Miguel Pérez-Mateo

Obesity Is a Definitive Risk Factor of Severity and Mortality in Acute Pancreatitis: An Updated Meta-Analysis

Background/Aims: Obesity is considered a risk factor in patients with acute pancreatitis. However, the relationship between obesity and mortality in this disease has not been confirmed definitively even in a previous meta-analysis. Since the publication of our previous meta-analysis, one study has been reported about the prognostic value of obesity in acute pancreatitis. We have performed a new meta-analysis to confirm the relationship between obesity and the outcome of acute pancreatitis. Data Sources: A MEDLINE search using ‘pancreatitis’, ‘obesity’ and ‘body mass index’ as search terms. Review Methods: Clinical studies which investigated the prognostic value of obesity in acute pancreatitis with the following criteria: (a) inclusion of mild and severe acute pancreatitis; (b) use of body mass index (BMI) as the measure of obesity; (c) definition of obesity as BMI ≧30 kg/m2; (d) definition of severity of acute pancreatitis according to the criteria established in the Atlanta Symposium. Five studies including patients with mild and severe acute pancreatitis and obesity measured by BMI were analyzed. The end points of the meta-analysis were the severity of acute pancreatitis, local complications, systemic complications and mortality. 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: Seven hundred and thirty-nine patients were included. There was no heterogeneity for the variables severity, systemic complications, local complications and mortality among the included studies. Severe acute pancreatitis was significantly more frequent in obese patients (OR 2.9, 95% CI 1.8–4.6). Furthermore, those patients developed significantly more systemic (OR 2.3, 95% CI 1.4–3.8) and especially local complications (OR 3.8, 95% CI 2.4–6.6). In this new analysis, mortality was also higher in obese patients (OR 2.1, 95% CI 1.0–4.8). Conclusion: Obesity is not only a risk factor for the development of local and systemic complications in acute pancreatitis: it also increases the mortality of this disease.

Antibodies to carbonic anhydrase and IgG4 levels in idiopathic chronic pancreatitis: relevance for diagnosis of autoimmune pancreatitis

Background: Increased serum antibodies against carbonic anhydrase II (CA-II Ab) or IgG4 levels have been reported in cases of autoimmune chronic pancreatitis (ACP). Aim: To assess the relevance of serum CA-II Ab and IgG4 levels for the diagnosis of ACP in idiopathic CP (ICP) versus alcoholic CP and Sjögren’s syndrome (SS). Subjects: This was a multicentre study involving 227 subjects divided into four groups: ICP (n = 54), normal controls (n = 54, paired by age and sex with ICP patients), alcoholic CP (n = 86), and SS (n = 33). Methods: CA-II Ab was measured by ELISA and confirmed by western blotting. A score of easy clinical use with major clinical, morphological, and biochemical parameters for the diagnosis of ACP was applied. Results: The percentage of patients with increased serum CA-II Ab was higher in the ICP group (28%) than in controls (1.9%) and in patients with alcoholic CP (10.5%), but lower than in patients with SS (64%). The proportion with elevated IgG4 levels was higher in the ICP group (15%) compared with controls (1.9%) and SS (0%) but not significantly different from alcoholic CP (8%). Most ICP patients (7/8) with high IgG4 levels exhibited increased CA-II Ab and a compatible ACP score. A definitive diagnosis of ACP by histological analysis was associated with other autoimmune disorders, an increase in both serum IgG4 and CA-II Ab levels, and IgG4 positive plasma cells. Conclusions: The increase in serum IgG4 levels was strongly associated with elevated CA-II Ab levels, manifestations compatible with ACP, and lymphoplasmacytic infiltration when surgical specimens were available.

Bacterial DNA in patients with cirrhosis and noninfected ascites mimics the soluble immune response established in patients with spontaneous bacterial peritonitis

Bacterial infections and severity of associated inflammatory reaction influence prognosis in patients with advanced cirrhosis. We compared the innate immune response to bacterial DNA (bactDNA) translocation with that caused by viable bacteria translocation in patients with spontaneous bacterial peritonitis and the relationship between the cytokine response and serum levels of bactDNA. The bactDNA translocation was investigated in 226 patients with cirrhosis and noninfected ascites, 22 patients with spontaneous bacterial peritonitis, and 10 patients with ascites receiving continuous norfloxacin. Serum and ascitic fluid tumor necrosis factor α, interferon‐γ, interleukin‐12, and nitric oxide metabolites were measured via enzyme‐linked immunosorbent assay. Bacterial genomic identifications were made via amplification and sequencing of the 16S ribosomal RNA gene and digital quantization with DNA Lab‐on‐chips. The bactDNA was present in 77 noninfected patients (34%) and in all cases of spontaneous bacterial peritonitis, even in those with culture‐negative ascitic fluid. No patient receiving norfloxacin showed bactDNA translocation. Levels of all cytokines were similar in patients with bactDNA translocation or spontaneous bacterial peritonitis and significantly higher than in patients without bactDNA or in those receiving norfloxacin. Serum bactDNA concentration paralleled levels of all cytokines and nitric oxide in a series of patients with bactDNA translocation or spontaneous bacterial peritonitis followed during 72 hours. Antibiotic treatment in the series of patients with spontaneous bacterial peritonitis did not abrogate bactDNA translocation in the short term. Conclusion: bactDNA translocation‐associated cytokine response is indistinguishable from that in patients with spontaneous bacterial peritonitis and is dependent on bactDNA concentration. Norfloxacin abrogates bactDNA translocation and cytokine response. (HEPATOLOGY 2008;47:978–985.)

Serum and ascitic fluid bacterial DNA: A new independent prognostic factor in noninfected patients with cirrhosis

We tested the hypothesis that the presence of bacterial DNA (bactDNA) in ascitic fluid and serum is associated with decreased survival in patients with cirrhosis. In a prospective, multicenter study, we analyzed the clinical evolution of 156 patients with cirrhosis and ascites (first or recurrence) with lower than 250 polymorphonuclear cells (PMN)/μL, negative ascites bacteriological culture, and absence of other bacterial infections being admitted for evaluation of large‐volume paracentesis, according to the presence of bactDNA at admission. Survival, causes of death, and successive hospital admissions were determined during a 12‐month follow‐up period. BactDNA was detected in 48 patients. The most prevalent identified bactDNA corresponded to Escherichia coli (n = 32/48 patients, 66.6%). Patients were followed for 12 months after inclusion and in this period 34 patients died: 16 of 108 (15%) bactDNA negative versus 18 of 48 (38%) bactDNA positive (P = 0.003). The most frequent cause of death was acute‐on‐chronic liver failure in both groups (7/16 and 9/18 in patients without or with bactDNA, respectively), although more prevalent in the first month of follow‐up in patients with presence of bactDNA (0 versus 4/7). When considering patients with model for end‐stage liver disease (MELD) score less than 15, mortality was significantly higher in those with presence of bactDNA. Spontaneous bacterial peritonitis developed similarly in patients with or without bactDNA at admission. Conclusion: The presence of bactDNA in a patient with cirrhosis during an ascitic episode is an indicator of poor prognosis. This fact may be related to the development of acute‐on‐chronic liver failure at short term and does not predict the development of spontaneous bacterial peritonitis. (HEPATOLOGY 2008;48:1924‐1931.)

Factors Predicting Mortality in Severe Acute Pancreatitis

Acute pancreatitis (AP) is a common disorder in which ensuing serious complications may lead to a fatal outcome in patients. Background/Aims: To describe a large series of patients with severe AP (SAP) who were admitted to our hospital and to identify factors predicting mortality. Patients and Methods: In a retrospective study, all patients with SAP diagnosed between February 1996 and October 2000 according to the Atlanta criteria were studied. Results: Out of a total of 363 AP patients, 67 developed SAP. The mean age of the patients was 69; the commonest etiology was biliary; 55.2% developed necrosis; the commonest systemic complication was respiratory failure (44.7%), followed by acute renal failure (35.8%) and shock (20.9%). A total of 31.3% of the patients died. Factors significantly related to mortality were age, upper digestive tract bleeding, acute renal failure, respiratory failure and shock by univariate analysis. However, pseudocysts seemed to have a protective effect. By multivariate analysis, independent prognostic factors were age, acute renal failure and respiratory failure. Conclusions: Patients with SAP mainly died due to systemic complications, especially acute renal failure and respiratory failure. Necrosis (in the absence or presence of infection) was not correlated with increased mortality. A pseudocyst was found to be a protective factor, probably because the definition itself led to the selection of patients who had survived multiorgan failure.

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 ≧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.

Bacterial DNA translocation is associated with systemic circulatory abnormalities and intrahepatic endothelial dysfunction in patients with cirrhosis

Presence of bacterial DNA in noninfected patients with cirrhosis and ascites is associated with a marked inflammatory response including activation of the inducible form of nitric oxide synthase and release of nitric oxide, similar to that observed in patients with spontaneous bacterial peritonitis. Although presence of bacterial DNA is associated with an impaired prognosis, no information is available regarding its hemodynamic consequences. Systemic and hepatic hemodynamics before and after a liquid test meal were assessed in a series of 75 noninfected patients with cirrhosis (55 with ascites). Bacterial DNA was measured by polymerase chain reaction. Bacterial DNA was detected only in patients with ascites. Clinical data and liver function were similar in ascitic patients with presence (n = 21) or absence of bacterial DNA (n = 34). Bacterial‐DNA(+) patients had significantly lower mean arterial pressure (P = 0.002) and systemic vascular resistance (P = 0.03) than bacterial‐DNA(−) patients. Cardiac output, cardiopulmonary pressures, hepatic venous pressure gradient (HVPG), and hepatic blood flow were similar in both groups. Thirty minutes after the test meal, in response to increased blood flow caused by postprandial hyperemia, there was a significantly greater increase in HVPG and impaired hepatic vasorelaxation in bacterial‐DNA(+) as compared with bacterial‐DNA(−) patients, which indicates hepatic endothelial dysfunction. Indeed, the increase in HVPG after the test meal significantly correlated with serum bacterial DNA concentration. Conclusion: Presence of bacterial DNA, a marker of bacterial translocation, is associated with aggravation of peripheral vasodilation and with worsening of intrahepatic endothelial dysfunction. (HEPATOLOGY 2010;.)

Influence of fluid therapy on the prognosis of acute pancreatitis: a prospective cohort study.

OBJECTIVES:Although aggressive fluid therapy during the first days of hospitalization is recommended by most guidelines and reviews on acute pancreatitis (AP), this recommendation is not supported by any direct evidence. We aimed to evaluate the association between the amount of fluid administered during the initial 24 h of hospitalization and the incidence of organ failure (OF), local complications, and mortality.METHODS:This was a prospective cohort study. We included consecutive adult patients admitted with AP. Local complications and OF were defined according to the Atlanta Classification. Persistent OF was defined as OF of >48-h duration. Patients were divided into three groups according to the amount of fluid administered during the initial 24 h: group A: <3.1 l (less than the first quartile), group B: 3.1–4.1 l (between the first and third quartiles), and group C: >4.1 l (more than the third quartile).RESULTS:A total of 247 patients were analyzed. Administration of >4.1 l during the initial 24 h was significantly and independently associated with persistent OF, acute collections, respiratory insufficiency, and renal insufficiency. Administration of <3.1 l during the initial 24 h was not associated with OF, local complications, or mortality. Patients who received between 3.1 and 4.1 l during the initial 24 h had an excellent outcome.CONCLUSIONS:In our study, administration of a small amount of fluid during the initial 24 h was not associated with a poor outcome. The need for a great amount of fluid during the initial 24 h was associated with a poor outcome; therefore, this group of patients must be carefully monitored.

Brain edema and inflammatory activation in bile duct ligated rats with diet‐induced hyperammonemia: A model of hepatic encephalopathy in cirrhosis

Studies of the pathogenesis of hepatic encephalopathy are hampered by the lack of a satisfactory animal model. We examined the neurological features of rats after bile duct ligation fed a hyperammonemic diet (BDL+HD). Six groups were studied: sham, sham pair‐fed, hyperammonemic, bile duct ligation (BDL), BDL pair fed, and BDL+HD. The BDL+HD rats were made hyperammonemic via an ammonia‐containing diet that began 2 weeks after operation. One week later, the animals were sacrificed. BDL+HD rats displayed an increased level of cerebral ammonia and neuroanatomical characteristics of hepatic encephalopathy (HE), including the presence of type II Alzheimer astrocytes. Both BDL and BDL+HD rats showed activation of the inflammatory system. BDL+HD rats showed an increased amount of brain glutamine, a decreased amount of brain myo‐inositol, and a significant increase in the level of brain water. In coordination tests, BDL+HD rats showed severe impairment of motor activity and performance as opposed to BDL rats, whose results seemed only mildly affected. In conclusion, the BDL+HD rats displayed similar neuroanatomical and neurochemical characteristics to human HE in liver cirrhosis. Brain edema and inflammatory activation can be detected under these circumstances. (HEPATOLOGY 2006;43:1257–1266.)

The detection of bacterial DNA in blood of rats with CCl4-induced cirrhosis with ascites represents episodes of bacterial translocation†

Bacterial DNA (bactDNA) is present in blood and ascitic fluid (AF) in a third of patients with cirrhosis and ascites, but whether this phenomenon represents episodes of bacterial translocation (BT), strictly considered when culture of mesenteric lymph nodes (MLNs) are positive, remains unknown. This study assessed the relationship between bactDNA detection in biological fluids and MLNs and went on to investigate the local and systemic inflammatory status according to its presence. Cirrhosis was induced in rats by ingestion of CCL4. A subgroup of five animals with cirrhosis received norfloxacin (5 mg/kg/day) for 7 days. MLNs and ascitic and pleural fluids were collected at laparotomy and cultured; samples were collected for identification of bactDNA and measurement of tumor necrosis factor‐alpha (TNF‐α), interleukin‐6 (IL‐6), and nitric oxide (NO). BactDNA was detected in MLNs in 12 of 19 animals (63.1%), corresponding in seven cases to culture‐positive MLNs, and in five to culture‐negative MLNs. BactDNA was detected in biological fluids in 11 of 19 animals (57.9%), and in all cases the same bacteria spp. detected in samples was present in MLNs. BactDNA was not detected in any biological sample from animals receiving norfloxacin. Tumor necrosis factor alpha (TNF‐α), IL‐6, and NO were similar in culture‐positive and culture‐negative/bactDNA‐positive samples, and significantly higher than those observed in animals with culture‐negative/bactDNA‐negative MLNs, animals with cirrhosis that were receiving norfloxacin, and controls. In conclusion, the presence of bactDNA in biological fluids in rats with cirrhosis constitutes a marker of BT, and it is associated with a marked inflammatory response, independent of the result of the culture. (HEPATOLOGY 2006.)