Viral dominance patterns in chronic hepatitis delta determine early response to interferon alpha therapy
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Viral dominance patterns in chronic hepatitis delta determine early response to interferon alpha therapy. / Lutterkort, G L; Wranke, A; Hengst, J; Yurdaydin, C; Stift, J; Bremer, B; Hardtke, S; Keskin, O; Idilman, R; Manns, M P; Dienes, H P; Falk, C; Wedemeyer, H; Heidrich, B.
In: J VIRAL HEPATITIS, Vol. 25, No. 11, 11.2018, p. 1384-1394.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Viral dominance patterns in chronic hepatitis delta determine early response to interferon alpha therapy
AU - Lutterkort, G L
AU - Wranke, A
AU - Hengst, J
AU - Yurdaydin, C
AU - Stift, J
AU - Bremer, B
AU - Hardtke, S
AU - Keskin, O
AU - Idilman, R
AU - Manns, M P
AU - Dienes, H P
AU - Falk, C
AU - Wedemeyer, H
AU - Heidrich, B
N1 - © 2018 John Wiley & Sons Ltd.
PY - 2018/11
Y1 - 2018/11
N2 - Chronic hepatitis D is caused by coinfection of hepatitis B and hepatitis D virus. While HDV is the dominant virus over HBV in the majority of cases, mechanisms and consequences of viral dominance are largely unknown. We aimed to investigate associations between viral dominance patterns and patients' characteristics and inflammatory features; 109 HDV-infected patients treated with PEG-IFNa-2α within the international multicentre, prospective HIDIT-2 trial were studied. Patients were classified as D- or B-dominant if the viral load of one virus exceeded that of the other virus by more than 1log10 . Otherwise, no viral dominance (ND) was described. We used Luminex-based multiplex technology to study 50 soluble immune mediators (SIM) in pretreatment samples of 105 HDV RNA-positive patients. Dominance of HDV was evident in the majority (75%) of cases. While only 7% displayed B-dominance, 17% showed nondominance. D-dominance was associated with downregulation of 4 interleukins (IL-2ra, IL-13, IL-16 and IL-18) and 5 chemokines/cytokines (CTACK (CCL27), MCP-1 (CCL2), M-CSF, TRAIL and ICAM-1) while no analyte was increased. In addition, D-dominance could be linked to a delayed HDV RNA response to pegylated interferon as patients with B-dominance or nondominance showed higher early HDV RNA responses (61% at week 12) than D-dominant patients (11%; P < .001). In conclusion, this study revealed unexpected effects of viral dominance on clinical and immunological features in chronic hepatitis delta patients. Individualizing PEG-IFNa-2α treatment duration should consider viral dominance. Overall, our findings suggest an activated but exhausted IFN system in D-dominant patients.
AB - Chronic hepatitis D is caused by coinfection of hepatitis B and hepatitis D virus. While HDV is the dominant virus over HBV in the majority of cases, mechanisms and consequences of viral dominance are largely unknown. We aimed to investigate associations between viral dominance patterns and patients' characteristics and inflammatory features; 109 HDV-infected patients treated with PEG-IFNa-2α within the international multicentre, prospective HIDIT-2 trial were studied. Patients were classified as D- or B-dominant if the viral load of one virus exceeded that of the other virus by more than 1log10 . Otherwise, no viral dominance (ND) was described. We used Luminex-based multiplex technology to study 50 soluble immune mediators (SIM) in pretreatment samples of 105 HDV RNA-positive patients. Dominance of HDV was evident in the majority (75%) of cases. While only 7% displayed B-dominance, 17% showed nondominance. D-dominance was associated with downregulation of 4 interleukins (IL-2ra, IL-13, IL-16 and IL-18) and 5 chemokines/cytokines (CTACK (CCL27), MCP-1 (CCL2), M-CSF, TRAIL and ICAM-1) while no analyte was increased. In addition, D-dominance could be linked to a delayed HDV RNA response to pegylated interferon as patients with B-dominance or nondominance showed higher early HDV RNA responses (61% at week 12) than D-dominant patients (11%; P < .001). In conclusion, this study revealed unexpected effects of viral dominance on clinical and immunological features in chronic hepatitis delta patients. Individualizing PEG-IFNa-2α treatment duration should consider viral dominance. Overall, our findings suggest an activated but exhausted IFN system in D-dominant patients.
KW - Adult
KW - Antiviral Agents/therapeutic use
KW - Clinical Trials as Topic
KW - Cytokines/blood
KW - DNA, Viral/blood
KW - Female
KW - Hepatitis B Surface Antigens/blood
KW - Hepatitis B virus/genetics
KW - Hepatitis D, Chronic/drug therapy
KW - Hepatitis Delta Virus/genetics
KW - Humans
KW - Interferon-alpha/therapeutic use
KW - Liver/pathology
KW - Male
KW - Middle Aged
KW - Polyethylene Glycols/therapeutic use
KW - RNA, Viral/blood
KW - Recombinant Proteins/therapeutic use
KW - Time Factors
KW - Treatment Outcome
KW - Viral Load
KW - Young Adult
U2 - 10.1111/jvh.12947
DO - 10.1111/jvh.12947
M3 - SCORING: Journal article
C2 - 29888837
VL - 25
SP - 1384
EP - 1394
JO - J VIRAL HEPATITIS
JF - J VIRAL HEPATITIS
SN - 1352-0504
IS - 11
ER -
