Predictors of Mortality in Patients with Spontaneous Bacterial Peritonitis

INTRODUCTION

Cirrhotic patients being immunocompromised are prone to acquiring infections very easily. One of the most common infections in patients with decompensated chronic liver disease is spontaneous bacterial peritonitis (SBP) which is described by the presence of ≥250/uL neutrophil count in ascitic fluid.^1,2 In a study done by Piano et al., there was a 27% prevalence of SBP in the cirrhotic population.³ The first episode associated of SBP is associated with a high mortality rate of 30%.⁴

Regarding the prompt diagnosis of SBP and predicting its recurrence, various different biochemical parameters have been analyzed in different studies. Ascitic calprotectin has been found to be an important marker of SBP diagnosis with a high negative predictive value (NPV).⁵ Similarly, in another study, serum and ascitic homocysteine levels were utilized in making a diagnosis of SBP.⁶ However, one study showed a significant association of ascitic calprotectin and ascitic fluid interferon-γ-induced protein (IP-10) with an increased rate of SBP recurrence.⁷

Recently, variable results have been obtained by multiple studies focusing on the evaluation of different markers of prognosis in SBP. Different serum and ascitic fluid parameters including various inflammatory markers along with Child Turcotte Pugh (CTP) score and model for end-stage liver disease (MELD) score have shown promise in establishing the prognosis in the SBP population.^8–11

Early identification of the factors predicting mortality in SBP patients is the best strategy for improving the overall survival in decompensated chronic liver disease (DCLD). Currently, the data is scarce in this regard and little research work has been done in this part of the world regarding the prognostic factors in the SBP population. Therefore, the main objective of our study was to identify the independent predictors of mortality in the SBP population.

MATERIALS AND METHODS

This prospective observational study was carried out at the Department of Hepatogastroenterology, from January 2022 to June 2023 after approval from the institutional review board.

All the patients aged between 18 and 65 years having decompensated chronic liver disease and diagnosed with SBP were included in the study. The excluded population comprised those who were on hemodialysis, those having a history of solid organ malignancy or transplantation, or those patients suffering from infections such as those caused by human immunodeficiency virus (HIV) or infections other than SBP.

Patients were recruited by the non-probability consecutive sampling technique. Based on the estimation from previous studies, a total number of patients with SBP included in the study was 142.¹² During the initial 12 months’ study period, 142 patients were enrolled for the study, i.e., from January 2022 to December 2022 and then these patients were observed for the next 6 months for the outcome.

RESULTS

A total number of cirrhotic patients having SBP was 142. Out of them, more than two-thirds of patients were males [98 (69%)] and more than two-thirds of patients [101 (71.1%)] had CTP class C at presentation. A most common cause of cirrhosis was viral hepatitis, i.e., hepatitis C followed by hepatitis B and then autoimmune hepatitis (Table 1). Out of 142 patients, 59 patients (41.5 %) did not survive the 6 months period while the majority (39/59) had mortality within the first 30 days.

Table 2 shows a comparison of baseline characteristics of patients between the survivors and non-survivors groups. The mean age of patients in both groups was the same. The majority of the patients in both groups were males. On univariate analysis, serum TLC, INR, ascitic TLC, ascitic neutrophils, ascitic lactate, ascitic LDH, CTP score, MELD-Na were significantly higher while serum albumin was significantly lower in the non-survivor group as compared to the survivor group. However, on multivariate Cox regression analysis, high serum TLC (p = 0.013), ascitic fluid lactate (p < 0.001) along with the high CTP (p = 0.041) and MELD-Na score (p = 0.037) at presentation are the factors that were independently associated with an increased mortality in the patients having SBP (Table 3).

The AUROC was generated to evaluate the optimal cut-off of the variables found on multivariate analysis (Fig. 1). Serum TLC >12, ascetic fluid lactate >22.5 mg/dL, CTP score > 9 and MELD-Na >18 showed good sensitivity, specificity in predicting 6 months mortality in SBP population.

DISCUSSION

Spontaneous bacterial peritonitis accounts for high morbidity and mortality rates in the cirrhotic population. It has high 1 month and 1 year mortality of around 30.3 and 63% respectively.² Many factors contribute to high mortality rates in patients with SBP including acute kidney injury (AKI), raised inflammatory markers, and severity of liver dysfunction.^10,13

In our study, we found that high TLC, INR, and presence of increased neutrophil count in ascitic fluid along with high ascitic lactate, ascitic LDH, CTP score, and MELD-Na along with low serum albumin were associated with decreased survival in patients with SBP. However, on multivariate analysis, the raised serum TLC, ascitic lactate, CTP score, and MELD-Na were significantly associated with high risk of mortality in this population. Child purcotte pugh score and MELD-Na are the known prognostic scores that are used in cirrhotic patients to determine the severity of liver disease. In one study, a model comprising MELD and age showed good discriminatory ability to predict prognosis and survival in SBP.⁴

The data regarding the role of high lactate levels in ascetic fluid as a prognostic marker in SBP patients is still scarce. Lactate is generated by the process of anerobic glycolysis during periods of stress, hypoxia, and sepsis.¹⁴ The levels of lactate in the serum and its clearance have been utilized in the studies to determine the outcome in cirrhotic patients and those patients who are critically ill and admitted to ICU settings.^15,16 However, ascitic fluid lactate was first utilized by Mani and his colleagues showing a good sensitivity and specificity in predicting mortality in the SBP population.¹² In one of our previous studies, we also found that high levels of lactate in ascitic fluid were an excellent prognosticator of mortality in SBP patients with an overall diagnostic accuracy of 85%.¹⁷ In concordance with previous studies, comparable results were also noted in the current study as along with other factors, ascitic fluid lactate showed an independent association with mortality in SBP patients (p-0.037).

In one study, done in the Spanish population by Poca and his colleagues, a model was developed to predict in-hospital deaths in patients with SBP that included serum urea, TLC, CTP, and mean arterial pressure.⁸ However, in our study, we found that high serum TLC and high CTP scores were independent predictors of mortality. In the former, patients suffering from HIV or HCC were included. However, we excluded these patients as both of these factors are confounders and can affect the outcome. These dissimilarities in the results can be best explained by the fact that the presence of either HIV or HCC in a cirrhotic patient can make them more susceptible to multi-organ failure resulting in raised serum urea levels, as explained by their model.

In the previous study done by Mani et al.,¹² alcoholic liver disease was the most common cause identified as the cause of chronic liver disease. However, in our study, viral hepatitis was found to be the predominant etiology of hepatitis C in more than one-third (51/142; 35.9%) of the patients reflecting the burden of hepatitis C in our region where Pakistan has the second highest number of hepatitis C cases globally.¹⁸

In our study, 1-month mortality was 27.6% and around 41% of the patients had mortality during 6-months’ period after the first episode of SBP whereas Mani et al. observed that 6-months’ mortality was found to be around 60% (38 patients out of 63) in patients with SBP which was much higher than in our study population.¹² One of the potential reasons for the decreased rates of mortality in our population can be explained by the difference in the population studied as the previously mentioned study was carried out in the European population while our population belonged to Asian ethnic origin.

In an Indian study, MELD-Na along with AKI and septic shock was found as independent predictors of 50 days in-hospital mortality in patients with SBP.¹¹ In one study from Egypt, MELD score, CTP score along with various clinical and biochemical parameters were associated with mortality in SBP.⁹ Model for end-stage liver disease is found to be a common predictor in most of the studies predicting mortality in SBP patients.

In one study conducted in Turkey by Iliaz et al.,¹⁰ 30 days mortality in SBP patients was found to be 26.1%. In the same study, authors determined the optimal cut-off value of MELD, i.e., 20.5 whereas in our study, we found similar 30-days mortality of 27.6% and MELD-Na of 18 as an optimal cut-off in determining mortality in SBP patients.

There were certain limitations that can be attributed to our study. At first, it was a single-centered study, with a small sample size and various etiologies of cirrhosis were included. For the further validation of our results, multi-centered studies with larger sample sizes are required.

CONCLUSION

Spontaneous bacterial peritonitis in cirrhotic patients is associated with a worse prognosis. In our study, we observed that prognostic scores such as CTP and MELD scores along with high serum TLC and Ascitic fluid lactate levels at presentation were associated with worse outcomes. Therefore, they can serve as the potential and reliable predictors of decreased survival in SBP patients. Hence, patients with SBP should be managed promptly with antibiotics with early listing and preference for early liver transplantation.

ORCID

Raja Taha Yaseen Khan https://orcid.org/0000-0002-5504-5084

REFERENCES

1. Bunchorntavakul C, Chamroonkul N, Chavalitdhamrong D. Bacterial infections in cirrhosis: A critical review and practical guidance. World J Hepatol 2016;8(6):307–321. DOI: 10.4254/wjh.v8.i6.307.

2. Arvaniti V, D’Amico G, Fede G, et al. Infections in patients with cirrhosis increase mortality four-fold and should be used in determining prognosis. Gastroenterology 2010;139(4):1246–1256.e1–e5. DOI: 10.1053/j.gastro.2010.06.019.

3. Piano S, SinghV, Caraceni P, et al. Epidemiology, predictors and outcomes of multi drug resistant (MDR) bacterial infections in patients with cirrhosis across the world. Final results of the “Global study”. Digestive and Liver Disease 2018;50(1Suppl):2–3. DOI: 10.1016/j.dld.2018.01.007.

4. Nobre SR, Cabral JE, Gomes JJ, et al. In-hospital mortality in spontaneous bacterial peritonitis: A new predictive model. Eur J Gastroenterol Hepatol 2008;20(12):1176–1181.. DOI: 10.1097/MEG.0b013e32830607a2.

5. Hadjivasilis A, Tzanis A, Ioakim KJ, et al. The diagnostic accuracy of ascitic calprotectin for the early diagnosis of spontaneous bacterial peritonitis: Systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2021;33(3):312–318. DOI: 10.1097/MEG.0000000000001813.

6. Abdel-Razik A, Eldars W, Elhelaly R, et al. Homocysteine: A new diagnostic marker in spontaneous bacterial peritonitis. Eur J Gastroenterol Hepatol 2018;30(7):779–785. DOI: 10.1097/MEG.0000000000001109.

7. Abdel-Razik A, Abdelsalam M, Gad DF, et al. Recurrence of spontaneous bacterial peritonitis in cirrhosis: Novel predictors. Eur J Gastroenterol Hepatol 2020;32(6):718–726. DOI: 10.1097/MEG.0000000000001578.

8. Poca M, Alvarado‐Tapias E, Concepción M, et al. Predictive model of mortality in patients with spontaneous bacterial peritonitis. Aliment Pharmacol Ther 2016;44(6):629–637. DOI: 10.1111/apt.13745.

9. Ahmed A, Morsy KH, Mohammad AN. Prognostic factors of short-term mortality in spontaneous bacterial peritonitis patients. The Egyptian Journal of Hospital Medicine 2022;88(1):4117–4120. DOI: 10.21608/ejhm.2022.255204.

10. Iliaz R, Ozpolat T, Baran B, et al. Predicting mortality in patients with spontaneous bacterial peritonitis using routine inflammatory and biochemical markers. Eur J Gastroenterol Hepatol 2018;30(7):786–791. DOI: 10.1097/MEG.0000000000001111.

11. Bal CK, Daman R, Bhatia V. Predictors of fifty days in-hospital mortality in decompensated cirrhosis patients with spontaneous bacterial peritonitis. World J Hepatol 2016;8(12):566–572. DOI: 10.4254/wjh.v8.i12.566.

12. Mani I, Alexopoulos T, Hadziyannis E, et al. An exploratory study of ascitic fluid lactate as prognostic factor of mortality in cirrhotic patients with spontaneous bacterial peritonitis. Eur J Gastroenterol Hepatol 2021;33(1S):e970–e977. DOI: 10.1097/MEG.0000000000002332.

13. Devani K, Charilaou P, Jaiswal P, et al. Trends in hospitalization, acute kidney injury, and mortality in patients with spontaneous bacterial peritonitis. J Clin Gastroenterol 2019;53(2):e68–e74. DOI: 10.1097/MCG.0000000000000973.

14. Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 2016;315(8):801–810. DOI: 10.1001/jama.2016.0287.

15. Drolz A, Horvatits T, Rutter K, et al. Lactate improves prediction of short‐term mortality in critically Ill patients with cirrhosis: A multinational study. Hepatology 2019;69(1):258–269. DOI: 10.1002/hep.30151.

16. Gao F, Huang XL, Cai MX, et al. Prognostic value of serum lactate kinetics in critically ill patients with cirrhosis and acute-on-chronic liver failure: A multicenter study. Aging (Albany NY) 2019;11(13):4446–4462. DOI: 10.18632/aging.102062.

17. Kumar D, Yaseen RT, qaiser Panezai M, et al. Ascitic fluid lactate level as a predictor of mortality in cirrhotic patients having spontaneous bacterial peritonitis (SBP). Cureus 2024;16(1):e53243. DOI: 10.7759/cureus.53243.

18. Mahmud S, Al Kanaani Z, Abu-Raddad LJ. Characterization of the hepatitis C virus epidemic in Pakistan. BMC Infect Dis 2019;19(1):809. DOI: 10.1186/s12879-019-4403-7.