Idiopathic noncirrhotic portal hypertension: current perspectives

Oliviero Riggio,1 Stefania Gioia,1 Ilaria Pentassuglio,1 Valeria Nicoletti,1 Michele Valente,2 Giulia d’Amati2 1Department of Clinical Medicine, Center for the Diagnosis and Treatment of Portal Hypertension, 2Department of Radiological, Oncological, and Pathological Sciences, Sapienza University of Rome, Rome, Italy Abstract: The term idiopathic noncirrhotic portal hypertension (INCPH) has been recently proposed to replace terms, such as hepatoportal sclerosis, idiopathic portal hypertension, incomplete septal cirrhosis, and nodular regenerative hyperplasia, used to describe patients with a hepatic presinusoidal cause of portal hypertension of unknown etiology, characterized by features of portal hypertension (esophageal varices, nonmalignant ascites, porto-venous collaterals), splenomegaly, patent portal, and hepatic veins and no clinical and histological signs of cirrhosis. Physicians should learn to look for this condition in a number of clinical settings, including cryptogenic cirrhosis, a disease known to be associated with INCPH, drug administration, and even chronic alterations in liver function tests. Once INCPH is clinically suspected, liver histology becomes mandatory for the correct diagnosis. However, pathologists should be familiar with the histological features of INCPH, especially in cases in which histology is not only requested to exclude liver cirrhosis. Keywords: idiopathic portal hypertension, obliterative portal venopathy, esophageal varices, splenomegal

Idiopathic noncirrhotic portal hypertension: current perspectives

Oliviero Riggio,1 Stefania Gioia,1 Ilaria Pentassuglio,1 Valeria Nicoletti,1 Michele Valente,2 Giulia d’Amati2 1Department of Clinical Medicine, Center for the Diagnosis and Treatment of Portal Hypertension, 2Department of Radiological, Oncological, and Pathological Sciences, Sapienza University of Rome, Rome, Italy Abstract: The term idiopathic noncirrhotic portal hypertension (INCPH) has been recently proposed to replace terms, such as hepatoportal sclerosis, idiopathic portal hypertension, incomplete septal cirrhosis, and nodular regenerative hyperplasia, used to describe patients with a hepatic presinusoidal cause of portal hypertension of unknown etiology, characterized by features of portal hypertension (esophageal varices, nonmalignant ascites, porto-venous collaterals), splenomegaly, patent portal, and hepatic veins and no clinical and histological signs of cirrhosis. Physicians should learn to look for this condition in a number of clinical settings, including cryptogenic cirrhosis, a disease known to be associated with INCPH, drug administration, and even chronic alterations in liver function tests. Once INCPH is clinically suspected, liver histology becomes mandatory for the correct diagnosis. However, pathologists should be familiar with the histological features of INCPH, especially in cases in which histology is not only requested to exclude liver cirrhosis. Keywords: idiopathic portal hypertension, obliterative portal venopathy, esophageal varices, splenomegal

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

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

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

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

Abstract 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

INHIBITORY CONTROL TASK: FOCUS ON THE DETECTION OF MINIMAL HEPATIC ENCEPHALOPATHY,

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 MH