TY  - JOUR
A1  - Rau, Monika
A1  - Schmitt, Johannes
A1  - Berg, Thomas
A1  - Kremer, Andreas E.
A1  - Stieger, Bruno
A1  - Spanaus, Katharina
A1  - Bengsch, Bertram
A1  - Romero, Marta R.
A1  - Marin, Jose J.
A1  - Keitel, Verena
A1  - Klinker, Hartwig
A1  - Tony, Hans-Peter
A1  - Müllhaupt, Beat
A1  - Geier, Andreas
T1  - Serum IP-10 levels and increased DPPIV activity are linked to circulating CXCR3+ T cells in cholestatic HCV patients
JF  - PLoS ONE
N2  - Background & aims
Serum interferon-gamma-inducible protein-10 (IP-10) is elevated in cholestatic liver diseases and predicts response to antiviral therapy in patients with chronic hepatitis C virus (HCV) infection. Dipeptidylpeptidase 4 (DPPIV) cleaves active IP-10 into an inactive form, which inhibits recruitment of CXCR3+ T cells to the liver. In this study the link between IP-10 levels, DPPIV activity in serum and CXCR3+ T cells is analysed in cholestatic and non-cholestatic liver patients.

Methods
In serum DPPIV activity (by enzymatic assay), IP-10 (by ELISA) and bile acids (BA) (by enzymatic assay) were analysed in 229 naive HCV genotype (GT) 1 patients and in 16 patients with cholestatic liver disease. In a prospective follow-up (FU) cohort of 27 HCV GT 1 patients peripheral CD3+CXCR3+, CD4+CXCR3+ and CD8+CXCR3+ cells were measured by FACS.

Results
In 229 HCV patients serum IP-10 levels correlated positively to DPPIV serum activity. Higher IP-10 levels and DPPIV activity were detected in cholestatic and in cirrhotic HCV patients. Increased IP-10 serum levels were associated with therapeutic non-response to antiviral treatment with pegylated-interferon and ribavirin. In the HCV FU cohort elevated IP-10 serum levels and increased BA were associated with higher frequencies of peripheral CD3+CXCR3+, CD4+CXCR3+ and CD8+CXCR3+ T cells. Positive correlation between serum IP-10 levels and DPPIV activity was likewise validated in patients with cholestatic liver diseases.

Conclusions
A strong correlation between elevated serum levels of IP-10 and DPPIV activity was seen in different cholestatic patient groups. Furthermore, in cholestatic HCV patients a functional link to increased numbers of peripheral CXCR3+ immune cells could be observed. The source of DPPIV release in cholestatic patients remains open.
KW  - hepatitis C virus
KW  - T cells
KW  - liver diseases
KW  - chemokines
KW  - cytotoxic T cells
KW  - immune cells
KW  - cirrhosis
KW  - bile
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177674
VL  - 13
IS  - 12
ER  - 
TY  - JOUR
A1  - Cornberg, Markus
A1  - Stoehr, Albrecht
A1  - Naumann, Uwe
A1  - Teuber, Gerlinde
A1  - Klinker, Hartwig
A1  - Lutz, Thomas
A1  - Möller, Hjördis
A1  - Hidde, Dennis
A1  - Lohmann, Kristina
A1  - Simon, Karl-Georg
T1  - Real-world safety, effectiveness, and patient-reported outcomes in patients with chronic hepatitis C virus infection treated with glecaprevir/pibrentasvir: updated data from the German Hepatitis C-Registry (DHC-R)
JF  - Viruses
N2  - Using data from the German Hepatitis C-Registry (Deutsche Hepatitis C-Register, DHC-R), we report the real-world safety and effectiveness of glecaprevir/pibrentasvir (GLE/PIB) treatment and its impact on patient-reported outcomes (PROs) in underserved populations who are not typically included in clinical trials, yet who will be crucial for achieving hepatitis C virus (HCV) elimination. The DHC-R is an ongoing, non-interventional, multicenter, prospective, observational cohort study on patients treated for chronic HCV infection in Germany. The data cutoff was 17 January 2021. The primary effectiveness endpoint was sustained virologic response at post-treatment Week 12 (SVR12). Safety outcomes were assessed in all patients receiving GLE/PIB. PROs were assessed using the SF-36 survey. Of 2354 patients, 1964 had valid SVR12 data (intention-to-treat analysis). Of these, 1905 (97.0%) achieved SVR12 with rates similar across the comorbidities analyzed, except for people who actively use drugs (PWUD (active)) (86.4%). Excluding those who discontinued treatment and did not achieve SVR12, or were reinfected with HCV, the rate was 99.3%, with similar results regardless of comorbidity. PWUD (active) and those with psychiatric disorders had the most meaningful improvements in PROs. Adverse events (AEs) occurred in 631/2354 patients (26.8%), and serious AEs in 44 patients (1.9%). GLE/PIB was highly effective and well tolerated in this real-world study of patient groups key to HCV elimination.
KW  - direct-acting antiviral
KW  - glecaprevir/pibrentasvir
KW  - hepatitis C virus
KW  - real world evidence
KW  - German Hepatitis C-Registry
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-281939
SN  - 1999-4915
VL  - 14
IS  - 7
ER  -