Transjugular intrahepatic portosystemic shunt with expanded-polytetrafuoroethylene-covered stents in non-cirrhotic patients with portal cavernoma.

AIMS: To evaluate the feasibility and efficacy of Transjugular intrahepatic portosystemic shunt (TIPS) in non-cirrhotic patients with symptomatic portal hypertension secondary to portal cavernoma. METHODS: Our cohort includes 13 consecutive patients. Eleven were considered for Transjugular intrahepatic portosystemic shunt placement for complications not manageable by medical/endoscopic treatment and two because of the need of oral anticoagulation in presence of high-risk varices. Expanded-polytetrafluoroethylene-covered stents were used in all. RESULTS: One of the 13 patients was excluded because of a thrombosis of the superior cava and jugular veins. In 10 patients, Transjugular intrahepatic portosystemic shunt was successfully implanted [83.3%; 95% confidence interval: 52-98%]. One patient had an early shunt dysfunction with recurrence of variceal bleeding which required an emergency surgical shunt. Late shunt dysfunction occurred in two patients, successfully treated with angioplasty and re-stenting. Two patients experienced an episode of encephalopathy. CONCLUSIONS: Transjugular intrahepatic portosystemic shunt is feasible in most of the patients with portal cavernoma and should be considered in those with severe complications uncontrolled by conventional therapy. The use of Transjugular intrahepatic portosystemic shunt to achieve a lifelong anticoagulation therapy in selected patients with high-risk varices may be another possible indication. These patients should be referred to selected Units with large experience in Transjugular intrahepatic portosystemic shunt placement.

Clinical efficacy of transjugular intrahepatic portosystemic shunt created with covered stents with different diameters: results of a randomized controlled trial.

BACKGROUND & AIMS: The incidence of post-TIPS hepatic encephalopathy (HE) could be reduced by using stents with a small diameter. The aim of this study was to compare the incidence of HE and the clinical efficacy of TIPS created with 8- or 10-mm PTFE-covered stents. METHODS: Consecutive cirrhotics submitted to TIPS for variceal bleeding or refractory ascites were randomized to receive a 8- or 10-mm covered stent. As recommended by our Ethical Committee, the trial was stopped after the inclusion of 45 patients. RESULTS: The two groups were comparable for age, sex, etiology, and psychometric performance. After TIPS, the portosystemic pressure gradient was significantly higher in the 8-mm stent group (8.9+/-2.7 versus 6.5+/-2.7 mmHg; p=0.007). Consequently, the probability of remaining free of complications due to portal hypertension was significantly higher in the 10-mm than in the 8-mm stent group: 82.9% versus 41.9% at one year; log-rank test, p=0.002. In particular, the persistence of ascites with the need for repeated paracentesis was significantly more frequent in the patients treated with 8-mm stent diameter for refractory ascites (log-rank test, p=0.008). The probability of remaining free of HE was similar in both groups. Cumulative survival rate was similar in both groups. CONCLUSIONS: The use of 8-mm diameter stents for TIPS leads to a significantly less efficient control of complications of portal hypertension. HE remains an unsolved major problem after TIPS.

Peripheral and splanchnic indole and oxindole levels in cirrhotic patients: a study on the pathophysiology of hepatic encephalopathy.

OBJECTIVES: Intestinal bacteria metabolize tryptophan into indole, which is then further metabolized into oxindole, a sedative compound putatively involved in the pathophysiology of hepatic encephalopathy (HE). The aim of this study was to measure indole and oxindole levels in patients with cirrhosis with or without HE and to establish whether an intestinal production and a hepatic metabolism of these substances exist. METHODS: We studied 10 healthy subjects (controls) and 51 cirrhotic patients: 17 without HE, 14 with a minimal HE, 8 with overt HE, and 12 who had undergone a transjugular intrahepatic portosystemic shunt (TIPS) procedure. In the last group, blood was collected from the artery, and the portal and hepatic veins during TIPS construction and from the peripheral veins before, immediately after, and at weekly intervals during the first month after TIPS. RESULTS: Plasma indole levels were significantly higher in patients with overt HE. Oxindole levels were higher in cirrhotics than in controls. Indole and ammonia were significantly correlated (r=0.66). Peripheral and splanchnic determinations showed that indole was produced in the intestine and cleared by the liver, similar to ammonia. TIPS implantation increased both indole and ammonia levels. After TIPS, the psychometric performance worsened in 4 of the 12 patients. The increase in indole plasma concentrations in these four patients was higher than in those who remained stable after undergoing TIPS. CONCLUSIONS: Indole correlates with HE and has a significant intestinal production and hepatic extraction; its level increases after TIPS and is related to psychometric performance. These data suggest that indole may be involved in the pathophysiology of HE.

Emerging issues in the use of transjugular intrahepatic portosystemic shunt (TIPS) for management of portal hypertension: time to update the guidelines?

Since its first introduction in the 1980s, transjugular intrahepatic portosystemic shunt has played an increasingly important role in the management and treatment of the complications of portal hypertension. In 2005, the American Association for the Study of Liver Diseases published the Practice Guidelines for the use of transjugular intrahepatic portosystemic shunt in the management of portal hypertension. Since then, technical advances and new interesting data on transjugular intrahepatic portosystemic shunt have been presented in the literature. The present review focus on the applications of transjugular intrahepatic portosystemic shunt and examines more recent studies on this topic; the current guidelines on the use of transjugular intrahepatic portosystemic shunt are also discussed. From the data presented in the most recent publications, it has become increasingly clear that the recommendations stemming from the current guidelines need to be reviewed and updated in several points. Changes in the American Association for the Study of Liver Diseases Practice Guidelines are needed for both common indications (variceal bleeding and refractory ascites) as well as uncommon ones (i.e., Budd-Chiari syndrome and portal cavernoma). In addition, a relevant technical advance has been the introduction of the polytetrafluoroethylene-covered stents, which greatly improved the patency and clinical efficacy of transjugular intrahepatic portosystemic shunt. Consequently, new studies are required to re-assess the role of transjugular intrahepatic portosystemic shunt performed with new covered stents as compared with other strategies in the management of portal hypertension.

Ascitic fluid analysis for diagnosis and monitoring of spontaneous bacterial peritonitis.

Polymorphonuclear (PMN) cell count in the ascitic fluid is essential for the diagnosis and management of spontaneous bacterial peritonitis (SBP). To date, PMN cell count is routinely performed by traditional manual counting. However, this method is time-consuming, costly, and not always timely available. Therefore, considerable efforts have been made in recent years to develop an alternative test for a more rapid diagnosis and monitoring of SBP. The use of urinary reagent strips was proposed to achieve an "instant" bedside diagnosis of SBP. A series of reports evaluated the urine strip test for SBP diagnosis and reported promising results. However, a recent large multicenter study revealed a surprising lack of diagnostic efficacy of the urine screening test for SBP diagnosis. Another method, more recently proposed as an alternative to the manual PMN count, is the measurement of lactoferrin in ascitic fluid, but the data available on the diagnostic value of this test are limited to a single study. However, both urinary reagent strips and ascitic lactoferrin tests are qualitative methods and need, therefore, to be further confirmed by standard cytology of the ascitic fluid. To date, the only quantitative method proposed as a valid alternative to manual PMN counting is automated blood cell counters, commonly used in all laboratories for blood cell counting. Data available in the literature on the diagnostic performance of this method are limited but very promising, and this tool seems to have the potential to replace the manual counting method.

Accuracy of the automated cell counters for management of spontaneous bacterial peritonitis.

AIM: To evaluate the accuracy of automated blood cell counters for ascitic polymorphonuclear (PMN) determination for: (1) diagnosis, (2) efficacy of the ongoing antibiotic therapy, and (3) resolution of spontaneous bacterial peritonitis (SBP). METHODS: One hundred and twelve ascitic fluid samples were collected from 52 consecutive cirrhotic patients, 16 of them with SBP. The agreement between the manual and the automated method for PMN count was assessed. The sensitivity/specificity and the positive/negative predictive value of the automated blood cell counter were also calculated by considering the manual method as the "gold standard". RESULTS: The mean +/- SD of the difference between manual and automated measurements was 7.8 +/- 58 cells/mm(3), while the limits of agreement were +124 cells/mm(3) [95% confidence interval (CI): +145 to +103] and -108 cells/mm(3) (95% CI: -87 to -129). The automated cell counter had a sensitivity of 100% and a specificity of 97.7% in diagnosing SBP, and a sensitivity of 91% and a specificity of 100% for the efficacy of the ongoing antibiotic therapy. The two methods showed a complete agreement for the resolution of infection. CONCLUSION: Automated cell counters not only have a good diagnostic accuracy, but are also very effective in monitoring the antibiotic treatment in patients with SBP. Because of their quicker performance, they should replace the manual counting for PMN determination in the ascitic fluid of patients with SBP.

Incidence, natural history, and risk factors of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt with polytetrafluoroethylene-covered stent grafts.

BACKGROUND AND AIMS: The aim of this study was to assess the incidence, natural history, and risk factors of hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS) with the new polytetrafluoroethylene (PTFE)-covered stent grafts in cirrhotic patients. PATIENTS AND METHODS: Seventy-eight cirrhotic patients treated by TIPS with PTFE-covered stent grafts and followed by the same medical team--according to a prospective protocol for diagnostic workup and surveillance strategy--were reviewed. The follow-up was 19.9 +/- 20.6 months. RESULTS: At least one episode of HE occurred in 35 of 78 (44.8%) patients. The probability of remaining free of HE was 53.8% (95% confidence interval [CI] 41.4-66.2] at 1 yr and 50.9% at 2 yr (95% CI 38.2-63.8%). The total number of HE episodes was 89. Fifty-five percent of the episodes were grades III-IV. The occurrence of HE tended to be constant during the follow-up, probably because of the very low incidence of shunt dysfunction (13.6% at 2 yr). Moreover, in six patients, a refractory HE required the reduction of the shunt diameter. One patient died due to variceal bleeding after this procedure. At a multivariate analysis, an older age, high creatinine levels, and low serum sodium and low albumin values were shown to be independent factors for the occurrence of HE. Serum creatinine level was the only variable related to the development of refractory HE at the logistic multivariate analysis. CONCLUSIONS: HE after TIPS with PTFE-covered stent grafts is frequent; its incidence is not confined to the first post-TIPS period, but it has the tendency to be frequent over time. Refractory HE occurred in 8% of patients and may be successfully managed by reducing the stent diameter. The selection of patients undergoing TIPS placement should be very accurate, especially for those subjects with abnormal creatinine level.

Efficacy of current guidelines for the treatment of spontaneous bacterial peritonitis in the clinical practice.

AIM: To verify the validity of the International Ascites Club guidelines for treatment of spontaneous bacterial peritonitis (SBP) in clinical practice. METHODS: All SBP episodes occurring in a group of consecutive cirrhotics were managed accordingly and included in the study. SBP was diagnosed when the ascitic fluid polymorphonuclear (PMN) cell count was > 250 cells/mm3, and empirically treated with cefotaxime. RESULTS: Thirty-eight SBP episodes occurred in 32 cirrhotics (22 men/10 women; mean age: 58.6 +/- 11.2 years). Prevalence of SBP, in our population, was 17%. Ascitic fluid culture was positive in nine (24%) cases only. Eleven episodes were nosocomial and 71% community-acquired. Treatment with cefotaxime was successful in 59% of cases, while 41% of episodes required a modification of the initial antibiotic therapy because of a less-than 25% decrease in ascitic PMN count at 48 h. Change of antibiotic therapy led to the resolution of infection in 87% of episodes. Among the cases with positive culture, the initial antibiotic therapy with cefotaxime failed at a percentage (44%) similar to that of the whole series. In these cases, the isolated organisms were either resistant or with an inherent insufficient susceptibility to cefotaxime. CONCLUSION: In clinical practice, ascitic PMN count is a valid tool for starting a prompt antibiotic treatment and evaluating its efficacy. The initial treatment with cefotaxime failed more frequently than expected. An increase in healthcare-related infections with antibiotic-resistant pathogens may explain this finding. A different first-line antibiotic treatment should be investigated.

High prevalence of spontaneous portal-systemic shunts in persistent hepatic encephalopathy: a case-control study.

Large spontaneous portal-systemic shunts have been occasionally described in patients with cirrhosis. This study was undertaken to assess the prevalence of portal-systemic shunts in patients with cirrhosis with recurrent or persistent hepatic encephalopathy (HE) as compared with patients with cirrhosis without HE. Fourteen patients with cirrhosis with recurrent or persistent HE (cases) and 14 patients with cirrhosis without previous or present signs of overt HE matching for age and degree of liver failure (controls) were studied. Each patient underwent neurological assessment and cerebral magnetic resonance (MR) imaging to exclude organic neurological pathological conditions. HE evaluation included psychometric performance (Trail-Making Test A), electroencephalogram (EEG), mental status examination and grading, arterial, venous, and partial pressure of ammonia determination. The presence of portal-systemic shunts was assessed by portal venous phase multidetector-row spiral computed tomography (CT). Large spontaneous portal-systemic shunts were detected in 10 patients with HE and in only 2 patients without HE (71% vs. 14%; chi square = 9.16; df = 1.0; P = .002). The patients with HE presented ascites (P = .002) and medium/large esophageal varices (P = .02) less frequently than the control group. In conclusion, our study suggests that large spontaneous shunts may often sustain the chronicity of HE; the presence of large shunts should be sought in patients with cirrhosis with recurrent or persistent HE.

The natural history of portal hypertensive gastropathy in patients with liver cirrhosis and mild portal hypertension.

BACKGROUND: Portal hypertensive gastropathy is a potential cause of bleeding in patients with liver cirrhosis. Studies on its natural history have often included patients submitted to endoscopic or pharmacological treatment for portal hypertension. PATIENTS AND METHODS: A total of 222 cirrhotic patients with mild degree of portal hypertension (i.e., with no or small varices at entry, without previous gastrointestinal bleeding and medical, endoscopic, or angiographic treatment) were followed up with upper endoscopy every 12 months for 47 +/- 28 months. RESULTS: Upon enrollment 48 patients presented portal hypertensive gastropathy (43 mild and 5 severe) and the presence of esophageal varices was the only independent predictor of the presence of this gastric lesion at multivariate analysis. The incidence of portal hypertensive gastropathy was 3.0% (1.1-4.9%) at 1 yr and 24% (18.1-29.9%) at 3 yr, while the progression was 3% (1-6.9%) at 1 yr and 14% (4.2-23.8%) at 3 yr. The presence of esophageal varices and the Child-Pugh class B or C at enrollment were predictive of the incidence of portal hypertensive gastropathy, while only Child-Pugh class B or C was correlated with the progression from mild to severe, at multivariate analysis. During follow-up 16 patients bled from portal hypertensive gastropathy (9 acutely and 7 chronically) and one patient died of exsanguination from this lesion. CONCLUSIONS: The natural history of portal hypertensive gastropathy is significantly influenced by the severity of liver disease and severity of portal hypertension. Acute bleeding from portal hypertensive gastropathy is infrequent but may be severe.

Polytetrafluoroethylene-covered stent grafts for TIPS procedure: 1-year patency and clinical results.

OBJECTIVES: Polytetrafluoroethylene (PTFE)-covered stent grafts appear to have the potential to improve TIPS patency, but data available are few and controversial. The aim of this prospective nonrandomized trial was to assess TIPS safety and 1-yr patency with a new commercially available PTFE-covered stent graft in comparison with a group of historical controls treated with conventional stents. METHODS: Between July 1992 and December 1999, 87 consecutive cirrhotics underwent TIPS with conventional stents, while from January 2000 to November 2001, 32 consecutive cirrhotics were treated with PTFE-covered stent grafts. All patients were followed by the same medical team according to a prospective protocol for a diagnostic work-up and a surveillance strategy. RESULTS: The two groups were comparable for age, sex, etiology, and severity of cirrhosis. The 1-yr probability of remaining free of shunt dysfunction tended to be higher in the covered stent group: 76.3% (95% CI = 58.7-93.9%) versus 57.5% (95% CI = 46.6-68.4%); log rank test: p = 0.055. However, stenoses inside the stent were significantly higher in patients with bare stents (88% vs 17%), while stenoses at the hepatic or portal vein were more frequent in PTFE-covered stent-graft group (50% vs 9% and 33% vs 3%, respectively), (chi2 = 15.42; df = 2.0; p = 0.0004). Stenoses inside the covered portion of the stent did not occur. One-year cumulative rebleeding, encephalopathy, and survival were similar. CONCLUSIONS: PTFE-covered stents are able to solve pseudointimal hyperplasia within the stent tract, but have a high incidence of hepatic or portal vein stenosis. Improvements in stent design and insertion techniques are necessary to fully achieve the potential benefit of this new device.

Validation of automated blood cell counter for the determination of polymorphonuclear cell count in the ascitic fluid of cirrhotic patients with or without spontaneous bacterial peritonitis.

OBJECTIVES: Polymorphonuclear (PMN) cell count in ascitic fluid is the most useful test for the diagnosis of spontaneous bacterial peritonitis (SBP). We evaluated the validity of an automated blood cell counter for the PMN determination in ascitic fluid by comparing it with the traditional hematologic method with a light microscope in a manual counting chamber. METHODS: A total of 130 ascitic fluid samples were collected from 74 consecutive cirrhotics. The agreement between the two techniques was assessed according to Bland and Altman's method. The sensitivity, specificity, and positive and negative predictive values of the automated blood cell counter were calculated by considering the diagnosis of SBP as a PMN count > or = 250 cells/mm(3), determined by the manual method as the "gold standard." RESULTS: The mean PMN counts assessed by the manual method and the automated blood cell counter were 124 +/- 301 cells/mm(3) and 130 +/- 339 cells/mm(3), respectively (p = 0.89, ns). The mean +/- SD of the difference between manual and automated measurements was 6 +/- 61 cells/mm(3), whereas the limits of agreement were +127 cells/mm(3) (95% CI = +108 to +147) and -115 cells/mm(3) (95%CI = -96 to -135). SBP was diagnosed in 11 patients. All but one were correctly identified with the automated blood cell counter, with a sensitivity of 94% and a specificity of 100%; positive and negative predictive values were 100% and 99.1%, respectively. CONCLUSIONS: The manual method and the automated blood cell counter have a good agreement in the PMN determination in ascitic fluid, and the automated blood cell counter is a reliable tool for rapid diagnosis of SBP.

Incidence and natural history of small esophageal varices in cirrhotic patients.

BACKGROUND/AIMS: The incidence and natural history of small esophageal varices (EV) in cirrhotics may influence the frequency of endoscopies and the decision to start a pharmacological treatment in these patients. METHODS: We prospectively evaluated 206 cirrhotics, 113 without varices and 93 with small EV, during a mean follow-up of 37+/-22 months. Patients with previous gastrointestinal bleeding or receiving any treatment for portal hypertension were excluded. Endoscopy was performed every 12 months. RESULTS: The rate of incidence of EV was 5% (95%CI: 0.8-8.2%) at 1 year and 28% (21.0-35.0%) at 3 years. The rate of EV progression was 12% (5.6-18.4%) at 1 year and 31% (21.2-40.8%) at 3 years. Post-alcoholic origin of cirrhosis, Child-Pugh's class (B or C) and the finding of red wale marks at first examination were predictors for the variceal progression. The two-years risk of bleeding from EV was higher in patients with small varices upon enrollment than in those without varices: 12% (95% CI: 5.2-18.8%) vs. 2% (0.1-4.1%); (P<0.01). Predictor for bleeding was the presence of red wale marks at first endoscopy. CONCLUSIONS: In patients with no or small EV, endoscopy surveillance should be planned taking into account cause and degree of liver dysfunction.

Malnutrition is a risk factor in cirrhotic patients undergoing surgery.

Cirrhotic patients may become candidates for elective and emergency surgery. This may be due to conditions requiring operations such as cholecystectomy, herniotomy, or gastrointestinal malignancies, more common in cirrhotics when compared with the general population, or to complications of the liver disease such as resectable hepatocellular carcinomas or surgical portosystemic shunts to treat portal hypertension. It has been estimated that 10% of cirrhotics undergo at least one operative procedure during the final 2 y of their lives. Many studies have documented a high risk of morbidity and mortality associated with surgical procedures in these patients, and several factors influencing the postoperative outcome have been identified. Malnutrition, which is frequently encountered in cirrhotic patients, has been shown to have an important impact on the surgical risk. A poor nutrition status also has been associated with a higher risk of complications and mortality in patients undergoing liver transplantation. Few data are available concerning the perioperative nutrition support in surgical cirrhotic patients. The results of these studies are sometimes encouraging in reporting that the nutrition therapy may improve the clinical outcome in cirrhotic patients undergoing general surgery and/or liver transplantation. The limited number of patients and their heterogeneity, however, do not allow definitive conclusions, and more research on this issue is needed.