Helicobacter pylori(H. pylori) is an ancient microorganism that has co-evolved with humans for over 60000 years. This bacterium typically colonizes the human stomach and it is currently recognized as the most common i...Helicobacter pylori(H. pylori) is an ancient microorganism that has co-evolved with humans for over 60000 years. This bacterium typically colonizes the human stomach and it is currently recognized as the most common infectious pathogen of the gastroduodenal tract. Although its chronic infection is associated with gastritis, peptic ulcer, dysplasia, neoplasia, MALT lymphoma and gastric adenocarcinoma, it has been suggested the possible association of H. pylori infection with several extragastric effects including hepatobiliary and pancreatic diseases. Since a microorganism resembling H. pylori was detected in samples from patients with hepatobiliary disorders, several reports have been discussed the possible role of bacteria in hepatic diseases as hepatocellular carcinoma, cirrhosis and hepatic encephalopathy, nonalcoholic fatty liver disease and fibrosis. Additionally, studies have reported the possible association between H. pylori infection and pancreatic diseases, especially because it has been suggested that this infection could change the pancreatic physiology. Some of them have related a possible association between the microorganism and pancreatic cancer. H. pylori infection has also been suggested to play a role in the acute and chronic pancreatitis pathogenesis, autoimmune pancreatitis, diabetes mellitus and metabolic syndrome. Considering that association of H. pylori to liver and pancreas diseases needs further clarification, our work offers a review about the results of some investigations related to the potential pathogenicity of H. pylori in these extragastric diseases.展开更多
AIM: To investigate the relationship between H pylori infection, blood ammonia concentration and hepatic encephalopathy (HE), and the effect of Hpylori eradication in cirrhotic patients. METHODS: From July 2003 to...AIM: To investigate the relationship between H pylori infection, blood ammonia concentration and hepatic encephalopathy (HE), and the effect of Hpylori eradication in cirrhotic patients. METHODS: From July 2003 to January 2005, 457 cirrhotic patients in five regions of Zhejiang Province were enrolled. Patients were evaluated for demographics, number connection test, Hpylori infection, liver impairment, blood ammonia concentration and HE. Patients with Hpylori infection were given I wk therapy with omeprazole plus clarithromycin and tinidazole. ^14C urea breath test was performed and mental symptoms and blood ammonia level were reassessed after RESULTS: Overall H pylori infection rate was 60.6%, and HE occurred in 47.5% of cirrhotic patients. Subclinical HE (SHE) was detected in 55 of 117 cirrhotic patients. Blood ammonia concentration in H pylori negative (n = 180) and positive (n = 277) cirrhotic patients was 53.8 ± 51.4 and 78.4 ± 63.6 μmol/L, respectively (P 〈 0.01), which was significantly reduced to 53.5 ± 37.7 μmol/L after bacterium eradication (n = 126) (P 〈 0.01). Blood ammonia was 97.5 ± 81.0 μmol/L in H pylori-positive cirrhotic patients, and this did not significantly change in those with persistent infection after Hpylori eradication (n = 11). HE was more frequently observed in patients with H pylori infection than in those without (58.5% vs 30.6%, P 〈 0.01). HE rate significantly dropped to 34.1% after H pylori eradiation (P 〈 0.01). H pylori prevalence significantly differed among cirrhotic patients with HE (74.4%), SHE (69.1%), and those without HE (53.2%) (P 〈 0.05). Blood ammonia level was significantly different among cirrhotic patients with HE (94.5 ± 75.6 μmol/L), SHE (59.9 ± 49.2 μmol/L), and without HE (47.3 ± 33.5 μmol/L) (P 〈 0.05). Logistic regression analysis showed that blood ammonia concentration, Child-Pugh stage, upper gastrointestinal bleeding, electrolyte disturbance, and urea nitrogen were risk factors for HE. CONCLUSION: H pylori infection is an important factor for inducing high blood ammonia concentration and HE in cirrhotic patients. H pylori eradication may be helpful for treatment and prevention of HE.展开更多
OBJECTIVE: To evaluate the effectiveness and safety of rhubarb-based Chinese herbal formulae(RCHF), which are widely used to treat hepatic encephalopathy(HE) in China.METHODS: Nine online databases were searched from ...OBJECTIVE: To evaluate the effectiveness and safety of rhubarb-based Chinese herbal formulae(RCHF), which are widely used to treat hepatic encephalopathy(HE) in China.METHODS: Nine online databases were searched from inception to November 22, 2016. Eligible studies were randomized controlled trials of Traditional Chinese Medicine(TCM) treatment for adult patients(≥ 18 years old) with HE. Outcomes such as mortality rate, clinical response rate, blood ammonia level, and alanine aminotransferase were evaluated between TCM group and control group.RESULTS: Thirty studies involving 2661 HE patients were analyzed. Most studies used RCHF treatment.Compared with conventional treatment as usual,lactulose, and vinegar, RCHF were associated with significant improvement in clinical response rate[risk ratio(RR) = 1.33, 95% confidence interval(CI) =1.25, 1.43, I2= 0%; RR = 1.26, 95% CI = 1.14, 1.38, I2=22%; and RR = 1.19, 95% CI = 1.06, 1.33, I2= 0%, respectively] and significant reductions in levels of blood ammonia and alanine aminotransferase. Only minor RCHF-associated adverse events, such as abdominal pain(0.3%), anal tenesmus(0.3%), and diarrhea(2.3%), were reported, and there were no significant differences in these events between the treatment group and the three types of control group.CONCLUSION: The findings suggest that RCHF may be an alternative treatment option for HE patients. More rigorous multicenter studies with larger samples and longer observational periods are needed to confirm these findings.展开更多
Hepatic encephalopathy(HE) is a major complication of cirrhosis resulting in significant socioeconomic burden, morbidity, and mortality. HE can be further subdivided into covert HE(CHE) and overt HE(OHE). CHE is a sub...Hepatic encephalopathy(HE) is a major complication of cirrhosis resulting in significant socioeconomic burden, morbidity, and mortality. HE can be further subdivided into covert HE(CHE) and overt HE(OHE). CHE is a subclinical, less severe manifestation of HE and requires psychometric testing for diagnosis. Due to the time consuming screening process and lack of standardized diagnostic criteria, CHE is frequently underdiagnosed despite its recognized role as a precursor to OHE. Screening for CHE with the availability of the Stroop test has provided a pragmatic method to promptly diagnose CHE. Management of acute OHE involves institution of lactulose, the preferred first-line therapy. In addition, prompt recognition and treatment of precipitating factors is critical as it may result in complete resolution of acute episodes of OHE. Treatment goals include improvement of daily functioning, evaluation for liver transplantation, and prevention of OHE recurrence. For secondary prophylaxis, intolerance to indefinite lactulose therapy may lead to non-adherence and has been identified as a precipitating factor for recurrent OHE. Rifaximin is an effective add-on therapy to lactulose for treatment and prevention of recurrent OHE. Recent studies have demonstrated comparable efficacy of probiotic therapy to lactulose use in both primary prophylaxis and secondary prophylaxis.展开更多
AIM: To assess whether portacaval anastomosis (PCA) in rats affects the protein expression and/or activity of glutaminase in kidneys, intestines and in three brain areas of cortex, basal ganglia and cerebellum and ...AIM: To assess whether portacaval anastomosis (PCA) in rats affects the protein expression and/or activity of glutaminase in kidneys, intestines and in three brain areas of cortex, basal ganglia and cerebellum and to explain the neurological alterations found in hepatic encephalopathy (HE). METHODS: Sixteen male Wistar rats weighing 250-350 g were grouped into sham-operation control (n=8) or portacaval shunt (n = 8). Twenty-eight days after the procedure, the animals were sacrificed. The duodenum, kidney and brain were removed, homogenised and mitochondria were isolated. Ammonia was measured in brain and blood. Phosphate-activated glutaminase (PAG) activity was determined by measuring ammonia production following incubation for one hour at 37 ℃ with O-phthalaldehyde (OPA) and specific activity expressed in units per gram of protein (pkat/g of protein). Protein expression was measured by immunoblotting. RESULTS: Duodenal and kidney PAG activities together with protein content were significantly higher in PCA group than in control or sham-operated rats (duodenum PAG activity was 976.95±268.87μkat/g of protein in PCA rats vs 429.19±126.92.μkat/g of protein in shamoperated rats; kidneys PAG activity was 1259.18±228.79 μkat/g protein in PCA rats vs 669.67±400.8 μkat/g of protein in controls, P〈0.05; duodenal protein content: 173% in PCA vs sham-operated rats; in kidneys the content of protein was 152% in PCA vs sham-operated rats). PAG activity and protein expression in PCA rats were higher in cortex and basal ganglia than those in shamoperated rats (cortex: 6646.6 ±1870.4 μkat/g of protein vs 3573.8± 2037.4 μkat/g of protein in control rats, P〈 0.01; basal ganglia, PAG activity was 3657.3± 1469.6 μkat/g of protein in PCA rats vs 2271.2±384 μkat/g of protein in sham operated rats, P〈0.05; In the cerebellum, the PAG activity was 2471.6±701.4 μkat/g of protein vs 1452.9 ±567.8 μkat/g of protein in the PCA and sham rats, respectively, P〈0.05; content of protein: cerebral cortex: 162% ±40% vs 100% ± 26%, P〈 0.009; and basal ganglia: 140% ±39% vs 100% ±14%, P〈0.05; but not in cerebellum: 100% ±25% vs 100% ± 16%, P= ns). CONCLUSION: Increased PAG activity in kidney and duodenum could contribute significantly to the hyperammonaemia in PCA rats, animal model of encephalopathy. PAG is increased in non-synaptic mitochondria from the cortex and basal ganglia and could be implicated in the pathogenesis of hepatic encephalopathy. Therefore, PAG could be a possible target for the treatment of HE or liver dysfunction.展开更多
文摘Helicobacter pylori(H. pylori) is an ancient microorganism that has co-evolved with humans for over 60000 years. This bacterium typically colonizes the human stomach and it is currently recognized as the most common infectious pathogen of the gastroduodenal tract. Although its chronic infection is associated with gastritis, peptic ulcer, dysplasia, neoplasia, MALT lymphoma and gastric adenocarcinoma, it has been suggested the possible association of H. pylori infection with several extragastric effects including hepatobiliary and pancreatic diseases. Since a microorganism resembling H. pylori was detected in samples from patients with hepatobiliary disorders, several reports have been discussed the possible role of bacteria in hepatic diseases as hepatocellular carcinoma, cirrhosis and hepatic encephalopathy, nonalcoholic fatty liver disease and fibrosis. Additionally, studies have reported the possible association between H. pylori infection and pancreatic diseases, especially because it has been suggested that this infection could change the pancreatic physiology. Some of them have related a possible association between the microorganism and pancreatic cancer. H. pylori infection has also been suggested to play a role in the acute and chronic pancreatitis pathogenesis, autoimmune pancreatitis, diabetes mellitus and metabolic syndrome. Considering that association of H. pylori to liver and pancreas diseases needs further clarification, our work offers a review about the results of some investigations related to the potential pathogenicity of H. pylori in these extragastric diseases.
文摘AIM: To investigate the relationship between H pylori infection, blood ammonia concentration and hepatic encephalopathy (HE), and the effect of Hpylori eradication in cirrhotic patients. METHODS: From July 2003 to January 2005, 457 cirrhotic patients in five regions of Zhejiang Province were enrolled. Patients were evaluated for demographics, number connection test, Hpylori infection, liver impairment, blood ammonia concentration and HE. Patients with Hpylori infection were given I wk therapy with omeprazole plus clarithromycin and tinidazole. ^14C urea breath test was performed and mental symptoms and blood ammonia level were reassessed after RESULTS: Overall H pylori infection rate was 60.6%, and HE occurred in 47.5% of cirrhotic patients. Subclinical HE (SHE) was detected in 55 of 117 cirrhotic patients. Blood ammonia concentration in H pylori negative (n = 180) and positive (n = 277) cirrhotic patients was 53.8 ± 51.4 and 78.4 ± 63.6 μmol/L, respectively (P 〈 0.01), which was significantly reduced to 53.5 ± 37.7 μmol/L after bacterium eradication (n = 126) (P 〈 0.01). Blood ammonia was 97.5 ± 81.0 μmol/L in H pylori-positive cirrhotic patients, and this did not significantly change in those with persistent infection after Hpylori eradication (n = 11). HE was more frequently observed in patients with H pylori infection than in those without (58.5% vs 30.6%, P 〈 0.01). HE rate significantly dropped to 34.1% after H pylori eradiation (P 〈 0.01). H pylori prevalence significantly differed among cirrhotic patients with HE (74.4%), SHE (69.1%), and those without HE (53.2%) (P 〈 0.05). Blood ammonia level was significantly different among cirrhotic patients with HE (94.5 ± 75.6 μmol/L), SHE (59.9 ± 49.2 μmol/L), and without HE (47.3 ± 33.5 μmol/L) (P 〈 0.05). Logistic regression analysis showed that blood ammonia concentration, Child-Pugh stage, upper gastrointestinal bleeding, electrolyte disturbance, and urea nitrogen were risk factors for HE. CONCLUSION: H pylori infection is an important factor for inducing high blood ammonia concentration and HE in cirrhotic patients. H pylori eradication may be helpful for treatment and prevention of HE.
基金Supported by Major Projects of National Science and Technology:the Study of Optimal Regimen for Integrative Treatment of Acute-on-chronic Liver Failure(No.2017zx1020-5506-002)Special Scientific Projects from The State Administration of Traditional Chinese Medicine of The People'S Republic of China:the Study on the Mechanism of Chinese Herbs for Chronic Liver Failure Focused on the Signaling Pathway of Lps/tlr4(No.Jdzx2015187)
文摘OBJECTIVE: To evaluate the effectiveness and safety of rhubarb-based Chinese herbal formulae(RCHF), which are widely used to treat hepatic encephalopathy(HE) in China.METHODS: Nine online databases were searched from inception to November 22, 2016. Eligible studies were randomized controlled trials of Traditional Chinese Medicine(TCM) treatment for adult patients(≥ 18 years old) with HE. Outcomes such as mortality rate, clinical response rate, blood ammonia level, and alanine aminotransferase were evaluated between TCM group and control group.RESULTS: Thirty studies involving 2661 HE patients were analyzed. Most studies used RCHF treatment.Compared with conventional treatment as usual,lactulose, and vinegar, RCHF were associated with significant improvement in clinical response rate[risk ratio(RR) = 1.33, 95% confidence interval(CI) =1.25, 1.43, I2= 0%; RR = 1.26, 95% CI = 1.14, 1.38, I2=22%; and RR = 1.19, 95% CI = 1.06, 1.33, I2= 0%, respectively] and significant reductions in levels of blood ammonia and alanine aminotransferase. Only minor RCHF-associated adverse events, such as abdominal pain(0.3%), anal tenesmus(0.3%), and diarrhea(2.3%), were reported, and there were no significant differences in these events between the treatment group and the three types of control group.CONCLUSION: The findings suggest that RCHF may be an alternative treatment option for HE patients. More rigorous multicenter studies with larger samples and longer observational periods are needed to confirm these findings.
文摘Hepatic encephalopathy(HE) is a major complication of cirrhosis resulting in significant socioeconomic burden, morbidity, and mortality. HE can be further subdivided into covert HE(CHE) and overt HE(OHE). CHE is a subclinical, less severe manifestation of HE and requires psychometric testing for diagnosis. Due to the time consuming screening process and lack of standardized diagnostic criteria, CHE is frequently underdiagnosed despite its recognized role as a precursor to OHE. Screening for CHE with the availability of the Stroop test has provided a pragmatic method to promptly diagnose CHE. Management of acute OHE involves institution of lactulose, the preferred first-line therapy. In addition, prompt recognition and treatment of precipitating factors is critical as it may result in complete resolution of acute episodes of OHE. Treatment goals include improvement of daily functioning, evaluation for liver transplantation, and prevention of OHE recurrence. For secondary prophylaxis, intolerance to indefinite lactulose therapy may lead to non-adherence and has been identified as a precipitating factor for recurrent OHE. Rifaximin is an effective add-on therapy to lactulose for treatment and prevention of recurrent OHE. Recent studies have demonstrated comparable efficacy of probiotic therapy to lactulose use in both primary prophylaxis and secondary prophylaxis.
基金Supported by funding from the Spanish Ministry of Health (grants # PI040384 and # 03/155-2002) awarded to the Spanish Network of Hepatic Encephalopathy Research and a grant from PAI (CTS-532)
文摘AIM: To assess whether portacaval anastomosis (PCA) in rats affects the protein expression and/or activity of glutaminase in kidneys, intestines and in three brain areas of cortex, basal ganglia and cerebellum and to explain the neurological alterations found in hepatic encephalopathy (HE). METHODS: Sixteen male Wistar rats weighing 250-350 g were grouped into sham-operation control (n=8) or portacaval shunt (n = 8). Twenty-eight days after the procedure, the animals were sacrificed. The duodenum, kidney and brain were removed, homogenised and mitochondria were isolated. Ammonia was measured in brain and blood. Phosphate-activated glutaminase (PAG) activity was determined by measuring ammonia production following incubation for one hour at 37 ℃ with O-phthalaldehyde (OPA) and specific activity expressed in units per gram of protein (pkat/g of protein). Protein expression was measured by immunoblotting. RESULTS: Duodenal and kidney PAG activities together with protein content were significantly higher in PCA group than in control or sham-operated rats (duodenum PAG activity was 976.95±268.87μkat/g of protein in PCA rats vs 429.19±126.92.μkat/g of protein in shamoperated rats; kidneys PAG activity was 1259.18±228.79 μkat/g protein in PCA rats vs 669.67±400.8 μkat/g of protein in controls, P〈0.05; duodenal protein content: 173% in PCA vs sham-operated rats; in kidneys the content of protein was 152% in PCA vs sham-operated rats). PAG activity and protein expression in PCA rats were higher in cortex and basal ganglia than those in shamoperated rats (cortex: 6646.6 ±1870.4 μkat/g of protein vs 3573.8± 2037.4 μkat/g of protein in control rats, P〈 0.01; basal ganglia, PAG activity was 3657.3± 1469.6 μkat/g of protein in PCA rats vs 2271.2±384 μkat/g of protein in sham operated rats, P〈0.05; In the cerebellum, the PAG activity was 2471.6±701.4 μkat/g of protein vs 1452.9 ±567.8 μkat/g of protein in the PCA and sham rats, respectively, P〈0.05; content of protein: cerebral cortex: 162% ±40% vs 100% ± 26%, P〈 0.009; and basal ganglia: 140% ±39% vs 100% ±14%, P〈0.05; but not in cerebellum: 100% ±25% vs 100% ± 16%, P= ns). CONCLUSION: Increased PAG activity in kidney and duodenum could contribute significantly to the hyperammonaemia in PCA rats, animal model of encephalopathy. PAG is increased in non-synaptic mitochondria from the cortex and basal ganglia and could be implicated in the pathogenesis of hepatic encephalopathy. Therefore, PAG could be a possible target for the treatment of HE or liver dysfunction.