Predictive value of high bacterial deoxyribonucleic acid levels in ascites on spontaneous bacterial peritonitis and adverse prognosis of patients with cirrhosis

doi:10.3877/cma.j.issn.1674-1358.2025.03.003

Abstract

Abstract:

Objective

To investigate the predictive efficacy and effect of bacterial DNA level in ascites on prognosis of bacterial peritoneal inflammation (SBP) of cirrhosis patients with ascites after removing cell-free DNA.

Methods

A single-center prospective cohort design was adopted, and a total of 230 patients with ascites due to liver cirrhosis who were hospitalized in Beijing YouAn Hospital, Capital Medical University from September 2021 to December 2022 were enrolled. Ascitic fluid samples were collected at admission and pretreated with Benzonase to remove free DNA. Bacterial DNA levels were then quantitatively measured using droplet digital PCR (ddPCR). Based on the ascitic bacterial DNA load at admission, patients were divided into high bacterial DNA load group [log (bacterial DNA) ≥ 2, 38 cases] and low bacterial DNA load group [log (bacterial DNA) < 2, 192 cases]. Independent risk factors for SBP within 30-days after hospitalized were analyzed by Logistic regression analysis, while the impact of bacterial DNA load on 90-days and 360-days of hospitalized survival were assessed by Cox regression and ROC curve analysis.

Results

The incidence of SBP in high bacterial DNA load group was 44.7% (17/38), significantly higher than that of low bacterial DNA load group (6.25%, 12/192), with significant difference (χ² = 42.81, P < 0.001). Multivariate Logistic regression analysis indicated that elevated bacterial DNA load in ascites [log (bacterial DNA) ≥ 2] (OR = 3.040, 95%CI: 1.605-5.756, P = 0.001), upper gastrointestinal bleeding (OR = 6.061, 95%CI: 2.315-15.625, P < 0.001), and chronic kidney disease (OR = 12.195, 95%CI: 4.504-32.258, P < 0.001) were all independent risk factors for the occurrence of SBP within 30 days in patients with cirrhotic ascites. A predictive model incorporating the MELD score, log (bacterial DNA) and neutrophil count was constructed to assess the risk of 90-days mortality. ROC curve analysis showed that the predictive performance of the combined model (AUC = 0.823) was superior to that of the MELD score alone (AUC = 0.754), with significant difference (Z = 2.823, P = 0.005). The 90-days and 360-days survival rates in high bacterial DNA load group (71.1% and 57.9%) were significantly lower than those of low bacterial DNA load group (84.4% and 79.2%), with significant differences (χ² = 2.99, P = 0.038;χ² = 6.68, P = 0.002).

Conclusions

Ascitic bacterial DNA levels after removal of free DNA have significant predictive value for the occurrence of SBP in patients with cirrhotic ascites. High bacterial DNA load in ascites is associated with lower survival rates of 90-days and 360-days after hospitalized, suggesting that bacterial translocation may play an important role in prognostic evaluation of liver cirrhosis.

Key words: Ascites, Bacterial deoxyribonucleic acid, Spontaneous bacterial peritonitis, Cirrhosis, Prognosis

Luyao Guo, Wei Hou, Jie Han, Haoxin Wu, Feili Wei, Zheng Wang, Wei Zhang, Kefei Wang, Shan Guo, Zhongjie Hu. Predictive value of high bacterial deoxyribonucleic acid levels in ascites on spontaneous bacterial peritonitis and adverse prognosis of patients with cirrhosis[J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2025, 19(03): 146-156.

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Figures/Tables 11

References 39

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临床特征	合计（230例）	腹水细菌DNA高载量组（38例）	腹水细菌DNA低载量组（192例）	统计量	P值
人口学特征
年龄（，岁）	57.90 ± 10.49	57.63 ± 10.44	57.95 ± 10.52	t = 0.173	0.863
性别（男/女，例）	180/50	31/7	149/43	χ² = 0.295	0.587^a
住院时长（，d）	15.63 ± 6.85	16.13 ± 7.8	15.53 ± 6.67	t =－0.497	0.620
实验室指标
AST[M（P₂₅，P₇₅），IU/L]	42.0（26.0，78.0）	41.00（24.75，80.75）	42.0（27.0，78.0）	Z =－0.621	0.535
ALT[M（P₂₅，P₇₅）），IU/L]	21.0（13.0，32.25）	20.50（15.00，38.75）	21（13.0，35.0）	Z =－0.26	0.795
TBil [M（P₂₅，P₇₅），mmol/L]	62.75（29.55，163.33）	67.50（22.50，206.53）	61.35（31.03，162.1）	Z =－0.31	0.757
INR [M（P₂₅，P₇₅））]	1.48（1.28，1.85）	1.49（1.28，1.87）	1.48（1.28，1.84）	Z =－0.353	0.724
ALB（，g/dl）	29.36 ± 4.42	28.11 ± 5.47	29.61 ± 4.16	t = 1.920	0.056
Cr [M（P₂₅，P₇₅），mmol/L]	75.0（59.0，110.75）	72.00（62.00，122.25）	75.0（58.75，108.5）	Z = 0.414	0.679
WBC [M（P₂₅，P₇₅），× 10⁹/L]	5.15（3.37，7.83）	6.55（4.08，10.02）	5.08（3.26，7.63）	Z =－2.167	0.030
HB [M（P₂₅，P₇₅），g/L]	93（73，114）	87.50（64.00，111.50）	93（75.25，114.75）	Z = 1.168	0.243
PLT[M（P₂₅，P₇₅），× 10⁹/L]	81（49，127.5）	74.00（42.00，147.00）	82.5（49.25，126.25）	Z = 0.268	0.798
评分
MELD（）	15.94 ± 8.23	16.26 ± 8.78	15.88 ± 8.14	t=－0.245	0.797
Child-Pugh（）	9.43 ± 1.72	9.42 ± 2.05	9.43 ± 1.66	t = 0.017	0.986
并发症 [例（%）]
消化道出血	22（9.6）	6（15.8）	16（8.3）	χ² = 1.268	0.260^b
肝性脑病	27（11.7）	5（13.2）	22（11.5）	χ² = 0.043	0.836^a
急性肾损伤	22（9.6）	3（7.9）	19（9.9）	χ² = 0.007	0.935^b
基础疾病 [例（%）]
高血压	36（15.7）	6（15.8）	30（15.6）	χ² = 0.001	0.980^b
2型糖尿病	50（21.7）	11（28.9）	39（20.3）	χ² = 1.390	0.238^b
慢性肾脏病	25（10.9）	6（15.8）	19（9.9）	χ² = 0.610	0.435^b
病死率 [例（%）]
90 d	43（18.7）	11（28.9）	32（16.7）	χ² = 3.290	0.070^a
360 d	56（24.3）	16（42.1）	40（20.8）	χ² = 3.290	0.005^a

临床特征	合计（230例）	腹水细菌DNA高载量组（38例）	腹水细菌DNA低载量组（192例）	统计量	P值
人口学特征
年龄（，岁）	57.90 ± 10.49	57.63 ± 10.44	57.95 ± 10.52	t = 0.173	0.863
性别（男/女，例）	180/50	31/7	149/43	χ² = 0.295	0.587^a
住院时长（，d）	15.63 ± 6.85	16.13 ± 7.8	15.53 ± 6.67	t =－0.497	0.620
实验室指标
AST[M（P₂₅，P₇₅），IU/L]	42.0（26.0，78.0）	41.00（24.75，80.75）	42.0（27.0，78.0）	Z =－0.621	0.535
ALT[M（P₂₅，P₇₅）），IU/L]	21.0（13.0，32.25）	20.50（15.00，38.75）	21（13.0，35.0）	Z =－0.26	0.795
TBil [M（P₂₅，P₇₅），mmol/L]	62.75（29.55，163.33）	67.50（22.50，206.53）	61.35（31.03，162.1）	Z =－0.31	0.757
INR [M（P₂₅，P₇₅））]	1.48（1.28，1.85）	1.49（1.28，1.87）	1.48（1.28，1.84）	Z =－0.353	0.724
ALB（，g/dl）	29.36 ± 4.42	28.11 ± 5.47	29.61 ± 4.16	t = 1.920	0.056
Cr [M（P₂₅，P₇₅），mmol/L]	75.0（59.0，110.75）	72.00（62.00，122.25）	75.0（58.75，108.5）	Z = 0.414	0.679
WBC [M（P₂₅，P₇₅），× 10⁹/L]	5.15（3.37，7.83）	6.55（4.08，10.02）	5.08（3.26，7.63）	Z =－2.167	0.030
HB [M（P₂₅，P₇₅），g/L]	93（73，114）	87.50（64.00，111.50）	93（75.25，114.75）	Z = 1.168	0.243
PLT[M（P₂₅，P₇₅），× 10⁹/L]	81（49，127.5）	74.00（42.00，147.00）	82.5（49.25，126.25）	Z = 0.268	0.798
评分
MELD（）	15.94 ± 8.23	16.26 ± 8.78	15.88 ± 8.14	t=－0.245	0.797
Child-Pugh（）	9.43 ± 1.72	9.42 ± 2.05	9.43 ± 1.66	t = 0.017	0.986
并发症 [例（%）]
消化道出血	22（9.6）	6（15.8）	16（8.3）	χ² = 1.268	0.260^b
肝性脑病	27（11.7）	5（13.2）	22（11.5）	χ² = 0.043	0.836^a
急性肾损伤	22（9.6）	3（7.9）	19（9.9）	χ² = 0.007	0.935^b
基础疾病 [例（%）]
高血压	36（15.7）	6（15.8）	30（15.6）	χ² = 0.001	0.980^b
2型糖尿病	50（21.7）	11（28.9）	39（20.3）	χ² = 1.390	0.238^b
慢性肾脏病	25（10.9）	6（15.8）	19（9.9）	χ² = 0.610	0.435^b
病死率 [例（%）]
90 d	43（18.7）	11（28.9）	32（16.7）	χ² = 3.290	0.070^a
360 d	56（24.3）	16（42.1）	40（20.8）	χ² = 3.290	0.005^a

指标	腹水细菌DNA高载量组（38例）	腹水细菌DNA低载量组（192例）	统计量	P值
SBP [例（%）]	17（44.70）	12（6.25）	χ² = 42.810^a	< 0.001
PMN [M（P₂₅，P₇₅），× 10⁹/L]	0.18（0.05，1.57）	0.03（0.01，0.05）	Z =－5.987	< 0.001
PCT [M（P₂₅，P₇₅），ng/ml]	0.39（0.14，2.24）	0.30（0.02，0.52）	Z =－2.265	0.024
WBC [M（P₂₅，P₇₅），× 10⁹/L]	6.55（4.08，10.02）	5.08（3.26，7.63）	Z =－2.167	0.030
NEUT [M（P₂₅，P₇₅），× 10⁹/L]	4.54（2.75，8.51）	3.41（2.07，5.57）	Z =－2.515	0.012
LYM [M（P₂₅，P₇₅），× 10⁹/L]	0.69（0.39，1.38）	0.81（0.45，1.17）	Z = 0.680	0.496
MONO [M（P₂₅，P₇₅），× 10⁹/L]	0.39（0.24，0.76）	0.44（0.28，0.67）	Z = 0.065	0.948
CRP（，mg/L）	20.85（8.62，47.68）	14.59（7.20，28.99）	t =－0.826	0.409
MELD评分（）	16.26 ± 8.78	15.88 ± 8.14	t =－0.245	0.797
CTP评分（）	9.42 ± 2.05	9.43 ± 1.66	t = 0.017	0.986

指标	腹水细菌DNA高载量组（38例）	腹水细菌DNA低载量组（192例）	统计量	P值
SBP [例（%）]	17（44.70）	12（6.25）	χ² = 42.810^a	< 0.001
PMN [M（P₂₅，P₇₅），× 10⁹/L]	0.18（0.05，1.57）	0.03（0.01，0.05）	Z =－5.987	< 0.001
PCT [M（P₂₅，P₇₅），ng/ml]	0.39（0.14，2.24）	0.30（0.02，0.52）	Z =－2.265	0.024
WBC [M（P₂₅，P₇₅），× 10⁹/L]	6.55（4.08，10.02）	5.08（3.26，7.63）	Z =－2.167	0.030
NEUT [M（P₂₅，P₇₅），× 10⁹/L]	4.54（2.75，8.51）	3.41（2.07，5.57）	Z =－2.515	0.012
LYM [M（P₂₅，P₇₅），× 10⁹/L]	0.69（0.39，1.38）	0.81（0.45，1.17）	Z = 0.680	0.496
MONO [M（P₂₅，P₇₅），× 10⁹/L]	0.39（0.24，0.76）	0.44（0.28，0.67）	Z = 0.065	0.948
CRP（，mg/L）	20.85（8.62，47.68）	14.59（7.20，28.99）	t =－0.826	0.409
MELD评分（）	16.26 ± 8.78	15.88 ± 8.14	t =－0.245	0.797
CTP评分（）	9.42 ± 2.05	9.43 ± 1.66	t = 0.017	0.986

影响因素	β值	S.E.值	Wald χ²值	OR值	95%CI	P值
男性	0.158	0.604	0.068	1.171	0.358～3.824	0.794
年龄	0.057	0.028	4.084	1.059	1.002～1.119	0.043
log（细菌DNA）	3.281	0.899	13.314	26.608	4.566～155.054	< 0.001
腹水总蛋白	0.021	0.028	0.569	1.022	0.967～1.080	0.451
腹水白蛋白	0.022	0.054	0.169	1.022	0.920～1.137	0.681
上消化道出血	1.192	0.631	3.570	3.294	0.956～11.364	0.049
肝性脑病	－18.888	8 380.814	0.000	0.000	0.000～0.000	0.998
急性肾损伤	0.345	0.798	0.187	1.412	0.296～6.741	0.665
高血压	－0.343	0.781	0.193	0.710	0.154～3.281	0.661
慢性肾脏病	1.794	0.611	8.614	6.014	1.815～20.000	0.003
2型糖尿病	0.944	0.549	2.955	2.571	0.132～1.142	0.068
PCT	－0.020	0.075	0.069	0.980	0.846～1.136	0.792
WBC	0.118	0.047	6.343	1.126	1.027～1.234	0.012
NEUT	0.133	0.052	6.512	1.143	1.031～1.266	0.011
LYM	0.417	0.390	1.140	1.517	0.706～3.261	0.286
MONO	0.896	0.651	1.894	2.450	0.684～8.777	0.169
HGB	0.001	0.005	0.039	1.001	0.992～1.010	0.844
PLT	0.000	0.003	0.021	1.000	0.994～1.007	0.886
CRP	0.010	0.006	2.798	1.010	0.998～1.023	0.094
ALT	－0.001	0.004	0.083	0.999	0.991～1.007	0.773
AST	0.000	0.001	0.040	1.000	0.998～1.002	0.842
白蛋白	0.005	0.064	0.006	1.005	0.887～1.139	0.937
TBil	－0.003	0.003	1.236	0.997	0.992～1.002	0.266
Cr	0.000	0.005	0.000	1.000	0.991～1.009	0.991
INR	－0.008	0.440	0.000	0.992	0.489～1.771	0.826
MELD评分	0.004	0.032	0.014	1.004	0.943～1.068	0.906
Child-Pugh评分	－0.204	0.161	1.606	0.815	0.595～1.118	0.205

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