TIPS versus paracentesis for cirrhotic patients with refractory ascites.

BACKGROUND: Refractory ascites (ie, ascites that cannot be mobilized despite sodium restriction and diuretic treatment) occurs in 10 per cent of patients with cirrhosis. It is associated with substantial morbidity and mortality with a one-year survival rate of less than 50 per cent. Few therapeutic options currently exist for the management of refractory ascites. OBJECTIVES: To compare transjugular intrahepatic portosystemic stent-shunts (TIPS) versus paracentesis for the treatment of refractory ascites in patients with cirrhosis. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register (January 2006), the Cochrane Central Register of Controlled Trials in The Cochrane Library (Issue 4, 2005), MEDLINE (1950 to January 2006), EMBASE (1980 to January 2006), CINAHL (1982 to August 2004), and Science Citation Index Expanded (1945 to January 2006). SELECTION CRITERIA: We included randomised clinical trials comparing TIPS and paracentesis with or without volume expanders for cirrhotic patients with refractory ascites. DATA COLLECTION AND ANALYSIS: We evaluated the methodological quality of the randomised clinical trials by the generation of the allocation section, allocation concealment, and follow-up. Two authors independently extracted data from each trial. We contacted trial authors for additional information. Dichotomous outcomes were reported as odds ratio (OR) with 95% confidence interval (CI). MAIN RESULTS: Five randomised clinical trials, including 330 patients, met the inclusion criteria. The majority of trials had adequate allocation concealment, but only one employed blinded outcome assessment. Mortality at 30-days (OR 1.00, 95% CI 0.10 to 10.06, P = 1.0) and 24-months (OR 1.29, 95% CI 0.65 to 2.56, P = 0.5) did not differ significantly between TIPS and paracentesis. Transjugular intrahepatic portosystemic stent-shunts significantly reduced the re-accumulation of ascites at 3-months (OR 0.07, 95% CI 0.03 to 0.18, P < 0.01) and 12-months (OR 0.14, 95% CI 0.06 to 0.28, P < 0.01). Hepatic encephalopathy occurred significantly more often in the TIPS group (OR 2.24, 95% CI 1.39 to 3.6, P < 0.01), but gastrointestinal bleeding, infection, and acute renal failure did not differ significantly between the two groups. AUTHORS' CONCLUSIONS: The meta-analysis supports that TIPS was more effective at removing ascites as compared with paracentesis without a significant difference in mortality, gastrointestinal bleeding, infection, and acute renal failure. However, TIPS patients develop hepatic encephalopathy significantly more often.

Paracentesis of ascitic fluid. A safe procedure.

A prospective study of 229 abdominal paracenteses performed on 125 patients with ascites revealed only two major complications (transfusion-requiring abdominal wall hematomas) in a single patient (0.9% of paracenteses and 0.8% of patients), and two minor complications (non-transfusion-requiring hematomas) in two patients (0.9% of paracenteses and 1.6% of patients). No paracentesis resulted in bacterial peritonitis or death. Abdominal paracentesis in patients with ascites is a safe procedure. Fear of complications of the procedure should not preclude performing a paracentesis, provided certain precautions are taken.

Effect of marked peripheral leukocytosis on the leukocyte count in ascites.

Patients with high peripheral leukocyte counts are sometimes found to have high leukocyte counts in ascitic fluid in the presence of negative cultures. To determine if peripheral leukocytosis (greater than or equal to 20 x 10(9)/L) by itself can result in high leukocyte or neutrophil counts in ascites, 29 patients were studied. A total of 31 paracenteses were performed in these patients as soon as the high peripheral leukocyte count was determined. Culture of ascitic fluid was performed using blood-culture bottles. The mean peripheral leukocyte count was 29.3 +/- 9.3 x 10(9)/L, with a mean neutrophil count of 19.9 +/- 6.5 x 10(9)/L. The mean ascitic fluid neutrophil count was 0.064 +/- 0.054 x 10(9)/L (range, 0.007 to 0.197 x 10(9)/L). No significant correlation was found between peripheral neutrophil (or leukocyte) count and neutrophil (or leukocyte) count in ascitic fluid. Marked peripheral leukocytosis (or neutrophilia) does not seem to have an effect on the leukocyte or neutrophil count in ascitic fluid.

Spontaneous vs secondary bacterial peritonitis. Differentiation by response of ascitic fluid neutrophil count to antimicrobial therapy.

A retrospective chart review revealed 24 patients who had at least one subsequent ascitic fluid neutrophil count within 14 days of the ascitic fluid analysis that was diagnostic of spontaneous bacterial peritonitis. The neutrophil count decreased (after antibiotic therapy was started) at an exponential rate, with a half-life of 34 +/- 35 hours. In none of four episodes of secondary bacterial peritonitis was there an exponential decline in neutrophil count after antimicrobial therapy was initiated. In fact, the first follow-up neutrophil count was greater than the baseline value in all four episodes. The response pattern of the ascitic fluid neutrophil count to antimicrobial therapy is helpful in differentiating spontaneous from secondary bacterial peritonitis.

Peritoneal lymphomatosis with ascites. A characterization.

Three patients had autopsy-proved peritoneal lymphomatosis with ascites. Ascitic fluid analysis was characteristic in that the total protein level was greater than 2.5 g/dL, the lactate dehydrogenase level was greater than 225 mU/mL (the upper limit of normal for serum), and the glucose level was less than 50 mg/dL in all patients. Atypical cells were noted on ascitic fluid cytologic studies, and peritoneoscopic biopsy specimens were diagnostic of lymphoma in all three cases. Gut ulceration was present in all patients; a gastric ulcer, a duodenal ulcer, and a colonic ulcer were found to have invasion by lymphoma at autopsy. No patient lived long enough to receive chemotherapy. Perhaps if the diagnosis of lymphoma could have been made earlier, their lives could have been prolonged.

Inoculation of blood culture bottles with ascitic fluid. Improved detection of spontaneous bacterial peritonitis.

The observation that only 42% of the cases of suspected spontaneous bacterial peritonitis at the University of New Mexico, Albuquerque, had positive cultures prompted a change in ascitic fluid culture technique such that a large volume (10 mL in toto) of ascitic fluid was inoculated into blood culture bottles at the bedside. This new method of culture increased the percentage of cases with positive cultures to 91% and decreased the interval between inoculation of the culture and detection of bacterial growth. This is a more sensitive method of culture than the conventional method in detecting spontaneous bacterial peritonitis.

Polymicrobial bacterascites. A unique entity in the spectrum of infected ascitic fluid.

A retrospective analysis of 1578 abdominal paracenteses revealed ten cases of polymicrobial bacterascites, ie, growth of multiple organisms in ascitic fluid with a neutrophil count less than 250 cells/cu mm. Six of the ten paracenteses that documented this condition were traumatic (bloody or producing feculent material). Clinical peritonitis developed in only one patient. No one died as a result of the infection. Polymicrobial bacterascites is rare (0.6% of paracenteses). It is frequently due to a traumatic paracentesis (bowel entry by the paracentesis needle), and is associated with low morbidity.

Disseminated macronodular cutaneous candidiasis in chronic alcoholism.

Disseminated candidiasis usually occurs in profoundly immunocompromised hosts. We described a case of disseminated macronodular cutaneous candidiasis in a man with no known risk for immunosuppression other than alcoholic liver disease and a second case of multiple macronodular cutaneous abscesses in an alcoholic man who had no evidence of systemic dissemination. One patient had testicular candidiasis, a previously unreported site of infection in disseminated candidiasis. Tests showed neutrophil and lymphocyte function to be normal; however, a marked defect in serum opsonization was demonstrated in one patient. It is postulated that chronic alcoholism with alcoholic liver disease resulted in impaired serum opsonization, which, in turn, predisposed these patients to candidal infection.

Bacterial peritonitis secondary to a perinephric abscess. Case report and differentiation from spontaneous bacterial peritonitis.

A cirrhotic patient is described who presented with Escherichia coli septic arthritis as the first manifestation of a perinephric abscess. Results of baseline abdominal paracentesis were unremarkable. After 10 days of antibiotics, abdominal paracentesis was repeated because of recurrence of fever; E. coli peritonitis was confirmed. Subsequent autopsy revealed a perinephric abscess. Development of bacterial peritonitis during antibiotic treatment is distinctly unusual in the "spontaneous" form of peritonitis and should raise suspicion of secondary bacterial peritonitis.

The spectrum of liver disease in systemic lupus erythematosus. Report of 33 histologically-proved cases and review of the literature.

The charts of 238 patients with systemic lupus erythematosus (SLE) were reviewed. Although not routinely screened for biochemical evidence of liver disease, 124 of 206 patients tested had at least one abnormal result, and 43 met strict criteria for the existence of liver disease. In most patients, a specific viral or drug etiology could not be implicated. The spectrum of liver disease in 33 patients from whom liver tissue was available included cirrhosis, chronic active hepatitis, granulomatous hepatitis, chronic persistent hepatitis and steatosis. Three of four cirrhotic patients demonstrated a peculiar form of cholestasis which resembled a "canalicular cast" of bile. Of the nine patients who had serial liver biopsies, four showed progression of their disease. Three patients died of liver failure. Liver involvement in SLE is more common than previously recognized. Severe and even fatal liver disease can occur.

Ascitic fluid and serum C-reactive protein concentrations in patients with and without peritonitis.

Seventy-five paired ascitic fluid and serum specimens were tested for C-reactive protein (CRP) concentrations with the use of laser nephelometry. There was no clear separation of the ascitic fluid or serum values of the 19 paired specimens obtained from patients with peritonitis from the 37 paired sterile portal-hypertension-related samples or from the 19 paired miscellaneous specimens. The ascitic fluid CRP concentrations of patients with sterile portal-hypertension-related ascites were not significantly different from those of infected specimens. However, the serum CRP values were significantly higher in patients with peritonitis than in patients with sterile portal-hypertension-related ascites. Ascitic fluid CRP does not appear to be a useful indicator of ascitic fluid infection.

The opacity of portal hypertension-related ascites correlates with the fluid's triglyceride concentration.

To determine if an elevated triglyceride concentration can explain the opacity of some cirrhotic ascites specimens, the authors measured triglyceride concentration by Coulter DACOS (Hialeah, FL) on 133 paired serum and ascitic fluid specimens. The specimens were categorized as clear or cloudy by coded visual inspection. In addition, the ascitic fluid specimens were inspected for a lipid supernatant after 48 hours of refrigeration at 4 degrees C. The ascitic fluid triglyceride concentration of the 87 clear specimens was 1.9 +/- 1.0 mmol/L compared with 7.0 +/- 4.6 mmol/L for the opalescent specimens (P less than 0.001). Only 17% of the clear specimens demonstrated any lipid layer after refrigeration, compared with 94% of opalescent specimens (P less than 0.001). The triglyceride concentrations were not significantly different between the serum samples obtained from patients with clear compared with opalescent ascites. The opacity of portal hypertension-related ascites appears to be related to the triglyceride concentration of the fluid.

Right atrial thrombus secondary to peritoneovenous shunt: successful removal with use of cardiopulmonary bypass.

A patient who had had a functioning peritoneovenous (LeVeen) shunt for 10 months presented with recurrent ascites and the superior vena cava syndrome. He was found to have a thrombus occluding the superior vena cava and extending into the right atrium. The thrombus was removed and the shunt was declotted during cardiopulmonary bypass.

Antimicrobial activity of 11 newer and investigational drugs tested against aerobic isolates from spontaneous bacterial peritonitis.

The in vitro susceptibility of 124 aerobic bacterial pathogens isolated from patients with spontaneous bacterial peritonitis (SBP) were tested against 11 antimicrobial agents, including parenteral or oral cephalosporins and fluoroquinolones. Most SBP isolates were Gram-negative organisms, and Escherichia coli and Klebsiella pneumoniae were responsible for 63% of the episodes evaluated. The fluoroquinolones (ciprofloxacin and ofloxacin) and the "fourth-generation" cephalosporin cefpirome were the most active agents against the Gram-negative bacteria. Commonly used cefotaxime and cefotaxime-desacetylcefotaxime (DES-CTX) combinations were also very active against Gram-negative bacteria with only few Enterobacter cloacae isolates being resistant (minimum inhibitory concentrations > 32 micrograms/ml). All streptococci were susceptible to cefotaxime, cefpirome, and cefdaloxime and to the cefotaxime-DES-CTX combinations, whereas only ofloxacin demonstrated acceptable activity against the enterococci. The widest spectrum of activity versus SBP isolates was found for ofloxacin (98% susceptibility) among the fluoroquinolones. For the beta-lactams, the widest spectrum of activity was demonstrated by cefpirome and the 2:1 cefotaxime-DES-CTX combination (93% susceptibility). These results indicate that the role of ofloxacin and newer parenteral or orally administered cephalosporins in the treatment of prophylaxis of SBP should be further evaluated.

TIPS versus paracentesis for cirrhotic patients with refractory ascites.

BACKGROUND: Ten per cent of cirrhotic patients develop refractory ascites, which carries substantial morbidity and has a one-year survival of less than 50 per cent. Patients with refractory ascites may benefit from transjugular intrahepatic portosystemic stent-shunts (TIPS). OBJECTIVES: To compare TIPS versus paracentesis standard treatment in patients with refractory ascites due to cirrhosis with regard to overall short- and long-term mortality, treatment efficacy, and complications. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register (July 2003), The Cochrane Central Register of Controlled Trials on The Cochrane Library (Issue 1, 2003), MEDLINE (1966 to July 2003), EMBASE (1980 to July 2003), and CINAHL (1982 to July 2003). We supplemented the searches with reading through scientific citations, review of citations in relevant primary articles, and hand-searched abstracts from national meetings. SELECTION CRITERIA: We included randomised clinical trials comparing TIPS and paracentesis with or without volume expanders for cirrhotic patients with refractory ascites. DATA COLLECTION AND ANALYSIS: We evaluated the methodological quality of the randomised clinical trials by the generation of the allocation section, allocation concealment, and follow-up. Two independent observers extracted data from each trial. We contacted trial authors for additional information. Dichotomous outcomes were reported as odds ratio (OR) with 95% confidence interval (CI). MAIN RESULTS: Four randomised clinical trials, including 264 patients, met the inclusion criteria. Methodological quality was moderate. Thirty-day mortality (OR 1.00, 95% CI 0.10 to 10.06, P = 1.0) and 24-month mortality (OR 1.17, 95% CI 0.52 to 2.66, P = 0.70) did not differ significantly between TIPS and paracentesis treatment. TIPS significantly reduced ascites re-accumulation at three months (OR 0.07, 95% CI 0.03 to 0.18, P < 0.00001) and at 12 months follow-up (OR 0.14, 95% CI 0.06 to 0.28, P < 0.00001). Hepatic encephalopathy occurred significantly more often in the TIPS group (OR 2.11, 95% CI 1.22 to 3.66, P = 0.008). Gastrointestinal bleeding (OR 0.82, 95% CI 0.36 to 1.84, P = 0.63), acute renal failure (OR 0.64, 95% CI 0.15 to 2.72, P = 0.55), septicemia/infection (OR 1.05, 95% CI 0.22 to 4.94, P = 0.96), and disseminated intravascular coagulation (OR 0.82, 95% CI 0.26 to 1.84, P = 0.63) did not differ significantly between groups. REVIEWERS' CONCLUSIONS: TIPS removed ascites more effectively than paracentesis. After 12 months, the beneficial effects of TIPS on ascites was still present. Mortality, gastrointestinal bleeding, septicemia/infection, acute renal failure, and disseminated intravascular coagulation did not differ significantly between the two groups. Hepatic encephalopathy occurred significantly more often in the TIPS group.

In vitro activity of levofloxacin and FK-037 against aerobic isolates from spontaneous bacterial peritonitis.

Spontaneous bacterial peritonitis is a potentially fatal complication of ascites, most often caused by the Enterobacteriaceae or streptococci. We have evaluated the in vitro activity of FK-037, a new cephalosporin, cefotaxime, cefpirome, ceftazidime, levofloxacin, and ofloxacin against a collection of 124 isolates from patients with spontaneous bacterial peritonitis. Levofloxacin (< or = 2 mg/L) was active against all isolates and ofloxacin (< or = 2 mg/L) against 98.4% of isolates. The cephalosporins (< or = 8 mg/L) were less active against cefpirome = 95.4%, FK-037 = 94.4%, and cefotaxime and ceftazidime = 91.1%. Given the high mortality associated with spontaneous bacterial peritonitis, clinical studies of the quinolones (specifically of levofloxacin) and the alternative cephalosporins presented for treatment of spontaneous bacterial peritonitis appears warranted.

Spontaneous bacterial peritonitis.

Spontaneous bacterial peritonitis is an infection of the ascitic fluid of patients who, in general, have severe chronic liver disease. Several variants of this disease exist including bacterascites, culture-negative neutrocytic ascites, and secondary bacterial peritonitis. Spontaneous bacterial peritonitis is frequently manifested by signs and symptoms of peritonitis although the findings may be subtle; however, occasionally it may be completely without clinical manifestation. The clinician must have a high index of suspicion in order to make this diagnosis at a relatively earlier stage of infection. An abdominal paracentesis is required to make the diagnosis of spontaneous bacterial peritonitis. This paracentesis should be performed on all patients who are admitted to the hospital for ascites and should be repeated if there is any manifestation of bacterial infection during the hospitalization. Patients with severe intrahepatic shunting--as manifested by marked redistribution of activity from the liver to the spleen and to the bone marrow on liver-spleen scan as well as patients with an ascitic fluid total protein concentration of less than 1 g/dl--appear to be particularly susceptible to bacterial infection of their ascites. In order to optimize the yield of ascitic fluid culture, it is probably appropriate to inject blood culture bottles with ascites at the bedside immediately after the abdominal paracentesis. The mortality of spontaneous bacterial peritonitis continues to be very high. Perhaps routine admission paracentesis and prompt empiric antibiotic therapy with a third-generation cephalosporin will decrease the mortality of this infection if the Gram stain of the ascitic fluid demonstrates bacteria or the ascitic fluid neutrophil count is greater than 250 cells/cu mm. Repeating the paracentesis after 48 hours of treatment to reculture the fluid and reassess the ascitic fluid neutrophil count appears to be the best way to assess efficacy of treatment. After 48 hours of treatment the ascitic fluid neutrophil count should be less than 50% of the original value if the antimicrobial therapy is appropriate. The optimal duration of antibiotic treatment is unknown; however, until controlled trials provide data regarding duration of treatment it is appropriate to treat with parenteral antibiotics for 10 to 14 days. Research is also needed to determine if there are measures which can be taken to prevent the development of spontaneous peritonitis.

Refractory ascites.

The first step in the approach to the ascites patient, after the history and physical examination, is to perform a diagnostic abdominal paracentesis for SAAG to determine whether portal hypertension is present (SAAG 1.1 g/dl or higher) or not (SAAG less than 1.1 gm/dl) (Table 1). Patients without portal hypertension probably do not have liver disease as the cause of their ascites formation and probably should not be treated with dietary sodium restriction and diuretics. Patients with portal hypertension-related ascites usually have chronic parenchymal liver disease and usually require hospitalization for diet education, diuretic treatment, and evaluation of the underlying liver disease. Approximately 90% of patients with ascites due to chronic parenchymal liver disease respond to dietary sodium restriction and diuretics. Because of the poor prognosis associated with ascites, patients who are good candidates for transplantation should be considered for listing when they develop this complication of their underlying liver disease. The 10% of patients with cirrhosis whose ascites is refractory to routine medical treatment must be offered alternative therapy. Transplant candidates should be listed, in my opinion, once they are documented to have diuretic-resistant ascites. Fortunately, alcoholics (who are usually not good candidates for transplantation) who abstain from alcohol may revert from diuretic-resistant to diuretic-sensitive ascites over a period of months. Chronic outpatient therapeutic paracentesis is the most popular short-term treatment for patients with diuretic-resistant ascites. Paracentesis can be used as a "bridge" to alternative therapies or can be continued indefinitely.(ABSTRACT TRUNCATED AT 250 WORDS)

Low-protein-concentration ascitic fluid is predisposed to spontaneous bacterial peritonitis.

To assess the risk of development of spontaneous bacterial peritonitis in relation to the ascitic fluid total protein concentration, routine admission abdominal paracentesis was performed on a group of 107 patients during 125 hospitalizations. The paracentesis was repeated if evidence of peritonitis developed during hospitalization. Twenty-one episodes of spontaneous peritonitis (or its culture-negative variant) were documented in 17 patients. The ascitic fluid protein concentration in the spontaneous peritonitis group (0.72 +/- 0.53 g/dl) was significantly lower (p less than 0.001) than that in the group of patients with sterile portal hypertension-related ascites (1.36 +/- 0.89 g/dl) and was significantly lower than that of patients with ascites due to miscellaneous causes. Of the patients whose initial sterile ascitic fluid protein concentration was less than or equal to 1.0 g/dl, 7 of 47 (15%) developed spontaneous peritonitis during their hospitalization; whereas only 1 of 65 (1.5%) patients who had an initial sterile ascitic fluid protein concentration greater than 1.0 g/dl developed spontaneous peritonitis. This difference in risk of development of peritonitis in relation to initial ascitic fluid protein concentration was also significant (p less than 0.01). Low-protein-concentration ascitic fluid predisposes to spontaneous bacterial peritonitis.