Expression of the large amino acid transporter SLC7A5/LAT1 on immune cells is enhanced in primary sclerosing cholangitis-associated cholangiocarcinoma and correlates with poor prognosis in cholangiocarcinoma.

Biliary tract cancers (BTC) are rare lethal malignancies arising along the biliary tree. Unfortunately, effective therapeutics are lacking and the prognosis remains dismal even for patients eligible for surgical resection. Therefore, novel therapeutic approaches along with early detection strategies and prognostic markers are urgently needed.

STAT activation in regulatory CD4 T cells of patients with primary sclerosing cholangitis.

Introduction: Regulatory CD4 T cells (Tregs) are pivotal for inhibition of autoimmunity. Primary sclerosing cholangitis (PSC) is an autoimmune cholestatic liver disease of unknown etiology where contribution of Tregs is still unclear. Activation of the JAK-STAT pathway critically modifies functions of Tregs.

Role of PAR1 -506 deletion/insertion polymorphism in primary sclerosing cholangitis.

Aim: Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease characterized by inflammation of the intra- and extrahepatic bile ducts. Pathogenesis of PSC is still enigmatic but is likely to be multifactorial. Recently, we identified an interleukin-6 (IL-6)-dependent signal transducer and activator of transcription 3 (STAT3) activation in CD4 TH1 and TH17 cells in PSC.

Torque Teno Virus Load Is Associated With Centers for Disease Control and Prevention Stage and CD4+ Cell Count in People Living With Human Immunodeficiency Virus but Seems Unrelated to AIDS-Defining Events and Human Pegivirus Load.

Background: Torque teno virus (TTV) is part of the human virome. TTV load was related to the immune status in patients after organ transplantation. We hypothesize that TTV load could be an additional marker for immune function in people living with HIV (PLWH).

IL-6-Dependent STAT3 Activation and Induction of Proinflammatory Cytokines in Primary Sclerosing Cholangitis.

Introduction: Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease with periductal inflammation and fibrosis. Genetic studies suggest inflammatory cytokines and IL-6-dependent activation of transcription factor STAT3 as pivotal steps in PSC pathogenesis. However, details of inflammatory regulation remain unclear.

High producer variant of lipoprotein lipase may protect from hepatocellular carcinoma in alcohol-associated cirrhosis.

Background & Aims: Progression of alcohol-associated liver disease (ALD) is driven by genetic predisposition. The rs13702 variant in the lipoprotein lipase (LPL) gene is linked to non-alcoholic fatty liver disease. We aimed at clarifying its role in ALD.

Single-cell RNA sequencing identifies a population of human liver-type ILC1s.

Group 1 innate lymphoid cells (ILCs) comprise a heterogeneous family of cytotoxic natural killer (NK) cells and ILC1s. We identify a population of "liver-type" ILC1s with transcriptional, phenotypic, and functional features distinct from those of conventional and liver-resident NK cells as well as from other previously described human ILC1 subsets. LT-ILC1s are CD49aCD94CD200R1, express the transcription factor T-BET, and do not express the activating receptor NKp80 or the transcription factor EOMES.

Genetic Variation of Is Not an Independent Risk Factor for Alcoholic Hepatocellular Carcinoma in Caucasian Patients.

Hepatocellular carcinoma (HCC) is a severe complication of advanced alcoholic liver disease, which is modulated by genetic predisposition. Identifying new genetic loci might improve screening. Genetic variation of SAMM50 was linked to HCC.

Transient flare of psoriasis under direct-acting antiviral therapy of chronic hepatitis C: A case report.

Extrahepatic manifestations of chronic hepatitis C virus (HCV) infection frequently involve the skin. Here, we report the case of a woman, who experienced a psoriasis exacerbation on DAA treatment, which lead to psoriasis resolution upon HCV clearance under continued treatment with elbasvir/grazoprevir.

Analysis of antibodies from HCV elite neutralizers identifies genetic determinants of broad neutralization.

The high genetic diversity of hepatitis C virus (HCV) complicates effective vaccine development. We screened a cohort of 435 HCV-infected individuals and found that 2%-5% demonstrated outstanding HCV-neutralizing activity. From four of these patients, we isolated 310 HCV antibodies, including neutralizing antibodies with exceptional breadth and potency.

TLR agonists enhance responsiveness of inflammatory innate immune cells in HLA-B*57-positive HIV patients.

HLA-B*57 affects the course of HIV infection. Under antiretroviral therapy, its effects cannot be explained by outstandingly efficient T cell responses alone but may also involve cells of innate immunity. Studying in vitro stimulation with Pam3CSK4, E.

The PNPLA3 I148M variant promotes lipid-induced hepatocyte secretion of CXC chemokines establishing a tumorigenic milieu.

The I148M variant of the Patatin-like phospholipase domain-containing 3 (PNPLA3) protein is associated with an increased risk for liver inflammation and hepatocellular carcinoma (HCC), but the underlying mechanism is unknown. We hypothesized that enhanced CXC chemokine secretion mediates hepatic inflammation that accelerates development of HCC. Expandable primary human (upcyte®) hepatocytes and human PLC/PRF/5 hepatoma cells were lentivirally transduced with both PNPLA3 I148M variants and stimulated with lipids.

FOXP3 Inhibitory Peptide P60 Increases Efficacy of Cytokine-induced Killer Cells Against Renal and Pancreatic Cancer Cells.

Background/aim: Cytokine-induced killer (CIK) cells are ex vivo expanded major histocompatibility complex (MHC)-unrestricted cytotoxic cells with promising effects against a variety of cancer types. Regulatory T-cells (T-reg) have been shown to reduce the effectiveness of CIK cells against tumor cells. Peptide P60 has been shown to inhibit the immunosuppressive functions of T-regs.

Survival of HIV/HCV co-infected patients before introduction of HCV direct acting antivirals (DAA).

HIV/HCV infection is supposed to substantially reduce survival as compared to HIV mono-infection. Here, we compared longtime-survival and causes of death in a cohort of HIV- and HIV/HCV-co-infected patients on combined antiretroviral therapy (cART), before introduction of HCV direct acting antivirals (DAA). 322 Caucasian patients with HIV (n = 176) and HIV/HCV-infection (n = 146) were enrolled into this study.

Observation of J/ψϕ Structures Consistent with Exotic States from Amplitude Analysis of B^{+}→J/ψϕK^{+} Decays.

The first full amplitude analysis of B^{+}→J/ψϕK^{+} with J/ψ→μ^{+}μ^{-}, ϕ→K^{+}K^{-} decays is performed with a data sample of 3  fb^{-1} of pp collision data collected at sqrt[s]=7 and 8 TeV with the LHCb detector. The data cannot be described by a model that contains only excited kaon states decaying into ϕK^{+}, and four J/ψϕ structures are observed, each with significance over 5 standard deviations. The quantum numbers of these structures are determined with significance of at least 4 standard deviations.

Increased peripheral CD4 regulatory T cells persist after successful direct-acting antiviral treatment of chronic hepatitis C.

Background & Aims: CD4 regulatory T cells (Tregs) expand during chronic hepatitis C virus (HCV) infection, inhibit antiviral immunity and promote fibrosis. Direct-acting antiviral agents (DAA) have revolutionized HCV therapy. However, it is unclear if Tregs are normalized after DAA-induced HCV elimination.

Evidence for Exotic Hadron Contributions to Λ_{b}^{0}→J/ψpπ^{-} Decays.

A full amplitude analysis of Λ_{b}^{0}→J/ψpπ^{-} decays is performed with a data sample acquired with the LHCb detector from 7 and 8 TeV pp collisions, corresponding to an integrated luminosity of 3  fb^{-1}. A significantly better description of the data is achieved when, in addition to the previously observed nucleon excitations N→pπ^{-}, either the P_{c}(4380)^{+} and P_{c}(4450)^{+}→J/ψp states, previously observed in Λ_{b}^{0}→J/ψpK^{-} decays, or the Z_{c}(4200)^{-}→J/ψπ^{-} state, previously reported in B^{0}→J/ψK^{+}π^{-} decays, or all three, are included in the amplitude models. The data support a model containing all three exotic states, with a significance of more than three standard deviations.

Model-Independent Evidence for J/ψp Contributions to Λ_{b}^{0}→J/ψpK^{-} Decays.

The data sample of Λ_{b}^{0}→J/ψpK^{-} decays acquired with the LHCb detector from 7 and 8 TeV pp collisions, corresponding to an integrated luminosity of 3  fb^{-1}, is inspected for the presence of J/ψp or J/ψK^{-} contributions with minimal assumptions about K^{-}p contributions. It is demonstrated at more than nine standard deviations that Λ_{b}^{0}→J/ψpK^{-} decays cannot be described with K^{-}p contributions alone, and that J/ψp contributions play a dominant role in this incompatibility. These model-independent results support the previously obtained model-dependent evidence for P_{c}^{+}→J/ψp charmonium-pentaquark states in the same data sample.