Assessing the Short-Term Prognosis of Patients with Cirrhosis Using the DIC Scores

Prediction of prognosis in patients with chronic liver disease is an art which is seldom supported by objective, reliable, and reproducible tools.[1] In patients with liver cirrhosis, the Model for End-stage Liver Disease (MELD) score was devised more than 20 years ago to assess the suitability of patients to transjugular intrahepatic portosystemic shunt, and its use soon became popular to assess the short-term prognosis of patients with cirrhosis and their candidacy to liver transplantation.[2] [3] [4] Despite some adjustments, such as the inclusion of sodium, the MELD score is used worldwide to assess the prognosis of patients with cirrhosis.[5] In these patients also coagulation indexes and degree of thrombocytopenia are associated with liver function derangement, as the majority of coagulation factors and thrombopoietin are synthesized by the liver, while platelets are also cleared from the circulation by the spleen due to increased portal pressure, and thus also these parameters are often used to indirectly evaluate the degree of liver dysfunction and portal hypertension.[6] [7] [8] Hypofibrinogenemia is often observed in patients with end-stage liver disease, and its presence—besides being variably associated with spontaneous or provoked bleeding—harbors an ominous prognosis.[9] [10] [11]

Recently, Grafeneder et al observed that the disseminated intravascular coagulation (DIC) score is able to predict 30-day mortality in a heterogeneous group of patients with very low fibrinogen levels and at least two pathological DIC parameters, with a statistically significant improved accuracy as compared with the MELD-Na score, although they observed that in the sub-group of patients with cirrhosis this prognostic improvement—though meaningful—was not statistically significant.[12] [13] [14] These results underscore the complexity of the relationship between coagulation indexes, liver dysfunction, and prognostic assessment of patients with liver disease, although they fell short to support the use of the DIC scores for the prediction of very short-term survival in patients with end-stage liver disease. The reasons behind this missed opportunity may either reside in the retrospective setting of the study, in the identification of patients by means of International Classification of Diseases coding, and in the inclusion of patients with heterogeneous conditions, or with the fact that in patients with very low fibrinogen (i.e., <150 mg/dL) and elevated MELD score, the DIC scores may truly fail to add further granularity to prognostication.

To verify whether the (partially negative) results of the study by Grafeneder et al might have been secondary to this bias, we prospectively assessed the prognosis of a series of consecutive patients with liver cirrhosis using the inclusion criteria set forth in their study, with the exclusion of a fibrinogen level <150 mg/dL, and compared the accuracy of the MELD-Na and DIC scores in assessing their prognosis. To this end, we studied 33 patients with liver cirrhosis at admission in our clinical ward, between August and November 2022, whose main characteristics are shown in [Table 1]. Most patients had decompensated liver disease and the 30-day mortality rate was 36.3%, with this figure mainly related to a high incidence of sepsis (27.3%) and bleeding (33.3%) in this population. [Fig. 1A] shows the receiver operating characteristics (ROC) curves for 30-day mortality of the MELD-Na, the International Society on Thrombosis and Haemostasis (ISTH) DIC-2001, and the ISTH DIC-2018 scores together with their accuracy figures. While all the scores adequately predicted the 30-day prognosis, we observed a numerically greater accuracy of the DIC scores over the MELD-Na score, although this difference did not reach statistical significance likely due to the small series. [Fig. 1B] shows the ROC curves for 90-day mortality of the MELD-Na, the ISTH DIC-2001, and the ISTH DIC-2018 scores together with their accuracy figures. This analysis shows similar accuracy of the ISTH DIC-scores and of the MELD-Na score, although the latter performed numerically better than both the ISTH DIC scores, without a statistically significant difference.[13] [14] This finding may be due to a better sensitivity of the MELD score in the setting where it was originally devised (i.e., 90 day). Lastly, the mortality rates at 30 and 90 days for the various DIC scores are reported in [Table 2].

Table 1 Main features at admission of the 33 patients with liver cirrhosis

Parameter	Value
Gender, male	26 (79.0)
Age, y	63 (53–70)
Child–Pugh, class
A	2 (6.1)
B	15 (45.5)
C	14 (42.4)
Platelet count, n x109	99 (76–177)
Fibrinogen, mg/dL	1.95 (1.35–2.46)
D-dimer, µg/L	3,380 (1.613–6.577)
Prothrombin activity, %	70 (56–81)
INR	1.64 (1.35–2.27)
Creatinine, mg/dL	0.9 (0.8–1.4)
Bilirubin, mg/dL	3.4 (1.-6.1)
Aspartate aminotransferase, UI/L	65 (34–137)
Alanine aminotransferase, UI/L	45 (22–89)
Na, mEq/L	136 (134–140)
C-Reactive protein, mg/L	17 (6–50)
Bleeding events after admission	11 (33.3)
Venous thromboembolic events after admission	0 (0)
Sepsis	9 (27.3)
MELD-Na, score	19 (15–26)
DIC-2001, score	3 (3–4)
DIC-2018, score	2 (1–3)
Deaths (30-day)	12 (36.3)
Deaths (90-day)	14 (42.4)
Time to death (d)	13 (9–20)
Causes of death
Sepsis	6 (18.2)
Multi organ failure	4 (12.1)
Bleeding	3 (9.1)
SARS-CoV-2 pneumonia	1 (3.0)
Diagnosis at admission
Hepatocellular carcinoma	2 (6.1)
Gastrointestinal bleeding	7 (21.2)
Ascites	21 (63.6)
Spontaneous bacterial peritonitis	2 (6.1)
Hepatic encephalopathy	1 (3.0)

Abbreviations: DIC, disseminated intravascular coagulation; INR, international normalized ratio; MELD, Model for End-stage Liver Disease; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Note: Data are shown as absolute number and (proportion) or median and (interquartile range).

Fig. 1 Receiver operating characteristics (ROC) curves for the prediction of 30-day (A) and 90-day (B) mortality of the Model for End-stage Liver Disease (MELD) score (dashed line), the International Society on Thrombosis and Haemostasis (ISTH) DIC-2001 score (solid black line), and ISTH DIC-2018 score (solid gray line), together with their respective cut-offs and accuracy figures (area under the ROC curve, sensitivity [Se], specificity [Sp]).

Table 2 Mortality rates for different International Society on Thrombosis and Haemostasis disseminated intravascular coagulation (ISTH DIC) scores

	30-day mortality, n/N (%)	90-day mortality, n/N (%)
ISTH DIC score 2001
0	0/1 (0)	0/1 (0)
1	1/5 (20.0)	1/5 (20.0)
2	2/10 (20.0)	3/10 (30.0)
3	3/9 (33.3)	3/9 (33.3)
4	2/4 (50.0)	3/4 (75.0)
5	2/2 (100)	2/2 (100)
6	2/2 (100)	2/2 (100)
ISTH DIC score2018
0	0/4 (0)	0/4 (0)
1	3/9 (33.3)	3/9 (33.3)
2	1/4 (25.0)	1/4 (25.0)
3	2/8 (25.0)	4/8 (50.0)
4	1/3 (33.3)	1/3 (33.3)
5	1/1 (100)	1/1 (100)
6	3/3 (100)	3/3 (100)
7	1/1 (100)	1/1 (100)

Abbreviations: DIC, disseminated intravascular coagulation; ISTH, International Society on Thrombosis and Haemostasis.

Note: Data are shown as number of death/total of patients for each DIC score values and (proportion).

To summarize, we feel that the results of the study by Grafeneder et al and our own seem to suggest that the DIC scores can be considered useful tools to predict short-term mortality of patients with cirrhosis, and once again underscore the complex interplay between liver disease and alteration in coagulation parameters. These data, due to the limitation related to the small sample size, are considered preliminary, and we feel that only future studies on larger series may be able to assess whether use of these scores may be preferred over traditional ones for the assessment of very short-term prognosis in patients with cirrhosis.

Publication History

Received: 02 December 2022

Accepted: 17 February 2023

Accepted Manuscript online:
20 February 2023

Article published online:
24 March 2023

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