The Spectrum of Portal Hypertension in the Gastrointestinal Tract

Portal hypertension has a very complex pathophysiology and is associated with markedly deranged hemodynamics. In spite of this fact, it has long been considered that esophagogastric varices and their bleeding are the main consequences of portal hypertension and that otherwise it would be of little clinical significance [1]. This idea, however, seems to be changing with developments in various imaging modalities and more thorough studies on the manifestations of portal hypertension in the gastrointestinal tract. Though it is true that esophageal varices are the most commonly encountered sequel of portal hypertension, which may lead to life-threatening bleeding, a myriad of lesions with significant clinical implications can be attributed either directly or indirectly to portal hypertension.

Esophagogastric varices and their bleeding are the best studied gastrointestinal manifestations of portal hypertension. They are easily accessible by gastrointestinal endoscopy which allows diagnosis and staging as well as effective therapy. Varices can, however, develop almost anywhere in the gastrointestinal tract. Those which develop outside the esophagogastric region were described by Lebrec & Benhamou as ectopic varices. They were found to occur in 1-3 % of patients with cirrhosis and have a much higher incidence in patients with extrahepatic portal hypertension (20 - 30 %) [2]. Varices have been found in the small intestine, colon, biliary system, vagina, bladder and peritoneum [2] [3] [4]. Small-bowel varices have been reported to cause life-threatening bleeding [5] [6] [7]. They are sometimes accessible by endoscopy, allowing effective hemostasis by sclerotherapy [7]. Varices have also been described in the gallbladder bed and around the bile duct and may lead to severe bleeding at surgery [8]. Varices throughout the colon have also been described [9]. Anorectal varices are the commonest ectopic varices with a prevalence as high as 78 %, but they have a low incidence of bleeding compared with esophageal varices [10]. They should be differentiated from hemorrhoids which occur in patients with portal hypertension with a prevalence comparable to that in the general population, though they may bleed more profusely [11].

In this issue of Endoscopy, Shudo and co-workers [12] review their database of 425 patients with portal hypertension in whom colonoscopy was performed. Among 40 patients with endoscopically evident rectal varices, 15 [38 %] were confirmed to be bleeding; this was a very high incidence of bleeding, which was not explained by the authors. Comparison of patients with bleeding rectal varices with those who did not bleed, with respect to age, sex, presence or absence of hepatocellular carcinoma, Child-Pugh score, indocyanine green test, grade and previous endoscopic management of esophageal varices, as well as endoscopic appearance of rectal varices, revealed that those with bleeding varices had a significantly increasing size of varices (grade of form) and a higher incidence of red-color signs. In a multivariate analysis the red-color sign was the only significant susceptibility factor for hemorrhage from rectal varices. Although this paper draws attention to the prevalence of rectal varices and their bleeding, it does not convince one to recommend routine colonoscopic examination for each patient with portal hypertension as the authors do. This is simply because, based on the current state of knowledge, even if we know that a patient has rectal varices, no prophylactic measures for the prevention of bleeding (irrespective of the bleeding risk) can be undertaken. This is in contrast to esophagogastric varices, which should be searched for in nonbleeding patients as there is a role for prophylaxis, for example, by portal pressure-lowering agents. Therefore, unless there is an evidence-based role for prophylaxis for rectal variceal bleeding, screening by colonoscopy seems to be of academic interest only, given also the relatively lower prevalence of rectal varices and bleeding therefrom.

Apart from the development of varices, portal hypertension has been implicated in the pathogenesis of morphological and functional changes throughout the gut. Portal hypertensive gastropathy (PHG; originally termed congestive gastropathy) was recognized and described by McCormack et al. The hallmarks of the lesions are ectatic vessels with insignificant inflammatory cellular infiltrate [13]. The prevalence of this entity among portal hypertensive patients has been found to be quite variable, ranging from 7 % to 41 % [14]. Furthermore, the exact role of portal hypertension in the pathogenesis of PHG has not yet been definitely elucidated [15]. Regarding that question, Marques Chaves et al. [16] conducted a study comparing the prevalence of PHG among cirrhotic patients with that in patients with hepatosplenic schistosomiasis, a disease known to cause portal hypertension with no significant effects on hepatocellular functions. Whereas the endoscopic features of both groups of patients revealed a statistically significantly higher incidence of PHG in cirrhotic patients (81.8 % vs. 33.3 % in schistosomiasis patients), particularly with regard to the mosaic-like pattern, the histopathology of macrobiopsies did not show a significant difference between the two groups. This discrepancy between endoscopic findings and histopathology actually adds to the dilemma, and raises the issue of the validation of endoscopy as a diagnostic tool for PHG in clinical studies, a problem encountered in several other published studies [17] [18].

Gastric antral vascular ectasia (GAVE) is another entity which was found to be associated with liver cirrhosis and portal hypertension, as well as other diseases such as atrophic gastritis, scleroderma and other autoimmune diseases [19] [20]. Although GAVE may be confused with PHG, the former has a distinct histopathological picture with ectatic mucosal vessels, fibrin thrombi and spindle cell proliferation. Two forms are known: the typical watermelon stomach with red stripes radiating from the pyloric ring, and the diffuse type which is commoner in cirrhosis [21]. GAVE may be a cause of iron-deficiency anemia and occult blood in stools in cirrhotic patients. Again the contribution of portal hypertension to the pathophysiology of these lesions is unknown as they may occur in patients without portal hypertension, as mentioned above [15].

Changes comparable to those of PHG have also been described in the small intestine and colon, respectively portal hypertensive enteropathy and portal hypertensive colopathy. Friable punctate areas of erythema, edema, granularity and friability and spider-like lesions are described in the literature [18] [22] [23] [24]. Such lesions are reported to cause significant bleeding, though this rarely happens [25] [26].

The effects of obliteration of esophagogastric varices on other manifestations of portal hypertension in the gastrointestinal tract have long been a matter of debate. In several studies, for example, an increased incidence of PHG following endoscopic obliteration of esophagogastric varices has been demonstrated [27] [28] [29]. The hypothesis could be that variceal obliteration, with subsequent reduction of blood flow through the portosystemic collaterals, could increase gastric mucosal congestion [27] [29] and lead to extension of portal hypertensive vasculopathic changes to more distal sites such as the duodenum and jeunum [30]. Others, however, have doubted such an effect, attributing the changes that may occur to the severity of portal hypertension in patients with bleeding varices rather than to obliteration of varices itself [31]. In this issue of Endoscopy, Misra and co-workers [32] describe their investigation of the effect of esophageal variceal obliteration by endoscopic ligation (EVL) on hemorrhoids, anorectal varices, and portal hypertensive colopathy. They found no significant change in the incidence of these lesions at 4-6 weeks after obliteration, which is in contrast to other reports [33] [34]. It could be argued, however, that a period of 4 - 6 weeks may be not sufficient for the development of significant changes. The authors explain these findings by the fact that “colonic mucosa and anorectal varices are furthest from the esophageal varices and the brunt of the congestion is borne by the adjacent gastric mucosa, resulting in an increase in the incidence of PHG.” However, the hypothesis of transmission of portal hypertensive effects more distally in the gastrointestinal tract seems to be an oversimplification; extensive hemodynamic studies in the various compartments of the portosystemic collateral circulation would be required before reaching such a notion. For example, we have previously demonstrated, in an endosonographic study of the superior portosystemic collateral circulation (taking the azygos vein as an index), that “compensatory changes” may occur following sclerotherapy of esophageal varices which may nullify any effect of variceal obliteration which might be transmitted distally. This includes, for example, the formation of periazygos collaterals [35] [36]. Considering the relatively small size of esophageal varices when compared with draining vessels as well as paramural collaterals (which are often huge and more numerous), the obliteration of intramural vessels seems to cause a minor effect which may show itself only locally. So, if obliteration proves to be really associated with more distal vasculopathic changes (which was not the case in the study of Misra et al. [32]), it remains to establish the cause of such an effect: is it produced directly by obliteration, or is it rather a manifestation of a more severe form of portal hypertension (and probably hepatocellular dysfunction) that is associated with bleeding from large-sized varices?

The spectrum of portal hypertension in the gastrointestinal tract still extends to include altered intestinal motility with delayed transit, mainly in the proximal part of the small intestine, which may predispose to bacterial overgrowth and malabsorption [37] [38]. Another reported complication of portal hypertension is cholangiopathy, which may occur in cases of extrahepatic portal venous obstruction. Strictures and caliber irregularities have been described in the biliary tree; however the condition is of little clinical significance [39].

In spite of several decades of extensive research on portal hypertension, many aspects of this syndrome are still obscure. Lesions seen in portal hypertensive patients can still not even be explained by the increase in portal pressure. The prevalence and incidence of many conditions show a very wide range in the published literature, which raises questions about interobserver variations and reproducibility of results. The three studies published in this issue of Endoscopy demonstrate some of the many difficulties encountered in clinical research on portal hypertension: the large number of variables to be considered and to be correlated, the validation of a gold standard for the diagnosis, and the lack of hemodynamic parameters in many studies.

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