Prevalence, causes and management of gastric varices – a literature review

Summary

Gastric varices, although less prevalent than esophageal varices, exhibit greater morbidity and mortality. This comprehensive literature review investigates the prevalence of gastric varices, diverse classification systems, and available management options. The spectrum of management modalities encompasses primary and secondary prevention, acute gastric variceal bleeding strategies, and preventive measures against rebleeding. A meticulous exploration of PubMed and Google Scholar over the past decade (2013 to 2023) shaped the inclusion criteria for adults aged 18 and above diagnosed with gastric varices, with or without variceal bleeding. Exclusion criteria eliminated non-gastric variceal causes of upper gastrointestinal bleeding and qualitative articles, resulting in 43 relevant records from the 190 initially identified. The diverse management landscape caters to the specific type of gastric varix, contributing to a varied treatment approach. Notably, endoscopic ultrasound--guided coil embolization coupled with glue injection has emerged as a promising intervention, demonstrating superior outcomes in addressing gastric varices. The evolving understanding of these varices and advancing therapeutic strategies underscore the dynamic nature of research in this critical medical domain.

Keywords:

gastric varices – upper gastrointestinal bleeding – classification – hemostasis – etiology – management options

Introduction

Gastric varices, dilated veins from portal hypertension, pose a significant risk of severe bleeding and adverse outcomes [1]. Though less common than esophageal varices, they can lead to intense, hard-to-control bleeding and increase the chances of transfusions and death [2]. Accounting for 3–30% of variceal bleeding, gastric varices result from various causes of portal hypertension [3]. Different classification systems based on location aid diagnosis, but optimal management lacks clear documentation due to the absence of large clinical trials. Treatment options, determined by varix characteristics, include vasoactive agents, balloon tamponade, and endoscopic and radiologic interventions. Success rates vary, and no standard guidelines exist, emphasizing the need for further research [4]. So, the goal was to conduct a literature review encompassing the epidemiology, etiology, diverse classification systems, and treatment approaches for gastric varices.

Methodology

Data was collected from PubMed and Google Scholar, including all quantitative research available on gastric varices from 2013 to 2023. The reporting system used for this literature review was the Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020 (PRISMA 2020) guidelines [5].

 

Eligibility criteria

All quantitative research on the prevalence, causes, classification systems, and management of gastric varices was included in this literature review. There were no limitations to body mass index (BMI), sex, or race. PICO criteria were used, and research studies that were used for this literature review fit these criteria. The population was adults (18 years and above) with a confirmed diagnosis of gastric varices; intervention was on any management option used; and comparison was on the various management options available. Exclusion criteria were all qualitative articles on gastric varices, as well as other causes of upper gastrointestinal bleeding that were not due to gastric varices.

 

Search strategy

Key words that were entered include gastric varices with/without the following words, and with the help of Boolean operators: upper gastrointestinal bleeding, classification, epidemiology, etiology, role of endoscopic ultrasound, and management (coiling and glue injection). An article matrix was used to summarise all of the research to be used. These were then organized thematically in a table and subsequently synthesized, analyzed, and presented.

 

Risk of bias

Risk of bias for the random controlled trials was assessed using the Cochrane Collaboration‘s Risk of Bias tool for randomized trials (RoB 2). Five main domains were assessed. These were the risk of bias in the selection of the reported result, risk of bias in the measurement of the outcome, risk of bias in missing outcome data, risk of bias due to deviations from the intended interventions (effect of adhering to intervention), risk of bias due to deviations from the intended interventions (effect of assignment to intervention), and risk of bias arising from the randomization process [6].

All the randomized controlled trials assessed were low risk.

 

Ethical considerations

Ethical approval for this research was applied for from the University of South Wales Ethics Subgroup and Faculty Research Ethics Committee. The project was started after the ethics committee approved it.

 

Selection of data

A total of 190 issues were retrieved from electronic databases and manual searches during the specified period (January 2013 to April 2023), as illustrated in Fig. 1, following the PRISMA 2020 guideline. For this literature review, 46 studies were utilized, comprising nine prospective randomized controlled trials, three observational follow-up studies, 31 literature/systematic reviews, and three sources from PRISMA and RoB-2 use. Tab. 1 presents characteristics of the epidemiological studies. The risk of bias in the nine randomized controlled trials was assessed using the Risk-of-bias VISualization (robvis) tool, depicted in Fig. 2.

 

 

Tab. 1. The characteristics of the epidemiological studies used for this literature review. Tab. 1. Charakteristika epidemiologických studií použitých pro tento přehled literatury. Authors                                     Year                  Study design                Sample    Mean age Study duration Dropout Sex ratio of study              size                                                          (years)     number   (M : F)
Orloff JM et al. [15]	2015	prospective RCT	588	49.5	for life		386 : 202
Hung TH et al. [25]	2016	prospective follow-up study	311	55.4	30 days	5	236 : 75
Shi D, Liu J [22]	2022	prospective RCT	158	57.23	6 months	4	44 : 114
Lobo MRA et al. [11]	2019	pilot RCT	32	53.5	9 months	2	13 : 19
Zeng X et al. [9]	2017	prospective RCT	96	54.5	6 months	2	67 : 29
Liu C et al. [30]	2019	clinical pilot RCT	107	54.6	2 months	0	82 : 25
Poudel CR et al. [20]	2022	open label RCT	74	48.15	8 weeks	3	61 : 13
Guo H et al. [13]	2021	prospective observational cohort	74	54.53	0.06–49 months	12	34 : 28
Sun X et al. [12]	2021	prospective, double-blind RCT	108	53.5	2 years	6	51 : 51
Lo GH et al. [10]	2020	prospective RCT	68	55	6 weeks	0	51 : 17
Tantau M et al. [22]	2014	prospective follow-up study	37	60.22	416.7 days	2	21 : 16
Robles-Medranda C et al. [33]	2020	interventional parallel RCT	60	61.7	12 months	0	35 : 25

 

Explanation

Definition

Gastric varices are a group of blood vessels in the stomach‘s submucosal or mucosal layer that is part of a large shunt network that connects both portal and systemic circulation [7].

 

Prevalence and Causes

Gastric varices, while not receiving as much attention as other variceal bleeding types, exhibit the highest mortality rates [8–10]. Severity of blood loss and rebleeding rates is more pronounced in gastric varices, with a 5% risk for small varices and 15% for medium and large varices [7]. Rebleeding probability ranges from 34 to 89% [11], and within a year of the initial bleeding episode, there is a 60% risk of rebleeding [12]. Mortality rates within six weeks after acute variceal hemorrhage is high, varying between 10–25% [8], 15–25% [13], and 10–20% [12]. Approximately 40–50% of patients with acute variceal bleeding may stop bleeding spontaneously, but they face a high rebleeding risk, particularly within the first five days [14]. Gastric varices are diagnosed in 65% of patients with portal hypertension [15], contributing significantly to the associated complications and high mortality rate [12]. About 30% of acute variceal bleeding cases are attributed to gastric varices [15]. Prevalence of gastric varices in patients with cirrhosis ranges from 15–17% [9] to 20% [8], with a slight increase seen in those with portal hypertension, reaching 25% [10].

Gastric varices, often associated with cirrhosis caused by viral hepatitis (Hepatitis B and C), alcoholic liver disease, and autoimmune hepatitis [8], are also prevalent in non-cirrhotic portal hypertension, especially splenic vein thrombosis [16]. Hepatic venous pressure gradient (HVPG) exceeding 10mmHg is a significant predictor for variceal evolution, but cardiofundal varices can bleed at a lower gradient of 10–12 mmHg. Once varices develop, progression from small to large varices occurs in 5–30% of cases. Child- -Pugh grade, either at diagnosis or worsening on follow-up, consistently influences variceal progression [17]. One-year risk of initial variceal bleeding is 5–15% [12], with varying risks based on the presence and size of varices at diagnosis. Cumulative risk of gastric varices bleeding at one year is 16%. At three years, it is 36%, and at five years it is 44% [18].

Predictors of variceal bleeding include size of the varix (the larger the varix, the higher the risk of bleeding), Child‘s grade in cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, gastric varix‘s location, and red wale marks seen on endoscopy [14,19]. Death from variceal hemorrhage can be as high as 20–80%, depending on other co-morbidities/complications present, such as an isolated event of variceal bleeding, encephalopathy, or ascites [20].

 

Classification

Various classification systems exist for gastric varices, the most prevalent being the Sarin classification, but others are also described below.

 

Sarin‘s classification

Sarin introduced the classification system in 1992, and has become the most widely utilized due to its user-friendly nature and its ability to provide therapeutic options for endoscopic management of gastric varices [21]. This classification system has four types of gastric varices, which include:

a)
Gastroesophageal varices type 1 (GOV 1): Esophageal varices (EV) that extend into the lesser curvature of the stomach, crossing the gastroesophageal junction. This type is the most common at 74% of all gastric varices.

b)
Gastroesophageal varices type 2 (GOV 2): EV that extend to the greater curvature of the stomach, extending to the fundus, thus crossing the gastroesophageal junction.

c)
Isolated gastric varices type 1 (IGV1): These varices are located solely in the fundus of the stomach, with none in the esophagus.

d)
Isolated gastric varices type 2 (IGV2): These varices are found in any part of the stomach except the cardio-fundal area and duodenal bulb. This type is very rarely seen in patients with cirrhosis.

 

Hashizome classification

Initially presented in 1990, Hashizome‘s classification refers to the underlying anatomy of vessels, incorporating form, location, and colour of the varix in its categorization. The form of the varix is further divided into three types, with the letter ‚F‘ being used:

a) tortuous (F1);

b) nodular (F2);

c) tumorous (F3).

 

Location of the varix classification under Hashizome is dependent on hemodynamic factors and is divided into five types, with the letter ‚L‘ being used:

a) anterior (La);

b) posterior (Lp);

c) lesser curvature (Ll);

d) greater curvature (Lg) of the cardia;

e) fundic area (Lf).

 

Within the Hashizome classification‘s colour subclassification, there are two types denoted by the letter ‚C.‘ Additionally, a term referred to as a red colour spot (RCS) is employed to describe the focal redness observed on the varix, characterized by a glossy thin wall. The colour classification is as follows:

a) white (Cw);

b) red (Cr).

Arakawa’s classification

Arakawa’s classification is divided into two main types with subtypes.

Type I: Branches located in the stomach wall are very few, with the supplying vessel, varix, and draining vessel forming one continuous vein that has an almost unchanged calibre:

Ia) One supplying vessel becomes a fundic varix.

Ib) Multiple supplying vessels join to become a varix, which drains into a single draining vessel.

 

Type II: The varix communicates with blood vessels in the stomach wall. Therefore, aside from the main blood vessels that supply and drain, there are also a lot of branching vessels found within the stomach wall [14].

 

Choi classification

Choi‘s classification was first described in 1983, and gastric varices are classified according to severity by using the ‚form‘. Under this classification, it has three groups:

F1 – mild;

F2 – moderate;

F3 – severe.

 

It is then subdivided into those associated with liver cirrhosis and splenic vein thrombosis or those without.

 

Hoskins and Johnson classification

Hoskin and Johnson first brought a full description of gastric variceal classification in 1988. This is also divided into three groups:

type 1: There are extensions inferior to the varix across the squamocolumnar junction.

type 2: The gastric varices are located in the fundus, but they appear to meet at the cardia with EV.

type 3: The gastric varices are present in the fundus or body of the stomach only without EV.

 

Mathur‘s classification

Mathur‘s classification was first described in 1988, and gastric varices were divided into five main types with some subgroups:

type 1: Esophageal varices are present, together with gastric varices at the lesser curvature.

type 2: Esophageal varices are present, together with gastric varices at the fundus.

2a) The fundal varices are restricted to the sub-cardiac area only.

2b) The fundal varices are diffuse in the fundus.

type 3: Isolated gastric varix that is only present at the fundus.

3a) The isolated fundal varix is secondary to splenic vein thrombosis.

3b) The isolated fundal varix is secondary to generalized portal hypertension.

type 4: There are esophageal varices that are in continuity with fundal varices, plus gastric varices found at the lesser curvature.

type 5: There are only gastric varices present and found at only the antrum (antral varices).

 

Iwase classification

This is divided into two types:

type 1: The gastric varix is called a localized gastric varix because it has one varicose vessel with an almost equal diameter to the inflow and outflow vein and no ramifications.

type 2: The gastric varix is called a diffuse gastric varix due to its multiple varicose vessels that have complex connected ramifications.

 

Japanese Society for Portal Hypertension

The Japanese Society for Portal Hypertension classification has five types, with the letters ‚Lg‘, followed by the letter that describes the part where the varix is found:

a)
The gastric varices are located at the fundus of the stomach (Lg-f).

b)
The gastric varices are located at the cardiac of the stomach (Lg-c).

c)
The gastric varices are located at the cardiac and fundus of the stomach (Lg c–f).

d)
The gastric varices are located at the antrum of the stomach (Lg-a).

e)
The gastric varices are located at the body of the stomach (Lg-b).

 

Italian endoscopic classification

There are two types in this classification:

type I gastric varices: These include all forms of gastroesophageal varices.

type II varices: These include all isolated gastric and ectopic varices.

 

Simple classification of gastric varices

Two main types are in this classification:

primary gastric varices: These are primary gastric varices that may or may not have a shunt.

secondary gastric varices: These are secondary gastric varices that arise after EV has been treated with endoscopic band ligation. These gastric varices have no portosystemic shunt.

 

Haemodynamic classification of gastric varices

Currently, this classification is preferred as it uses hemodynamics of the vessels (afferent vessel or efferent vessel or both) in classifying the condition or hemodynamics based on balloon-occluded transvenography. This helps in choosing the right treatment modality for gastric varices.

 

Based on the portosystemic afferent/efferent system

The portosystemic circulation can sometimes be complex in understanding the various mechanisms. Figures 3a, b show a clear diagram of the afferent and efferent flows and their various connections, adapted from Abby Philips and Sahney [21].

 

Kiyosue classification

In using the Kiyosue classification, either the afferent vein or efferent vein is used.

 

Kiyosue classification based on afferent vein hemodynamics

type 1: The varix is supplied by one afferent vein.

type 2: The varix is supplied by several afferent veins.

type 3: The varix is supplied by one or several afferent veins indirectly via a shunt.

 

Kiyosue classification based on efferent vein hemodynamics

type A: One draining shunt

type B: One draining shunt, gastro-renal shunt, and several collateral veins:

type B1) The collateral veins are small.

type B2) The collateral veins are medium-sized.

type B3) The collateral veins are large, with elevated flow but no shunt.

type C: There are two or more shunts present, with no collaterals.

type C1) The second shunt is small and can‘t be catheterized.

type C2) The second shunt is large and can be catheterized.

type D: A main shunt is absent, and drainage of the varices is via small collaterals.

 

Saad-Caldwell classification

Efferent vein hemodynamics align with the Kiyosue classification from types A to D. However, Saad-Caldwell introduces subdivisions for type D.

 

Saad-Caldwell classification based on afferent vein hemodynamics

type 1: One afferent vein (left gastric vein) supplies the varix.

type 2: The afferent vein supplying the varix is either the posterior gastric vein or the short gastric vein.

type 3: Several afferent veins supply the varix, with the same dominance among afferent veins.

type 4: Several afferent veins supplying the varix are created due to a splenic vein thrombosis.

 

Saad-Caldwell classification based on efferent vein hemodynamics.

type A: One draining shunt.

type B: One draining shunt and several collateral veins.

type B1) The collateral veins are small.

type B2) The collateral veins are medium-sized.

type B3) The collateral veins are large, with elevated flow but no shunt.

type C: There are two or more shunts present.

type C1) The second shunt is small and can‘t be catheterized.

type C2) The second shunt is large and can be catheterized.

type D: A main shunt is absent, and drainage of the varices is via small collaterals.

type D1: Systemic vein drainage predominance is not evident. The predominant veins may be any vein from the inferior phrenic, hemiazygos tributaries, intercostal veins, or adrenal veins.

type D2: There is a predominant systemic vein drainage, 4.3 mm in diameter, via unconventional systemic veins. However, the morphology is similar to that of type D1.

 

Hirota-BORV Classification

Hirota-BORV classification is based on only the efferent vein hemodynamics, and it is the same as the Kiyosue classification (based on the efferent vein hemodynamics) from type A–D. The only difference is the addition of a fifth type.

type A: One draining shunt.

type B: One draining shunt and several collateral veins.

type B1) The collateral veins are small.

type B2) The collateral veins are medium-sized.

type B3) The collateral veins are large, with elevated flow but no shunt.

type C: There are two or more shunts present:

type C1) The second shunt is small and can‘t be catheterized.

type C2) The second shunt is large and can be catheterized.

type D: A main shunt is absent, and drainage of the varices is via small collaterals.

type E: Balloon occlusion procedure is not possible because the gastro-renal shunt is too large.

 

Haemodynamic classification based on balloon-occluded transvenography

Hirota classification

There are five groups under this classification. It uses real-time views of gastric variceal angiographic opacification:

grade 1: No collateral veins were seen, and the gastric varices were adequately opacified.

grade 2: Small and few collateral veins are present, and the gastric varix contrast opacification is more than or equal to 3 minutes.

grade 3: Few medium to large collateral veins are present, and the gastric varix contrast opacification is partial, disappearing within 3 minutes.

grade 4: A lot of large collaterals are present, and the gastric varix is non-contrast opacified.

grade 5: With a shunt size too big for balloon occlusion and with associated fast blood flow, gastric varix opacification is minimal.

 

Fukuda classification

Fukuda classification is divided into four main types:

type 1: The left gastric vein is dominant within the gastric variceal complex.

type 2: Separate veins dominate the gastroesophageal complex. The dominant vein for the oesophageal varix component is the left gastric vein, whilst that of the gastric varix component is either the posterior gastric vein or superior gastric vein.

type 3: This gastric variceal system is very complex, comprising dominant feeding veins from both the right and left sides.

type 4: This gastric variceal system dominates only the right side.

 

Matsumoto classification

Matsumoto classification is divided into two types. This classification helps prognosticate the exacerbation of EV after treating gastric varices with an embolization procedure.

type 1: There is portosystemic flow in the gastro-renal shunt:

type 1A) There is an associated hepatoportal flow.

type 1B) There is an associated hepatofugal flow.

type 2: There is no portosystemic flow in the gastro-renal shunt:

type 2A) There is an associated hepatoportal flow.

type 2B) There is an associated hepatofugal flow.

 

Emergency treatment

The primary objective during acute variceal hemorrhage is the swift control of bleeding within the initial six weeks to minimize the risk of rebleeding and death [20,22]. In cases of acute gastric variceal bleeding, immediate attention involves securing the airways, stabilizing the patient‘s hemodynamics, and providing intensive care [23]. Protecting the airways includes the use of an endotracheal tube, and packed cells are administered judiciously to maintain a hemoglobin target of 7–8 g/dl. Systolic blood pressure is kept at a minimum of 70 mmHg for diagnostic and therapeutic endoscopy [24]. Intragastric balloon tamponade with the Linton-Nachlas tube, having a large gastric balloon capacity of 600 millilitres, is employed while awaiting definitive treatment. However, it is limited to 24 hours in actively bleeding cases [23].

Bacterial infection, prevalent in 50–60% of cirrhotic patients, increases rebleeding risks; therefore, antibiotic prophylaxis is beneficial. Vasoactive drugs such as somatostatin or terlipressin are administered as a part of the initial treatment before the endoscopic procedure in acute variceal hemorrhages [15,20]. In a study conducted by Orloff et al. (2015), octreotide acetate was administered intravenously at a dose of 50 micrograms/hour as an initial emergency treatment to control bleeding. Subsequent endoscopic therapy (sclerotherapy or band ligation) was performed within 8 hours and repeated at intervals until all varices were obliterated. Another study by Hung et al. (2016) [25] compared the efficacy of terlipressin to somatostatin as adjuvants to endoscopic sclerotherapy. Adjuvant vasoactive agents, administered for 3–5 days upon confirmation of active gastric variceal bleeding, reduced the risk of 7-day mortality, lowered transfusion requirements, and shortened hospitalization. No significant difference in mortality risk was observed between terlipressin and somatostatin, making either agent a viable choice based on availability. However, a study by Poudel et al. (2022) found that the use of terlipressin after endoscopic therapy did not provide additional benefits in terms of rebleeding and mortality, but increased adverse effects with prolonged use. Participants receiving terlipressin for 2- or 5-days post-procedure did not show added benefits compared to the control group, which received intravenous normal saline and was followed up for 8 weeks.

Management

Management of bleeding gastric varices has been vague, challenging, and still uncertain [15,22]. Moreover, controlled trials for gastric varices are limited and typically have small sample sizes [26]. The varied causes of variceal hemorrhage include 27 further compounds that lack standardization in treatment options. The management of gastric varices can be broadly divided into:

1. Pharmacologic:

a) Nonselective beta-blockers.

2. Endoscopic:

a) Gastric variceal sclerotherapy;

b) Gastric variceal band ligation;

c) Gastric variceal obturation with glue;

d) Thrombin injection/inorganic hemostatic powder spray.

3. Endoscopic ultrasound-guided therapy

4. Radiologic intervention:

a) Balloon-occluded Retrograde Transvenous Obliteration (BRTO);

b) Transjugular Intrahepatic Portosystemic Shunt (TIPS).

 

Fig. 3 (adapted by [27]) provides a diagrammatic summary of the management of gastric varices using Sarin‘s classification. While not exhaustive, it offers a concise overview of the management approach for gastric varices.

 

Nonselective beta-blockers

Nonselective beta-blockers (NSBBs) are employed to reduce portal vein pressure, enhance survival, and lower the occurrence of hepatic encephalopathy. Although limited primary prophylaxis studies exist for gastric varices, Luo and HernándezGea (2022) [28] recommend NSBBs for preventing bleeding in high-risk gastric varices. These high-risk indicators include varix size exceeding 5mm, poor liver function, and presence of red colour signs. NSBBs are non-invasive and help prevent cirrhosis decompensation, aligning with approvals from the American Association for the Study of Liver Diseases and Baveno VI consensus [24]. As a secondary preventive measure for those with prior variceal bleeding, NSBBs reduce rebleeding rates in only 50% of patients achieving a hemodynamic response, as measured by a reduction in the hepatic venous pressure gradient (HVPG). However, some patients with low HVPG still experience a high rebleeding rate, prompting Guo et al. (2021) [13] to conduct a prospective study on the importance of changes in free hepatic venous pressure (FHVP) in predicting variceal bleeding. The study revealed an increased risk of bleeding when FHVP rose by ≥1.75 mmHg.

 

Gastric variceal sclerotherapy

Endoscopic sclerotherapy, effective for managing esophageal varices, exhibits reduced efficacy in treating gastric varices [14]. The sclerosants employed, such as ethanolamine oleate, absolute alcohol, and tetradecyl sulfate, have shown variable success [23]. While endoscopic sclerotherapy proves effective (60–100%) for acute gastric variceal bleeding, its high rebleeding rate (90%) and associated complications, including ulcers induced by the procedure, pose challenges [14,24]. Difficulty arises from substantial blood flow in gastric varices, washing away the sclerosant, necessitating large amounts for effectiveness and heightening side effects. Sclerotherapy is particularly effective for gastric varices not located at the fundal area due to difficulties in endoscope access and high blood flow in this region [27].

Complications linked to gastric variceal sclerotherapy encompass fever, mucosal ulcerations, rebleeding, retrosternal and abdominal pain, perforations, and mediastinitis. Wani et al. (2015) [14] proposed a combined endoscopic therapy involving variceal band ligation and injection sclerotherapy for secondary prophylaxis. However, its use in acute hemorrhage is cautioned, as it may prolong procedures, heighten iatrogenic risks, and demand advanced technical skills.

 

Gastric variceal band ligation

Endoscopic variceal band ligation, a primary approach for esophageal varices, isn‘t standard for gastric varices due to limitations [8], a high rebleeding likelihood, and mixed evidence [14]. Band ligators, limited by size, suit only moderately or small-sized gastric varices (<2 cm) [27]. They may temporarily control bleeding in small type 1 gastro-oesophageal variceal bleeding until definitive management [24]. For larger gastric varices, banding can lead to band detachment, causing severe rebleeding from ulceration at the placement site [26]. Rebleeding risks rise with larger detachable snares for bigger varices [27]. The use of detachable snares and nylon loops is limited to tuberous or protuberant nodular gastric varices [8].

 

Gastric variceal obturation with glue

Cyanoacrylate glue, a rapid-polymerizing monomer tissue adhesive, hardens varices upon contact with blood, forming casts and achieving obturation [14,24]. N-butyl-2-cyanoacrylate (histoacryl) and isobutyl-2-cyano- acrylate (bucrylate) are common glue types for endoscopic injection, with other options such as 2-octyl-cyanoacrylate (Dermabond) and Glubran 2 (a histoacryl and methacryloxysulfolane mixture) [23]. Despite glue injection being considered the primary therapy for gastric varices, debates persist regarding its use, although studies generally favor its efficacy [9,22]. Glue injection achieves hemostasis in 87–100% of cases, with a potential embolism risk of up to 4% [10,29]. The sandwich method, involving priming the injector catheter with lipiodol before and after glue use, is preferred for glue administration, reducing adverse events, minimizing glue volume, and preventing endoscope and needle clogging [9].

Glue can be administered undiluted or diluted with oil, commonly lipiodol, in variable proportions. Undiluted glue, particularly cyanoacrylate mixed with methacryloxysulfolane (Glubran 2), is favoured for its slower polymerization time and reduced complications [14,24]. Dilution alternatives include normal saline, with studies showing comparable outcomes using a 1: 1 mixture with cyanoacrylate [12,24].

Zeng et al. (2017) [9] compared lipiodol with lauromacrogol in the sandwich method for endoscopic glue injection, revealing lauromacrogol as a safe and efficient alternative for gastric varices treatment, using less glue and reducing the risk of ectopic embolism. Liu et al. (2019) [30] also endorsed lauromacrogol in their study. Sun et al. (2021) [12] conducted a prospective trial combining endoscopic glue injection with partial splenic embolization, yielding improved clinical parameters compared to those without splenic embolization.

While prophylactic antibiotics are typically not recommended for elective endoscopic glue injection, Liu et al. (2019) [30] reported reduced clinical incidences with antibiotic use in the peri- and postoperative period. Complications associated with tissue adhesive injection in gastric varices encompass needle adherence, embolism, fistula, sepsis [9], fever, abdominal pain, gastric ulcers, and potentially serious outcomes like cerebral embolization, stroke, portal vein embolization, splenic infarction, and pulmonary emboli [10,14].

 

Endoscopic thrombin injection

Thrombin, available in both bovine and human forms, is a sterile lyophilized powder used for inducing hemostasis by converting fibrinogen to a fibrin clot and promoting platelet aggregation [24]. The human form is preferred due to a lower risk of allergic reactions and concerns about spongiform encephalopathy and Creutzfeldt-Jakob syndrome associated with the bovine form [10,19,23]. Thrombin is effective in coagulating a litre of blood in less than a minute with a minimal 5 millilitres [24]. It has shown success in challenging cases, such as Sarin‘s classification of gastro-oesophageal varix type 2 patients [14]. Reconstituted with 5 mL of distilled water to a concentration of 250 U/millilitre, thrombin is administered at an average dose of 1,500 to 2,000 U [17]. In a randomized controlled trial comparing thrombin with glue injection for gastric variceal hemorrhage, both demonstrated high efficacy in achieving hemostasis. Still, thrombin was easier to administer, caused no equipment damage or distant thrombosis, and had a superior safety profile over six weeks with lower complications [10]. For cases of glue injection failure, the inorganic absorbent hemostatic powder spray TC-325 can be used in patients with refractory gastric variceal hemorrhage, and it has shown promise in controlling post-banding ulcer bleeding, even though further studies are needed [24,31].

 

Endoscopic ultrasound-guided treatment

Endoscopic ultrasound (EUS) -guided treatment, a relatively new approach for gastro-oesophageal varices, includes techniques like coil application, cyanoacrylate injection, or their combination. EUS-guided cyanoacrylate injection, introduced in 2007 [28], is not only effective for managing variceal haemorrhage, but also aids in accurate identification, treatment planning, and evaluating treatment efficacy [14]. EUS excels in diagnosing gastric varices compared to endoscopy, utilizing color Doppler to differentiate from other structures [24].

Various EUS-guided treatments, such as EUS-guided glue injection, EUS- -guided coil embolization, glue injection, EUS-guided thrombin injection, EUS-guided coil and thrombin injection, EUS-guided coil and gelatine use, EUS--guided sclerotherapy, EUS-guided intrahepatic portosystemic shunt (EIPS), or EUS-guided partial splenic embolization (PSE) and combinations thereof, offer diverse options [18]. The use of both glue and coils with synthetic fibres aims to prevent thromboembolic events, and the technique involves several steps, including vessel measurement and coil release through a fine needle aspirate needle [14]. However, EUS-guided coil embolization is more expensive and needs more technical expertise than the EUS-guided glue application [32].

Studies comparing different EUS- -guided treatments indicate the efficacy and safety of these approaches. Robles-Medranda et al., (2020) [33] found that combining coil embolization and cyanoacrylate injection yielded better outcomes than using coil embolization alone. A meta-analysis by McCarty et al., (2020) [34] supported the superiority of combined EUS-coil and cyanoacrylate over individual treatments in terms of technical and clinical success rates. Moreover, Tantau et al., (2014) [22] and Lobo et al., (2019) [11] highlighted the efficacy of EUS-guided treatments, demonstrating benefits such as lower rebleeding rates compared to traditional methods like band ligation. Emergency portacaval shunt (PCS) was found to be superior in long- -term outcomes compared to endoscopic therapy (ET) [15].

 

Radiological intervention

Primary radiological interventions for gastric varices include BRTO and TIPS. Each approach has its pros and cons. Nevertheless, concurrent use of both BRTO and TIPS improves hemostasis and mitigates complications linked to elevated portal pressure encountered in BRTO [27].

Balloon-occluded retrograde transvenous obliteration (BRTO)

Introduced in 1996, BRTO targets gastric varices with a gastro-renal shunt, which serves as a conduit for radiological intervention. Achieving hemostasis in acute gastric variceal bleeding ranges from 76 to 100%, with a rebleeding rate of 0 to 15.4% [14]. Before BRTO, contrast- -enhanced computed tomography/mag- netic resonance imaging was crucial for vascular tree analysis and procedural planning [28].

The procedural steps involve using a 5-French catheter with an inflated balloon inserted through the transfemoral or internal jugular vein to the left adrenal vein. The balloon‘s size is determined at the narrowest point near the renal vein, followed by advancing the catheter to occlude the outflow vessels of the gastrorenal shunt. Retrograde venography assesses gastric varices and major collateral veins. Sclerosants or coils are then injected into these veins. The inflated balloon remains until abdominal radiography indicates stasis of the sclerosant, a process lasting up to 20 hours before removal.

Khakwani et al., (2023) [27] mentioned other modifications for BRTO currently in use that reduce the procedure time. Modifications include coil-assisted retrograde transvenous obliteration (CARTO), plug-assisted retrograde transvenous obliteration (PARTO), selective BRTO, and balloon-occluded antegrade transvenous obliteration (BATO). These modifications are used based on the type of gastric varix (portosystemic anatomy) and operator experience, which also play an important role. The difference between these modifications and BRTO is permanent obliteration of the shunt and use of a coil or vascular plugging. Selective BRTO also causes embolization of only the varices; therefore, it mitigates complications associated with the standard BRTO and uses fewer sclerosants. Its absolute contraindication is observed in patients with splenic and portal vein thrombosis, where it can lead to splenic ischemia by the accumulation of blood [27].

Also, other complications with BRTO use include abdominal pain, pyrexia, hemoglobinuria, pleural effusion, balloon rupture, renal impairment, shock, atrial fibrillation, and an increase in portal pressure after the procedure leading to exacerbated oesophageal varices and ascites occurrence [14,27]. Exacerbation of the oesophageal varices ranges from 30–68%, and this can be avoided by doing pre-shunt-occlusion endoscopy with prophylactic band ligation for the oesophageal varices present [24]. The sclerosant used for BRTO (ethanolamine oleate) has side effects that are related to the amount used for the procedure. These side effects include allergic reactions that can lead to cardiogenic shock, pulmonary infarction resulting from pulmonary embolism, renal dysfunction, and intravascular hemolysis, leading to hemoglobinuria in about 49–100% of the cases.

 

Tab. 2. Advantages and disadvantages of BRTO and TIPS.
Tab. 2. Výhody a nevýhody BRTO a TIPS.

TIPS	BRTO
technical                stent placement bypassing the liver and connecting the portal and systemic territory	occlusion of portosystemic shunt using sclerosing agents
advantages            reduce portal hypertension and other PH-related compli- cations (ascites, EV) can be used in patients with portal vein thrombosis	increase portal vein flow and may improve liver function does not increase HE
disadvantages         may induce hepatic failure and aggravate cardiac myopathy increase risk of post-procedure HE	increase portal hypertension and may aggravate EV and ascites cannot be performed in cases of portal vein thrombosis
HE – hepatic encephalopathy; PH – portal hypertension; EV – oesophageal varices

 

 

Transjugular intrahepatic portosystemic shunt (TIPS)

TIPS is an invasive surgical shunt that is used as salvage therapy for refractory gastric variceal hemorrhage or elective therapy (pre-emptive TIPS) for the prevention of gastric variceal rebleeding [14]. TIPS switches blood flow from the portal blood circulation through the inferior vena cava to the heart, thereby reducing portal pressure [27]. TIPS is the preferred treatment method for failed medical and endoscopic therapy, with the rate of hemostasis being 87–100% in acute refractory gastric variceal hemorrhage. Polytetrafluoroethylene (PTFE) --covered stent for the TIPS shunt is recommended [14] as covered stents have a more elevated potency rate [31] and are likely to improve survival rate [27].

Using TIPS alone is discouraged due to its limited efficacy, as evidenced by a 65% patency of the gastric varix, a rebleeding rate ranging from 13 to 53%, and a 15% 90-day mortality rate after sole TIPS placement [24,35]. Two theories explain this reduced effectiveness: the variability in the blood flow rate within the gastrorenal shunt, rendering large shunts unaffected by TIPS, and the location of common portal venous inflow vessels, with TIPS being less effective for gastric varices associated with dominant posterior gastric or short gastric veins [35]. Combining TIPS with gastric variceal embolization enhances TIPS efficacy [28].

However, TIPS use has drawbacks, leading to complications such as encephalopathy, myelopathy, and shunt stenosis. Shunt stenosis occurs in 18–82% of patients, with a 50% cumulative risk of encephalopathy within five years [23]. Depending on the anatomy of the variceal complex, a combination of endovascular therapies is more effective. For example, in Kiyosue Type C2, combining TIPS and shunt embolization gives a better outcome [24]. Tab. 2, as adapted by Luo and Hernández-Gea (2022) [28], compares the advantages of BRTO with TIPS.

A systematic review and meta-analysis done by Giri et al., (2023) [36] assessing eight gastric varices treatment modalities (endoscopic thrombin injection, endoscopic glue injection, endoscopic variceal band ligation, EUS-guided coil application, EUS-guided glue injection, EUS-guided coil plus glue application, TIPS, and BRTO) revealed that BRTO and EUS-guided coil plus glue application were the most effective in maximally obliterating gastric varices and reducing overall bleeding rates. Thrombin injection and EUS-guided coil application had the lowest expectation of moderate to severe adverse events. Additionally, EUS-guided coil plus glue application and TIPS showed the lowest likelihood of overall mortality.

 

Conclusion

Prevalence of gastric varices has still been relatively lower than oesophageal varices, even with increased investigative modalities, such as EUS-guided investigation. However, treatment of gastric varices is still varied, with no consensus on the preferred modality, though EUS-guided coil with glue injection has shown superior results in most studies.

 

Recommendation

Due to the low prevalence of gastric varices, collaborative studies across regions will help get a large sample size on the various treatment modalities to help reach a consensus on the management algorithm for gastric varices.