33% had some degree of fibrosis being 60% > grado1C, and 3 patients had cirrhosis. The fibrosis is associated with the number of features MS (p <0.05). CONCLUSIONS: NASH is common in adults with features of MS, and the risk increases with the number of traits that are suffering. Dyslipidemia is the only feature of MS predictor of NASH. Age factor has been a protector of NASH in our population. In addition, fibrosis is a common finding. Therefore, we suspect NASH in any adult with MS traits even when no prior evidence of liver. Tabla 1. -differences between NASH and non-NASH Non-NASH NASH P Age (years) 69/ 17 60, 50/ 15, 50 0, 02 Hypertension 17 (37, 0) 29 (63, 0)

1 Dyslipemia 5 (16, 7) 25 check details (83, 3) 0, 01 Diabetes 6 (35, 3) 11(64, 7) 1 Obesity 17 (36, 2) 30 (63, 8) 1 Number of features MS One Two Three Four Five 13 (44, 8) 8 (38,

1)6 (28, 6) 0 (0, 0) 0 (0, 0) 16(55, 2) 13(61, 9) 15(71, 4) 2 (100, 0) 2 (100, 0) 0, 07 click here Disclosure: The following people have nothing to disclose: Victor Aguilar-Urbano, Teresa Pereda, Juana Gonzalo-Marfn, Pedro Moreno-Mejlas, Julio Bercedo, Jose Verdugo, Francisco Moya-Donoso, Francisco Femandez-Cano, Francisco Rivas-Ruiz, Norberto Gandara-Adan, J. M. Navarro BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) is associated with a higher prevalence of insomnia and gastroesophageal reflux disease (GERD). NAFLD encompasses nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). The association of insomnia with learn more GERD in

NAFLD remains unknown. The present study investigated the relationships between GERD symptoms and insomnia in subjects with biopsy-proven NAFLD. Methods: One hundred twenty three patients with biopsy-proven NAFLD (median age: 59) were enrolled in this study. Insomnia was assessed by the Athens Insomnia Scale (AIS), a self-assessment psychometric instrument designed for quantifying sleep difficulty based on the ICD-10 criteria. Patients with AIS of more than 6 were considered as insomniacs. GERD symptoms were evaluated by using a frequency scale for the symptoms of GERD (FSSG). Patients with FSSG scores of more than 8 were considered as positive. Logistic regression models were used to evaluate the association of insomnia with GERD, after adjusting for potential confounders. Thirteen NAFLD patients with GERD symptoms were administrated a proton pump inhibitor (PPI), rabeprazole (RPZ) (10mg/day) for 12 weeks to investigate the effect on insomnia. Results: Overall, 62% were female, and 71% were obese. The prevalence of NAFLD with AIS> 6 and FSSG score > 8 was 28% and 25%, respectively. Liver biopsy revealed 40 NAFL and 83 NASH. There were no differences between the two groups in FSSG and AIS. Overall, AIS was positively correlated only with FSSG among clinical parameters. AIS did not correlate with histological steatosis, grade, and fibrosis. The levels of yGT, HOMA-IR, and FSSG were significantly higher in insomniacs compared to noninsomniacs.

33% had some degree of fibrosis being 60% > grado1C, and 3 patients had cirrhosis. The fibrosis is associated with the number of features MS (p <0.05). CONCLUSIONS: NASH is common in adults with features of MS, and the risk increases with the number of traits that are suffering. Dyslipidemia is the only feature of MS predictor of NASH. Age factor has been a protector of NASH in our population. In addition, fibrosis is a common finding. Therefore, we suspect NASH in any adult with MS traits even when no prior evidence of liver. Tabla 1. -differences between NASH and non-NASH Non-NASH NASH P Age (years) 69/ 17 60, 50/ 15, 50 0, 02 Hypertension 17 (37, 0) 29 (63, 0)

1 Dyslipemia 5 (16, 7) 25 Selleck Rapamycin (83, 3) 0, 01 Diabetes 6 (35, 3) 11(64, 7) 1 Obesity 17 (36, 2) 30 (63, 8) 1 Number of features MS One Two Three Four Five 13 (44, 8) 8 (38,

1)6 (28, 6) 0 (0, 0) 0 (0, 0) 16(55, 2) 13(61, 9) 15(71, 4) 2 (100, 0) 2 (100, 0) 0, 07 see more Disclosure: The following people have nothing to disclose: Victor Aguilar-Urbano, Teresa Pereda, Juana Gonzalo-Marfn, Pedro Moreno-Mejlas, Julio Bercedo, Jose Verdugo, Francisco Moya-Donoso, Francisco Femandez-Cano, Francisco Rivas-Ruiz, Norberto Gandara-Adan, J. M. Navarro BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) is associated with a higher prevalence of insomnia and gastroesophageal reflux disease (GERD). NAFLD encompasses nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). The association of insomnia with selleck chemicals llc GERD in

NAFLD remains unknown. The present study investigated the relationships between GERD symptoms and insomnia in subjects with biopsy-proven NAFLD. Methods: One hundred twenty three patients with biopsy-proven NAFLD (median age: 59) were enrolled in this study. Insomnia was assessed by the Athens Insomnia Scale (AIS), a self-assessment psychometric instrument designed for quantifying sleep difficulty based on the ICD-10 criteria. Patients with AIS of more than 6 were considered as insomniacs. GERD symptoms were evaluated by using a frequency scale for the symptoms of GERD (FSSG). Patients with FSSG scores of more than 8 were considered as positive. Logistic regression models were used to evaluate the association of insomnia with GERD, after adjusting for potential confounders. Thirteen NAFLD patients with GERD symptoms were administrated a proton pump inhibitor (PPI), rabeprazole (RPZ) (10mg/day) for 12 weeks to investigate the effect on insomnia. Results: Overall, 62% were female, and 71% were obese. The prevalence of NAFLD with AIS> 6 and FSSG score > 8 was 28% and 25%, respectively. Liver biopsy revealed 40 NAFL and 83 NASH. There were no differences between the two groups in FSSG and AIS. Overall, AIS was positively correlated only with FSSG among clinical parameters. AIS did not correlate with histological steatosis, grade, and fibrosis. The levels of yGT, HOMA-IR, and FSSG were significantly higher in insomniacs compared to noninsomniacs.

29 However, several studies have suggested that progression to fibrosis and cirrhosis occurs in 5%-15% of patients despite abstinence.30, 31 In one study, continued alcohol use (>40 g/day) increased the risk of progression to cirrhosis to 30%, and fibrosis or cirrhosis to 37%.32 Fibrosis is believed to start in the perivenular area and is influenced by the amount of alcohol ingested.33, 34 Perivenular fibrosis and deposition of fibronectin occurs in 40%-60% of patients who ingest

more than 40-80 g/daily for an average of 25 years. Perivenular sclerosis has been identified as a significant XL184 chemical structure and independent risk factor for the progression of alcoholic liver injury to fibrosis or cirrhosis.33, 35 Progression of ALD culminates in the development of cirrhosis, which is usually micronodular, but may occasionally be mixed micronodular and macronodular.36 A subset of patients with ALD will develop severe alcoholic hepatitis (AH), which has a substantially worse short-term prognosis.37 AH also represents a spectrum of disease, ranging from mild injury to severe, life-threatening injury, and often presents acutely against a background of chronic liver disease.38, 39 The true prevalence is unknown, but histologic studies of patients with ALD suggest that AH may

be present in as many as 10%-35% of hospitalized alcoholic patients.40–42 Typically, Lorlatinib molecular weight symptomatic patients present with advanced liver disease, with concomitant cirrhosis in more than 50%, and superimposed acute decompensation. Even patients with a relatively

mild presentation, however, are at high risk of progressive liver injury, with cirrhosis developing in up to 50%.43, 44 The likelihood that AH will progress to permanent damage is increased among those who continue to abuse alcohol. Abstinence from alcohol in one small series did not guarantee complete recovery. Only 27% of abstaining patients had histologic normalization, whereas 18% progressed to cirrhosis, and the remaining patients selleck products had persistent AH when followed for up to 18 months.45 Unlike many other hepatotoxins, the likelihood of developing progressive alcohol-induced liver disease or cirrhosis is not completely dose-dependent, because it occurs in only a subset of patients. A number of risk factors have been identified that influence the risk of development and progression of liver disease. The amount of alcohol ingested (independent of the form in which it is ingested) is the most important risk factor for the development of ALD.46 The relationship between the quantity of alcohol ingested and the development of liver disease is not clearly linear.47, 48 However, a significant correlation exists between per capita consumption and the prevalence of cirrhosis.49 The risk of developing cirrhosis increases with the ingestion of >60-80 g/day of alcohol for 10 years or longer in men, and >20 g/day in women.

8 years. In their study, gastric cancer developed in persons infected with H. pylori but not in the uninfected persons, which is a conclusive evidence that H. pylori has a crucial role in the development of gastric cancer. In Japan,

intestinal type mucosal gastric cancer without concomitant lymph node metastasis is usually treated with endoscopic resection,[4] which removes the tumor and surrounding mucosa such that metachronous gastric cancer could develop at sites other than that of the endoscopic resection. Fukase et al.[5] investigated the prophylactic effect of H. pylori eradication on the development of metachronous gastric carcinoma after endoscopic resection for early gastric cancer. After endoscopic treatment, they randomly assigned patients to receive H. pylori eradication regimen or not. The cumulative incidence IWR-1 supplier of gastric cancer was significantly higher in the non-eradication therapy group than in the group undergoing eradication treatment. They concluded Midostaurin nmr that prophylactic eradication of H. pylori after endoscopic resection of early gastric cancer should be performed to prevent the development of metachronous gastric carcinoma. As to the gastric remnant, the effect of H. pylori eradication on the development of metachronous gastric carcinoma has not been clearly determined.

Evaluation of the risk of cancer in the intact stomach mucosa requires monitoring of atrophic or intestinal metaplastic changes. In the remnant stomach, however, evaluation can be confounded by H. pylori infection and by reflux of bile, intestinal juice or pancreatic juice, both of which are important risk factors for secondary carcinogenesis in the remnant stomach mucosa.[6, 7] It has been reported that H. pylori infection plays a major role in gastritis of the remnant stomach after Billroth I anastomosis, whereas see more bile reflux is the major cause after the Billroth II procedure.[8] The remnant stomach after Billroth II anastomosis is a complicated circumstance because it is affected by H. pylori infection and bile reflux. Kato et al.[9] measured

the gastric juice pH of the patients who had undergone distal gastrectomy and H. pylori eradication therapy. pH levels in these patients were normalized after eradication in the remnant stomach, and they predicted that this effect may reduce the risk of secondary stomach carcinogenesis. Our hypothesis is that H. pylori infection triggers the development of histological inflammation in the remnant stomach after Billroth I anastomosis, which increases the risk of gastric carcinogenesis. The aim of this study was to clarify whether eradicating the bacteria results in normalization of the histological abnormalities, which may consequently reduce the risk of cancer in the remnant stomach. To more clearly understand the role of H. pylori rather than bile acid in the development of metachronous gastric carcinoma, we focused on patients with a remnant stomach after Billroth I anastomosis.

Methods: Six-week-old www.selleckchem.com/products/midostaurin-pkc412.html (n = 12) and 14-week-old (n = 12) homozygous mutant

rats at the white spotting locus (Ws/Ws rat) were used. Rats were handled daily by the same person and submitted to water avoidance stress (WAS) daily for 13 days. Rats were exposed to stress session for 1 hr/day in the morning for 13 days and their fecal pellet output (FPO) were counted during WAS or sham WAS. Rats were euthanized after completion of stress experiment and whole colon was collected. Immunohistochemistry for mast cell tryptase and PAR-2 were performed in the proximal and distal Vemurafenib part of colon. Results: There was no difference in body weight change during stress experiment

between WAS and sham WAS group. WAS group exhibited increased FPO during 13 days compared to sham stress. This effect was significant for both aged Ws/Ws rat. MC were nearly absent in the colonic mucosa of 14-week-old Ws/Ws rat. In 6-week-old Ws/Ws rats, number of MC in the colonic mucosa were statistically increased by WAS compared to sham WAS. PAR-2 cells were statistically increased by WAS only in the 14-week-old Ws/Ws rat. Increased MC and PAR-2 cells by WAS were observed mainly in the proximal colon. Conclusion: Chronic psychological stress increased colonic motility independently to the presence

of mast cell in the colonic mucosa. And psychological stress increased not only mast cells but also other inflammatory cells preferentially in the proximal colon. Key click here Word(s): 1. Psychological stress; 2. mast cell; 3. colon; 4. Ws/Ws rat; Presenting Author: WANGZHI MO Additional Authors: HOUXIAO HUA Corresponding Author: HOUXIAO HUA Affiliations: Division of Gastroenterology, Union Hospital, Tongji Medical College Objective: To explore the role of SRF-IEG on the formation of visceral hypersensitivity induced by acute restraint stress. Methods: 12 male Sprague-Dawley rats were randomly divided into control group and acute restraint stress group (model group). Visceral hypersensitivity was made by acute restraint stress for 2 h. The colorectal distension (CRD) with different pressure were performed and abdominal withdrawal reflex (AWR) scores were observed during CRD. The visceral hypersensitivity was determined by AWR scores.

Methods: Six-week-old buy Selumetinib (n = 12) and 14-week-old (n = 12) homozygous mutant

rats at the white spotting locus (Ws/Ws rat) were used. Rats were handled daily by the same person and submitted to water avoidance stress (WAS) daily for 13 days. Rats were exposed to stress session for 1 hr/day in the morning for 13 days and their fecal pellet output (FPO) were counted during WAS or sham WAS. Rats were euthanized after completion of stress experiment and whole colon was collected. Immunohistochemistry for mast cell tryptase and PAR-2 were performed in the proximal and distal MK-8669 ic50 part of colon. Results: There was no difference in body weight change during stress experiment

between WAS and sham WAS group. WAS group exhibited increased FPO during 13 days compared to sham stress. This effect was significant for both aged Ws/Ws rat. MC were nearly absent in the colonic mucosa of 14-week-old Ws/Ws rat. In 6-week-old Ws/Ws rats, number of MC in the colonic mucosa were statistically increased by WAS compared to sham WAS. PAR-2 cells were statistically increased by WAS only in the 14-week-old Ws/Ws rat. Increased MC and PAR-2 cells by WAS were observed mainly in the proximal colon. Conclusion: Chronic psychological stress increased colonic motility independently to the presence

of mast cell in the colonic mucosa. And psychological stress increased not only mast cells but also other inflammatory cells preferentially in the proximal colon. Key learn more Word(s): 1. Psychological stress; 2. mast cell; 3. colon; 4. Ws/Ws rat; Presenting Author: WANGZHI MO Additional Authors: HOUXIAO HUA Corresponding Author: HOUXIAO HUA Affiliations: Division of Gastroenterology, Union Hospital, Tongji Medical College Objective: To explore the role of SRF-IEG on the formation of visceral hypersensitivity induced by acute restraint stress. Methods: 12 male Sprague-Dawley rats were randomly divided into control group and acute restraint stress group (model group). Visceral hypersensitivity was made by acute restraint stress for 2 h. The colorectal distension (CRD) with different pressure were performed and abdominal withdrawal reflex (AWR) scores were observed during CRD. The visceral hypersensitivity was determined by AWR scores.

4F). Moreover, a recent study with cultured hepatic stellate cells deficient for TNFR1 or TNFR2, or both TNFR1 and TNFR2,12 confirmed a critical role for TNFR1 in the development of liver fibrosis. Notably, the level of fibrosis observed in p55Δns/+ mice PD-0332991 cell line was significantly lower compared to p55Δns/Δns mice, being an exception of the dominant nature of the TNFR1 mutation. The reason for this is still unclear. Elevated levels of the liver enzymes ALT and AST are often used as surrogate markers for advanced liver injury. However, ALT levels are persistently normal in more than half of the patients

with NAFLD and biopsy-proven NASH,39 suggesting that the presence of NASH does not necessarily correlate with higher levels of these liver transaminases. In line with this,

we demonstrated that AST and ALT Ivacaftor mouse levels were not increased in HFD-fed p55Δns/Δns mice despite the existence of NASH. A NASH-like phenotype without overt changes in liver enzymes has also been observed in the low-density lipoprotein receptor (LDLR) knockout mice fed a high fat cholesterol diet.40 As elevated levels of circulating liver enzymes are a prerequisite for patients to undergo a liver biopsy,3, 39 we urgently need better, noninvasive methods to assess hepatic inflammation and fibrosis and properly diagnose disease severity. As chronic low-grade inflammation has a broad role in driving the pathogenesis of systemic insulin resistance,37 we assessed whether hepatic inflammation in p55Δns/Δns mice was associated with the development of hepatic or systemic insulin resistance. We found no signs of glucose intolerance or hepatic insulin resistance in p55Δns/Δns mice fed a chow diet compared to littermate controls (Fig. 6A,C,E). Insulin resistance

developed readily in mice fed an HFD for 12 weeks, but was no worse in p55Δns/Δns mice with the nonshedding mutation (Fig. 6B,D,F). Furthermore, older p55Δns/Δns mice fed a chow diet for 1 year were not prone to developing insulin resistance (data not shown), nor did 12 weeks of HFD starting at the age of 1 year accelerate the development of insulin resistance in p55Δns/Δns mice compared to control mice (data not shown). Our data see more therefore indicate that TNFR1 signaling is not essential for the development of insulin resistance in mice. As several reports have raised doubts on the importance of the TNFR1, TNFR2, and TNFα signaling in contributing to obesity-induced insulin resistance,14, 17, 19 our data provide yet another piece of evidence against the prevailing concept that the TNFα pathway mediates HFD-induced insulin resistance in the obesity research field. Moreover, ob/ob mice lacking TNFα/TNFR-function are only partly protected from obesity-induced insulin resistance,16 which also suggests that other pathways play an important role in its development.

4F). Moreover, a recent study with cultured hepatic stellate cells deficient for TNFR1 or TNFR2, or both TNFR1 and TNFR2,12 confirmed a critical role for TNFR1 in the development of liver fibrosis. Notably, the level of fibrosis observed in p55Δns/+ mice Selleck Rucaparib was significantly lower compared to p55Δns/Δns mice, being an exception of the dominant nature of the TNFR1 mutation. The reason for this is still unclear. Elevated levels of the liver enzymes ALT and AST are often used as surrogate markers for advanced liver injury. However, ALT levels are persistently normal in more than half of the patients

with NAFLD and biopsy-proven NASH,39 suggesting that the presence of NASH does not necessarily correlate with higher levels of these liver transaminases. In line with this,

we demonstrated that AST and ALT Fulvestrant mouse levels were not increased in HFD-fed p55Δns/Δns mice despite the existence of NASH. A NASH-like phenotype without overt changes in liver enzymes has also been observed in the low-density lipoprotein receptor (LDLR) knockout mice fed a high fat cholesterol diet.40 As elevated levels of circulating liver enzymes are a prerequisite for patients to undergo a liver biopsy,3, 39 we urgently need better, noninvasive methods to assess hepatic inflammation and fibrosis and properly diagnose disease severity. As chronic low-grade inflammation has a broad role in driving the pathogenesis of systemic insulin resistance,37 we assessed whether hepatic inflammation in p55Δns/Δns mice was associated with the development of hepatic or systemic insulin resistance. We found no signs of glucose intolerance or hepatic insulin resistance in p55Δns/Δns mice fed a chow diet compared to littermate controls (Fig. 6A,C,E). Insulin resistance

developed readily in mice fed an HFD for 12 weeks, but was no worse in p55Δns/Δns mice with the nonshedding mutation (Fig. 6B,D,F). Furthermore, older p55Δns/Δns mice fed a chow diet for 1 year were not prone to developing insulin resistance (data not shown), nor did 12 weeks of HFD starting at the age of 1 year accelerate the development of insulin resistance in p55Δns/Δns mice compared to control mice (data not shown). Our data this website therefore indicate that TNFR1 signaling is not essential for the development of insulin resistance in mice. As several reports have raised doubts on the importance of the TNFR1, TNFR2, and TNFα signaling in contributing to obesity-induced insulin resistance,14, 17, 19 our data provide yet another piece of evidence against the prevailing concept that the TNFα pathway mediates HFD-induced insulin resistance in the obesity research field. Moreover, ob/ob mice lacking TNFα/TNFR-function are only partly protected from obesity-induced insulin resistance,16 which also suggests that other pathways play an important role in its development.

On average, patients with cirrhosis had significantly higher ammonia and tryptophan derivatives concentrations than healthy volunteers, as well as elevated inflammatory markers (Table 1). Patients with alcohol-related cirrhosis had significantly

lower sodium and higher CRP and IL-6 concentrations than their counterparts with non–alcohol-related cirrhosis (Table 2). Thirteen (18%) patients had mild hyponatremia, 47 (65%) had mild-moderate anemia, 37 (54%) had high CRP, 41 (61%) had high IL-6, 48 (72%) had high TNFα, 40 (71%) had hyperammonemia, 58 (86%) had high indole, and 43 (64%) had high oxindole. Patients with abnormal PHES had significantly higher CRP (17 ± 22 versus 7 ± 6; P < 0.01), IL-6 (32 ± 54 versus 12 ± 13; P < 0.05), and TNFα find protocol (17 ± 8 versus 11 ± 7; P < 0.001) concentrations than their counterparts with normal PHES (Fig. 1,

Table 3). Significant, this website consistent correlations were observed between stand-alone psychometric test results and CRP, IL-6, and TNFα (Table 4). CRP and TNFα concentrations were also independent predictors of an abnormal PHES performance (overall model, χ2 = 16; CRP, β [± SE] = 0.10 ± 0.04, P = 0.02; TNFα, β = 0.09 ± 0.04, P = 0.03); a trend (0.05 < P < 0.1) was maintained also when the degree of hepatic failure, either in the form of the Child-Pugh or MELD score, was taken into account. Patients with abnormal EEG had significantly higher indole (430 ± 270 versus 258 ± 255; P < 0.01) and ammonia (66 ± 35 versus 45 ± 27; P < 0.05) concentrations than their counterparts with normal EEG (Fig. 2, Table 3). Significant correlations were observed between spectral EEG indices and a number of laboratory variables; these correlations were more consistent for ammonia and IL-6 (Table 5). Indole and ammonia concentrations were independent predictors of an abnormal EEG (overall model, χ2 = 15; indole, β = 0.003 ± 0.001, P = 0.008; ammonia, β = 0.02 ± = 0.01, P = 0.03); this also held true for indole

(overall model, χ2 = 20; β = 0.004 ± 0.001, P = 0.005) when the degree of hepatic failure, either in the form of the Child-Pugh or MELD score, was taken into account. Seven patients were lost to follow-up. Of the remaining 65 patients, 20 died (median, 11 months [interquartile range, 6-23 months]) and 14 underwent transplantation (median, 10 months [interquartile range, 3-16 months]). During the follow-up period, 15 (23%) patients developed an episode click here of HE requiring in-hospital admission (median, 7 months [interquartile range, 3-14 months]). No differences in the length of survival or the risk of developing HE over the follow-up period were observed in relation to the etiology of cirrhosis (alcohol-related versus non–alcohol-related). Both the PHES and EEG analysis (categorical [PHES/EEG normal or abnormal] or continuous/semicontinuous variables [total PHES score, EEG mean dominant frequency]) were independent predictors of death (Table 6) and occurrence of HE-related hospitalization (Fig. 3, Table 7).

On average, patients with cirrhosis had significantly higher ammonia and tryptophan derivatives concentrations than healthy volunteers, as well as elevated inflammatory markers (Table 1). Patients with alcohol-related cirrhosis had significantly

lower sodium and higher CRP and IL-6 concentrations than their counterparts with non–alcohol-related cirrhosis (Table 2). Thirteen (18%) patients had mild hyponatremia, 47 (65%) had mild-moderate anemia, 37 (54%) had high CRP, 41 (61%) had high IL-6, 48 (72%) had high TNFα, 40 (71%) had hyperammonemia, 58 (86%) had high indole, and 43 (64%) had high oxindole. Patients with abnormal PHES had significantly higher CRP (17 ± 22 versus 7 ± 6; P < 0.01), IL-6 (32 ± 54 versus 12 ± 13; P < 0.05), and TNFα GSK1120212 nmr (17 ± 8 versus 11 ± 7; P < 0.001) concentrations than their counterparts with normal PHES (Fig. 1,

Table 3). Significant, Ku-0059436 price consistent correlations were observed between stand-alone psychometric test results and CRP, IL-6, and TNFα (Table 4). CRP and TNFα concentrations were also independent predictors of an abnormal PHES performance (overall model, χ2 = 16; CRP, β [± SE] = 0.10 ± 0.04, P = 0.02; TNFα, β = 0.09 ± 0.04, P = 0.03); a trend (0.05 < P < 0.1) was maintained also when the degree of hepatic failure, either in the form of the Child-Pugh or MELD score, was taken into account. Patients with abnormal EEG had significantly higher indole (430 ± 270 versus 258 ± 255; P < 0.01) and ammonia (66 ± 35 versus 45 ± 27; P < 0.05) concentrations than their counterparts with normal EEG (Fig. 2, Table 3). Significant correlations were observed between spectral EEG indices and a number of laboratory variables; these correlations were more consistent for ammonia and IL-6 (Table 5). Indole and ammonia concentrations were independent predictors of an abnormal EEG (overall model, χ2 = 15; indole, β = 0.003 ± 0.001, P = 0.008; ammonia, β = 0.02 ± = 0.01, P = 0.03); this also held true for indole

(overall model, χ2 = 20; β = 0.004 ± 0.001, P = 0.005) when the degree of hepatic failure, either in the form of the Child-Pugh or MELD score, was taken into account. Seven patients were lost to follow-up. Of the remaining 65 patients, 20 died (median, 11 months [interquartile range, 6-23 months]) and 14 underwent transplantation (median, 10 months [interquartile range, 3-16 months]). During the follow-up period, 15 (23%) patients developed an episode see more of HE requiring in-hospital admission (median, 7 months [interquartile range, 3-14 months]). No differences in the length of survival or the risk of developing HE over the follow-up period were observed in relation to the etiology of cirrhosis (alcohol-related versus non–alcohol-related). Both the PHES and EEG analysis (categorical [PHES/EEG normal or abnormal] or continuous/semicontinuous variables [total PHES score, EEG mean dominant frequency]) were independent predictors of death (Table 6) and occurrence of HE-related hospitalization (Fig. 3, Table 7).