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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. 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). 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. 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.

The Multimatrix® (MMX®) preparation MMX® is a recently obtained drug formulation developed to facilitate release of high concentrations of active drugs into the colon, with a homogeneous distribution along all colonic segments, particularly the most distal ones; the distal colonic tracts, indeed, are the most difficult to reach in significant amounts when a drug is given orally. The MMX® formulation is characterized by a lipophilic matrix dispersed in a hydrophilic structure. Indeed, in the last few years, MMX® technology has been widely used in the development of various drugs for the treatment of inflammatory and infectious gastrointestinal diseases localized in the colon. In particular, MMX® mesalamine, budesonide and parnaparin formulations have been investigated in patients with ulcerative colitis, and the first two have reached worldwide registration for the treatment of this disease. Moreover, MMX®-rifamycin is being positively tested in the treatment of colonic bacterial infections, including traveler’s diarrhea. MMX® technology is, thus, proving to be a very effective formulation for the treatment of various colonic diseases. This effectiveness has been related not only to specific colonic delivery, but also to its ability to act in a once-daily dosage, thus favouring patients’ adherence to prescribed schedules of treatment. The effective delivery of the active molecule to the site of need in the colon is also associated with very low systemic absorption and very low rates of adverse events (AEs). In this paper, we have reviewed all clinical trials performed with an MMX®-bound drug and all possible real-life reports, in order to give an overall evaluation of MMX®.

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.

In Europe, transjugular intrahepatic portosystemic shunt (TIPS) is considered the primary treatment for gastric varix (GV) bleeding to reduce portal hypertension. However, in Asian countries, balloon-occluded retrograde transvenous obliteration (BRTO) and its variants plug/coil assisted transvenous retrograde obliteration (PARTO/CARTO) are the preferred approaches. The purpose of this study is to report a European single-center experience in the use of PARTO/CARTO techniques for the treatment of GVs in patients with portal hypertension, focusing on the effectiveness and safety of the procedure. All the procedures involving the PARTO/CARTO techniques performed from 2019 to 2023 were retrospectively evaluated. Technical success was defined as the complete obliteration of both the GVs and the gastro-renal (GR) shunt on review of the Computed Tomography (CT) scan performed 3 days after the procedure. The obliteration rate was also evaluated through performing CT scans 1 and 12 months after the procedure, and through endoscopic follow-up at 3 and 6 months. Additionally, major and minor complications were reported. The study involved seven patients, with a technical success of 100%. During follow-up, there were no episodes of variceal rebleeding or upper gastrointestinal bleeding. Two patients developed ascites, which resolved with medical therapy. One patient exhibited focal portal thrombosis, which was successfully treated with heparin. PARTO/CARTO techniques demonstrated high technical and clinical success rates, offering advantages over traditional BRTO. The use of coils and plugs simplifies the procedure, eliminates sclerosing agents, and prevents complications associated with balloon guiding catheters.

Hepatic encephalopathy (HE) affects the survival and quality of life of patients with cirrhosis. However, longitudinal data on the clinical course after hospitalization for HE are lacking. The aim was to estimate mortality and risk for hospital readmission of cirrhotic patients hospitalized for HE. We prospectively enrolled 112 consecutive cirrhotic patients hospitalized for HE (HE group) at 25 Italian referral centers. A cohort of 256 patients hospitalized for decompensated cirrhosis without HE served as controls (no HE group). After hospitalization for HE, patients were followed-up for 12 months until death or liver transplant (LT). During follow-up, 34 patients (30.4%) died and 15 patients (13.4%) underwent LT in the HE group, while 60 patients (23.4%) died and 50 patients (19.5%) underwent LT in the no HE group. In the whole cohort, age (HR 1.03, 95% CI 1.01-1.06), HE (HR 1.67, 95% CI 1.08-2.56), ascites (HR 2.56, 95% CI 1.55-4.23), and sodium levels (HR 0.94, 95% CI 0.90-0.99) were significant risk factors for mortality. In the HE group, ascites (HR 5.07, 95% CI 1.39-18.49) and BMI (HR 0.86, 95% CI 0.75-0.98) were risk factors for mortality, and HE recurrence was the first cause of hospital readmission. In patients hospitalized for decompensated cirrhosis, HE is an independent risk factor for mortality and the most common cause of hospital readmission compared with other decompensation events. Patients hospitalized for HE should be evaluated as candidates for LT.

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. 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. 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. In this trial, long-term HA administration prolongs overall survival and might act as a disease modifying treatment in patients with decompensated cirrhosis. Italian Medicine Agency.

Transjugular intrahepatic portosystemic shunt (TIPS) has been used since more than 25 years to treat some of the complications of portal hypertension, especially variceal bleeding and ascites refractory to conventional therapy. TIPS establishes a communication between the portal and hepatic veins, inducing the blood to shift from the splanchnic circulation into the systemic vascular bed with the aim of decompressing the portal venous system, and avoids the major complications of portal hypertension. However, the shunt of the portal blood into the systemic circulation is the cause of one of the major complications of the procedure: the post-TIPS hepatic encephalopathy (HE). To date, few pharmacological treatment has been proven effective to prevent this complication and thus, the identification of patients at high risk of post-TIPS hepatic encephalopathy and the patients’ carefully selection is the only way to prevent this frequent complication.

Minimal hepatic encephalopathy (MHE) is a frequent complication of hepatic encephalopathy (HE) and can affect up to 80% of patients with liver cirrhosis. It is characterized by the lack of obvious clinical signs and the presence of alterations detectable using psychometric or electrophysiological testing focused on attention, working memory, psychomotor speed and visuospatial ability. Ideally, each patient should be tested for this condition because, despite the absence of symptoms, it has severe repercussions on daily life activities. It may be responsible for an inability to drive, sleep disturbances, risk of falls and inability to work. Some studies have highlighted its prognostically unfavorable role on mortality and risk of “overt” HE (OHE). Finally, MHE severely affects the lives of patients and caregivers, altering their quality of life and their socioeconomic status. Several treatments have been proposed for MHE treatment, including non-absorbable disaccharides, poorly absorbable antibiotics, such as rifaximin, probiotics and branched-chain amino acids, with promising results. For this reason, early diagnosis and intervention with appropriate measures is essential, with the aim of improving both performance on psychometric tests, as well as clinical aspects related to this condition.

Purpose of the Review Non-cirrhotic portal hypertension (NCPH) includes a heterogeneous group of conditions. The aim of this paper is to make an overview on the denominations, diagnostical features and management of porto-sinusoidal vascular disease (PSVD) and chronic portal vein thrombosis (PVT) being the main causes of NCPH in the Western world. Recent Findings The management of NCPH consists in the treatment of associated diseases and of portal hypertension (PH). PH due to PSVD or PVT is managed similarly to PH due to cirrhosis. TIPS placement and liver transplantation are considerable options in patients with refractory variceal bleeding/ascites and with progressive liver failure. Anticoagulation is a cornerstone both in the treatment of thrombosis in PSVD and in the prevention of thrombosis recurrence in patients with portal cavernoma. Summary Physicians should be aware of the existence of PSVD and chronic PVT and actively search them in particular settings. To now, the management of portal hypertension-related complications in NCPH is the same of those of cirrhosis. Large cooperative studies on the natural history of NCPH are necessary to better define its management.

The prevalence of minimal hepatic encephalopathy (MHE), in particular in different subgroups, remains unknown. This study aimed to analyze the prevalence of MHE in different subgroups to identify patients at high risk and to pave the way for personalized screening approaches. In this study, data of patients recruited at 10 centers across Europe and the United States were analyzed. Only patients without clinical signs of hepatic encephalopathy were included. MHE was detected using the Psychometric Hepatic Encephalopathy Score (PHES, cut-off < or ≤-4 depending on local norms). Clinical and demographic characteristics of the patients were assessed and analyzed. In total, 1,868 patients with cirrhosis with a median model for end-stage liver disease (MELD) of 11 were analyzed (Child-Pugh [CP] stages: A 46%, B 42%, and C 12%). In the total cohort, MHE was detected by PHES in 650 patients (35%). After excluding patients with a history of overt hepatic encephalopathy, the prevalence of MHE was 29%. In subgroup analyses, the prevalence of MHE in patients with CP A was low (25%), whereas it was high in CP B or C (42% and 52%). In patients with a MELD score <10, the prevalence of MHE was only 25%, but it was 48% in patients with a MELD score ≥20. Standardized ammonia levels (ammonia level/upper limit of normal of each center) correlated significantly, albeit weakly with PHES (Spearman ρ = -0.16, P < 0.001). The prevalence of MHE in patients with cirrhosis was high but varied substantially between diseases stages. These data may pave the way for more individualized MHE screening approaches.