Prediction of Hepatocellular Carcinoma and Other Liver-Related Events in Chronic Hepatitis B Patients With Metabolic Dysfunction or Metabolic Dysfunction-Associated Steatotic Liver Disease.

Introduction: Metabolic dysfunction and metabolic dysfunction-associated steatotic liver disease (MASLD) are associated with an increased risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). We aimed to study risk factors for HCC and to assess the performance of the PAGE-B score in this population.

Methods: We included CHB patients with ≥ 1 metabolic comorbidity from nine centres.

Impact of Socio-Economic, Behavioural and Clinical Factors on Liver Disease Progression in Individuals With HIV and Hepatitis B.

Background And Aims: Little is known about the contribution of sociodemographic and behavioural factors to developing liver disease in individuals with an HIV and chronic hepatitis B virus (HBV) co-infection. We aimed to quantify the impact of these factors on incident liver disease in individuals with HIV/HBV receiving care in the Netherlands.

Methods: We used data from the Dutch observational ATHENA cohort combined with Statistics Netherlands.

Dolutegravir/Lamivudine Is Noninferior to Continuing Dolutegravir- and Non-Dolutegravir-Based Triple-Drug Antiretroviral Therapy in Virologically Suppressed People With Human Immunodeficiency Virus: DUALING Prospective Nationwide Matched Cohort Study.

Background: Confirming the efficacy of dolutegravir/lamivudine in clinical practice solidifies recommendations on its use.

Methods: Prospective cohort study (DUALING) in 24 human immunodeficiency virus (HIV) treatment centers in the Netherlands. HIV RNA-suppressed cases were on triple-drug antiretroviral regimens without prior virological failure or resistance and started dolutegravir/lamivudine.

Dynamics of Low-Level Viremia and Immune Activation after Switching to a Darunavir-Based Regimen.

There is an ongoing debate regarding whether low-level viremia (LLV), in particular persistent LLV, during HIV treatment with optimal adherence originates from low-level viral replication, viral production, or both. We performed an observational study in 30 individuals with LLV who switched to a boosted darunavir (DRV)-based therapy. In-depth virological analyses were used to characterize the viral population and the (activity) of the viral reservoir.

Hepatocellular carcinoma risk in sub-Saharan African and Afro-Surinamese individuals with chronic hepatitis B living in Europe.

Background & Aims: Sub-Saharan African (SSA) ethnicity has been associated with a higher risk of hepatocellular carcinoma (HCC) among individuals with chronic hepatitis B in cross-sectional studies. However, the incidence of HCC and performance of HCC risk scores in this population are unknown.

Methods: We conducted an international multicenter retrospective cohort study of all consecutive HBV-monoinfected individuals of SSA or Afro-Surinamese (AS) ethnicity managed at sites in the Netherlands, the United Kingdom and Spain.

Persistent Transmission of HCV among Men Who Have Sex with Men despite Widespread Screening and Treatment with Direct-Acting Antivirals.

Background: In the Netherlands, unrestricted access to direct-acting antivirals (DAAs) halved the incidence of acute hepatitis C virus (HCV) infections among HIV-infected men who have sex with men (MSM). To develop strategies that can further reduce the spread of HCV, it is important to understand the transmission dynamics of HCV. We used phylogenetic analysis of a dense sample of MSM to provide insight into the impact of unrestricted access to DAAs on HCV transmission in the Netherlands and in Belgium.

How to use quality indicators for antimicrobial stewardship in your hospital: a practical example on outpatient parenteral antimicrobial therapy.

Background: Antimicrobial stewardship (AMS) teams are responsible for performing an AMS programme in their hospitals that aims to improve the quality of antibiotic use. Measuring the quality of antimicrobial use is a core task of a stewardship team. Measurement provides insight into the current quality of antibiotic use and allows for the establishment of goals for improvement.

Clinical practice of hepatitis B screening in patients starting with chemotherapy: A survey among Dutch oncologists.

Objective: Screening for hepatitis B virus (HBV) before chemotherapy is recommended by international guidelines; still, the HBV screening rate is low, and patients remain at risk for HBV reactivation (HBVr). Because HBVr is a serious and preventable condition, we conducted a survey to evaluate the screening behaviour of oncologists in the Netherlands.

Methods: We conducted an anonymous digital survey by email to all practicing medical oncologists.

HCV micro-elimination in individuals with HIV in the Netherlands 4 years after universal access to direct-acting antivirals: a retrospective cohort study.

Background: In the Netherlands, access to direct-acting antivirals (DAAs) against hepatitis C virus (HCV) has been unrestricted for chronic infection since 2015. We evaluated whether the nationwide incidence of HCV infections in individuals with HIV has changed since 2015.

Methods: In this retrospective cohort study, data from the ATHENA cohort of people with HIV aged 18 years or older attending any of the 24 HIV treatment centres in the Netherlands between 2000 and 2019 were assessed.

Treatment of acute hepatitis C genotypes 1 and 4 with 8 weeks of grazoprevir plus elbasvir (DAHHS2): an open-label, multicentre, single-arm, phase 3b trial.

Background: Direct-acting antivirals effectively treat chronic hepatitis C virus (HCV) infection but there is a paucity of data on their efficacy for acute HCV, when immediate treatment could prevent onward transmission. We assessed the efficacy of grazoprevir plus elbasvir treatment in acute HCV infection and investigated whether treatment can be shortened during the acute phase of HCV infection.

Methods: The Dutch Acute HCV in HIV study number 2 (DAHHS2) study was a single-arm, open-label, multicentre, phase 3b trial.

Mucosal-associated invariant T-cell frequency and function in blood and liver of HCV mono- and HCV/HIV co-infected patients with advanced fibrosis.

Background & Aims: Mucosal-associated invariant T (MAIT) cells are important innate T cells with antimicrobial and immunoregulatory activity, recently found to be depleted in blood of patients with HIV and HCV mono-infections. In this study, we assessed the impact of HIV, HCV and HCV/HIV co-infection on circulating and intrahepatic MAIT-cells and correlations with liver fibrosis.

Methods: In this cross-sectional study, nine healthy subjects, nine HIV, 20 HCV and 22 HCV/HIV co-infected patients were included.

Immune activation in prolonged cART-suppressed HIV patients is comparable to that of healthy controls.

Sustained immune activation during chronic HIV infection is considered to augment co-morbidity and mortality. Effective combination antiretroviral therapy (cART) has shown to dampen immune activation especially during the first year cART, but the effects of long-term cART in patients without major comorbidities remains under-investigated. We performed a comprehensive analysis including cellular, intracellular and plasma biomarkers to study the effect of cART on immune parameters in 5 groups of 10 HIV patients.

Decreased pro-inflammatory immune responses during recurrent acute HCV infections in HIV co-infected patients.

Patients in high-risk groups continue to transmit the hepatitis C virus (HCV) and frequently experience reinfections. Since little is known regarding the immune response to HCV during reinfection, we compared primary and consecutive acute HCV infections in patients with an HIV infection, and focused on the cytokine bridging innate to adaptive immunity. We observed that the serum levels of IL-12p40, MIP-1β, MIG and IP-10 increased during primary acute HCV infection, but not during subsequent secondary acute reinfections.

Frequencies of Circulating MAIT Cells Are Diminished in Chronic HCV, HIV and HCV/HIV Co-Infection and Do Not Recover during Therapy.

Objective: Mucosal-associated invariant T (MAIT) cells comprise a subpopulation of T cells that can be activated by bacterial products and cytokines to produce IFN-γ. Since little is known on MAIT cells during HCV infection, we compared their phenotype and function in comparison to HIV and HCV/HIV co-infected patients, and determined the effect of IFN-α-based and direct-acting antiviral therapy on MAIT cells of HCV patients.

Methods: Blood samples from patients with chronic HCV (CHCV), virologically suppressed HIV, acute HCV/HIV co-infection (AHCV/HIV) and healthy individuals were examined by flowcytometry for phenotype and function of MAIT and NK cells.

Boceprevir, peginterferon and ribavirin for acute hepatitis C in HIV infected patients.

Background & Aims: Acute hepatitis C virus infections (AHCV) are prevalent among HIV positive men having sex with men and generally treated with pegylated interferon-alpha (PegIFN) and ribavirin (RBV) during 24weeks. The addition of a protease inhibitor could shorten therapy without loss of efficacy.

Methods: We performed an open-label, single arm study to investigate the efficacy and safety of a 12-week course of boceprevir, PegIFN and RBV for AHCV genotype 1 infections in 10 Dutch HIV treatment centers.

The Intrahepatic T Cell Compartment Does Not Normalize Years After Therapy-Induced Hepatitis C Virus Eradication.

Little is known about the immune status in liver and blood of patients with chronic hepatitis C virus (HCV) infection long after therapy-induced viral clearance. In this study, we demonstrate that, 4 years after clearance, regulation of HCV-specific immunity in blood by regulatory T cells (Tregs) and the immunosuppressive cytokines interleukin 10 and transforming growth factor β is still ongoing. Importantly, analysis of liver specimens collected 4 years after HCV clearance shows that intrahepatic Tregs are still present in all patients, suggesting that liver T cells remain regulated.

Gene expression profiling to predict and assess the consequences of therapy-induced virus eradication in chronic hepatitis C virus infection.

Unlabelled: Systems biology has proven to be a powerful tool to identify reliable predictors of treatment response in chronic hepatitis C virus (HCV) infection. In the present study, we studied patients with chronic HCV infection who responded to interferon (IFN)-based therapy, as evidenced by an absence of HCV RNA at the end of treatment, and focused on two issues that have not received much attention. First, we evaluated whether specific genes or gene expression patterns in blood were able to distinguish responder patients with a viral relapse from responder patients who remained virus negative after cessation of treatment.

Role of T cell immunity in hepatitis C virus infections.

Chronic infections with the hepatitis C virus (HCV) are a major global health issue. Viral replication is restricted to hepatocytes, and occurs for decades at high replication rates. Over the last decade, it became accepted that HCV-specific CD4(+) and CD8(+) T cells are crucial for protective immunity to HCV.

Negative regulation of hepatitis C virus specific immunity is highly heterogeneous and modulated by pegylated interferon-alpha/ribavirin therapy.

Specific inhibitory mechanisms suppress the T-cell response against the hepatitis C virus (HCV) in chronically infected patients. However, the relative importance of suppression by IL-10, TGF-β and regulatory T-cells and the impact of pegylated interferon-alpha and ribavirin (PegIFN-α/ribavirin) therapy on these inhibitory mechanisms are still unclear. We revealed that coregulation of the HCV-specific T-cell responses in blood of 43 chronic HCV patients showed a highly heterogeneous pattern before, during and after PegIFN-α/ribavirin.

Retention of CD4+ CD25+ FoxP3+ regulatory T cells in the liver after therapy-induced hepatitis C virus eradication in humans.

Following infection with the hepatitis C virus (HCV), in most cases immunity fails to eradicate the virus, resulting in slowly progressing immunopathology in the HCV-infected liver. We are the first to examine intrahepatic T cells and CD4(+) CD25(+) FoxP3(+) regulatory T cells (Treg) in patients chronically infected with HCV (chronic HCV patients) during and after antiviral therapy by collecting multiple aspiration biopsy samples from the liver at different time points. We found that intrahepatic Treg frequencies were increased upon alpha interferon and ribavirin administration in about 50% of chronic HCV patients, suggesting stronger regulation of intrahepatic immunity by Treg during antiviral therapy.