Journalof K-lepatology, 1992; 14: 249-252 @ 1992 Elsevier Science Publishers B.V. All rights reserved. 0168-8278/92:$05.00

249

I-IEPAT 00978

.A. Runyon,

.R. Antillon and J.G.

utchison

Liver Unit, University of Soutkern California School of Medicine, Downey, CA, United States of America (Received

3 December 1990)

Patients with low protein ascites and deficient ascitic fluid opsonic activity have been shown to be unusually predisposed to development of spontaneous bacterial peritonitis. Survivors of spontaneous peritonitis frequently develop recurrent infection. Diuresis has been shown to increase the ascitic fluid opsonic activity of patients who have never had spontaneous bacterial peritonitis. Patients with adequate opsonic activity are protected from ascitic fluid infection. Theoretically, the subset of patients who develop spontaneous peritonitis may have such severe liver disease that (i) their ascites is refractory to diuretic therapy or (ii) their ascitic fluid opsonic activity does not increase in response to diuresis. In this sr~dy, opsonic activity and concentrations of total protein and complement components were measured in the ascitic fluid of 11 patients who were hospitalized with spontaneous bacterial peritonitis and who responded to oral diuretics. The mean values of all of these parameters were found to increase significantly comparing the end-of-diuresis samples to the specimens that were diagnostic of ascitic fluid infection. Patients who survive spontaneous bacterial peritonitis are able to increase their ascitic fluid total protein and opsonic activity in response to diuresis. This increase in endogenous antimicrobial activity may help prevent recurrence of ascitic fluid infection.

Opsonic activity is the property of a body fluid that enhances the ability of phagocytes, e.g. neutrophils, to kill bacteria (1). Qpsonic activity is largely mediated by complement and is measured in vitro. Low protein concentration (~1 g/dl) ascitic fluid has been shown to be deficient in complement and opsonic activity (1). The ascitic fluid concentrations of total protein and complement components do not change during spontaneous bacterial peritonitis (SBP) (2,3). Patients with low protein ascites and patients with deficient ascitic fluid opsonic activity have been shown to be unusually predisposed to development of SBP (3,4). Conversely, patients with adequate ascitic fluid opsonic activity have been shown to be protected from spontaneous ascitic fluid infection (3). Survivors of spontaneous peritonitis frequently develop recurrent in-

fection, e.g. 69% recur in 1 year (5). Diuresis has been shown to increase ascitic fluid opsonic activity; but only patie* :s who have never had SBP have been studied (6,7). Theoretically, patients who develop spontaneous peritonitis may have (i) such severe liver disease and resulting renal impairment that they are unable to diurese or (ii) such severe complement insufficiency that their baseline ascitic fluid complement concentration is so low that their opsonic activity does not increase in response to diuresis. This study was performed to address these issues.

ethnds

Patients hospitalized at Ranch0 Los Amigos Medical

* This work was presented on May 13,199O at the Annual Meeting of the Arrsrican Association for the Study of Liver Diseases in San Antonio. TX (Gastroenterology 1990;98: A626). Correspondence: B.A. Runyon, M.D., Department its, Iowa City, IA 52242, U.S.A.

of Medicine, Gastroenterology/I-Iepatology

Division, University of Iowa Hospitals and Cfin-

B.A.RUNYON et al.

250

Patients diagnosed as having SBP or CNNA were treated with a broad spectrum antibiotic for 5-10 days. Meanwhile inpatient diuresis was initiated using furosemide plus a potassium-sparing diuretic (spironolactone or amiloride). Patients who diuresed and lost weight underwent a repeat (60 ml) paracentesis at the end of their weight loss immediately before the fluid was completely gone. No therapeutic paracenteses were performed on patients who responded well to diuretics because of the known complement-depleting effects of large-volume paracenteses (7). If necessary the final diagnostic paracentesis was performed with the patient in the handknee position (10) to obtain the last few milliliters of fluid. Patients signed informed consent for participation in this Institutional Review Board approved study. Student’s paired r-test, chi-squared test with Yates’ correction, and Wilcoxon’s ranked sign test were used for statistical analysis. A p-value of co.05 was considered significant. I

NITIAL

I FtNAL

y_ 1. Ascitic fluid total protein concentration at the beginning and end of diuresis.

Center for treatment of cirrhotic ascites were candidates for participation in this study. Routine abdominal paracentesis was performed at the time of admission and the fluid was cultured at the bedside in blood culture bottles (8). Paracentesis was repeated for signs or symptoms of infection. Cell counts were performed using a manual hemocytometer; differential white cell counts were manually performed on Wright-stained smears. Ascitic fluid total protein was measured by the biuret method. Aliquots of ascitic fluid and serum were transported to the laboratory on ice and then rapidly stored at -70 “C for subsequent measurement of opsonic activity by a standard assay (1) and for measurement of the complement components C3 and C4 by nephelometry (3). SBP was defined as ascitic fluid infection in which the ascitic fluid culture grew pathogenic bacteria, the neutrophi1 count was 2250 cells/mm’, and there was no evident intra-abdominal surgically-treatable source of infection. Culture-negative neutrocytic ascites (CNNA) was defined as ascitic fluid infection in which the ascitic fluid culture grew no pathogenic bacteria, the neutrophil count was 2250 cells/mm3, there was no evident intra-abdominal surgically-treatable source of infection, and there was no other explanation for the ascitic fluid neutrocytosis, e.g., hemorrhage into ascites peritoneal carcinomatosis, pancreatitis, or tuberculosis (9).

Between September of 1986 and April of 1988,36 patients with cirrhosis and spontaneous bacterial peritonitis or culture-negative neutrocytic ascites were screened for entry into the study. Only 11 (30.6%) completed the

FINAL

INITIAL

Fig. 2.

Ascitic fluid opsonic activity at the beginning and end of diuresis.

EFFECT OF DILJRESIS ON QPSONIC ACTIVITY IN SBP

251 numbers of patients precluded achievement of statistical significance (0.05 < p < 0.1). e duration of diuresis for those who completed the study was 29 1 19 days. Weight loss was 13.9 + 7.4 kg. edian diuretic doses were 200 mg/d spironolactone and 80 mg/d furosemide. Ten (91%) of the eleven patients had SBP; one had CNNA. There were four Escherichia coli episodes, two Strepeococcus pneumoniae, two Klebsiella pneumoniae, one non-enterococcal group strep, and one Streptococcus viridam group. The results of the ascitic fluid analyses are displayed in Table 1 and in Figs. l-4. Patients who survived spontaneous bacterial peritonitis (or culture-negative neutrocytic ascites) and completed the study had detectable baseline ascitic fluid complement concentrations and were able to increase their ascitic fluid opsonic activity and concentrate their ascitic fluid complement and total protein in response to diuresis. Serum complement did not increase during diuresis.

I

I

FINAl

NITIAL Fig. 3. Ascitic

fluid C, concentration at the beginning and end of diuresis.

study. The remairider did not diurese (17 patients), died before diuresis could be achieved (four patients), were discharged prior to the end of diuresis (&ret, patients), or had no ascites at the time of the final paracentesis (one patient). A comparison of the hospitalization survival of the 11 patients who diuresed to that of the 17 who didn’t diurese revealed a statistically significant difference, 91% VS. 29%, respectively @ < 0.01). None of the patients who diuresed developed SBP, whereas 29% of those who didn’t diurese developed SBP. Unfortunately, the small

TABLE

In vitro, low protein concentration ascitic fluid has been shown to lack antimicrobial activity, i.e. opsonic activity 0). In vivo, patients with low protein ascites and deficient ascitic fluid opsonic activity have been shown to be unusu-

1

Comparison of ascitic fluid and serum parameters at the beginning and end of diuresisa Prior to

P

End of diuresis

co.01

diuresis Ascitic fluid Total protein (g/dl) Opsonic activity -(logkill)

C3(m&W G (mg/dl) Serum analysis Serum C, (mg/dl) Serum C, (mg/dl)

0.7 + 0.5 0.21 + 0.05

eo.01

1.5 + 0.8 0.89 f 0.62

6.2 + 4.5 1.2 + 0.8

co.01 J. Recurrence of spontaneous bacteria1 peritonitis in cirrhosis: frequency and predictive factors, Hepatology 1988; 8: 27-31.