Z Gastroenterol 2021; 59(08): e345-e347
DOI: 10.1055/s-0041-1734278
POSTER
Hepatologie

Immunoglobulin subtypes and complement levels exhibit distinct dynamics across advanced chronic liver disease stages and predict first or further decompensation

B Simbrunner
Medical University of Vienna, Vienna, Austria
,
L Hartl
Medical University of Vienna, Vienna, Austria
,
M Jachs
Medical University of Vienna, Vienna, Austria
,
DJ Bauer
Medical University of Vienna, Vienna, Austria
,
B Scheiner
Medical University of Vienna, Vienna, Austria
,
R Paternostro
Medical University of Vienna, Vienna, Austria
,
A Stättermayer
Medical University of Vienna, Vienna, Austria
,
M Pinter
Medical University of Vienna, Vienna, Austria
,
M Trauner
Medical University of Vienna, Vienna, Austria
,
M Mandorfer
Medical University of Vienna, Vienna, Austria
,
T Reiberger
Medical University of Vienna, Vienna, Austria
› Author Affiliations
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    Background and Aims Cirrhosis-associated immune dysfunction has been described to occur in advanced chronic liver disease(ACLD), but underlying mechanisms remain poorly defined. Complement factors and immunoglobulins(Ig) are important components of innate and adaptive immunity but have not been systematically assessed across distinct ACLD stages.

    Methods Serum levels of complement factors C3c and C4, CH50 activity, as well as IgA, tissue-transglutaminase-IgA(TTG-IgA), IgM, IgG(including IgG subtypes 1-4), CRP and IL-6 levels were measured in 188 prospectively recruited ACLD patients undergoing hepatic venous pressure gradient(HVPG) measurement. Patients with acute decompensation and infections were excluded. The EASL clinical disease staging (S0-S3;[Table]) system was applied.

    Results The study cohort had a median HVPG of 17(12-21)mmHg and 116(61 %) had decompensated ACLD. HVPG and MELD, as well as CRP and IL-6 increased with ACLD stages ([Table]). C3c levels significantly decreased in stages S2 and S3, and C4 and CH50 were lower in S3 (vs. S0;all p<0.05;Bonferroni-adjusted). Furthermore, IgA levels and TTGIgA increased in S2 and S3 (vs. S0;all p<0.05;Bonferroni-adjusted), while IgM and IgG (including IgG subtypes) remained similar. IgA and TTG-IgA correlated significantly (Spearman’s ρ=0.811;p<0.001) and were linked to CRP (IgA ρ=0.369; TTG-IgA ρ=0.300;p<0.001) and IL-6 (Spearman’s ρ;IgA ρ=0.534; TTG-IgA ρ=0.454; p<0.001). During a median follow-up period of 8.20 (4.03-15.3) months, IgA (per 25mg/dL; aHR:1.03;1.00-1.06;p = 0.025), TTG-IgA (aHR: 1.27;1.04-1.55;p = 0.018), and IgG-4 (per 25mg/dL; aHR:1.06; 1.021.11; p = 0.001) displayed predictive value for first or further decompensation, when adjusted for MELD and IL-6 levels (assessed by Cox regression).

    Conclusion Patients with decompensated ACLD showed increased serum IgA levels and decreased complement levels. IgA/TTG-IgA (commonly linked to the mucosal immune system) and IgG4 (associated with the induction of immune tolerance) levels predicted first/further decompensation, suggesting that these factors are relevant for the progression of ACLD.Further (mechanistic) studies should validate these findings and investigate their association with cirrhosis-associated immune dysfunction.

    Tab. 1

    Compensated ACLD(n = 73)

    Decompensated ACLD(n = 116)

    P-value

    Stage 0

    Stage 1 Bleeding(n = 6)

    Stage 2 Non-bleeding decomp-ensation(n = 61)

    Stage 3 Further decomp-ensation(n = 49)

    Age (years)

    59 (51-66)

    55 (54-60)

    57 (50-65)

    57 (49-66)

    0.904

    Sex (M, %)

    48 (66)

    4 (67)

    41 (67)

    33 (67)

    0.997

    Etiology (n, %)-ALD-Viral-ALD + Viral-NASH-Cholestatic-Other

    21 (29)22 (30)2 (3)13 (18)9 (12)6 (8)

    1 (17)4 (66)0 (0)0 (0)0 (0)1 (17)

    40 (66)3 (5)2 (3)1 (2)4 (7)11 (18)

    30 (61)4 (8)6 (12)1 (2)2 (4)6 (12)

    < 0.001

    HVPG (mmHg)

    13 (10-18)

    15 (12-22)

    20 (16-22)

    19 (15-23)

    < 0.001

    MELD Score (points)

    9 (8-11)

    10 (9-11)

    12 (10-15)

    13 (11-16)

    < 0.001

    CRP (mg/dL)

    0.21 (0.09-0.42)

    0.13 (0.07-0.59)

    0.41 (0.16-0.91)

    0.51 (0.24-1.31)

    < 0.001

    IL-6 (pg/mL)

    5.12 (2.81-8.57)

    5.56 (4.41-13.1)

    9.74 (5.49-17.9)

    15.3 (9.83-29.0)

    < 0.001

    C3c (mg/dL)

    101 (86.8-116)

    105 (83.5-117)

    86.8 (70.2-102)

    81.0 (64.8-92.2)

    < 0.001

    C4 (mg/dL)

    16.1 (10.6-21.1)

    16.1 (13.8-16.9)

    13.6 (10.3-17.1)

    12.0 (9.05-15.7)

    0.006

    CH50 (U/mL)

    55.2 (48.6-60.0)

    52.9 (44.1-60.0)

    54.6 (40.0-60.0)

    45.2 (32.0-54.4)

    0.004

    IgA (mg/dL)

    302 (212-430)

    284 (257-418)

    445 (298-604)

    488 (312-680)

    < 0.001

    IgM (mg/dL)

    118 (70.7-171)

    112 (53.8-297)

    159 (92.4-240)

    144 (87.9)

    0.140

    IgG (mg/dL)

    1350 (1085-1690)

    1510 (1273-1675)

    1500 (1240-1890)

    1470 (1220-1760)

    0.115

    IgG-1 (mg/dL)

    860 (691-1095)

    1145 (763-1340)

    1030 (813-1315)

    954 (799-1200)

    0.222

    IgG-2 (mg/dL)

    322 (255-429)

    208 (165-386)

    339 (241-542)

    361 (257-454)

    0.219

    IgG-3 (mg/dL)

    52.1 (34.8-72.6)

    49.8 (29.4-64.6)

    58.5 (37.5-98.3)

    59.2 (34.5-100)

    0.174

    IgG-4 (mg/dL)

    47.2 (22.2-80.4)

    65.7 (43.3-100)

    49.0 (23.6-151)

    72.2 (28.1-148)

    0.352

    TTG-IgA (U/mL)

    1.30 (1.00-2.50)

    1.50 (1.00-2.66)

    2.10 (1.30-3.00)

    2.30 (1.30-3.30)

    0.002


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    Publication History

    Article published online:
    01 September 2021

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