Persistent Hepatic Encephalopathy Research Articles

Interventional embolisation for patients with cirrhosis and recurrent or persistent hepatic encephalopathy related to spontaneous portosystemic shunts: protocol for a prospective, non-randomised controlled study

IntroductionThe presence of spontaneous portosystemic shunts (SPSS) has been identified to be associated with hepatic encephalopathy (HE) in patients with cirrhosis. Nevertheless, the role of interventional embolisation in managing such...

Spleen transient elastography predicts actuarial survival after liver transplantation.

Splenic transient elastography (TE) correlates with increased portal pressure. Little data are available in the post liver transplantation (LTx) setting. Three months after LTx, we performed splenic TE in 125 LTx recipients. Mean splenic TE values were 29.4 (±6.3; range, 21.6-49.2) kPa. Splenic TE correlated with reduced time to development until persistent ascites (30 events, OR =1.082, 95% CI: 1.034-1.133; P=0.001), hepatorenal syndrome (8 events, OR =1.109, 95% CI: 1.015-1.211; P=0.022) and hepatic encephalopathy (16 events, OR =1.136, 95% CI: 1.066-1.211; P=0.000). In Cox univariate analysis, splenic TE served as a predictor of actuarial survival free of liver (OR =1.114, 95% CI: 1.050-1.182; P<0.001) and remained an independent risk factor associated with reduced actuarial survival free of LTx in multivariate analysis (OR =1.103, 95% CI: 1.026-1.186; P=0.008). Splenic TE measurement at 3 months after LTx serves as a robust predictor of survival in LTx recipients.

Role of circadian rhythm and autonomic nervous system in liver function: a hypothetical basis for improving the management of hepatic encephalopathy.

Hepatic encephalopathy (HE) is a common, incapacitating complication of cirrhosis that affects many patients with cirrhosis. Although several therapies have proven effective in the treatment and prevention of this condition, several patients continue to suffer from covert disease or episodes of relapse. The circadian rhythm has been demonstrated to be pivotal for many body functions, including those of the liver. Here, we explore the impact of circadian rhythm-dependent signaling on the liver and discuss the evidence of its impact on liver pathology and metabolism. We describe the various pathways through which circadian influences are mediated. Finally, we introduce a novel method for improving patient response to drugs aimed at treating HE by utilizing the circadian rhythm. A digital system that introduces a customization-based technique for improving the response to therapies is presented as a hypothetical approach for improving the effectiveness of current medications used for the treatment of recurrent and persistent hepatic encephalopathy.

Early, late, or no shunt embolization in patients with cirrhosis- and portosystemic shunt-related hepatic encephalopathy.

Portosystemic shunts (PSS) are associated with recurrent or persistent hepatic encephalopathy (HE), severe portal hypertensive (PHT) complications, and poor survival in cirrhosis patients. Shunt embolization improves HE in patients with recurrent or persistent HE. The role of early shunt embolization (ESE) in comparison with no and late SE (LSE) in cirrhosis patients with PSS and associated clinical outcomes are not studied. ESE was defined as occlusion of PSS in patients with the first episode of spontaneous HE, while LSE was that when performed in patients with recurrent/persistent PSS-related HE. We retrospectively analyzed (November 2016 to March 2019) clinical outcomes, liver disease severity, and survival between patients undergoing ESE (n = 22) vs. LSE (n = 23) and compared ESE with matched historical controls (n = 22) not undergoing shunt embolization, followed-up for 18months. Males predominated, and the lienorenal type of shunt was the most frequent. Significantly larger and multiple shunts were noted in the LSE group. Arterial ammonia, total bilirubin, and Child-Pugh scores were significantly higher at baseline in the LSE group. Post-procedure length of stay in the intensive unit (mean 0.6 vs. 2.1days; p = 0.04), infections (31.8% vs. 66.7% beyond 100days; p = 0.02), recurrence of HE in first 9months (4.5% vs. 28.6%; p = 0.03), and liver- and PHT-related clinical events beyond 10months were significantly higher in LSE compared with those in the ESE group respectively. HE beyond 10months was comparable between both the groups. 18.2% died in ESE while 60.87% died in the LSE group (p = 0.002). Compared with patients on only standard medical care, the occurrence of ascites, variceal bleeding, recurrence of HE, and portal vein thrombosis were significantly lower in those undergoing ESE, even though differences in survival were not significant. Our study demonstrates the benefits of ESE of large PSS in patients with cirrhosis, probably by improving survival through a reduction in liver and PHT events that warrant validation through prospective randomized controlled multicenter trials.

Spontaneous porto-systemic shunts in liver cirrhosis: Clinical and therapeutical aspects.

Spontaneous porto-systemic shunts (SPSS) are frequent in liver cirrhosis and their prevalence increases as liver function deteriorates, probably as a consequence of worsening portal hypertension, but without achieving an effective protection against cirrhosis' complications. Several types of SPSS have been described in the literature, each one associated with different clinical manifestations. In particular, recurrent or persistent hepatic encephalopathy is more frequent in patients with splenorenal shunt, while the presence of gastric varices and consequently the incidence of variceal bleeding is more common in gastrorenal shunt. In the advanced stage, the presence of large SPSS can lead to the so called “portosystemic shunt syndrome”, characterized by a progressive deterioration of hepatic function, hepatic encephalopathy and, sometimes, portal vein thrombosis. The detection of SPSS in patients with liver cirrhosis is recommended in order to prevent or treat recurrent hepatic encephalopathy or variceal bleeding.

Sustained viral response to direct acting antivirals in a decompensated HCV-related cirrhotic patient after both partial splenic embolization and percutaneous transhepatic obliteration for persistent hepatic encephalopathy

Sustained viral response to direct acting antivirals in a decompensated HCV-related cirrhotic patient after both partial splenic embolization and percutaneous transhepatic obliteration for persistent hepatic encephalopathy

Modification of splenic stiffness on acoustic radiation force impulse parallels the variation of portal pressure induced by transjugular intrahepatic portosystemic shunt.

Spleen and liver stiffness (LS) measured by acoustic radiation force impulse (ARFI) imaging has been shown to be useful in identifying patients with portal hypertension. The study aims to establish if the modification of portal pressure induced by a transjugular intrahepatic portosystemic shunt (TIPS) parallels the modification of spleen or LS measured by ARFI in order to understand if ARFI may be used to monitor the modification of portal pressure in patients with cirrhosis. Thirty-eight patients with severe portal hypertension underwent LS and spleen stiffness (SS) before TIPS and 1week after TIPS. Portal atrial gradient (PAG) was measured before and after the shunt opening. Portal atrial gradient decreased significantly from 19.5 to 6mmHg (P<0.001). SS decreased significantly after TIPS (pre-TIPS 3.7m/s vs post-TIPS 3. 1m/s; P<0.001), and LS was also significantly modified by TIPS (pre-TIPS 2.8m/s vs post-TIPS 2.4m/s; P=0.003). PAG and SS values measured before and after TIPS were significantly correlated (r=0.56; P<0.001); on the other hand, PAG and LS were not (r=0.19; P=0.27). Two patients developed a persistent hepatic encephalopathy refractory to medical treatment and were submitted to the reduction of the stent diameter. The modification of SS was parallel to the modification of PAG. Spleen stiffness is superior to LS in detecting the modification of portal pressure induced by TIPS. This makes SS a potential non-invasive method to monitor the modification of portal hypertension. Further investigations are needed to establish applicability and clinical utility of this promising tool in the treatment of portal hypertension.

Spontaneous thrombosis of large splenorenal shunt during balloon-occluded retrograde transvenous obliteration in a patient with chronic persistent hepatic encephalopathy. Is this catheter assisted trans-venous occlusion?

Large spontaneous portosystemic shunts in cirrhosis are implicated in recurrent and/or chronic persistent hepatic encephalopathy. In long standing cases, these shunts lead to portal vein thrombosis and hepatic dysfunction. Balloon-occluded retrograde transvenous obliteration (BRTO) is an endovascular technique that is usually employed for shunt closure in the patients manifesting the features of chronic hepatic encephalopathy. There are several reports documenting systemic and portal vein thrombosis as a part of the procedure. We report first time a patient in whom the difficult and partial BRTO procedure led to the extensive thrombosis of the large splenorenal shunt itself without sclerosant instillation.

Short-Term Comparison of Magnetic Resonance Imaging and Spectroscopy in Persistent Canine Hepatic Encephalopathy Before and After Treatment

Objective: To compare magnetic resonance imaging (MRI) and spectroscopy (MRS) findings in dogs affected by persistent hepatic encephalopathy (HE) before and after treatment and assess any correlation between plasma ammonia levels and metabolite concentrations.Methods: In dogs with persistent HE, plasma ammonia measurement, brain MRI and single voxel MRS were performed before and 4 months after treatment. The concentrations of N-acetyl aspartate, (NAA) glutamate-glutamine complex (Glx), creatine (Cr), choline (Cho) and myo-inositol (mI) as well as the MRI findings werecompared and the correlation with plasma ammonia concentration was evaluated. Statistical analysis included Shapiro Wilk test, Student t-test and linear-fit regression.Results: Twenty dogs were enrolled. Initial MRI and MRS showed alterations in 18/20 and 20/20 dogs respectively. The MRI findings were normalized in dogs aged less than 3 years. Comparing post-treatment metabolite concentrations with the control group, no statistically significant differences were evident for dogs aged less than 3 years, whereas dogs aged more than 5 years showed a persistent but not significant reduction in NAA and mI, with a statistically significant increase in Glx. In dogs younger than 3 years, but not in dogs older than 5 years, a positive correlation was detected between plasma ammonia levels and Glx (r=0.80, p=0.041) and a negative correlation between ammonia level and NAA (r=-0.96, p=0.03) and between NAA and Glx (r=-0.87, p=0.037). No correlation was observed for Cr, Cho and mI.Conclusion: In young dogs MRI and MRS findings of persistent HE can normalize after effective treatment whereas abnormalities are still detected in older dogs. MRI and MRS could therefore be useful in the short-term treatment response evaluation of persistent canine HE.

Embolization of spontaneous portosystemic shunts for management of severe persistent hepatic encephalopathy

Embolization of spontaneous portosystemic shunts for management of severe persistent hepatic encephalopathy

Hepatic failure in pregnancy successfully treated by online hemodiafiltration: Chronic hepatitis B virus infection without viral genome mutation

A 23-year-old nulliparous woman, a hepatitis B virus (HBV) carrier with stable liver functions, presented with exacerbation of viral replication (HBV DNA level >9.0 log copies/mL) in gestational week 26. During the subsequent follow up without antiviral therapy, she was hospitalized with progression to hepatic failure in gestational week 35. Following initiation of antiviral therapy with lamivudine, emergent cesarean delivery was conducted for fetal safety. Liver atrophy and persistent hepatic encephalopathy (stage 2) necessitated artificial liver support (ALS) involving online hemodiafiltration (HDF) and plasma exchange. She regained full consciousness after the sixth online HDF session. ALS was terminated after the seventh online HDF session. On day 33 of hospitalization, she was discharged home without sequelae. Genetic analysis of the HBV strain isolated from her serum showed that this strain had genotype C. Direct full-length sequencing identified no known mutations associated with fulminant hepatitis B. HBV-related hepatic failure observed in the present case might have been related to perinatal changes in the host immune response.

Complex partial non-convulsive status epilepticus masquerading as hepatic encephalopathy: a case report

IntroductionHepatic encephalopathy is usually suspected in patients who are cirrhotic with neuropsychiatric manifestations. We present a case of suspected hepatic encephalopathy that did not respond to standard empiric therapy and was eventually diagnosed as non-convulsive status epilepticus of complex partial type. Our patient responded dramatically to anti-convulsive therapy.Case presentationWe report the case of a 45-year-old African-American man with hepatitis C virus cirrhosis and human immunodeficiency virus who presented to our facility with a one-day history of confusion and a variable mental status. Our patient’s vital signs were stable and all his electrolytes were within normal range. A clinical diagnosis of hepatic encephalopathy was made and our patient was started on empiric therapy with lactulose and rifaximin. Our patient did not respond to therapy. After five days of treatment, alternative diagnoses were sought and a neurology consult was requested. An electroencephalogram was eventually performed which showed seizure activity in the right parietal lobe. A diagnosis of non-convulsive status epilepticus was made and our patient was started on oral levetiracetam. On day two of therapy, our patient was alert and oriented. He continues to do well on follow-up approximately one year after discharge.ConclusionsNon-convulsive status epilepticus should be considered in the differential diagnosis of patients with suspected hepatic encephalopathy who do not respond to empirical treatment. Further studies are needed to investigate the incidence of this entity in patients with persistent hepatic encephalopathy.

Encephalopathy and liver transplantation

Liver transplantation (LT) candidates experience frequently episodic or persistent hepatic encephalopathy. In addition, these patients can exhibit neurological comorbidities that contribute to cognitive impairment in the pre-transplant period. Assessment of the respective contribution of hepatic encephalopathy or comorbidities in the cognitive manifestations is critical to estimate the neurological benefits of restoring liver function. Magnetic resonance imaging and spectroscopy are useful to assess the impact of liver failure or comorbidities. This assessment is critical to decide liver transplant in difficult cases. In the early postoperative period, LT is commonly complicated by a confusional syndrome. The possible role of persisting hepatic encephalopathy in its development has not been clearly established. The origin is usually considered multifactorial and relates to complications following LT, such as infections, rejection, primary liver dysfunction, immunosuppressors, etc.… The diagnosis and treatment is based in the recognition of comorbidities and optimal care of metabolic disturbances. Several studies have demonstrated recovery of cognitive function after LT in patients that have exhibited hepatic encephalopathy. However, some deficits may persist specifically among patients with persistent HE. Other factors present before LT that contribute to a worse neuropsychological outcome after LT are diabetes mellitus and alcohol consumption. Long-term after LT, cognitive function may worsen in relation to vascular risk factors.

Encefalopatía hepática crónica en paciente con cirrosis biliar primaria

Chronic or persistent hepatic encephalopathy is a complication that develops in 1% of patients with chronic liver disease. We report a new case of this complication in a patient with primary biliary cirrhosis. A 69-year-old woman with stage IV primary biliary cirrhosis presented with a 6-month history of progressive memory deficits, tremors and somewhat clumsy gait. Examination revealed sub-jaundiced skin tone, short-term memory deficits, fine distal bilateral tremor in the upper extremities and generalized hyperreflexia with spread of the reflexogenic zone. The hemogram showed mild pancytopenia, hypertransaminasemia, cholestatic pattern, lengthened thromboplastin time and hypocholinesterasemia. Wilson's disease was excluded and a cranial magnetic resonance imaging scan showed a bilateral hyperintense globus pallidus on T1-weighted sequences, which, together with the symptoms, were compatible with the diagnosis. Chronic liver diseases may cause chronic hepatic encephalopathy. Gastroenterologists should be familiar with this entity.

Decreased white matter lesion volume and improved cognitive function after liver transplantation

Focal T2-weighted white matter lesions (WML) on brain magnetic resonance imaging (MRI), mimicking those seen in cerebrovascular small-vessel disease described in patients with persistent hepatic encephalopathy, decreased in volume with the improvement of hepatic encephalopathy. This outcome has been interpreted as a decrease in the edema that it is proposed to be involved in the pathogenesis of hepatic encephalopathy. We designed a study to further investigate potential changes in focal WML in the brains of patients with cirrhosis following liver transplantation and to study the relationship between these changes and overall cognitive function. We used MRI to measure the volume of supratentorial focal WML and a neuropsychological examination to assess cognitive function before and after liver transplantation in 27 patients with cirrhosis without signs of overt hepatic encephalopathy. Baseline MRI identified focal T2-weighted lesions in 19 patients (70.3%). The presence of WML was associated with older age but not with vascular risk factors, severity of liver function, or psychometric tests. A significant reduction in lesion volume was observed after liver transplantation (from a median of 1.306 cm(3) to 0.671 cm(3), P = 0.001). This decrease correlated with an improvement in an index of global cognitive function (r = -0.663; P < 0.001). This evolution indicates that lesion volume is partially related to a reversible type of tissue damage, which is compatible with brain edema. Focal WML probably induced by age-related microvascular injury can decrease their volume with liver transplantation. The associated improvement of cognitive function supports a relationship between brain edema and minimal hepatic encephalopathy.

High Prevalence of Spontaneous Portal-Systemic Shunts in Persistent Hepatic Encephalopathy: A Case-Control Study *

Large spontaneous portal-systemic shunts have been occasionally described in patients with cirrhosis. This study was undertaken to assess the prevalence of portal-systemic shunts in patients with cirrhosis with recurrent or persistent hepatic encephalopathy (HE) as compared with patients with cirrhosis without HE. Fourteen patients with cirrhosis with recurrent or persistent HE (cases) and 14 patients with cirrhosis without previous or present signs of overt HE matching for age and degree of liver failure (controls) were studied. Each patient underwent neurological assessment and cerebral magnetic resonance (MR) imaging to exclude organic neurological pathological conditions. HE evaluation included psychometric performance (Trail-Making Test A), electroencephalogram (EEG), mental status examination and grading, arterial, venous, and partial pressure of ammonia determination. The presence of portal-systemic shunts was assessed by portal venous phase multidetector-row spiral computed tomography (CT). Large spontaneous portal-systemic shunts were detected in 10 patients with HE and in only 2 patients without HE (71% vs. 14%; chi square = 9.16; df = 1.0; P = .002). The patients with HE presented ascites (P = .002) and medium/large esophageal varices (P = .02) less frequently than the control group. In conclusion, our study suggests that large spontaneous shunts may often sustain the chronicity of HE; the presence of large shunts should be sought in patients with cirrhosis with recurrent or persistent HE.

Continuing Defect in Cerebral Energy Metabolism in Patients with Persistent Hepatic Encephalopathy (PHE): Monitoring with 31P Mrs

Continuing Defect in Cerebral Energy Metabolism in Patients with Persistent Hepatic Encephalopathy (PHE): Monitoring with 31P Mrs

Exclusion of the colon for chronic hepatic encephalopathy

Summary Results in one patient with persistent hepatic encephalopathy and a second with chronic recurrent encephalopathy have been reported. Their progressive neuropsychiatric deterioration in spite of good medical management led to exclusion of the colon with ileorectal anastomoses with excellent short-term results. The pathogenesis of ammonia intoxication and the development of the surgical concept for this condition is discussed.