Severe Acute Liver Injury After Hepatotoxic Medication Initiation in Real-World Data.

Importance: Current approaches to classify the hepatotoxic potential of medications are based on cumulative case reports of acute liver injury (ALI), which do not consider the size of the exposed population. There is little evidence from real-world data (data relating to patient health status and/or the delivery of health care routinely collected from sources outside of a research setting) on incidence rates of severe ALI after initiation of medications, accounting for duration of exposure.

Objective: To identify the most potentially hepatotoxic medications based on real-world incidence rates of severe ALI and to examine how these rates compare with categorization based on case reports.

Integrated phenotyping of the anti-cancer immune response in HIV-associated hepatocellular carcinoma.

Background & Aims: HIV-seropositivity shortens survival in patients with hepatocellular carcinoma (HCC). Although risk factors for HCC including HCV infection can influence T cell phenotype, it is unknown whether HIV can influence functional characteristics of the T cell infiltrate.

Methods: From the Liver Cancer in HIV biorepository, we derived 129 samples of transplanted (76%) or resected (20%) HCC in eight European and North American centres.

A Learning Health System Approach to Long COVID Care.

Background: Global initiatives to mitigate COVID-19 transmission have shifted health system priorities to management of patients with prolonged long COVID symptoms. To better meet the needs of patients, clinicians, and systems, a learning health system approach can use rapid-cycle methods to integrate data and real-world experience to iteratively evaluate and adapt models of long COVID care.

Observations: Employees in the Veterans Health Administration formed a multidisciplinary workgroup.

Influence of Cancer on COVID-19 Incidence, Outcomes, and Vaccine Effectiveness: A Prospective Cohort Study of U.S. Veterans.

Purpose: Coronavirus disease 2019 (COVID-19) has been a constant health threat since its emergence. Amongst risk factors proposed, a diagnosis of cancer has been worrisome. We report the impact of cancer and other risk factors in US Veterans receiving care at Veterans Administration (VA) Hospitals, their adjusted odds ratio (aOR) for infection and death, and report on the impact of vaccines on the incidence and severity of COVID-19 infections in Veterans without/with cancer.

Tocilizumab in patients hospitalised with COVID-19 pneumonia: Efficacy, safety, viral clearance, and antibody response from a randomised controlled trial (COVACTA).

Background: In COVACTA, a randomised, placebo-controlled trial in patients hospitalised with coronavirus disease-19 (COVID-19), tocilizumab did not improve 28-day mortality, but shortened hospital and intensive care unit stay. Longer-term effects of tocilizumab in patients with COVID-19 are unknown. Therefore, the efficacy and safety of tocilizumab in COVID-19 beyond day 28 and its impact on Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) clearance and antibody response in COVACTA were investigated.

Tocilizumab in Hospitalized Patients with Severe Covid-19 Pneumonia.

Background: Coronavirus disease 2019 (Covid-19) is associated with immune dysregulation and hyperinflammation, including elevated interleukin-6 levels. The use of tocilizumab, a monoclonal antibody against the interleukin-6 receptor, has resulted in better outcomes in patients with severe Covid-19 pneumonia in case reports and retrospective observational cohort studies. Data are needed from randomized, placebo-controlled trials.

COVID-19 in spinal cord injury patients at a veterans administration hospital: A case series.

Objective: To describe the clinical features and disease course of COVID-19 in veterans with spinal cord injury (SCI).

Design: Case series of consecutive veterans with SCI treated at a single center.

Setting: SCI Unit at an urban Veterans Administration hospital at the epicenter of the COVID-19 pandemic in the US.

Brief Report: Accuracy of FIB-4 for Cirrhosis in People Living With HIV and Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) may develop in the absence of cirrhosis in HIV, and determining how often this occurs can provide insights into mechanisms of carcinogenesis. Studies evaluating the prevalence of cirrhosis in the setting of HCC among people living with HIV (PLWH) often rely on noninvasive markers, such as the Fibrosis-4 Index for Hepatic Fibrosis (FIB-4). However, the accuracy of FIB-4 for cirrhosis in the setting of HCC has not been determined among PLWH.

Ombitasvir/paritaprevir/ritonavir and dasabuvir±ribavirin for chronic HCV infection in US veterans with psychiatric disorders.

Hepatitis C virus (HCV) infections are more common among US veterans receiving care through Veterans Affairs (VA) Medical Centers than among the general population. Historically, HCV therapies had lower efficacy rates in VA patients, possibly due to common comorbidities such as psychiatric disorders and substance abuse. The direct-acting antivirals ombitasvir/paritaprevir/ritonavir and dasabuvir (OBV/PTV/r+DSV)±ribavirin (RBV) are approved in the US for HCV genotype 1 (GT1)-infected adults with or without cirrhosis.

HIV RNA, CD4+ Percentage, and Risk of Hepatocellular Carcinoma by Cirrhosis Status.

Background: Despite increasing incidence of hepatocellular carcinoma (HCC) among HIV-infected patients, it remains unclear if HIV-related factors contribute to development of HCC. We examined if higher or prolonged HIV viremia and lower CD4+ cell percentage were associated with HCC.

Methods: We conducted a cohort study of HIV-infected individuals who had HIV RNA, CD4+, and CD8+ cell counts and percentages assessed in the Veterans Aging Cohort Study (1999-2015).

Differences in Pathology, Staging, and Treatment between HIV and Uninfected Patients with Microscopically Confirmed Hepatocellular Carcinoma.

Background: The incidence of hepatocellular carcinoma (HCC) is substantially higher among HIV-infected (HIV) than uninfected persons. It remains unclear if HCC in the setting of HIV infection is morphologically distinct or more aggressive.

Methods: We evaluated differences in tumor pathology in a cohort of HIV and uninfected patients with microscopically confirmed HCC in the Veterans Aging Cohort Study from 2000 to 2015.

Adherence to pan-genotypic glecaprevir/pibrentasvir and efficacy in HCV-infected patients: A pooled analysis of clinical trials.

Background & Aims: Adequate adherence to hepatitis C virus (HCV) treatment is believed to be a key component of treatment success because non-adherence can potentially result in treatment failure and the emergence of resistant viral variants. This analysis assessed factors associated with non-adherence to glecaprevir/pibrentasvir (G/P) therapy and the impact of non-adherence on sustained virological response at post-treatment week 12 (SVR12) rates in HCV genotype (GT) 1-6-infected patients.

Methods: Adherence was calculated by pill counts at study visits during treatment, and defined as having a lowest treatment adherence of ≥80% and ≤120% at each study visit.

Influence of HIV Infection on the Natural History of Hepatocellular Carcinoma: Results From a Global Multicohort Study.

Purpose: Conflicting evidence indicates that HIV seropositivity may influence the outcome of patients with hepatocellular carcinoma (HCC), a leading cause of mortality in people with HIV. We aimed to verify whether HIV affected the overall survival (OS) of patients with HCC, independent of treatment and geographic origin.

Patients And Methods: We designed an international multicohort study of patients with HCC accrued from four continents who did not receive any anticancer treatment.

Multimethod assessment of baseline depression and relationship to hepatitis C treatment discontinuation.

Objective The primary study objective is to determine which measures of depression are associated with early discontinuation of hepatitis C virus infection treatment and to determine which measure best characterizes the depression that develops during treatment. Methods Seventy-eight treatment-naïve subjects who initiated pegylated interferon/ribavirin treatment for hepatitis C virus infection were included. Baseline depression was assessed with the Structured Interview for the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), the Hamilton Depression Rating Scale, and the Beck Depression Inventory-II.

Hepatitis C in Patients With Minimal or No Hepatic Fibrosis: The Impact of Treatment and Sustained Virologic Response on Patient-Reported Outcomes.

Background: While the necessity of treatment of hepatitis C virus (HCV)-infected patients with advanced liver disease is widely accepted, the benefit of treating patients without significant liver disease is less well established. Our aim was to assess the effect of treating HCV in patients with no or minimal fibrosis (Metavir stage F0-F1) on patient-reported outcomes (PROs).

Methods: HCV-infected patients with F0-F1 from 16 clinical trials were included.

The albumin-bilirubin grade uncovers the prognostic relationship between hepatic reserve and immune dysfunction in HIV-associated hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is a leading cause of liver-related mortality in people living with HIV, where co-infection with hepatotropic viruses accelerates the course of chronic liver disease.

Aim: To evaluate whether the albumin-bilirubin (ALBI) grade, a more accurate marker of liver dysfunction in HCC, might identify patients with progressive liver dysfunction in the context of HIV/hepatitis co-infection.

Methods: Using uni- and multi-variable analyses, we studied the albumin-bilirubin grade as a predictor of overall survival (OS) in a large, multi-center cohort of patients with HIV-associated HCC recruited from 44 centres in 9 countries within the Liver Cancer in HIV study group.

Glecaprevir and Pibrentasvir in Patients with HCV and Severe Renal Impairment.

Background: Chronic hepatitis C virus (HCV) infection is more prevalent among patients who have chronic kidney disease than among those who do not have the disease. Patients with chronic kidney disease who also have HCV infection are at higher risk for progression to end-stage renal disease than those who have chronic kidney disease without HCV infection. Patients with both HCV infection and advanced chronic kidney disease have limited treatment options.

Efficacy of 8 Weeks of Sofosbuvir, Velpatasvir, and Voxilaprevir in Patients With Chronic HCV Infection: 2 Phase 3 Randomized Trials.

Background & Aims: Patients with chronic hepatitis C virus (HCV) infection have high rates of sustained virologic response (SVR) after 12 weeks of treatment with the nucleotide polymerase inhibitor sofosbuvir combined with the NS5A inhibitor velpatasvir. We assessed the efficacy of 8 weeks of treatment with sofosbuvir and velpatasvir plus the pangenotypic NS3/4A protease inhibitor voxilaprevir (sofosbuvir-velpatasvir-voxilaprevir).

Methods: In 2 phase 3, open-label trials, patients with HCV infection who had not been treated previously with a direct-acting antiviral agent were assigned randomly to groups given sofosbuvir-velpatasvir-voxilaprevir for 8 weeks or sofosbuvir-velpatasvir for 12 weeks.

Sofosbuvir and Velpatasvir for the Treatment of Hepatitis C Virus in Patients Coinfected With Human Immunodeficiency Virus Type 1: An Open-Label, Phase 3 Study.

Background: A safe, simple, effective, and pan-genotypic regimen to treat hepatitis C virus (HCV) infection in patients coinfected with human immunodeficiency virus type 1 (HIV-1) remains a medical need. We assessed the efficacy and safety of the NS5B polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir for HCV in patients coinfected with HIV-1.

Methods: This phase 3, open-label, single-arm study at 17 sites in the United States enrolled patients with HCV of any genotype and HIV-1 coinfection, including those with compensated cirrhosis.

Greater decline in memory and global neurocognitive function in HIV/hepatitis C co-infected than in hepatitis C mono-infected patients treated with pegylated interferon and ribavirin.

The human immunodeficiency virus (HIV), hepatitis C virus (HCV), and the treatment of HCV with pegylated interferon and ribavirin (IFN/RBV) have been associated with neurocognitive and psychiatric abnormalities. The goal of this research was to prospectively evaluate neurocognitive functioning among a group of HCV mono-infected and HIV/HCV co-infected patients during the first 24 weeks of IFN/RBV treatment while accounting for practice effects, normal variations in change over time, and variations in IFN/RBV treatment exposure. Forty-four HCV mono-infected and 30 HIV/HCV co-infected patients were enrolled in a prospective study of patients beginning on IFN/RBV for chronic HCV infection.

Ribavirin-Free Regimen With Sofosbuvir and Velpatasvir Is Associated With High Efficacy and Improvement of Patient-Reported Outcomes in Patients With Genotypes 2 and 3 Chronic Hepatitis C: Results From Astral-2 and -3 Clinical Trials.

Background: Until recently, the approved treatment regimens for patients with hepatitis C virus (HCV) genotypes (GTs) 2 and 3 contain sofosbuvir (SOF) and ribavirin (RBV) for 12 or 24 weeks. The impact of RBV-free pan-genotypic regimen with SOF and velpatasvir (SOF/VEL) on patient-reported outcomes (PROs) of patients with genotype 2 and 3 has not been described.

Methods: PROs data were collected from participants of ASTRAL-2 and ASTRAL-3 studies before, during, and after treatment using 4 PRO instruments (Short Form-36, Chronic Liver Disease Questionnaire-HCV, Functional Assessment of Chronic Illness Therapy-Fatigue, and Work Productivity and Activity Index: Specific Health Problem), and compared between the SOF/VEL and SOF + RBV groups.