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.

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.

Early events in spontaneous bacterial peritonitis.

Insight into the very early events in the pathogenesis of spontaneous bacterial peritonitis.

Tumor necrosis factor-alpha, interleukin-6, and nitric oxide in sterile ascitic fluid and serum from patients with cirrhosis who subsequently develop ascitic fluid infection.

Ascitic fluid infection probably results from repeated episodes of bacteremia and seeding of ascitic fluid. The outcome of these episodes of colonization is probably a function of serum and ascitic fluid defense mechanisms and the virulence of the organism. Patients who develop spontaneous bacterial peritonitis may have serum and ascitic fluid characteristics that are different from those who do not develop infection. We prospectively collected serum and ascitic fluid specimens at the time of admission from patients with sterile cirrhotic ascites, and tested these specimens for interleukin-6, tumor necrosis factor-alpha, and nitric oxide and compared these results as well as other characteristics of patients who did not develop infection to those who did. An elevated baseline serum tumor necrosis factor-alpha as well as an increased proportion of polymorphonuclear leukocytes in sterile ascitic fluid from patients who subsequently developed infection probably represent a subclinical activation of defense mechanisms from prior silent colonizations with bacteria.

Small-diameter portacaval H-graft shunt: a paradigm shift back to surgical shunting in the management of variceal bleeding in patients with preserved liver function.

Small-diameter portacaval H-graft (SDPHG) shunts are partial portosystemic shunts that control variceal bleeding while preserving nutrient blood flow to the liver, minimizing postoperative encephalopathy and liver failure. Since July 1, 1997, we placed SDPHG shunts in 18 patients (age, 52.1 +/- 2.6 years; range, 35 to 72 years) with cirrhosis (Child's class A, B, and C in 6, 10, and 2 patients, respectively) and refractory variceal bleeding who were not candidates for transplantation. Ten procedures (55.6%) were urgent or emergent. SDPHG shunts effectively reduced the portacaval pressure gradient (18 +/- 3 v 5 +/- 2 mm Hg; P <.05). Surgical times (210 +/- 11 minutes), estimated blood losses (358.3 +/- 107.8 mL), transfusion requirements (0 transfusions in 10 patients; 55.6%; mean, 0.9 +/- 0.3 units), and postoperative hospitalization (7.7 +/- 1.0 days) were excellent. Surgical mortality (30 days) was 0%. During 14. 0 +/- 1.9 months (range, 1.1 to 29.1 months) of follow-up, 4 patients (22.2%) died, including both patients with Child's class C cirrhosis. The cumulative 1-year survival rate was 82.1% (Child's class A, B, and C, 83.3%, 90%, and 0%, respectively). Long-term survivors had significantly lower preoperative Child-Pugh scores compared with nonsurvivors (7.8 +/- 0.3 v 9.5 +/- 1.0; P <.05). Postoperative encephalopathy developed in 3 survivors (20%). Fifteen patients (83.3%) have not experienced rebleeding; shunt failure led to rebleeding in only 1 patient (5.6%). SDPHG shunt placement can be performed with low morbidity and surgical mortality. Nontransplantation candidates with Child's class A and B cirrhosis have excellent long-term survival with this safe, effective, and definitive treatment for refractory variceal bleeding.

Effect of long-term trimethoprim-sulfamethoxazole prophylaxis on ascites formation, bacterial translocation, spontaneous bacterial peritonitis, and survival in cirrhotic rats.

Selective intestinal decontamination with norfloxacin is useful in preventing spontaneous bacterial peritonitis in cirrhotic patients and also in cirrhotic rats. The emergence of norfloxacin-resistant infections in these patients warrants a search for alternative therapies. The aim of this study was to evaluate the effect of long-term trimethoprim-sulfamethoxazole administration on carbon tetrachloride (CCl4) -induced cirrhosis in rats with specific attention to intestinal flora, bacterial translocation, spontaneous bacterial peritonitis (SBP), and survival. Male Sprague-Dawley rats received CCl4 administered weekly by gavage. After eight weeks of CCl4 administration rats were randomly allocated into two groups. Group I received daily overnight trimethoprim-sulfamethoxazole diluted in phenobarbital water during follow-up and group II did not. The rats were killed when gravely ill, and a laparotomy was performed to culture samples of cecal stool, mesenteric lymph nodes, and portal and inferior vena caval blood. There was a trend toward a reduction in the incidence of bacterial translocation (8/17 vs 11/14, respectively) and SBP (5/17 vs 7/14, respectively) in treated rats that were killed just before death compared to untreated rats. A decrease in the incidence of bacterial translocation caused by gram-negative bacilli was observed in group I (17.6% vs 78.6%, P < 0.01). The development of ascites was delayed in group I (P < 0.05) and survival was prolonged in group I (P < 0.05), despite a higher CCl4 dose in this group (P < 0.05). In conclusion, long-term prophylactic trimethoprim-sulfamethoxazole administration in CCl4-induced cirrhosis in rats delayed the development of ascites, prolonged survival, and reduced the incidence of gram-negative bacterial translocation but not of SBP, without increasing gram-positive episodes. These data suggest that trimethoprim-sulfamethoxazole might be a good alternative to norfloxacin for preventing gram-negative bacterial translocation.

Management of adult patients with ascites caused by cirrhosis.

Ascites is the most common of the major complications of cirrhosis. The development of ascites is an important landmark in the natural history of cirrhosis and has been proposed as an indication for liver transplantation. The initial evaluation of a patient with ascites should include a history, physical evaluation, and abdominal paracentesis with ascitic fluid analysis. Treatment should consist of abstinence from alcohol, sodium restricted diet, and diuretics. This regimen is effective in approximately 90% of patients. The treatment options for the diuretic-resistant patients include serial therapeutic paracenteses, liver transplantation, and peritoneovenous shunting.

Intestinal bacterial overgrowth and bacterial translocation in cirrhotic rats with ascites.

BACKGROUND/AIMS: Translocation of indigenous bacteria from the gut lumen of cirrhotic animals to mesenteric lymph nodes appears to be an important step in the pathogenesis of spontaneous bacterial peritonitis. However, the sequence of events leading to translocation remains unclear. One of the most predictable risk factors for translocation is overgrowth of gut bacterial flora. The present study was designed to compare the intestinal aerobic bacterial flora of cecal stools at the time of sacrifice between cirrhotic and normal rats and to evaluate the role of intestinal aerobic bacterial overgrowth in bacterial translocation in cirrhotic rats. METHODS: Thirty-five male Sprague-Dawley rats with carbon tetrachloride-induced cirrhosis and ascites and 10 normal rats were included in this study. Cirrhotic rats were sacrificed when ill and samples of ascitic fluid, mesenteric lymph nodes and cecal stool were taken for detecting quantitatively aerobic bacteria. RESULTS: Total intestinal aerobic bacterial count in cecal stool at the time of sacrifice was significantly increased in cirrhotic rats with bacterial translocation with or without spontaneous bacterial peritonitis compared to cirrhotic rats without bacterial translocation (p<0.001 and p<0.001, respectively) and to normal rats (p<0.001 and p<0.001, respectively). Of the 42 species of bacteria translocating to the mesenteric lymph nodes, 41 (97.6%) were found in supranormal numbers in the stool at the time of sacrifice. CONCLUSIONS: Carbon tetrachloride-induced cirrhotic rats with bacterial translocation have increased total intestinal aerobic bacteria count, and intestinal bacterial overgrowth appears to play an important role in bacterial translocation in this experimental model of cirrhosis in rats.

Historical aspects of treatment of patients with cirrhosis and ascites.

The most striking feature of the history of treatment of patients with cirrhosis and ascites is the recurring cycle of initial enthusiasm for a new modality based on uncontrolled observations, followed by reports of complications and failures and/or negative randomized control trials (RCTs). The RCTs tend to be performed rather late, after it is realized that there are problems with the new treatment. In 1975 Tom Chalmers made a plea for randomization of the first patient treated with a new modality. The appropriateness of performing RCTs very early in the evaluation of a new treatment cannot be overemphasized today. Carefully designed RCTs that focus on appropriate subsets of patients and evaluate clinically important endpoints (rather than easier-to-measure, but unimportant indirect endpoints) are the keys to "evidence-based medicine" that will lead to the best outcomes for our patients. If we do not remember that uncontrolled studies regularly lead us into years or even decades of "blind alleys" of investigation, we are destined to repeat the mistakes of the past.

Treatment of patients with cirrhosis and ascites.

The treatment of patients with cirrhosis and fluid overload has undergone substantial change in recent years, because of new information regarding old treatments, as well as new treatments. The goals of treatment are to maximize life expectancy and quality of life. Development of ascites is a landmark in the natural history of cirrhosis signaling poor life expectancy, in general. Patients who are appropriate candidates for liver transplantation should undergo evaluation for this procedure after development of ascites. Patients awaiting transplantation as well as non-candidates for this procedure should be managed by restriction of dietary sodium and prescription of diuretics. This approach is effective in controlling fluid overload in > 90% of patients. Only the 10% who fail this simple medical treatment should be considered for second-line therapy.

Ascitic fluid adenosine deaminase insensitivity in detecting tuberculous peritonitis in the United States.

Tuberculous peritonitis, although common in Third World countries, remains an uncommon cause of ascites in the United States. Ascitic fluid adenosine deaminase (ADA) activity has been proposed as a useful diagnostic test. The aim of this retrospective study was to determine the clinical utility of ascitic fluid ADA activity in diagnosing tuberculous peritonitis in a U.S. patient population. A total of 368 ascitic fluid specimens from a well-characterized ascitic fluid bank, including tuberculous peritonitis (n = 7), tuberculous peritonitis in the setting of cirrhosis (n = 10), and consecutive specimens of widely varied etiologies (n = 351) were analyzed for ADA activity by ultraviolet spectrophotometry at 265 nm. The overall sensitivity of the ADA determination in diagnosing tuberculous peritonitis was only 58.8%, and the specificity was 95.4%. The accuracy of ADA determination (93.8%) compared favorably with that of the common ascitic fluid tests of white blood cell (WBC) count (>500/mm3), total protein (>2.5 g/dL), and combined WBC count and total protein (45.8%, 74.4%, and 81.3%, respectively). However, ADA was only 30% sensitive in detecting tuberculous peritonitis in the setting of cirrhosis, and cirrhosis was present in 59% of the tuberculous peritonitis patients in our population. In addition, malignancy-related ascites (13%) and bacterial peritonitis specimens (5.8%) occasionally yielded false-positive results. In conclusion, our results indicate that the ascitic fluid ADA activity has good accuracy but poor sensitivity and imperfect specificity in a U.S. patient population in which the prevalence of tuberculosis is low and underlying cirrhosis is common.

Spontaneous bacterial peritonitis: pathogenesis, diagnosis, and management.

Spontaneous bacterial peritonitis (SBP) is a common and potentially fatal complication of cirrhosis. Multiple variants of this infection have been described during the past decade; each has a slightly different clinical setting and outcome. The pathogenesis of spontaneous ascitic fluid infection appears to involve translocation of bacteria from the gut to the mesenteric lymph nodes, depressed reticuloendothelial phagocytic activity, and deficient ascitic fluid antibacterial activity. A high index of suspicion of this infection and a low threshold for performing an abdominal paracentesis are required to detect infection early, when survival is most likely. The diagnosis of SBP is based on ascitic fluid analysis, specifically polymorphonuclear cell count and culture (in blood culture bottles). Treatment with a third-generation cephalosporin achieves a cure rate in more than 80% of patients. Despite the improvement in short-term survival during the last decade, the long-term prognosis of cirrhotic patients who survive an episode of SBP remains poor because of the severity of the underlying liver disease and the high rate of recurrence of infection. Selective intestinal decontamination to prevent SBP should be considered in patients at high risk for development of this infection, including hospitalized cirrhotic patients with gastrointestinal hemorrhage or with low ascitic fluid total protein concentration. Because SBP is a marker for poor prognosis in patients with cirrhosis, survivors of an episode of this infection should also be considered for liver transplantation.

Effect of selective bowel decontamination with norfloxacin on spontaneous bacterial peritonitis, translocation, and survival in an animal model of cirrhosis.

Selective bowel decontamination with the orally administered quinolone antibiotic, norfloxacin, has been shown to suppress gut gram-negative bacteria and help prevent gram-negative infections in cirrhotic patients who are at high risk of bacterial infection. Because this drug does not eradicate gram-positive organisms, it is conceivable that gram-positives could replace the suppressed gram-negatives in the gut and lead to subsequent infection. Also the effect of norfloxacin on translocation (as defined by culture positivity of mesenteric lymph nodes) has received little attention. In this study, the effect of oral norfloxacin on translocation, bacterial peritonitis, and survival was investigated in an animal model of carbon tetrachloride-induced cirrhosis and ascites. Treated rats received daily doses of orally administered norfloxacin from the onset of cirrhosis until they died or were killed. Controls received no antibiotic. Norfloxacin led to a reduction in bacterial peritonitis from 70% in untreated cirrhotic controls to 28% in treated cirrhotic rats; these data were statistically significant (P = .012). There was no effect on overall translocation rate (28% with norfloxacin vs. 50% without norfloxacin) (P > .1). Gram-positives were isolated in 100% of the bacterial peritonitis episodes and in 71.4% of culture-positive mesenteric lymph nodes in treated animals compared with only 25% of peritonitis episodes and 10% of culture-positive mesenteric lymph nodes of untreated cirrhotic controls (P < .01 for peritonitis and P < .05 for translocation). The survival rate was not different between groups (P > .1).(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.