Gastric Antral Vascular Ectasia: Resolution of Bleeding and Stabilization of Hematocrit Following Orthotopic Liver Transplantation

Abstract

Gastric Antral Vascular Ectasia (GAVE) is an uncommon cause of chronic gastrointestinal bleeding and iron deficiency anemia in the geriatric population. It is often associated with cirrhosis of the liver and is hypothesized to result from synthetic liver dysfunction. Treatment options include argon plasma coagulation, endoscopic band ligation, and radiofrequency ablation. An orthotopic liver transplant may be effective for patients with advanced liver disease. In this case report, we describe a 60-year-old woman with a history of cirrhosis secondary to nonalcohol-related steatohepatitis (NASH) and GAVE syndrome who presented with abdominal pain and melena. She had multiple prior episodes of gastrointestinal bleeding, leading to long-term transfusion dependency. An urgent esophagogastroduodenoscopy revealed the presence of GAVE with active bleeding. The patient was supported with blood transfusions and transferred to a transplant center, where she underwent orthotopic liver transplantation. Following the transplantation, her hemoglobin levels improved and remained stable. She was no longer noted to require any further blood transfusions during outpatient follow-up visits. This case report substantiates the role of synthetic liver dysfunction in the development of GAVE. Also, it suggests that patients with advanced cirrhosis and refractory GAVE may benefit from liver transplantation as a potential treatment option.

1. Introduction

Within the geriatric population, gastric antral vascular ectasia (GAVE) syndrome, also referred to as “watermelon” stomach, is a rare, under-reported, yet significant cause of chronic gastrointestinal (GI) bleeding and iron deficiency anemia.1 It is characterized by a dilation of small blood vessels in the antrum of the stomach, leading to increased susceptibility to bleeding.2,3 GAVE is closely correlated with cirrhosis of the liver and portal hypertension; however, it has also been linked to autoimmune connective tissue disorders (e.g., systemic sclerosis, systemic lupus erythematosus, scleroderma, Sjogren’s syndrome), chronic renal failure, and diabetes mellitus as underlying pathologies.4–7

Esophagogastroduodenoscopy (EGD) with argon coagulation plasma (APC) is the current treatment of choice. Endoscopic band ligation (EBL) and radiofrequency ablation (RFA) are other treatment options.8 Up to 14 % of patients may be refractory to these treatments.8 Previous small studies have demonstrated that orthotopic liver transplant may be an effective method of treatment for GAVE and associated anemia in those patients with a history of advanced liver disease.9 This paper aims to examine a patient with GAVE and discuss the syndrome to contribute to a more comprehensive understanding of this often-underrepresented condition. We report a case of a 60-year-old female with GAVE syndrome as a complication of NASH-related cirrhosis that resolved status post orthotopic liver transplantation.

2. Case presentation

A 60-year-old woman with a history of cirrhosis of the liver, diagnosed via biopsy in 2014, of unclear etiology (presumed to be from autoimmune hepatitis) and multiple prior hospital admissions for upper GI bleeding caused by GAVE presented to our hospital with two days of right upper quadrant abdominal pain. She reported three melenic bowel movements and an episode of hematemesis.

Past medical history is significant for cirrhosis complicated by multiple decompensations, including ascites, hepatic encephalopathy (HE), and variceal bleeding. She was on the waitlist to receive a liver transplant. She was on lactulose and rifaximin and had previously been on prednisone 30 mg and azathioprine. About five years ago, she underwent a TIPS (trans jugular intrahepatic portosystemic shunt) procedure for variceal bleeding. She experienced recurrent hospitalizations, with nearly monthly episodes of bleeding in the previous three years. However, the frequency of bleeding decreased over the previous year, with only four reported events. Each hospitalization necessitated 2–3 units of packed red blood cell (pRBC) transfusions and an EGD that revealed moderate GAVE, often accompanied by oozing and/or bleeding in the antrum. APC interventions were performed on each occasion, effectively achieving hemostasis. She was taking pantoprazole 40 mg two times daily. Her most up-to-date alpha-fetoprotein (AFP) levels were within normal limits. A surveillance CT abdomen a week prior to presentation indicated the absence of liver masses but was concerning for TIPS dysfunction and eccentric thrombus.

Physical examination was notable for a distended, non-tender abdomen. Melena was noted on digital rectal examination. Laboratory findings showed a hemoglobin of 6.7 g/dL (baseline 9–10 g/dL); platelet count of 74K; bilirubin 3.4 mg/dL; AST 96 U/L; ALT 53 U/L; INR of 1.62. The remainder of the chemistry panel and partial thromboplastin time (PTT) were within reference ranges. Her MELD-Na score at this time was 30. An urgent EGD was pursued, which demonstrated gastritis and gastric erosions in the antrum (Fig. 1A). There was evidence of GAVE with bleeding in the distal body and antrum (Fig. 1B). Biopsies were taken (results shown in Fig. 3A), and a hemoclip was placed to prevent biopsy-related bleeding (Fig. 1C). The GAVE lesion was treated with APC (Fig. 1D). Multiple packed red blood cell transfusions were required during the hospitalization to maintain a hematocrit above 21 %. Subsequent ultrasound of the abdomen showcased a cirrhotic liver without focal lesions (red arrowhead, Fig. 2D) and splenomegaly (white arrowhead, Fig. 2E). A large volume ascites (white arrows, Fig. 2A, B, and 2C; yellow arrowhead, Fig. 2D) and a contracted gallbladder with gallstones but no sonographic evidence of acute inflammation was noted. TIPS was patent. Hepatic and portal venous ultrasound with doppler showed patent main portal and main right hepatic veins with normally directed flow and no evidence of portal or hepatic venous thrombosis, stenosis, or occlusion (white arrows, Fig. 2F). A follow-up EGD three days after presentation showed resolution of active bleeding associated with the GAVE lesions (Fig. 1E and F). Serial abdominal paracenteses were required over the duration of the stay for worsening, medically refractory ascites. TIPS was evaluated by the interventional radiology team, and a revision was performed with an improvement in the shunt gradient from 37 to 20 mmHg.

Fig. 1.

These are the images of Esophagogastroduodenoscopy (EGD) illustrating gastric erosions (image A) and GAVE with bleeding (image B). In response, a biopsy was performed and a hemoclip was placed (image C). GAVE was treated with argon plasma coagulation (image D). A follow-up EGD three days later showed that the erosions persisted (image E), but GAVE was no longer bleeding (image F).

Fig. 3.

These are hematoxylin and eosin-stained histologic sections of stomach biopsy and liver biopsy respectively. Image A shows gastric antral-type mucosa with ectactic vessels, fibrin thrombi, fibromuscular proliferation, and markedly reactive changes, consistent with gastric antral vascular ectasia. Image B shows significant bridging fibrosis, consistent with cirrhosis.

Fig. 2.

These are the images of ultrasound showing large-volume ascites noted throughout the abdomen (white arrows in A, B and C). Image D shows atrophied, cirrhotic liver (yellow arrowhead) measuring 9 cm in length with associated ascites (red arrowhead). Note splenomegaly (white arrowhead) in image E. Image F is a hepatic/portal venous doppler sonographic image demonstrating patent TIPS with normal blood flow (white arrows).

She was then transferred to a transplant center and underwent orthotopic liver transplantation. Her post-operative period was uncomplicated. Explant biopsy showed inactive cirrhosis with NASH (Fig. 3B). Although a repeat EGD was not performed following transplantation, the patient appeared to be in good general health and had no further episodes of GI bleeding or transfusion requirements. Her hemoglobin improved and remained stable between 13 and 14 g/dL, and her platelet count improved to 150–170K.

3. Discussion

Around 4 % of non-variceal upper GI bleeding cases are attributable to GAVE.10 It usually manifests as iron deficiency anemia resulting from chronic blood loss but can also potentially induce severe acute GI bleeding. The typical age of onset is around 73 years, and females are predominantly affected.5,10

The pathogenesis is not well understood. It has been hypothesized that mechanical stress on the gastric antrum caused by pyloric prolapse and disturbed motility, as well as increased levels of neuroendocrine hormones such as gastrin, vasoactive intestinal polypeptide, serotonin, prostaglandin E2, nitric oxide, and glucagon in cirrhotic patients, can lead to mucosal microvascular damage and the development of GAVE.8,11 GAVE in cirrhotic patients is thought to be related to the decline in liver function rather than portal hypertension, which is supported by some case reports and case series showing its complete resolution following liver transplantation.9 However, treatments aimed at reducing portal hypertension, such as TIPS or beta-blockers, do not appear to have any effect.11

Diagnosis is by endoscopy and biopsy. The GAVE score, which includes three parameters (co-existing ectasia and/or fibrin thrombi, spindle cell proliferation, and fibro hyalinosis), was put forth for the diagnosis.12 It was shown to have higher diagnostic accuracy (80 %) in distinguishing GAVE from portal hypertensive gastropathy (PHG). Both GAVE and PHG are associated with cirrhosis, appear similar on endoscopy, and hence, can be mistaken for each other. However, it must be noted that GAVE is less common of the two, involves the antrum, and is more commonly associated with anemia. In contrast, PHG typically occurs in the corpus and fundus.13

Treatment options can be divided into three main types: endoscopic, pharmacologic, and surgical. Endoscopic procedures usually require several sessions to control bleeding successfully. APC is the standard for endoscopic therapy due to its low cost, availability, ease of use, and low complication rate.8 RFA and EBL have emerged as alternatives in refractory cases. In a randomized control trial, Elhen Dawny and colleagues compared the safety and effectiveness of EBL and APC over a six-month period and found that both procedures were equally effective. However, APC required fewer transfusions and procedure sessions than EBL.14 Furthermore, a number of prospective and retrospective studies evaluated the use of RFA in patients who have not responded to APC, with results demonstrating a reduction in transfusion requirements. Therefore, patients with GAVE who have not responded to APC and band ligation may benefit from RFA as a treatment option.15–18 Alternative endoscopic techniques such as cryotherapy, coagulation snare, and sclerotherapy exist, but have less supporting evidence, are less readily available, and are more expensive.

Pharmacological approaches can be used when endoscopic therapy is not effective or feasible. These include estrogen–progesterone, octreotide, corticosteroids, tranexamic acid, cyclophosphamide, thalidomide, serotonin antagonist, and calcitonin.16 In extreme cases, surgical treatment with antrectomy and Billroth I anastomosis can be considered in non-cirrhotic patients where other treatments have failed.19,20 However, this option may not be feasible in cirrhotic patients due to high morbidity and mortality.21 Liver transplantation has been found to be the only permanent curative measure for recurrent bleeding in GAVE patients with underlying cirrhosis, as demonstrated by a recent case series.9 While a repeat endoscopy was not performed in our patient, hematocrit had improved and stabilized, suggesting the resolution of GAVE associated bleeding with liver transplantation. Our case report provides additional evidence that the underlying mechanism of GAVE is a decrease in synthetic liver function and suggests orthotopic liver transplantation as a curative treatment option.

4. Conclusion

GAVE is a treatable cause of GI bleeding that can cause significant morbidity and mortality in cirrhotic patients. We present an unusual case of a cirrhotic patient with upper GI bleeding from GAVE who had not responded to primary endoscopic therapy and TIPS procedure, but achieved transfusion independence after undergoing orthotopic liver transplantation. Our case adds to the growing body of literature that suggests that liver transplantation can effectively resolve bleeding from GAVE in cirrhotic patients, and supports the theory that synthetic liver dysfunction, rather than portal hypertension, is the underlying mechanism for GAVE.