[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.

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.

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.

[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.

Valor prognóstico da fibronectina plasmática e da classificação de Child-Pugh na cirrose hepática alcoólica: estudo comparativo / Prognostic value of plasmatic fibronectin and Child-Pugh classification in alcoholic cirrhotic patients: a comparative study

OBJETIVOS: Avaliar o valor prognóstico da fibronectina plasmática (FN), comparativamente à classificação numérica de Child-Pugh e os parâmetros bioquímicos que a compõem, no acompanhamento prospectivo de portadores de cirrose alcoólica durante 18 meses. MÉTODOS: Incluídos 50 pacientes com cirrose alcoólica, diagnosticada por biópsia ou critérios clínico-bioquímicos, excluídos aqueles com hepatocarcinoma ou hemorragia digestiva, infecção ou ingestão alcoólica continuada nos últimos 30 dias. A idade média do grupo foi 51,3±12,6 anos, 72 por cento deles do sexo masculino e classificados 17 como Child-Pugh A, 18 como B e 15 como C. Os valores das bilirrubinas foram dosados pelo método automatizado, eletroforese de proteínas em acetato de celulose e o tempo de protrombina pelo método de Quick. A FN plasmática foi dosada por imunodifusão radial, com anticorpos contra FN humana em géis de agarose a 1 por cento. RESULTADOS: Um paciente foi excluído por óbito de causa não natural e 12 foram a óbito por doença hepática. Os melhores preditores de óbito foram a pontuação de Child-Pugh [escore>10, risco relativo (RR) de 11,33) e os valores de bilirrubina (>2,5mg/dL, RR=9,47). A concentração de FN foi significantemente maior nos sobreviventes que naqueles que foram a óbito (185±66 mg/L x 131±38mg/L, p<0,01), com RR = 6,59 para FN<165mg/L. Valores de FN acima desse valor de corte, entretanto, foram os melhores indicadores de sobrevida desde que 96,5 por cento desses 29 pacientes estavam vivos ao final de 18 meses de seguimento. CONCLUSAO: Embora apresente menor acurácia em predizer o risco de óbito desses pacientes, valores de FN plasmática> 165mg/L foram melhores indicadores de sobrevida que a classificação de Child-Pugh e seus parâmetros bioquímicos isolados.

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.

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.

Transjugular intrahepatic portosystemic shunt for trauma?

We report a case of successful emergency TIPS placement to control intra-abdominal bleeding after blunt abdominal trauma in a patient with severe cirrhosis and portal hypertension.

Severe bleeding following endoscopic variceal ligation: should EVL be avoided in Child C patients?

In the last decade there has been an evolution in the treatment of bleeding oesophageal varices. Endoscopic variceal ligation (EVL) is one of those new techniques that not only has shown to be more effective than sclerotherapy, but also causes less side effects, resulting in less episodes of rebleeding and improving survival. We describe severe bleeding in 3 patients after EVL, occurring between 5 and 10 days after the initial ligation. Two Child C patients could not be resuscitated and died shortly after this event. Severely impaired clotting function as a result of the liver disease and the greater size of the ulcers induced by EVL may contribute to this dramatic complication. Severe bleeding due to postligation ulceration may lead to death, which occurred in 2 of our Child C patients. Since more and more endoscopists are using EVL in the treatment of oesophageal variceal bleeding, they should be aware of the possible complications caused by this rather new technique.

Increased circulating leptin in alcoholic cirrhosis: relation to release and disposal.

Leptin is a cytokine peptide that decreases appetite and thereby food intake and increases energy expenditure. It is produced in fat cells, but recent animal experiments have shown expression of leptin in modified stellate hepatic cells. Because a change in circulating leptin in cirrhosis could be caused by an altered production rate, altered disposal rate, or both, the present study was undertaken to identify regions of leptin overflow into the blood stream and regions of leptin extraction. Patients with alcoholic cirrhosis (n = 16) and control patients without liver disease (n = 12) were studied during catheterization with elective blood sampling from different vascular beds. Blood samples for leptin determination (radioimmunoassay) were taken simultaneously from artery/hepatic vein, artery/renal vein, artery/iliac vein, and artery/cubital vein. Patients with cirrhosis had significantly increased circulating leptin (7.3 vs. control 2.6 ng/mL, P <.002) that correlated directly to ascitic-free body mass index (r = 0.71, P <.005). A significant renal extraction ratio of leptin was observed in control patients (0. 16) and in patients with cirrhosis (0.07), but the latter value was significantly lower than in the control patients (-44%, P <.05) and inversely correlated to serum creatinine (r = -0.60, P <.05). A significant, but equal, hepatosplanchnic extraction of leptin was observed in cirrhotic patients and control patients (0.08 vs. 0.07). In patients with cirrhosis a significant cubital venous-arterial difference in leptin was observed, but not in control patients. The iliac venous/arterial leptin ratio was significantly above 1.0 in both groups and of similar size (1.16 vs. 1.15), but a higher difference in concentration was found in the cirrhotic patients (+33%, P <.05). The spillover rates of leptin in cirrhotic patients may be even higher than estimated from the increased systemic veno-arterial gradients. In conclusion, the elevated circulating leptin in patients with cirrhosis is most likely caused by a combination of decreased renal extraction and increased release from subcutaneous abdominal, femoral, gluteal, retroperitoneal pelvic, and upper limb fat tissue areas. The hepatosplanchnic bed drained through hepatic veins could not be identified as a source of increased circulating leptin in cirrhosis, but a contribution by the portosystemic collateral flow cannot be excluded.

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.

Enfermedad hepática alcohólica en el Hospital Universitario de la samaritana (HUS) de Santafé de Bogotá, D.C

Se presenta un estudio clínico prospectivo, descriptivo de 5 años de duración, llevado cabo en la unidad de Gastroenterología del Hospital Universitario de La Samaritana (HUS), realizado 121 pacientes con Enfermedad hepática alcohólica. Fueron notorios el predominio del sexo masculino, la procedencia rural, prolongado tiempo de consumo, los altos volúmenes ingeridos, el predominio de bebidas fermentadas; el avanzado estado de deterioro clínico de los pacientes al momento de la evaluación; lo cual se corroboró mediante la clasificación de CHILD-PUGH

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.

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.

Video laparoscopy for the treatment of bleeding esophageal varices.

Bleeding from esophageal varices is the major cause of death in patients with portal hypertension. The ideal surgical procedure should effectively control bleeding, with as little impairment of liver function as possible and with low rates of encephalopathy. Based on this objective, we propose the azygoportal disconnection (APD) with splenic artery ligation, and suturing of the gastric and esophageal varies without opening the esophagus, by video laparoscopy. With the patient placed in a semigynecologic position, we use five trocars, and the intervention begins by dissection of the diaphragmatic hiatus and isolation of the esophagus. Then devascularization of the gastric fundus is accomplished. After that, dissection and ligature between clips of the splenic artery are performed. The surgery proceeds with dissection and ligation of the vessels of the lesser curvature. After orally introducing a 12-mm Fouchet probe, we suture the varices of the distal esophagus transmurally, with interrupted sutures. The procedure is accomplished with a floppy Nissen valve. Between March 1994 and May 1995, four patients were treated with this method, two men and two women with a mean age of 54 years. All of them had hepatic cirrhosis. Three patients were classified Child B and the other Child C. Surgical indication in all subjects was persistent bleeding of the esophageal varices, after failure of such clinical attempts as endoscopic sclerosis and tamponade with the Sangstaken-Blakemore balloon. The operation mean time was 177 min. Neither bleeding nor hemodynamic changes occurred during the surgery. The patients were sent to the intensive care unit (ICU) postoperatively for a mean time of 3 days, and they were discharged from the hospital between days 8 and 10. The evolution demonstrated stabilization of the hepatic function and regression of the varices from grades III and IV to grade I. No bleeding recurred. Although this study had a small number of patients, we believe that this operation made by mini-invasive technique permits a quick recovery, reducing the global morbidity of this procedure.