The additive value of sarcopenia,myosteatosis and hepatic encephalopathy in the predictivity of model for end-stage liver disease

BackgroundSince the use of the Model for End-Stage Liver Disease (MELD) score for establishing the prognosis of cirrhotic patients has been introduced, questions have been raised whether complications of liver cirrhosis would provide additional information. Myosteatosis, sarcopenia and hepatic encephalopathy (HE) are frequent in cirrhosis and may affect prognosis.Aim of the study was analyzing if these factors are independently related to survival and may improve the accuracy of MELD.Methods249 cirrhotics that underwent abdominal CT-scan were enrolled. For each patient, information about previous episodes of HE and muscle alterations were obtained. Patients were followed until transplantation or death.ResultsHistory of HE, MELD, sarcopenia and myosteatosis were independently associated with mortality. The MELD-Sarco-Myo-HE score added accuracy to the MELD score alone for 6- and 3-months mortality. By removing HE, as the only not quantifiable parameter of the model, no relevant decrease in accuracy for 6- and 3-months mortality detection was observed.ConclusionsThe accuracy of MELD in predicting 3- and 6-months mortality may be improved by considering the muscle alterations. A model considering the above parameters may classify more accurately over 30% of the patients.     

肝硬化患者血浆亮啡肽,神经肽Y含量的变化及临床意义

目的　探讨肝硬化患者血浆亮啡肽（ＬＥＮＫ）、神经肽Ｙ（ＮＰＹ）含量的变化规律及其临床意义。方法用放射免疫法检测４９例肝硬化患者血浆ＬＥＮＫ、 ＮＰＹ含量，并以１８例慢性肝炎、１４例急性肝炎和１０名健康者作对照。结果　肝硬化患者血浆ＬＥＮＫ含量显著高于正常人和急、慢性肝炎（Ｐ＜０．０５），有腹水、肝性脑病者分别显著高于无腹水和无肝性脑病者（Ｐ＜０．０５）；而血浆ＮＰＹ水平肝硬化患者明显下降（Ｐ＜０．０５），有腹水或肝性脑病者下降更明显（Ｐ＜０．０５）。结论肝硬化患者血浆ＬＥＮＫ、ＮＰＹ等内源性神经肽水平明显变化，且以有腹水、肝性脑病等严重并发症者更为明显，提示这些神经肽可能参与了肝硬化患者的高动力状态循环异常，并与腹水及肝性脑病形成有关。     

Transendothelial migration of leukocytes is promoted by plasma from a subgroup of immune thrombocytopenic purpura patients with small-vessel ischemic brain disease

We previously described a subgroup of immune thrombocytopenic purpura (ITP) patients presenting with recurring transient ischemic attack-like symptoms and progressive cognitive impairment due to small vessel disease (SVD) seen in the brain. They presented minimal bleeding despite thrombocytopenia, and platelet activation was elevated compared to classic ITP. On the hypothesis that the blood-brain barrier (BBB) is compromised in this subgroup, we investigated the effect of plasma from SVD-ITP patients on the transendothelial migration of leukocytes (TEML). Brain microvascular endothelial cells (BMVEC) were grown to confluence on 6.5-microm pore filters and plasma from 10 healthy controls, 20 classic ITP, and 5 SVD-ITP were added and incubated 24 hr. Then 1 x 10(5) monocytes (U937) were added and the number migrated through the EC monolayer after 6 hr was measured by flow cytometry. The effect on TEML of danazol was also assessed. We found that plasma from SVD-ITP but not classic ITP induced 10-fold rise in EC activation marker CD62E and a sevenfold increase in TEML, to 38.5% +/- 12.5% of cells migrated, compared to normal controls (5.6% +/- 1.2%) or classic ITP (6.1% +/- 0.2%), P < 0.001. Preincubation of U937 with endothelial microparticles (EMP) increased TEML by 20.0% +/- 6.4% with SVD-ITP plasma, significantly more than with classic ITP or control plasmas, P = 0.003. Pretreatment of cultures with danazol (100 microg/mL) inhibited TEML by 25% in all wells tested, whether or not EMP were added. In summary, SVD-ITP plasma activates EC and augments TEML, suggesting plasma-mediated BBB dysfunction in this syndrome. Danazol modestly but significantly inhibited TEML.     

Ammonia and Endogenous Benzodiazepine-like Compounds in the Pathogenesis of Hepatic Encephalopathy

Background: Ammonia and endogenous benzodiazepines (BDZs) are two of the most important agents among those taken into consideration in the pathogenesis of hepatic encephalopathy (HE). Methods: Venous ammonia and endogenous BDZs sera levels were assayed in 58 liver cirrhosis patients (34 male, 24 female) free of commercial BDZs. Endogenous BDZs were measured by binding assay after high-performance liquid chromatography purification. Ammonia was assessed by colorimetric test. Results: Endogenous BDZs and ammonia were significantly higher in Child-Pugh class C than in class B and class A (P &lt; 0.05), correlating to the severity of the liver dysfunction but not with the degree of HE. A significant difference, in fact, was noted between degree 0 (no HE) versus III-IV of HE (P &lt; 0.05), but not between degrees I-II versus III-IV. Regression analysis performed to find a correlation between the ammonia and BDZ levels in HE resulted negative. Conclusion: Clinical evidence is provided in cirrhotic patients that ammonia and endogenous BDZ levels do not correlate with each other in the outcome of HE.     

Anticoagulation Therapy in Patients with Liver Cirrhosis is Associated With an Increased Risk of Variceal Hemorrhage

ObjectiveThe belief that cirrhotic patients are “auto-anticoagulated” often results in anticoagulation therapy being withheld in these patients. We aimed to understand patterns of use of anticoagulation and to determine the risk of bleeding complications in cirrhotic patients.MethodsWe retrospectively analyzed 320 cirrhotic patients treated with anticoagulation therapy from July 15, 2014 to January 30, 2018. We performed bivariate and multivariate analyses to identify risk factors for clinically relevant bleeding. We conducted a separate analysis using propensity score matching to compare bleeding rates of a noncirrhotic cohort group on anticoagulation to anticoagulated patients with cirrhosis.ResultsNonalcoholic steatohepatitis (47%) was the most common cause of cirrhosis, and 49% were classified as Child-Pugh class B, a mean model for end-stage liver disease score of 14 and Charlson comorbidity index of 7. Anticoagulation was initiated for atrial fibrillation/atrial flutter in 56% of patients; warfarin was used in 57% of patients and concomitant use of antiplatelet therapy in 25%. Bleeding occurred in 18%, with upper gastrointestinal bleeding (53%) being the most common source. In the propensity-matched cohort, bleeding rates were higher in cirrhotics than in control patients who were matched for baseline characteristics. In multivariate analysis of the cirrhotic patients, the presence of esophageal varices was associated with higher odds of clinically relevant bleeding.ConclusionAnticoagulated cirrhotic patients who have esophageal varices are at an increased risk of bleeding. We recommend that patients with cirrhosis and esophageal varices who require anticoagulation have their varices managed carefully prior to initiation of anticoagulation.     

Proton magnetic resonance spectroscopy (1H-MRS) findings for the brain in patients with liver cirrhosis reflect the hepatic functional reserve

OBJECTIVE: Proton magnetic resonance spectroscopy (1H-MRS) has been used to assess the metabolic changes in the brain in patients with liver cirrhosis. Decreased myo-inositol and increased glutamine levels were noted to be the most sensitive spectroscopic markers for cirrhotic patients with hepatic encephalopathy (HE). The purpose of this study was to assess how the abnormalities seen on the 1H-MRS of the brain in patients with liver cirrhosis are related to clinical and laboratory parameters. METHODS: In a prospective study, localized 1H-MRS was performed in the basal ganglia and parietal white matter regions in liver cirrhosis patients with (n = 48) and without (n = 52) HE and chronic hepatitis (CH) (n = 15), and in normal controls (n = 20). RESULTS: Among cirrhotic patients, the myo-inositol levels were significantly lower (p < 0.01) and the glutamine levels were higher (p < 0.05) for patients with HE than for those without HE. The myo-inositol and glutamine levels, respectively, were inversely (r = -0.50; p < 0.001) and linearly (r = 0.50; p < 0.001) related to the Child-Pugh score. However, by subgroup analysis of Child-Pugh class C patients, there were no significant differences in the myo-inositol and glutamine levels between cirrhotic patients with (n = 40) and without HE (n = 24). A follow-up study of eight cirrhotic patients with HE showed no significant differences in the myo-inositol and glutamine levels after clinical improvement of HE. CONCLUSIONS: The abnormalities seen on the 1H-MRS of the brain of patients with liver cirrhosis are not likely to reflect the severity of HE or acute alteration in the level of consciousness. Rather, we believe they represent the chronic metabolic derangement of the brain associated with hepatic functional reserve.     

Complications Requiring Hospital Admission and Causes of In-Hospital Death over Time in Alcoholic and Nonalcoholic Cirrhosis Patients

Background/Aims

Data on the epidemiology of alcoholic cirrhosis, especially in Asian countries, are limited. We compared the temporal evolution of patterns of alcoholic and nonalcoholic cirrhosis over the last decade.

Methods

We retrospectively examined the inpatient datasets of five referral centers during 2002 and 2011. The study included patients who were admitted due to specific complications of liver cirrhosis. We compared the causes of hospital admissions and in-hospital deaths between patients with alcoholic and nonalcoholic cirrhosis.

Results

Among the included 2,799 hospitalizations (2,165 patients), 1,496 (1,143 patients) were from 2002, and 1,303 (1,022 patients) were from 2011. Over time, there was a reduction in the rate of hepatic encephalopathy (HE) as a cause of hospitalization and an increase in the rate of hepatocellular carcinoma. Deaths that were attributable to HE or spontaneous bacterial peritonitis (SBP) significantly decreased, whereas those due to hepatorenal syndrome (HRS) significantly increased over time in patients with alcoholic cirrhosis. However, in patients with nonalcoholic cirrhosis, hepatic failure and HRS remained the principal causes of in-hospital death during both time periods.

Conclusions

The major causes of in-hospital deaths have evolved from acute cirrhotic complications, including HE or SBP to HRS in alcoholic cirrhosis, whereas those have remained unchanged in nonalcoholic cirrhosis during the last decade.     

Non-neoplastic Portal Vein Thrombosis in HCV Cirrhosis Patients: is it an Immuno-Inflammatory Disorder?

Background and aimsPortal vein thrombosis (PVT) is a critical complication in cirrhotic patients. We explored the role of the activated factor VII-antithrombin (FVIIa-AT) complex and enhanced monocytic tissue factor (TF) expression in the development and prediction of non-neoplastic PVT in cirrhotic patients.Material and methodsA total of 30 HCV-cirrhosis patients were included in our study. They were compared to 35 cirrhotic patients without PVT, 15 non-cirrhotic patients with PVT, and 15 healthy controls. The plasma level of the FVIIa-AT complexes was analyzed by ELISA. MIF CD142, CD86, and HLA-DR on monocytes (CD14) were determined by flow cytometry.ResultsCompared with cirrhotic patients without PVT, cirrhotic patients with PVT had comparable plasma values of FVIIa, AT, and the FVIIa-AT complex. However, they had significantly lower values compared to non-cirrhotic patients with PVT and healthy controls. Cirrhotic patients with PVT had increased monocytic TF expression (MIF CD142) compared to non-PVT cirrhotic patients and healthy controls [86.5 (93.5) vs. 18 (32.0) and 11.0 (6.0), respectively; p < 0.001 for each]. However, cirrhosis PVT could not be distinguished from non-cirrhosis PVT. The area under the ROC curve of MIF CD142 was 0.759 (0.641-0.876; p = 0.000) at an optimal cut-off value of 45, which yielded a sensitivity of 60% and a specificity of 77.1%, as well as a PPV and NPV of 69.2% for each.ConclusionEnhanced expression of monocytic TF may have a role in the development and prediction of non-neoplastic PVT in HCV-cirrhosis patients. Large multicenter studies are necessary to validate our results.     

Intestinal permeability in patients with chronic liver diseases: Its relationship with the aetiology and the entity of liver damage

BackgroundAlteration in intestinal permeability may be an important factor in the pathogenesis of both the progression of some chronic liver diseases and the onset of some complications in patients with liver cirrhosis.AimsTo investigate the relationships between intestinal permeability, portal hypertension, alcohol use, plasma levels of pro-inflammatory cytokines, and nitric oxide, expressed as s-nitrosothiols, and nitrite levels in patients with various types and degrees of chronic liver diseases.Methods134 healthy volunteers and 83 patients with chronic liver damage entered the study. Intestinal permeability was assessed with the lactulose/mannitol test. Plasma levels of tumour necrosis factor-alpha, interleukin-6, and nitrite and total s-nitrosothiols were determined.ResultsIntestinal permeability was altered in patients with advanced liver disease and impaired in 15–35% of patients without cirrhosis. Independent factors for intestinal permeability alteration were age, portal hypertension, alcohol use, and diabetes. Plasma levels of inflammatory cytokines and nitrosothiols were significantly higher in patients with altered intestinal permeability.ConclusionsAn intestinal permeability evaluation in patients with chronic liver diseases might clarify the significance of intestinal permeability in the pathophysiology of both the progression of liver damage, and the occurrence of complications that accompany liver cirrhosis.     

One-week losartan administration increases sodium excretion in cirrhotic patients with and without ascites

Background. Losartan, a highly selective angiotensin II type 1 receptor antagonist, has been reported to have a significant portal hypotensive effect in cirrhotic patients. A recent study also showed that losartan exerted a dramatic natriuretic effect in preascitic cirrhosis. The influence of losartan on renal hemodynamics and sodium homeostasis in cirrhotic patients with ascites is unclear. This study was undertaken to evaluate the renal effects of 1-week losartan treatment in cirrhotic patients with and without ascites. Methods. All 12 patients in the study received a daily oral dose of 25 mg losartan for 7 consecutive days. Effective renal plasma flow, urine volume, creatinine clearance, 24h urine sodium excretion and fractional excretion of sodium, blood urea nitrogen, and serum creatinine were measured before and after treatment. Results. In cirrhotic patients without ascites, creatinine clearance, 24-h urinary sodium excretion, and fractional excretion of sodium were significantly increased after losartan administration. Effective renal plasma flow and serum creatinine showed almost no change after treatment. In cirrhotic patients with ascites, creatinine clearance, 24-h urinary sodium excretion, fractional excretion of sodium, and effective renal plasma flow were significantly increased after losartan administration. In addition, the magnitudes of the increases in the fractional excretion of sodium and in the 24-h urinary sodium excretion were greater in cirrhotic patients with ascites than in those without ascites. Conclusions. One-week treatment with losartan increases sodium excretion in association with an improvement of renal function in cirrhotic patients with and without ascites. The natriuretic effect was more profound in cirrhotic patients with ascites than in those without ascites. Received: May 1, 2001 / Accepted: August 24, 2001     

Impact of portal vein thrombosis on the efficacy of endoscopic variceal band ligation

BackgroundInfluence of portal vein thrombosis on efficacy of endoscopic variceal banding in patients with cirrhosis or extrahepatic portal vein obstruction has never been evaluated. Aim of the study was to assess influence of thrombosis on rate and time to eradication in cirrhosis and extrahepatic portal vein obstruction undergoing banding, compared to cirrhotic patients without thrombosis.MethodsRetrospective analysis of 235 consecutive patients (192 with cirrhosis without thrombosis, 22 cirrhosis and thrombosis and 21 extrahepatic portal vein obstruction) who underwent banding. Banding was performed every 2–3 weeks until eradication; endoscopic follow-up was performed at 1, 3, 6 months, then annually.ResultsEradication was achieved in 233 patients. Median time to eradication in cirrhotic patients with portal vein thrombosis vs. cirrhotic patients without thrombosis was 50.9 days (12–440) vs. 43.4 days (13–489.4); log-rank: 0.04; patients with extrahepatic portal vein obstruction vs. cirrhotic patients without thrombosis 63.9 days (31–321.6) vs. 43.4 days (13.0–489.4); log-rank: 0.008. Thrombosis was shown to be the only risk factor for longer time to eradication.ConclusionsPortal vein thrombosis per se appears to be the cause of a longer time to achieve eradication of varices but, once eradication is achieved, it does not influence their recurrence.     

Critical flicker frequency for quantification of low-grade hepatic encephalopathy

Subclinical hepatic encephalopathy (SHE) is currently diagnosed by psychometric tests or neurophysiologic techniques. In view of its sociomedical relevance, simple and reproducible tests for routine diagnosis are required. This study evaluates critical flicker-frequency thresholds for quantification of low-grade hepatic encephalopathy. A total of 115 patients (92 with cirrhosis, 23 controls) were analyzed for HE severity (mental state, computerized psychometric tests), and the threshold frequencies at which light pulses are perceived as fused (fusion frequency) or flickering light (critical flicker frequency [CFF]). CFF was a highly reproducible parameter with little age, day-time, and training dependency. CFFs in cirrhotic patients without HE (HE 0) were not different from those found in noncirrhotic controls. Significantly lower CFFs were found in cirrhotic patients with subclinical or manifest HE, and the various HE groups separated from each other at a high level of significance (P <.01). By using a CFF cut-off value of 39 Hz, a 100% separation of patients with manifest HE from noncirrhotic controls and HE 0 cirrhotic patients was obtained. SHE patients separated from HE 0 cirrhotic patients with high sensitivity (55%) and specificity (100%). The HE severity-dependent differences were found in both, alcoholic and posthepatitic cirrhosis. Statistically significant correlations (P <.01) were found between CFFs and individual psychometric tests. Aggravation of preexisting HE after transjugular intrahepatic portosystemic stent shunt (TIPS) implantation was accompanied by a corresponding decrease of CFF, whereas improvement of HE increased CFF. In conclusion, CFF is a sensitive, simple, and reliable parameter for quantification of low-grade HE severity in cirrhotic patients and may be useful for the detection and monitoring of SHE.     

Management of Hepatic Encephalopathy Not Responsive to First-Line Treatments

Purpose of review

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. 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 findings

Recent studies investigated the role of fecal microbiota transplantation in the treatment of HE with promising results, but further investigations are needed.

Summary

In 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.

     

Circulating levels of pentraxin-3 (PTX3) in patients with liver cirrhosis

BackgroundDespite the circulating levels of PTX3 were related to the severity of various diseases, there are no studies investigating its role in patients with liver cirrhosis. We aimed to study PTX3 levels in patients with liver cirrhosis.Material and methodsA prospective cohort study included 130 patients hospitalized for acute decompensation of liver cirrhosis, 29 stable cirrhotic outpatients and 32 healthy controls evaluated in a tertiary hospital in Southern Brasil.ResultsThe median PTX3 level was significantly higher in stable cirrhotic patients compared to controls (2.6 vs. 1.1 ng/mL; p < 0.001), hospitalized cirrhotic patients compared to controls (3.8 vs. 1.1 ng/mL; p < 0.001), and hospitalized cirrhotic patients compared to stable cirrhotic patients (3.8 vs. 2.6 ng/ mL; p = 0.001). A positive correlation was found between PTX3 and serum creatinine (r = 0.220; p = 0.012), Chronic Liver Failure -Sequential Organ Failure Assessment score (CLIF-SOFA) (r = 0.220; p = 0.010), MELD (r = 0.279; p = 0.001) and Child-Pugh score (r = 0.224; p = 0.010). Significantly higher levels of PTX3 were observed in patients on admission with ACLF (8.9 vs. 3.1 ng/mL; p < 0.001) and MELD score ≥ 20 (6.6 vs. 3.4 ng/mL; p = 0.002). Death within 90 days occurred in 30.8% of patients and was associated with higher levels of PTX3 (5.3 vs. 3.4 ng/mL; p = 0.009). The probability of Kaplan-Meier survival was 77.0% in patients with PTX-3 < 5.3 ng mL (upper tercile) and 53.5% in those with PTX3 ≥ 5.3 ng/mL (p = 0.002).ConclusionThese results indicate the potential for use of PTX3 as an inflammatory biomarker for the prognosis of patients with hepatic cirrhosis.     

Changes in brain catecholamine levels in human cirrhotic hepatic encephalopathy

Hepatic encephalopathy (HE) is currently felt to be secondary to a disturbance in the metabolism of cerebral catecholamines with a decline in dopamine and noradrenaline and a rise in the false neurotransmitter octopamine. The aim of this study was to evaluate brain tissue levels of dopamine, noradrenaline, and octopamine in patients with cirrhosis and HE. This study includes 34 patients: 22 were cirrhotic, 12 were control subjects. Among the 22 cirrhotic patients, 19 had HE, three did not. Tissue specimens were obtained at necropsy from the locus niger, caudate nucleus, hypothalamus, thalamus and frontal cortex, and from the frontal cortex during neurosurgical procedures. Our results showed that (1) dopamine and noradrenaline levels are identical in cirrhotic patients with or without HE and in patients without liver disease (P < 0.05); (2) octopamine levels are higher in control subjects than in patients with cirrhosis and HE. In conclusion, there is no decline in dopamine and noradrenaline levels in the brain tissues of cirrhotic patients with HE, and this is in contradication with the animal findings; octopamine levels are not raised. Hepatic encephalopathy in human liver cirrhosis does not seem to be secondary to a disturbance in cerebral catecholamines.     

Adenosine deaminase activity in tuberculous peritonitis among patients with underlying liver cirrhosis

AIM:To investigate the value of adenosine deaminase (ADA) for early detection of tuberculous peritonitis (TBP) among cirrhotic patients METHODS:We retrospectively analyzed 22 patients with TBP from July 1990 to June 2010 Twenty-five cirrhotic patients with uninfected ascites were prospectively enrolled as the cirrhosis control group from July 2010 to June 2011 An additional group of 217 patients whose ascites ADA levels were checked in various clinical conditions were reviewed from July 2008 to June 2010 as the validation group RESULTS:The mean ascites ADA value of cirrhoticpatients with TBP (cirrhotic TBP group, n = 8) was not significantly different from that of non-cirrhotic patients (non-cirrhotic TBP group, n = 14; 58 1 ± 18 8 U/L vs 70 6 ± 29 8 U/L, P = 0 29), but the mean ascites ADA value of the cirrhotic TBP group was significantly higher than that of the cirrhosis control group (58 1 ± 18 8 U/L vs 7 0 ± 3 7 U/L, P 0 001) ADA values were correlated with total protein values (r = 0 909, P 0 001) Using 27 U/L as the cut-off value of ADA, the sensitivity and specificity were 100% and 93.3%, respectively, for detecting TBP in the validation group CONCLUSION:Even with lower ADA activity in ascites among cirrhotic patients, ADA values were significantly elevated during TBP, indicating that ADA can still be a valuable diagnostic tool.     

Spontaneous portosystemic shunt embolization in liver transplant recipients with recurrent hepatic encephalopathy

Introduction and objectivesSpontaneous portosystemic shunts (SPSS) are a common cause of recurrent hepatic encephalopathy (HE). Shunt occlusion is an effective and safe procedure when performed in patients with cirrhosis and preserved liver function. We aimed to describe our experience with SPSS embolization after liver transplantation (LT).PatientsWe identified five patients who underwent SPSS embolization after LT. Clinical, biochemical and technical procedure data were collected.ResultsAt presentation, all patients had developed graft cirrhosis and HE after LT. Median Model for End-stage Liver Disease (MELD) at embolization was 9 (range 7-12), median Child-Pugh was 8 (range 7-9). Splenorenal and mesocaval shunt were the most frequent types of SPSS found. Three patients have been completely free of HE. Of the two patients who had HE recurrence after embolization, one patient had two episodes of HE which was controlled well with medications. The other patient required three embolizations because of recurrent HE. Median follow-up was 4.4 years (range 1.0-5.0) and MELD score at last follow up was 13 (range 10-18) and median Child-Pugh score B, 7 points (range 5-12).ConclusionsSPSS can be considered as a cause of HE after LT. SPSS embolization is feasible and safe in LT recipients.     

New findings on cerebral ammonia uptake in HE using functional 13N-ammonia PET

PET is a functional imaging technique suitable for studies of brain ammonia metabolism. Dynamic ¹³N-ammonia PET yields time-courses of radioactivity concentrations in brain (PET camera) and blood (samples). Ahl et al. (Hepatology 40:73–79, 2004) and Keiding et al. (Hepatology 43:42–50, 2006) analysed such data in patients with HE by a kinetic model accounting for transfer of ¹³N-ammonia across the blood–brain barrier (BBB) and intracellular formation of ¹³N-glutamine. Initial unidirectional ¹³N-ammonia transfer across BBB was characterized by the permeability-surface area product PS_BBB (ml blood min⁻¹ ml⁻¹ tissue). There was a tendency to lower PS_BBB values in patients with cirrhosis and HE than in patients with cirrhosis without HE and healthy controls but the differences were not statistically significant. Keiding et al. (Hepatology 43:42–50, 2006) also calculated PS_met (ml blood min⁻¹ ml⁻¹ tissue) as a measure of the combined transfer of ¹³N-ammonia across BBB and subsequent intracellular metabolism of ¹³N-ammonia; neither did this PS-value show significant difference between the groups of subjects. Net flux of ammonia from blood into intracellular metabolites was linearly correlated to arterial ammonia. In conclusion, basic brain ammonia kinetics was not changed significantly in patients with cirrhosis +/- HE compared to healthy controls. Blood ammonia seems to be the more important factor for increased brain ammonia uptake in HE.     

Olfactory Function is Affected in Patients with Cirrhosis Depending on the Severity of Hepatic Encephalopathy

Introduction and aim. Olfactory functions are altered to a variable degree by chronic liver disease. Few studies including only small populations of patients emphasized the possibility of hepatic encephalopathy (HE) influencing olfactory nervous tasks. So far, no study has explicitly focused on olfactory function depending on the severity of HE as assessed by objective diagnostic procedures. Thus we performed a study using the “Sniffin’ Sticks” test system, critical flicker-fusion frequency (CFF) and clinical West Haven criteria.Material and methods. 54 cirrhotic patients with liver cirrhosis were included. Furthermore, 43 adult volunteers participating as a non-cirrhotic control group. Olfactory testing was performed using the “Sniffin’ Stick” test battery (Burghart Medizintechnik, Wedel, Germany) which renders a widely-used tool both in clinical and research settings for the assessment of olfactory threshold, odor identification and discrimination. Several complications of cirrhosis were diagnosed by reference methods. Statistical analysis of cirrhosis-associated complications and their relation to olfactory function was performed. Assessment of HE and classification of different stages were performed according to clinical criteria (West- Haven criteria) and according to CFF, which was determined using a portable analyzer.Results. Olfactory function was significantly reduced in cirrhotic patients (in 61.1%) compared to controls (p < 0.001). Among cirrhotics patients, the prevalence of olfactory deficits (hyposmia, anosmia) increased with the severity of HE as assessed by CFF and clinical criteria (p = 0.008 and p = 0.097, respectively). No correlation was observed between olfactory deficits and severity of liver disease as assessed by Child-Pugh-Score, etiology of cirrhosis and complications of cirrhosis such as ascites and portal venous hypertension.Conclusions. Olfactory testing serves as a screening tool for HE and may faciliate grading of HE-severity.     

Chromogranin A levels in chronic liver disease and hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC) is the relevant cause of death in patients with compensated cirrhosis. Alpha-fetoprotein (AFP) is used for screening HCC, with limited success.AimWe evaluated plasma chromogranin A (CgA) as a marker of HCC.PatientsCgA plasma levels and AFP serum levels were prospectively measured in 30 patients with HCC, 14 with cirrhosis, 79 with chronic hepatitis and 65 controls.MethodsCgA was measured with an enzyme-linked immunosorbent assay (DAKO A/S Glostrup, Denmark). AFP was measured by electrochemiluminoimmunoassay (Elecsys, Roche S.p.A., Italy).ResultsCgA levels were significantly higher in the three groups of patients than in controls and in patients with HCC they were significantly higher than in chronic hepatitis patients [median 44.5 (interquartile range 21–145.9) U/L vs. 15.3 (10.9–29.25) U/L, p < 0.001]. AFP values were above the upper reference limit in 75% of patients with HCC, 50% of cirrhotic patients and 11% of chronic hepatitis patients (p < 0.005). CgA values significantly correlated with AFP levels (r_s = 0.42, p < 0.0001). The overall diagnostic accuracy of CgA was 75% (CI 66–82), with a sensitivity of 70% (CI 50.6–85.2) and a specificity of 67% (CI 55.9–76.3).ConclusionsDespite the evidence of higher CgA levels in patients with HCC, this test has low-diagnostic accuracy. Its pathophysiological meaning remains unknown, even if it could suggest an endocrine phenotype of HCC.