| Abstract|| |
The aim of the study: to evaluate primary ascitic fluid infection (PAFI) among patients with chronic liver disease (CLD), to study the incidence, clinical features, laboratory findings and short term prognosis of PAFI and also to evaluate factors that may affect incidence and prognosis. . Patients and Methods: Seventy eight patients with CLD were studied between July 1996- to July 1997 in Baghdad Teaching Hospital. Results: thirteen patients developed PAFI (16.7%), no significant differences in the age or gender between the infected and the non-infected groups were found. (P>0.05). The incidence of PAFI is significantly higher among patients with Child's Pugh class C (P<0.005). Low ascitic fluid protein (<10g/L) was more common among the infected group, yet this does not reach statistical significance (P>0.05). The presenting symptoms were abdominal pain (53.8%), fever (46.2%); abdominal tenderness (38.5%), encephalopathy (30.7%), hypotension (15.3%), full triad (15.3%) and asymptomatic patients at presentation were (30.7%). Ascitic fluid culture (by conventional methods) was positive in 46%. All the culture positive samples grew Gram-negative bacilli; E. coli being the most common microorganism (50%). Among five parameters (age, positivity of ascitic fluid culture, severity of CLD, presence of encephalopathy and lack of peritoneal irritation signs), only the increased age seems to be associated with higher in-hospital mortality.
Keywords: ascitic fluid, infection, spontaneous bacterial peritonitis, and chronic liver disease.
|How to cite this article:|
Khalaf ARS, AL-Myahi MH. Primary ascitic fluid infection in patients with chronic liver diseases. Saudi J Gastroenterol 2001;7:62-8
| Introduction|| |
Primary ascitic fluid infection (PAFI) is defined as an infection of preexisting ascites in the absence of any obvious intra-abdominal source  . it is a well-recognized serious complication of patients with chronic liver disease and ascites. Primary ascitic fluid infection includes spontaneous bacterial peritonitis (SBP) as a main reorganized entity. Spontaneous bacterial peritonitis has been defined as an ascitic fluid infection with growth of bacteria in the culture of ascitic fluid  . However, Runyon and Hoefs in subsequent report defined culture-negative neutrocytic ascites (CNNA)  , as a variant of SBP. Another variant of PAFI is monomicrobial nonneutrocytic bacterascitis (MNBA)  . There is special association between CLD and PAFI. This syndrome has been reported in patients with ascites due to other causes ,, . Bacteria may enter the peritoneum through the gastrointestinal tract where there is deranged local mucosal barrier in patients with CLD  . In addition, small bowel bacterial overgrowth occurs in 33-75% of patients with CLD , . Fallopian tube More Detailss are also implicated as a possible route of entry of microorganisms to the peritoneal cavity .
The liver is the major organ involved with the removal of bacteria from blood stream  . The reticuloendothelial system (RES) phagocytic activity, is impaired in patients with cirrhosis and it is consistently lower in patients with cirrhosis than in normal controls  . Patients with cirrhosis have also global deficits in host defense ,, . Ascitic fluid from those patients showed diminished C3 concentration  . In addition, low ascitic fluid protein concentration reduces its opsonic activity rendering the patients more susceptible to develop SBP , . The aim of this study is to define the prevalence of PAFI, the relationship between ascitic fluid total protein concentration and the occurrence of peritonitis and to evaluate the short term prognosis and factors that might affect the prognosis.
| Patients and Methods|| |
Seventy eight patients with CLD and ascites were studied during the period from July 1996-July 1997. They were the inpatients at the Medical Units of Baghdad Teaching Hospital and Gastroenterology, Hepatology Center in Baghdad. Detailed history and clinical examinations were carried out for each patient and the following investigations were performed: complete blood count, erythrocyte sedimentation rate, blood urea, serum creatinine, blood sugar, serum sodium and potassium, total serum bilirubin (direct and indirect), serum aminotransferase enzymes, serum alkaline phosphate, total serum protein and electrophoresis, prothrombin time, partial thromboplastin time, viral markers for hepatitis B and C infection, general urine examination, chest x-ray, upper GI endoscopy and abdominal ultrasound. Liver biopsy was done when feasible.
All patients underwent paracenthesis within 48 hours of admission, which was repeated during hospitalization if abdominal pain, fever, hepatic encephalopathy, or increasing peripheral leukocytosis developed. Ascitic fluid was obtained for total and differential white blood cells count, red blood cells count, total protein measurement, sugar levels, cytology examination, Ziehl-Nelson stain for acid fast bacilli and culture on blood and on chocolate or MacConkay agar and inoculated on aerobic environment of 35C for 48 hours. If there was no growth by 48 hours, the fluid culture was considered to be negative. Culture for acid fast stain was done when feasible. Ascitic fluid amylase measurement was done for those who have elevated ascitic white blood cell count but negative ascitic fluid culture. In 31 patients, the diagnosis of CLD was made on histopathological examination of liver biopsy. In the rest, the diagnosis of CLD was done on clinical basis. The findings of conglomeration of physical signs such as jaundice, hepatomegaly and/or splenomegaly, ascites and/or oedema, spider naevi, clubbing of fingers, palmer erythema ..etc. together with abnormal liver function tests such as elevated aminotransferase, lowered serum albumin, elevated gamma golbulin, prolonged prothrombin time and the presence of esophageal varices, or abnormal findings on abdominal ultrasonography suggestive of CLD  .
Spontaneous bacterial peritonitis was defined as a combination of a positive ascitic fluid culture, an ascitic fluid polymorphonuclear leukocytes (PMN) count greater than 250-x10 6 cells/L and no evident intra-abdominal source of infection ,,, .
The diagnosis of CNNA was applied to patients who met all the following criteria:
(1) Ascitic fluid PMN count greater than 500 x 10 6 cell/L (2) Negative ascitic fluid culture.(3) Absence of intra-abdominal source of infection. (4) No antibiotic treatment within 30 days. (5) No alternative explanation for an elevated ascitic fluid neutrophil count e. g. pancreatitis, tuberculosis, peritoneal carcinomatosis or hemorrhage into ascites , .
Monomicrobial non-neutrocytic bacterascitis (MNBA) was defined as PMN count less than 250 x 10 6 cell/L and positive culture  . Ascites secondary to malignancy and haemorrhagic ascites were excluded. All patients with elevated ascitic fluid WBC count and negative culture were underwent ascitic fluid and serum amylase measurements in addition to clinical evaluation and imaging technique to exclude pancreatitis  . Erect abdominal x-ray and polymicrobial ascitic fluid culture was required to diagnose perforated viscus ,.
Tuberculous peritonitis was suspected when the elevated ascitic fluid WBCs were mainly composed of lymphocytes , . All of our patients with PAFI were treated by ampicillin and gentamycin for 10-14 or up to two days after disappearance of fever , . The cure of SBP was established when all clinical and laboratory signs of infection disappeared and culture performed after antibiotic withdrawal were negative  .
Statistical analysis were performed using the student's t test, Chi square (X) test and Fisher exact probability test when appropriate. A P value of <0.05 was considered significant. Results were expressed as mean + SD (standard deviation)  .
| Results|| |
Seventy eight patients (45 male and 33 female aged 2-71 years) had CLD. On the basis of previously defined criteria, they were divided into those with PAFI and the non-infected group [Table - 1]. Thirteen patients developed primary ascitic fluid infection (incidence = 16.7%), three of them with SBP, seven with CNNA and three with MNBA. There was no significant difference in the age between the infected and the non-infected groups (p>0.05). Incidence of PAFI among females (21.2%), is higher than among males (13.3%) but this does not reach the statistical significance (p>0.3).
The relationship between the severity of CLD as measured by Child's Pugh score system  and the development of PAFI is summarized in [Table - 2]. The incidence of PAFI among patients as per Child's class was 13/51(25.5%) for Child's C and 0/26(0%) for Child's B. The incidence is significantly higher among patients with Child's class C (P>0.0015). The relationship between ascitic fluid total protein concentration and the occurrence of peritonitis is summarized in [Table - 3]. Though the incidence of peritonitis among patients in whom ascitic fluid protein <10gm/L (19.6%) is higher than those in whom ascitic fluid protein >10gm/L (13.5%), yet this does not reach statistical significance.
Abdominal pain was the most common presenting symptoms followed by fever, abdominal tenderness, encephalopathy, and hypotension in decreasing order of sequence [Table - 6]. Only 15.3% of PAFI patients presented with full triad of abdominal pain (with or without tenderness), fever and encephalopathy. On the contrary 30.7% were asymptomatic at presentation. [Table - 4] shows the results of laboratory findings of patients with PAFI. None of the PAFI patients showed peripheral leukocytosis or neutrophilia. Out of 13 patients with PAFI, ascitic fluid culture was positive in six (46%). All culture positive samples grew monomicrobial growth of Gram negative bacilli, E coli being the most common microorganism (three out of six (50%)). There were two growth of klebsiella and one growth of unclassified Grame negative bacilli.
Three patients died in hospital of 13 (in-hospital mortality was 23%). The infection was the direct cause of death in only one of them, the other two died after improvement, one of them died following massive gastrointestinal bleeding and the other died suddenly likely due to cardiac arrest. All of them were males. [Table - 5] compares between the survivors and the non-survivors groups. Five parameters were studied as possible risk factors for the increased in-hospital mortality. The mean age of the nonsurvivors was significantly higher than that of the survivors, all the non-survivors have positive ascitic fluid culture, while only 30% of the survivors are culture positive, yet this does not reach a statistical significance. No significant difference in the frequency of encephalopathy between the survivors and the non-survivors was observed. Lack of potential irritation signs had no influence on survival. There was no significant difference in Child's Pugh score between the survivors and the non-survivors. From these five parameters, age of the patient seems to be the only important factor, which significantly associated with increased inhospital mortality rate.
| Discussion|| |
Primary ascitic fluid infection is considered to be one of the important complications of CLD. Its incidence in our study was 16.7%, various studies reported comparable figures. In Spain, Garcia et al found the incidence as 16%  . While in Argentina Olmos et al found the incidence as 13%  , and Horing et al in Germany found the incidence 18%  . However, Conn and Fessel (USA), Hurwich et al (USA) and Fiaccadori and Pedretti (Italy) reported the following incidence 8%, 7%, 7% respcctively ,, . Higher figures reported at north India by Puriet et al  where the incidence was 30%. The difference in frequency of occurrence of PAFI is possibly related to differences in etiological factors of CLD in various geographical areas and differences in criteria of diagnosis of PAFI and criteria of patients' selection. Age and sex seems to have no effect on the incidence of PAFI. All of our patients who developed PAFI were at Child's Pugh score C. Puri et al  demonstrated that 95% of the patients who developed this complication were in Child's Pugh score C. this emphasizes the role of the liver in the local and systemic defense mechanism against infection. However, Hurwich et al  showed no significant correlation between severity of CLD and occurrence of peritonitis. The incidence of peritonitis in patients in whom ascitic fluid protein < 10gm/L is more than in patients in whom ascitic fluid protein > 10 gm/L, yet the difference does not reach statistical significance. This finding is in agreement with Hurwich et al  , who reported similar result. However, Runyon et al ,, proposed that ascitic fluid opsonization capacity is directly correlated to ascitic protein concentration and this explains the observed predisposition to infection in patients with low ascitic fluid protein concentration.
Perhaps defects in serum bactericidal function, chemoattraction, low levels of fibronectin and impaired PMN or monocyte function ,,,, may explain the occurrence of the infection inpatients with erased ascitic fluid protein concentration >10gm/L.
An interesting observation is the absence of peripheral leukocytosis in our patients with PAFI. This is in contradiction to other studies which stated that peripheral leukocytosis is very common , . We have no explanation for that and it needs further studies to verify this finding. Forty six percent of our patients showed positive ascitic fluid culture and this figure are similar to other studies using conventional culture methods , . All of culture positive samples grew Gram negative bacilli, E. coli being the most common microorganism (50%), this is comparable to the studies done by Wilcox et al  , Gomez et a1  and Saez et al  .
Our study revealed high incidence of CNNA(7/l3) among the infected group, the yield of the ascitic fluid culture can be improved by inoculation of ascitic fluid into blood culture bottle at beside, which had not been done in this study  .
Comparison in clinical features among our study and other studies is summarized in [Table - 7]. In this study abdominal pain is the most frequent presenting feature, followed by fever and abdominal tenderness. This comes in accord with Kline et al  who showed similar order of symptoms and signs though at different frequencies. However, Conn and Fessel  and Wilcox et al  , estimated that fever is the most common presenting feature to be followed by abdominal pain, encephalopathy and abdominal tenderness. In our study asymptomatic patients constitute a relatively high percentage (30.7%). This may be due to high index of suspicion and earlier diagnosis of PAFI before full spectrum of symptoms and signs appeared. Twelve of thirteen patients (92.3%) have elevated serum bilirubin level. Other studies showed similar results , .
The over all in-hospital mortality of PAFI varies among various studies. In-hospital mortality in our series was 23%, which is in agreement with Liovet et al  , who reported rather a close figure of 17%, while Akriviadis and Runyon  have higher figures 46%, Kline et al  found a 60% mortality and Olmos et al  70%. Henz et al  and Chu et al  reported different figures of mortality according to the difference of subtypes of primary ascitic fluid infection (whether SBP, CNNA, or MNBA).
Many factors may affect the prognosis of SBP, Henz et al  found that prognosis was worse in patients with Child's class C, in patients lacking symptoms or signs of peritoneal irritation, in patients with septic shock and in patients with elevated serum creatinine levels at the time of diagnosis. Mihas et al  found that the presence of encephalopathy or renal insufficiency was associated with a high mortality rate. In our series, we have studied five factors and their effect on the in-hospital mortality (age, positivity of ascitic fluid culture, severity of CLD as judged by Child's Pugh score number, presence of encephalopathy and lack of peritoneal irritation signs). We found only the increased age seems to be associated with higher inhospital mortality. However, such conclusion needs to be taken cautiously as the number of the studied patients was limited.
In conclusion, PAFI is one of the important and serious complications of CLD and occurs in considerable proportion. Hence it should be looked for in every patient with CLD especially among elderly patients and those with more advanced disease. Ascitic fluid total protein < l Ogm/L may not be sensitive predictor of risk of peritonitis. Abdominal pain, tenderness and fever are common with SBP and should be taken seriously in any patient with CLD.
We recommend diagnostic paracenthesis to be done for every patient with CLD admitted to the hospital since one third of the patients with PAFI are asymptomatic. Mortality is relatively high and special care should be delivered to the elderly patients with PAFI since aging adversely affects short-term prognosis.
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Abdul-Raheem S Khalaf
consultant physician, Madinat Zayed Hospital, P. O. Box 50018 Dubai. U.A. E
Source of Support: None, Conflict of Interest: None
[Table - 1], [Table - 2], [Table - 3], [Table - 4], [Table - 5], [Table - 6], [Table - 7]