Screening for hepatic encephalopathy (HE) that does not cause obvious disorientation or asterixis (minimal HE MHE/grade 1 HE) is important. We examined if the animal naming test (ANT1) (maximum ...number of animals listed in 1 minute) is useful in this context. In total, 208 healthy controls, 40 controls with inflammatory bowel disease, and 327 consecutive patients with cirrhosis underwent the ANT1. Patients were tested for MHE by the psychometric HE score, and 146 were assessed by electroencephalography; 202 patients were followed up regarding the occurrence of overt HE and death. In the healthy controls, ANT1 was influenced by limited education (<8 years) and advanced age (>80 years, P < 0.001). Using an age and education adjusting procedure, the simplified ANT1 (S‐ANT1) was obtained. An S‐ANT1 of <10 animals was abnormal. Of the patients, 169 were considered unimpaired, 32 as having HE ≥grade 2, and 126 as having MHE/grade 1 HE. This group had lower S‐ANT1 than unimpaired patients (12 ± 0.4 versus 16 ± 0.7, P < 0.001) and higher S‐ANT1 than those with HE ≥grade 2 (4 ± 0.9). In grade 1 HE the S‐ANT1 was lower than in MHE. Following receiver operating characteristic analysis (Youden's index), 15 animals produced the best discrimination between unimpaired and MHE/grade 1 HE patients. Thus, a three‐level score (0 for S‐ANT1 ≥15, 1 for 10 ≤ S‐ANT1 < 15, 2 for S‐ANT1 <10) was obtained. This score was correlated both to the psychometric HE score (P < 0.0001) and to electroencephalography (P = 0.007). By sample random split validation, both S‐ANT1 and its three‐level score showed prognostic value regarding the 1‐year risk of overt HE and death. No inflammatory bowel disease control had S‐ANT <15. Conclusion: The S‐ANT1 is an easily obtainable measure useful for the assessment of HE. (Hepatology 2017;66:198–208).
Spontaneous portosystemic shunts (SPSS) are common in cirrhosis. Their characterization and clinical implications remain unclear.
To devise a system of assessment of these shunts, and assess their ...clinical implications
We retrospectively studied patients with cirrhosis who underwent imaging in a liver transplant program. A novel index was computed to assess total SPSS -the diameter of a circle having an area equivalent to the sum of the areas of all the existing shunts. This ‘SPSS equivalent diameter’ was compared with the clinical variables.
Among 127 patients, 70% (CI95% 62–77) had SPSS, and 57% (CI95% 62–77) had multiple SPSS. The risk for SPSS was related to the severity of cirrhosis (Child-Pugh B/C vs. A: OR 2.4 CI95% 1.1–5.4) and alcoholic aetiology (OR 2.9 CI95% 1.2–7.1). The SPSS equivalent diameter was related to a history of HE, cognitive impairment (EEG/PHES) and ammonia(p<0.05). The diameter of the inferior cava vein >19.5 mm was a predictor of large SPSS (AUC 0.77, CI95%:0.68–0.87, p ≤ 0.001).
The SPSS equivalent diameter, a comprehensive assessment of portosystemic shunting, was associated with severity of liver disease, hyperammonemia, and cognitive dysfunction. The diameter of the inferior vena cava was a good predictor of SPSS.
AIM:To investigate the agreement and prognosticvalue of different measures of covert hepatic encephalopathy(CHE).METHODS:One-hundred-and-thirty-two cirrhotic outpatients underwent ...electroencephalography(EEG),paper-and-pencil psychometry(PHES)and critical flicker frequency,scored on the original/modified(CFFo/CFFm)thresholds.Eighty-four patients underwent Dopplerultrasound to diagnose/exclude portal-systemic shunt.Seventy-nine were followed-up for 11±7 mo in relation to the occurrence of hepatic encephalopathy(HE)-related hospitalisations.RESULTS:On the day of study,36%had gradeⅠHE,42%abnormal EEG,33%abnormal PHES and 31/21%abnormal CFFo/CFFm.Significant associations were observed between combinations of test abnormalities;however,agreement was poor(Cohen’sκ<0.4).The prevalence of EEG,PHES and CFFo/CFFm abnormalities was significantly higher in patients with gradeⅠovert HE.The prevalence of EEG and CFFm abnormalities was higher in patients with shunt.The prevalence of EEG abnormalities was significantly higher in patients with a history of HE.During follow-up,10 patients died,10were transplanted and 29 had HE-related hospitalisations.GradeⅠHE(P=0.004),abnormal EEG(P=0.008)and abnormal PHES(P=0.04)at baseline all predicted the subsequent occurrence of HE;CFF did not.CONCLUSION:CHE diagnosis probably requires a combination of clinical,neurophysiological and neuropsychological indices.
Background/Aims
: The incidence and natural history of small esophageal varices (EV) in cirrhotics may influence the frequency of endoscopies and the decision to start a pharmacological treatment in ...these patients.
Methods
: We prospectively evaluated 206 cirrhotics, 113 without varices and 93 with small EV, during a mean follow-up of 37±22 months. Patients with previous gastrointestinal bleeding or receiving any treatment for portal hypertension were excluded. Endoscopy was performed every 12 months.
Results
: The rate of incidence of EV was 5% (95%CI: 0.8–8.2%) at 1 year and 28% (21.0–35.0%) at 3 years. The rate of EV progression was 12% (5.6–18.4%) at 1 year and 31% (21.2–40.8%) at 3 years. Post-alcoholic origin of cirrhosis, Child–Pugh's class (B or C) and the finding of red wale marks at first examination were predictors for the variceal progression. The two-years risk of bleeding from EV was higher in patients with small varices upon enrolment than in those without varices: 12% (95% CI: 5.2–18.8%) vs. 2% (0.1–4.1%); (
P
<0.01). Predictor for bleeding was the presence of red wale marks at first endoscopy.
Conclusions
: In patients with no or small EV, endoscopy surveillance should be planned taking into account cause and degree of liver dysfunction.
Beta-blockers are extensively used to prevent variceal bleeding in patients with large esophageal varices. It is not established if beta-blockers delay the growth of small varices.
A total of 161 ...patients with cirrhosis and small esophageal varices (F1 according to the classification of Beppu et al.) without previous bleeding were enrolled. A total of 83 patients were randomized to nadolol (dose adjusted to decrease resting heart rate by 25%; mean dose given, 62 +/- 25 mg/day) and 78 to placebo. The principal end point was occurrence of large esophageal varices (F2 or F3 according to the classification of Beppu et al.). Endoscopic examination was performed after 12, 24, 36, 48, and 60 months of follow-up. Mean follow-up was 36 months.
The 2 groups were well matched for demographic and clinical characteristics. During the study period, 9 patients randomized to nadolol and 29 randomized to placebo had growth of esophageal varices. At the end of follow-up, the cumulative risk was 20% versus 51% (P < 0.001) (absolute risk difference, 31%; 95% confidence interval, 17%-45%). When possible confounding factors were taken into account, treatment was a significant factor predicting growth of varices (odds ratio, 4.0; 95% confidence interval, 1.95-8.4). The cumulative probability of variceal bleeding was also lower in patients randomized to nadolol (P = 0.02). Survival was not different (P = 0.33). Adverse effects resulting in withdrawal of drug occurred in 9 in the nadolol group and one in the placebo group (P = 0.01).
This study suggests that beta-blocker prophylaxis of variceal bleeding in patients with compensated cirrhosis should be started when small esophageal varices are present.
Alström syndrome (ALMS) is an ultra-rare monogenic disease characterized by insulin resistance, multi-organ fibrosis, obesity, type 2 diabetes mellitus (T2DM), and hypertriglyceridemia with high and ...early incidence of non-alcoholic fatty liver disease (NAFLD). We evaluated liver fibrosis quantifying liver stiffness (LS) by shear wave elastography (SWE) and steatosis using ultrasound sonographic (US) liver/kidney ratios (L/K) in 18 patients with ALMS and 25 controls, and analyzed the contribution of metabolic and genetic alterations in NAFLD progression. We also genetically characterized patients. LS and L/K values were significantly higher in patients compared with in controls (
< 0.001 versus
= 0.013). In patients, LS correlated with the Fibrosis-4 Index and age, while L/K was associated with triglyceride levels. LS showed an increasing trend in patients with metabolic comorbidities and displayed a significant correlation with waist circumference, the homeostasis model assessment, and glycated hemoglobin A1c. SWE and US represent promising tools to accurately evaluate early liver fibrosis and steatosis in adults and children with ALMS during follow-up. We described a new pathogenic variant of exon 8 in
. Patients with ALMS displayed enhanced steatosis, an early increased age-dependent LS that is associated with obesity and T2DM but also linked to genetic alterations, suggesting that
could be involved in liver fibrogenesis.
Portal hypertension is primarily caused by the increase in resistance to portal outflow and secondly by an increase in splanchnic blood flow, which worsens and maintains the increased portal ...pressure. Increased portal inflow plays a role in the hyperdynamic circulatory syndrome, a characteristic feature of portal hypertensive patients. Almost all the known vasoactive systems/substances are activated in portal hypertension, but most authors stress the pathogenetic role of endothelial factors, such as COX-derivatives, nitric oxide, carbon monoxide. Endothelial dysfunction is differentially involved in different vascular beds and consists in alteration in response both to vasodilators and to vasoconstrictors. Understanding the pathogenesis of portal hypertension could be of great utility in preventing and curing the complications of portal hypertension, such as esophageal varices, hepatic encephalopathy, ascites.
Epidemiological studies indicate that a growing number of cirrhotic patients will develop hepatocellular carcinoma (HCC) in the next decade. Recent findings have demonstrated that Squamous cell ...carcinoma antigen 1 (SCCA1) and 2 (SCCA2) isoforms, now classified as serpinB3 and serpinB4, are over-expressed in HCC, but not in normal liver. As reported, high levels of circulating SCCA-IgM immunocomplexes in patients with cirrhosis are significantly associated with HCC development.
To ascertain whether IgM-linked SCCA isoforms circulate in patients with chronic liver disease, compared to total SCCA-IgM levels.
79 patients with chronic liver disease were studied, including 17 patients with chronic hepatitis, 36 patients with cirrhosis and 26 with HCC. 28 blood donors were used as control. Monoclonal antibodies against serpinB3 and serpinB4 were used as catcher antibodies to set up specific ELISA assays, while total SCCA-IgM immunocomplexes were detected by commercially available ELISA assay. Overall, the results revealed a better diagnostic sensitivity of total SCCA-IgM assay, compared to both serpinB3 and serpinB4 IgM-linked assays. SerpinB4-IgM median values obtained with SCC103 antibody were moderately higher in patients with cirrhosis than in those with HCC, median values: 0.168 (IQR 0.140-0.427) vs. 0.140 (IQR 0.140-0.278), (p = 0.177). A trend toward decreasing serpinB4-IgM/serpinB3-IgM median ratio was observed in patients with advanced liver disease, being 1.08 in patients with HCC, 1.10 in patients with cirrhosis and 1.40 in patients with chronic hepatitis (p = 0.079).
IgM-linked SCCA isoforms in serum of patients with chronic liver diseases were quantified for the first time. Although the number of patients was limited, this preliminary study reveals that the relative balance of the two serpin isoforms is altered in HCC and it is characterized by a lower serpinB4-IgM/serpinB3-IgM ratio, determined by lower serpinB4 levels.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
AIM:To evaluate the most cost-effectiveness strategy for preventing variceal growth and bleeding in patients with cirrhosis and small esophageal varices.METHODS:A stochastic analysis based on ...decision trees was performed to compare the cost-effectiveness of beta-blockers therapy starting from a diagnosis of small varices(Strategy 1)with that of endoscopic surveillance followed by beta-blockers treatment when large varices are demonstrated(Strategy 2),for preventing variceal growth,bleeding and death in patients with cirrhosis and small esophageal varices.The basic nodes of the tree were gastrointestinal endoscopy,inpatient admission and treatment for bleeding,as required.All estimates were performed using a Monte Carlo microsimulation technique,consisting in simulating observations from known probability distributions depicted in the model.Eight-hundred-thousand simulations were performed to obtain the final estimates.All estimates were then subjected to Monte Carlo Probabilistic sensitivity analysis,to assess the impact of the variability of such estimates on the outcome distributions.RESULTS:The event rate(considered as progression of varices or bleeding or death)in Strategy 124.09%(95%CI:14.89%-33.29%)was significantly lower than in Strategy 260.00%(95%CI:48.91%-71.08%).The mean cost(up to the first event)associated with Strategy 1823£(95%CI:106£-2036£)was not significantly different from that of Strategy 2799£(95%CI:0£-3498£).The cost-effectiveness ratio with respect to this endpoint was equal to 50.26£(95%CI:-504.37£-604.89£)per event avoided over the four-year follow-up.When bleeding episodes/deaths in subjects whose varices had grown were included,the mean cost associated with Strategy 1 was 1028£(95%CI:122£-2581£),while 1699£(95%CI:171£-4674£)in Strategy 2.CONCLUSION:Beta-blocker therapy turn out to be more effective and less expensive than endoscopic surveillance for primary prophylaxis of bleeding in patients with cirrhosis and small varices.
Hepatorenal syndrome is a severe complication of advanced liver cirrhosis, in patients with ascites and marked circulatory dysfunction. It is clearly established that it has a functional nature, and ...that it is related to intense renal vasoconstriction. Despite its functional origin, the prognosis is very poor. In the present review, the most recent advances in diagnosis, pathophysiology, and treatment are discussed. Recent developments in pathophysiology are the basis of the new therapeutic strategies, which are currently under evaluation in randomised clinical trials.