To describe the pathophysiology, clinical presentation, natural history, and therapy of portal hypertensive gastropathy (PHG) based on a systematic literature review.

Computerized search of the literature was performed via PubMed 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.

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-intrahepatic-portosystemic-shunt and liver transplantation are highly successful ultimate therapies because they reduce the underlying portal hypertension.

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.

The pathophysiology of peptic ulcer disease (PUD) in liver cirrhosis (LC) and chronic hepatitis has not been established. The aim of this study was to assess the role of portal hypertension from PUD in patients with LC and chronic hepatitis.

We analyzed the medical records of 455 hepatic vein pressure gradient (HVPG) and esophagogastroduodenoscopy patients who had LC or chronic hepatitis in a single tertiary hospital. The association of PUD with LC and chronic hepatitis was assessed by univariate and multivariate analysis.

A total of 72 PUD cases were detected. PUD was associated with LC more than with chronic hepatitis (odds ratio [OR]: 4.13, p = 0.03). In the univariate analysis, taking an ulcerogenic medication was associated with PUD in patients with LC (OR: 4.34, p = 0.04) and smoking was associated with PUD in patients with chronic hepatitis (OR: 3.61, p = 0.04). In the multivariate analysis, taking an ulcerogenic medication was associated with PUD in patients with LC (OR: 2.93, p = 0.04). However, HVPG was not related to PUD in patients with LC or chronic hepatitis.

According to the present study, patients with LC have a higher risk of PUD than those with chronic hepatitis. The risk factor was taking ulcerogenic medication. However, HVPG reflecting portal hypertension was not associated with PUD in LC or chronic hepatitis (Clinicaltrial number NCT01944878).

Few large population-based studies have compared the occurrence of peptic ulcer bleeding (PUB) in cirrhotic and noncirrhotic patients.

To investigate if cirrhotic patients have higher risk of PUB than the general population and to identify possible risk factors of PUB in cirrhotic patients.

Using the National Health Insurance Research Database, a nationwide population-based dataset in Taiwan and matching age, gender, comorbidities and ulcerogenic medication by propensity score, 4013 cirrhotic patients, 8013 chronic hepatitis patients and 7793 normal controls were compared. The log-rank test was used to analyse differences in accumulated PUB-free survival rates between the groups. Cox proportional hazard regressions were performed to evaluate independent risk factors for PUB in all patients and identified risk factors of PUB in cirrhotic patients.

During the 7-year follow-up, cirrhotic patients had significantly higher incidences of PUB than chronic hepatitis patients and controls, respectively (P < 0.001 by log-rank test). By Cox proportional hazard regression analysis, cirrhosis was independently associated with increased risk of PUB (hazard ratio: 4.22; 95% CI 3.37-5.29, P < 0.001) after adjusting for age, gender, economic status, underlying comorbidities and ulcerogenic medication. Age, male, diabetes, chronic renal disease, history of gastro-oesophageal variceal bleeding and use of nonsteroidal anti-inflammatory drugs were risk factors for PUB in cirrhotic patients.

Cirrhotic patients have a significantly higher risk of peptic ulcer bleeding after adjustments for possible confounding factors like age, gender, economic status, underlying comorbidities and ulcerogenic medication.

The relationship between Helicobacter pylori infection and gastroduodenal lesions in chronic liver disease remains controversial.

Evaluate the evidence of the role of H. pylori infection in gastroduodenal lesions in patients with chronic liver disease.

Forty-six patients with chronic liver disease were matched with 27 dyspeptic persons for age and sex. The gastroduodenal lesions were portal hypertension gastropathy, erosion and peptic ulcer. All patients underwent upper endoscopy: two biopsies were taken in the antrum and in the gastric body. The biopsies were used for Giemsa staining.

A gastroduodenal lesions were found in 38 (82.6%) patients with liver disease and was significantly more frequent than among controls (P = 0.002). H. pylori infection was detected at histological assessment in 13 (28.2%) patients with chronic liver disease and in 17 (62.9%) controls. The odds ratio (OR) showed an interaction statistically significant between gastroduodenal lesions and chronic liver disease (P = 0.04; OR = 5.1; 95% CI = 1.6-17.3). When adjusted for the presence of H. pylori OR was significantly with H. pylori negative (OR 13.0 IC 95%, 1.4-327.9).

Patients with chronic liver disease showed higher risk of developing gastroduodenal lesions regardless of the presence of the H. pylori infection.

Proton pump inhibitors (PPI) are very effective in inhibiting acid secretion and are extensively used in many acid related diseases. They are also often used in patients with cirrhosis sometimes in the absence of a specific acid related disease, with the aim of preventing peptic complications in patients with variceal or hypertensive gastropathic bleeding receiving multidrug treatment. Contradicting reports support their use in cirrhosis and evidence of their efficacy in this condition is poor. Moreover there are convincing papers suggesting that acid secretion is reduced in patients with liver cirrhosis. With regard to Helicobacter pylori (H pylori) infection, its prevalence in patients with cirrhosis is largely variable among different studies, and it seems that H pylori eradication does not prevent gastro-duodenal ulcer formation and bleeding. With regard to the prevention and treatment of oesophageal complications after banding or sclerotherapy of oesophageal varices, there is little evidence for a protective role of PPI. Moreover, due to liver metabolism of PPI, the dose of most available PPIs should be reduced in cirrhotics. In conclusion, the use of this class of drugs seems more habit related than evidence-based eventually leading to an increase in health costs.

The incidence and risk factors of gastrointestinal diseases in pre-liver transplant population are still a matter of debate. In a retrospective analysis, we addressed two questions: (1) Are there any lesions that occur at a higher prevalence than in the general population, and (2) are there patient characteristics that could predict their presence?

All asymptomatic patients that successfully entered the waiting list of liver transplantation were recorded. We also compared results with those obtained from a control group of non-cirrhotic patients undergoing screening for colorectal cancer. Main outcome measures were the incidence and description of upper/lower gastrointestinal findings after screening endoscopic examination.

We retrospectively evaluated from April 2004 to July 2007 a total of 80 liver transplant candidates. The most frequent pathologies were esophageal varices (71.2% of subjects), portal hypertensive gastropathy (51.2%), hemorrhoids (22.5%), and colonic polyps (18.7%). Comparison with 80 non-cirrhotic patients matched for age and sex demonstrated an increased frequency in the cirrhotic group of ulcerative colitis (6.2 vs 0%; p = 0.02) and portal hypertensive colopathy (12.5 vs 0%; p = 0.001) in non-cirrhotic of diverticulosis (10 vs 25%; p = 0.01) and hemorrhoids (22.5 vs 40%; p = 0.02). The univariate analysis showed no significant correlation between colonic polyps and patients' variables, except a mild correlation with age not confirmed at the multivariate analysis.

The incidence of some benign gastrointestinal pathologies in liver transplant candidates is different from the asymptomatic population but not that of colorectal cancer or colonic polyps.

There is little information available regarding the consequences of living-donor liver transplantation (LDLT) for upper gastrointestinal lesions. We retrospectively compared the pre- and posttransplant incidences of noninfectious reflux esophagitis, portal hypertensive gastropathy (PHG), esophageal varix, gastroduodenal ulcer, Helicobacter pylori infection, and abnormal gastroesophageal valve in 29 adult patients (16 males, 13 females) who underwent LDLT for end-stage liver disease. Here we present four findings from this study. First, the posttransplant incidence of noninfectious esophagitis was significantly higher than the pretransplant incidence (27.6% vs. 3.4%; P < 0.001), irrespective of postoperative use of standard-dose H2RA. Second, PHG and esophageal varix, which were noted in 65.5% and 96.6% of pretransplant recipients, respectively, spontaneously resolved postoperatively in all cases. Third, H. pylori infection, which was observed in 50.0% of preoperative recipients, decreased to 5.6% postoperatively, although no significant difference was observed between the pre- and the posttransplant incidences of gastroduodenal ulcer (6.9% vs. 6.9%). Finally, the incidence of abnormal gastroesophageal valve did not change following LDLT (34.5% vs. 34.5%). In conclusion, this study suggests that noninfectious reflux esophagitis occurs more frequently following LDLT. Although the disease is the results of a very complex interaction of various factors, spontaneous resolution of PHG and serendipitous H. pylori eradication might have contributed to increased incidence of postoperative esophagitis, possibly through gastric acid hypersecretion. In contrast, morphological change of the gastroesophageal valve was not considered to be the cause of this disease. Because this study was a retrospective analysis of a small population of LDLT recipients, prospective randomized controlled studies of a sufficient number of cases are required to substantiate these conclusions.

We evaluated, employing a logistic regression model, the association between Helicobacter pylori infection and cirrhosis in a cohort of 106 patients (57 males; mean age, 52.9 years; range, 20-78 years) with chronic hepatitis C virus (HCV) from Rosario, Argentina. HCV was confirmed by ELISA and PCR. H. pylori status was determined by ELISA. Of the 106 patients evaluated, 47 (44.3%) had cirrhosis. A total of 70.2% (33/47) of cirrhotic patients and 47.5% (28/59) of noncirrhotic patients were H. pylori-positive. In univariate analyses, cirrhosis was associated with age (P = 0.016) and H. pylori-positive status (P = 0.019) but not with gender (P = 0.28) or length of infection (P = 0.35). In multivariate analysis, H. pylori infection (P = 0.037; OR = 2.42; 95% CI = 1.06-5.53) and age (P = 0.033; OR = 1.04; 95% CI = 1.00-1.07) of patients remained significant and independently associated with cirrhosis. In conclusion, our results demonstrate an association between H. pylori infection and cirrhosis in patients with hepatitis C virus.

The role of Helicobacter pylori in patients with cirrhosis and increased prevalence of peptic ulcers is still poorly defined. The objective is to evaluate the effect of H pylori eradication on ulcer recurrence in patients with cirrhosis.

The study was conducted at a single, tertiary, referral hospital with 1200 beds. Patients with cirrhosis and duodenal ulcers were tested for H pylori and were enrolled in the study. Patients with positive H pylori received eradication therapy. Patients with duodenal ulcers received antisecretory therapy and regular endoscopic examinations. Main outcome measurements were the recurrence of duodenal ulcers within 1 year.

A total of 104 patients with cirrhosis and duodenal ulcers were enrolled. Fifty-four patients (52%) were H pylori positive, and 50 patients (48%) were H pylori negative. Forty-four patients received antimicrobial treatment and 36 patients achieved eradication of H pylori. Recurrent duodenal ulcers within 1 year were noted in 21 of 36 patients (58%) who achieved H pylori eradication. Recurrent duodenal ulcers also were noted in 8 of the 18 patients (44%) who remained H pylori positive and in 24 of the patients (48%) who were H pylori negative since their enrollment in the study (p = 0.53). The limitation was a relatively small sample size.

The results of our study showed that the prevalence of H pylori in patients with cirrhosis and duodenal ulcers was only 52%. Eradication of H pylori in patients with cirrhosis and duodenal ulcers did not effectively reduce the recurrence of ulcers.

Portal hypertensive gastropathy is a relatively recently described entity that is an important cause of bleeding in portal hypertension. This article focuses on the endoscopic diagnosis of portal hypertensive gastropathy, including a review of different proposed scoring systems, and briefly examines the epidemiology, pathogenesis, and treatment of portal hypertensive gastropathy.

Standard esophagogastroduodenoscopy (EGD) is costly and uses conscious sedation that cirrhotic patients may tolerate poorly. This study aimed to determine the feasibility and acceptance of unsedated esophagoscopy with an ultrathin battery-powered endoscope (BPE) in cirrhotic patients for diagnosing esophageal varices (EV).

We first studied the prevalence of significant gastroduodenal pathology that could be missed if only esophagoscopy were performed in cirrhotic patients undergoing liver transplant evaluation. A prospective study was then done to evaluate a BPE in EV screening. Unsedated per-oral endoscopy was first done by a single endoscopist using a BPE, followed by EGD by a second endoscopist who was masked to the BPE result. A visual analog score was used to determine patient tolerance. Patients were asked about their preference for endoscopy in the future. A paired Student t test and the kappa statistic were used in the statistical analysis.

In the retrospective study, 199 patients were reviewed; three patients (1.5%) had gastric ulcers, and two patients (1%) had duodenal ulcers. In the prospective study, 28 cirrhotic patients (16 women) were evaluated. EV were diagnosed in 14 patients with a BPE, and 13 were confirmed by standard EGD (sensitivity and negative predictive value 100%, specificity and positive predictive value 93%, kappa = 0.93). EV were graded as large in one and small in 13 patients with a BPE, but small varices diagnosed in one patient were not confirmed on EGD. Both procedures were well tolerated by all patients. Twenty-seven of 28 patients preferred unsedated endoscopy with a BPE over EGD.

Unsedated endoscopy with a BPE is safe and well tolerated. The diagnostic accuracy of a BPE for diagnosing EV is the same as by EGD. Esophagoscopy with a BPE is a potential alternative to EGD for EV screening.

The primary prevention of bleeding from esophageal varices is a major therapeutic issue requiring early screening of esophageal varices. Our aim was to study the diagnostic accuracy of non-endoscopic means for the diagnosis of esophageal varices.

Sixty-three clinical, biochemical, endoscopic and Doppler ultrasound variables were prospectively recorded in 207 consecutive patients with chronic liver disease. Diagnostic accuracy was evaluated by discriminant analysis, first globally using all variables with diagnostic accuracy > or = 65% in univariate analysis, then by stepwise regression.

A) whole group (n=207), 1) diagnosis of esophageal varices: diagnostic accuracy was globally 81%, and 81% with 1 variable: irregular liver surface at ultrasound, 2) Diagnosis of large esophageal varices (grades 2+3): diagnostic accuracy was globally 80%, and 79% with 2 variables: prothrombin index, gamma-globulins. B) patients with cirrhosis (n=116), 1) diagnosis of esophageal varices: diagnostic accuracy was globally 71%, and 72% with 2 variables: platelet count, prothrombin index, 2) diagnosis of large esophageal varices (grades 2+3): diagnostic accuracy was globally 71%, and 72% with 3 variables: platelet count, prothrombin index, spider naevi. The ROC curve showed that the best threshold for the diagnostic accuracy of platelet count was 160 G/l providing a sensitivity of 80% and a specificity of 58%. Platelet count > or = 260 G/l has a negative predictive value > or = 91%.

Using a few non-endoscopic criteria, esophageal varices can be correctly diagnosed in 81% of patients with chronic liver disease and in 71% of patients with cirrhosis. These results show that the non-invasive screening of patients who are candidates for the primary prevention of variceal bleeding is possible, but should be improved before being used in a clinical setting.

We designed an animal model in order to clarify whether Helicobacter pylori infection causes the gastric mucosal lesion frequently seen in cirrhotic patients.

Ammonia (NH3) solution was given to rats with carbon tetrachloride-induced cirrhosis. The gastric mucosal hexosamine (Hx) content and histopathological findings in the cirrhotic rats were analysed and compared with those of the intact liver rats. Moreover, the usefulness of geranylgeranylacetone (GGA) was investigated in both rat groups. Both rat groups were subdivided according to the treatment as follows: a control group, an NH3 (0.02% solution) group, and an NH3 + GGA (400 mg/kg per day) group; and fed for 4 weeks.

The gastric mucosal Hx content of the control group of the cirrhotic rats (16.7 +/- 5.2 microg/mg) was significantly lower than that of the control group of the intact liver rats (26.6 +/- 4.5 microg/mg, P < 0.05). In the cirrhotic rats, the Hx content of both the NH3 (31.9 +/- 13.1 microg/mg) and the NH3 + GGA group (31.9 +/- 9.8 microg/mg) was significantly higher than the Hx content of the control group (P < 0.05). Microscopically, in the cirrhotic rats, while scattered mucosal erosions were recognized in three of five rats of the NH3 group, there were no erosions in any rats of the NH3 + GGA group.

These data suggest that the gastric mucosal defence mechanism is defective in liver cirrhosis and that NH3 enhances this defensive mechanism by acting as mild irritant; however, in some cirrhotics this results in gastric erosion due to excessive irritation. Geranylgeranylacetone protects the gastric mucosa against NH3 irritation in cirrhotics without enhancing the Hx content. Thus, H. pylori infection may be a possible cause of the gastric mucosal lesion in patients with liver cirrhosis. The mechanism of the therapeutic effect of GGA is not due to an enhancement of the gastric mucosal Hx content.

The incidence of esophageal and gastric varices and portal hypertensive gastropathy (PHG) has been well studied in cirrhotic patients. Because little is known of the prevalence of other upper and lower gastrointestinal tract pathology in pre-liver transplant candidates, we retrospectively studied the prevalence of and factors associated with these findings.

One hundred and twenty pre-liver transplant candidates underwent esophagogastroduodenoscopy to evaluate for varices, and 71 of them also underwent flexible sigmoidoscopy to screen for colorectal carcinoma. The association of upper and lower GI tract pathology with Child-Pugh Class, etiology of cirrhosis, and signs of portal hypertension, including presence and size of esophageal varices, presence of gastric varices, PHG, ascites, and splenomegaly, was analyzed using univariate and multivariate analysis.

Etiology of cirrhosis among 87 men and 33 women (mean age, 52 yr) included 25% hepatitis C, 27% hepatitis C/alcohol, 15% alcohol, 10% primary sclerosing cholangitis/primary biliary cirrhosis, 9% cryptogenic, 8% metabolic, and 6% hepatitis B. Prevalence of Child-Pugh Classes A, B, and C were 34%, 49%, and 17%, respectively; 73% of patients had esophageal varices (23% were large), 62% PHG (23% were severe), and 16% gastric varices. Excluding varices and PHG, endoscopic findings in the upper GI tract (n = 120) included: 13% esophagitis/ulcers, 7.5% gastritis, 8% duodenitis, 2% Barrett's esophagus, 3% duodenal ulcers, and 2% gastric ulcers. Findings in the lower gastrointestinal tract (n = 71) included 21% adenomatous polyps, 21% internal hemorrhoids, 15% diverticulosis, 7% rectal varices, 3% colopathy, and 3% vascular ectasias. Univariate analysis revealed that there was a significant association between rectal varices and severe PHG (p < 0.05). This association was not maintained when multivariate analysis was performed.

Among all the findings, only rectal varices and colopathy were of higher prevalence in the pre-liver transplant population than that reported for the general population. No significant associations were found between these gastrointestinal tract lesions and patient characteristics.

The aim of this study was to investigate the clinical and epidemiological factors associated with the appearance of peptic ulcer in patients with cirrhosis and, in particular, the role of Helicobacter pylori infection.

A total of 201 of 220 consecutive patients included in a prospective study that aimed to evaluate the effect of dietary intervention on cirrhotic complications and survival underwent upper gastrointestinal endoscopy. At entry, an epidemiological and clinical questionnaire was completed and the presence of peptic ulcer disease or esophageal varices at endoscopy was prospectively collected. Sera were obtained and stored at -70 degrees C until analyzed, being tested afterward for Helicobacter pylori antibodies using a commercial ELISA kit.

Eleven of 201 patients had borderline anti-Helicobacter pylori IgG titers and were excluded from further analysis. In the remaining 190 patients, point prevalence of peptic ulcer was 10.5% and lifetime prevalence 24.7%. Multivariate analysis selected male sex (OR 2.3; 95%CI 1.09-4.89) and Helicobacter pylori seropositivity (OR: 1.7, 95%CI 1.02-2.81) as the variables independently related to peptic ulcer disease.

Male sex and seropositivity for Helicobacter pylori are the major risk factors for peptic ulcer in cirrhosis.

In the present article we describe updated information concerning the clinical feature of portal-hypertensive gastropathy (PHG), which is characterized by mucosal and submucosal vascular dilatation without inflammation. Although this lesion represents non-variceal bleeding, there is a wide variation of its prevalence. Portal pressure and some humoral factors may play important roles in its pathogenesis. Gastric acid secretory activity is reduced, whereas the gastric mucosal barrier is impaired. With regard to gastric mucosal haemodynamics, whether 'overflow' (i.e. active congestion) or 'stasis' (i.e. passive congestion) cause gastric mucosal hyperaemia is not known. A severe lesion is a potential source of bleeding, while mild lesions are of little clinical significance and endoscopic variceal obliteration aggravates PHG in some patients. In the treatment of PHG, pharmacological (e.g. propranolol), surgical (e.g. portosystemic shunt) and radiological (e.g. transjugular intrahepatic portosystemic shunt) procedures may be useful in preventing bleeding from PHG.

Endoscopic laser Doppler velocimetry is a simple non-invasive method to measure gastric mucosal blood flow. The present study is an attempt to determine a correlation, if any, between gastric mucosal blood flow and the hepatic perfusion index in patients with portal hypertensive gastropathy and their relationship to the severity of liver disease. Thirty patients with portal hypertensive gastropathy due to cirrhosis of the liver (eight class A, 13 class B, nine class C, according to Child-Pugh Classification) and six normal subjects were recruited into the study. In all subjects, the gastric mucosal blood flow and venous vasomotor reflex response was measured at two sites: the lesser and greater curvature, using endoscopic laser Doppler velocimetry. The hepatic perfusion index was measured using dynamic liver scintigraphy. The hepatic perfusion index (ratio of arterial/portal venous perfusion) in normal subjects and patients with portal hypertensive gastropathy belonging to Child-Pugh class A, B and C were 0.36 +/- 0.02, 0.53 +/- 0.08, 0.62 +/- 0.14 and 1.04 +/- 0.28, respectively. The gastric mucosal blood flow was similar in Child's A, B and C cases, while the venous vasomotor reflex response was reduced according to the Child-Pugh score (Child's A 37.4 +/- 5.4%, normal control 62.3 +/- 10.9%, Child's B 38.3 +/- 18.2%, Child's C 22.5 +/- 15.2%) and was statistically significant. The gastric mucosal blood flow and hepatic perfusion index are inversely correlated. The hepatic perfusion index altered with grading of cirrhotic change. This study confirms that the severity of portal hypertensive gastropathy is correlated with Child-Pugh score.

The main objective of this prospective study was to evaluate the independent diagnostic accuracy of gastroesophageal endoscopic signs for cirrhosis.

Endoscopic signs were evaluated in vivo by one observer and on standardized videotape recordings by a consensus opinion of two endoscopists, with the stomach and esophagus examined both separately ("blind video") and together ("unblind video") in 168 consecutive patients with cirrhosis (n = 91), with non-cirrhotic liver disease (n = 29), and without liver disease (n = 48). The results were then tested in 149 different patients.

Discriminant analysis of the "blind video" examination, considered to be the reference examination, showed that esophageal varices and portal hypertensive gastropathy had independent diagnostic accuracy (> or = 87%) for cirrhosis regardless of control group. However, in the "unblind video" and in in vivo examinations with different control groups, these results were altered. Prior knowledge of gastric patterns influenced the assessment of esophageal patterns. There was no independent association between portal hypertensive gastropathy or esophageal varices and the etiology of liver disease or the Child-Pugh score.

When methodologic biases are eliminated, esophageal varices and portal hypertensive gastropathy have independent diagnostic accuracy for cirrhosis: esophageal varices had a diagnostic accuracy of 77% at the first step and increased to 89% with portal hypertensive gastropathy at the second step.

We have evaluated gastric mucus generation (study 1) and the effects of tetraprenylacetone on gastric mucus generation (study 2) in cirrhotic patients with portal hypertension. Study 1: Included were 50 noncirrhotics (group A), 25 cirrhotics without portal hypertension (group B), and 25 cirrhotics with portal hypertension (group C). The antrum, corpus, and fundus mucus generation was assessed by hexosamine concentration using biopsy specimens. In groups A and B, the antrum hexosamine concentration was significantly higher compared with the corpus (P < 0.01, P < 0.01) and the fundus (P < 0.01). In contrast, the hexosamine concentration at each location was similar in group C. Furthermore, the antrum hexosamine concentration of group C was significantly lower compared with that of group A (P < 0.05). In study 2, a double-blind design, 300 mg of tetraprenylacetone was administered for four weeks in 10 cirrhotics with portal hypertension and placebo in 10. The regional hexosamine concentrations were measured before and after drug administration. Placebo administration did not change hexosamine concentration at each location. In contrast, tetraprenylacetone increased the antrum and corpus hexosamine concentration (P < 0.01, P < 0.05), although the fundus concentration did not change. These data suggest that cirrhotics with portal hypertension have reduced gastric antral mucus generation and tetraprenylacetone normalizes this.

Portal hypertensive gastropathy and duodenopathy are distinct clinical and endoscopic entities. Data on factors influencing the development of these lesions are still emerging. Data on portal hypertensive duodenopathy are scarce. We prospectively studied 230 patients with liver cirrhosis and oesophageal varices attending the liver clinic of the Sanjay Gandhi Post Graduate Institute of Medical Sciences. One hundred and forty-two patients had no history of upper gastrointestinal bleeding, while the remainder had bled in the past. Endoscopic appearances were recorded before starting patients on a sclerotherapy programme. Forty-four patients were re-evaluated after variceal eradication. The frequency of portal hypertensive gastropathy (PHG) and duodenopathy (PHD) was 61 and 14%, respectively. Mild PHG was present in 85% and was severe in the rest. Portal hypertensive duodenopathy was mild in 50%, while in the other half it was severe. There was no relationship of PHG and PHD to: (i) a history of upper gastrointestinal bleed; (ii) size of oesophageal varices; (iii) aetiology of liver cirrhosis; or (iv) liver function status as assessed by Child Pugh's scores (P = NS for all). The prevalence of PHG was higher in those patients with oesophagogastric varices (74 of 107; 69%) compared with patients with oesophageal varices alone (68 of 123; 55%; P < 0.05). However, no such increase in frequency of PHD was noted in patients with oesophagogastric varices. Sclerotherapy increased the frequency of PHG. Twenty-four patients had PHG before starting sclerotherapy, while it was noted in 33 patients 1-3 months after variceal eradication (P < 0.05). In contrast, there was no increase in the prevalence of portal hypertensive duodenopathy after sclerotherapy (P = NS). There was no correlation between endoscopic and histological changes of PHG and PHD. In conclusion, PHG is quite frequent in patients with cirrhosis and its frequency increases with the presence of oesophagogastric varices and after sclerotherapy. However, the frequency of PHD is low and is not affected by the factors studied.

Portal hypertensive gastropathy is characterized by a hyperdynamic circulatory state in the gastric mucosa. We assessed the effect of bolus injection of somatostatin on gastric mucosal perfusion in a rat model of portal hypertension. We tested the hypothesis that somatostatin will reduce gastric mucosal perfusion in portal hypertension.

Portal hypertension was induced by two-stage portal vein ligation (PVL). Two weeks after PVL significant elevation of portal venous pressure was demonstrated. Gastric mucosal hemodynamic changes were measured by reflectance spectrophotometry, which records the indexes of mucosal hemoglobin oxygen saturation (ISO2) and mucosal hemoglobin concentration (IHB).

After an intravenous bolus of 1 microgram somatostatin significant reductions of ISO2 and IHB were demonstrated in the rats with PVL (ISO2, -34 +/- 5%; IHB, -15 +/- 2%) and the controls (ISO2, -26 +/- 4%; IHB, -15 +/- 2%). A dose-response relationship was shown by using 0.01, 0.1, and 1 microgram of somatostatin. Somatostatin did not induce other hemodynamic changes except a transient drop in systemic blood pressure of 8-10%.

The significant reductions of gastric mucosal ISO2 and IHB by somatostatin support the hypothesis that somatostatin is capable of attenuating the hyperdynamic circulatory state in the gastric mucosa of rats with portal hypertension and may have a beneficial effect on portal hypertensive gastropathy. This hypothesis deserves to be evaluated in clinical studies.

The epidemiological and clinical characteristics of peptic ulcer were studied in 324 of 368 consecutive patients with cirrhosis of the liver during a mean period of 1.2 (+/- 0.61) years. Peptic ulcer prevalence rates in patients with cirrhosis were as follows: point prevalence 11.7%, period prevalence 15.1%, and life-time prevalence 24.2%. The annual incidence rate observed in 140 patients with cirrhosis undergoing endoscopic follow up was 4.3%. Ulcers were asymptomatic in more than 70% of patients. The peptic ulcer complication rate at entry was 20% in the whole group and 40% in those who had not a previous diagnosis of peptic ulcer when admitted to the study. Peptic ulcer was more frequent among HBsAg+ cirrhotics (p = 0.05). Patients with more severely decompensated cirrhosis also had a higher frequency of asymptomatic ulcers (p = 0.04), gastric ulcers (p = 0.01) and asymptomatic gastric ulcers (p = 0.005). After diagnosis, during endoscopic follow up, gastric ulcer in patients with cirrhosis tended to heal slowly and recurred with higher frequency than in controls without cirrhosis (p = 0.04). Seventy-nine per cent of peptic ulcer recurrences were asymptomatic in patients with cirrhosis. There were no complications during the follow-up period: this could be due to the regular timing of endoscopy, which permitted early detection and treatment of the recurrences, thus preventing further complications.

To assess the significance of McCormack's gastric mucosal signs for diagnosing portal hypertension, 100 controls and 100 patients with cirrhosis and portal hypertension underwent endoscopy. Each endoscopic recording was reviewed by multiple blinded observers to reduce bias. Individual signs more frequently observed in patients with cirrhosis and portal hypertension than in controls were fine pink speckling (20% versus 8%, p < 0.05), the snakeskin pattern (30% versus 5%, p < 0.01), and cherry-red spots (15% versus 3%, p < 0.01). In contrast, the prevalence of superficial reddening was similar in the two groups (7% versus 13%, NS). Overall, these gastric mucosal signs also appeared more commonly in patients with portal hypertension than in controls (54% versus 27%, p < 0.01); the sensitivity, specificity, and accuracy of McCormack's signs (overall assessment) for diagnosing portal hypertension were 54%, 73%, and 64%, respectively. Corresponding figures for modified McCormack's signs (exclusion of superficial reddening) were 50%, 85%, and 68%. However, these figures were still lower than those for gastroesophageal varices (72%, 100%, and 86%). We conclude that (1) superficial reddening is not a specific finding in patients with portal hypertension, and (2) gastric mucosal findings are of low sensitivity and specificity for diagnosing portal hypertension compared with gastroesophageal varices.

Helicobacter pylori was found to be a promoter factor of peptic ulcer that has an incidence higher in patients with hepatic cirrhosis. To clarify the role between H. pylori and peptic ulcer in patients with hepatic cirrhosis, a serological test (ELISA test, HEL-p, AMRAD, Australia), was used to measure the presence of H. pylori of patients with hepatic cirrhosis. Within two years, 108 cirrhotic patients who had received a panendoscopic examination were enrolled in this study. There were 79 males and 27 females with a mean age of 53.2 years. Sixty-four cases had positive serum HBsAg and 44 had negative serum. The results showed that the prevalence of Helicobacter pylori in cirrhosis was 43.5% (47/108). There was no difference of HEL-p-positive rate between peptic ulcer and normal gastroduodenal mucosa (45.2% vs 46.1%, P > 0.05). According to this study, there appears to be no relation between peptic ulcer and H. pylori in patients with hepatic cirrhosis. The etiology of peptic ulcer in cirrhotic patients need further study.

The gastrojet, a closed loop pH feedback infusion pump capable of maintaining intragastric pH at a target value by infusing H2 blockers at variable rates, was used to assess factors influencing the quantity of famotidine required to maintain intragastric pH above 4 for 24 hours in 34 fed patients with duodenal ulcers. The following factors were considered: sex, age, duration of the disease, previous bleeding, previous poor response to H2 blockers (ulcer unhealed at six weeks, or recurrence within three months during maintenance treatment), activity of the ulcer disease, smoking habits, cirrhosis. The patients had taken no antisecretory drugs for the 15 days before the study. Two standardised meals were given during the study period (from 1000 to 1000). Fifty ml of famotidine (4 mg/ml) was loaded into infusion bags and the pump was programmed to deliver the drug intravenously at 11 rates varying from 0 to 40 microliters/min. The target pH was 4. Mean famotidine use was 111 mg (range 33 to 200), the 23 hour median pH was 5.3, and the mean time during which pH was above 4 was 75.4%. There was a negative correlation (p < 0.001) between famotidine delivery and the inhibition of gastric acidity. Statistical analysis showed that only cirrhosis significantly influenced drug delivery, median pH, and the time during which pH was above 4. Mean drug delivery in the cirrhotic and non-cirrhotic patients was 135 v 97 mg (p < 0.04), 23 hour median pH was 4.7 v 5.6 (p < 0.01), and the mean time at pH > 4 was 65.9 v 81.6% (p < 0.01). There were large interindividual variations in famotidine requirements, but not only cirrhosis was predictive of dose requirement. These results suggest that the appropriate amount of famotidine to treat duodenal ulcer in cirrhotic patients is probably higher than the usually recommended dose.

Stomach function and secretions are altered significantly in patients with cirrhosis, both with or without portal hypertension. This review covers the abnormalities of gastric acid and pepsin secretion, and gastrin release. Histological and endoscopic changes, and the impaired cytoprotection associated with cirrhosis, are discussed in the context of abnormal gastric secretion. In addition, the symptomatology and association of H. pylori, and treatment of duodenal ulceration in cirrhosis are discussed. It is clear from this review that additional studies are needed to further understand gastric function in cirrhotic patients.

Although congestive gastric mucosal circulation has been suggested in patients with portal-hypertensive gastropathy, whether it is due to "active" (overflow) or "passive" (stasis) congestion is not known. To answer this question, we assessed regional gastric mucosal blood flow with laser Doppler flowmetry in 57 patients with portal hypertension and 30 controls. Twelve patients had portal-hypertensive gastropathy of the antrum: in eight it was mild and in four it was severe. Portal-hypertensive gastropathy of the corpus was seen in 32 patients: it was mild in 24 and severe in 8. Thus prevalence of portal-hypertensive gastropathy was higher in the corpus than in the antrum (p < 0.01). In the antrum, gastric mucosal blood flow was significantly lower (p < 0.05) in patients with severe portal-hypertensive gastropathy (0.54 +/- 0.27 V) than in controls (1.12 +/- 0.44 V), whereas the values in patients without portal-hypertensive gastropathy (0.90 +/- 0.35 V) and with mild portal-hypertensive gastropathy (0.91 +/- 0.31 V) were not significantly different from the values in controls (p < 0.05 on one-way analysis of variance). In the corpus, gastric mucosal blood flow was significantly lower in patients with mild (0.75 +/- 0.25 V) or severe portal-hypertensive gastropathy (0.42 +/- 0.22 V) than in controls (1.16 +/- 0.37 V) (p < 0.01 and p < 0.01, respectively) whereas the value in patients without portal-hypertensive gastropathy (0.99 +/- 0.37 V) was not significantly different from values in controls (p < 0.01 on one-way analysis of variance).(ABSTRACT TRUNCATED AT 250 WORDS)

There is now substantial clinical evidence to suggest that portal hypertensive gastropathy is an important source of gastrointestinal bleeding in patients with portal hypertension. Although a relatively uncommon presenting feature in such patients, it appears to become progressively more frequent and important the longer such patients with bleeding oesophageal varices survive after treatment by endoscopic sclerotherapy. It is now being increasingly recognized as the most important cause of haemorrhage after oesophageal varices in such patients. The endoscopic and histological characteristics of the condition are now well established but from a clinical point of view it is important to distinguish it from a number of other disorders. The pathogenesis of portal hypertensive gastropathy is poorly understood; venous congestion secondary to portal hypertension undoubtedly plays an important role but this is not thought to account entirely for the condition since abnormalities in the arterial blood supply are also observed. Many abnormalities in gastric mucosal function have been reported but it is unclear whether these are secondary disturbances or whether they play an important primary role in the development of the condition. Animal studies to date have not been helpful due to the lack of a satisfactory experimental model. Portocaval shunt surgery cures portal hypertensive gastropathy but propranolol has been shown to be highly effective in controlling haemorrhage from this condition and should now be considered the treatment of choice. The mechanism of action is unclear, and it remains to be shown whether other beta-blockers, or indeed any other drugs, are useful in treating this disorder.

Portal hypertensive gastropathy is a recently recognized important complication of cirrhosis. In the present study, the clinical features, portohepatic hemodynamics, and hepatic function were investigated in a series of 47 patients with cirrhosis. Mild gastropathy was found in 15 patients (32%) and severe gastropathy in 17 patients (36%). The presence of gastropathy seemed to be independent of age, sex, cause of cirrhosis, or grade of gastroesophageal varices. However, severe gastropathy was associated with an increase in portal venous pressure gradient (vs. control, P less than 0.01; vs. mild gastropathy, P less than 0.01), an increase in hepatic sinusoidal resistance (vs. control, P less than 0.01; vs. mild gastropathy, NS), and a decrease in hepatic blood flow (vs. control, P less than 0.01; vs. mild gastropathy, NS). In addition, patients with severe gastropathy had impaired metabolic activity of the liver, which was assessed by intrinsic clearance of indocyanine green (vs. control, P less than 0.01; vs. mild gastropathy, NS). These observations may have important therapeutic implications in patients with cirrhosis and portal hypertensive gastropathy.

In a double-blind, crossover study, 10 cirrhotic patients (Child B rating) with steatorrhoea (daily output of faecal fat greater than 8 g) and dyspepsia were placed on a controlled diet for 14 days. Patients then received 150 mg ursodeoxycholic acid (UDCA) or placebo twice daily for 14 days. Faecal fat excretion was reduced from 14.7 to 10.6 g/day by UDCA and dyspepsia symptom scores were also reduced. Serum aspartate aminotransferase concentrations declined significantly (P less than 0.02) following UDCA treatment, whereas serum bile acid levels increased from 35 to 40.5 microM and the percentage of UDCA increased to 22%. It is concluded that UDCA may be useful for many of the symptoms present in patients with liver cirrhosis.