|Year : 2014 | Volume
| Issue : 4 | Page : 665-670
Stomach hemodynamics in liver cirrhosis
Ibrahim M Boghdadi1, Ehab A Abd El-atty1, Ashraf G Dala1, Ahmed S Kabeel2
1 Department of Internal Medicine, Faculty of Medicine, Menoufya University, Menoufya, Egypt
2 Department of Internal Medicine, Elbagour Hospital, Elmenofya, Egypt
|Date of Submission||09-Jan-2014|
|Date of Acceptance||10-Apr-2014|
|Date of Web Publication||22-Jan-2015|
Ahmed S Kabeel
Department of General medicine El-Bagour Hospital, Elmonofia
Source of Support: None, Conflict of Interest: None
A review of changes in stomach hemodynamics in patients with liver cirrhosis.
Data sources: medical text books, medical journals, and medical websites that have updated researches with key words (stomach hemodynamics) in the title of the paper.
Study selection: systematic reviews that addressed stomach hemodynamics and studies that addressed gastric vascular changes in liver cirrhosis.
Data extraction: a special search was conducted at midline with the key words stomach and hemodynamics in the title of the paper; extraction was performed, including the assessment of the quality and the validity of the papers that met with the prior criteria that describe the review.
Data synthesis: the main result of the review. Each study was reviewed independently; the data obtained were rebuilt in a new language according to the need of the researcher and arranged into topics through the article.
Transjugular intrahepatic portosystemic stentshunt or surgically created shunts are excellent salvage procedures. Over the next decade, the management of patients with varices may improve with the availability of additional pharmacological agents that specifically target intrahepatic circulation, improved endoscopic techniques, and a greater availability of liver transplantation.
Gastroesophageal varices should be treated as for esophageal varices, whereas fundal varices do not respond well to therapeutic modalities used in esophageal varices. Pharmacological therapies, presumably reducing portal pressure and gastric blood flow, have been used to treat acute bleeding. Transjugular intrahepatic portosystemic stentshunt and shunt surgery have not been analyzed extensively as a treatment for acute or chronic portal hypertensive gastropathy bleeding. Secondary prophylaxis of portal hypertensive gastropathy bleeding with nonselective b-blockers is recommended.
Keywords: Gastric varices, liver cirrhosis, portal hypertensive gastropathy, stomach hemodynamics
|How to cite this article:|
Boghdadi IM, Abd El-atty EA, Dala AG, Kabeel AS. Stomach hemodynamics in liver cirrhosis. Menoufia Med J 2014;27:665-70
| Introduction|| |
Most clinicians would agree that the pathophysiological mechanisms of varices are interrelated with the gastric mucosal changes of portal hypertension (PH), which is one of the major complications of chronic liver disease (CLD), resulting in the development of portosystemic collaterals that include esophageal and gastric varices (GV) and portal hypertensive gastropathy (PHG) .
Endoscopic evaluation of GV provides adequate information for diagnosis and management; cross-sectional imaging can be useful in certain special situations. Computed tomography (CT) portography, contrast-enhanced MR angiography, and multidetector CT have been used to determine the extraluminal extent of large GV and to determine completeness of obturation of the entire GV complex, particularly when balloon-occluded retrograde transvenous obliteration (BRTO) and its variations are used .
However, using noninvasive parameters including the platelet count (PC), the spleen size, and the PC/spleen diameter ratio are noninvasive methods for the assessment of the development of varices as alternatives to endoscopy .
| Materials and methods|| |
The guidance published by the Centre for Reviews and Dissemination was used to assess the methodology and outcomes of the studies. This review was reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement. The institutional review board and ethics committee approved this study.
A systematic search of several bibliographical databases was performed to identify relevant reports in any language. These included MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, TRIP database, Clinical Trials Registry, ISI Web of Knowledge, and Web of Science. Articles electronically published ahead of print were included. The search was performed in the electronic databases from the start of the database up to 2013.
All the studies were independently assessed for inclusion. They were included if they fulfilled the following criteria.
Participants: patients with liver cirrhosis.
Interventions: therapeutic modalities of treating hepatic fibrosis and PH with upper gastric endoscopy.
Outcomes: regression of PH and GVs.
If the studies did not fulfill the above criteria, they were excluded. Articles in non-English languages were translated. The article title and abstracts were screened initially, and then, the selected articles were read in full and further assessed for eligibility. All references from eligible articles were reviewed to identify additional studies.
Study quality assessment included whether ethical approval was gained, the prospective design, the specified eligibility criteria, whether appropriate controls were used, whether adequate follow-up was achieved, and defined outcome measures such as regression of liver cirrhosis and changes in gastric hemodynamics.
The quality of all the studies was assessed. Important factors included the prospective study design, attainment of ethical approval, evidence of a power calculation, the specified eligibility criteria, appropriate controls, specified outcome measures, and adequate follow-up. It was expected that confounding factors would be reported and controlled for and appropriate data analysis would be made in addition to an explanation of the missing data.
Because of the heterogeneity in postoperative follow-up periods and outcome measures reported, it was not possible to pool the data and perform a meta-analysis. Comparisons were made by a structured review.
| Results|| |
Transjugular intrahepatic portosystemic shunt (TIPS) or surgically created shunts are excellent salvage procedures. Over the next decade, the management of patients with varices may improve with the availability of additional pharmacological agents that specifically target the intrahepatic circulation, improved endoscopic techniques, more efficacious coated stents for TIPS, and a greater availability of liver transplantation.
| Discussion|| |
Hemodynamic principles and causes of portal hypertension
PH is a pathologic increase in the portal venous pressure gradient between the portal vein and the inferior vena cava. It results from changes in the portal resistance together with changes in the portal inflow as defined by Ohm's law:
P (pressure) = Q (blood flow) × R (resistance)
The mechanism of the increase in portal pressure depends on the site and the cause of PH, cirrhosis being the most common cause in the western world .
The diagnosis of PH can be made in several ways. Clinically, patients with cirrhosis can be diagnosed with PH by the presence of ascites, varices, or both. Imaging studies such as Doppler ultrasonography, CT, and MRI can also aid in diagnosing PH and in defining the anatomical features of the portal vein. Findings suggestive of PH include splenomegaly, portal vein dilation, portal vein occlusion, collateral vessel formation, decreasing PCs, and ascites with a serum-ascites-albumin gradient of 1.1 g/dl or more. However, these methods do not perform well in identifying subclinical PH, in delineating the type of PH, or in quantifying the extent of PH .
The gastric variceal system
This is a collective term that includes gastrorenal shunts (GRS) and GVs (central variceal part of the GVs) with or without the afferent portal venous feeders. The BRTO procedure for managing GVs is performed by placing a balloon in the GRS (usually distally) and refluxing the sclerosant into the GRS, the GVs, and possibly the afferent portal venous feeders. What is trapped and obliterated by the BRTO procedure is in essence the GVs or complex .
GVs can be divided into (a) an afferent (portal venous inflow) part, (b) a central variceal part, and (c) an efferent (systemic venous outflow) part.
Afferent (portal venous inflow) feeder(s)
These are the portal venous branches that come out of the splenic vein and supply the GVs. The central variceal part of the gastric variceal system is composed of true submucosal intragastric varices and false extragastric varices. The communication between the extragastric and the intragastric varices is a perforator vein or a varix.
Efferent systemic venous drainage
This can vary in complexity from the very simple (only a GRS) to multiple additional draining systemic veins (commonly the inferior phrenic vein or the pericardio-phrenic vein) that vary in significance .
Risk factors for bleeding esophagogastric varices
Bleeding from GVs is generally considered to be more severe than that from esophageal varices (EVs), but it occurs less frequently. We review the risk factors for bleeding EVs and GVs. GVs were divided into two groups: cardiac varices and fundal varices (FVs), that is, varices involving the fundus alone or varices involving both the cardia and the fundus. Elevated pressure in the portal vein and a large size of varices are risk factors for bleeding EVs. Red color signs are elevated red areas that are important for predicting the risk of variceal bleeding, and red wale markings, dilated venules oriented longitudinally on the mucosal surface, have been considered to be signs with the highest risk. Constipation, vomiting, severe coughing, and excessive consumption of alcohol may precipitate rupture of EVs .
Portal hypertensive gastropathy
PHG is a term used to define the endoscopic findings of a gastric mucosa with a characteristic mosaic-like pattern with or without red spots, a common finding in patients with PH; these endoscopic findings correspond to dilated mucosal capillaries without inflammation .
The pathogenesis of PHG is complex and many controversies exist. Although the pathogenesis of PHG is not completely understood, evidence suggests that the key factor for the development of PHG is PH .
Peripheral circulating endothelial cells (CEC) have been proposed as a prognostic marker in cardiovascular diseases. Cirrhosis and PH are associated with vascular injury, and yet little is known about the CEC count under these conditions. The CEC count and the PC were evaluated in patients with cirrhosis and correlated with markers of PH/disease severity. The median CEC count and the CEC/PC ratio are significantly elevated in patients with cirrhosis. CEC/PC increased in patients with decompensated cirrhosis. These data provide a rationale for larger validation studies to assess whether CEC may have prognostic utility in patients with cirrhosis and PH .
Vascular anatomy and hemodynamics of gastric varices
Spontaneous portosystemic splenorenal or GRS commonly develop between the splenic vein (splenorenal shunt) or GVs, respectively, and connect through the inferior phrenic or the suprarenal vein to the left renal vein. Such shunts, collectively termed GRS, are more common in GV (60-85% of cases) than in EV (17-21% of cases). Precisely what determines the predominant collateral pathways that develop in a given individual with PH remains unknown; however, the size and the length of the potential collateral vessel are likely to play a role .
Clinical presentation and the natural history of gastric varices
GV are discovered most commonly during the screening of PH patients for varices or at the time of the first variceal bleeding, at which time the bleeding is usually caused by associated EV and uncommonly originates from bleeding GV. A number of patients with GV may also present with hepatic encephalopathy .
Diagnosis of portal hypertension and gastric varices
PH is suspected clinically in a patient with stigmata of CLD such as jaundice, spider nevi, palmer erythema, Dupuytren contractures, gynecomastia, testicular atrophy, and splenomegaly. Caput medusae, which are dilated veins around the umbilicus, suggest an intrahepatic cause of PH. The presence of ascites with splenomegaly makes the presence of EVs even more likely. A bruit may be heard in the left or the right upper quadrant in patients with a splanchnic arteriovenous fistula as a cause of PH, whereas a venous hum in the epigastrium represents collateral flow in the falciform ligament. Alterations in the mental status and asterixis, although rarely presenting findings, may be evident; laboratory studies also usually reveal evidence of hepatic dysfunction .
Clinical predictors of varices and portal hypertensive gastropathy in patients with chronic liver disease
Yang et al.  analyzed retrospectively 232 patients with CLD who underwent both upper endoscopy and liver CT within an interval of 3 months. The multidimensional index (M-Index) for the spleen volume was obtained from the multiplication of the splenic length, width, and thickness, as measured by CT. The multivariate analysis revealed that platelet, albumin, and the M-Index were independently associated with the presence of varices and PHG. They combined three independent parameters and developed a varices and PHG (VAP) scoring system=[platelet count (/mm 3 )×albumin (g/dl)]/[M-Index (cm 3 )]. The area under the receiver operating characteristic curve of the VAP score was 0.850 (95% confidence interval, 0.801-0.899). A VAP cut-off value of 861 had a sensitivity of 85.3%, a positive likelihood ratio of 3.17, and a negative predictive value of 86.4%. For predicting high-risk lesions for bleeding, with a cut-off value of 861, the sensitivity was 92.0%, the positive likelihood ratio was 2.20, and the negative predictive value was 96.4% .
Diagnostic imaging of gastric varices
Endoscopic ultrasonography is considered to be very useful in the evaluation of GVs, whereas MRI and CT allow the assessment of the entire portal venous system ,.
In contrast, esophagogastroduodenoscopy is considered as the gold standard for the diagnosis of gastroesophageal varices .
Treatment of portal hypertensive gastropathy and gastric varices
Pharmacological therapy consists of splanchnic vasoconstrictors (vasopressin and analogues, somatostatin and analogues, nonselective b-blockers) and venodilators (nitrates). Vasoconstrictors act by producing splanchnic vasoconstriction and by reducing portal venous inflow. Venodilators theoretically act by decreasing intrahepatic and/or portocollateral resistance. However, all available venodilators (e.g. isosorbide mononitrate) have a systemic hypotensive effect, and the decrease in portal pressure appears to be more related to hypotension (i.e. a decrease in flow) rather than to a decrease in resistance .
The commonly used Sengstaken-Blakemore or Minnesota tubes are not usually efficacious in controlling bleeding from FVs owing to the small volume of the gastric balloon (200 ml). The Linton-Nachlas tube has a 600 ml volume single gastric balloon and seems to be more effective in controlling fundal variceal bleeding in up to 50% of the patients, although 20% will rebleed subsequently .
Traditional variceal sclerotherapy involves the injection of sclerosants such as ethanolamine olate or absolute alcohol intravariceally or perivariceally (or both), resulting in endothelial damage and thrombosis of blood and subsequent sclerosis of the varix. However, this has been very successful in the treatment of EV bleeding and in the eradication of EV .
Compared with endoscopic injection sclerotherapy or esophageal variceal ligation (EVL), endoscopic variceal obturation with a tissue adhesive such as N-butyl-cyanoacrylate or isobutyl-2-cyanoacrylate is more effective for acute fundic gastric variceal bleeding. The results include a better rate of controlling the initial hemorrhage and a lower rebleeding rate. A relatively large prospective randomized trial that compared gastric variceal obturation with N-butyl-cyanoacrylate against EVL in patients with acute gastric variceal hemorrhage demonstrated that the control rate of active bleeding was similar in both groups ,.
Ramesh and colleagues also reported their experience with the use of human thrombin in 13 patients. Interestingly, the rates of hemostasis and rebleeding from GVs were 92 and 0%, respectively. Thrombin may leak into the systemic circulation in the case of GVs with a high flow volume and associated with a giant gastrorenal shunt. Intravascular injection of thrombin could then induce disseminated intravascular coagulation or pulmonary embolism .
Beriplast P consists of two components: fibrinogen with factor VIII and human thrombin. Beriplast P has been used with the aim of achieving hemostasis against intra-abdominal oozing during surgery. The procedure requires a double-lumen injector to mix the two contents simultaneously on the surface of the bleeding tissue. There are two uncontrolled studies that have been reported recently, showing the efficacy of Beriplast P in patients with gastric variceal bleeding .
Transjugular intrahepatic portosystemic shunt
TIPS is used in cirrhotic patients with liver failure and bleeding EVs as a bridging method until they are able to undergo liver transplantation. It has not been recognized as the first-line therapy for gastric variceal bleeding. However, when uncontrolled bleeding from GVs with endoscopic or pharmacologic treatment are encountered, TIPS might be a choice for salvage treatment. It has been reported that the control rate of gastric variceal bleeding with TIPS is over 90% .
A meta-analysis revealed significantly better survival and significantly less frequent shunt failure in patients undergoing surgical shunting compared with TIPS .
Devascularization of the upper stomach with splenectomy
Splenectomy was not recommended previously in younger patients because of the overwhelming postsplenectomy infection, a potentially rapidly fatal septicemia. However, surgical technology and vaccination (for example against pneumococcus) has recently developed to the extent that these problems are now largely resolved. The non-rebleeding rate of 100% over a 5-year follow-up shows that this operation could be the most reliable and promising procedure of a salvage therapy for uncontrolled gastric variceal bleeding .
Balloon-occluded retrograde transvenous obliteration
BRTO has been developed and established as a superior effective treatment for fundic GVs and hepatic encephalopathy in Japan .
Argon plasma coagulation has also been combined with EVL to prevent variceal recurrence. Recently, a randomized trial was conducted and it was established that band ligation plus argon plasma coagulation allows for very rapid eradication of varices and a low recurrence rate, with no obvious recorded complications, but it has the disadvantage of being the most expensive technique and requires special equipment that is available only in a few endoscopic centers .
A new surgical approach is laparoendoscopic transgastric histoacryl injection of GVs: this new technique enables us to inject GV with a suitable amount of glue material under direct vision without harming the endoscope. The use of this procedure is recommended in patients fit for surgery and in those who have failed endoscopic injection sclerotherapy  [Table 1] and [Table 2].
|Table 2: Current therapies and their effect on the portal venous inflow, the portal resistance, and the portal pressure |
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According to the evidence derived from this study, we recommend that early diagnosis and control of PH and liver cirrhosis will lead to better control and less complications of gastric varices and hematemesis and less morbid drawbacks in hepatic patients.
| Conclusion|| |
GOV1 should be treated as for EV, whereas FVs do not respond well to therapeutic modalities used in EV. Pharmacological therapies, presumably reducing portal pressure and gastric blood flow, have been used to treat acute bleeding: propanolol, a nonselective b-blocker, has been used most frequently. TIPS and shunt surgery have not been analyzed extensively as a treatment for acute or chronic PHG bleeding, but they appear to decrease the severity of PHG. Secondary prophylaxis of PHG bleeding with nonselective b-blockers is recommended.
| Acknowledgements|| |
The authors thank all supervisors and participants.
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]