Improvement Of Hepatic Encephalopathy Research Articles

Effect of an Autotaxin Inhibitor, 2-(4-Chlorophenyl)-7-methyl-8-pentylimidazo[1,2-a] Pyrimidin-5(8H)-one (CBT-295), on Bile Duct Ligation-Induced Chronic Liver Disease and Associated Hepatic Encephalopathy in Rats.

The role of autotaxin (ATX)-lysophosphatidic acid (LPA) is yet to be explored in the context of liver cirrhosis and associated encephalopathy. Our objective of this study was to evaluate the role of an ATX inhibitor in biliary cirrhosis and associated hepatic encephalopathy in rats. The preliminary investigation revealed significant impairment in liver function, which eventually led to the development of hepatic encephalopathy. Interestingly, LPA levels were significantly increased in the plasma, liver, and brain of rats following bile duct ligation. Subsequently, we tested the efficacy of an ATX inhibitor, CBT-295, in bile duct-induced biliary cirrhosis and neuropsychiatric symptoms associated with hepatic encephalopathy. CBT-295 showed good oral bioavailability and favorable pharmacokinetic properties. CBT-295 exhibited a significant reduction in inflammatory cytokines like TGF-β, TNF-α, and IL-6 levels, also reduced bile duct proliferation marker CK-19, and lowered liver fibrosis, as evident from reduced collagen deposition. The reversal of liver fibrosis with CBT-295 led to a reduction in blood and brain ammonia levels. Furthermore, CBT-295 also reduced neuroinflammation induced by ammonia, which is characterized by a significant reduction in brain cytokine levels. It improved neuropsychiatric symptoms such as locomotor activities, cognitive impairment, and clinical grading scores associated with hepatic encephalopathy. The improvement in hepatic encephalopathy observed with the ATX inhibitor could be the result of its hepatoprotective action and its ability to attenuate neuroinflammation. Therefore, inhibition of ATX-LPA signaling can be a multifactorial approach for the treatment of chronic liver diseases.

Serum metabolomics can predict improvement in hepatic encephalopathy in patients with acute-on-chronic liver failure

Serum metabolomics can predict improvement in hepatic encephalopathy in patients with acute-on-chronic liver failure

COMPARATIVE STUDY OF METRONIDAZOLE AND RIFAXIMIN IN PATIENTS WITH HEPATIC ENCEPHALOPATHY

Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome due to liver brokenness, especially in patients with cirrhosis or intense liver failure. The study's main objective is to find the comparative effectiveness of metronidazole and rifaximin in patients with hepatic encephalopathy. This prospective comparative study was conducted at Islamabad Medical and Dental College, Islamabad, over six months, from January 2023 to July 2023. The study population consisted of adult patients (age 18 years and above) diagnosed with hepatic encephalopathy admitted to the hospital's medical wards or gastroenterology department during the study duration. Patients with a confirmed diagnosis of hepatic encephalopathy based on clinical and laboratory criteria were included in the study. Out of the 150 patients enrolled in the study, 75 were randomized to receive metronidazole (Group A) and 75 to receive rifaximin (Group B). All patients completed the 10-day treatment period, and there were no dropouts during the study. In Group A (metronidazole), 60 out of 75 patients (80%) showed improvement in hepatic encephalopathy based on the West Haven criteria. In Group B (rifaximin), 70 out of 75 patients (93.33%) showed improvement in hepatic encephalopathy based on the West Haven criteria. The improvement in hepatic encephalopathy was significantly higher in Group B (rifaximin) compared to Group A (metronidazole) (p < 0.05).

A227 THE EFFECTIVENESS OF PEG 3350 COMPARED TO LACTULOSE FOR THE TREATMENT OF ACUTE HEPATIC ENCEPHALOPATHY IN ADULT CIRRHOTIC PATIENTS: A SYSTEMATIC REVIEW AND META-ANALYSIS

BackgroundCirrhosis is the leading cause of liver-related death globally. Hepatic encephalopathy (HE) leads to significant morbidity and mortality. Lactulose is the current gold standard treatment for HE; it eliminates nitrogenous waste from the gut. Polyethylene glycol 3350–electrolyte solution (PEG) is a safe, common and effective purgative with recent studies suggesting its efficacy resulting in faster resolution of HE and shorter hospital length of stay.AimsTo assess the efficacy and safety of PEG 3350 compared to lactulose in adult cirrhotic patients 18 years of age and older with overt hepatic encephalopathy on patient important outcomes including: improvement of hepatic encephalopathy, hospital length of stay and mortality.MethodsWe reviewed databases MEDLINE, EMBASE, OVID, CINAHL, Cochrane Database, PubMed, Trip database, the grey literature, and clinicaltrials.gov from inception to December 2020: PROSPERO CRD42021257641. Search strategy was developed in conjunction with medical librarian. Randomized controlled trials (RCTs), either published or non-published, were included in the review. Continuous data was analyzed using mean difference with random-effects model. Dichotomous data was analyzed using the Mantel-Haenszel method using random-effects model. Statistical effect-size heterogeneity was assessed using Chi2 test and quantifying the relative proportion of variation using I2 statistic. The overall certainty of evidence will be assessed using the Grading of Recommendations, Assessment, Development and Evaluations system (GRADE).ResultsFrom the 68 studies, 16 were assessed for full text review from which 5 studies were included in the meta-analysis representing a total of 351 patients. The primary outcome of mean change in Hepatic Encephalopathy Scoring Algorithm (HESA) at 24-hours from baseline demonstrated an improvement in the PEG group compared to lactulose group [Mean difference (MD)= 0.60, 95% CI (0.20, 1.01)]. In comparison to lactulose, PEG also demonstrated a shorter hospital length of stay [MD = -1.00, 95% CI (-1.99, -0.01)], shorter time to HE resolution [MD= -1.49, 95% CI (-1.81, -1.16)] and showed a mortality benefit [RR=0.35, 95% CI (0.13 to 0.92)]. There was no significant difference between change in ammonia levels at 24 hours [MD= -25.80, 95% CI (-95.39, 43.78)].ConclusionsPEG leads to a faster improvement and resolution of HE when compared to the current standard of care, lactulose. Funding AgenciesNone

A comparative study to determine the short-term mortality and clinical improvement in hepatic encephalopathy using either rifaximin and or lactulose

Background: Hepatic encephalopathy can be reversed by correcting precipitating factors and efficiently managed by lactulose and or rifaximin.
 Aims and Objective: The aim of this study to compare the effectiveness of three different modes of treatment in our study populations.
 Materials and Methods: Ninety patients of decompensated chronic liver diseases were selected and randomised to treat with either lactulose or rifaximin or both lactulose and rifaximin (30 patients in each group) for 7 days. Clinical outcome and short term mortality were noted in each group of treatment. This study was to review the comparison of the effectiveness of Rifaximin (1200mg/day , in 3 divided doses ) alone or in combination with Lactulose (60gram/day ,in divided doses) or Lactulose (60gram/day) alone to reduce the short term mortality and clinical improvement in hepatic encephalopathy of any grade of any cause in adult (>18 years) admitted patients of decompensated chronic liver diseases.
 Result: Clinical improvement was noted in all three modes of treatment but there is no statistically significant difference in clinical improvement of hepatic encephalopathy when compared amongst each of three modes of treatment. There was obvious reduction of short term mortality or clinical down gradation of hepatic encephalopathy grade after 7 days treatment using lactulose or rifaximin or combined lactulose and rifaximin but there was no statistically significant difference in this regard among these three modes of treatment.
 Conclusion: All three modes of treatment are equally effective though combination therapy is little better.

Carnitine status before and after paracentesis in patients with ascites and liver cirrhosis and improvement of subjective symptoms by intravenous administration of carnitine ― Initial study

Carnitine status before and after paracentesis in patients with ascites and liver cirrhosis and improvement of subjective symptoms by intravenous administration of carnitine ― Initial study

Application of the Molecular Adsorbent Recirculating System in Type 1 Hepatorenal Syndrome in the Course of Alcohol-Related Acute on Chronic Liver Failure.

BackgroundThis study aimed to evaluate the Molecular Adsorbent Recirculating System (MARS) effectiveness in patients with alcohol-related acute-on-chronic liver failure (AoCLF) complicated with type 1 hepatorenal syndrome (HRS). So far, MARS efficacy and safety has been demonstrated in various acute liver failure scenarios.Material/MethodsData from 41 MARS procedures (10 patients with type 1 HRS, in the course of alcohol-related AoCLF were considered for this study. Biochemical tests of blood serum were performed before and after each procedure. The condition of patients was determined before and after the treatment with the use of the model for end-stage liver disease – sodium (MELD-Na) and the stage of encephalopathy severity based on the West Haven criteria.ResultsDuring the observation period (20.5±13.9 days), 5 patients died, and the remaining 5 surviving patients were discharged from the hospital. In the group of 10, the 14-day survival, starting from the first MARS treatment, was 90%. The MARS procedure was associated with a 19% reduction in bilirubin (27.5±6.1 versus 22.3±4.0 mg/dL, P<0.001), 37% reduction in ammonia (44.1±22.5 versus 27.6±20.9 P<0.001), 27% reduction in creatinine (1.5±1.0 versus 1.1±0.6 mg/dL, P<0.001) and 14% reduction urea (83.8±36.1 versus 72.1±33.3, P<0.001) in blood serum samples, with stable hemodynamic parameters. In the group of patients discharged from the clinic (n=5), the MARS treatments resulted in an improvement in hepatic encephalopathy (West Haven; P=0.043), as well as a reduction in the MELD-Na score (P=0.015).ConclusionsMARS is a hemodynamically safe method for supporting the function of the liver and the kidneys. Application of the MARS reduces the symptoms of encephalopathy in patients with alcohol-related type 1 HRS.

Extracorporeal liver support in patients with liver failure: a systematic review and meta-analysis of randomized trials.

Acute liver failure (ALF) and acute on chronic liver failure (ACLF) are associated with significant mortality and morbidity. Extracorporeal liver support (ECLS) devices have been used as a bridge to liver transplant; however, the efficacy and safety of ECLS are unclear. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to examine the efficacy and safety of ECLS in liver failure. We searched MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials from inception through March 13, 2019. RCTs comparing ECLS to usual care in ALF or ACLF were included. We used the Grading of Recommendations Assessment, Development and Evaluation approach to assess the certainty of the evidence. We identified 25 RCTs (1796 patients). ECLS use was associated with reduction in mortality (RR 0.84; 95% CI 0.74, 0.96, moderate certainty) and improvement in hepatic encephalopathy (HE) (RR 0.71; 95% CI 0.60, 0.84, low certainty) in patients with ALF or ACLF. The effect of ECLS on hypotension (RR 1.46; 95% CI 0.98, 2.2, low certainty), bleeding (RR 1.21; 95% CI 0.88, 1.66, moderate certainty), thrombocytopenia (RR 1.62; 95% CI 1.0, 2.64, very low certainty) and line infection (RR 1.92; 95% CI 0.11, 33.44, low certainty) was uncertain. ECLS may reduce mortality and improve HE in patients with ALF and ACLF. The effect on other outcomes is uncertain. However, the evidence is limited by risk of bias and imprecision, and larger trials are needed to better determine the effect of ECLS on patient-important outcomes.

Coil-Assisted Retrograde Transvenous Obliteration: A Valid Treatment for Gastric Variceal Hemorrhage and Hepatic Encephalopathy

AbstractCoil-assisted retrograde transvenous obliteration (CARTO) has evolved as a simpler and perhaps safer alternative to balloon-occluded retrograde transvenous obliteration (BRTO). The efficacy of BRTO has been established, and early data supports the use of CARTO in similar situations. In a small series of patients with gastric variceal hemorrhage treated with CARTO, complete portosystemic shunt occlusion, complete variceal obliteration, and no rebleeding during the follow-up period were observed in all patients. In a larger, unpublished study, an improvement in hepatic encephalopathy was observed in over 80% of patients treated with CARTO. In addition, overall liver function was markedly improved in 1 month. As for complications, new or worsened ascites and esophageal varices were observed in 24% and 30%, respectively. Overall, CARTO is an effective treatment of gastric variceal hemorrhage and hepatic encephalopathy with high technical and clinical success rates. Compared with plug-assisted retrograde transvenous obliteration (PARTO), CARTO can be used to safely close larger shunts with a comparable efficacy and complication profiles.

Improvement of Hepatic Encephalopathy by Application of Peritoneal Dialysis in a Patient with Non-End-Stage Renal Disease

Improvement of Hepatic Encephalopathy by Application of Peritoneal Dialysis in a Patient with Non-End-Stage Renal Disease

Can zinc enhance response interferon therapy for patients with HCV-related liver disease?

Patients with liver disease may be at risk of zinc depletion. Zinc supplementation has been shown to contribute to inhibition of liver fibrosis and improvement in hepatic encephalopathy. However, little is known about the anti-inflammatory effect of zinc on hepatitis C virus (HCV)-related chronic liver disease. The standard of care for chronic HCV has improved markedly since the approval of interferon (IFN) therapy more than a decade ago. Over the past 20 years, IFN therapy has improved to more effectively eliminate the virus, progressing from single IFN therapy to combination therapy with ribavirin (RBV) and finally to pegylated IFN (PEG-IFN) therapy. However, even combined therapy with PEG-IFN and RBV for 48 wk is unable to eliminate the virus in some 40% of hepatitis C cases, particularly those with genotype 1b and high viral load. Treatment options for patients who have relapsed or are refractory to treatment with PEG-IFN and RBV therefore need to be critically assessed. This paper overviews the relationship between chronic liver disease and zinc metabolism.

Systematic review and meta‐analysis of randomized trials on probiotics for hepatic encephalopathy

The objective of this systematic review and meta-analysis was to assess the efficacy of probiotics and synbiotics in patients with hepatic encephalopathy. Eligible trials were identified by searching electronic databases including MEDLINE, the Cochrane Library, Science Citation Index and Embase, abstract proceedings, reference lists and ongoing trial registers until 13 October 2010. We included randomized controlled trials comparing probiotics and synbiotics with no intervention, placebo or lactulose in patients with hepatic encephalopathy. The primary outcome measure was improvement in hepatic encephalopathy. RESULTS were expressed as risk rates (RR) with confidence intervals (CI) and intertrial heterogeneity as I(2) . Seven trials with a total of 393 patients were analyzed. Compared to placebo or lactulose, treatment with probiotics or synbiotics significantly improved hepatic encephalopathy (RR = 1.40, 95% CI = 1.05-1.86, I(2) = 5%). Probiotics decreased arterial ammonia (weighted mean difference 15.95; 95% CI = 26.72-3.28; I(2) = 68%), but not venous ammonia (weighted mean difference 5.23; 95% CI = 21.77-11.30; I(2) = 89%). Treatment with probiotics or synbiotics did not significantly affect the psychometric tests. Overall adverse events were reported in four trials with no difference between probiotics and placebo groups (RR = 0.32, 95% CI = 0.04-2.57; I(2) = 59%). Regression analysis showed evidence of small-study effects. The present meta-analysis suggests that probiotics may be an effective treatment of hepatic encephalopathy, though rigorous evaluation in standardized, randomized, clinical trial with clinically relevant outcomes is still needed.

Artificial liver support devices as treatment option for liver failure

Non-biological artificial liver support (ALS) devices aim to remove albumin-bound and water-soluble toxins arising as a result of liver failure. They do not directly improve the liver synthetic capacity. The currently most used devices combine haemodialysis with albumin dialysis (MARS) or plasma separation and filtration (Prometheus). These devices have been used as a treatment for different types of liver failure: acute liver failure, acute-on-chronic liver failure and primary non- or poor-function after liver transplantation. Overall these devices are found to be safe. The following beneficial effects have been documented: improvement of jaundice, amelioration of haemodynamic instability, reduction of portal hypertension, lowering of intracranial pressure and improvement of hepatic encephalopathy. However, recently multicentre controlled trials failed to show a beneficial effect on transplant-free survival. Therefore the use of these devices at present seems only justified as a bridge to liver transplantation.

Molecular Adsorbent Recirculating System as Artificial Support Therapy for Liver Failure

Molecular Adsorbent Recirculating System (MARS) is an artificial liver support system that has been developed for patients with liver failure until the liver regains function or as a bridge to transplantation. We conducted a meta-analysis to examine the efficacy of this promising therapy. We searched MEDLINE, EMBASE, and the Cochrane Registry of Controlled Trials databases, and abstracts from the proceedings of several scientific meetings. Patients with acute, acute on chronic, and hyperacute liver failure were included and we compared MARS with standard medical therapy. Randomized and nonrandomized controlled trials were included and Molecular Adsorbent Recirculating System was the intervention used. We evaluated net change in total bilirubin levels, improvement in hepatic encephalopathy and mortality. Nine randomized controlled trials and one nonrandomized controlled study met criteria and were included. By meta-analysis, MARS resulted in a significant decrease in total bilirubin levels (net change -7.0 mg/dl; 95% CI -10.4, -3.7; p < 0.001) and in an improvement in the West-Haven grade of hepatic encephalopathy (odds ratio [OR] 3.0; 95% CI 1.9, 5.0; p < 0.001). There was no beneficial effect on mortality (OR 0.91; 95% CI 0.64, 1.31; p = 0.62). The limitations of this study include a small sample size, an inability to blind with significant heterogeneity among studies, and variable definitions of liver failure. The Molecular Adsorbent Recirculating System is associated with a significant improvement in total bilirubin levels and hepatic encephalopathy but has no impact on survival. Large studies are required to assess the merit of this promising therapy on patient-centered outcomes.

L‐Ornithine‐l‐aspartate in the management of hepatic encephalopathy: A meta‐analysis

Hepatic encephalopathy continues to be a major clinical problem and the current decade has not witnessed major therapeutic breakthroughs in this area. L-ornithine-l-aspartate (LOLA) is not frequently used as there are still some reservations about its benefits. The present study aimed to assess the effectiveness and safety of LOLA in the management of hepatic encephalopathy. We used the method recommended by the Cochrane Collaboration to perform a meta-analysis of randomized controlled trials of LOLA therapy for hepatic encephalopathy including three randomized controlled trials. Three randomized trials randomizing 212 patients were included. LOLA versus placebo had a significant effect on improvement of hepatic encephalopathy (relative risk 1.89; 95% CI 1.32 to 2.71; P = 0.0005). This comparison showed no statistical heterogeneity (P = 0.85 and chi(2) = 0.09). Subgroup analysis showed that LOLA could be effective versus placebo in trials with grade I or II overt hepatic encephalopathy patients (relative risk 1.87; 95% CI 1.30 to 2.68; P = 0.0007) and had no significant effect in trials with subclinical hepatic encephalopathy patients (relative risk 1.69; 95% CI 0.72 to 3.94; P = 0.23). Adverse effects were observed in only three patients treated with LOLA in one report. LOLA benefited patients with overt hepatic encephalopathy (I or II), whereas these data do not support the use of LOLA for patients with subclinical hepatic encephalopathy.

Albumin dialysis improves hepatic encephalopathy and decreases circulating phenolic aromatic amino acids in patients with alcoholic hepatitis and severe liver failure

IntroductionThe aim of this study was to assess the effects of albumin dialysis on hepatic encephalopathy and circulating levels of amino acids in severe alcoholic hepatitis.MethodsThe study was carried out in nine patients with severe alcoholic hepatitis and four with primary biliary cirrhosis treated with the molecular adsorbent recirculating system. Besides standard liver function tests, circulating levels of ammonia, total, branched chain and aromatic amino acids, the presence and severity of hepatic encephalopathy, and number connection test were measured before and after each treatment.ResultsThere were eight episodes of encephalopathy in patients with alcoholic hepatitis. Albumin dialysis was associated with significant improvement in encephalopathy (p = 0.02), and a decrease in total amino acid levels (2490 ± 152 μM to 2229 ± 114 μM, p < 0.001). Moreover, the Fischer's ratio, which was significantly lower in patients with alcoholic hepatitis (1.32 ± 0.08) than in controls (3.20 ± 0.16), increased by 17% after albumin dialysis (p < 0.02) because of a significant decrease in phenolic aromatic amino acids (193 ± 17 μM to 165 ± 9 μM, p = 0.04). No differences were observed in circulating ammonia. Changes in phenolic aromatic amino acids and the Fischer's ratio were more prominent in patients with encephalopathy and higher bilirubin removal. Albumin dialysis did not significantly affect the amino acid profile in the controls.ConclusionsAlbumin dialysis results in a significant decrease in circulating phenolic aromatic amino acids and improvement of hepatic encephalopathy in patients with severe liver failure.

Extracorporeal albumin dialysis

Patients with liver failure still present a high mortality. It can only be significantly improved by the rare resource of liver transplantation. Extracorporeal liver support devices have been developed to temporarily support liver detoxification. Artificial devices without hepatocytes ("liver dialysis" or "albumin dialysis") are already widely used in Europe. The two best-known systems, MARS and Prometheus, use a different technical approach to remove water-soluble as well as albumin-bound toxins from the blood. In MARS, toxins diffuse along a concentration gradient through an albumin-impermeable membrane into a secondary circuit that is pre-filled with an albumin solution. The albumin is continuously "recycled" inside the secondary circuit by different adsorber and low flux dialysis. In contrast, Prometheus includes an albumin-permeable filter allowing separation of the albumin fraction into the secondary circuit where the albumin-bound toxins are directly removed by two adsorbers. Thereafter, high flux dialysis is performed inside the primary circuit. For both extracorporeal systems, an improvement of hepatic encephalopathy and biochemical markers such as bilirubin is consistently reported. In-vivo comparisons of both systems showed significantly higher extraction capacities for protein-bound and water-soluble substances under Prometheus than under MARS treatment. Possible pathophysiological mechanisms could be a reduction of portal pressure or a removal of vasoactive cytokines. However, only few randomised controlled trials with low patient numbers and conflictive results regarding patient survival exist. Nevertheless, a Cochrane meta-analysis revealed a significant survival benefit for extracorporeal liver support devices in patients with acute-on-chronic liver failure. Other promising indications are severe refractory cholestatic pruritus, intoxication with protein-bound substances and graft dysfunction after liver transplantation. As large randomised controlled multi-center trials are currently underway, better evidence will be available soon to define the clinical role of extracorporeal liver support devices.

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.

Recovery of Brain Dopamine Metabolism by Branched-chain Amino Acids in Rats With Acute Hepatic Failure

A decrease in the serum ratio of branched-chain amino acids (BCAAs) to aromatic amino acids (Fischer ratio) reflects the severity of hepatic encephalopathy, and clinical improvement by dietary augmentation with BCAAs has been demonstrated. As behavioral alteration results from changes in central neurotransmission, we investigated the role of BCAA administration on changes in the levels of central neurotransmitters in acute liver injury. Male Wistar rats were subjected to liver ischemia by occluding the left portal vein and hepatic artery for 90 minutes. A 4% BCAA solution containing valine, leucine, and isoleucine was intraperitoneally administered 3 times (8 mL/kg, each) at 1 hour, 6 hours, and 24 hours after vascular reperfusion, and changes in the extracellular concentrations of neurotransmitter amino acids, monoamines, and their metabolites were evaluated in the striatum by a microdialysis procedure. Although the extracellular concentration of dopamine was affected by neither liver ischemia nor BCAA injections, the level of 3,4-dihydroxyphenylacetic acid, a metabolite of dopamine, decreased to 34% in the ischemic group 24 hours after reperfusion. The 3,4-dihydroxyphenylacetic acid level was normalized by treatments with BCAAs. The improvement of deranged cerebral dopaminergic activity may be a contributing factor in the improvement of hepatic encephalopathy by BCAAs.

Decrease in the Volume of White Matter Lesions with Improvement of Hepatic Encephalopathy

MR imaging has found abnormalities compatible with low-grade edema in the brain of patients with cirrhosis that have been related to hepatic encephalopathy. We present 3 patients with hepatic encephalopathy who exhibit supratentorial focal or diffuse white matter lesions compatible with small-vessel brain disease. The volume and number of white matter lesions reduced with the improvement of hepatic encephalopathy, suggesting the participation of the blood-brain barrier in the pathogenesis of brain edema in hepatic encephalopathy.