Role of Helicobacter pylori infection and its eradication in patients with subclinical hepatic encephalopathy

AIMS: Helicobacter pylori infection in cirrhotic patients has been associated with episodes of hepatic encephalopathy (HE), although conclusive data are still lacking. This prospective study has evaluated the prevalence of H. pylori infection in 37 patients with advanced cirrhosis of the liver and subclinical hepatic encephalopathy (SHE), diagnosed by changes in psychometric tests and/or electrophysiological tests, as well as the repercussion of H. pylori eradication on ammonaemia and the evolution of this disorder. RESULTS: A positive result for H. pylori infection was obtained in 22/37 (59%) patients. Initial fasting blood levels of ammonia were high in both groups. Infected and non-infected patients showed similar levels (62.05 mmol/l v. 62.5 mmol/l), which were lowered by the standard diet, although statistical significance was only reached in the infected patient group (53.05 +/- 26 mmol/l; P < 0.05). Infection was eradicated in 19 patients, but no reduction of blood levels of ammonia was observed after H. pylori eradication among infected patients (52.37 +/- 29 mmol/l). No change has been found in either group after the administration of diet or antimicrobials with regard to psychometric and/or electrophysiological tests. CONCLUSIONS: H. pylori infection does not contribute significantly to high blood levels of ammonia in patients with advanced cirrhosis and SHE. Likewise, H. pylori eradication does not induce any improvement in the psychometric and/or electrophysiological tests used to define SHE.     

Helicobacter pylori, hyperammonemia and subclinical portosystemic encephalopathy: effects of eradication

BACKGROUND/AIMS: An involvement of Helicobacter pylori in the development of hepatic encephalopathy in cirrhotic patients has been proposed, but data confirming such an association are lacking. This prospective study aimed to assess whether ammonia levels and indicators of subclinical portosystemic encephalopathy were influenced by H. pylori status in a series of 62 cirrhotic patients. The effects of H. pylori eradication on such parameters were also investigated. METHODS: Fasting blood ammonia levels, mental state, number connection test, flapping tremor, and EEG tracings were recorded at baseline, and in H. pylori-positive patients (as diagnosed by rapid urease test and 14C-urea breath test) these parameters were reassessed 2 months following eradication therapy. RESULTS: In this series of non-advanced cirrhotic patients, the prevalence of H. pylori infection was 52%. No significant differences were observed between H. pylori+ and H. pylori- cases with respect to fasting venous blood ammonia concentration (47+/-24 vs. 43+/-22 micromol/l) or to the remaining parameters assessing portosystemic encephalopathy. In addition, H. pylori eradication failed to induce any significant variation in either fasting blood ammonia levels (from 45+/-23 to 48+/-26 micromol/l) or neurologic disturbances. CONCLUSION: These results indicate that H. pylori infection is not a major contributing factor to either fasting blood ammonia levels or parameters assessing subclinical portosystemic encephalopathy in patients with non-advanced liver cirrhosis.     

Effect of H pylori infection and its eradication on hyperammo-nemia and hepatic encephalopathy in cirrhotic patients

AIM: To investigate the relationship between H pylori infection, blood ammonia concentration and hepatic encephalopathy (HE), and the effect of H pylori 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, H pylori infection, liver impairment, blood ammonia concentration and HE. Patients with H pylori infection were given 1 wk therapy with omeprazole plus clarithromycin and tinidazole. 14C urea breath test was performed and mental symptoms and blood ammonia level were reassessed after bacterium eradication.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 nmol/L, respectively (P < 0.01), which was significantly reduced to 53.5 ± 37.7 nmol/L after bacterium eradication (n = 126) (P < 0.01). Blood ammonia was 97.5 ± 81.0 nmol/L in H py/ori-positive cirrhotic patients, and this did not significantly change in those with persistent infection after H pylori 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 nmol/L), SHE (59.9 ± 49.2 nmol/L), and without HE (47.3 ± 33.5 nmol/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.     

Helicobacter pylori, gastric juice, and arterial ammonia levels in patients with cirrhosis

Helicobacter pylori urease activity is a potential source of ammonia in the stomach of patients with cirrhosis. However, the possible role of H. pylori in the pathogenesis of hepatic encephalopathy deserves further investigations. The current study evaluates the relationship among H. pylori infection, gastric juice ammonia concentrations, and arterial ammonia levels in patients with cirrhosis. Overall, 14 patients with cirrhosis with overt hepatic encephalopathy, 19 with subclinical hepatic encephalopathy, and 13 without encephalopathy were enrolled. All patients underwent upper endoscopy, and gastric biopsy specimens were taken for H. pylori assessment (rapid urease test, histology, and culture). A gastric juice sample and an arterial blood sample were obtained for ammonia level assessment. Patients with overt encephalopathy had both higher arterial ammonia levels and a more severe hepatic impairment than the remaining patients, whereas gastric juice ammonia concentrations did not differ among the three groups. H. pylori prevalence was similar among groups. Patients with H. pylori infection had significantly higher gastric juice ammonia concentrations than those without infection (2.3 +/- 1.3 vs. 0.9 +/- 0.6 mmol/L, respectively; p = 0.003); however, no difference in arterial ammonia levels emerged between the two groups (37.7 +/- 18.6 vs. 37.6 +/- 18.8 micromol/L, respectively). No significant correlation was found between gastric juice ammonia concentrations and arterial ammonia levels. The data suggest that liver impairment remains crucial in ammonia disposal in patients with cirrhosis, whereas H. pylori infection does not seem to play a major role in the pathogenesis of hyperammonemia in these patients.     

Effect of H pylori infection and its eradication on hyperammo-nemia and hepatic encephalopathy in cirrhotic patients

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 nit     

幽门螺杆菌感染对高氨血症和肝性脑病发病的影响

目的了解幽门螺杆菌(Hp)感染和血氨水平、肝性脑病(HE)发病的关系,并探讨根除Hp对血氨水平和HE发生的影响。方法2003年7月-2005年1月在浙江省5个地区收集肝硬化住院患者,记录患者的一般资料、数字连接试验结果、Hp感染情况、肝功能Child-Pugh分级、血氨水平和HE情况。Hp(+)患者予“奥美拉唑+克拉霉素+替硝唑”1周根除治疗,1个月后查~(14)C尿素呼气试验,并记录患者的神经精神症状和血氨水平。结果(1)共收集肝硬化住院患者457例,Hp感染率60．6%,HE发生率47．5%。检出亚临床肝性脑病(SHE)患者55例,SHE占未发生HE肝硬化患者的47．0%(55/117)。(2)Hp(+)和Hp(-)肝硬化患者血氨浓度分别为(78．4±63．6)μmoL/L和(53．8±51．4)μmol/L(P＜0．01);根除Hp后血氨显著下降至(53．5±37．7)μmol/L(P＜0．01)。Hp(+)和Hp(-)肝硬化患者HE发生率差异有统计学意义(58．5%比30．6%,P＜0．01);根除Hp后HE发生率下降至34．1%(P＜0．01)。(3)HE、SHE和肝硬化患者的Hp感染率分别为74．4%、69．1%和53．2%(P＜0．05)。三组患者的血氨水平分别为(94．5±75．6)μmol/L、(59．9±49．2)μmol/L和(47．3±33．5)μmol/L(P＜0．05)。结论Hp感染是引起肝硬化高氨血症和并发HE的重要因素,根除Hp有利于治疗和预防HE的发生。     

Minimal hepatic encephalopathy: time to recognise and treat

Minimal hepatic encephalopathy represents a part of the spectrum of hepatic encephalopathy and is the mildest form. While patients with hepatic encephalopathy have impaired intellectual functioning, personality changes, altered levels of consciousness, and neuromuscular dysfunction, patients with minimal hepatic encephalopathy have no recognisable clinical symptoms of hepatic encephalopathy but have mild cognitive and psychomotor deficits. The prevalence of minimal hepatic encephalopathy has been reported to vary between 30% and 84% in patients with liver cirrhosis and is higher in patients with poor liver function. The diagnosis is usually made by neuropsychological and/or neurophysiological testing in cirrhotic patients who are otherwise normal on neurological examination. Minimal hepatic encephalopathy is a clinically significant disorder that impairs the health-related quality of life, predicts the development of overt encephalopathy and is probably associated with a poor prognosis. Thus screening all patients with cirrhosis for minimal hepatic encephalopathy using psychometric testing is recommended. Pharmacologic therapy is recommended for patients diagnosed with minimal hepatic encephalopathy. The pathogenesis of minimal hepatic encephalopathy is considered similar to that of overt hepatic encephalopathy and ammonia plays a key role. Thus ammonia lowering agents such as lactulose, L-ornithine and L-aspartate that have good safety profiles are recommended. Future studies will better define the role of probiotics, levocarnitine and sodium benzoate.     

Hepatic encephalopathy and Helicobacter pylori: a critical reappraisal

Hepatic encephalopathy (HE) is a frequent complication of liver cirrhosis, and plasma ammonia plays a pivotal role in its pathogenesis. Ammonia disposal in cirrhotics depend on intricately balanced enzyme and transport systems, involving liver, large and small bowel, muscle, and kidney. Recently, it has been suggested that Helicobacter pylori could contribute to hyperammonemia in cirrhotics, but conflicting data are available in the literature. This is a systematic review of experimental (animals and humans), epidemiological, case-control, and prospective studies, to evaluate the arguments in favor and against the role of H. pylori in HE pathogenesis. Although H. pylori produces ammonia in the stomach, several studies have shown that both basal ammonia levels and HE prevalence did not significantly differ between cirrhotics with and without infection. Moreover, some prospective studies have documented that both blood ammonia levels and mental status in HE cirrhotics are not significantly affected by H. pylori eradication. Even if a small sub-group of cirrhotics with both a high bacterial density and more severe hepatic impairment seems to benefit by bacterial eradication, data indicate that ammonia production in the stomach by H. pylori urease appears to be inadequate to clinically affect ammonia disposal in the majority of cirrhotic patients. Further studies are warranted in this field.     

Effect of Helicobacter pylori eradication on serum ammonia levels in patients with chronic liver disease.

BACKGROUND: Helicobacter pylori infection has been implicated in the development of encephalopathy in chronic liver disease (CLD); this is possibly due to increased production of ammonia by the action of bacterial urease on urea in the gastric lumen. AIM: To evaluate whether H. pylori eradication in patients with CLD affects arterial ammonia levels. METHODS: Forty-six patients with CLD (40 alcoholic, 6 post hepatitis B; Child's class A 7, B 17, C 22) and 36 patients with symptoms of acid-peptic disease (APD) underwent gastrointestinal endoscopy and biopsy; gastric biopsies were evaluated for H. pylori status using rapid urease test and histology. H. pylori-positive subjects received quadruple-drug eradication therapy for 2 weeks. Fasting arterial plasma ammonia levels were estimated before and after eradication of H. pylori. RESULTS: H. pylori infection was present in 21 of 46 (45.7%) patients with CLD and 23 of 36 (63.9%) with APD. At baseline, mean (SD) ammonia levels were higher in the CLD group (97.4 [10.9] versus 81.3 [7.7] mcg/dL in the APD group; p = 0.0001), irrespective of H. pylori status. Amongst patients with liver disease, arterial ammonia levels were similar in the H. pylori-positive and -negative patients (94.1 [9.7] and 100.2 [11.3] mcg/dL, respectively); however, ammonia levels were higher in patients in Child's class C (102.7 [11.4] mcg/dL/dL) than in those in class A (88.4 [1.6] mcg/dL; p < 0.002) or B (94.1 [9.7] mcg/dL; p < 0.002). In patients with APD, ammonia levels were higher in H. pylori-positive patients (85.3 [6.4] versus 74.1 [3.3] mcg/dL; p < 0.001). After eradication of H. pylori infection, ammonia levels decreased to 88.4 (10.0) mcg/dL in CLD and 76.7 (4.8) mcg/dL in APD (p = 0.001 as compared to baseline). There was no difference in post-eradication ammonia levels between Child's classes. CONCLUSION: Levels of arterial blood ammonia are higher in CLD than in APD, and correlate with severity of liver disease. H. pylori eradication was associated with reduction in arterial ammonia levels in patients with CLD.     

Gastrin and antral G cells in course of Helicobacter pylori eradication： Six months follow up study

ABM: To assess long-term effects of Helicobacter pylori (H pylori) eradication on antral G cell morphology and function in patients with and without duodenal ulcer (DU). METHODS: Consecutive dyspeptic patients referred to the endoscopy entered the study. Out of 39 H pylori positive patients, 8 had DU (Hpylori+DU) and 31 gastritis (Hpylori +G). Control groups consisted of 11 uninfected dyspeptic patients (CG1) and 7 healthy volunteers (CG2). Basal plasma gastrin (PGL), antral tissue gastrin concentrations (ATGC), immunohistochemical and electron microscopic characteristics of G cells were determined, prior to and 6 mo after therapy. RESULTS: We demonstrated elevated PGL in infected patients compared to uninfected controls prior to therapy. Elevated PGL were registered in all H pylori+patients (H pylori +DU: 106.78±22.72 pg/mL, H pylori+G: 74.95±15.63, CG1: 68.59±17.97, CG2: 39.24±5.59 pg/mL, P<0.01). Successful eradication (e) therapy in H pylori+patients lead to significant decrease in PGL (H pylori+DU:59.93±9.40 and H pylori+Ge: 42.36±10.28 pg/mL, P<0.001). ATGC at the beginning of the study were similar in infected and uninfected patients and eradication therapy lead to significant decrease in ATGC in H pylori+gastritis, but not in DU patients. In the H pylori+DU patients, the mean number of antral G cells was significantly lower in comparison with all other groups (P<0.01), but after successful eradication was close to normal values found in controls. By contrast, G cell number and volume density were significantly decreased (P<0.01) in H pylori+Ge group after successful eradication therapy (294±32 and 0.31±0.02, respectively), in comparison to values before eradication (416±40 and 0.48±0.09). No significant change of the G cell/total endocrine cell ratio was observed during the 6 mo of follow up in any of the groups. A reversible increase in G cell secretory function was seen in all infected individuals, demonstrated by a more prominent secretory apparatus. However, differences between DU and gastritis group were identified. CONCLUSION: H pylori infection induces antral G cell hyperfunction resulting in increased gastrin synthesis and secretion. After eradication therapy complete morphological and functional recovery is observed in patients with gastritis. In the DU patients some other factors unrelated to the H pylori infection influence antral G cell morphology and function.     

幽门螺杆菌感染与肝性脑病的相关性

目的探讨肝硬化患者幽门螺杆菌（H．pylori）感染和肝性脑病（HE）发病的相关性。方法收集110例符合诊断标准的肝硬化患者,详细记录H．pylori检测结果、血氨水平、数字连接试验（NCT）结果、HE临床症状。其中71例H．pylori阳性者随机分为观察组和对照组,观察组予泮托拉唑钠肠溶胶囊＋克拉霉素缓释片＋奥硝唑胶囊进行根除治疗,1周后复查血氨。结果H．pylori阳性肝硬化患者的血氨水平及HE的发生率明显高于Hpylori阴性的肝硬化患者,两者差异有统计学意义（P〈0．05）;tt．pylori阳性者中观察组行H．pylori根除治疗,血氨下降明显优于对照组（P〈0．05）。结论H．pylori感染可使肝硬化患者血氨水平升高,根除H．pylori治疗对降低肝性脑病的发生有重要的临床意义。     

Is Helicobacter pylori eradication indicated in cirrhotic patients with peptic ulcer disease?

INTRODUCTION: The association between H. pylori infection and peptic ulcer disease (PUD) and the efficacy of eradication of H. pylori in treating ulcer disease in cirrhotic patients remains controversial. This study was carried out to ascertain the prevalence and significance of H. pylori in cirrhotic patients with PUD and to assess the need for anti H. pylori thrapy METHODS: Three groups of patients were studied . These were patients with (A) cirrhosis and PUD, (B) uncomplicated PUD and (C) cirrhosis without PUD. H. pylori status was determined by endoscopic urease test . Eradication therapy was given with a four drug regimen and repeat endoscopy was done three months later to detect ulcer healing as well as H. pylori status with PUD in groups A and B. RESULTS: Cirrhotic patients with PUD had a significantly lesser prevalence of H. pylori compared to uncomplicated ulcer patients (46.9 % vs 80 %; p = 0.04). While H. pylori eradication rates were similar between cirrhotic and non cirrhotic patients, ulcer healing rate was significantly lesser in cirrhotic patients ( 48 % vs 80.9 %) . Majority of residual ulcers in cirrhotic patients were negative for H. pylori. CONCLUSION: Eradication of H. pylori does not reduce the residual ulcer rate indicating that H. pylori infection might not be a significant risk factor for PUD in cirrhotic patients. Hence, routine H. pylori eradication might not be warranted in patients with cirrhosis and peptic ulcer disease.     

Helicobacter pylori eradication dramatically improves inflammation in the gastric cardia

OBJECTIVES: Inflammation of the gastric cardia, i.e., "carditis," has been associated with Helicobacter pylori (H. pylori) infection; however, some investigators believe carditis to be a histological marker for gastroesophageal reflux disease. The aim of this study was to investigate the role of H. pylori eradication on the grade of carditis scored according to the updated Sydney classification. METHODS: Consecutive patients presenting for upper endoscopy underwent systematic gastric biopsies (eight antral, 12 corpus, and four cardia). Patients with H. pylori infection and carditis were identified and followed prospectively before and after H. pylori treatment. At pretreatment and, on average, 2 yr after eradication of H. pylori, the degree of inflammation in the gastric cardia and H. pylori status were blindly assessed by a single pathologist. RESULTS: A total of 31 patients with H. pylori infection and carditis were identified. The mean age was 70 yr (range: 37-81 yr); all were male. Four were African-American and 27 were Caucasian. All patients were treated with standard anti-H. pylori therapy, including a proton pump inhibitor in combination with two antibiotics for 2 wk. Eradication of H. pylori was successful in 23 patients (group I), whereas eight patients had persistent infection (group II). Patients were followed after eradication therapy for a mean of 23.2 months (range: 6-48 months). After eradication therapy, there was a significant decrease (p < 0.0001) in the carditis scores (activity and inflammation scores) in group I, whereas the scores remained unchanged in group II patients. In both groups, there were no significant changes in the degree of intestinal metaplasia or atrophy. There were four patients with intestinal metaplasia, and one with atrophy. CONCLUSIONS: There is a dramatic improvement in the degree of inflammation and activity scores in the gastric cardia of patients with successful H. pylori eradication compared to those with persistent infection. By fulfilling one of Koch's postulates (i.e., improvement in the disease after cure of the possible etiological organism), these data support H. pylori as being the etiological agent for carditis in this group of patients.     

Role of Helicobacter pylori infection in hyperammonemia and subclinical hepatic encephalopathy in cirrhosis of liver.

INTRODUCTION: Gastric Helicobacter pylori infection is believed to be associated with a higher risk of hepatic encephalopathy among patients with cirrhosis of liver. However, the role of this infection in causation of subclinical hepatic encephalopathy has not been studied in detail. METHODS: Patients with cirrhosis of liver but no hepatic encephalopathy underwent venous blood ammonia measurement, psychometric tests (number connection tests [NCT] and figure connection tests [FCT]), and gastric biopsies for presence of H. pylori infection. The results of blood ammonia and psychometric tests in the H. pylori-positive and -negative study subjects were compared. RESULTS: Of 58 patients with liver cirrhosis studied, 31 had evidence of gastric H. pylori infection. Venous blood ammonia levels were comparable in patients with (median 29 mmol/L; range 18-47) and without (34 [15-48] mmol/L; p=ns) H. pylori infection. The time taken to complete NCT trail A (median 37 s [range 25-69] versus 36.5 [26-62]), NCT trail B (64 s [48-91] versus 63.5 [42-88]), FCT trail A (59 s [31-115] versus 58 [38-590]) and FCT trail B (76 s [55-187] versus 82 [36-125]) were similar in those with and those without H. pylori infection. For each of the four tests, the proportion of subjects with abnormal test results was similar among H. pylori-positive and -negative subjects. CONCLUSION: Presence of H. pylori infection among patients with cirrhosis of liver but no overt hepatic encephalopathy is not associated with increase in blood ammonia concentration or deterioration in psychomotor function.     

Helicobacter pylori infection in patients with liver cirrhosis: facts and fictions

Helicobacter pylori infection could play a role in different clinical alterations observed in cirrhosis, from gastroduodenal lesions to hepatic encephalopathy. Although its prevalence in cirrhotics is similar to that in controls, H. pylori infection is responsible for the increased prevalence of peptic ulcer observed in these patients. The ammonia production by H. pylori urease does not seem to increase blood ammonia levels during cirrhosis, indicating that its role in hepatic encephalopathy could be marginalized in clinical practice. Dual and triple therapies have been shown to be equally effective for H. pylori eradication in these patients.     

Breath and blood ammonia in liver cirrhosis

BACKGROUND/AIMS: Hyperammonemia causes dysfunction of multiple organs in patients with cirrhosis, including hepatic encephalopathy. Blood ammonia concentrations are monitored with respect to disease progression and efficacy of treatment. Fetor hepaticus, the characteristic breath odor in hepatic encephalopathy has called little quantitative attention to breath ammonia. We studied the dynamics of ammonia metabolism in cirrhosis in terms of the relationship between breath and blood ammonia. METHODOLOGY: Breath and blood ammonia levels were measured simultaneously in 20 cirrhotic patients and in 10 healthy volunteers. Breath ammonia was measured using ammonia electrodes in collected expired air. Helicobacter pylori serum antibody titers were also measured, since the organism produces ammonia. RESULTS: Blood ammonia correlated positively with breath ammonia in patients with cirrhosis. Breath ammonia levels were significantly higher in cirrhotic patients (0.745 ppm) than in controls (0.278 ppm), and higher in cirrhotic patients with hyperammonemia (0.997 ppm) than in those without (0.558 ppm). Breath and blood ammonia decreased together with treatment of hyperammonemia. H. pylori seropositivity was 20% in controls, 27.3% in cirrhotic patients with normal blood ammonia, and 66.7% in those with hyperammonemia. CONCLUSIONS: Breath ammonia measurement may be useful in diagnosis, treatment assessment, and follow-up in hepatic encephalopathy.     

Helicobacter pylori infection delays ulcer healing in patients operated on for perforated duodenal ulcer.

BACKGROUND: A majority of duodenal ulcers are associated with Helicobacter pylori infection; eradication of the infection improves ulcer healing and reduces the ulcer recurrence rate. However, the frequency of H. pylori infection in patients with perforated duodenal ulcer is not clearly established. We studied the frequency of H. pylori infection in patients with perforated duodenal ulcer and its impact on their clinical presentation. METHODS: All patients presenting with perforated duodenal ulcer underwent emergency laparotomy and simple omental patch repair. Postoperatively they received standard antibiotics for 1-2 weeks along with ranitidine; ranitidine alone was continued thereafter till an endoscopy 4-6 weeks later. Positive rapid urease test along with identification of H. pylori on histology was taken as evidence of H. pylori infection. Patients who received anti-H. pylori therapy or nonsteroidal anti-inflammatory drugs (NSAIDs) postoperatively and/or proton pump inhibitors or antibiotics, during 4 weeks preceding the endoscopy, were excluded. RESULTS: 30 patients (27 men; mean [SD] age 32.9 [9.7 years]) presenting during the period June 1999 to October 2000 were studied. Upper gastrointestinal endoscopy was done 10.9 (6.3) weeks after surgery. Seventeen (56.6%) patients were infected with H. pylori; this group had significantly more men (17/17 versus 10/13 among uninfected) and fewer NSAID users (2/17 vs. 7/13). Median duration of epigastric pain before presentation was 18 weeks in the H. pylori-infected group as compared to one week in the non-infected group (p<0.001). Significantly more patients continued to have epigastric pain after surgery in the infected group (7/17 vs. 0/13). At endoscopy, active duodenal ulcer was present in 13 of 17 patients with evidence of H. pylori infection and none of the noninfected patients (p<0.001). Age, sex, duration between surgery and endoscopy, NSAID use, smoking and maintenance ranitidine use had no impact on ulcer healing after the surgery. CONCLUSIONS: In patients operated on for perforated duodenal ulcer, H. pylori infection was the only significant factor responsible for persistence of ulcer after surgery. We advocate H. pylori eradication therapy in patients operated on for perforated duodenal ulcer.     

Oral Tryptophan Challenge Studies in Cirrhotic Patients: No Evidence of Neuropsychiatric Changes

Hepatic encephalopathy is a frequent complication of cirrhosis. Abnormalities of5-hydroxytryptamine (5-HT) and its metabolites are recognized and may contribute to its pathogenesis. We therefore studied the effect of an oral tryptophan load (6–18 g) upon psychometric test scores and analyzed EEG's in alcoholic cirrhotic patients. Eight patients had had previous encephalopathic episodes related to variceal bleeds and one patient was awaiting a liver transplant. Five out of the 10 patients had at least one abnormal baseline psychometric test. Following tryptophan challenge there were no changes in blood ammonia but plasma tryptophan levels were elevated approximately 10-fold (p <0.01× 10^–7). Nevertheless, there were no statistically significant changes in psychometric testing or analyzed EEG frequency distribution. All patients reported nausea or vomiting while one patient developed a short-lived serotonin like syndrome. We conclude that in this group of patients, an oral tryptophan load does not induce or worsen subclinical hepatic encephalopathy. If the high blood levels of tryptophan seen in these studies are able to influence cerebral neurotransmitter synthesis, the results do not support a primary role for abnormalities of 5-HT neurotransmission in hepatic encephalopathy.     

Analysis of risk factors for chronic hepatic encephalopathy: the role of Helicobacter pylori infection

Objective: Elevated blood ammonia is an important pathogenic factor of hepatic encephalopathy. Although colonic bacteria are considered the main source of ammonia, the stomach in subjects with urease-producing Helicobacter pylori ( H. pylori ) is an alternative site. The objective of this study was to determine whether H. pylori is associated with this complication.
Methods: After assessing liver function and portal hypertension, 55 cirrhotics were evaluated for encephalopathy and H. pylori infection. Response to 2 weeks of amoxicillin (2 g/day) and omeprazole (40 mg/day) was then assessed in 17 (13 H. pylori -positive, four H. pylori -negative) encephalopathic subjects.
Results: H. pylori infection was more common (  67% vs 33%  ,   p = 0.004  ) among encephalopathic patients. Additional factors associated with encephalopathy included older age (  60.1 ± 1.5 vs 49.8 ± 2.4 yr  ,   p = 0.001  ), lower albumin (  3.17 ± 0.08 vs 3.69 ± 0.12 g/dl  ,   p = 0.001  ), higher total bilirubin (  2.24 ± 0.20 vs 1.53 ± 0.23 mg/dl  ,   p = 0.034  ), greater ascites score (  0.8 ± 0.1 vs 0.3 ± 0.1  ,   p = 0.01  ), greater diuretic score (  1.1 ± 0.1 vs 0.3 ± 0.1  ,   p = 0.002  ), and greater modified Child score (  6.7 ± 0.3 vs 5.1 ± 0.3  ,   p = 0.001  ). When adjusted for severity of cirrhosis and age, H. pylori continued to demonstrate a statistical association (   p = 0.039  ). After anti- H. pylori therapy, symptomatology in infected encephalopathic patients appeared to improve, whereas noninfected subjects were unaffected.
Conclusions: In cirrhotic patients, H. pylori infection is associated with hepatic encephalopathy, especially in younger patients with decompensated liver disease.     

The effect of gastrin-releasing peptide on gastrin and somatostatin messenger RNAs in humans infected with Helicobacter pylori

BACKGROUND & AIMS: Gastrin-releasing peptide stimulates gastrin secretion but also inhibits its release via somatostatin. Exogenous gastrin-releasing peptide stimulates a greater increase in plasma gastrin concentrations in patients infected with Helicobacter pylori than in uninfected controls. Because this infection suppressed gastric mucosal somatostatin, we studied whether the increased gastrin response was a result of an abnormal response of the somatostatin cell. METHODS: Patients without dyspeptic ulcers received an infusion of either gastrin-releasing peptide or saline on separate occasions. Acid secretion was measured, and gastric biopsy specimens were taken for gastrin and somatostatin messenger RNA (mRNA) analysis and H. pylori diagnosis. RESULTS: In response to gastrin-releasing peptide, the increase in plasma gastrin concentrations in the infected patients was significantly higher than in the uninfected. Antral gastrin mRNA also increased significantly in the infected group but decreased significantly in the uninfected group. Basal somatostatin was lower in the infected group; gastrin-releasing peptide produced a significant increase in antral somatostatin mRNA concentration in infected, but not uninfected, patients. CONCLUSIONS: The somatostatin cell responds to gastrin-releasing peptide in H. pylori infection. Gastrin-releasing peptide normally inhibits gastrin mRNA expression, but inhibition is deficient in H. pylori infection, possibly because of low stimulated somatostatin levels. (Gastroenterology 1997 Jun;112(6):1940-7)