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.

Relaxation of corpus cavernosum, which is mediated by nitric oxide (NO) released from non-adrenergic non-cholinergic (NANC) neurotransmission, is critical for inducing penile erection and can be affected by many pathophysiological conditions. However, the peripheral effect of liver cirrhosis on erectile function is as yet unknown. The aim of the present study was to investigate the effect of biliary cirrhosis on NANC-mediated relaxation of rat corpus cavernosum and the possible roles of endocannabinoid and nitric oxide systems in this model.

Cirrhosis was induced by bile duct ligation. Controls underwent sham operation. Four weeks later, strips of corpus cavernosum were mounted in a standard organ bath and NANC-mediated relaxations were obtained by applying electrical field stimulation.

The NANC-mediated relaxation was enhanced in corporal strips from cirrhotic animals. Anandamide potentiated the relaxations in both groups. Either AM251 (CB(1) antagonist) or capsazepine (vanilloid VR(1) antagonist), but not AM630 (CB(2) antagonist), prevented the enhanced relaxations of cirrhotic strips. Either the non-selective NOS inhibitor L-NAME or the selective neuronal NOS inhibitor L-NPA inhibited relaxations in both groups, but cirrhotic groups were more resistant to the inhibitory effects of these agents. Relaxations to sodium nitroprusside (NO donor) were similar in tissues from the two groups.

Cirrhosis potentiates the neurogenic relaxation of rat corpus cavernosum probably via the NO pathway and involving cannabinoid CB(1) and vanilloid VR(1) receptors.

Time-course studies revealed the increased susceptibility of the gastric mucosa to noxious injury in portal hypertension correlates with the level of elevated portal venous pressure and hyperglucagonemia. Whether acute elevation of portal venous pressure by exogenous glucagon aggravates such injury is not known. We tested the hypothesis that glucagon in a dose sufficient to acutely elevate portal venous pressure aggravates noxious injury of the gastric mucosa in rats with portal hypertension. Infusion of a portal hypotensive dose of somatostatin should reverse these changes. In anesthetized rats with portal vein ligation, glucagon, somatostatin or the combination was administered intravenously in a randomized, coded fashion. Acidified ethanol-induced gastric mucosal injury was determined. Portal venous pressure and gastric mucosal perfusion and oxygenation (reflectance spectrophotometry) were monitored to confirm the effects of the respective intravenous treatments. Exogenous glucagon exacerbated acidified ethanol-induced gastric mucosal injury. The exacerbation was attenuated by somatostatin. These changes paralleled the portal hypertensive and hypotensive effects of glucagon and somatostatin, respectively. Our data suggest that a unique mechanism is triggered with the onset of portal hypertension. In an antagonistic manner, glucagon and somatostatin modulate this novel mechanism that controls portal venous pressure and susceptibility of the gastric mucosa to noxious injury.

Spontaneous bacterial peritonitis is a common illness in patients with cirrhosis and ascites that occurs without any apparent focus of infection. Bacterial translocation plays an important role in spontaneous bacterial peritonitis and it is evident from a variety of studies that the gut is a major source of this bacteria. Gut motility alterations, along with bacterial overgrowth and changes in intestinal permeability, probably play a role in this bacterial translocation. The present review looks at the role of the intestine in spontaneous bacterial peritonitis induced by liver cirrhosis and the factors influencing bacterial translocation in this disease.

Patients with liver cirrhosis and portal hypertension frequently exhibit a multitude of alterations of hormones and metabolism, but the relation of these alterations to liver function, degree of blood shunting, and hepatic encephalopathy remains unclear.

Twenty-four patients were randomised to mesocaval interposition shunt (MIS) and 21 patients to repeated sclerotherapy (ST). Several peptide hormones, amino acids and lysosomal enzymes were monitored during a 4 year follow-up period.

Insulin and glucagon levels were elevated in the MIS group compared to pre-therapy levels, whereas the gastrin level was significantly higher in the ST group. Pancreatic polypeptide, somatostatin and vasoactive intestinal peptide levels were not affected by either treatment. The branched chain amino acids valine, leucine and isoleucine serum levels were all elevated after ST, and the arginine, proline and tyrosine levels were higher in the MIS group at follow-up. Other amino acids were not changed, neither were the lysosomal enzymes beta-hexosaminidase nor beta-glucoronidase during this longterm follow-up.

MIS or repeated ST treatment only affected serum levels of hormones, amino acids and lysosomal enzymes to a limited extent. In this trial, the type of treatment had only a small influence on these parameters during long term follow-up.