Altered brain iron deposition in patients with minimal hepatic encephalopathy: an MRI quantitative susceptibility mapping study.

AIM: To explore the use of quantitative susceptibility mapping (QSM) in assessing changes in brain iron deposits and their association with cognitive function in patients with minimal hepatic encephalopathy (MHE). MATERIALS AND METHODS: The study cohort comprised 27 cases with hepatitis B-associated cirrhosis with MHE (MHE group), 25 with hepatitis B-associated cirrhosis without MHE (NMHE group), and 25 healthy controls (HC group). Iron deposits in the bilateral frontal white matter, caudate nucleus (CN), putamen, globus pallidus, thalamus, red nucleus, substantia nigra (SN), hippocampus, and dentate nucleus were measured by QSM. The associations between iron deposition with the time taken to complete number connection tests A (NCT-A) and the score on digital-symbol test (DST) were analysed. RESULTS: Susceptibility values differed significantly in the bilateral CN, left thalamus, right SN, and left hippocampus in the MHE group compared with the other groups and were positively associated with the times taken to complete the NCT-A in the bilateral CN, left thalamus, and right SN and negatively associated with DST scores in the bilateral CN, left TH, and left HP. CONCLUSION: Reduced cognitive function in MHE patients was significantly associated with abnormally increased iron deposition in certain brain areas. The quantification of brain iron deposition by QSM may thus be an objective and accurate means of evaluating MHE.

Intrahepatic Portosystemic Shunt via the Right Adrenal Vein in an Asymptomatic Cirrhotic Patient.

PURPOSE: Intrahepatic Portosystemic Shunts (PSSs) draining to the Inferior Vena Cava (IVC) via the right adrenal vein has been reported as very rare, and all the patients who have been recorded have had hepatic encephalopathy. Here, we present a patient with intrahepatic PSS via the right adrenal vein diagnosed incidentally without encephalopathy. CASE PRESENTATION: A 51-year-old patient, who was diagnosed with chronic liver parenchyma disease and a suspecting nodule on the ultrasound was examined by Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). A 4 cm in diameter Hepatocellular Carcinoma (HCC) was detected. In addition to HCC, an abnormal shunt between the right posterior portal vein and the IVC via the right adrenal vein was also detected. RESULTS: To the best of our knowledge, this is the first case with intrahepatic PSS via the right adrenal vein diagnosed incidentally in the absence of encephalopathy and the fourth case with this abnormal shunt in English literature. CONCLUSION: Intrahepatic PSS via the right adrenal vein is rare. It may be asymptomatic at the time of diagnosis but has the potential to cause various problems, later on, especially hepatic encephalopathy. The radiologist must be aware of this abnormal shunt.

The independent risk factors for abnormal head computed tomography in patients with hepatic encephalopathy.

It's known that head computed tomography (CT) is used excessively to exclude intracranial hemorrhage in patients with hepatic encephalopathy (HE) in the emergency department. However, the independent risk factors for abnormal head CT in patients with HE have not been studied extensively to date. In this retrospective study, patients with an ammonia level of >90 U/L who were clinically considered HE and had head CT were included. The characteristics of patients with abnormal head CT and independent risk factors for abnormal CT were investigated. Three hundred seventy-eight patients were included in the study. CT findings of 18 (4.8%) of the patients were abnormal: 12 had intracranial hemorrhage, 1 had an ischemic stroke, and 5 had an intracranial mass. Intracranial hemorrhage (odds ratio [OR] 12.5), history of recent trauma (OR 23.4), history of active malignancy (OR 10.3), thrombocyte count <100.000/µL (OR 4.3), and international normalized ratio ≥1.5 (OR 3.2) were found to be independent risk factors for abnormal head CT. Head CT scan may be considered in patients with HE if any of the following are present: intracranial bleeding history, recent trauma history, active malignancy, platelet count <100,000/µL, and international normalized ratio >1.5.

Neuromarkers from Whole-Brain Functional Connectivity Reveal the Cognitive Recovery Scheme for Overt Hepatic Encephalopathy after Liver Transplantation.

Neurocognitive impairment is present in cirrhosis and may be more severe in cirrhosis with overt hepatic encephalopathy (OHE). Liver transplantation (LT) can restore liver function, but how it reverses the impaired brain function is still unclear. MRI of resting-state functional connectivity can help reveal the underlying mechanisms that lead to these cognitive deficits and cognitive recovery. In this study, 64 patients with cirrhosis (28 with OHE; 36 without OHE) and 32 healthy control subjects were recruited for resting-state fMRI. The patients were scanned before and after LT. We evaluated presurgical and postsurgical neurocognitive performance in cirrhosis patients using psychomotor tests. Network-based statistics found significant disrupted connectivity in both groups of cirrhotic patients, with OHE and without OHE, compared with control subjects. However, the presurgical connectivity disruption in patients with OHE affected a greater number of connections than those without OHE. The decrease in functional connectivity for both OHE and non-OHE patient groups was reversed after LT to the level of control subjects. An additional hyperconnected network (i.e., higher connected than control subjects) was observed in OHE patients after LT. Regarding the neural-behavior relationship, the functional network that predicted cognitive performance in healthy individuals showed no correlation in presurgical cirrhotic patients. The impaired neural-behavior relationship was re-established after LT for non-OHE patients, but not for OHE patients. OHE patients displayed abnormal hyperconnectivity and a persistently impaired neural-behavior relationship after LT. Our results suggest that patients with OHE may undergo a different trajectory of postsurgical neurofunctional recovery compared with those without, which needs further clarification in future studies.

A radiomics model of liver CT to predict risk of hepatic encephalopathy secondary to hepatitis B related cirrhosis.

PURPOSE: To build a radiomics model of liver contrast-enhanced computed tomography (CT) to predict hepatic encephalopathy secondary to Hepatitis B related cirrhosis. MATERIALS AND METHODS: This study consisted of 304 consecutive patients with first-diagnosed hepatitis B related cirrhosis. 212 and 92 patients were randomly computer-generated into training and testing cohorts, among which 38 and 21 patients endured HE, respectively. 356 radiomics features of liver were extracted from portal venous-phase CT data, and 3 clinical features were collected from medical record. After data were standardized by Z-score, we used least absolute shrinkage and selection operator to choose useful radiomics features. Ultimately, three predictive models including a radiomics model, a clinical model and an integrated model of radiomics and clinical features were built by analysis of R-software. Predictive performance was tested by multivariable logistic regression, and evaluated by area under receiver-operating characteristic curve (AUC), and accuracy. RESULTS: 19 radiomics features of liver CT were selected. The selected radiomics features and 3 relevant clinical features were applied to develop a radiomics model, a clinical model, and an integrated model of both radiomics and clinical features. The integrated model showed better performance than the radiomics model or clinical model to predict HE (AUC = 0.94 vs. 0.91 or 0.76, and 0.87 vs. 0.86 or 0.73; accuracy = 0.93 vs. 0.89 or 0.83, and 0.83 vs. 0.84 or 0.77) in the training and testing cohorts, respectively. CONCLUSION: The integrated model of radiomics and clinical features could well predict HE secondary to hepatitis B related cirrhosis.

Hepatic encephalopathy: a rare cause of focal seizures in chronic liver disease.

Hepatic encephalopathy (HE) is an extremely rare cause of focal seizures and is usually a diagnosis of exclusion when more commoner causes such as infection, autoimmune and malignancy have been discounted. The literature reports patients with generalised cerebral oedema and rarely status epilepticus, but these are often in the context of acute liver failure as opposed to chronic liver disease. Here we discuss a case of HE leading to focal neurological deficits and seizures in a 48-year-old woman with a background of chronic alcoholic liver disease. MRI scan showed extensive left-sided tempo-parietal-occipital cortical oedema and electroencephalogram showed widespread moderate HE with runs of epileptiform discharges. The treatment involves antiepileptic therapy as well as standard management of HE with laxatives, rifaximin and optimisation of nutrition.

Altered cognitive control network is related to psychometric and biochemical profiles in covert hepatic encephalopathy.

The cognitive control network (CCN) is a network responsible for multiple executive functions, which are impaired in covert hepatic encephalopathy (CHE). We aimed to use functional connectivity (FC) magnetic resonance imaging to test the hypothesis that CHE manifested with disconnection within the CCN, which is associated with impaired neuropsychiatric and biochemical profiles. CHE was detected with abnormally low psychometric hepatic encephalopathy scores (PHES) (total cut-off score <-4). Two seeds in the dorsal anterior cingulate cortex (dACC) and the dorsolateral prefrontal cortex (DLPFC) were used to calculate the FC map within the CCN. Pearson correlation analysis was performed between the CCN and psychometric, biochemical profiles including ammonia, Interleukin (IL)-6, and tumor necrosis factor (TNF)-α. Eighteen CHE, 36 non-HE (NHE) cirrhotic patients and 36 controls were studied. Significant differences in FC were noted among groups, which revealed CHE patients had a lower FC in the bilateral lateral occipital cortex (seed in the bilateral dACC) and in the right lateral occipital and precuneus cortices (seed in the left DLPFC) (P < 0.05, corrected) compared with NHE. Progressively decreased FC in the left precentral gyrus within the CCN was noted from control, NHE to CHE. PHES positively and biochemistry negatively correlated with FC in the CCN. In conclusion, CHE patients showed aberrant FC within the CCN which is correlated with both cognitive dysfunction and biochemical profiles. Ammonia and pro-inflammatory cytokines may contribute to the occurrence of aberrant connectivity. Impaired FC within the CCN may serve as a complementary biomarker for CHE.

Detection of Hepatic Encephalopathy on 18F-FDG PET/CT Brain Images in a Patient With Decompensated Liver Cirrhosis.

We present a case of decompensated liver cirrhosis with ascites, which had history of asterixis, impaired balance with swaying gait along with mild irritability since 1 month. F-fluorodeoxyglucose PET/CT (FDG-PET/CT) performed to rule out malignancy did not reveal any abnormal FDG avid lesion suspicious for malignancy but showed hypermetabolism in the bilateral basal ganglia and thalamus with reduced metabolism in cerebral cortices and cerebellum, suggesting hepatic encephalopathy.

A Head CT is Unnecessary in the Initial Evaluation of A Cirrhotic Patient with Recurrent Hepatic Encephalopathy.

INTRODUCTION AND AIM: The evaluation to determine the cause of hepatic encephalopathy consists primarily of laboratory testing to rule out infections and metabolic causes. Despite lack of evidence, it is a common practice amongst clinicians to obtain a head CT as part of their initial evaluation in a cirrhotic presenting with recurrent episodes of hepatic encephalopathy. MATERIAL AND METHODS: Medical records of all cirrhotic adults admitted to a tertiary care hospital from 2007 to 2010 with hepatic encephalopathy were reviewed. RESULTS: In 67 patients, there were 147 episodes of hepatic encephalopathy where a head CT was performed. Six CTs had intracranial findings explaining hepatic encephalopathy. Two patients had focal neurologic findings on physical exam with no history of trauma, one had a history of trauma with no focal neurologic deficits and two had both a history of trauma and focal neurologic findings. Only one case revealed an intracranial hemorrhage with neither a preceding history of trauma nor positive neurological signs. The overall prevalence of intracranial findings in hepatic encephalopathy was 4% (6/147) and 0.6% (1/142) in the absence of trauma or focal neurologic findings. Laboratory and clinical variables including mean levels of ammonia, sodium, creatinine, bilirubin, albumin, platelet count, INR, encephalopathy grade and MELD score did not have a statistically significant impact on head CT findings (P > .05). CONCLUSION: In conclusion, the yield of a head CT in determining the cause of change in mental status is extremely low in patients with cirrhosis who present with recurrent hepatic encephalopathy.

Hepatic encephalopathy secondary to a splenorenal shunt that manifested a long time after a liver transplantation.

Splenorenal shunts are a rare cause of hyperammonemia and hepatic encephalopathy in the absence of cirrhosis. We report the case of a woman, who presented hepatic encephalopathy, with a normal functioning graft, after 14 years of liver transplantation, confirmed by liver biopsy.

The genotypic and phenotypic spectrum of MTO1 deficiency.

BACKGROUND: Mitochondrial diseases, a group of multi-systemic disorders often characterized by tissue-specific phenotypes, are usually progressive and fatal disorders resulting from defects in oxidative phosphorylation. MTO1 (Mitochondrial tRNA Translation Optimization 1), an evolutionarily conserved protein expressed in high-energy demand tissues has been linked to human early-onset combined oxidative phosphorylation deficiency associated with hypertrophic cardiomyopathy, often referred to as combined oxidative phosphorylation deficiency-10 (COXPD10). MATERIAL AND METHODS: Thirty five cases of MTO1 deficiency were identified and reviewed through international collaboration. The cases of two female siblings, who presented at 1 and 2years of life with seizures, global developmental delay, hypotonia, elevated lactate and complex I and IV deficiency on muscle biopsy but without cardiomyopathy, are presented in detail. RESULTS: For the description of phenotypic features, the denominator varies as the literature was insufficient to allow for complete ascertainment of all data for the 35 cases. An extensive review of all known MTO1 deficiency cases revealed the most common features at presentation to be lactic acidosis (LA) (21/34; 62% cases) and hypertrophic cardiomyopathy (15/34; 44% cases). Eventually lactic acidosis and hypertrophic cardiomyopathy are described in 35/35 (100%) and 27/34 (79%) of patients with MTO1 deficiency, respectively; with global developmental delay/intellectual disability present in 28/29 (97%), feeding difficulties in 17/35 (49%), failure to thrive in 12/35 (34%), seizures in 12/35 (34%), optic atrophy in 11/21 (52%) and ataxia in 7/34 (21%). There are 19 different pathogenic MTO1 variants identified in these 35 cases: one splice-site, 3 frameshift and 15 missense variants. None have bi-allelic variants that completely inactivate MTO1; however, patients where one variant is truncating (i.e. frameshift) while the second one is a missense appear to have a more severe, even fatal, phenotype. These data suggest that complete loss of MTO1 is not viable. A ketogenic diet may have exerted a favourable effect on seizures in 2/5 patients. CONCLUSION: MTO1 deficiency is lethal in some but not all cases, and a genotype-phenotype relation is suggested. Aside from lactic acidosis and cardiomyopathy, developmental delay and other phenotypic features affecting multiple organ systems are often present in these patients, suggesting a broader spectrum than hitherto reported. The diagnosis should be suspected on clinical features and the presence of markers of mitochondrial dysfunction in body fluids, especially low residual complex I, III and IV activity in muscle. Molecular confirmation is required and targeted genomic testing may be the most efficient approach. Although subjective clinical improvement was observed in a small number of patients on therapies such as ketogenic diet and dichloroacetate, no evidence-based effective therapy exists.

Osmotic Demyelination Unrelated to Hyponatremia.

Osmotic demyelination unrelated to hyponatremia is rarely reported. We present a case of osmotic demyelination in a patient with hypernatremia in the absence of preceding hyponatremia and review previously reported cases of osmotic demyelination in nonhyponatremic patients. We conclude that a rapid increase in serum sodium concentration and plasma tonicity even in the absence of preceding hyponatremia may surpass the brain's capacity for adaptation to hypertonicity and lead to osmotic demyelination in predisposed individuals. Risk factors for osmotic demyelination in patients with chronic hyponatremia and without hyponatremia are probably similar and are usually associated with states of limited brain osmolyte response, such as alcoholism, liver disease (including those undergoing orthotopic liver transplantation), malnutrition, malignancy, pregnancy/postpartum state, severe illness/sepsis, adrenal insufficiency, and metabolic derangements. Clinicians should be vigilant in identifying individuals who may, even in the absence of hyponatremia, have increased susceptibility to osmotic demyelination and avoid rapid fluctuations in serum sodium concentrations in such patients.

Recurrent hyperammonemic encephalopathy. Embolization of the portosystemic shunt.

We present the case of a recurrent hyperammonaemic encephalopathy due to a portosystemic shunt that was successfully treated by embolization.

Portal systemic shunt between the hepatic portal vein and right renal vein in a patient with multifocal hepatocellular carcinoma: Case report.

Portal hypertension is a clinical syndrome characterized by the development of collateral circulation and portosystemic shunts, as well as ascites and hepatic encephalopathy. We present the case of a large portosystemic shunt between the hepatic portal vein and aneurysmal right renal vein in a cirrhotic 64-year-old man with thrombosis of the portal vein and hepatocellular carcinoma. This is a very rare clinical manifestation which, to our knowledge, has been described only once previously in the literature. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 45:524-527, 2017.

Hybrid Surgery for Portosystemic Encephalopathy in a Patient with Liver Cirrhosis: a case report.

Regarding the treatment for a portosystemic shunt, surgical or interventional radiological closure of the shunt was established. Interventional radiology including balloon-occluded retrograde transvenous obliteration can worsen portal hypertension and create a large thrombus close to the major venous system in the case of a huge portosystemic shunt. In contrast, it is also difficult to treat some cases through surgery alone when huge complicated shunts exist very deep in the body. Herein, we report a successful case of surgical shunt ligation for portosystemic encephalopathy in a hybrid operation room that enabled intraoperative angiography and computed tomography. A 62-year-old woman with chronic hepatitis C was referred to our hospital due to high levels of serum ammonia and hepatic encephalopathy. She had a massive, complicated portosystemic shunt from the inferior mesenteric vein to the left renal vein but did not have esophageal or gastric varices. It was difficult to occlude the portosystemic shunt by interventional radiologic techniques because the shunt had an extremely large amount of blood flow and many collateral routes. We performed the shunt ligation in the hybrid operation room. Intraoperative angiography provided detailed information about the portosystemic shunt, such as direction or volume of blood flow and collateral routes in real time. Her encephalopathy disappeared completely and she remains healthy with improved liver functional reserve to date. In conclusion, this is a successful case of a hybrid operation for an extremely large and complicated portosystemic shunt, providing for intraoperative angiography as a safe and reliable surgical treatment for portosystemic encephalopathy in patients with liver cirrhosis.

Who Orders a Head CT?: Perceptions of the Cirrhotic Bleeding Risk in an International, Multispecialty Survey Study.

OBJECTIVE: Traditional coagulopathic indices, including elevated international normalized ratio, do not correlate with bleeding risk in patients with cirrhosis. For this reason, head computed tomography (CT) has a low yield in cirrhotic patients with altered mental status and no trauma history. The initial diagnostic evaluation, however, is often made by nongastroenterologists influenced by the so-called "coagulopathy of cirrhosis." We sought to examine the prevalence, impact, and malleability of this perception in an international, multispecialty cohort. DESIGN: An electronic survey was distributed to internal medicine, surgery, emergency medicine, and gastroenterology physicians. Respondents were presented with a cirrhotic patient with hepatic encephalopathy, no history of trauma, and a nonfocal neurological examination. Respondents rated likelihood to order head CT at presentation, after obtaining labs [international normalized ratio (INR) 2.4 and platelets 59×10/µL], and finally after reading the results of a study demonstrating the low yield of head CT in this setting. RESULTS: In total, 1286 physicians from 6 countries, 84% from the United States. Of these, 62% were from internal medicine, 25% from emergency medicine, 8% from gastroenterology, and 5% from surgery. Totally, 47% of respondents were attending physicians. At each timepoint, emergency physicians were more likely, and gastroenterologists less likely, to scan than all other specialties (P<0.0001). Evidence on the low yield of head CT reduced likelihood to scan for all specialties. Qualitative analysis of open-ended comments confirmed that concern for "coagulopathy of cirrhosis" motivated CT orders. CONCLUSIONS: Perceptions regarding the coagulopathy of cirrhosis, which vary across specialties, impact clinical decision-making. Exposure to clinical evidence has the potential to change practice patterns.

Long-term clinical and radiological improvement of chronic acquired hepatocerebral degeneration after obliteration of portosystemic shunt: Report of a case.

Neurological manifestations are common in patients with decompensated cirrhosis. The majority of these patients show hepatic encephalopathy or chronic acquired (non-Wilsonian) hepatocerebral degeneration (CAHD). They characteristically present with dysarthria, ataxia, involuntary movements, and altered mental status. Neuroradiological examination in patients with hepatic encephalopathy often shows abnormal signals in multiple regions of the brain, such as the pallidum, putamen, caudate nucleus, hemispheric white matter, and ventral midbrain. The pathogenesis of hepatic encephalopathy and CAHD is poorly understood and the response to conventional therapies is often poor. We report a male patient with cirrhosis of unknown cause, who developed slowly progressive cerebellar truncal and limb ataxia and slurred speech. Magnetic resonance imaging (MRI) showed focal T2 hyperintensity in bilateral dentate nuclei and middle cerebellar peduncles (MCPs). After treatment by obliteration of the portosystemic shunt, clinical manifestations and MRI abnormalities were dramatically improved. He was followed for six years until he died of uncontrollable bleeding due to hepatocellular carcinoma. At the last examination 9 months before death, he showed no apparent aggravation of neurological symptoms, and no abnormal signal intensities in the MCPs and supratentorial compartment. The clinical course and changes of brain MRI findings of this case are extremely rare, suggesting that obliteration of the portosystemic shunt may be effective for CAHD over long term.

Simultaneous combined balloon-occluded retrograde transvenous obliteration and partial splenic embolization for portosystemic shunts.

PURPOSE: To evaluate the efficacy and safety of simultaneous combined balloon-occluded retrograde transvenous obliteration (B-RTO) and partial splenic embolization (PSE) for gastric varices and/or hepatic encephalopathy. MATERIALS AND METHODS: B-RTO was performed in 19 consecutive patients with gastric varices and/or hepatic encephalopathy, of whom 10 received simultaneous combined B-RTO and PSE (group 1) and nine received B-RTO monotherapy (group 2). To evaluate the safety of these techniques, we analyzed 20 patients who received PSE monotherapy during the same period as a control group (group 3). Outcomes were retrospectively assessed. RESULTS: No significant differences were observed in baseline characteristics among the three groups except for significantly lower platelet counts and larger spleen volumes in group 3. In all cases in groups 1 and 2, gastric varices disappeared and hepatic encephalopathy improved after treatment. Procedure times were not significantly different between groups 1 and 2 (P = .7435). In group 1, the volume of sclerosing agent required for B-RTO was significantly lower (P = .0355) and exacerbation of esophageal varices was significantly less frequent (P = .0146) than in group 2. Few serious complications occurred in patients who received combined therapy. CONCLUSIONS: This study indicates that concomitant PSE may help diminish the increase in portal venous pressure after B-RTO for portosystemic shunts, and may allow a reduction in the volume of hazardous sclerosing agent used. It is worth evaluating the efficacy of simultaneous B-RTO and PSE in a prospective study.