Cesare Efrati

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. (HEPATOLOGY 2005;42:1158–1165.)

Role of determination of partial pressure of ammonia in cirrhotic patients with and without hepatic encephalopathy

BACKGROUND/AIMS To compare venous, arterial and partial pressure of ammonia (pNH(3)) in 27 consecutive cirrhotics with hepatic encephalopathy, 15 cirrhotics without hepatic encephalopathy and nine controls; to reevaluate all parameters after the improvement of encephalopathy. METHODS Patients were studied by clinical examination and psychometric testing. pNH(3) was calculated from arterial ammonia and pH. RESULTS In patients with encephalopathy, each form of ammonia was higher than in both controls and patients without encephalopathy. The correlation with the severity of hepatic encephalopathy was similar for venous (r=0.72), arterial ammonia (r=0.76) and pNH(3) (r=0.75). The sensitivity and specificity of each variable in correctly classifying the patients as having or not having hepatic encephalopathy was also similar. Each form of ammonia decreased after the resolution or amelioration of symptoms. However, even in the 17 patients with complete resolution of hepatic encephalopathy, all three ammonia determinations resulted unchanged or increased in some patients. CONCLUSIONS Despite the significant correlation between pNH(3) and hepatic encephalopathy, our study suggests that neither pNH(3) nor arterial ammonia are, from a clinical point of view, more useful than venous ammonia: all three determinations being limited both for the diagnosis of hepatic encephalopathy and for the clinical management of the patients.

Modifications of cardiac function in cirrhotic patients treated with transjugular intrahepatic portosystemic shunt (TIPS).

OBJECTIVE:The implantation of a transjugular intrahepatic portosystemic shunt (TIPS) has been shown to exacerbate the hyperdynamic circulation and might induce a significant cardiac overload. We investigated cardiac function before and 1, 3, 6, and 12 months after the TIPS procedure in cirrhotic patients.METHODS:Eleven patients with nonalcoholic cirrhosis were evaluated. Cardiovascular parameters were assessed by two-dimensional Doppler echocardiography.RESULTS:After TIPS, the left ventricular diastolic diameter increased from 26.5 ± 1.8 mm (basal) to 30.0 ± 2.8 mm (6 months) (p < 0.05), whereas the ejection fraction showed a slight increase (basal, 64.5 ± 3.3; 6 months, 68.1 ± 3.2). The left ventricular pre-ejection period and the isovolumetric relaxation time decreased transiently at 1 month (p < 0.05). An increased velocity in all of the components of pulmonary venous flow (systolic, diastolic, and atrial) documented the accelerated fluxes induced by the procedure. The estimated pulmonary systolic arterial pressure also increased at 1 month (29.5 ± 1.4 vs 44.1 ± 1.4 mm Hg, p < 0.05). All of these modifications reverted after 6 months.CONCLUSIONS:Our study demonstrates that nonalcoholic cirrhotic patients, without cardiovascular pathologies, show transient modifications in cardiac dimension and function for 3–6 months after TIPS caused by the increased volume load shunted to the heart.

Effect of sodium benzoate on blood ammonia response to oral glutamine challenge in cirrhotic patients: a note of caution

OBJECTIVE:The administration of sodium benzoate provides an alternative pathway for the disposal of waste nitrogen and this substance has been used to treat patients with urea cycle defects and more recently cirrhotics with hepatic encephalopathy. The aim of the study was to assess the ammonia-lowering effect of benzoate in cirrhotic patients without overt hepatic encephalopathy.METHODS:Glutamine challenge, a method to induce an increase of blood ammonia, was performed in six cirrhotics before and after 5 days of benzoate treatment (10 g/day). Number Connection Test and Posners Attention Test were also performed before and after benzoate treatment.RESULTS:Blood ammonia increased after the glutamine load both before (from 66 ± 12 μg/dl to 123 ± 34 μg/dl and 179 ± 53 μg/dl after 30 and 60 min, respectively; ANOVA p= 0.0004) and after benzoate treatment (from 102 ± 27 μg/dl to 185 ± 49 μg/dl and 250 ± 39 μg/dl after 30 and 60 min, respectively; ANOVA p= 0.00001). However, after benzoate treatment, the basal values (102 ± 27 vs 66 ± 12 μg/dl; p= 0.01) and peak increments of ammonia (166 ± 56 μg/dl vs 102 ± 40 μg/dl; p= 0.04) were significantly higher than before. The Number Connection test and the Posners test were not altered by benzoate treatment.CONCLUSIONS:Benzoate increased both the basal and postglutamine ammonia levels. These results confirm what has already been observed in experimental animals and suggest a note of caution in the use of sodium benzoate in cirrhotic patients.

Effect of lactitol on blood ammonia response to oral glutamine challenge in cirrhotic patients: evidence for an effect of nonabsorbable disaccharides on small intestine ammonia generation

Objective:Nonabsorbable disaccharides are widely used to decrease blood ammonia concentration. Their principal mode of action is the modification of pH and bacterial flora in the colon. The aim of the present study was to test the hypothesis that these drugs may also reduce small intestine ammonia generation.Methods:Eight male cirrhotics without overt hepatic encephalopathy received 20 g of glutamine in 100 ml of water. Venous samples for whole blood ammonia were taken before, 30 and 60 min after the load. Immediately after the last blood sample the patients were submitted to the following psychometric tests: number connection test, Posners attention test, and Sternberg paradigm. After the first glutamine load, patients were started on lactitol (initial dose 20 g, three times a day). Once two bowel movements/day were obtained and maintained for at least 5 days, oral glutamine challenge and psychometric tests were repeated.Results:Ammonia increased significantly after the glutamine load (from 83 ± 13 to 164 ± 30 μg/dl at 30 min and 210 ± 29 μg/dl at 60 min; mean ±SE; p= 0.006 analysis of variance) but not after glutamine load after lactitol treatment (from 77 ± 17 to 111 ± 21 μg/dl and 142 ± 24 μg/dl; p= not significant). The peak increment (127 ± 24 vs 65 ± 18 μg/dl; p= 0.008) of ammonia elevation was significantly smaller during lactitol administration. The patients’ psychometric performance after the glutamine load did not differ significantly after lactitol treatment.Conclusions:Lactitol reduces the elevation in blood ammonia that follows oral glutamine challenge. Because enterally administered glutamine is efficiently absorbed in the jejunum and, in part, metabolized to ammonia we suggest that lactitol affects small intestine ammonia generation probably by shortening the residence time of intestinal contents.

Helicobacter pylori eradication: Sequential therapy and Lactobacillus reuteri supplementation

AIM To evaluate the role of sequential therapy and Lactobacillus reuteri (L. reuteri) supplementation, in the eradication treatment of Helicobacter pylori (H. pylori). METHODS H. pylori infection was diagnosed in 90 adult dyspeptic patients. Patients were excluded if previously treated for H. pylori infection or if they were taking a proton pump inhibitor (PPI), H2-receptor antagonist or antibiotics. Patients were assigned to receive one of the following therapies: (1) 7-d triple therapy (PPI plus clarithromycin and amoxicillin or metronidazole) plus L. reuteri supplementation during antibiotic treatment; (2) 7-d triple therapy plus L. reuteri supplementation after antibiotic treatment; (3) sequential regimen (5-d PPI plus amoxicillin therapy followed by a 5-d PPI, clarithromycin and tinidazole) plus L. reuteri supplementation during antibiotic treatment; and (4) sequential regimen plus L. reuteri supplementation after antibiotic treatment. Successful eradication therapy was defined as a negative urea breath test at least 4 wk following treatment. RESULTS Ninety adult dyspeptic patients were enrolled, and 83 (30 male, 53 female; mean age 57 ± 13 years) completed the study. Nineteen patients were administered a 7-d triple treatment: 11 with L. reuteri supplementation during and 8 after therapy. Sixty-four patients were administered a sequential regimen: 32 with L. reuteri supplementation during and 32 after therapy. The eradication rate was significantly higher in the sequential group compared with the 7-d triple regimen (88% vs 63%, P = 0.01). No difference was found between two types of PPI. No difference in eradication rates was observed between patients submitted to L. reuteri supplementation during or after antibiotic treatment. Compliance with therapy was excellent in all patients. No difference in adverse effects was observed between the different antibiotic treatments and between patients submitted to L. reuteri supplementation during and after antibiotic treatment. There was a low incidence of adverse effects in all groups of patients with sequential therapy, probably due to the presence of the L. reuteri supplementation. CONCLUSION The sequential treatment regimen achieved a significantly higher eradication rate of H. pylori compared with standard 7-d regimen. L. reuteri supplementation could reduce the frequency and the intensity of antibiotic-associated side-effects.

Effect of Blood Ammonia Elevation Following Oral Glutamine Load on the Psychometric Performance of Cirrhotic Patients

Oral glutamine challenge is a method to increase blood ammonia and may be used to study the ammonia lowering effect of drugs potentially useful in hepatic encephalopathy (HE). We tested its influence on the psychometric performance of 18 cirrhotic patients without HE. Twelve nonencephalopatic cirrhotic patients were studied before and after glutamine load (20 g in 100 mL tap water) and six patients before and after placebo (100 mL tap water) by using the Number Connection Test (NCT), the Covert Visual Attention Orienting Test (CVAOT), and the Scan Test (SCT). Blood ammonia increased significantly after glutamine (from 79 ± 34 to 211 ± 66 μg/dL) but not after placebo (from 94 ± 41 to 88 ± 26). No difference in the NCT was found before and after glutamine load or placebo. The CVAOT was similar after glutamine challenge and placebo, nor any interaction between Loads (glutamine or placebo) × Cue position was found, suggesting that glutamine load did not influence attention-orienting. SCT results were also similar after glutamine and placebo, suggesting a lack of influence on the working memory. Glutamine challenge is a safe method to induce hyperammonemia in nonencephalopatic cirrhotic patients and, therefore, to study the efficacy of ammonia lowering treatments.

Intractable Hepatic Encephalopathy After Tips with Polytetrafluoroethylene-covered Stent-Graft

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TIPS: Refractory Ascites and Encephalopathy

The transjugular intrahepatic portosystemic shunt (TIPS) has been recently introduced in clinical practice for the management of cirrhotic patients with portal hypertension-related complications. In the majority of the patients submitted to TIPS for variceal bleeding who also had ascites, the latter complication improved or disappeared completely after the procedure (LABERGE 1993; ROSSLE et al. 1994). The same result was observed after surgical portacaval shunts (ORLOFF 1970; BURCHELL et al. 1968). In fact, portal hypertension is a major determinant in the formation of ascites and both these operations are capable of inducing a rapid and significant reduction of the portal pressure. Moreover, it has recently been shown that all patients treated with TIPS who present either de novo or with recurrent ascites have a portal pressure gradient> 12 mmHg (CASADO et al. 1998), indicating that recurrence of portal hypertension is essential for the development of ascites after TIPS.