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ABSTRACT: Transjugular intrahepatic portosystemic shunt (TIPS) has been used for more than 20 years to treat some of the complications of portal hypertension. When TIPS was initially proposed, it was claimed that the optimal calibration of the shunt could allow an adequate reduction of portal hypertension, avoiding, at the same time, the occurrence of hepatic encephalopathy (HE), a neurologic syndrome. However, several clinical observations have shown that HE occurred rather frequently after TIPS, and HE has become an important issue to be taken into consideration in TIPS candidates and a problem to be faced after the procedure.
Clinics in Liver Disease 02/2013; 16(1):133-46. · 3.18 Impact Factor
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Silvia Nardelli,
Ilaria Pentassuglio,
Chiara Pasquale, Lorenzo Ridola,
Federica Moscucci,
Manuela Merli,
Concetta Mina,
Massimo Marianetti,
Mariangela Fratino,
Chiara Izzo,
Carlo Merkel,
Oliviero Riggio
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ABSTRACT: HRQoL is impaired in cirrhosis. Establishing the relevance of depression, anxiety, alexithymia and cirrhosis stage on the patients' HRQoL. Sixty cirrhotics underwent a neuropsychological assessment, including ZUNG-SDS, STAI Y1-Y2 and TAS-20. Minimal hepatic encephalopathy (MHE) was detected by PHES, HRQoL by Short-Form-36 (SF-36). Depression was detected in 34 patients (57 %, 95%CI = 44-70 %), state-anxiety in 16 (27 %, 95%CI = 15-38 %), trait-anxiety in 17 (28 %, 95%CI = 17-40 %), alexithymia in 14 (31 % 95%CI = 16-46 %) and MHE in 22 (37 %, 95%CI = 24-49 %). Neuropsychological symptoms were unrelated to cirrhosis stage, hepatocellular carcinoma or MHE. A significant correlation was observed among psychological test scores and summary components of SF-36. At multiple linear regression analysis including Child-Pugh and MELD scores, previous-HE and the psychological test scores as possible covariates, alexithymia and depression as well as to the Child-Pugh score were significantly related to the SF-36 mental component; while trait-anxiety was the only variable significantly and independently related to the SF-36 physical component. Depression, state and trait-anxiety and alexithymia symptoms are frequent in cirrhotics and are among the major determinants of the altered HRQoL.
Metabolic Brain Disease 01/2013; · 2.20 Impact Factor
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ABSTRACT: Despite the impact of hepatic encephalopathy on quality of life and prognosis, easily administered tests for its diagnosis are still lacking.
To assess the usefulness of the Scan package, a three-level-difficulty computerised reaction time test, to diagnose varying degrees of hepatic encephalopathy.
Sixty-one cirrhotic patients underwent clinical evaluation, paper-and-pencil psychometry and the Scan package; 32 healthy controls served as reference.
Twenty-nine patients were classified as unimpaired, 15 as having minimal and 17 as having overt hepatic encephalopathy. All healthy controls were able to complete the Scan package; in contrast, the number of patients who were able to complete three/two/one part decreased in parallel with the degree of encephalopathy (χ(2)=17, p=0.01). Reaction times in all three parts increased significantly with the severity of encephalopathy. However, the profile of increase was different [group: F(3,77)=26, p<0.0001; test: F(2,154)=277, p<0.0001; group×test: F(6,154)=7, p<0.0001], with different parts being more/less sensitive to varying degrees of encephalopathy.
The Scan package seems useful for the diagnosis of hepatic encephalopathy and covers a considerable portion of its spectrum of severity.
Digestive and Liver Disease 07/2012; 44(11):957-60. · 3.05 Impact Factor
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ABSTRACT: It has been observed that overt hepatic encephalopathy (HE) is accompanied by a persistent cognitive defect, suggesting that HE may not be fully reversible. The health-related quality-of-life (HRQoL) has been shown to be impaired by cirrhosis, and, according to some reports, influenced by minimal HE. Little is known about the effect of previous HE on HRQoL.
To investigate the relative impact of previous HE and minimal HE on HRQoL in a group of consecutively hospitalized cirrhotic patients.
Seventy five consecutive cirrhotic patients were evaluated using the Psychometric HE Score (PHES) and simplified Psychometric HE Score (SPHES) to detect the presence of minimal HE and using SF-36 to assess the HRQoL, both corrected for age and education. Eighteen of them had previous bouts of overt HE.
Minimal HE was significantly more frequent in patients with previous HE than in those without (p < 0.001), independently on the method used for the diagnosis (PHES or SPHES). A deeper impairment in several domains of SF-36 was observed in patients with previous bouts of overt HE, in those with ascites, as well as in those with decompensated cirrhosis. At multivariate analysis, ascites, MELD score and previous HE were independently related to the mental-component-summary (MCS) of SF-36, whereas ascites was the only variable independently associated with the physical-component-summary (PCS) of SF-36. Minimal HE (independently on the method used for its diagnosis) impaired only one domain of SF-36.
These data suggest that previous bouts of HE, despite their complete clinical resolution, play an independent role in producing a persistent impairment in HRQoL of cirrhotics.
Liver international: official journal of the International Association for the Study of the Liver 11/2011; 31(10):1505-10. · 3.82 Impact Factor
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Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 07/2011; 9(7):624-5. · 5.64 Impact Factor
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ABSTRACT: Hepatic macrophages (Kupffer cells) undergo inflammatory activation during the development of portal hypertension in experimental cirrhosis; this activation may play a pathogenic role or be an epiphenomenon. Our objective was to study serum soluble CD163 (sCD163), a sensitive marker of macrophage activation, before and after reduction of portal venous pressure gradient by insertion of a transjugular intrahepatic portosystemic shunt (TIPS) in patients with cirrhosis.
sCD163 was measured in 11 controls and 36 patients before and 1, 4 and 26 weeks after TIPS. We used lipopolysaccharide binding protein (LBP) levels as a marker of endotoxinaemia. Liver function and clinical status of the patients were assessed by galactose elimination capacity and Model for End Stage Liver Disease score.
The sCD163 concentration was more than threefold higher in the patients than in the controls (median 5.22 mg/l vs 1.45 mg/l, p<0.001). The sCD163 was linearly related to the portal venous pressure gradient (r(2)=0.24, p<0.001), also after adjustment for cirrhosis status. The sCD163 concentration was 12% higher in the hepatic than in the portal vein (p<0.02). The LBP level was 70% higher in the patients (52.2 vs 30.4 μg/l, p<0.001). During follow-up after TIPS, the sCD163 concentration did not change while LBP almost normalised.
Kupffer cells were activated in patients with liver cirrhosis in parallel with their portal hypertension. The activation was not alleviated by the mechanical reduction of portal hypertension and the decreasing signs of endotoxinaemia. The findings suggest that Kupffer cell activation is a constitutive event that may play a pathogenic role for portal hypertension.
Gut 06/2011; 60(10):1389-93. · 10.11 Impact Factor
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ABSTRACT: The psychometric hepatic encephalopathy score (PHES), which includes 5 psychometric tests, is a standard for the diagnosis of minimal hepatic encephalopathy (HE). We investigated whether a simplified PHES (SPHES) is as useful as the whole PHES.
The PHES was determined for 79 cirrhotic patients (the training group), who were followed up for the development of overt HE. Backward logistic regression was performed by eliminating stepwise variables--removal did not impair regression. A separate series of 65 patients was used as a validation group.
The PHES was abnormal in 45 patients. The SPHES, determined from the digit symbol, serial dotting, and line tracing tests, did not differ significantly from the full PHES; 24 of the 79 patients developed overt HE. The likelihood of developing overt HE was higher among patients with an abnormal PHES (log-rank P = .003) or SPHES (P = .004). By using Cox regression and model for end-stage liver disease scores to analyze data from patients with previous HE and transjugular intrahepatic portosystemic shunts, PHES (relative risk, 4.16; P = .003) and SPHES (relative risk, 3.70; P = .004) were the only variables associated with the development of overt HE. The accuracy of the SPHES was confirmed in the validation group.
A simplified PHES is as good as the PHES in diagnosing minimal HE and in predicting the occurrence of overt HE.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 03/2011; 9(7):613-6.e1. · 5.64 Impact Factor
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Fabrizio Fanelli,
Stefania Angeloni,
Filippo Maria Salvatori,
Chiara Marzano,
Emanuele Boatta,
Manuela Merli,
Plinio Rossi,
Adolfo Francesco Attili, Lorenzo Ridola,
Federica Cerini,
Oliviero Riggio
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ABSTRACT: To evaluate the feasibility and efficacy of Transjugular intrahepatic portosystemic shunt (TIPS) in non-cirrhotic patients with symptomatic portal hypertension secondary to portal cavernoma.
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.
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.
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.
Digestive and Liver Disease 01/2011; 43(1):78-84. · 3.05 Impact Factor
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ABSTRACT: Bacterial infections are a frequent and serious burden among patients with cirrhosis because they can further deteriorate liver function. We assessed the epidemiology, risk factors, and clinical consequences of bacterial infections in hospitalized cirrhotic patients.
In a cohort of hospitalized cirrhotic patients (n = 150) referred to a tertiary care setting, all episodes of bacterial infections were recorded prospectively. Infections were classified as community-acquired (CA), health care-associated (HCA), or hospital-acquired (HA). Site of infection, characteristics of bacteria, and prevalence of antibiotic resistance were reported; consequences for liver function and patient survival were evaluated.
Fifty-four infections were observed among 50 patients (12 CA, 22 HCA, and 20 HA). Bacterial resistance was more frequent among patients with HCA or HA infections (64% of isolates). Mortality was 37% from HA, 36% from HCA, and 0% from CA infections. Independent predictors of infection included a previous infection within the past 12 months (P = .0001; 95% confidence interval [CI], 2.2-10.6), model of end-stage liver disease score ≥ 5 (P = .01; 95% CI, 1.3-6.1), and protein malnutrition (P = .04; 95% CI, 1.5-10). Infectious episodes worsened liver function in 62% of patients. Patients with infection more frequently developed ascites, hepatic encephalopathy, hyponatremia, hepatorenal syndrome, or septic shock. Child class C (P = .006; 95% CI, 1.67-23.7), sepsis (P = .005; 95% CI, 1.7-21.4), and protein malnutrition (P = .001; 95% CI, 2.8-38.5) increased mortality among patients in the hospital.
In hospitalized cirrhotic patients, the most frequent infections are HCA and HA; these infections are frequently resistant to antibiotics. As infections worsen, liver function deteriorates and mortality increases. Cirrhotic patients should be monitored closely for infections.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 11/2010; 8(11):979-85. · 5.64 Impact Factor
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ABSTRACT: The Inhibitory Control Test has been proposed as a tool to detect the persistence of cognitive defects after the resolution of overt hepatic encephalopathy (OHE). We tested learning abilities of cirrhotic patients using the Psychometric Hepatic Encephalopathy Score (PHES).
One hundred six cirrhotic patients who agreed to be examined twice within 3 days were studied using the PHES. Twenty-seven patients had previous OHE; of the remaining 79 patients, 34 were affected by minimal HE and 45 were normal.
Among patients without previous OHE, PHESs significantly improved at the second examination; this learning effect was present in the patients with or without minimal HE. To the contrary, learning ability was lost in patients with previous OHE. Even among the 8 patients with history of HE and normal PHESs in the first examination, repeated testing showed a lack of learning capacity.
HE is not a fully reversible condition. Residual cognitive impairments should be evaluated by specific tests, based on patients' learning capacities.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 10/2010; 9(2):181-3. · 5.64 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
Journal of Hepatology 08/2010; 53(2):267-72. · 9.26 Impact Factor
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Piero Amodio, Lorenzo Ridola,
Sami Schiff,
Sara Montagnese,
Chiara Pasquale,
Silvia Nardelli,
Ilaria Pentassuglio,
Maria Trezza,
Chiara Marzano,
Cristiana Flaiban,
Paolo Angeli,
Giorgia Cona,
Patrizia Bisiacchi,
Angelo Gatta,
Oliviero Riggio
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ABSTRACT: Quantification of the number of noninhibited responses (lures) in the inhibitory control task (ICT) has been proposed for the diagnosis of minimal hepatic encephalopathy (MHE). We assessed the efficacy of ICT compared with recommended diagnostic standards.
We studied patients with cirrhosis and healthy individuals (controls) who underwent the ICT at 2 centers (center A: n=51 patients and 41 controls, center B: n=24 patients and 14 controls). Subjects were evaluated for MHE by psychometric hepatic encephalopathy score (PHES). Patients from center B also were assessed for MHE by critical flicker frequency and spectral electroencephalogram analyses.
Patients with cirrhosis had higher ICT lures (23.2+/-12.8 vs 12.9+/-5.8, respectively, P<.01) and lower ICT target accuracy (0.88+/-0.17 vs 0.96+/-0.03, respectively, P<.01) compared with controls. However, lures were comparable (25.2+/-12.5 vs 21.4+/-13.9, respectively, P=.32) among patients with/without altered PHES (center A). There was a reverse, U-shaped relationship between ICT lure and target accuracy; a variable adjusting lures was devised based on target accuracy (weighted lures at center B). This variable differed between patients with and without MHE. The variable weighted lures was then validated from data collected at center A by receiver operator characteristic curve analysis; it discriminated between patients with and without PHES alterations (area under the curve=0.71+/-0.07). However, target accuracy alone was as effective as a stand-alone variable (area under the curve=0.81+/-0.06).
The ICT is not useful for the diagnosis of MHE, unless adjusted by target accuracy. Testing inhibition (lures) does not seem to be superior to testing attention (target accuracy) for the detection of MHE.
Gastroenterology 08/2010; 139(2):510-8, 518.e1-2. · 11.68 Impact Factor
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ABSTRACT: 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.
Digestive and Liver Disease 07/2010; 42(7):462-7. · 3.05 Impact Factor
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Hepatology 06/2010; 51(6):2237-8. · 11.66 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
The American Journal of Gastroenterology 06/2010; 105(6):1374-81. · 7.28 Impact Factor
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ABSTRACT: Type-C hepatic encephalopathy (HE) is a severe complication of cirrhosis, which seriously affects quality of life and is strongly related to patient survival. Treatment based on a classical pharmacological approach that is aimed at reducing the production of gut-derived toxins, such as ammonia, is still under debate. Currently, results obtained from clinical trials do not support any specific treatment for HE and our competence in testing old and new treatment modalities by randomized controlled trials with appropriate clinically relevant end-points urgently needs to be improved. On the other hand, patients who are at risk for HE are now identifiable, based on studies on the natural history of the disease. Today, very few studies that are specifically aimed at establishing whether HE may be prevented are available or in progress. Recent studies have looked at non absorbable disaccharides or antibiotics and other treatment modalities, such as the modulation of intestinal flora. In the treatment of severe stage HE, artificial liver supports have been tested with initial positive results but more studies are needed.
World journal of gastrointestinal pharmacology and therapeutics. 04/2010; 1(2):54-63.
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Journal of Gastroenterology 03/2010; 45(3):346-7; author reply 348. · 4.16 Impact Factor
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ABSTRACT: Hepatic encephalopathy (HE) is a severe complication of cirrhosis, seriously affecting the patients' quality of life. The classical approach aimed at reducing the production of gut-derived toxins, such as ammonia, is under debate as, at the moment, the information obtained from the clinical trials does not support any specific treatment for HE.
i) To discuss present therapeutic strategies and possible future developments; ii) to identify areas of medical needs and iii) to suggest the ideal design and methodology for randomized controlled trials (RCTs) in HE.
Current approaches were obtained from already available RCTs or from experimental animal studies. Those approaches developed from studies on HE pathophysiology were considered as working hypotheses for future therapies.
Our competence in testing old and new treatment modalities by RCTs with appropriate clinically relevant end points should urgently be improved. The patients at risk of HE are identifiable, and studies specifically aimed at establishing whether HE may be prevented or not are needed. As far as new treatment modalities are concerned, RCTs on the modulators of the intestinal bacterial flora and on the molecular adsorbent recirculating system are already available, but further studies are needed to confirm these promising approaches.
Expert Opinion on Emerging Drugs 07/2009; 14(3):537-49. · 3.21 Impact Factor
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Oliviero Riggio,
Cesare Efrati,
Carlo Catalano,
Federica Pediconi,
Oriano Mecarelli,
Neri Accornero,
Francesca Nicolao,
Stefania Angeloni,
Andrea Masini, Lorenzo Ridola,
Adolfo F Attili,
Manuela Merli
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ABSTRACT: 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 12/2005; 42(5):1158-65. · 11.66 Impact Factor
