Pegylated Interferon Alfa Research Articles

Association of hepatitis B core antibody level and hepatitis B surface antigen clearance in HBeAg-negative patients with chronic hepatitis B

ABSTRACT Predicting hepatitis B surface antigen (HBsAg) clearance is important for chronic hepatitis B (CHB) patients receiving pegylated interferon-alfa (Peg-IFN) therapy. We aimed to determine the predictive value of serum hepatitis B core antibody (anti-HBc) for HBsAg clearance. A total of 189 HBeAg-negative CHB patients who received Peg-IFN based therapy were retrospectively included and classified into two groups: nucleos(t)ide analogues (NAs) add-on Peg-IFN group (add-on group, n = 94) and Peg-IFN combined with NAs or Peg-IFN monotherapy group (combination or monotherapy group, n = 95). After 48 weeks of treatment, 27.5% (52/189) and 15.9% (30/189) of patients achieved HBsAg clearance and seroconversion, respectively. Patients in the combination or monotherapy group tended to achieve relatively higher HBsAg clearance (31.6% vs. 23.4%, p = 0.208) and seroconversion (21.1% vs. 10.6%, p = 0.050) rates than those in the add-on group. In combination or monotherapy group, anti-HBc levels at week 12 were lower in patients with HBsAg clearance (9.0 S/CO vs. 9.9 S/CO, p < 0.001) and seroconversion (8.8 S/CO vs. 9.8 S/CO, p < 0.001) than those without. Anti-HBc level at week 12 was an independent predictor of HBsAg clearance and seroconversion. Patients with lower anti-HBc levels at week 12 showed a more significant decline in HBsAg levels during treatment. Combination of anti-HBc at week 12 and baseline HBsAg could identify over 70% of patients who achieved HBsAg clearance after 48 weeks of treatment. In addition to HBsAg, anti-HBc level could be used as a promising marker for selecting HBeAg-negative CHB patients who are more likely to respond to Peg-IFN-based therapy.

A randomized, double-blind, placebo-controlled phase 3 study to assess efficacy and safety of ropeginterferon alfa-2b in patients with early/lower-risk primary myelofibrosis

Primary myelofibrosis (PMF) is the most aggressive of the myeloproliferative neoplasms and patients require greater attention and likely require earlier therapeutic intervention. Currently approved treatment options are limited in their selective suppression of clonal proliferation resulting from driver- and coexisting gene mutations. Janus kinase inhibitors are approved for symptomatic patients with higher-risk PMF. Additionally, most ongoing clinical studies focus on patients with higher-risk disease and/or high rates of transfusion dependency. Optimal treatment of early/lower-risk PMF remains to be identified and needs randomized clinical trial evaluations. Pegylated interferon alfa is recommended for symptomatic lower-risk PMF patients based on phase 2 non-randomized studies and expert opinion. Ropeginterferon alfa-2b (ropeg) is a new-generation pegylated interferon-based therapy with favorable pharmacokinetics and safety profiles, requiring less frequent injections than prior formulations. This randomized, double-blind, placebo-controlled phase 3 trial will assess its efficacy and safety in patients with “early/lower-risk PMF”, defined as pre-fibrotic PMF or PMF at low or intermediate-1 risk according to Dynamic International Prognostic Scoring System-plus. Co-primary endpoints include clinically relevant complete hematologic response and symptom endpoint. Secondary endpoints include progression- or event-free survival, molecular response in driver or relevant coexisting gene mutations, bone marrow response, and safety. Disease progression and events are defined based on the International Working Group criteria and well-published reports. 150 eligible patients will be randomized in a 2:1 ratio to receive either ropeg or placebo. Blinded sample size re-estimation is designed. Ropeg will be administered subcutaneously with a tolerable, higher starting-dose regimen. The study will provide important data for the treatment of early/lower-risk PMF for which an anti-clonal, disease-modifying agent is highly needed.

Long-term antiviral therapy is associated with changes in the profile of transcriptionally active HBV integration in the livers of patients with CHB.

Hepatitis B virus (HBV) integration exists throughout the clinical course of chronic hepatitis B (CHB). This study investigated the effects of long-term antiviral therapy on the level and profiles of transcriptionally active HBV integration. Serial liver biopsies and paired blood samples were obtained from 16, 16, and 22 patients with CHB at baseline, 78, and 260 weeks of entecavir monotherapy or combined with pegylated interferon alfa, respectively. Serum HBV biomarkers were longitudinally assessed. RNA-seq and HIVID2 program was used to identify HBV-host chimeric RNAs transcribed from integrated DNA. The counts of HBV integration reads were positively related to both serum HBV DNA levels (r = 0.695, p = 0.004) and HBeAg titers (r = 0.724, p = 0.021) at baseline, but the positive correlation exited only to the serum HBsAg levels after 260 weeks of antiviral therapy (r = 0.662, p = 0.001). After 78 weeks of antiviral therapy, the levels of HBV integration expression decreased by 12.25 folds from baseline. The viral junction points were enriched at the S and HBx genes after the long-term antiviral therapy. HBs-FN1 became one of the main transcripts, with the mean proportion of HBs-FN1 in all integrated expression increased from 2.79% at baseline to 10.54% at Week 260 of antiviral treatment. Antiviral therapy may reduce but not eliminate the HBV integration events and integration expression. Certain integration events, such as HBs-FN1 can persist in long-term antiviral treatment.

Diagnosis and treatment of viral hepatitisB andD in 2024

Despite the availability of vaccines, hepatitisB remains asignificant cause of fulminant hepatitis, liver cirrhosis and hepatocellular carcinoma worldwide. The increase in reported hepatitisB cases in Germany is attributed to factors such as immigration and the hepatitisB surface antigen (HBsAg) screening introduced in 2020 as part of health check-ups. The indication for treatment depends on various factors, including the level of hepatitisB virus (HBV) DNA and inflammatory activity. Nucleos(t)ide analogues are the preferred treatment option, but functional cure, defined as HBsAg loss, is rare. In principle, treatment with nucleos(t)ide analogues should usually be discontinued after loss of HBsAg, but can be stopped earlier under certain conditions and is currently the subject of ongoing research. Pregnancy and immunosuppression in the context of hepatitisB require special attention. In addition, apossible hepatitisD virus co-infection must always be taken into account, which is why every HBsAg-positive person should be tested for anti-HDV. Since 2020, the entry inhibitor bulevirtide has become anew treatment option alongside pegylated interferon alfa, which represents asignificant advance in the treatment landscape.

A novel TRIM22 gene polymorphism promotes the response to PegIFNα therapy through cytokine-cytokine receptor interaction signaling pathway in chronic hepatitis B.

Pegylated interferon alfa (PegIFNα) has limited efficacy in the treatment of chronic hepatitis B (CHB). Although many biomarkers related to hepatitis B virus (HBV) have been proposed to stratify patients, the response rate to PegIFNα is still unsatisfactory. Herein, our data suggest that the single-nucleotide polymorphism (SNP) rs10838543 in TRIM22 potentiates a positive clinical response to PegIFNα treatment in patients with hepatitis B e antigen-positive CHB by increasing the levels of IFNL1, CCL3, and CCL5. These observations can help guide treatment decisions for patients with CHB to improve the response rate to PegIFNα.

Association of Alanine Aminotransferase Flares to Hepatitis B Surface Decline During Tenofovir Alone or With Pegylated Interferon Alfa.

We aimed to determine whether the intensity of alanine aminotransferase (ALT) flares during antiviral therapy is associated with the level of hepatitis B surface antigen (HBsAg) decline. Quantitative HBsAg was determined during tenofovir monotherapy or tenofovir plus peginterferon alfa-2a in 201 participants with hepatitis B e antigen-positive or -negative chronic hepatitis B. A multivariable analysis identified factors associated with a shorter time to reduction in HBsAg. Fifty flares occurred during treatment of which 74% were moderate (ALT >5-10 × upper limit of normal) or severe (ALT >10 × upper limit of normal). These flares were associated with greater HBsAg decline compared with no flares. Significantly faster times to HBsAg decline >1 log 10 IU ( P = 0.04) and to HBsAg level <100 IU/mL ( P = 0.01) were observed with severe flares. Flare severity is a potentially important factor associated with shorter time to HBsAg reduction. These findings can be useful when evaluating HBsAg response to evolving hepatitis B virus therapies.

LBO-02 - Safety and efficacy of VIR-2218 with or without pegylated interferon alfa in virally-suppressed participants with chronic hepatitis B virus infection: post-treatment follow-up

LBO-02 - Safety and efficacy of VIR-2218 with or without pegylated interferon alfa in virally-suppressed participants with chronic hepatitis B virus infection: post-treatment follow-up

Comparison of Pegylated Interferon Alfa Therapy in Combination with Tenofovir Alafenamide Fumarate or Tenofovir Disoproxil Fumarate for Treatment of Chronic Hepatitis B Patients.

The study aims to evaluate the effectiveness of a tenofovir alafenamide fumarate (TAF) and pegylated interferon alfa (PegIFN-α) regimen compared to a tenofovir disoproxil fumarate (TDF) and PegIFN-α therapy in patients with chronic hepatitis B (CHB). Patients who were treated with PegIFN-α in combination with TAF or TDF were retrospectively enrolled. The primary outcome measured was the HBsAg loss rate. The rates of virological response, serological response for HBeAg, and normalization of alanine aminotransferase (ALT) were also calculated. The cumulative incidences of response rates were compared between the two groups using Kaplan-Meier analysis. A total of 114 patients were retrospectively enrolled in the study, with 33 receiving TAF plus PegIFN-α treatment and 81 receiving TDF plus PegIFN-α treatment. The HBsAg loss rate for the TAF plus PegIFN-α group was 15.2% at 24 weeks and 21.2% at 48 weeks, while the TDF plus PegIFN-α group had rates of 7.4% at 24 weeks and 12.3% at 48 weeks (P=0.204 at 24 weeks, P=0.228 at 48 weeks). In subgroup analysis of HBeAg positive patients, the TAF group had a higher HBsAg loss rate of 25% at week 48, compared to 3.8% in the TDF group (P=0.033). According to Kaplan-Meier analysis, the TAF plus PegIFN-α group achieved virological response more quickly than the TDF plus PegIFN-α group (p=0.013). There was no statistical difference in HBeAg serological rate or ALT normalization rate. There was no significant difference in the HBsAg loss between the two groups. However, subgroup analysis revealed that TAF plus PegIFN-α treatment had a higher HBsAg loss rate than TDF plus PegIFN-α treatment in HBeAg-positive patients. Additionally, TAF plus PegIFN-α treatment demonstrated better virological suppression for CHB patients. Therefore, TAF plus PegIFN-α treatment regimen is recommended for CHB patients who aim to achieve functional cure.

Downregulated KLF2 in polycythemia vera and essential thrombocythemia induces prothrombotic gene expression.

Thromboses are major causes of morbidity and mortality in polycythemia vera (PV) and essential thrombocythemia (ET) diseases associated with JAK2V617F mutation. However, themolecular mechanism(s) of increased thrombosis in PV and ET remain unknown. Kruppel-like factor 2 (KLF2) is a transcription factor that regulates expression of genes associated with inflammation and thrombosis; the absence of KLF2 in neutrophils causes thrombosis by inducing tissue factor. We studied the role of KLF2 in regulating prothrombotic gene expression in PV and ET. Neutrophils and platelets KLF2 expression in PV and ET was lower than the controls. Furthermore, in patients with thromboses, KLF2 transcripts were lower in platelets than those without thromboses. JAK2V617F allelic burden was inversely correlated with KLF2 transcript levels, suggesting JAK-STAT pathway may downregulate KLF2 expression. Whole transcriptome analyses of neutrophils and plateletsshowed that a lower KLF2 expression was associated with an upregulation of KLF2-regulated thrombotic genes. In addition, low KLF2 expression in platelets positively correlated with thrombotic events. In patients with PV and ET, KLF2 expression was induced by pegylated interferon alfa (PegINF-α) but not by hydroxyurea treatments. These data suggest that KLF2 may be a regulator of PV and ET thrombosis and a novel therapeutic target to prevent thrombosis.

Dynamic changes of the proportion of HLA-DR and CD38 coexpression subsets on T lymphocytes during IFN-based chronic hepatitis B treatment.

To investigate the changes of human leukocyte antigen DR (HLA-DR) and CD38 coexpression subsets on T lymphocytes following interferon (IFN) therapy for those who have chronic hepatitis B (CHB). A prospective cohort of CHB patients participated in this study. CHB patients without IFN treatment (including naïve and nucleoside [nucleotide] analogs [NAs]-treated patients) were given pegylated interferon alfa (Peg-IFNα) treatment. Peripheral blood samples were taken at baseline, 4 weeks and 12-24 weeks of Peg-IFNα treatment. For the patients who entered the Peg-IFNα plateau phase due to the stagnation of the decrease in HBsAg, and Peg-IFNα was discontinued and Peg-IFNα therapy was resumed after an interval of 12-24 weeks. During the interval, they received first-line NAs treatment. Peripheral blood samples were collected at the baseline of the plateau phase, 12-24 weeks of intermittent treatment, and 12-24 weeks of Peg-IFNα retreatment. The peripheral blood samples were taken to determine virological, serological and biochemical indices of hepatitis B virus (HBV), and T lymphocyte related phenotypes were detected using flow cytometry. In the process of long-term treatment of Peg-IFNα, the percentage of HLA-DR+CD38dim subsets increased significantly at first, then decreased gradually, while the percentage of HLA-DR+CD38hi subsets markedly increased. During long-term Peg-IFNα treatment, there was a considerable negative correlation between HBsAg and the HLA-DR+CD38hi subset percentage. The persistent high proportion of HLA-DR+CD38hi subsets was related to the occurrence of Peg-IFNα plateau phase. After Peg-IFNα intermittent treatment, the percentage of HLA-DR+CD38hi subsets decreased significantly. After Peg-IFNα retreatment, the level of HBsAg began to decrease again. At the same time, the percentage of HLA-DR+CD38hi subsets significantly increased, but it was still lower than that at the baseline level. The spectrum of HLA-DR and CD38 coexpression subsets on T lymphocytes changed during the long-term treatment of IFN. The establishment of the IFN plateau phase was linked to the persistence of a considerable proportion of HLA-DR+CD38hi subsets on T lymphocytes. IFN intermittent treatment could significantly reduce the proportion of HLA-DR+CD38hi subsets, helping regain the antiviral efficacy of IFN during IFN retreatment.

NOVEL ENTRY INHIBITORS FOR VIRAL HEPATITIS D TREATMENT: BULEVIRTIDE

Chronic hepatitis D virus infection is the most severe form of viral hepatitis. Hepatitis delta virus (HDV) is a faulty RNA virus that needs hepatitis B virus surface antigen (HBsAg) for the completion of its life cycle. Hepatitis B virus (HBV) receptor, sodium taurocholate cotransporting polypeptide (NTCP), is used by HDV to infect hepatocytes. The replication of the HDV genome, which is a circular single-stranded RNA and encodes for a single HDAg that occurs in two forms (S-HDAg and L-HDAg), is carried out by the host RNA polymerases. Antiviral therapy is urgently needed to protect patients from hepatocellular carcinoma or end-stage liver disease and poses an important public health issue in many countries. There is still a need for efficient pharmacological therapies for chronic hepatitis D (CHD). A good strategy to stop new infections is to stop virus from entering cells. A new virion entry inhibitor called bulevirtide is now a promising treatment for both infections because it prevents the virion from entering the hepatocyte through the hepatic sodium/taurocholate cotransporting polypeptide Before bulevirtide's conditional approval by the EMA (European Medicines Agency) in July 2020 for the treatment of chronic HDV infection in adult patients with compensated liver disease, therapy options were restricted to the off-label use of pegylated interferon alfa. (NTCP) receptor. We will outline the most recent discoveries about the HDV life cycle that have prompted the development of noveldrug bulevirtide.

Immunological and virological findings in a patient with exceptional post-treatment control: a case report

Although antiretroviral therapy (ART) is effective in suppressing viral replication, HIV-1 persists in reservoirs and rebounds after ART has been stopped. However, a very few people (eg, elite and post-treatment controllers) are able to maintain viral loads below detection limits without ART, constituting a realistic model for long-term HIV remission. Here, we describe the HIV control mechanisms of an individual who showed exceptional post-treatment control for longer than 15 years. We report the case of a Hispanic woman aged 59 years with sexually acquired acute HIV infection, who was included in an immune-mediated primary HIV infection trial involving a short course of ciclosporine A, interleukin-2, granulocyte macrophage colony-stimulating factor, and pegylated interferon alfa, followed by analytical treatment interruption. We did the following viral assays: total and integrated HIV-1 DNA in CD4 T cells and rectal tissue, quantitative viral outgrowth assay, HIV-1 infectivity in peripheral blood mononuclear cells and CD4 T-cell cultures and viral inhibitory activity by natural killer (NK) and CD8 T cells. NK and T-cell phenotypes were determined by flow cytometry. HLA, killer cell immunoglobulin-like receptors, Δ32CCR5, and NKG2C alleles were genotyped. After ART and immunomodulatory treatment, the person maintained undetectable plasma viral load for 15 years. HIV-1 subtype was CFR_02AG, CCR5-tropic. We found progressive reductions in viral reservoir during the 15-year treatment interruption: total HIV DNA (from 4573·50 copies per 106 CD4 T cells to 95·33 copies per 106 CD4 T cells) and integrated DNA (from 85·37 copies per 106 CD4 T cells to 5·25 copies per 106 CD4 T cells). Viral inhibition assays showed strong inhibition of in vitro HIV replication in co-cultures of CD4 T cells with autologous NK or CD8 T cells at 1:2 ratio (75% and 62%, respectively). Co-cultures with NK and CD8 T cells resulted in 93% inhibition. We detected higher-than-reference levels of both NKG2C-memory-like NK cells (46·2%) and NKG2C γδ T cells (64·9%) associated with HIV-1 control. We described long-term remission in a woman aged 59 years who was treated during primary HIV infection and has maintained undetectable viral load for 15 years without ART. Replication-competent HIV-1 was isolated. NKG2C-memory-like NK cells and γδ T cells were associated with the control viral replication. Strategies promoting these cells could bring about long-term HIV remission. Fondo Europeo para el Desarrollo Regional (FEDER), SPANISH AIDS Research Network (RIS), Fondo de Investigación Sanitaria (FIS), HIVACAT, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CERCA Programme/Generalitat de Catalunya, la Caixa Foundation, and Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC). For the Spanish translation of the abstract see Supplementary Materials section.

TREATMENT OF A PATIENT DIAGNOSED WITH ERDHEIM CHESTER'S DISEASE IN COOPERATION WITH PLASTIC SURGERY AND HEMATOLOGY

Erdheim Chester disease (ECD) is a rare non-Langerhans histiocytic multisystem disorder. ECD is most commonly manifested as multifocal sclerotic long bone lesions. Orbital and intraocular manifestations are rare. We report an unusual bilateral orbital presentation as xanthomatous infiltration of ECD. A 56-year-old male was admitted due to papular lesions on both eyelids. Eyelid tissue histology showed histiocytic infiltration consistent with ECD. BRAF V600E mutation (-). In the first year, PET-CT showed new lesions on the lymph node, eyelids, knees and elbows. Laboratory investigation was within normal apart of mild increased CRP. The disorder was unresponsive to pegylated interferon alfa. With cladribine of 3 courses and surgical intervention he achieved a nearly normal facial appearance. Uncontrolled cell survival, differentiation, and proliferation of histiocytes in ECD result in soft tissue thickening and progressed to chronic fibrotic disease which may be unresponsive to medical treatments and requires surgical interventions.

Ther-O-10 - Real-world study of the use of pegylated interferon alfa for treatment of primary cutaneous T-cell lymphomas: an EORTC CLTF study

Ther-O-10 - Real-world study of the use of pegylated interferon alfa for treatment of primary cutaneous T-cell lymphomas: an EORTC CLTF study

Antivirals against HCV infection: the story thus far.

Remarkable scientific breakthroughs have been made in the stride towards the development of potent and tolerable hepatitis C regimens within the last three decades. Earlier approaches involved the use of pegylated interferon alfa and ribavirin as standard-of-care treatment. Treating genotype 1a infection with this regimen which was at that time considered the gold standard for hepatitis C virus therapy was rife with challenges; safety and toxicity issues necessitated a rigorous quest for alternative regimens. Deeper understanding of the pathogenesis of hepatitis C virus ushered in the era of direct acting antiviral agents. These agents have been the subject of intensive research in the last two decades, leading to the development of drug classes such as protease inhibitors (e.g., grazoprevir), NS5A inhibitors (e.g., daclatasvir) and NS5B inhibitors (e.g., sofosbuvir). While many are still under development, several have been approved for hepatitis C therapy. A number of studies investigating the combination of direct acting antiviral agents with or without pegylated interferon and/or ribavirin for the treatment of chronic hepatitis have demonstrated sustained virologic response of > 90%. Given the array of direct acting antiviral agents currently available, the present landscape of hepatitis C therapy is now characterized by a gradual transition to all-oral interferon-free regimens. Despite these milestones, the WHO global target of eliminating hepatitis C as a public health problem by 2030 seems uncertain. In this review, we provide a concise account of the evolution and advancements in the development of anti-HCV regimens.

PATIENT WITH LIVER DISORDERS: EXPLORATION TOOLS AND TREATMENT

The evaluation of the liver structure can be done through invasive and non-invasive imaging methods. Noninvasive methods include abdominal ultrasound, transient hepatic elastography (Fibroscan). biomarkers such as hyaluronic acid (HA), alpha-2 macroglobulin, laminin, fibronectin, Fibroindex or panels such as Fibrotest-actiTest. Liver biopsy, the most invasive method of assessing the structure of the liver and the lesions present, is still indicated in certain reserved cases, when the diagnosis remains uncertain despite all the investigations. Antiviral therapy in Romania for hepatitis B virus includes the administration of pegylated interferon alfa 2a and various nucleoside/nucleotide analogs (ANN): adefovir, entecavir, tenofovir, lamivudine. IFNα is the most effective antiviral treatment in children, regarding the seroconversion of Hbe Ag to anti Hbe Ac and the disappearance of Hbs Ag. Sustained response is defined as maintaining the response to treatment for at least 6 months after its discontinuation.

The Impact of IL28B Gene Polymorphisms on Drug Responses

The Impact of IL28B Gene Polymorphisms on Drug Responses

Pregnancy Management and Outcomes in Patients with Myeloproliferative Neoplasms

▪Introduction:While BCR-ABL1 negative myeloproliferative neoplasms (MPN) are typically diagnosed in the sixth decade of life, approximately 20% of patients are diagnosed before the age of 40 years. Patients with MPN of reproductive age are being increasingly encountered in clinical practice. Concurrently, there has been increased awareness of the risks of pregnancy complications in patients with MPN and the importance of MPN-specific management to help mitigate these risks. MPN are associated with thrombotic and hemorrhagic complications, and pregnancy may amplify the thrombotic risk. Additionally, MPN may be associated with an increased risk of placental dysfunction and associated complications of preeclampsia, fetal growth restriction, preterm delivery and fetal loss. The aim of this observational study was to report on pregnancy outcomes in a modern cohort of patients with MPN managed according to consensus recommendations.Methods:We conducted a retrospective review of patients with MPN and pregnancy evaluated at either the Princess Margaret Cancer Centre or Mount Sinai Hospital in Toronto, Canada between January 1, 2010 and December 31, 2020. Diagnoses were defined according to the WHO 2016 criteria using information available from hospital records. Descriptive statistics were used to describe selected baseline characteristics. Categorical variables were summarized with counts and percentages.Results:A total of 32 patients with MPN and pregnancy were included in the study (Table 1). The median age at the time of the index pregnancy was 33 (range 21 - 45) years. The most common MPN diagnosis was essential thrombocythemia (ET, n=15), followed by polycythemia vera (PV, n=9) and primary myelofibrosis (PMF, n=8). Driver mutation data was available for 30 patients: 17 (57%) had mutated JAK2, 5 (17%) CALR, and 9 (30%) had no driver mutation identified. Five patients had a prior history of venous thrombosis, all of which were portal vein thrombosis, and 2 patients had a history of bleeding events. Information on antenatal treatment was available for 22 patients: 18 (82%) patients received aspirin, 3 (14%) received antenatal low molecular weight heparin (LMWH) and 3 (14%) received interferon (IFN; interferon alpha 2b in 2 cases and pegylated interferon alfa 2a in 1); 16 (73%) received post-partum LMWH.Information on maternal complications was available for 22 patients. There were 2 thrombotic events (1 antepartum and 1 postpartum) and 1 postpartum hemorrhage. There were no cases of preeclampsia. Of 22 pregnancies, there were 19 live births (86%), 2 first trimester losses (9%) and 1 second trimester loss (5%). Gestational age was 37 weeks or more in 16/17 (94%) and was 33 weeks for 1 patient. Vaginal deliveries were performed in 11/20 (55%) cases and 9/20 (45%) were Cesarean deliveries.Discussion:This observational study represents a modern cohort of MPN patients treated according to consensus recommendations. Our findings highlight that MPN patients have better pregnancy outcomes than those previously described in the literature. Limitations of this retrospective study include a small sample, missing data, and potential underreporting of early pregnancy loss. Pregnancy in patients with MPN is associated with unique risks that may be reduced with interventions such as antepartum aspirin, IFN in higher risk patients, and postpartum LMWH. That not all standard risk patients were managed with aspirin and postpartum LMWH suggests educational opportunities exist for hematologists and maternal-fetal medicine physicians involved in the care of these patients. [Display omitted] DisclosuresGupta: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS-Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Honoraria; Pfizer: Consultancy; Roche: Consultancy; Constellation Pharma: Consultancy, Honoraria; Sierra Oncology: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Research Funding. Malinowski: Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy. Maze: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene-BMS: Honoraria; Takeda: Research Funding; PharmaEssentia: Research Funding; Kronos Bio: Research Funding.

HBcrAg Levels Are Associated With Virological Response to Treatment With Interferon in Patients With Hepatitis Delta.

Standard treatment of hepatitis delta virus (HDV) infection remains pegylated‐interferon alfa (peg‐IFNα) in most centers, which is not only associated with rather low efficacy but several adverse events. Hepatitis B core‐related antigen (HBcrAg) is linked to intrahepatic covalently closed circular DNA levels and has previously been suggested as response predictor in IFN‐based treatment of hepatitis B virus (HBV) mono‐infection. This study aimed to investigate the value of HBcrAg in the management of patients with HBV/HDV co‐infection undergoing peg‐IFNα treatment. The Hep‐Net‐International‐Delta‐Hepatitis‐Intervention Trial‐2 study included 120 patients co‐infected with HBV/HDV. Patients were treated for 96 weeks with peg‐IFNα and either tenofovir or placebo. Ninety‐nine patients with HDV‐RNA results 24 weeks after end of treatment (FU24) were included in this analysis, of whom 32 patients (32.3%) had undetectable HDV RNA at FU24. HBcrAg was measured at baseline, week 12, 24, 48, 96, and FU24. HBcrAg levels showed no significant correlation with HDV RNA but were significantly linked to treatment outcome. HBcrAg levels < 4.5 log IU/mL at baseline, week 24, and week 48 had high negative predictive value (NPV) for achieving undetectable HDV RNA at FU24 (81.8%, 87.1% and 95.0%, respectively). Similarly, HBcrAg levels at week 96 were significantly higher in patients with viral relapse until FU24 (3.0 vs. 3.63 log IU/mL; P = 0.0089). Baseline, week 24, and week 48 HBcrAg levels were also associated with the likelihood of achieving HBsAg level < 100 IU/mL at FU24 (HBcrAg < 3.0 log IU/mL: NPV 91.7%, 90.4% and 92.3%, respectively). Test statistics improved when combining HBcrAg with additional viral and clinical parameters. Conclusion: HBcrAg is linked to treatment response to peg‐IFNα in patients with HBV/HDV co‐infection and could be a promising marker to determine treatment futility.

Hepatitis E Virus Infection-Immune Responses to an Underestimated Global Threat.

Infection with the hepatitis E virus (HEV) is one of the main ubiquitous causes for developing an acute hepatitis. Moreover, chronification plays a predominant role in immunocompromised patients such as transplant recipients with more frequent severe courses. Unfortunately, besides reduction of immunosuppression and off-label use of ribavirin or pegylated interferon alfa, there is currently no specific anti-viral treatment to prevent disease progression. So far, research on involved immune mechanisms induced by HEV is limited. It is very difficult to collect clinical samples especially from the early phase of infection since this is often asymptomatic. Nevertheless, it is certain that the outcome of HEV-infected patients correlates with the strength of the proceeding immune response. Several lymphoid cells have been identified in contributing either to disease progression or achieving sustained virologic response. In particular, a sufficient immune control by both CD4+ and CD8+ T cells is necessary to prevent chronic viral replication. Especially the mechanisms underlying fulminant courses are poorly understood. However, liver biopsies indicate the involvement of cytotoxic T cells in liver damage. In this review, we aimed to highlight different parts of the lymphoid immune response against HEV and point out questions that remain unanswered regarding this underestimated global threat.