[Clinical value of virtual touch tissue quantification and PGA index in evaluation of alcoholic liver fibrosis].

OBJECTIVE: To explore the clinical value of virtual touch tissue quantification (VTQ) technique and the PGA index [prothrombin time (P), γ-glutamyl transpeptadase (GG) and apolipoprotein A1 (ApoAl)] in evaluating the degree of liver fibrosis in alcoholic patients.
 METHODS: A total of 64 patients with long-term alcohol history were enrolled for this study. The liver ultrasonography elasticity was examined by VTQ techniques, the VTQ value was assessed in the liver target region, and then the PGA index was calculated. According the liver biopsy biological results, a golden standard, the patients were divided into a non-fibrosis group (n=11), a fibrosis group (n=10), a significant fibrosis group (n=14) and a cirrhosis group (n=29). The diagnostic value of VTQ and PGA index were compared in alcoholic patients following the classification of liver fibrosis.
 RESULTS: The elastography VTQ values were (1.38±0.33), (1.49±0.30), (1.76±0.22) and (2.28±0.53) m/s; while the PGA indexes were 2.09±0.94, 2.30±1.06, 3.57±1.09, and 2.21±1.99 in the non-fibrosis group, the fibrosis group, the significant fibrosis group and the cirrhosis group, respectively. The VTQ value and PGA index were positively correlated with the classification of liver fibrosis (VTG: r=0.719, PGA: r=0.683; both P<0.01).
 CONCLUSION: The alcoholic liver fibrosis can be assessed by noninvasive VTQ technology and PGA index. As a real-time ultrasound elastography technique, VTQ is more accurate than the PGA index. Combination of the two methods is helpful for early diagnosis and treatment in the patients with alcoholic liver fibrosis.

Evaluation of quantitative portal venous, hepatic arterial, and total hepatic tissue blood flow using xenon CT in alcoholic liver cirrhosis: comparison with liver cirrhosis C.

BACKGROUND/AIMS: Xenon computed tomography (Xe-CT) is a noninvasive method of quantifying and visualizing tissue blood flow (TBF). For the liver, Xe-CT allows separate measurement of hepatic arterial and portal venous TBF. The present study evaluated the usefulness of Xe-CT as a noninvasive diagnostic procedure for measuring hepatic TBF in alcoholic liver cirrhosis (AL-LC), compared with liver cirrhosis C (C-LC). METHODS: Xenon computed tomography was performed on 12 patients with AL-LC and 17 patients with C-LC. The severity of LC was classified according to Child-Pugh classification. Correlations between hepatic TBF and Child-Pugh classification were examined. Correlations of hepatic TBF in Child-Pugh class A to C-LC and AL-LC were also examined. RESULTS: The mean portal venous TBF (PVTBF) was significantly lower in AL-LC than in C-LC (p=0.0316). Similarly, the mean total hepatic TBF (THTBF) was significantly lower in AL-LC than in C-LC (p=0.0390). PVTBF displayed a significant negative correlation with Child-Pugh score (r=-0.396, p=0.0368). CONCLUSIONS: Measurement of hepatic TBF using Xe-CT is useful as a noninvasive, objective method of assessing the state of the liver in chronic liver disease.

Distinct cellular responses differentiating alcohol- and hepatitis C virus-induced liver cirrhosis.

BACKGROUND: Little is known at the molecular level concerning the differences and/or similarities between alcohol and hepatitis C virus induced liver disease. Global transcriptional profiling using oligonucleotide microarrays was therefore performed on liver biopsies from patients with cirrhosis caused by either chronic alcohol consumption or chronic hepatitis C virus (HCV). RESULTS: Global gene expression patterns varied significantly depending upon etiology of liver disease, with a greater number of differentially regulated genes seen in HCV-infected patients. Many of the gene expression changes specifically observed in HCV-infected cirrhotic livers were expectedly associated with activation of the innate antiviral immune response. We also compared severity (CTP class) of cirrhosis for each etiology and identified gene expression patterns that differentiated ethanol-induced cirrhosis by class. CTP class A ethanol-cirrhotic livers showed unique expression patterns for genes implicated in the inflammatory response, including those related to macrophage activation and migration, as well as lipid metabolism and oxidative stress genes. CONCLUSION: Stages of liver cirrhosis could be differentiated based on gene expression patterns in ethanol-induced, but not HCV-induced, disease. In addition to genes specifically regulating the innate antiviral immune response, mechanisms responsible for differentiating chronic liver damage due to HCV or ethanol may be closely related to regulation of lipid metabolism and to effects of macrophage activation on deposition of extracellular matrix components.

Serum concentration of zinc, copper, manganese and magnesium in patients with liver cirrhosis.

The role of trace elements in the pathogenesis of liver cirrhosis and its complications is still not clearly understood. Serum concentrations of zinc, copper, manganese and magnesium were determined in 105 patients with alcoholic liver cirrhosis and 50 healthy subjects by means of plasma sequential spectrophotometer. Serum concentrations of zinc were significantly lower (median 0.82 vs. 11.22 micromol/L, p < 0.001) in patients with liver cirrhosis in comparison to controls. Serum concentrations of copper were significantly higher in patients with liver cirrhosis (median 21.56 vs. 13.09 micromol/L, p < 0.001) as well as manganese (2.50 vs. 0.02 micromol/L, p < 0.001). The concentration of magnesium was not significantly different between patients with liver cirrhosis and controls (0.94 vs. 0.88 mmol/L, p = 0.132). There were no differences in the concentrations of zinc, copper, manganese and magnesium between male and female patients with liver cirrhosis. Only manganese concentration was significantly different between Child-Pugh groups (p = 0.036). Zinc concentration was significantly lower in patients with hepatic encephalopathy in comparison to cirrhotic patients without encephalopathy (0.54 vs. 0.96 micromol/L, p = 0.002). The correction of trace elements concentrations might have a beneficial effect on complications and maybe progression of liver cirrhosis. It would be recommendable to provide analysis of trace elements as a routine.

Abdominal operations in patients with cirrhosis: still a major surgical challenge.

BACKGROUND: Hepatic transplantation and portasystemic shunts can be safely performed in patients with advanced liver disease, whereas other abdominal procedures appear to have a much higher mortality rate. This study reviews the outcomes of patients with cirrhosis after the full spectrum of abdominal operations. METHODS: In a 12-year period, 92 patients diagnosed with cirrhosis required either an emergent or elective abdominal operation. There were four categories of operations: cholecystectomy in 17 patients, hernia in 9, gastrointestinal tract in 54, and other procedures in 12. Fifty-five clinical, laboratory, and operative variables were analyzed to identify factors predictive of poor outcome. RESULTS: Coagulopathy developed in 24 patients (27%) and sepsis in 15 (16%). The mortality rate after emergent operations was 50%, compared to 18% for elective cases (p = 0.001). Other factors that predicted mortality included the presence of ascites (p = 0.006), encephalopathy (p = 0.002), and elevated prothrombin time (p = 0.021). The mortality in Child's class A patients was 10%, compared to 30% in class B and 82% in class C patients. CONCLUSIONS: Patients with cirrhosis undergoing elective or emergent operations are at a significant risk of developing postoperative complications leading to death. The most accurate predictor of outcome is the patient's preoperative Child's class.

Chondrex (YKL-40), a potential new serum fibrosis marker in patients with alcoholic liver disease.

OBJECTIVES: Chondrex (YKL-40) is a mammalian member of a protein family that includes bacterial chitinases. The pattern of its expression in certain tissues such as human liver or cartilage suggests a function in remodelling or degradation of extracellular matrix. The purpose of this study was to assess whether circulating YKL-40 might be a serum fibrosis marker in alcoholics. METHODS: Plasma YKL-40 was determined in 146 consecutive heavy drinkers (106 men, 40 women; mean age, 49.2 +/- 9.0 years). Liver biochemical parameters and serum fibrosis markers such as hyaluronate were also measured. Fibrosis and inflammation in liver biopsy were evaluated using a semi-quantitative scoring system. RESULTS: Plasma YKL-40 increased in parallel with the severity of fibrosis (P<0.00001). YKL-40 also increased in the presence of hepatic inflammation (P<0.01). Receiver operating characteristic curves of Chondrex revealed that a threshold of 330 microg/l gave a specificity of 88.5%; however, the sensitivity was only 50.8%. Only 11.5% of patients without severe fibrosis displayed a Chondrex plasma level above this threshold. A positive correlation was found between Chondrex and hyaluronate (r=0.40, P<0.0001), and a negative correlation was shown between Chondrex and the prothrombin index (r=-0.37, P<0.0001). CONCLUSIONS: The severity of liver fibrosis is associated with elevated circulating Chondrex levels. The overlap in YKL-40 values prevents use of Chondrex in a screening programme. High levels of Chondrex (above 330 microg/l) are predictive of severe liver fibrosis. Increased plasma YKL-40 may reflect the remodelling of liver fibrosis in alcoholics.

Postprandial de novo lipogenesis in alcoholic liver cirrhosis: relationship with fuel homeostasis and nutritional status.

The prevalence and nutritional consequences of postprandial de novo lipogenesis were evaluated in 24 stable alcoholic cirrhotic patients. Energy expenditure and the rates of nutrient oxidation were assessed by indirect calorimetry after an overnight fast and 2 h after a standard meal supplying 15 kcal/kg (63 kJ/kg) of body weight. Postprandially, net lipogenesis occurred in 16 patients (group L+) as shown by a respiratory quotient clearly above 1.00 (P < 0.01). The rate of lipid oxidation remained positive in 8 patients (group L-). The main mechanism involved in this metabolic pathway appeared to be a sharp postprandial hyperinsulinaemia. When compared to group L+, patient group L- showed an impaired thermic effect of food (P < 0.05), a lower rate of glucose oxidation (P < 0.05) and a mild hyperketonaemia (P < 0.05) at fasting levels. Muscular and fat masses were lower (respectively P < 0.05 and P = 0.05) and the severity of the disease as assessed by the Child-Pugh classification was more pronounced in this group (P < 0.02). The occurrence of postprandial lipogenesis in stable cirrhotic patients is related to better nutritional status. Such a metabolic pathway may explain the nutritional heterogeneity of cirrhotics and is likely to have an effect on the benefits of refeeding.

Evaluation of nutritional practice in hospitalized cirrhotic patients: results of a prospective study.

OBJECTIVE: We evaluated the impact of malnutrition and nutrition practice in 396 hospitalized cirrhotic patients (Child stages A, B, and C: 60, 169, and 167 patients) in a readaptative unit for liver diseases. METHODS: Triceps skinfold thickness and mid-arm muscle circumference were measured at admission, and spontaneous dietary intake was evaluated at admission and during hospital stay. RESULTS: Ascites was associated with impairment of nutrition status: 49% and 30.4% of non-ascitic patients, 49.1% and 40.5% of patients with mild ascites, and 65.5% and 48.3% of patients with tense ascites had mid-arm muscle circumferences and triceps skinfold thicknesses, respectively, below the fifth percentile of a reference population (P < 0.05 and P = 0.02, respectively). Decrease in dietary intake paralleled worsening of liver failure: 48% and 34% of Child A patients, 51.7% and 35.8% of Child B patients, and 80.3% and 62.9% of Child C patients at admission had caloric intakes below 30 kcal/kg of body weight and protein intakes below 1 g/kg of body weight, respectively (P < 0.001). Mortality rate was 15.4% during hospital stay; Child-Pugh score (P = 0.0014), age (P = 0.0029), severe septic complications (P = 0.0050), and decrease in caloric intake during hospital stay (P = 0.0072) were independently associated with mortality. Twenty-four patients received enteral feeding that was initiated before admission in four patients and after 12.4 +/- 8.3 d of hospitalization in 20 patients because of low caloric intake (<25 kcal/kg) despite oral supplements. Patients receiving enteral feeding were older (P < 0.01), had a higher Child-Pugh score (P < 0.01), and a higher mortality rate (P < 0.001) than other patients. CONCLUSIONS: Hospitalized cirrhotic patients have a high prevalence rate of malnutrition, and most do not satisfy their nutritional requirements. Decrease in caloric intake is an independent risk factor of short-term mortality. Enteral nutrition after failure of oral supplementation has no clinical benefit. Tube feeding may be indicated earlier in the course of the disease.

Single dose pharmacokinetics of manidipine in hepatic impaired patients and healthy controls.

The pharmacokinetics and safety of a single oral dose of 20 mg manidipine dihydrochloride have been studied in 8 patients with mild to moderate hepatic impairment (grade A or B in Child's classification, or score < or = 7 in Pugh's modification of Child's classification), and in 12 healthy subjects. They received one 20 mg manidipine dihydrochloride tablet with 100 ml of tap water after a standard breakfast. Manidipine was determined using HPLC with electrochemical detection from plasma samples taken up to 24 or 36 h after dosing. The medication was well tolerated. A trend toward higher Cmax, AUC, and MRT was observed in patients with a more severe hepatic impairment, as a consequence of reduction in the liver metabolic function. Patients with grade A hepatic impairment did not exhibit significantly altered pharmacokinetics with respect to healthy subjects, while grade B impairment patients had significantly higher AUC and MRT. Tmax values pointed to reduced absorption rate in patients compared to healthy subjects; the changes were more evident in grade B than grade A patients, although statistical significance was not reached. The reduction in absorption rate in grade B patients is probably related to their higher mean age, since this effect has been reported for manidipine. The pharmacokinetics of manidipine seem only modified in patients with a certain degree of hepatic impairment (at least Pugh grade 6 and Child grade B); therefore, adaptation of the dosing regimen does not seem to be generally recommendable, but should be modulated according to the liver status of the patient.

Coagulation inhibitors in alcoholic liver cirrhosis.

In the present study we have analyzed the relationship between coagulation inhibitors (antithrombin III, protein C and S, thrombomodulin), liver function impairment, and plasma activity of the endothelium-derived proteins plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) in 27 alcoholic cirrhotic patients and 25 controls. Cirrhotics showed decreased values of all the mentioned parameters except for thrombomodulin, PAI-1, and t-PA. Thrombomodulin and t-PA levels were higher in cirrhotics. No relationship was observed between thrombomodulin and t-PA or PAI-1. Protein C and antithrombin III levels were significantly lower in Child's C patients, whereas no correlation was found between t-PA and thrombomodulin and hepatic function derangement. PAI-1 activity was normal in our patients.

Definitive surgical treatment of cholelithiasis in selective patients with liver cirrhosis.

A review of 132 cirrhotic patients with cholelithiasis was carried out. Of the 87 patients who underwent definitive surgical procedures for gallstones, patients of Child's A grade had less operative blood loss, blood transfusion and shorter hospital stay than those of B and C grades. No mortality in cirrhotic patients with Child's A and B grade was found in both emergency and elective surgery. Emergency operation in patients with Child's C grade resulted in more operative blood loss and requirement than elective surgery. Patients in this grade had also a higher morbidity rate and four deaths ensued. Of the 83 survivals after definitive procedures, 78 patients (93.9%) were still alive in the following 62.8 months without any biliary tract symptoms. Of patients who survived after cholecystolithotomy, 6 patients (33.3%) had recurrent stones in the same follow-up period. Therefore, we recommend that definitive biliary surgery be selectively carried out in cirrhotic patients in Child's A and B grade. However, a conservative approach is more suitable in Child's C patients in emergency conditions and definitive procedures should be considered when their liver function improves.

[Prognostic value of plasmatic fibronectin and Child-Pugh classification in alcoholic cirrhotic patients. A comparative study]. / Valor prognóstico da fibronectina plasmática e da classifição de Child-Pugh na cirrose hepática alcoólica. Estudo comparativo.

BACKGROUND: To assess the prognostic value of plasmatic fibronectin (FN), compared to numeric Child-Pugh classification and its biochemical parameters in patients with alcoholic cirrhosis followed prospectively during a 18 months-period. METHODS: Fifty patients with the diagnosis of cirrhosis by hepatic biopsy or clinical and biochemical criteria, were included in the study after the exclusion of hepatocarcinoma and GI bleeding, infection or continous alcohol ingestion in the last 30 days. The mean age was 51.3+/-12.6 years, being 72% males and 17 of them were classified as Child-Pugh A, 18 as B and 15 as C. Serum bilirubin concentration was measured in autoanalyzer, protein electrophoresis was performed on cellulose acetate and prothrombin time by the Quick test. Plasmatic FN was assessed by radial immunodiffusion with anti-human FN in 1% agarose gel slabs. RESULTS: One patient was excluded because no natural death and 12 died owing to hepatic disease. The numeric Child-Pugh [score > 10, Relative Risk (RR)=11.33] and total bilirubins (> 2.5 mg/dL, RR=9.47) were the best predictors of death. Mean plasmatic FN concentration was significantly higher among those who survived when compared with those who died (185+/-66 mg/L x 131+/-38 mg/L, p<0.01), with a RR=6.59, for FN < 165 mg/L. Higher levels of FN, on the other hand, were the best variable to predict survival, since 96% of these 29 patients were alive at the end of follow-up. CONCLUSION: Although having less accuracy in predicting the risk of death of these patients, plasmatic FN > 165 mg/L was better predictor of survival than Child-Pugh score or any one of its biochemical parameters.

Understanding oesophageal varices.

This article describes the aetiology of oesophageal varices, the variety of treatment options available and the physiological and psychological nursing needs of patients undergoing these treatment regimes. Its purpose is to produce a balanced overview, looking at nursing care in the acute period and the long-term support required to meet the complex needs of these patients and their carers. After reading this article you should be able to: Identify what lifestyle risk factors are associated with patients who have oesophageal varices. Describe the underlying physiology that promotes the development of oesophageal varices. State what treatment options are available and their associated complications. Recognise the needs of carers and staff when attending to this client group. Prepare an action plan for the long-term support of a patient prone to further bleeding episodes.

[Effect of fibroscopic sclerotherapy of hemorrhaging esophageal varices on survival in alcoholic liver cirrhosis (comparative retrospective study)]. / Nyelöcsö visszérrepedésböl eredö vérzés fiberoszkópos szklerotizáló kezelésének hatása a túlélésre alkoholos eredetú mäjcirrhosisban (Osszehasonlító, retrospektív tanulmány).

UNLABELLED: Between 1983 and 1992 altogether 638 alcoholic cirrhotic patients had been treated because of acute esophageal variceal bleeding. In 96 cases the treatment were carried out in the following circumstances; volume and coagulation factor substituate, vasopressin or glypressin and nitroglycerin, urgent endoscopy and ballontamponade but in 47 cases an urgent sclerotherapy were also performed. The survival, cases of rebleeding,-from the first bleeding events-of the 49 nonsclerosed patients were compared to those of the 47 sclerosed one. CONCLUSIONS: 1. The endoscopic sclerotherapy proved to be life-saving procedure. 2. Within 30 days the nonsclerosed patients died twice as much number than the slcerosed patients. 3. The lengths of the survival period were found four and half times so long at the sclerosed patients than in nonsclerosed patients (535 versus 125 days). 4. The numbers of the rebleeding were not less at the sclerosed patients than the nonsclerosed subjects. 5. The lengths of the nonbleeding period was found triple so long at the sclerosed patients than in nonsclerosed patients. 6. The survival of the "Child C" patients at the sclerosed and nonsclerosed patients, too. The authors come to conclusion that by the fiberendoscopic sclerotherapy an increase in the survival time of the patients with acute esophageal variceal bleeding in alcoholic cirrhosis can be achieved.

[Hepatitis and cirrhosis of the liver (classification, morphology and morphological differential diagnosis]. / Gepatiti, tsirroz pecheni (klassifikatsiia, morfologiia, morfologicheskaia differentsial'naia diagnostika).

The current classification of hepatitis and hepatocirrhosis is evaluated on the basis of the literature analysis and the study of the author's own material. Morphological criteria for differential diagnosis of liver diseases of viral and alcohol etiology are proposed. A clinical pathologist examining a liver biopsy may confirm or establish the etiology of the disease, determine the degree of activity and compensation of the process. An analysis of these criteria helps a clinician to choose the method of treatment and to determine the prognosis of the disease.

Outcome in decompensated alcoholic cirrhotic patients with acute variceal bleeding.

BACKGROUND: Variceal bleeding (VB) is the leading cause of death in cirrhotic patients with oesophageal varices. We evaluated the efficacy of emergency endoscopic intervention in controlling acute variceal bleeding and preventing rebleeding and death during the index hospital admission in a large cohort of consecutively treated alcoholic cirrhotic patients after a first variceal bleed. METHODS: From January 1984 to August 2011, 448 alcoholic cirrhotic patients (349 men, 99 women; median age 50 years) with VB underwent endoscopic treatments (556 emergency, 249 elective) during the index hospital admission. Endoscopic control of initial bleeding, variceal rebleeding and survival after the first hospital admission were recorded. RESULTS: Endoscopic intervention alone controlled VB in 394 patients (87.9%); 54 also required balloon tamponade. Within 24 hours 15 patients rebled; after 24 hours 61 (17%, n=76) rebled; and 93 (20.8%) died in hospital. No Child-Pugh (C-P) grade A patients died, while 16 grade B and 77 grade C patients died. Mortality increased exponentially as the C-P score increased, reaching 80% when the C-P score exceeded 13. CONCLUSION: Despite initial control of variceal haemorrhage, 1 in 6 patients (17%) rebled during the first hospital admission. Survival (79.2%) was influenced by the severity of liver failure, with most deaths occurring in C-P grade C patients.

Morphometry in histopathology. An image analysis workstation for the pathology laboratory.

OBJECTIVE: To investigate the value of morphometry in comparative histologic analysis of diseases, fixing a set of parameters suitable for analysis and to create a general strategy for data storage and economical data management. STUDY DESIGN: To establish the following fundamental principles for morphometric measurements: (1) linear measurements to determine the distance between two points by using an eyepiece graticule with an engraved scale or alternatively with a ruler on a projected microscopic image or photograph; (2) Stereology based on geometric probability, allowing features in three dimensions to be measured from two-dimensional images; and (3) a computerized image processing and analysis system for image capture, storage and analysis using specialized software and hardware. RESULTS: Measurement procedures were demonstrated in different parameters using regenerative nodules of alcoholic cirrhosis as a model. Comparative analysis between primary biliary cirrhosis, alcoholic cirrhosis, posthepatitic cirrhosis and hepatocellular carcinoma showed the highest regenerative activity in posthepatitic cirrhosis. CONCLUSION: With current advances in computer technology, rapid, automatic measurements can be made from tissue sections and a variety of practical applications for the pathology laboratory, such as nuclear morphometry for comparison of different kinds of liver diseases, including classification of hepatocellular carcinoma.

Abnormal tissue oxygenation in patients with cirrhosis and liver failure.

Systemic haemodynamic and hepatic venous pressures, arterial and mixed venous gases and arterial lactate concentration were measured in 35 patients with histologically proven alcoholic cirrhosis who had been classified into three groups (A, B and C). Eight alcoholic patients without cirrhosis on liver biopsy were also studied. Compared with group A patients, group C patients had significantly higher hepatic venous pressure gradient, cardiac index, O2 transport and arterial lactate concentration and significantly lower systemic vascular resistance, arteriovenous O2 content difference and O2 uptake. In group B patients, corresponding values fell between those of groups A and C. Group A patients, unlike group C patients, were not significantly different from patients without cirrhosis with respect to cardiac index, systemic vascular resistance, O2 uptake and arterial lactate concentration. Our results suggest that in patients with cirrhosis, liver failure-associated hyperdynamic circulation may be accompanied by an abnormal tissue oxygenation.