Alcohol-related liver disease phenotype impacts survival after an acute variceal bleeding episode.

BACKGROUND & AIMS: Alcohol-related hepatitis (AH) encompasses a high mortality. AH might be a concomitant event in patients with acute variceal bleeding (AVB). The current study aimed to assess the prevalence of AH in patients with AVB and to compare the clinical outcomes of AH patients to other alcohol-related liver disease (ALD) phenotypes and viral cirrhosis. METHODS: Multicentre, observational study including 916 patients with AVB falling under the next categories: AH (n = 99), ALD cirrhosis actively drinking (d-ALD) (n = 285), ALD cirrhosis abstinent from alcohol (a-ALD) (n = 227) and viral cirrhosis (n = 305). We used a Cox proportional hazards model to calculate adjusted hazard ratio (HR) of death adjusted by MELD. RESULTS: The prevalence of AH was 16% considering only ALD patients. AH patients exhibited more complications. Forty-two days transplant-free survival was worse among AH, but statistical differences were only observed between AH and d-ALD groups (84 vs. 93%; p = 0.005), when adjusted by MELD no differences were observed between AH and the other groups. At one-year, survival of AH patients (72.7%) was similar to the other groups; when adjusted by MELD mortality HR was better in AH compared to a-ALD (0.48; 0.29-0.8, p = 0.004). Finally, active drinkers who remained abstinent presented better survival, independently of having AH. CONCLUSIONS: Contrary to expected, AH patients with AVB present no worse one-year survival than other patients with different alcohol-related phenotypes or viral cirrhosis. Abstinence influences long-term survival and could explain these counterintuitive results.

The Spanish Pancreatic Club recommendations for the diagnosis and treatment of chronic pancreatitis: part 1 (diagnosis).

Chronic pancreatitis (CP) is a relatively uncommon, complex and heterogeneous disease. The absence of a gold standard applicable to the initial phases of CP makes its early diagnosis difficult. Some of its complications, particularly chronic pain, can be difficult to manage. There is much variability in the diagnosis and treatment of CP and its complications amongst centers and professionals. The Spanish Pancreatic Club has developed a consensus on the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts on this disease. A list of questions was drafted, and two experts reviewed each question. Then, a draft was produced and shared with the entire panel of experts and discussed in a face-to-face meeting. This first part of the consensus addresses the diagnosis of CP and its complications.

The Spanish Pancreatic Club's recommendations for the diagnosis and treatment of chronic pancreatitis: part 2 (treatment).

Chronic pancreatitis (CP) is a complex disease with a wide range of clinical manifestations. This range comprises from asymptomatic patients to patients with disabling symptoms or complications. The management of CP is frequently different between geographic areas and even medical centers. This is due to the paucity of high quality studies and clinical practice guidelines regarding its diagnosis and treatment. The aim of the Spanish Pancreatic Club was to give current evidence-based recommendations for the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts on this disease. These experts were selected according to clinical and research experience in CP. A list of questions was made and two experts reviewed each question. A draft was later produced and discussed with the entire panel of experts in a face-to-face meeting. The level of evidence was based on the ratings given by the Oxford Centre for Evidence-Based Medicine. In the second part of the consensus, recommendations were given regarding the management of pain, pseudocysts, duodenal and biliary stenosis, pancreatic fistula and ascites, left portal hypertension, diabetes mellitus, exocrine pancreatic insufficiency, and nutritional support in CP.

Assessing the short- and long-term prognosis of patients with cirrhosis and acute variceal bleeding.

OBJECTIVE: to evaluate the efficacy of various indicators in predicting short- and long-term survival in patients with cirrhosis and acute variceal bleeding. MATERIAL AND METHODS: prognostic indicators were calculated for a cohort of 201 cirrhotic patients with acute variceal bleeding hospitalized in our center, a third-level teaching hospital. The studied variables were: age, sex, etiology of cirrhosis, endoscopic findings, previous variceal bleeding episodes, human immunodeficiency virus (HIV) infection, hepatocellular carcinoma (HCC), infection during episode, and Child-Turcotte-Pugh (CTP) and Model for End-stage Liver Disease (MELD) scores within 24 hours of bleeding onset. Patients were followed up for at least 6 months until death, liver transplantation, or end of observation. RESULTS: median follow-up was 66.85 weeks (range 0-432.4). The 6-week, 3-month, 12-month and 36-month mortality rates were 22.9, 24.9, 34.3, and 39.8%, respectively. Age >= 65 years, presence of HCC, CTP score >=10, and MELD score >= 18 were the variables associated with mortality in the multivariate analysis. The accuracy of MELD scores as predictors of 6-week, 3-month, 12-month, and 36-month mortality was better than that of CTP scores (c-statistics: 6 week MELD 0.804, CTP 0.762; 3-month MELD 0.794, CTP 0.760; 12-month MELD 0.766, CTP 0.741; 36 month MELD 0.737, CTP 0.717). CONCLUSION: MELD and CTP scores together with age and a diagnosis of hepatocellular carcinoma are useful indicators to assess the short- and long-term prognosis of patients with acute variceal bleeding.

[A cost-effectiveness study of hepatic venous pressure gradient measurement in the secondary prevention of variceal bleeding]. / Estudio coste-efectividad sobre la medición del gradiente de presión venosa hepática en la profilaxis secundaria de la hemorragia digestiva varicosa.

OBJECTIVE: variceal rebleeding is common following a first episode of hemorrhage in cirrhotic patients. The objective of this study was to determine the cost-effectiveness of monitoring hepatic venous pressure gradient (HVPG) to guide secondary prophylaxis. METHODS: we created a Markov decision model to calculate cost-effectiveness for two strategies: Group 1: HVPG monitoring to decide treatment -when portal pressure was reduced by at least 20 percent or HVPG was less than 12 mmHg after beta-blocker administration, patients received beta-blockers; when portal pressure did not meet these criteria therapy was endoscopic band ligation. Group 2: in this group there was no monitoring of HVPG. Patients with large varices received treatment with beta-blockers combined with EBL; patients with small varices received beta-blockers plus isosorbide mononitrate. RESULTS: there was no recurrent variceal bleeding in group 1 for good responders, and for 17% of poor responders. In group 2 a 25% rebleeding rate was detected in patients with small varices and 13% for those with big varices. Overall cost in group 1 was 14,100.49 euros, and 14,677.16 in group 2. CONCLUSIONS: HVPG measurement is cost-effective for the secondary prophylaxis of variceal bleeding.

A comparison of two different dosages of somatostatin combined with sclerotherapy for the treatment of acute esophageal variceal bleeding: a prospective randomized trial.

BACKGROUND: the association of somatostatin (SMT) with endoscopic therapy in patients with cirrhosis and variceal bleeding significantly improves the control of the bleeding episode, and hemodynamic data have shown that a dosage of 500 mg/h allows a more marked reduction of portal pressure versus the usual dosage of 250 mg/h. AIM: to assess if the 500 mg/h dosage is associated with an improved outcome. METHODS: sixty-two patients with variceal bleeding were included in the study. Patients were randomized to receive the usual dosage of SMT (group I: 250 mg/h), or a double dosage (group II: 500 mg/h), together with emergency endoscopic sclerotherapy. RESULTS: the control of the bleeding episode was similar in both groups of patients. Early rebleeding was less frequent in patients receiving double vs. single dosage of SMT (p = 0.06). When considering patients with advanced liver disease (Child-Pugh B or C) early rebleeding was significantly less frequent in patients receiving the 500 mg/h dose of SMT (39 vs. 13%, p = 0.03). CONCLUSIONS: the perfusion of higher doses of SMT (500 mg/h) in association with emergency sclerotherapy in patients with cirrhosis and esophageal hemorrhage significantly decreases the rate of early rebleeding in patients with more advanced stages of liver disease.

Functional status of beta-2-adrenoceptor in isolated membranes of mature erythrocytes from patients with cirrhosis and oesophageal varices.

Propranolol is a widely used drug for prophylaxis of variceal bleeding in patients with cirrhosis, but not all patients show an adequate clinical response. This variability may be in relation to beta adrenoceptor activity, but no information is available in this setting. Thirty-nine patients with advanced cirrhosis and presence of oesophageal varices were sequentially included. We studied the function of beta-2-adrenoceptor in isolated membranes of mature erythrocytes obtained from patients by measuring cyclic AMP (cAMP) production before and after isoproterenol. Blood samples obtained from 11 healthy volunteers were used as control. Patients showed a six-fold increase in the mean basal cAMP production as compared to healthy volunteers. Isoproterenol produced a small, non-significantly and highly variable increase in the AC activity in patients compared with controls. cAMP values remain stable after three months of continuous treatment with oral beta-blockers in both groups. Patients without antecedent of variceal bleeding or with an active alcohol intake showed a significantly higher isoproterenol effect. In conclusion, beta-receptor function in human erythrocytes membranes is altered in patients with cirrhosis and oesophageal varices.

Pharmacokinetic variations of acetaminophen according to liver dysfunction and portal hypertension status.

AIM: To study the pharmacokinetic and metabolism profiles of a single dose of acetaminophen in patients with cirrhosis. METHODS: Oral acetaminophen (1000 mg) was administered to seven healthy subjects and 14 patients with cirrhosis (nine Child-Pugh A or B and five Child-Pugh C grade), being five without and nine with oesophageal varices. Plasma levels of acetaminophen and its metabolites were determined by HPLC. RESULTS: Patients showed a higher mean area under the curve concentration-time (67.4 +/- 22.4 mg h/L vs. 38.8 +/- 4.3 mg h/L; P = 0.01), a lower clearance (166.7 +/- 85.0 mL/min vs. 367.8 +/- 62.5 mL/min; P = 0.01) and higher elimination half-life (3.8 +/- 1.1 h vs. 2.0 +/- 0.4 h; P = 0.01) of acetaminophen than healthy volunteers. The appearance in blood and the urinary excretion of metabolites in patients did not differ from healthy subjects. Absorption profile was faster in patients. Patients with lower mean and systolic arterial pressure had lower AUC of acetaminophen, independently of liver dysfunction stage. CONCLUSIONS: Patients with cirrhosis had a higher AUC and lower clearance of acetaminophen. Acetaminophen attained earlier therapeutic concentrations in patients with oesophageal varices. Mean and systolic arterial pressures were significantly associated with AUC suggesting the importance of the haemodynamic function on the pharmacokinetics of acetaminophen in patients with cirrhosis.

Is obesity a risk factor in acute pancreatitis? A meta-analysis.

BACKGROUND/AIMS: Obesity has been associated with a worse prognosis in acute pancreatitis. According to some authors, obesity favours the development of local complications, while according to other reports obese patients presented more frequently systemic complications. Few studies find a relationship between obesity and mortality in acute pancreatitis. We conducted a meta-analysis of several reports that evaluate the relationship between obesity and the outcome of acute pancreatitis in order to assess its prognostic role in this disease. METHODS: A MEDLINE search was conducted from 1965 to December 2002 with search terms including obesity, body mass index (BMI) and pancreatitis. A total of 12 reports were identified. Of these, only four studies included patients with mild and severe acute pancreatitis and measured obesity by BMI. The end points of the meta-analysis were the severity of acute pancreatitis, local complications, systemic complications and mortality. Obesity was defined when BMI was > or =30 kg/m2. Pooled odds ratio (OR) and confidence intervals (CI) were calculated according to the Mantel-Haenszel method, and heterogeneity was assessed by the multiplicative inverse variance method. RESULTS: A total of 607 patients were evaluated. There was no heterogeneity for the variables severity, systemic complications, local complications and mortality among the included studies. Severe AP was significantly more frequent in obese patients (OR 2.6, 95% CI 1.5-4.6). Furthermore, those patients developed significantly more systemic (OR 2.0, 95% CI 1.1-4.6) and local complications (OR 4.3, 95% CI 2.4-7.9). Mortality in obese patients was only slightly higher (OR 1.3, 95% CI 0.5-3.6). CONCLUSION: Obesity is a prognostic factor favouring the development of systemic and local complications in this disease. Therefore, it should be used routinely as part of the initial assessment of the severity of a case of acute pancreatitis.

[Etiology of upper gastrointestinal bleeding of peptic origin: role of Helicobacter pylori and NSAIDs]. / Etiología de la hemorragia digestiva alta de origen péptico: papel de Helicobacter pylori y los antiinflamatorios no esteroideos.

INTRODUCTION: Upper gastrointestinal bleeding continues to be a severe and frequent complication in ulcerative disease. Etiologic diagnosis in these patients is highly important in order to initiate appropriate treatment and prevent bleeding recurrence. OBJECTIVE: 1. To investigate the prevalence of Helicobacter pylori infection and use of NSAIDs in patients with upper gastrointestinal hemorrhage of peptic origin. 2. To analyze the strategy used for the diagnosis of H. pylori in our previous work. PATIENTS AND MEHTODS: Seventy-three patients with endoscopically-diagnosed upper gastrointestinal bleeding of peptic origin were included in the study. The use of NSAIDs was investigated. H. pylori infection was diagnosed if one of the following tests was positive: urease test, histology, breath test. RESULTS: H. pylori infection was found in 92% of duodenal ulcers and in 88% of gastric ulcers. Fifty-six percent of the patients had taken NSAIDs. Excluding these patients resulted in an H. pylori infection rate of 96.7%. The diagnosis was based on urease test in 46%. In the remaining patients, breath test and histology were required. CONCLUSIONS: The main etiology in patients with upper gastrointestinal bleeding of peptic origin is H. pylori infection followed by the use of NSAIDs, and these two factors frequently coexist. The strategy of performing a urease test and, when this is negative, performing histological study and a breath test, is valid and allows a diagnosis of H. pylori infection to be made even if patients are receiving treatment that could make diagnosis difficult.

Colonic wall thickening in patients with cirrhosis and portal hypertension.

OBJECTIVE: To determine the prevalence of colonic wall thickening (CWT) and its relation with other clinical and radiological findings of portal hypertension. EXPERIMENTAL DESIGN: Retrospective observational study. The follow-up period was at least 1 year. The colon wall was considered to be thickened when it measured > 6 mm. SUBJECTS: The study included 63 patients, what were admitted in Liver Unit of University and General Hospital of Alicante with hepatic cirrhosis who had an abdominal CT scan performed between March 1996 and December 1998. RESULTS: 21 (33.3%) patients showed CWT. This finding was particularly associated with the presence of collateral circulation [ OR = 10.3(1.5-100.8)] and portal thrombosis [OR = 12.8(1.4-118.4)] p<0.05. Patients with CWT tended to develop spontaneous bacterial peritonitis (CWT 14.3% vs no CWT 4.8%) [RR = 3(0.5 -16.6)] but this did not reach statistical significance (p= 0.18). CONCLUSIONS: A third of the patients with cirrhosis and portal hypertension present colonic wall thickening. This finding is related to radiological features and clinical consequences of portal hypertension.

Endotoxin and anti-endotoxin antibodies in the prognosis of acute pancreatitis.

AIMS: We investigate the behaviour of endotoxin in patients with acute pancreatitis and its relationship with the development of complications. EXPERIMENTAL DESIGN: Prospective study. PATIENTS: We assessed plasmatic endotoxin and anti-core endotoxin antibodies (EndoCab IgG and IgM) levels on first and third days from admission in patients with acute pancreatitis episodes, classifying them as mild or severe according to Atlanta's criteria. RESULTS: Nineteen patients were included, seven with severe pancretitis (36.8%) and twelve with mild pancreatitis (63.2%). Endotoxin levels were similar on first day in both mild and severe pancreatitis, and higher in the latter on third day (p > 0.05). Patients with severe pancretitis had lower EndoCab IgM levels on first and third days from admission (day 1: 18.3 vs 33.3 MU/ml, p < 0.01; day 3: 18.4 vs 33.4 MU/ml, p < 0.05). When analysed separately systemic and local complications, we observed, in the same days, a decrease of EndoCab IgM levels in patients who developed systemic complications (day 1: 18.3 vs 32.7 MU/ml, p = 0.01; day 3: 18.3 vs 35.1 MU/ml, p < 0.01). EndoCab IgG levels were also lower in severe acute pancreatitis in both determinations, but differences weren't significant. CONCLUSIONS: EndoCab levels decrease early in severe acute pancreatitis, mainly if systemic complications are present. This antibody depletion is greater for IgM than IgG, and seems to occur earlier than an increase in endotoxemia.

[Fecal elastase-1 determination in the diagnosis of chronic pancreatitis]. / Determinación de la elastasa-1 fecal en el diagnóstico de la pancreatitis crónica.

UNLABELLED: The diagnosis of chronic pancreatitis is based on morphological and functional data. To evaluate exocrine function, the secretin-cholecystokinin test is the gold standard but this is invasive and frequently unavailable. Recently, fecal elastase-1 determination has been investigated as an indirect test of pancreatic function. OBJECTIVE: To evaluate the diagnostic value of fecal elastase-1 in chronic pancreatitis by comparing it with other indirect methods of evaluating pancreatic function such as the urine pancreolauryl test and fecal chymotrypsin determination. To do this, we analyzed the three diagnostic methods in four groups of patients: group I (14 patients with confirmed chronic pancreatitis); group II (5 patients with recurrent episodes of acute alcoholic pancreatitis; group III (9 patients with non-pancreatic diarrhea); group IV (8 patients with other gastrointestinal diseases). RESULTS: Compared with the control groups (groups III and IV), patients in groups I and II presented lower levels of fecal elastase-1 (groups I-II: 88 mcg/g, groups III-IV: 635 mcg/g, p < 0.0001), fecal chymotrypsin (4.3 U/g and 29.3 U/g, respectively, p < 0.0001), and pancreolauryl (14% and 54%, respectively, p < 0,001). In the diagnosis of confirmed chronic pancreatitis (group I) the fecal elastase-1 and pancreolauryl tests showed a sensitivity of 85.6% and 78.5%, respectively. However, in group II, the most sensitive test was the pancreolauryl test (80% versus 60% for the chymotrypsin test and only 40% for the fecal elastase-1 test). In contrast, the fecal elastase-1 test showed the highest specificity (94.1% versus 88.2% for the fecal chymotrypsin test and 81.3% for the pancreolauryl test). CONCLUSION: Fecal elastase-1 determination is an effective indirect method in the diagnosis of patients with advanced chronic pancreatitis. However, when the disease is in the early stages, its sensitivity is no greater than that of other indirect tests. The greatest advantage of this test is its high specificity.

Comparison of diagnostic methods for Helicobacter pylori infection in patients with upper gastrointestinal bleeding.

BACKGROUND: Accuracy of the most frequently used tests for diagnosing Helicobacter pylori infection in patients with upper gastrointestinal bleeding of peptic origin is determined. METHODS: Seventy-eight patients with endoscopically-proven upper gastrointestinal bleeding of peptic origin were included. The presence of H. pylori was considered when observed from the histology or, if negative, when serology and breath test were both positive. Accuracy of the rapid urease test was estimated in accordance with results obtained with other diagnostic methods. RESULTS: Lesions causing gastrointestinal bleeding were 56 duodenal ulcers, 13 gastric ulcers, 7 pyloric channel ulcers, 13 acute lesions of the gastric mucosa and 16 erosive duodenitis. H. pylori infection was present in 68 patients (87.2%). Forty-four patients had received non-steroidal anti-inflammatory drugs. The sensitivity/specificity (%) of the diagnostic methods was 48.5/100 for the rapid urease test, 91/77.8 for the breath test, 89.5/80 for serology and 86.3/100 for histology. The prior consumption of proton-pump inhibitors and antibiotics induced false-negative results in the rapid urease test and breath test, with no effect on serology and histology. CONCLUSIONS: The prevalence of H. pylori infection in patients with upper gastrointestinal bleeding from peptic lesions is high. Sensitivity of the rapid urease test for diagnosing H. pylori is low in this setting. Cases with negative rapid urease test need the combination of two or more additional tests if diagnosis is to be achieved. Cases with positive rapid urease test do not need further investigation for diagnosis.

Development of quinolone-resistant strains of Escherichia coli in stools of patients with cirrhosis undergoing norfloxacin prophylaxis: clinical consequences.

BACKGROUND/AIM: Norfloxacin prophylaxis decreases the incidence of bacterial infections in high-risk cirrhotic patients, but may promote the development of quinolone-resistant gram-negative bacteria in stools, and eventually lead to infections due to these bacteria. The aim of the study was to evaluate the prevalence of quinolone-resistant strains of E. coli in stools on admission, and the characteristics of any nosocomial infections. METHODS: Eighty-three consecutively hospitalized cirrhotic patients were included in this prospective study. The presence of quinolone-resistant strains of E. coli in stools on admission, and the characteristics of any nosocomial infections were recorded. RESULTS: Fourteen out of 83 patients (16.8%) showed quinolone-resistant E. coli in stools (Group I), and 69 did not (Group II). Thirteen out of 14 from Group I (92.8%) and 17/69 (24.6) from Group II had received primary or secondary prophylaxis with norfloxacin (p<0.001). During hospitalization, 12/12 (100%) of patients from Group I and 25/66 (37.8%) of patients from Group II underwent norfloxacin prophylaxis. Three bacterial infections in patients from Group I, 3 from Group II patients receiving norfloxacin and 16 from Group II patients not receiving norfloxacin were recorded (p<0.05). No infections due to quinolone-resistant E. coli were observed in patients colonized with these bacteria. Treatment with norfloxacin induced the development of quinolone-resistant E. coli in 6/14 (42.8%) patients in a mean time of 18.5+/-9.8 days. CONCLUSIONS: The development of quinolone-resistant strains of E. coli is significantly associated with previous administration of norfloxacin prophylaxis. However, in our series this fact is not associated with an increased incidence of quinolone-resistant E. coli or other gram-negative infections.

Obesity: a prognostic factor of severity in acute pancreatitis.

This study was conducted to assess the prognostic value of obesity in acute pancreatitis and to determine the role played by obesity-associated diseases in the course of the disease. We prospectively studied 49 patients with acute pancreatitis who were divided into three groups according to their body mass index (BMI). There were 22 patients in group I (BMI < or = 25 kg/m2, normal or low weight); 15 in group II (BMI >25 and < or = 29 kg/m2, overweight); and 12 in group III (BMI >29 kg/m2, obese). Other anthropometric parameters also were measured. The severity of pancreatitis was assessed according to the Atlanta classification system. Systemic complications were significantly more common among obese than nonobese patients (p < 0.05). Patients with severe pancreatitis had a higher body-fat percentage, measured by the subscapular skin-fold thickness, and a larger abdominal circumference than patients with mild pancreatitis. Although hypertensive or diabetic patients developed more systemic complications, the multivariate analysis demonstrated that the presence of these underlying diseases did not modify the prognostic role of obesity in acute pancreatitis. We conclude that obesity is a prognostic factor of outcome in acute pancreatitis. Obesity-associated diseases do not vary the prognostic value of obesity. It seems that truncal adiposity is the kind of obesity related to worse outcome of acute pancreatitis.