Long-term albumin administration in decompensated cirrhosis (ANSWER): an open-label randomised trial.

BACKGROUND: Evidence is scarce on the efficacy of long-term human albumin (HA) administration in patients with decompensated cirrhosis. The human Albumin for the treatmeNt of aScites in patients With hEpatic ciRrhosis (ANSWER) study was designed to clarify this issue. METHODS: We did an investigator-initiated multicentre randomised, parallel, open-label, pragmatic trial in 33 academic and non-academic Italian hospitals. We randomly assigned patients with cirrhosis and uncomplicated ascites who were treated with anti-aldosteronic drugs (≥200 mg/day) and furosemide (≥25 mg/day) to receive either standard medical treatment (SMT) or SMT plus HA (40 g twice weekly for 2 weeks, and then 40 g weekly) for up to 18 months. The primary endpoint was 18-month mortality, evaluated as difference of events and analysis of survival time in patients included in the modified intention-to-treat and per-protocol populations. This study is registered with EudraCT, number 2008-000625-19, and ClinicalTrials.gov, number NCT01288794. FINDINGS: From April 2, 2011, to May 27, 2015, 440 patients were randomly assigned and 431 were included in the modified intention-to-treat analysis. 38 of 218 patients died in the SMT plus HA group and 46 of 213 in the SMT group. Overall 18-month survival was significantly higher in the SMT plus HA than in the SMT group (Kaplan-Meier estimates 77% vs 66%; p=0·028), resulting in a 38% reduction in the mortality hazard ratio (0·62 [95% CI 0·40-0·95]). 46 (22%) patients in the SMT group and 49 (22%) in the SMT plus HA group had grade 3-4 non-liver related adverse events. INTERPRETATION: In this trial, long-term HA administration prolongs overall survival and might act as a disease modifying treatment in patients with decompensated cirrhosis. FUNDING: Italian Medicine Agency.

Influence of the Menstrual Cycle Phase on Pain Perception and Analgesic Requirements in Young Women Undergoing Gynecological Laparoscopy.

CONTEXT: The influence of the gonadal hormones on some aspects of the human physiology has been studied with uncertain results. Still a confusion exists in relation to the real effects of the female hormones on the perception of pain. The existing data refer mainly to experimental studies and have provided results not always useful in the clinical practice. DATA SOURCE: This study was designed to detect whether there are differences in the perception of the postoperative pain in women, during two clearly defined phases of hormonal asset: luteal and follicular phases. CONCLUSION: The results of this study have demonstrated that in postoperative female patients pain is perceived significantly more in the luteal phase of the menstrual period, than in the follicular phase. This could suggest that female in child-bearing age should be scheduled for elective surgery preferentially during the follicular phase, unless differently necessary. It would guarantee a more comfortable postoperative period, with reduced necessity of analgesics.

The animal naming test: An easy tool for the assessment of hepatic encephalopathy.

Screening for hepatic encephalopathy (HE) that does not cause obvious disorientation or asterixis (minimal HE [MHE]/grade 1 HE) is important. We examined if the animal naming test (ANT1 ) (maximum number of animals listed in 1 minute) is useful in this context. In total, 208 healthy controls, 40 controls with inflammatory bowel disease, and 327 consecutive patients with cirrhosis underwent the ANT1 . Patients were tested for MHE by the psychometric HE score, and 146 were assessed by electroencephalography; 202 patients were followed up regarding the occurrence of overt HE and death. In the healthy controls, ANT1 was influenced by limited education (<8 years) and advanced age (>80 years, P < 0.001). Using an age and education adjusting procedure, the simplified ANT1 (S-ANT1 ) was obtained. An S-ANT1 of <10 animals was abnormal. Of the patients, 169 were considered unimpaired, 32 as having HE ≥grade 2, and 126 as having MHE/grade 1 HE. This group had lower S-ANT1 than unimpaired patients (12 ± 0.4 versus 16 ± 0.7, P < 0.001) and higher S-ANT1 than those with HE ≥grade 2 (4 ± 0.9). In grade 1 HE the S-ANT1 was lower than in MHE. Following receiver operating characteristic analysis (Youden's index), 15 animals produced the best discrimination between unimpaired and MHE/grade 1 HE patients. Thus, a three-level score (0 for S-ANT1 ≥15, 1 for 10 ≤ S-ANT1 < 15, 2 for S-ANT1 <10) was obtained. This score was correlated both to the psychometric HE score (P < 0.0001) and to electroencephalography (P = 0.007). By sample random split validation, both S-ANT1 and its three-level score showed prognostic value regarding the 1-year risk of overt HE and death. No inflammatory bowel disease control had S-ANT <15. CONCLUSION: The S-ANT1 is an easily obtainable measure useful for the assessment of HE. (Hepatology 2017;66:198-208).

Gut-derived endotoxin stimulates factor VIII secretion from endothelial cells. Implications for hypercoagulability in cirrhosis.

BACKGROUND & AIMS: Patients with cirrhosis display enhanced blood levels of factor VIII, which may result in harmful activation of the clotting system; however, the underlying mechanism is unknown. METHODS: We performed a cross-sectional study in patients with cirrhosis (n=61) and matched controls (n=61) comparing blood levels of factor VIII, von Willebrand factor (vWf), lipopolysaccharide (LPS) and positivity for Escherichia coli DNA. Furthermore, we performed an in vitro study to investigate if LPS, in a concentration range similar to that found in the peripheral circulation of cirrhotic patients, was able to elicit factor VIII secretion from human umbilical vein endothelial cells (HUVEC). RESULTS: Patients with cirrhosis displayed higher serum levels of LPS (55.8 [42.2-79.9] vs. 23.0 [7.0-34.0]pg/ml, p<0.001), factor VIII (172.0 [130.0-278.0] vs. 39.0 [26.0-47.0]U/dl, p<0.0001), vWf (265.0 [185.0-366.0] vs. 57.0 [48.0-65.0]U/dl, p<0.001) and positivity for Escherichia coli DNA (88% vs. 3%, p<0.001, n=34) compared to controls. Serum LPS correlated significantly with factor VIII (r=0.80, p<0.001) and vWf (r=0.63, p<0.001). Only LPS (beta-coefficient=0.70, p<0.0001) independently predicted factor VIII levels. The in vitro study showed that LPS provoked factor VIII and vWf release from HUVEC via formation and secretion of Weibel-Palade bodies, a phenomenon blunted by pre-treating HUVEC with an inhibitor of Toll-like receptor 4. CONCLUSIONS: The study provides the first evidence that LPS derived from gut microbiota increases the systemic levels of factor VIII via stimulating its release by endothelial cells. Lay summary: Cirrhosis is associated with thrombosis in portal and systemic circulation. Enhanced levels of factor VIII have been suggested to play a role but the underlying mechanism is still unclear. Here we show that patients with cirrhosis display a concomitant increase of factor VIII and lipopolysaccharide (LPS) from Escherichia coli and suggest that LPS contributes to the release of factor VIII from endothelial cells.

Cognitive Impairment Predicts The Occurrence Of Hepatic Encephalopathy After Transjugular Intrahepatic Portosystemic Shunt.

OBJECTIVES: Hepatic encephalopathy (HE) is a major problem in patients treated with TIPS. The aim of the study was to establish whether pre-TIPS covert HE is an independent risk factor for the development of HE after TIPS. METHODS: Eighty-two consecutive cirrhotic patients submitted to TIPS were included. All patients underwent the PHES to identify those affected by covert HE before a TIPS. The incidence of the first episode of HE was estimated, taking into account the nature of the competing risks in the data (death or liver transplantation). RESULTS: Thirty-five (43%) patients developed overt HE. The difference of post-TIPS HE was highly significant (P=0.0003) among patients with or without covert HE before a TIPS. Seventy-seven percent of patients with post-TIPS HE were classified as affected by covert HE before TIPS. Age: (sHR 1.05, CI 1.02-1.08, P=0.002); Child-Pugh score: (sHR 1.29, CI 1.06-1.56, P=0.01); and covert HE: (sHR 3.16, CI: 1.43-6.99 P=0.004) were associated with post-TIPS HE. Taking into consideration only the results of PHES evaluation, the negative predicting value was 0.80 for all patients and 0.88 for the patients submitted to TIPS because of refractory ascites. Thus, a patient with refractory ascites, without covert HE before a TIPS, has almost 90% probability of being free of HE after TIPS. CONCLUSIONS: Psychometric evaluation before TIPS is able to identify most of the patients who will develop HE after a TIPS and can be used to select patients in order to have the lowest incidence of this important complication.

Reduced Plasma Levels of sCD14 and I-FABP in HIV-infected Patients with Mesalazine-treated Ulcerative Colitis.

BACKGROUND: Microbial translocation (MT) is a shared feature of HIV infection and inflammatory bowel disease (IBD). AIMS: This study was conducted to assess the impact of IBD (and particularly ulcerative colitis, UC) on plasma markers of MT and immune activation in HIV+ subjects. METHODS: A cross-sectional study was conducted in 3 groups of patients: HIV+/UC+(group HIV/UC); HIV+/UC- (group HIV); HIV-/UC+(group UC). Plasma levels of soluble CD14 (sCD14), intestinal fatty acid-binding protein (I-FABP), and endotoxin core antibodies (endoCAB) were measured as plasma markers of MT. Inflammation and immune activation were evaluated by measuring plasma levels of IL-6, IL-21, TNF-alpha, and high-sensitivity C-reactive protein (hs-CRP). T- and B-cells subpopulations were characterized by FACS analysis. RESULTS: Seven patients were enrolled in group HIV/UC, 9 in HIV, and 10 in UC. All HIV-positive patients had plasma values of HIV-1 RNA<37 copies/mL for at least 12 months and good immunological recovery. All patients with UC were treated with oral mesalazine. Markers of MT, immune activation, and inflammation were not increased in subjects with HIV/UC. In fact, they had lower levels of I-FABP (p=0.001) and sCD14 (p=0.007) when compared to other patients groups. Positive correlations were found between I-FABP and sCD14 (r=.355, p=0.076). Frequency of T- and B-cell subsets did not differ among groups. CONCLUSIONS: Our results suggest that UC does not worsen MT, inflammation, or immune activation in HIV-infected subjects. The anti-inflammatory activity of chronic mesalazine administration on intestinal mucosa may contribute to this finding.

No effect of albumin infusion on the prevention of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt.

Hepatic encephalopathy (HE) is a major problem in patients submitted to TIPS. Previous studies identified low albumin as a factor associated to post-TIPS HE. In cirrhotics with diuretic-induced HE and hypovolemia, albumin infusion reduced plasma ammonia and improved HE. Our aim was to evaluate if the incidence of overt HE (grade II or more according to WH) and the modifications of venous blood ammonia and psychometric tests during the first month after TIPS can be prevented by albumin infusion. Twenty-three patients consecutively submitted to TIPS were enrolled and treated with 1 g/Kg BW of albumin for the first 2 days after TIPS followed by 0,5 g/Kg BW at day 4th and 7th and then once a week for 3 weeks. Forty-five patients included in a previous RCT (Riggio et al. 2010) followed with the same protocol and submitted to no pharmacological treatment for the prevention of HE, were used as historical controls. No differences in the incidence of overt HE were observed between the group of patients treated with albumin and historical controls during the first month (34 vs 31 %) or during the follow-up (39 vs 48 %). Two patients in the albumin group and three in historical controls needed the reduction of the stent diameter for persistent HE. Venous blood ammonia levels and psychometric tests were also similarly modified in the two groups. Survival was also similar. Albumin infusion has not a role in the prevention of post-TIPS HE.

A Model for Predicting Development of Overt Hepatic Encephalopathy in Patients With Cirrhosis.

BACKGROUND & AIMS: Overt hepatic encephalopathy (HE) affects patients' quantity and quality of life and places a burden on families. There is evidence that overt HE might be prevented pharmacologically, but prophylaxis would be justified and cost effective only for patients at risk. We aimed to identify patients with cirrhosis at risk for overt HE. METHODS: We collected data from October 2009 through December 2012 for 216 consecutive patients with cirrhosis (based on liver biopsy, 96 patients with minimal HE), admitted to the Gastroenterology Unit at the University of Rome. Patients were followed up and evaluated for an average of 14.7 ± 11.6 months; development of overt HE was recorded. We analyzed end-stage liver disease scores, shunt placement, previous overt or minimal HE, psychometric hepatic encephalopathy score (PHES), and levels of albumin, bilirubin, creatinine, and sodium to develop a prediction model. We validated the model in 112 patients with cirrhosis seen at the University of Padua and followed up for 12 ± 9.5 months. RESULTS: During the follow-up period, 68 patients (32%) developed at least 1 episode of overt HE. Based on multivariate analysis, the development of overt HE was associated with previous HE, minimal HE (based on PHES), and level of albumin less than 3.5 g/dL (area under curve [AUC], 0.74). A model that excluded minimal HE but included albumin level and previous HE also identified patients who would develop overt HE (AUC, 0.71); this difference in AUC values was not statistically significant (P = .104). Both models were validated in the independent group of patients (3 variables: AUC, 0.74; 95% confidence interval, 0.66-0.83; and 2 variables: AUC, 0.71; 95% confidence interval, 0.63-0.78). CONCLUSIONS: We developed and validated a model to identify patients with cirrhosis at risk for overt HE based on previous HE, albumin levels, and PHES. If PHES was not available, previous HE and albumin levels still can identify patients at risk. Psychometric evaluation is essential for patients with no history of HE. These findings should aid in planning studies of pharmacologic prevention of overt HE.

Small hepatic veins Budd-Chiari syndrome.

Budd-Chiari syndrome is a rare disorder characterized by hepatic venous outflow obstruction at any level from the small hepatic veins to the atrio-caval junction, in the absence of heart failure or constrictive pericarditis. Various imaging modalities are available for investigating the gross hepatic vascular anatomy but there are rare forms of this disease where the obstruction is limited to the small intrahepatic veins, with normal appearance of the large hepatic veins at imaging. In this cases only a liver biopsy can demonstrate the presence of a small vessels outflow block. We report two cases of small hepatic veins Budd-Chiari syndrome.

Breast gel based on Boswellia serrata, Betaine and myo-Inositol improves cyclic mastodynia in fertile women: A retrospective clinical study.

BACKGROUND: The management of mastodynia plays a central role in improving women quality of life. Despite its high occurrence, specific therapeutic guidelines for mastalgia are still lacking. Available therapies include unspecific anti-inflammatories, even though they may often expose to undesirable effects and low compliance. OBJECTIVE: The aim of this study was to highlight the efficacy of the topical application of combined natural molecules including Boswellia serrata, Betaine and myo-Inositol in improving cyclic mastalgia. METHODS: In this retrospective pilot clinical study, patients with cyclic mastalgia applied a specific breast gel for three months. The severity of the pain was measured through the Visual Analogue Score (VAS) in the treated group compared to untreated one. Treated patients also filled in a questionnaire evaluating acceptance and safety of the breast gel. RESULTS: This pilot clinical study demonstrated for the first time the efficacy of the topical application of a breast gel based on Betaine, Boswellia serrata, and myo-Inositol in improving cyclic mastodynia. The completed questionnaires also revealed high levels of acceptance, as both safety and compliance. CONCLUSIONS: Besides confirming the positive effects of these natural molecules in the management of conditions affecting breast physiology - so far evaluated as oral supplementation - the obtained results pave the way for further studies supporting the use of such molecules as a tailored medical device in the management of breast pain, thus also opening toward a combined oral and topical approach.

Increased risk of cognitive impairment in cirrhotic patients with bacterial infections.

BACKGROUND & AIMS: A causal relationship between infection, systemic inflammation, and hepatic encephalopathy (HE) has been suggested in cirrhosis. No study, however, has specifically examined, in cirrhotic patients with infection, the complete pattern of clinical and subclinical cognitive alterations and its reversibility after resolution. Our investigation was aimed at describing the characteristics of cognitive impairment in hospitalized cirrhotic patients, in comparison with patients without liver disease, with and without infection. METHODS: One hundred and fifty cirrhotic patients were prospectively enrolled. Eighty-one patients without liver disease constituted the control group. Bacterial infections and sepsis were actively searched in all patients independently of their clinical evidence at entry. Neurological and psychometric assessment was performed at admission and in case of nosocomial infection. The patients were re-evaluated after the resolution of the infection and 3months later. RESULTS: Cognitive impairment (overt or subclinical) was recorded in 42% of cirrhotics without infection, in 79% with infection without SIRS and in 90% with sepsis. The impairment was only subclinical in controls and occurred only in patients with sepsis (42%). Multivariate analysis selected infection as the only independent predictor of cognitive impairment (OR 9.5; 95% CI 3.5-26.2; p=0.00001) in cirrhosis. The subclinical alterations detected by psychometric tests were also strongly related to the infectious episode and reversible after its resolution. CONCLUSIONS: Infections are associated with a worse cognitive impairment in cirrhotics compared to patients without liver disease. The search and treatment of infections are crucial to ameliorate both clinical and subclinical cognitive impairment of cirrhotic patients.

Depression, anxiety and alexithymia symptoms are major determinants of health related quality of life (HRQoL) in cirrhotic patients.

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.

Evidence of persistent cognitive impairment after resolution of overt hepatic encephalopathy.

BACKGROUND & AIMS: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: HE is not a fully reversible condition. Residual cognitive impairments should be evaluated by specific tests, based on patients' learning capacities.

A simplified psychometric evaluation for the diagnosis of minimal hepatic encephalopathy.

BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: A simplified PHES is as good as the PHES in diagnosing minimal HE and in predicting the occurrence of overt HE.

Improving the inhibitory control task to detect minimal hepatic encephalopathy.

BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Previous overt hepatic encephalopathy rather than minimal hepatic encephalopathy impairs health-related quality of life in cirrhotic patients.

BACKGROUND: 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. AIM: To investigate the relative impact of previous HE and minimal HE on HRQoL in a group of consecutively hospitalized cirrhotic patients. PATIENTS/METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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.

Natural history of patients with non cirrhotic portal hypertension: Comparison with patients with compensated cirrhosis.

BACKGROUND: The knowledge of natural history of patients with portal hypertension (PH) not due to cirrhosis is less well known than that of cirrhotic patients. AIM: To describe the clinical presentation and the outcomes of 89 patients with non-cirrhotic PH (25 with non-cirrhotic portal hypertension, INCPH, and 64 with chronic portal vein thrombosis, PVT) in comparison with 77 patients with Child A cirrhosis. METHODS: The patients were submitted to a standardized clinical, laboratory, ultrasonographic and endoscopic follow-up. Variceal progression, incidence of variceal bleeding, portal vein thrombosis, ascites and survival were recorded. RESULTS: At presentation, the prevalence of varices, variceal bleeding and ascites was similar in the 3 groups. During follow-up, the rate of progression to varices at risk of bleeding (p < 0.0001) and the incidence of first variceal bleeding (p = 0.02) were significantly higher in non-cirrhotic then in cirrhotic patients. A PVT developed in 32% of INCPH patients and in 18% of cirrhotics (p = 0.02). CONCLUSIONS: In the patients with non-cirrhotic PH variceal progression is more rapid and bleeding more frequent than in cirrhotics. Patients with INCPH are particularly prompt to develop PVT. This observational study suggests that the management of patients with non-cirrhotic PH should take into consideration the natural history of portal hypertension in these patients and cannot be simply derived by the observation of cirrhotic patients.

Office hysteroscopic-guided selective tubal chromopertubation: acceptability, feasibility and diagnostic accuracy of this new diagnostic non-invasive technique in infertile women.

The aim of this study was to evaluate accuracy, tolerability and side effects of office hysteroscopic-guided chromoperturbations in infertile women without anaesthesia. Forty-nine infertile women underwent the procedure to evaluate tubal patency and the uterine cavity. Women with unilateral or bilateral tubal stenosis at hysteroscopy with chromoperturbation, and women with bilateral tubal patency who did not conceive during the period of six months, underwent laparoscopy with chromoperturbation. The results obtained from hysteroscopy and laparoscopy in the assessment of tubal patency were compared. Sensitivity, specificity, accuracy, positive-predictive value and negative-predictive value were used to describe diagnostic performance. Pain and tolerance were assessed during procedure using a visual analogue scale (VAS). Side effects or late complications and pregnancy rate were also recorded three and six months after the procedure. The specificity was 87.8% (95% CI: 73.80-95.90), sensitivity was 85.7% (95% CI 57.20-98.20), positive and negative predictive values were 70.6% (95% CI: 44.00-89) and 94.7% (95% CI: 82.30-99.40), respectively. Pregnancy rate (PR) within six months after performance of hysteroscopy with chromoperturbation was 27%. Office hysteroscopy-guided selective chromoperturbation in infertile patients is a valid technique to evaluate tubal patency and uterine cavity.

Hepatic encephalopathy in patients with non-cirrhotic portal hypertension: Description, prevalence and risk factors.

BACKGROUND: Hepatic encephalopathy (HE) is a common complication of cirrhosis but it is less studied in patients with non-cirrhotic portal hypertension (NCPH). AIMS: To describe the prevalence of cognitive impairment (overt and covert HE) in NCPH patients and to identify the risk factors for its development. METHODS: 51 patients with NCPH, 35 with chronic portal vein thrombosis (PVT) and 16 with idiopathic non-cirrhotic portal hypertension (INCPH), were evaluated for the presence of previous or present overt HE (OHE). The psychometric hepatic encephalopathy score and the SCAN battery were used to detect the presence of covert HE (CHE). 34 compensated cirrhotic patients were used as control. In NCPH patients, abdominal scans were performed to detect the presence of shunts. RESULTS: None of the patients experienced OHE at evaluation while 5.7% of PVT and 12.5% of INCPH patients referred at least one documented episode of previous OHE, similarly to patients with cirrhosis (14.7%). Even if lower than in patients with cirrhosis (64.7%), a considerable proportion of patients with chronic PVT (34.3%) and INCPH (25%) had CHE (p=0.008). The presence of a large portal-systemic shunt was the only factor significantly correlated to cognitive impairment in NCPH patients. CONCLUSION: HE is a tangible complication of NCPH and is mainly related to the presence of portal-systemic shunts.