Gastro-intestinal permeability is increased in patients with limited systemic sclerosis

OBJECTIVE: to evaluate gastro-intestinal (GI) permeability in patients with limited systemic sclerosis (LSS) at baseline and after oral acetylsalicylic acid (ASA). METHODS: 13 patients with LSS and 10 controls were studied. Baseline GI permeability was assessed with orally administered sucrose, mannitol, and lactulose. Gastric lesions and Helicobacter status were investigated by endoscopy. In 5 patients and 6 controls (with normal baseline permeability) the GI permeability response was assessed after oral ASA. RESULTS: compared with controls, gastric (p<0.05) and intestinal (p<0.02) permeability was higher in LSS patients, at baseline. After oral ASA gastric permeability (sucrose) increased in both groups (controls: 186%, LSS: 265%), whereas the lactulose/mannitol ratio raised significantly only in LSS (+31% and +148%; p<0.05 vs controls). CONCLUSIONS: baseline permeability is altered in LSS; the exaggerated response of the small intestine to ASA may represent a genetically determined or a disease-related dysfunction of the mucosal barrier.     

Nodules in antrum after variceal eradication a new finding in patients with portal hypertension

Portal hypertension is known to cause esophageal varices, gastric varices and portal hypertensive gastropathy (PHG). The prevalence of gastric varices and PHG is known to increase after eradication of esophageal varices. PHG includes the presence of a mucosal mosaic pattern, cherry red spots, and/or black-brown spots and gastric vascular ectasia (GAVE). Patients with portal hypertension in whom esophageal varices were eradicated were on follow up endoscopy for detection of recurrence of esophageal varices. Their status of PHG was assessed and patients antral nodules were enrolled. Twenty patients with antral nodules were identified over one year. Fifteen out of 20 patients had cirrhosis as etiology of portal hypertension, three had non-cirrhotic portal hypertension and two had extra-hepatic portal vein thrombosis. GAVE was seen more commonly (n=8, 40%) in patients with PHG with nodules. PHG with antral nodules is a novel endoscopic finding present both in cirrhotic and non-cirrhotic portal hypertension with unknown pathogenesis, and is seen more commonly in patients with eradicated varices who are on long-term follow up.     

Underlying mechanism of portal hypertensive gastropathy in cirrhosis: A hemodynamic and morphological approach

Background and Aim:  Portal hypertensive gastropathy (PHG) is an important cause of bleeding in patients with cirrhosis associated with portal hypertension. Histologically, the condition is characterized by dilation of the mucosal and submucosal vessels of the stomach; however, its mechanisms remain unclear. The aim of the present cross-sectional study was to evaluate the role of portal and systemic hemodynamic features, humoral factors and hepatocellular function in the development and severity of PHG in patients with cirrhosis.
Methods:  Forty-six patients with cirrhosis of different etiologies underwent endoscopy. Portal hypertension was evaluated by hepatic venous pressure gradient (HVPG). The gastric mucosa was analyzed using two diagnostic methods: endoscopy according to the McCormack criteria and histological by histomorphometric analysis.
Results:  The prevalence of PHG according to the endoscopic and histomorphometric methods was 93.4% and 76.1%, respectively. There were no statistically significant differences in HVPG measurements between the patients with mild (16.0 ± 5.9 mmHg) and severe PHG (16.9 ± 6.5 mmHg; P  = 0.80) or between patients who did not have (15.2 ± 8.0 mmHg) and those who had PHG (16.3 ± 5.7 mmHg). No correlation was found between the presence or severity of PHG and systemic vascular resistance index ( P  = 0.53 and 0.34, respectively), Child–Pugh classification ( P  = 0.73 and 0.78, respectively) or glucagon levels ( P  = 0.59 and 0.62, respectively).
Conclusions:  The present data show no correlation between the presence or the severity of PHG and portal pressure, Child–Pugh classification or systemic hemodynamics, suggesting that other factors may be involved in the physiopathology of PHG, such as local gastric mucosal factors or other underlying factors.     

The effects of transjugular intrahepatic portosystemic shunt on portal hypertensive gastropathy

In addition to variceal bleeding, haematemesis may occur due to haemorrhagic gastritis in patients with portal hypertension. This has been known as portal hypertensive gastropathy (PHG). We have evaluated the effects of the transjugular intrahepatic portosystemic shunt (TIPS) on portal venous pressure (PVP) and endoscopic gastric mucosal changes observed in patients with portal hypertension. We performed TIPS in 12 patients with complications due to portal hypertension as follows: variceal bleeding in nine patients (bleeding from oesophageal varices in seven and gastric varices in two), refractory ascites in three and haemorrhage from severe PHG in one. Endoscopic examinations were performed before and after TIPS for all patients. Changes of PVP and gastric mucosal findings on endoscopy were analysed. Before TIPS, PHG was seen in 10 patients. Portal venous pressure decreased from an average of 25.1 ± 8.8 to 17.1 ± 6.2 mmHg after TIPS ( P < 0.005). On endoscopy, PHG improved in nine of 10 patients. Oesophagogastric varices improved in eight of 11 patients. In one patient with massive haematemesis, haemorrhage from severe PHG completely stopped after TIPS. Because TIPS effectively reduced PVP, this procedure appeared to be effective for the treatment of uncontrollable PHG.     

Effect of Helicobacter pylori and eradication therapy on gastrointestinal permeability. Implications for patients with seronegative spondyloarthritis

OBJECTIVE: Disruption of intestinal barrier function, followed by increased antigen load, may possibly trigger joint inflammation. In seronegative spondyloarthritis (SpA) both gut inflammation and altered intestinal permeability have been reported. We evaluated the influence of Helicobacter pylori and nonsteroidal antiinflammatory drugs (NSAID) on gastrointestinal (GI) permeability in SpA. Twenty SpA patients (7 women, mean age 47 +/- 13 SD yrs), 30 patients with endoscopic gastritis (EndG; 17 women, mean age 48 +/- 14 yrs), and 35 healthy controls (16 women, mean age 40 +/- 15 yrs) were studied. No patient was undergoing antisecretory therapy. In the SpA group, 8 patients were chronically taking NSAID and 12 took NSAID occasionally, none during the month before the study. All subjects were assessed for gastroduodenal (sucrose) and intestinal (lactulose/mannitol) permeability test and H. pylori status (urea breath test). RESULTS: H. pylori affected GI permeability in both SpA and EndG patients. After eradication therapy, sucrose excretion remained increased in SpA and reverted to normal in EndG patients, whereas lactulose/mannitol test became comparable to controls in both groups. SpA patients taking chronic NSAID had increased gastroduodenal permeability only when H. pylori-positive. In SpA patients, GI permeability did not correlate with clinical activity or biochemical inflammation. CONCLUSION: In SpA, H. pylori and NSAID contribute to impaired GI permeability. Eradication therapy may help to maintain epithelial barrier function and possibly influence clinical improvement in patients with SpA.     

Gastric mucosal responses to intrahepatic portosystemic shunting in patients with cirrhosis

BACKGROUND & AIMS: The response of gastric mucosal lesions in cirrhotic patients with portal hypertension, namely, portal hypertensive gastropathy (PHG) and gastric vascular ectasia (GVE), to transjugular intrahepatic portosystemic shunts (TIPS) is not known. METHODS: Clinical and laboratory evaluation, upper gastrointestinal endoscopy, and Doppler ultrasonography were performed before placement of TIPS and 6 weeks, 3 months, and 6 months after TIPS in 54 patients. Thirty patients had mild PHG, 10 had severe PHG, and 14 had GVE. RESULTS: Approximately 75% of the patients with severe PHG responded to TIPS as shown by improvement in endoscopic findings and by a decrease in transfusion requirements; 89% of patients with mild PHG had endoscopic resolution. Patients with GVE had neither endoscopic resolution nor a decrease in transfusion requirements after TIPS. There was no difference in mortality between the 2 groups. CONCLUSIONS: The results support the position that severe PHG and GVE may be different lesions. Mild and severe PHG respond to TIPS. Because GVE does not respond to TIPS, we recommend that TIPS be avoided for the treatment of gastrointestinal bleeding associated with GVE.     

Effect of transjugular intrahepatic portosystemic shunt formation on portal hypertensive gastropathy and gastric circulation

OBJECTIVES: The aim of this study was to investigate the effect of a transjugular intrahepatic portosystemic shunt (TIPS) on portal hypertensive gastropathy (PHG) and gastric hemodynamics. METHODS: A total of 16 patients with cirrhosis and portal hypertensive gastropathy were prospectively studied. Of these, 12 patients underwent TIPS for esophageal varices and four for refractory ascites. Gastric mucosal blood flow (GMBF) was assessed by laser Doppler flowmeter, and total blood flow (TBF) in submucosa and mucosa by near-infrared endoscopy. Portal venous pressure was obtained by a transducer during the TIPS procedure. The severity of portal hypertensive gastropathy was classified as none, mild, or severe. The examinations were performed before and 2 wk after the procedure. RESULTS: TIPS significantly reduced portal venous pressure. PHG improved in all four patients with severe PHG and in five of 12 patients with mild PHG after treatment. Gastric mucosal blood flow increased from 49.0 to 55.6 ml/min/100 g after TIPS. In contrast, TBF decreased from 0.35/s to 0.27/s after treatment. Liver function tests showed no significant changes before and after the procedure. CONCLUSIONS: It is considered that TIPS may have a beneficial effect on PHG at least for a short time. The mechanism by which PHG improves may be closely related to the improvement of the injured gastric perfusion in cirrhotic patients with PHG.     

Intestinal permeability in patients with chronic liver diseases: Its relationship with the aetiology and the entity of liver damage

BackgroundAlteration in intestinal permeability may be an important factor in the pathogenesis of both the progression of some chronic liver diseases and the onset of some complications in patients with liver cirrhosis.AimsTo investigate the relationships between intestinal permeability, portal hypertension, alcohol use, plasma levels of pro-inflammatory cytokines, and nitric oxide, expressed as s-nitrosothiols, and nitrite levels in patients with various types and degrees of chronic liver diseases.Methods134 healthy volunteers and 83 patients with chronic liver damage entered the study. Intestinal permeability was assessed with the lactulose/mannitol test. Plasma levels of tumour necrosis factor-alpha, interleukin-6, and nitrite and total s-nitrosothiols were determined.ResultsIntestinal permeability was altered in patients with advanced liver disease and impaired in 15–35% of patients without cirrhosis. Independent factors for intestinal permeability alteration were age, portal hypertension, alcohol use, and diabetes. Plasma levels of inflammatory cytokines and nitrosothiols were significantly higher in patients with altered intestinal permeability.ConclusionsAn intestinal permeability evaluation in patients with chronic liver diseases might clarify the significance of intestinal permeability in the pathophysiology of both the progression of liver damage, and the occurrence of complications that accompany liver cirrhosis.     

Portal hypertensive gastropathy: A systematic review of the pathophysiology,clinical presentation,natural history and therapy

AIM: To describe the pathophysiology, clinical presentation, natural history, and therapy of portal hypertensive gastropathy(PHG) based on a systematic literature review.METHODS: Computerized search of the literature was performed via Pub Med using the following medical subject headings or keywords: "portal" and "gastropathy"; or "portal" and "hypertensive"; or "congestive" and "gastropathy"; or "congestive" and "gastroenteropathy". The following criteria were applied for study inclusion: Publication in peer-reviewed journals, and publication since 1980. Articles were independently evaluated by each author and selected for inclusion by consensus after discussion based on the following criteria: Well-designed, prospective trials; recent studies; large study populations; and study emphasis on PHG. RESULTS: PHG is diagnosed by characteristic endoscopic findings of small polygonal areas of variable erythema surrounded by a pale, reticular border in a mosaic pattern in the gastric fundus/body in a patient with cirrhotic or non-cirrhotic portal hypertension. Histologic findings include capillary and venule dilatation, congestion, and tortuosity, without vascular fibrin thrombi or inflammatory cells in gastric submucosa. PHG is differentiated from gastric antral vascular ectasia by a different endoscopic appearance. The etiology of PHG is inadequately understood. Portal hypertension is necessary but insufficient to develop PHG because many patients have portal hypertension without PHG.PHG increases in frequency with more severe portal hypertension, advanced liver disease, longer liver disease duration, presence of esophageal varices, and endoscopic variceal obliteration. PHG pathogenesis is related to a hyperdynamic circulation, induced by portal hypertension, characterized by increased intrahepatic resistance to flow, increased splanchnic flow, increased total gastric flow, and most likely decreased gastric mucosal flow. Gastric mucosa in PHG shows increased susceptibility to gastrotoxic chemicals and poor wound healing. Nitrous oxide, free radicals, tumor necrosis factor-alpha, and glucagon may contribute to PHG development. Acute and chronic gastrointestinal bleeding are the only clinical complications. Bleeding is typically mild-to-moderate. Endoscopic therapy is rarely useful because the bleeding is typically diffuse. Acute bleeding is primarily treated with octreotide, often with concomitant proton pump inhibitor therapy, or secondarily treated with vasopressin or terlipressin. Nonselective β-adrenergic receptor antagonists, particularly propranolol, are used to prevent bleeding after an acute episode or for chronic bleeding. Iron deficiency anemia from chronic bleeding may require iron replacement therapy. Transjugular-intrahepaticportosystemic-shunt or liver transplantation is highly successful ultimate therapies because they reduce the underlying portal hypertension.CONCLUSION: PHG is important to recognize in patients with cirrhotic or non-cirrhotic portal hypertension because it can cause acute or chronic GI bleeding that often requires pharmacologic therapy.     

Gastroduodenal and intestinal permeability in primary biliary cirrhosis

OBJECTIVES: To evaluate gastrointestinal permeability in primary biliary cirrhosis (PBC), using a sensitive method to detect epithelial damage, and to correlate it with the Mayo score, histological stage, ascites, spontaneous bacterial peritonitis, endoscopic signs of portal hypertension and Helicobacter pylori infection. METHODS: Fifty consecutive patients with PBC and 39 patients with cirrhosis of other aetiologies (non-PBC) were enrolled in the study. Coeliac disease was initially ruled out in all participants. Permeability was assessed using sucrose (gastro-duodenum) and lactulose-mannitol (intestine). RESULTS: Sucrose excretion was above the limit in both PBC and non-PBC patients. Twenty-two per cent of PBC patients had an increased result for the lactulose-mannitol test compared to 12.8% of non-PBC cirrhotic patients. PBC patients had high sucrose excretion levels irrespective of the presence of any oesophageal varices, which significantly increased the gastroduodenal permeability in non-PBC patients only when associated with hypertensive gastropathy. Sucrose excretion was significantly enhanced by hypertensive gastropathy in non-PBC patients (P < 0.001) but not in PBC patients. No significant correlation was found in either group between gastrointestinal permeability and the other parameters. CONCLUSIONS: Gastrointestinal permeability is increased in PBC. Portal hypertension contributes to altered gastric mucosal permeability in non-PBC cirrhosis, whereas different epithelial dysfunction can be hypothesized in PBC.     

The natural history of portal hypertensive gastropathy: influence of variceal eradication

OBJECTIVE: The natural history and likelihood of bleeding from portal hypertensive gastropathy (PHG) present in patients with portal hypertension before endoscopic variceal obliteration may differ from that in patients who develop PHG during or after variceal eradication. METHODS: A total of 967 variceal bleeders who had achieved variceal eradication by endoscopic sclerotherapy in the recent past were prospectively studied. In all, 88 (9.1%) patients (cirrhosis in 54, noncirrhotic portal fibrosis in 18, and extrahepatic portal vein obstruction in 16) had distinct mucosal lesions. PHG alone was present in 78, PHG with gastric antral vascular ectasia (GAVE) in eight, and GAVE alone in two patients. PHG was graded as mild or severe and according to whether present before (group A) or after endoscopic intervention (group B). Patients underwent regular endoscopy at follow-up to see if the PHG was transitory (disappearing within 3 months), persistent (no change), or progressive. Bleeding from PHG lesions was defined as acute or chronic. RESULTS: Twenty-two (26%) patients had PHG before (group A) and 64 (74%) developed PHG after variceal eradication (group B). During a mean follow-up of 25.1 +/- 14.2 months, PHG lesions disappeared in group A in only two patients (9%), but in group B in 28 (44%) patients (p < 0.05). PHG lesions more often progressed in the former as compared to the latter (18% vs 9.4%, p = NS). The incidence of bleeding was higher in group A than group B (32% vs 4.7%, p < 0.02). Bleeding from PHG occurred in 10 patients (11.6%); seven of them were from group A, and all had either progressive (n = 3) or persistent (n = 4) lesions. CONCLUSIONS: PHG developing after variceal eradication is often transitory and less severe. If PHG is pre-existing, endoscopic therapy for varices could worsen the PHG, with a likelihood of bleeding. Such patients may be benefited by concomitant beta-blocker therapy.     

Portal hypertension and portal hypertensive gastropathy in patients with liver cirrhosis: a haemodynamic study

BACKGROUND/AIM: The relationships between the levels of portal hypertension and the morphologic alterations of gastric mucosa in patients with liver cirrhosis--generally described as portal hypertensive gastropathy--are poorly defined. PATIENTS: In total, 62 patients with cirrhosis of different aetiologies, were examined by endoscopy and measurement of portal hypertension by hepatic venous pressure gradient. RESULTS: Portal hypertensive gastropathy was observed in 49 cases; six patients showed gastric antral vascular ectasia always associated with gastric lesions described as severe portal hypertensive gastropathy with different localizations. Hepatic venous pressure gradient showed severe portal hypertension in 37 cases, and averaged 17.7 +/- 4.3 mmHg. It was much higher in patients with severe lesions (p=0.0004). Hepatic venous pressure gradient in patients with endoscopic signs of isolated antral gastropathy was lower (p=0.04) than in those with isolated lesions in body-fundus. No relationship was found between hepatic function, as assessed by the Child-Pugh score, and portal hypertensive gastropathy. CONCLUSIONS: The present data suggest that the severity of portal hypertensive gastropathy is related to portal hypertension, but portal hypertension is not the sole determinant of the occurrence of endoscopic abnormalities of gastric mucosa. The derangement of liver function does not appear to play any role in the occurrence of portal hypertensive gastropathy.     

Effect of laparoscopic splenectomy on portal hypertensive gastropathy in cirrhotic patients with portal hypertension

Aim:  This study investigated the relationship between portal hypertensive gastropathy (PHG) and splenomegaly, and the effect of laparoscopic splenectomy on PHG in cirrhotic patients with portal hypertension.
Methods:  Seventy patients with liver cirrhosis and portal hypertension were prospectively studied. Indication for laparoscopic splenectomy was bleeding tendency in 10 patients, induction of interferon in 45, treatment of hepatocellular carcinoma in seven, and treatment for endoscopic injection sclerotherapy-resistant esophagogastric varices in eight. The severity of PHG was classified into none, mild, or severe according to the classification by McCormack et al. The severity of liver disease was classified using the Child–Pugh score. All patients underwent upper gastrointestinal endoscopy before and 1 month after the operation.
Results:  The prevalence of PHG was significantly correlated with the severity of liver disease using the Child–Pugh score. The severity of PHG was significantly correlated with the resected spleen volume. One month after the operation, PHG was improved in 16 of 17 patients with severe PHG and in 12 of 32 with mild PHG. The Child–Pugh score showed a significant improvement (6.8 ± 1.4 to 6.2 ± 1.2) at 3 months after laparoscopic splenectomy ( P  < 0.0001).
Conclusions:  PHG may be associated with splenomegaly, and laparoscopic splenectomy may have a beneficial effect on PHG, at least for a short time.     

Leaky gut in alcoholic cirrhosis: a possible mechanism for alcohol-induced liver damage

Objective: Only 30% of alcoholics develop cirrhosis, suggesting that the development of alcohol-induced liver injury requires one or more additional factors. Animal studies have shown that gut-derived endotoxin is one such factor. Because increased intestinal permeability has been shown to cause endotoxemia, we hypothesized that increased gastrointestinal permeability contributes to the pathogenesis of alcoholic liver disease. This study aimed to measure gastroduodenal and intestinal permeability in alcoholics with and without chronic liver disease and in nonalcoholic subjects with chronic liver disease. Methods: Gastroduodenal permeability was assessed by measurement of urinary excretion of sucrose after oral administration. Intestinal permeability was assessed by measurement of urinary lactulose and mannitol after oral administration of these sugars. Results: Alcoholics with no liver disease showed a small but significant increase in sucrose excretion. Alcoholics with chronic liver disease demonstrated a marked and highly significant increase in urinary sucrose excretion relative to the controls, to the alcoholics with no liver disease, and to the nonalcoholics with liver disease. Alcoholics with chronic liver disease demonstrated a marked and highly significant increase in both lactulose absorption and in the urinary lactulose/mannitol ratio (alcoholics 0.703 vs controls 0.019,   p = 0.01  ). In contrast, alcoholics with no liver disease and nonalcoholics with liver disease showed normal lactulose absorption and normal lactulose/mannitol ratio. Conclusion: Because only the alcoholics with chronic liver disease had increased intestinal permeability, we conclude that a "leaky" gut may be a necessary cofactor for the development of chronic liver injury in heavy drinkers.     

门脉高压性胃病的病理观察及其影响因素分析

目的 探讨门脉高压性胃病（PHG）的病理特点，分析PHG的影响因素。材料方法 对36例肝炎后肝硬化PHG患者的胃黏膜活检组织光、电镜下观察并进行幽门螺杆菌特殊染色，乙型肝炎病毒（HBV）表面抗原（HBsAg)和核心抗原（HBcAg)免疫组化染色。结果 胃黏膜血管扩张、内皮细胞连接松散、黏膜上皮和间质水肿等血管病变是PHG共同的病理改变。幽门螺杆菌（HP）感染率为77．8％（28／36），而胃黏膜乙型肝炎病毒（HBV）感染对PHG影响的证据不足。结论 PHG有其较特征性的病理改变；幽门螺杆菌感染和高酸可能是影响PHG的重要因素，抗感染和抗酸治疗有其理论基础。     

The Differing Effects of Acute and Chronic Alcohol on Gastric and Intestinal Permeability

Objective: Acute and chronic alcohol intake cause GI symptoms because of either alcohol-induced structural or functional abnormalities. In theory, the disruption of the integrity of the gut mucosa should be reflected by changes in the absorption of molecular probes, such as lactulose, mannitol, and sucrose. Accordingly, we investigated the effects of acute and chronic ethanol on the permeability of the gastric and small intestinal mucosa. Methods: We measured the absorption of sucrose, mannitol, and lactulose in 20 controls and 18 alcoholics within 3 days after their last drink. We evaluated the reversibility of the abnormalities in alcoholics by repeat testing after 7 to 14 days of sobriety. The acute effects of ethanol in normal controls and abstinent alcoholics were also studied after the administration of ethanol by both the oral and IV routes. Results: The absorptions of lactulose and sucrose in chronic alcoholics were normal. However, the alcoholics demonstrated a significant decrease in mannitol absorption and a corresponding increase in the lactulose/mannitol ratio. Both parameters returned to normal after a period of sobriety. Acute ethanol did not significantly affect mannitol or lactulose absorption, whereas oral ethanol significantly increased sucrose absorption. Conclusions: Chronic ethanol re-versibly affects the integrity of small intestinal villi without significantly affecting gastrointestinal permeability. In contrast, a single oral dose of ethanol increases gas-troduodenal permeability but has no effect on the lactulose or mannitol permeability of the small intestine. These regional changes in gut permeabilities may contribute to alcohol-induced GI symptoms.     

病毒性肝炎患者的胃镜表现

目的：探讨病毒性肝炎患者的胃镜表现。方法：２６４例肝炎病人中肝硬变１７３例,慢性肝炎６１例,急性肝炎３０例,分别观察其胃镜下胃粘膜改变的特征及其与临床的关系。结果：门脉高压性胃病、消化道溃疡及糜烂性胃炎、浅表性胃炎、Ｈｐ阳性等均为病毒性肝炎患者的常见胃镜表现。门脉高压性胃病多发性在胃底、胃体;溃疡多发生于胃窦及球部。门脉高压性胃病及胃粘膜糜烂的范围和程度与食道静脉曲张程度相关。结论：病毒性肝炎患者     

肝硬化患者胃黏膜前列腺素E2的研究

目的研究肝硬化患者胃黏膜前列腺素E2(PGE2)及意义。方法选取肝硬化患者60例及慢性胃炎、非溃疡性消化不良(NUD)患者各80例,行上消化道内镜检查,取胃窦及胃体各1块黏膜组织,用RIA法检测PGE2含量。结果(1)肝硬化组胃黏膜PGE2含量明显低于慢性胃炎及NUD组。(2)在肝硬化患者中,胃黏膜PGE2含量门脉高压胃病(PHG)组明显低于非PHG组,肝源性溃疡(HU)组亦明显低于非HU组,而与肝功能分级无关。结论(1)肝硬化胃黏膜防御机制减弱。(2)肝硬化胃黏膜PGE2的异常参与PHG及HU的形成。     

Sugar tests detect celiac disease among first-degree relatives

OBJECTIVES: First-degree relatives of patients with celiac disease are at high risk for developing the disease themselves. Detection of serum antibodies and intestinal permeability tests have been useful to identify candidates for intestinal biopsies. Recently it was demonstrated that abnormal sucrose permeability is a very sensitive marker of active disease. Our objectives in this prospective study were (1) to assess the screening value of permeability tests, and (2) to compare the usefulness of these markers with that of the celiac disease-related serology in screening for celiac disease in a cohort of first-degree relatives of well-known patients. METHODS: We performed sugar tests in 66 first-degree relatives of probands. Subjects ingested 450 ml of a solution containing sucrose (100 g), lactulose (5 g), and mannitol (2 g). Subsequently, a complete overnight urine collection was obtained. Measurement of sugars was performed by high-performance liquid chromatography. All relatives were evaluated for antigliadin (type IgA and IgG) and endomysial antibodies and subjects positive for any test underwent intestinal biopsy. RESULTS: Twelve relatives were diagnosed as having small intestinal mucosal atrophy. Increased sucrose permeability was detected in 9 (75%) of these patients. Four false-positive determinations were found but all had gastric erosions, which is known to increase sucrose permeability independently of duodenal damage. Increased lactulose/mannitol ratios were observed in all new celiac patients. An additional nine relatives had positive results; however, four of them did not accept intestinal biopsy and the remaining five did not seem to have histological evidence of disease. Endomysial antibodies were detected in 11 of 12 patients and no false-positive cases were observed. Antigliadin antibodies were 75% sensitive and 88% specific. CONCLUSIONS: Our study demonstrated that screening using the endomysial antibody test is highly sensitive and specific for detecting celiac disease; however, almost 10% can be missed. The addition of lactulose/mannitol permeability testing to the screening protocol allowed us to detect all relatives who actually presented with evidence of gluten sensitivity. Sucrose permeability exhibited a lower sensitivity; however, it did detect other endoscopically visible lesions.     

Abnormal Intestinal Permeability in Primary Biliary Cirrhosis

Antimitochondrial antibodies (AMAs) found in patients with primary biliary cirrhosis (PBC) cross-react with bacterial proteins and hence molecular mimicry has been proposed as a mechanism for AMA development. Alterations in gastrointestinal permeability would provide a potential route for increased exposure of gut flora to the immune system. In this study we aimed to compare the measured gastrointestinal permeability in patients with PBC to that in patients with liver disease (hepatitis C) and healthy control populations. Subjects drank a mixture of sucrose, lactulose, and mannitol dissolved in water. Eight-hour urinary excretion of the sugars was measured to assess intestinal permeability. Antiendomysial antibody testing was performed to exclude subclinical celiac disease. Eighty-six patients with PBC were evaluated and compared to 69 hepatitis C patients and 155 healthy controls. The mean urinary excretion of sucrose in the PBC patients (133.89 ± 72.56 mg) was significantly higher than that in hepatitis C patients (101.07±63.35) or healthy controls (89.46±41.76) (P=0.0001), suggesting abnormal gastric or proximal small intestinal permeability. Sucrose excretion was not increased among patients with hepatitis C compared to healthy controls. The ratio of lactulose:mannitol excretion, reflecting small bowel permeability, was also elevated in the PBC group (0.017±0.012) compared to healthy controls (0.012±0.007) (P=0.0001) but was equal to that found among patients with hepatitis C (0.016±0.011) (P=NS). We conclude that the permeability of both the stomach and the small bowel is increased in patients with PBC, however, it is unclear if it is a cause, consequence, or manifestation of the disease.