Aims Antiviral drugs are safe and effective in the third trimester to prevent intrauterine transmission of hepatitis B virus, and are recommended for hepatitis B virus ( HBV) infected gravid mothers (between weeks 28 and 32) with high viral load, followed by postnatal hepatitis B immunization in the newborn. We estimated the comparative efficacy of antiviral drugs for prevention of vertical transmission of HBV, through a network meta-analysis of clinical trials. Methods We conducted a comprehensive search of MEDLINE, EMBASE and published proceedings from major liver meetings from January 1980 to November 2014. We conducted pair-wise meta-analyses and Bayesian framework using Markov chain Monte Carlo methods, combining direct and indirect evidence for any given pair of treatments. Results Seventeen clinical trials involving 2764 newborns of hepatitis B surface antigen seropositive mothers were eligible for analysis. There were no clinical trials involving tenofovir or entecavir. On pair-wise meta-analyses, telbivudine (hazard ratio, HR 0.12, 95% confidence interval ( CI) 0.04-0.37; I2 = 0%), and Lamivudine ( HR 0.40, 95% CI 0.24-0.65; I2 = 0%), were more effective than placebo in reducing vertical transmission of HBV in high viremic hepatitis B e antigen ( HBeAg)-positive chronic Hepatitis B Chinese patients. Sensitivity analyses limited to studies with HBeAg seropositive mothers revealed similar results. Conclusions Based on a Bayesian network meta-analysis of clinical trials, combining direct and indirect treatment comparisons, telbivudine appears to be more effective than Lamivudine for preventing vertical transmission of HBV infection. Trials assessing the efficacy of tenofovir or entecavir compared to placebo or other antiviral drugs are lacking. [ABSTRACT FROM AUTHOR]

Background & Aims HCV Council 2014, like its predecessor HCV Council 2011, assembled leading clinicians and researchers in the field of hepatitis C to critically evaluate current data regarding best practices for managing patients with chronic hepatitis C virus ( HCV). Methods Clinical practice statements were developed that reflect the areas of potential controversy with high clinical impact. Faculty members were responsible for reviewing the literature to support or reject these statements. After a review and comprehensive discussion of the data, the HCV Council faculty voted on the nature of the evidence and the level of support for each statement. Results The results of the detailed analysis with expert opinion are summarized in this article. Conclusion Numerous questions regarding optimal management of certain populations and clinical scenarios remain unanswered. The discussion in the article provides a summary of evidenced-based expert opinion that may help guide clinicians as additional information is developed. [ABSTRACT FROM AUTHOR]

BSTRACT Purpose The absence of validated methods to identify hepatic decompensation in cohort studies has prevented a full understanding of the natural history of chronic liver diseases and impact of medications on this outcome. We determined the ability of diagnostic codes and liver-related laboratory abnormalities to identify hepatic decompensation events within the Veterans Aging Cohort Study (VACS). Methods Medical records of patients with hepatic decompensation codes and/or laboratory abnormalities of liver dysfunction (total bilirubin ≥ 5.0 g/dL, albumin ≤ 2.0 g/dL, INR ≥ 1.7) recorded 1 year before through 6 months after VACS entry were reviewed to identify decompensation events (i.e., ascites, spontaneous bacterial peritonitis, variceal hemorrhage, hepatic encephalopathy, hepatocellular carcinoma) at VACS enrollment. Positive predictive values (PPVs) of diagnostic codes, laboratory abnormalities, and their combinations for confirmed outcomes were determined. Results Among 137 patients with a hepatic decompensation code and 197 with a laboratory abnormality, the diagnosis was confirmed in 57 (PPV, 42%; 95%CI, 33%-50%) and 56 (PPV, 28%; 95%CI, 22%-35%) patients, respectively. The combination of any code plus laboratory abnormality increased PPV (64%; 95%CI, 47%-79%). One inpatient or ≥2 outpatient diagnostic codes for ascites, spontaneous bacterial peritonitis, or variceal hemorrhage had high PPV (91%; 95%CI, 77%-98%) for confirmed hepatic decompensation events. Conclusion An algorithm of 1 inpatient or ≥ 2 outpatient codes for ascites, peritonitis, or variceal hemorrhage has sufficiently high PPV for hepatic decompensation to enable its use for epidemiologic research in VACS. This algorithm may be applicable to other cohorts. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]