P0548 : Impaired anti-HBV vaccine response in non-cirrhotic chronic HCV patients compared to healthy controls

In persons with chronic hepatitis C virus (HCV) infections, superinfection by hepatitis A virus (HAV) or hepatitis B virus (HBV) can cause serious complications, including fulminating hepatitis or increased severity of hepatitis. Therefore, it is important to adequately protect persons with chronic HCV infections by immunization. Suboptimal response to vaccines has been reported in patients with chronic liver disease. The present article reviews HAV and HBV vaccine responses reported in the literature when administered to individuals with chronic HCV infection, and reviews current national and international recommendations.RESULTS: Persons with chronic HCV respond well to HAV vaccine, but studies exploring HBV vaccine efficacy in this population have equivocal results. Vaccine schedules and participant characteristics differ among studies, and most do not adjust for confounders. Some studies found no difference in HBV vaccine response between patients with chronic HCV and controls. However, HBV vaccine response was generally reduced in those with cirrhosis and HCV genotype 1. Organizations recommend HAV and HBV vaccines for persons with chronic HCV, but do not suggest alterations in schedule or dose.RECOMMENDATIONS: Because HAV vaccine response is good and routine laboratory testing may not detect lower levels of vaccine-induced anti-HAV, the standard HAV vaccine schedule is recommended without postimmunization testing. HBV vaccine should be administered early in the course of chronic HCV infection because response may be lower in patients with cirrhosis. Reflex testing of anti-HCV reactive sera for anti-HAV and hepatitis B surface antibody can facilitate appropriate follow-up and timely immunization. Determination of postimmunization hepatitis B surface antibody, especially in patients with cirrhosis or genotype 1, will allow HBV vaccine boosters to be offered.

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Multi-Omic Data Integration Allows Baseline Immune Signatures to Predict Hepatitis B Vaccine Response in a Small Cohort

Frontiers in Immunology ◽

10.3389/fimmu.2020.578801 ◽

2020 ◽

Vol 11 ◽

Author(s):

Casey P. Shannon ◽

Travis M. Blimkie ◽

Rym Ben-Othman ◽

Nicole Gladish ◽

Nelly Amenyogbe ◽

...

Keyword(s):

Hepatitis B ◽

Vaccine Development ◽

Effective Means ◽

Interaction Network ◽

Effective Vaccine ◽

Molecular Characteristics ◽

Vaccine Response ◽

Hbv Vaccine ◽

Fecal Microbiome ◽

Vaccine Responses

BackgroundVaccination remains one of the most effective means of reducing the burden of infectious diseases globally. Improving our understanding of the molecular basis for effective vaccine response is of paramount importance if we are to ensure the success of future vaccine development efforts.MethodsWe applied cutting edge multi-omics approaches to extensively characterize temporal molecular responses following vaccination with hepatitis B virus (HBV) vaccine. Data were integrated across cellular, epigenomic, transcriptomic, proteomic, and fecal microbiome profiles, and correlated to final HBV antibody titres.ResultsUsing both an unsupervised molecular-interaction network integration method (NetworkAnalyst) and a data-driven integration approach (DIABLO), we uncovered baseline molecular patterns and pathways associated with more effective vaccine responses to HBV. Biological associations were unravelled, with signalling pathways such as JAK-STAT and interleukin signalling, Toll-like receptor cascades, interferon signalling, and Th17 cell differentiation emerging as important pre-vaccination modulators of response.ConclusionThis study provides further evidence that baseline cellular and molecular characteristics of an individual’s immune system influence vaccine responses, and highlights the utility of integrating information across many parallel molecular datasets.

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HCV Activates Somatic L1 Retrotransposition—A Potential Hepatocarcinogenesis Pathway

Cancers ◽

10.3390/cancers13205079 ◽

2021 ◽

Vol 13 (20) ◽

pp. 5079

Author(s):

Praveen D. Sudhindar ◽

Daniel Wainwright ◽

Santu Saha ◽

Rachel Howarth ◽

Misti McCain ◽

...

Keyword(s):

Viral Clearance ◽

Hcv Rna ◽

Transcript Expression ◽

Healthy Controls ◽

Rna Seq ◽

Common Cause ◽

Damage Repair ◽

Huh7 Cells ◽

Chronic Hcv

Hepatitis C virus (HCV) is a common cause of hepatocellular carcinoma (HCC). The activation and mutagenic consequences of L1 retrotransposons in virus-associated-HCC have been documented. However, the direct influence of HCV upon L1 elements is unclear, and is the focus of the present study. L1 transcript expression was evaluated in a publicly available liver tissue RNA-seq dataset from patients with chronic HCV hepatitis (CHC), as well as healthy controls. L1 transcript expression was significantly higher in CHC than in controls. L1orf1p (a L1 encoded protein) expression was observed in six out of 11 CHC livers by immunohistochemistry. To evaluate the influence of HCV on retrotransposition efficiency, in vitro engineered-L1 retrotransposition assays were employed in Huh7 cells in the presence and absence of an HCV replicon. An increased retrotransposition rate was observed in the presence of replicating HCV RNA, and persisted in cells after viral clearance due to sofosbuvir (PSI7977) treatment. Increased retrotransposition could be due to dysregulation of the DNA-damage repair response, including homologous recombination, due to HCV infection. Altogether these data suggest that L1 expression can be activated before oncogenic transformation in CHC patients, with HCV-upregulated retrotransposition potentially contributing to HCC genomic instability and a risk of transformation that persists post-viral clearance.

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Low response rates to hepatitis B vaccine in patients with chronic hepatitis C

International Journal of Community Medicine and Public Health ◽

10.18203/2394-6040.ijcmph20214248 ◽

2021 ◽

Vol 8 (11) ◽

pp. 5189

Author(s):

Cláudia Alexandra Pontes Ivantes ◽

Tiago Zibetti Dos Passos ◽

João Marcelo Marchi Moraes ◽

Nicole Espindula Mattar ◽

Tereza Reck ◽

...

Keyword(s):

Immune Response ◽

Chronic Hepatitis ◽

Hepatitis C ◽

Hepatitis B ◽

Chronic Hepatitis C ◽

Smoking Status ◽

Response Rates ◽

Vaccine Response ◽

Genotype 3 ◽

Hbv Vaccine

Background: Hepatitis B is an infectious disease with converging routes of transmission with hepatitis C, making vaccination important in hepatitis C infected people. The objective was to evaluate the vaccine response against hepatitis B virus (HBV) in patients with chronic hepatitis C virus (HCV).Methods: Retrospective observational study was conducted between November 2018 and April 2020. Subjects with anti-HBs levels ≥10 mUI/ml were considered protected against HBV and those with chronic HCV who did not receive at least one dose of the vaccine schedule or with anti-HBc reagent or even with anti-HBs positive prior to the first dose documented in the HBV vaccine record were excluded. The immune response rates to VHB vaccine in patients with HCV was obtained and different variables were analysed.Results: The study group was compound of 370 subjects. The majority (55.7%) were male, with a median age of 55.6±11 years. Regarding present or past smoking, 56.9% of patients reported that were active or past tobacco users. HCV genotype 1 corresponded to 59.7% of the cases, followed by genotype 3 (36.88%). One hundred and fourteen (30.9%) of the patients had liver cirrhosis. The immune response to complete HBV vaccine was 62.3%, whereas the response to a single dose was 57.1% (p=1). Only the age of the patient at first dose (p=0.030), smoking status (p=0.017) and the presence of cirrhosis (p=0.046) influenced the immune response to HBV vaccine.Conclusions: The rate of immune response to standard schedule of HBV vaccination in patients with HCV was low (62.3%).

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Humoral and cellular responses to mRNA vaccines against SARS-CoV2 in patients with a history of CD20-B-cell depleting therapy

10.1101/2021.07.04.21259848 ◽

2021 ◽

Author(s):

Matthias B. Moor ◽

Franziska Suter-Riniker ◽

Michael P. Horn ◽

Daniel Aeberli ◽

Jennifer Amsler ◽

...

Keyword(s):

Immune Responses ◽

B Cell ◽

Vaccine Dose ◽

Lymphocyte Subpopulation ◽

University Hospital ◽

Healthy Controls ◽

Vaccine Response ◽

Treatment History ◽

History Of ◽

Anti Cd20

Background B-cell depleting therapies increase COVID19 morbidity and mortality. For this specific population, evidence-based vaccination strategies are lacking. Here, we investigated humoral and cell mediated immune responses to SARS-CoV2 mRNA-based vaccines in patients receiving CD20-B-cell depleting agents for autoimmune disease, malignancy, or transplantation. Methods Patients at the Bern University Hospital with a treatment history of anti-CD20 depleting agents (rituximab or ocrelizumab) were enrolled for analysis of humoral and cell-mediated immune responses (by IFN-g release assay) after completing vaccination against SARS-CoV2. Primary outcome was the the anti-spike antibody response in anti-CD20-treated patients (n=96) in comparison to immunocompetent controls (n=29). Results Anti-spike IgG antibodies were detected in 49% of patients 1.79 months after the second vaccine dose (interquartile range, IQR: 1.16-2.48) compared to 100% of controls (p<0.001). SARS-CoV2 specific interferon-g; release was detected in 17% of patients and 86% of healthy controls (p<0.001). Only 5% of patients, but 86% of healthy controls showed positive reactions in both assays, respectively (p<0.001). Time since last anti-CD20 therapy (7.6 months), peripheral CD19+ (>27/ul), and CD4+ lymphocyte count (>653/ul) predicted humoral vaccine response (area under the curve [AUC]: 62% [CI 56-78], 67% [CI 58-80] and 67% [CI 54-79], (positive predictive value [PPV]: 0.76, 0.7 and 0.71). Conclusion This study provides evidence for blunted humoral and cell-mediated immune responses elicited by SARS-CoV2 mRNA vaccines in patients with CD20-depleting treatment history. Lymphocyte subpopulation counts are associated with vaccine response in this highly vulnerable population. (Funded by Bern University Hospital, ClinicalTrials.gov number, NCT04877496)

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Machine learning-based single cell and integrative analysis reveals that baseline mDC predisposition predicts protective Hepatitis B vaccine response

10.1101/2021.02.22.21251864 ◽

2021 ◽

Author(s):

Brian Aevermann ◽

Casey P. Shannon ◽

Mark Novotny ◽

Rym Ben-Othman ◽

Bing Cai ◽

...

Keyword(s):

Machine Learning ◽

Single Dose ◽

Dendritic Cell ◽

Hepatitis B ◽

Single Cell ◽

Immune Cell ◽

Serum Antibody ◽

Vaccine Response ◽

Hbv Vaccine ◽

Antibody Levels

AbstractVaccination to prevent infectious disease is one of the most successful public health interventions ever developed. And yet, variability in individual vaccine effectiveness suggests a better mechanistic understanding of vaccine-induced immune responses could improve vaccine design and efficacy. We have previously shown that protective antibody levels could be elicited in a subset of recipients with only a single dose of the hepatitis B virus (HBV) vaccine. Why some, but not all, recipients responded in this way was not clear. Using single cell RNA sequencing of sorted innate immune cell subsets, we identified two distinct myeloid dendritic cell subsets (NDRG1-expressing mDC2 and CDKN1C-expressing mDC4), the ratio of which at baseline (pre-vaccination) predicted immune response to a single dose of HBV vaccine. Our results suggest that the participants in our vaccine study were in one of two different dendritic cell dispositional states at baseline – an NDRG2-mDC2 state in which the vaccine elicited an antibody response after a single immunization or a CDKN1C-mDC4 state in which the vaccine required two or three doses for induction of antibody responses. Genes expressed in these mDC subsets were used as an approach for feature selection prior to the construction of a predictive model using supervised canonical correlation machine learning. The resulting model showed an improved ability to predict serum antibody titers in response to vaccination. Taken together, these results suggest that the propensity of circulating dendritic cells toward either activation or suppression, their “dispositional endotype”, could dictate response to vaccination. The fact that these mDCs could be modulated via TLR stimulation could guide progress towards design of effective single dose vaccination strategies.

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The Relationship between Inflammatory Marker Levels and Hepatitis C Virus Severity

Gastroenterology Research and Practice ◽

10.1155/2016/2978479 ◽

2016 ◽

Vol 2016 ◽

pp. 1-5 ◽

Cited By ~ 5

Author(s):

Qitian He ◽

Quan He ◽

Xue Qin ◽

Shan Li ◽

Taijie Li ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Inflammatory Marker ◽

Healthy Controls ◽

Red Cell ◽

Distribution Width ◽

Bivariate Logistic Regression ◽

Related Liver Disease ◽

Chronic Hcv ◽

The Relationship

Background. Red cell distribution width (RDW) and platelet-lymphocyte ratio (PLR) have been studied in a variety of etiological diseases. We aim to investigate the relationship between RDW and PLR and the severity of hepatitis C virus- (HCV-) related liver disease. Methods. We included fifty-two chronic HCV and 42 HCV-related cirrhosis patients and 84 healthy controls. Hematological and virological parameters and liver function biomarkers of HCV-related patients at admission were recorded. Results. RDW, RDW-to-platelet (RPR), and 1/PLR values in HCV-related cirrhosis patients were significantly higher than in chronic HCV patients and healthy controls (all P<0.001). The aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR), AST-to-platelet ratio index (APRI), and fibrosis index based on the four factors (FIB-4) scores in HCV-related cirrhosis patients were significantly higher than in chronic HCV patients (all P<0.001). The areas under the curve of the RDW, RPR, and 1/PLR for predicting cirrhosis were 0.791, 0.960, and 0.713, respectively. Bivariate logistic regression analysis showed that RDW could independently predict the presence of cirrhosis in chronic HCV patients. Conclusions. RDW, RPR, and PLR may be potential markers for estimating HCV severity.

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Vaccine serologic responses among transplant patients associate with COVID-19 infection and T peripheral helper cells

10.1101/2021.07.11.21260338 ◽

2021 ◽

Author(s):

Jacob E. Lemieux ◽

Amy Li ◽

Matteo Gentili ◽

Cory A. Perugino ◽

Zoe F. Weiss ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

B Cell ◽

Cd4 T Cells ◽

Lung Transplant ◽

T Cell Subsets ◽

Healthy Controls ◽

Transplant Recipients ◽

Vaccine Response ◽

Lung Transplant Recipients

Background: Therapeutically immunosuppressed transplant recipients exhibit attenuated responses to COVID-19 vaccines. To better understand the immune alterations that determined poor vaccine response, we correlated quantities of circulating T and B cell subsets at baseline with longitudinal serologic responses to SARS-CoV-2 mRNA vaccination in heart and lung transplant recipients. Methods: Samples at baseline and at approximately 8 and 30 days after each vaccine dose for 22 heart and lung transplant recipients with no history of COVID-19, four heart and lung transplant recipients with prior COVID-19 infection, and 12 healthy controls undergoing vaccination were analyzed. Anti-spike protein receptor binding domain (RBD) IgG and pseudovirus neutralization activity were measured. Proportions of B and T cell subsets at baseline were comprehensively quantitated. Results: At 8-30 days post vaccination, healthy controls displayed robust anti-RBD IgG responses, whereas heart and lung transplant recipients showed minimally increased responses. A parallel absence of activity was observed in pseudovirus neutralization. In contrast, three of four (75%) transplant recipients with prior COVID-19 infection displayed robust responses at levels comparable to controls. Baseline levels of activated PD-1+ HLA-DR+ CXCR5- CD4+ T cells (also known as T peripheral helper [TPH] cells) and CD4+ T cells strongly predicted the ability to mount a response. Conclusions: Immunosuppressed patients have defective vaccine responses but can be induced to generate neutralizing antibodies after SARS-CoV-2 infection. Strong correlations of vaccine responsiveness with baseline TPH and CD4+ T cell numbers highlights a role for T helper activity in B cell differentiation into antibody secreting cells during vaccine response.

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