Outcome of gastric antral vascular ectasia and related anemia after orthotopic liver transplantation

BACKGROUNDGastric antral vascular ectasia (GAVE) is a significant complication of cirrhosis. Numerous medical, surgical, and endoscopic treatment modalities have been proposed with varied satisfactory results. In a few small studies, GAVE and associated anemia have resolved after orthotopic liver transplantation (OLT). AIMTo assess the impact of OLT on the resolution of GAVE and related anemia.METHODSWe retrospectively reviewed clinical records of adult patients with GAVE who underwent OLT between September 2012 and September 2019. Demographics and other relevant clinical findings were collected, including hemoglobin levels and upper endoscopy findings before and after OLT. The primary outcome was the resolution of GAVE and its related anemia after OLT.RESULTSSixteen patients were identified. Mean pre-OLT Hgb was 7.7 g/dL and mean 12 mo post-OLT Hgb was 11.9 g/dL, (P = 0.001). Anemia improved (defined as Hgb increased by 2g) in 87.5% of patients within 6 to 12 mo after OLT and resolved completely in half of the patients. Post-OLT esophagogastroduodenoscopy was performed in 10 patients, and GAVE was found to have resolved entirely in 6 of those patients (60%). CONCLUSIONAlthough GAVE and associated anemia completely resolved in the majority of our patients after OLT, GAVE persisted in a few patients after transplant. Further studies in a large group of patients are necessary to understand the causality of disease and to better understand the factors associated with the persistence of GAVE post-transplant.     

Prevalence of metabolic syndrome in cirrhotics with gastric antral vascular ectasia

Background and aimsGastric antral vascular ectasia (GAVE) is characterized by angliodysplastic lesions that can cause upper gastrointestinal bleeding (UGIB). The mechanism behind GAVE and its association with other diseases remains unknown. We investigated the association of metabolic syndrome in cirrhotic GAVE patients when compared to esophageal variceal hemorrhage (EVH) patients.MethodsWe performed a retrospective review of 941 consecutive esophagogastroduodenoscopies (EGDs) for UGIB at a medical center between 2017 and 2019. The GAVE group consisted of EGD or biopsy diagnosed cirrhotic GAVE patients, and the EVH group consisted of EVH patients with active bleeding or stigmata of recent hemorrhage on EGD. Baseline variables including co-morbidities and cirrhotic etiology were recorded. Continuous variables were compared using Wilcoxon test and categorical variables were compared using Chi-square or Fisher's exact test. Multiple logistic regression analysis evaluated the association between GAVE and covariates.ResultsThe final cohort had 96 GAVE and 104 EVH patients. Mean BMI was significantly higher in the GAVE cohort (32.6 vs 27.9, p < 0.0001) in addition to diabetes, hypertension, and hyperlipidemia (53.1% vs 37.5%; 76% vs 47.1%; 38.5% vs 14.4%; respectively, all p < 0.05). Non-alcoholic steatohepatitis (NASH) cirrhosis was more prevalent in GAVE than EVH patients (50% vs 24%, p = 0.0001). Multiple logistics regression revealed female sex, increased BMI, hypertension, and hyperlipidemia all having significantly higher risk of GAVE (all p < 0.05).ConclusionOur data indicates that when compared to cirrhotics patients with EVH, cirrhotics with GAVE have increased risk of metabolic syndrome. This may play a role in the underlying pathophysiology of GAVE.     

Diagnosis and management of gastric antral vascular ectasia

Gastric antral vascular ectasia (GAVE) is an uncommon but often severe cause of upper gastrointestinal (GI) bleeding, responsible of about 4% of non-variceal upper GI haemorrhage. The diagnosis is mainly based on endoscopic pattern and, for uncertain cases, on histology. GAVE is characterized by a pathognomonic endoscopic pattern, mainly represented by red spots either organized in stripes radially departing from pylorus, defined as watermelon stomach, or arranged in a diffused-way, the so called honeycomb stomach. The histological pattern, although not pathognomonic, is characterized by four alterations:vascular ectasia of mucosal capillaries, focal thrombosis, spindle cell proliferation and fibrohyalinosis, which consist of homogeneous substance around the ectatic capillaries of the lamina propria. The main differential diagnosis is with Portal Hypertensive Gastropathy, that can frequently co-exists, since about 30% of patients with GAVE co-present a liver cirrhosis. Autoimmune disorders, mainly represented by Reynaud’s phenomenon and sclerodactyly, are co-present in about 60% of patients with GAVE; other autoimmune and connective tissue disorders are occasionally reported such as Sjogren’s syndrome, systemic lupus erythematosus, primary biliary cirrhosis and systemic sclerosis. In the remaining cases, GAVE syndrome has been described in patients with chronic renal failure, bone marrow transplantation and cardiac diseases. The pathogenesis of GAVE is still obscure and many hypotheses have been proposed such as mechanical stress, humoural and autoimmune factors and hemodynamic alterations. In the last two decades, many therapeutic options have been proposed including surgical, endoscopic and medical choices. Medical therapy has not clearly shown satisfactory results and surgery should only be considered for refractory severe cases, since this approach has significant mortality and morbidity risks, especially in the setting of portal hypertension and liver cirrhosis. Endoscopic therapy, particularly treatment with Argon Plasma Coagulation, has shown to be as effective and also safer than surgery, and should be considered the first-line treatment for patients with GAVE-related bleeding.     

Neuroendocrine cell proliferations in gastric antral vascular ectasia

Gastric antral vascular ectasia is a recently recognized cause of chronic gastrointestinal blood loss. Immunohistochemical and electron-microscopic studies were performed on the surgically resected antrum of a patient with antral vascular ectasia. These revealed extraepithelial and intraepithelial neuroendocrine cell proliferations. Staining for a wide range of neural and endocrine markers demonstrated that these cells contain large quantities of 5-hydroxytryptamine and vasoactive intestinal polypeptide. Gastric vascular ectasia is of unknown etiology but has been associated with achlorhydria and liver cirrhosis. The findings suggest that locally released neurotransmitters may be responsible for local vasodilation and hence a propensity to bleed.     

Treatment of gastropathy and gastric antral vascular ectasia in patients with portal hypertension

Opinion statement Portal hypertensive gastropathy (PHG) and gastric antral vascular ectasia (GAVE) are two distinct gastric mucosal lesions that may cause acute and/or chronic upper gastrointestinal hemorrhage in patients with cirrhosis. Whereas PHG is associated with portal hypertension, GAVE may present in patients without portal hypertension or liver disease. Diagnosis is made upon visualization of the characteristic lesions with upper gastrointestinal endoscopy, although the differential may be difficult at times. PHG is characterized endoscopically by a mosaic pattern with or without red signs and a proximal distribution. PHG mainly causes chronic blood loss and anemia in patients with cirrhosis but also can cause acute hemorrhage. First-line therapy for chronic hemorrhage from PHG is a nonselective β-blocker (propranolol or nadolol) and iron supplementation. If bleeding/anemia are not controlled with these measures and the patient is transfusion-dependent, shunt therapy (transjugular intrahepatic portosystemic shunt [TIPS] or shunt surgery) should be considered. Management of acute bleeding from PHG, an infrequent event, should be accomplished with a vasoactive drug, somatostatin (or its analogues) or terlipressin. If bleeding responds, the patient must be switched to a nonselective β-blocker. Shunt therapy should be considered in patients who rebleed or continue to bleed despite adequate β-blocker therapy. GAVE is less common than PHG. It is characterized by red spots without a background mosaic pattern, typically in the gastric antrum. When lesions have a linear distribution, the lesion is called “watermelon stomach.” GAVE is a cause of chronic gastrointestinal bleeding and anemia in patients with cirrhosis. If lesions are localized, first-line therapy is argon plasma coagulation. In more diffuse lesions, therapy with argon plasma coagulation is more complicated. Preliminary data suggest that cryotherapy may be a reasonable option for diffuse GAVE lesions. Neither β-blockers nor TIPS reduces the bleeding risk in patients with GAVE and thus should not be used in this setting.     

Endoscopic biopsy is diagnostic in gastric antral vascular ectasia

Gastric antral vascular ectasia was endoscopically diagnosed in seven patients. Pathologic characteristics of this entity were defined retrospectively, by studying endoscopic pinch biopsy slides from these seven patients and antrectomy specimens from five patients. A scoring system was developed, and the seven patients were compared prospectively with various control groups. Abnormalities of mucosal vessels (fibrin thrombi and/or ectasia) consistently distinguished patients from control antrectomies, normal biopsies, acute gastritis biopsies and atrophic gastritis biopsies (P=0.02, all comparisons). Spindle cell proliferation into mucosa also was characteristic of gastric antral vascular ectasia, distinguishing this disease from normals, acute gastritis, and atrophic gastritis (P0.039, each comparison). The presence of abnormal mucosal vessels (fibrin thrombi and/or ectasia) and spindle cell proliferation was similar in patient antrectomies compared to patient endoscopic biopsies. Therefore, we conclude that endoscopic biopsies can reliably diagnose gastric antral vascular ectasia, a vascular disorder characterized by abnormal mucosal vessels and spindle cell proliferation.     

Endoscopic band ligation for refractory gastric antral vascular ectasia associated with liver cirrhosis

An 84-year-old woman with unknown liver cirrhosis was admitted to our hospital in October 2008 with anemia due to recurrent gastric antral vascular ectasia (GAVE). At 78 years of age, argon plasma coagulation (APC) was performed for GAVE, and between 79 and 83 years of age, APC was carried out five times for recurrent episodes of GAVE presenting as anemia. Upon hospitalization, she was found to have anemic conjunctivae and the laboratory findings were red blood cells 245 × 10⁴/mm³ and hemoglobin 7.7 g/dL. During this period, endoscopic band ligation (EBL) was performed for the recurrent refractory GAVE. EBL was first applied to the most distal antrum, and subsequent EBLs were performed more proximally. Two weeks after initial EBL treatment, endoscopy revealed both ulcers and shrinking of GAVE in the stomach. Fourteen months later, no further recurrence of GAVE was observed by endoscopy. This patient had no episodes of bleeding during the 20 month period since she was treated with EBL, and has a hemoglobin value of 10.1 g/dL. The histologic changes that occur with GAVE exist in the mucosal and submucosal region of the stomach; therefore, EBL may be effective for refractory GAVE because of obliterating submucosal vascular plexus.     

A novel endoscopic ablation of gastric antral vascular ectasia

An 80-year-old woman was admitted to our hospital because of tarry stool with iron deficiency anemia. Her past history included autoimmune hepatitis. Esophagogastroduodenal endoscopy was performed to investigate the bleeding source and revealed multiple linear gastric vascular malformations in the antrum and cardia, compatible with Gastric antral vascular ectasia (GAVE). Endoscopic ablation was carried out with the tip of the hot biopsy forceps without opening at soft coagulation mode of 80W. The patient tolerated the procedure well and there were no complications associated with endoscopic therapies. After two sessions of endoscopic ablation her anemia improved to around 10 g/dL, an increase of 3.6 g/dL. Various endoscopic treatments have been described to manage GAVE. The most popular is argon plasma coagulation (APC), although APC is associated with over-distension induced by the argon plasma gas. To avoid over-distension and to reduce the abdominal discomfort/pain of this patient, we have used hot biopsy forceps instead of APC. Our case suggests that this procedure is effective, easy and convenient, as no special equipment or skill is necessary.     

Post-transplant gastric antral vascular ectasia after intra-venous busulfan regimen

We report a 74-year-old female with chronic myelogenous leukemia (CML) in accelerated phase with pre-existing severe type 2 diabetes (T2D) and hemorrhagic gastric ulcers who was successfully treated with nilotinib. We first considered second-generation tyrosine kinase inhibitors for the treatment of this patient, as they elicit a superior response compared with imatinib. We next selected nilotinib, rather than dasatinib, since the increased risk of bleeding associated with dasatinib represented a greater risk of fatality than aggravation of T2D with nilotinib. After improvement of hemorrhagic gastric ulcers and T2D with exogenous insulin therapy, we began nilotinib administration; insulin dose was increased to maintain her glucose levels whereas urine C-peptide level decreased. Conversely, when nilotinib was discontinued due to liver dysfunction, the dosage of injected insulin was decreased and urine C-peptide levels increased. After re-starting nilotinib, the required dose of insulin gradually increased again, and urine C-peptide level decreased, indicating that nilotinib may have impaired secretion of endogenous insulin. The patient obtained a complete cytogenetic response after 3 months of nilotinib treatment. Her T2D has since been well controlled by insulin therapy. To our knowledge, this is the first report that nilotinib treatment for patients with severe T2D may induce a reversible decrease in endogenous insulin secretion, although the precise underlying mechanisms remain unknown. We highly recommend sufficient screening and early intervention with exogenous insulin therapy for diabetic CML patients who receive nilotinib.     

Endoscopic mucosal resection for recurrent gastric antral vascular ectasia

Gastric antral vascular ectasia (GAVE) is an overt or occult source of gastrointestinal bleeding. Despite several therapeutic approaches have been successfully tested for preventing chronic bleeding, some patients present recurrence of GAVE lesions. To the best of our knowledge, we report the first case, of a 86-year-old woman who presented severe iron-deficiency anemia due to GAVE and showed recurrence of GAVE lesion despite the intensive argon plasma coagulation treatment. We performed endoscopic mucosal resection of bleeding GAVE with resolution of anemia.     

Endoscopic follow-up study of development of gastric antral vascular ectasia associated with liver cirrhosis

Gastric antral vascular ectasia is an important cause of chronic gastrointestinal blood loss. However, its development and progression have not yet been clarified. We investigated its early lesions and progression by reviewing endoscopic films of five patients with gastric antral vascular ectasia followed for liver cirrhosis. In all patients, early findings were prepyloric red spots. In two patients, anemia due to gastrointestinal bleeding was already observed when vascular lesions were confined to the distal antrum. In the other three patients, anemia was observed 1–2 years after they showed a diagnostic pattern of gastric antral vascular ectasia. The vascular lesions gradually thickned and extended throughout the antrum, with the complete picture shown in 1.5–5 years. The pattern of distribution was classified into three types: diffuse spotty, diffuse confluent, and striped. These types could be predicted before the complete formation. Gastric antral vascular ectasia associated with liver cirrhosis started as prepyloric red spots and extended to the proximal antrum in various ways and varying time courses of less than 5 years; this entity may cause hemorrhage even in the early stage.     

Radiofrequency ablation for gastric antral vascular ectasia and radiation proctitis

Gastric antral vascular ectasia (GAVE) and chronic radiation proctitis (CRP) are well-known causes of repeated gastrointestinal bleeding and iron deficiency anemia. Argon plasma coagulation (APC) is the most common endoscopic therapy used, but some patients need multiple APC sessions. Radiofrequency ablation (RFA) is recently used in GAVE and CRP treatment with promising results. In this case series, we analyzed data for 15 patients with GAVE and 5 patients with CRP that had multiple prior APC treatment. They were treated with RFA HALO 90 catheter (HALO90 Ablation Catheter System; Covidien, GI Solutions, Sunnyvale, CA) in our tertiary referral center. A total of 20 patients received 32 RFA procedures (8 in the CRP group and 24 in the GAVE group). The median number of the procedures was 2 (range 1–4). The hemoglobin levels in the GAVE group were 83 g/L pre-RFA and 98 g/L post-RFA and in the CRP group, 86 g/L pre-RFA and 103 g/L post-RFA. A total of 16/20 patients (80%) were transfusion-free after the completion of RFA treatment. Technical success of the treatment was 95% (19/20 patients). RFA can be safely and successfully used in APC refractory GAVE and CRP patients.     

Endoscopic laser treatment of diffuse gastric antral vascular ectasia.

Eight patients (six women and two men) were found to have iron deficiency anaemia due to diffuse gastric antral vascular ectasia. The mean age of the patients was 74.6 years (range 57-83). All required repeated blood transfusions (mean 18 units/year) before treatment. Five patients were classified as having the ''watermelon stomach'' (group A) and three the ''honeycomb stomach'' (group B), according to criteria described in previous reports. All were treated using neodymium:YAG laser photocoagulation. Significant endoscopic improvement and reduction in blood requirements were noticed in group A in which only one patient required a transfusion after treatment. Results in group B were disappointing. One patient was operated on and the other two still require blood transfusions. Laser treatment was safe in both groups and no major complications were encountered.     

Disappearance of gastric antral vascular ectasia after percutaneous transhepatic obliteration

We report on a patient with severe iron deficiency anemia due to gastric antral vascular ectasia (GAVE), complicating hepatocellular carcinoma (HCC) and esophageal varices. Esophago-gastro-duodenoscopy (EGDS) 6 months after transarterial embolization (TAE) for the HCC and percutaneous transhepatic obliteration (PTO) for esophageal varices, showed the absence of GAVE. As GAVE did not recur in spite of the recurrence of the tumor thrombus later, lowered antral congestion by PTO might be the main cause of disappearance of GAVE. This case suggests that PTO may be an effective treatment against GAVE with portal hypertension with uncontrollable bleeding.     

Clinical comparisons between two subsets of gastric antral vascular ectasia

BACKGROUND: The lesions of gastric antral vascular ectasia take two endoscopic forms, diffuse red spots and red stripes. In addition, they are often associated with cirrhosis. The main aim of the present retrospective study was to determine whether differences in endoscopic appearance and presence or absence of cirrhosis have relationships to clinical features and course. METHODS: Gastric antral vascular ectasia in 30 patients was classified into 2 endoscopic subtypes, punctate type (21 patients) and striped type (8 patients); only 1 patient could not be categorized to either type. The 30 patients were divided into groups based on the presence (25) or absence (5) of cirrhosis. RESULTS: All patients with punctate-type vascular ectasias had cirrhosis, whereas only 38% of patients with the striped type had cirrhosis. All patients without cirrhosis had the striped pattern. For patients with the 2 endoscopic types as well as those with and without cirrhosis, the outcomes of endoscopic treatment were similar. CONCLUSIONS: The findings of the present study suggest that cirrhosis is strongly associated with the development of punctate-type vascular ectasias. The endoscopic appearance of vascular ectasias and the presence or absence of cirrhosis did not determine outcome of patients.     

Antral motility in patients with cirrhosis with or without gastric antral vascular ectasia.

Gastric motility has not been extensively studied in patients with cirrhosis and gastric antral vascular ectasia (GAVE) may be associated with antropyloric dysfunction. This study therefore looked at antral motility using ultrasound in patients with alcoholic cirrhosis with or without GAVE. Twenty six patients were included: 10 patients with cirrhosis without GAVE, eight patients with cirrhosis and GAVE, and eight controls without liver disease. Measurement of antral area and antral contractions (amplitude and frequency) was performed for three hours after ingestion of a standardised solid-liquid meal. Antral area half time (mean (SD)) was not significantly increased in patients with cirrhosis without GAVE (84 (42) min), but increased by 120% (123 (43) min; p < 0.01) in patients with GAVE compared with controls (56 (26) min). GAVE patients exhibited the same frequency and amplitude of antral contractions at each time point as controls and had the same tendency to increase these values over time although this was attenuated in the late postprandial phase. In contrast, cirrhotic patients without GAVE exhibited a significantly higher frequency and amplitude of antral contractions during the initial postprandial phase but showed no change in either frequency or amplitude over time. In conclusion, in cirrhosis there is an abnormal antral motor response to a meal, which has a different pattern over time in patients with or without GAVE.