Stefania Gioia

Sarcopenia Is Risk Factor for Development of Hepatic Encephalopathy After Transjugular Intrahepatic Portosystemic Shunt Placement

Background & Aims Hepatic encephalopathy (HE) is an important complication in patients with cirrhosis who received transjugular intrahepatic portosystemic shunts (TIPS). We investigated whether a decrease in muscle mass was associated independently with the occurrence of HE after TIPS. Methods We performed a prospective study of 46 consecutive patients with cirrhosis (mean age, 58.6 ± 9.1 y; mean model for end‐stage liver disease score, 11.3 ± 3.3; mean Child–Pugh score, 7.6 ± 1.5) who received TIPS from January 2013 through December 2014 at a tertiary center in Rome, Italy. All patients underwent computed tomography analysis at the level of the third lumbar vertebrae to determine the skeletal muscle index; sarcopenia was defined by sex‐specific cut‐off values. We estimated the incidence of the first episode of HE after TIPS, taking into account the competing risk nature of the data (death or liver transplantation). Results Twenty‐six patients (57%) were found to have sarcopenia. Twenty‐one patients (46%) developed overt HE in the 7 ± 9 months after TIPS placement; all of these patients were sarcopenic, according to the skeletal muscle index. Of the 25 patients without HE after TIPS, only 5 had sarcopenia. In multivariate analysis, model for end‐stage liver disease score (subdistribution hazard ratio, 1.16; 95% confidence interval, 1.01–1.34; P = .043) and sarcopenia (subdistribution hazard ratio, 31.3; 95% confidence interval, 4.5–218.07; P < .001) were associated independently with the development of HE after TIPS placement. Conclusions In a prospective study of 46 patients with cirrhosis, we found muscle wasting, probably owing to reduced processing of ammonia, to be associated with the development of HE after TIPS placement. Sarcopenia should be considered in selecting patients for TIPS therapy. Nutritional status should be evaluated in patients with sarcopenia before TIPS placement, which might reduce the incidence of 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.

Idiopathic noncirrhotic portal hypertension: current perspectives.

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.

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.

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.

How to Design a Multicenter Clinical Trial in Hepatic Encephalopathy

The design of clinical trials on Hepatic Encephalopathy (HE) is not an easy task, in fact there are several issues related to the performance of clinical trials in HE that have impeded progress in the field, mainly because most of the studies on HE therapy were performed before the era of rigorous Randomized Controlled Trials (RCTs). In this review we discuss the major problems affecting previously published trials on HE treatments aiming to provide evidences, suggestions and indications to prepare well designed RCTs in three different settings: (1) management of hospitalized patients with episodic HE; (2) secondary prophylaxis in patients following an episode of HE; and (3) management of minimal/covert HE.

Radiological intervention for shunt related encephalopathy

Hepatic Encephalopathy (HE) is a neuropsychiatric syndrome that occurs in up to 30% of patients with cirrhosis. HE may be a consequence of pure liver failure, as in patients with fulminant hepatitis, or of the combination of liver failure and portal-systemic shunting, as in patients with liver cirrhosis. Several clinical and pathophysiologic observations suggest the importance of portal-systemic shunts in the development of HE. Episodes of HE are usually related to precipitating events, such as infections or gastrointestinal bleeding; a minority of cirrhotic patients experienced a chronic HE, refractory to standard medical treatment. This latter type of HE should be related to spontaneous or radiological (such as Transjugular Intrahepatic Portosystemic Shunt (TIPS)) portal systemic shunts, that could be restricted or occluded in patients with chronic HE. Both TIPS reduction and shunt occlusion are radiological procedures, safe and effective to ameliorate neurological symptoms in patients with refractory HE.

Non cirrhotic portal hypertension secondary to oxaliplatin therapy: Incidence and presentation

Background: Recently, several studies have identified a possible relationship between the therapy with oxaliplatin and the development of non-cirrhotic portal hypertension. However, the incidence and the way of presentation of the disease in series of patients treated with oxaliplatin have not been yet described. The aim of the study is to search for the development of radiological signs of portal hypertension (PH) in a series of patients submitted to therapy with oxaliplatin.

Proton pump inhibitors are associated to minimal and overt hepatic encephalopathy and increase mortality in cirrhotics

Minimal hepatic encephalopathy (MHE) is a subclinical cognitive impairment frequently observable in patients with cirrhosis. Proton pump inhibitors (PPIs) can contribute to small‐bowel bacterial overgrowth, but no study has investigated the link between PPIs and MHE. We investigated the relationship between MHE and PPI use as well as the role of PPI use in the development of overt HE and survival. Consecutive patients with cirrhosis (n = 310) were included in the study and followed up for 14.1 ± 12.3 months. At entry, MHE was diagnosed when the Psychometric Hepatic Encephalopathy Score was ≤–4. Data were analyzed by logistic regression for the factors associated with MHE and by time‐related models for overt HE development and survival. At inclusion, 131 out of 310 patients with cirrhosis (42%) were affected by MHE. One hundred and twenty‐five patients (40%) were using PPIs. The variables independently associated with the presence of MHE were PPI use, previous overt HE, low albumin, low sodium, and age. During follow‐up, the development of overt HE was higher (64% versus 25%, P < 0.001) and overall survival lower (41% versus 81%, P < 0.001) in PPI users than in nonusers. Variables independently associated with the development of overt HE were PPIs, history of overt HE, low albumin, MHE, and age, while variables independently associated with mortality were PPIs, development of overt HE, Model for End‐Stage Liver Disease score, low sodium, and age. Conclusion: The study identifies a potentially removable factor associated with the presence of MHE and related to the development of overt HE and survival in patients with liver cirrhosis.

Management of Hepatic Encephalopathy Not Responsive to First-Line Treatments

Purpose of reviewHepatic encephalopathy (HE) is a neuropsychiatric syndrome that occurs in up to 30% of patients with cirrhosis. HE may be a consequence of pure liver failure, as in patients with fulminant hepatitis, or of the combination of liver failure and portal-systemic shunting, as in patients with liver cirrhosis. Episodes of HE are usually related to precipitating events, such as infections or gastrointestinal bleeding; a minority of cirrhotic patients experienced a chronic HE, refractory to standard medical treatment. The prevention of HE recurrence, after the first episode of HE, could be obtained by the administration of prophylactic therapy with lactulose, rifaximin or a combination of both.The aim of this review is to clarify some key points in the management of cirrhotic patients with HE, not responsive to first line treatment.Recent findingsRecent studies investigated the role of fecal microbiota transplantation in the treatment of HE with promising results, but further investigations are needed.SummaryIn a cirrhotic patient with acute cognitive impairment, the correct diagnosis of HE, after excluding other causes of neurological diseases, is mandatory for the correct management of the precipitating factors and for the treatment. In patients not responsive to standard treatment, the probable precipitating factors have not been correctly identified, multiple precipitating events are coexisting or a new precipitating event is superimposed.In some patients with recurrent HE, characterized by persistent alterations in neurological symptoms, without specific precipitants events, the presence of spontaneous or iatrogenic shunts should be investigated.