**3. Pathophysiology**

The pathophysiology of GAVE remains unknown; however, several mechanisms have been proposed including gastric dysmotility or autoimmune reactivity to gastric blood vessels [10–12]. A study on antral motility revealed an increase in antral area transit time with cirrhosis and GAVE when compared to controls [10]. Chronic recurrent trauma can lead to fibromuscular hyperplasia and vascular ectasia. Reduced gastrin levels have also been identified in GAVE patients when compared to patients with severe PTH and normal controls [13]. Prostaglandins E2 (PGE2) levels were found significantly elevated when compared to controls [14]. GAVE is not associated with portal hypertension and treatments aimed to decrease portal pressure have no role in treatment of GAVE [15].

The pathogenesis of PHG is related to increased resistance to portal blood flow in patients with liver disease, and concomitant elevation in portal pressure [16]. In patients with portal hypertension, approximately 70% develop PHG [17]. Resolution of PHG and its recurrence has been observed in patients with cirrhosis posttransjugular intrahepatic portosystemic shunt (TIPS) placement, and in noncirrhotic patients with postsurgical decompression of the portal system [17–19]. However, the linear correlation between the severity of portal hypertension and that of PHG is controversial. In a prospective study of 331 patients, it was reported that severe PHG showed a significantly shorter expected survival time than mild PHG (median survival time, 77.6 ± 9.6 months in severe PHG) [20]. The study concluded that PHG was associated with severity of portal hypertension and prognosis in patients with cirrhosis. However, other studies have been unable to demonstrate a correlation between the severity of portal hypertension and that of PHG [21–23].

Other molecular mediators at the mucosal level have been implicated in the development of PHG including tumor necrosis factor (TNF)-α, endothelin-1 (ET-1), nitric oxide (NO), and prostaglandins [21, 24]. Interestingly, patients with cirrhosis and PHG have abnormal blood circulation, which makes them susceptible to reduced delivery of oxygen to the gastric mucosa [21, 25]. This phenomenon modifies blood circulation which enables reduced resistance of gastric mucosa to irritants in patients with cirrhosis and portal hypertension [26].
