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  - Unnewehr, Markus
A1  - Stich, August
T1  - Fighting Hepatitis B in North Korea: Feasibility of a Bi-modal Prevention Strategy
JF  - Journal of Korean Medical Science
N2  - In North Korea, the prevalence of hepatitis B is high due to natural factors, gaps in vaccination, and the lack of antiviral treatment. Aid projects are urgently needed, however impeded by North Korea's political and economical situation and isolation. The feasibility of a joint North Korean and German humanitarian hepatitis B prevention program was assessed. Part 1: Hepatitis B vaccination catch-up campaign. Part 2: Implementation of endoscopic ligation of esophageal varices (EVL) by trainings in Germany and North Korea. By vaccinating 7 million children between 2010 and 2012, the hepatitis B vaccination gap was closed. Coverage of 99.23% was reached. A total of 11 hepatitis B-induced liver cirrhosis patients (mean age 41.1 yr) with severe esophageal varices and previous bleedings were successfully treated by EVL without major complications. A clinical standard operating procedure, a feedback system and a follow-up plan were developed. The bi-modal preventive strategy was implemented successfully. Parts of the project can serve as an example for other low-income countries, however its general transferability is limited due to the special circumstances in North Korea.
KW  - therapy
KW  - hepatitis B
KW  - Democratic People's Republic of Korea
KW  - ligation
KW  - cirrhosis
KW  - diagnosis
KW  - infection
KW  - health
KW  - primary prophylaxis
KW  - mass vaccination
KW  - esophagoscopy
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-138773
VL  - 30
ER  -