5,557

Non-Invasive Predictors of Moderate–Large Esophageal Varices in Compensated Cirrhotic Patients

Irsan Hasan1, Chyntia Olivia Maurine Jasirwan1, Imelda Maria Loho2, Saut Horas Hatoguan Nababan1, Steven Zulkifly1, Anugrah Dwi Handayu1

1 Hepatobiliary Division, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia, Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia;
2 Department of Gastroenterology and Hepatology, “Dharmais” Hospital, Indonesian National Cancer Center, Jakarta, Indonesia.

Conflict-of-interest statement: The author(s) declare(s) that there is no conflict of interest regarding the publication of this paper.

Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http: //creativecommons.org/licenses/by-nc/4.0/

Correspondence to: Irsan Hasan, Hepatobiliary Division, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia, Cipto Mangunkusumo National General Hospital, Jalan Diponegoro No. 71, Central Jakarta, Indonesia, 10430.
Email: irsan_h@yahoo.com
Telephone: +62-21-31900924

Received: February 25, 2021
Revised: March 15, 2021
Accepted: March 18, 2021
Published online: April 21, 2021

ABSTRACT

Aim: to identify a non-invasive and low-cost tool that could predict the presence of moderate-to-large EV in compensated cirrhotic patients to lower the number of unnecessary endoscopies.

Materials and Methods: A cross-sectional study was conducted in newly diagnosed patients with non-Child-Pugh C liver cirrhosis, without a history of variceal bleeding. The presence and degree of esophageal varices were determined during endoscopy. Univariate and multivariate logistic regression were used to identify independent predictors for the presence of esophageal varices.

Results: Of the 180 patients enrolled in this study, EV was found in 99 patients (55%). Moderate-large varices were detected in 23.3% and 51.7% of patients with CP-A and CP-B class, respectively. In univariate analysis, CP class B, low platelet count (≤ 100 000/μL), increased bipolar diameter (≥ 135 mm), and ratio of platelet count to bipolar spleen diameter (≤ 847) were associated with the presence of moderate-to-large EV. In multivariate analysis, CP class and ratio of platelet count to bipolar spleen diameter were associated with the presence of moderate-to-large EV. The AUC, sensitivity, and specificity of combined predictors were 0.76, 88% and 55.4%, respectively.

Conclusion: Platelet count/bipolar spleen diameter ratio value of ≤ 847 could be used as a non-invasive predictor of the presence of moderate-to-large EV in compensated cirrhotic patients. Future validation in a larger cohort is needed before applying this parameter in clinical practice.

Key words: Non-invasive predictors; Compensated cirrhosis; Esophageal varices

© 2021 The Author(s). Published by ACT Publishing Group Ltd. All rights reserved.

Hasan I, Jasirwan COM, Loho IM, Nababan SHH, Zulkifly S, Handayu AD. Non-Invasive Predictors of Moderate–Large Esophageal Varices in Compensated Cirrhotic Patients. Journal of Gastroenterology and Hepatology Research 2021; 10(2): 3478-3482 Available from: URL: http://www.ghrnet.org/index.php/joghr/article/view/3105

INTROUDUCTION

Esophageal varices (EV) is a severe complication of portal hypertension in liver cirrhotic patients. In newly diagnosed liver cirrhotic patients, more than 50% of patients had EV during screening procedure. The incidence rate of varices in this population is 4.5% per year[1,2]. The presence of EV has been associated with the degree of severity in liver cirrhosis. The prevalence of EV in cirrhotic patients with compensated and decompensated cirrhosis were 30% and 60%, respectively[3]. The progression rate from small to moderate large size varices was 12% and 31% at 1 and 3 years, respectively. The increase of variceal diameter was associated with elevated pressure on the varices wall, which was at a critical point resulting in rupture and life-threatening bleeding[4].

Approximately 20% of patients with EV had a minimum of one episode of variceal hemorrhage (VH) in one year after the diagnosis of EV. The North Italian Endoscopic Club (NIEC) index has been developed to predict the risk of first variceal hemorrhage episode in cirrhotic patients. It includes three variables, i.e. CP class, size of varices, and severity of red wale marks[5]. The mortality rate due to the bleeding episode varies from less than 10% in CP-A class to more than 33% in CP-C liver cirrhotic patients[6].

Due to the high mortality rate of VH, prevention of variceal bleeding is one of the primary goals of the management of liver cirrhotic patients. Screening of EV and gastric varices (GV) through esophagogastroduodenoscopy (EGD) is currently recommended for all newly diagnosed liver cirrhotic patients, as stated in Practice Guidance by the American Association for the Study of Liver Diseases (AASLD) and World Gastroenterology Organisation (WGO) Global Guidelines[7,8]. However, in daily clinical practice, only 40% of patients with compensated cirrhosis are found to have EV[9]. Furthermore, EGD screening is also an invasive and costly procedure. Due to the high risk of bleeding in moderate-to-large EV, a non-invasive and cost-effective examination is needed to predict the presence of moderate-to-large EV in non-CP-C liver cirrhotic patients.

MATERIALS AND METHODS

Study Design and Sample Size

A cross-sectional study was conducted to determine the predictors of EV in cirrhotic patients classified as CP-A and CP-B. Data was collected in the Hepatology Clinic and Integrated Procedure Room of the Hepatobiliary Division of our hospital between June 2017 and June 2018. The minimal sample size was calculated using rule of thumbs method (10 samples for each variable)[10]. As many as seven potential parameters were used in this study, therefore a minimum of 70 subjects were recruited to perform a multivariate analysis.

Patients

All liver cirrhotic patients classified as CP-A or CP-B classes, aged 18 years or older, and who would undergo EGD procedure for EV screening, were included. The exclusion criteria in this study were: (1) patients who had a history of upper gastrointestinal bleeding, propranolol or other beta-blocker consumption, and previous EGD procedure; (2) patients who were administered blood transfusion within four weeks before blood sampling was performed; and (3) patients with hepatocellular carcinoma (HCC), aplastic anemia, idiopathic thrombocytopenia purpura (ITP), and other hematologic disorders causing thrombocytopenia. Informed consent letters were obtained from each patient who participated in this study. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation by local ethic committee of the Faculty of Medicine Universitas Indonesia and with the Helsinki Declaration of 1975, as revised in 2000.

Diagnosis and Classification of Cirrhosis

Diagnosis of cirrhosis was established based on: (1) stigmata of cirrhosis (spider naevi, palmar erythema, gynecomastia, ascites, splenomegaly) on physical examination; (2) characteristic findings of liver cirrhosis (heterogenous liver echostructure, nodular liver surface, widening of portal and splenic vein, narrowing of hepatic vein) on ultrasound (US); and (3) fibrosis stage F4 on transient elastography (FibroScan®) examination. The CP scoring system was used to assess the degree of severity and survival rate of cirrhotic patients. Child-Pugh class was determined by five parameters (serum bilirubin, serum albumin, international normalized ratio (INR) value, presence of ascites, and presence of encephalopathy) and classified into three classes according to the CP total score, including (1) CP class A (5-6); (2) CP class B (7-9) and (3) CP class C (10-15).

Grading of Esophageal Varices

According to EGD findings, EV was classified into three categories: (1) small varices, which appear as slight protrusion above the esophageal mucosal surface; (2) moderate-sized varices, which occupy < 1/3 of the esophageal lumen, and (3) large-sized varices, which occupy >1/3 lumen of the esophagus. In this study, we categorized the EV findings into two groups. The first group is no-to-small varices group and the other is moderate-to-large varices group.

Spleen bipolar diameter and portal vein diameter: Spleen bipolar diameter and portal vein diameter were determined by ultrasound and expressed in millimeters (mm). Platelet count was obtained from venous blood sample mixed with EDTA anticoagulant. The ratio of platelet count/spleen bipolar diameter was calculated by dividing platelet count (n/μL) with spleen bipolar diameter (mm).

Data Analysis

All normally distributed numerical data was presented in mean and standard deviation or in median and range if not normally distributed. Categorical data was presented in absolute and relative frequencies. Univariate analysis was performed with Chi-Square test or Fisher’s exact test. All predictors with p-value less than 0.2 in univariate analysis were included in multivariate analysis with logistic regression method. All predictors with p-value less than 0.5 in multivariate analysis were considered statistically significant. All data was analyzed with SPSS 20.0 statistical package.

RESULTS

Clinical characteristics of the patients

As many as 180 cirrhotic patients with CP class A and B were enrolled between June 2017 and February 2020. Of these patients, 120 patients were classified into CP class A and 60 patients were classified as CP class B. Baseline characteristics are shown in Table 1. The majority of patients were male and the most common etiologies of cirrhosis were hepatitis B and hepatitis C.

Esophageal varices events in cirrhotic patients

Esophageal varices were detected in 46.7% and 71,7% of patients with CP class A and B, respectively. Large varices were found in 25 of 120 patients (20.8%) with CP class A and 27 of 60 patients (45%) with CP class B. The prevalence of EV and their grading are shown in Table 2. As moderate-large varices were treated equally in clinical practice, patients with moderate and large varices were classified as one group for the analysis.

Table 1 Baseline characteristics of the study participants.
Variables Esophageal varices (moderate-large) (n=59) Esophageal varices (no or mild) (n=121)
Sex: n (%)  
Male38 (64.4)81 (66.9)
Age (years), median (range)50 (34-74 years)57 (22-88 years)
Etiology: n (%)  
Hepatitis B28 (47.5)50 (41.3)
Hepatitis C21 (35.6)61 (50.4)
Hepatitis B and C2 (3.4)1 (0.8)
NASH1 (1.7)1 (0.8)
Autoimmune Hepatitis1 (1.7)1 (0.8)
Non B and Non C5 (8.5)7 (5.2)
Unknown1 (1.7)0 (0)
Child Pugh Classification: n (%)  
A28 (47.5)92 (76)
B31 (52.5)29 (24)
Hemoglobin: median (range) (g/dL)11.30 (7.50-16.50)13.40 (7.20-17.0)
Leucocyte: mean (SD)(103/µL)4.69 (2.20-9.70)6.29 (2.28)
Platelet: median (range) (103/µL)81 (20-280)134 (33-640)
INR: median (range)1.02 (0.96-1.55)1.0 (0.87-10.90)
Albumin: median (range) (g/dL)3.34 (1.94-4.60)4.0 (2.13-6.20)
Bilirubin: median (range) (mg/dL)1.53 (0.40-8.65)1.01 (0.21-6.12)
Portal vein diameter: mean (SD) (mm)11.90 (3.26)11.13 (2.55)
Spleen bipolar diameter: mean (SD) (mm)138.88 (25.84)117.55 (25.03)

Table 2 Esophageal Varices and Grading in CP-A and CP-B Patients.
Variables Child-Pugh A (n=120) Child-Pugh B (n=60)
Esophageal Varices, n (%)
No64 (53.3)17 (28.3)
Yes56 (46.7)43 (71.7)
Esophageal Varices Grading, n (%)
Normal64 (53.3)17 (28.3)
Small28 (23.3)12 (20)
Moderate 3 (2.5)4 (6.7)
Large25 (20.8)27 (45)

Factors Associated with Moderate – Large EV in Cirrhotic Patients

In univariate analysis, the presence of moderate-to-large grade of EV in cirrhotic patients was associated with Chile-Pugh class B, low platelet count (≤ 100,000/µL), increased bipolar spleen diameter (≥ 135 mm), and ratio of platelet count to bipolar spleen diameter ≤ 847, as shown in Table 3. In multivariate analysis, CP class and platelet count/bipolar spleen diameter ratio were associated with the presence of moderate-large EV in cirrhosis (Table 4). The area under the curve (AUC) of CP class and ratio of platelet count/bipolar spleen diameter was 0.76 (p = 0.001; 95% CI 0.70-0.84), with sensitivity and specificity of 88% and 55.4%, respectively (Figure 1).

Figure 1 Receiver-operating curves (ROC) of platelet count/bipolar spleen diameter ratio for prediction of moderate-large esophageal varices (estimated AUC = 0.76; 95% CI 0,70-0,84).

Table 3 Univariate analysis of factors associated with moderate-large esophageal varices.
VariablesOR (95% CI)p-value
Sex  
Female1-
Male0.89 (0.47-1.72)0.865
Age  
< 50 years1-
≥ 50 years0.51 (0.27-0.97)0.055
Child Pugh Class  
A1-
B3.51 (1.82-6.79)<0.001
Platelet count  
> 100.000 /µL1-
≤ 100.000 /µL3.97 (2.06-7.65)<0.001
Portal Vein Diameter  
< 13 mm1-
≥ 13 mm1.94 (0.99-3.77)0.074
Bipolar Spleen Diameter  
< 135 mm1-
≥ 135 mm5.50 (2.78-10.88)<0.001
Platelet count / bipolar spleen diameter ratio  
< 847 mm1-
≥ 847 mm6.17 (3.07-12.41)<0.001

Table 4 Predictors of the presence of moderate-large EV in cirrhosis.
PredictorsOR (95% CI)p-value
Child-Pugh class B 2.80 (1.37-5.70)0.005
Rasio of platelet to bipolar spleen diameter 5.39 (2.63-11.02)<0.001

DISCUSSION

Liver cirrhosis is an irreversible fibrosis or scarring process in the liver due to chronic inflammation, which represents the late stage of chronic liver disease. The cirrhotic process is initiated by asymptomatic compensated condition, which is followed by decompensated cirrhosis as the disease progresses. In compensated cirrhosis, the portal pressure is relatively normal or slightly elevated. Ascites, encephalopathy, jaundice, and EV were developed in decompensated cirrhosis due to elevated portal pressure (portal hypertension) and reduced liver function[11].

Of the 75 patients with EV, moderate-large varices were found in 23 patients with CP-A and 23 patients with CP-B class. Child-Pugh classification has been developed to predict the survival rate of liver cirrhotic patients and categorize the degree of severity in liver function[12]. In multivariate analysis, there is a statistical significant difference of CP class and patients with CP class B had 3.34 higher risk of developing EV. These results coincide with the results of studies by Sumon et al[13], Thapa et al[14], and Ashraf et al[15].

Several non-invasive parameters have been extensively studied to predict the presence of EV, including platelet count, spleen diameter size, platelet count/spleen diameter ratio, portal vein diameter and degree of ascites. However, none of the above provide consistent results in predicting the presence of EV. In multivariate analysis, the ratio of platelet count / bipolar spleen diameter was associated with moderate-large sized of EV during EGD screening.

AASLD recommends the combination of liver stiffness measurement with transient elastography (TE) and platelet count as non-invasive test in the diagnosis of gastroesophageal varices, in order to exclude patients with low risk of having moderate–large varices[7]. However, the availability of TE tools is limited in developing countries, including Indonesia. Sharma SK et al found low platelet count as an independent predictor of the presence of large varices, besides palpable spleen. Patients with platelet count >105 000/μL had 80% probability for the absence of large EV, with an AUC of 0.76[16]. Different results were shown by Qamar et al[17] who found that platelet count of less than 100 000/μL could not be used as a non-invasive predictor of EV. In this study, plalelet count of less than 100 000/μL was found associated with the presence of moderate-large EV.

Thrombocytopenia is one of the most common complications in patients with chronic liver disease. There are three basic mechanisms for low platelet clount in cirrhosis patients, including reduced production, increased destruction, and sequestration. The sequestration process is initiated with portal hypertension which resulted in enlarged spleen and splenic sequestration of platelets. The most common mechanism of reduced platelet production is the reduction of thrombopoietin (TPO), a hemapoietic growth factor produced primarily in the liver. Other etiologies are bone marrow supression by viral infection, particulary HCV and the adverse effect of antiviral treatment, especially interferon-based therapy. The increased destruction of platelet is caused by shear stress, bacterial translocation, sepsis, and hyperfibrinolysis[18,19].

Enlarged spleen was often observed in liver cirrhotic patients and was associated with a higher risk of complications related to portal hypertension. The spleen diameter was significantly increased in decompensated cirrhosis, as compared to compensated cirrhosis[20]. A systematic review reported bipolar spleen diameter >150 mm in ultrasonography examination might be used as an alternative tool for VE diagnosis in liver cirrhosis[21]. Several mechanisms of splenomegaly have been known, such as portal congestion, fibrosis, and tissue hyperplasia[22].

The use of the ratio of low platelet count/spleen bipolar diameter to predict the presence of EV in cirrhotic patients was first proposed by Giannini et al[23]. in 2003. They found that application of platelet count alone could be misleading and that platelet count/spleen bipolar diameter ratio was the only predictor independently associated with the presence of EV. The negative predictive value (NPV) of the value of platelet count/spleen bipolar diamter ratio of 909 was 100%, in order to predict the presence of EV. A recent meta-analysis reported the use of platelet count to spleen diameter ratio with a cutoff value of 909 showed the AUC value for any varices was 0.88. Cirrhotic patients with ratio < 909 are recommended to be evaluated with EGD procedure[24].

Abu El Makarem et al[25]. used a different cut-off value of platelet count/spleen diameter ratio. With a cut-off value of 939.7, the AUC, sensitivity, and specificity were 0.84, 100%, 86.3%, respectively. Another study from Baig et al[26] applied the cut-off value of 1014, with AUC value, sensitivity, and specificity as high as 0.94, 98.1%, and 86%, respectively. In our study, a lower cut-off value of 847 was established. It is probable that the difference is due to the different characteristic of the study population. The patient selection in our study was limited to cirrhotic patients with CP class A and B, instead of any CP class. A lower cut-off is needed to select those patients with CP class A or B, who do not need endoscopy screening at diagnosis of cirrhosis.

In summary, our results indicate that ratio of platelet count to bipolar spleen diameter of ≤ 847 could be used as a non-invasive predictor of the presence of moderate-large EV in compensated cirrhotic patients. However, our findings need to be validated in other cohort with a larger number of samples before any application in clinical practice.

Funding

This work was funded by the Operational Research’s Grant of Cipto Mangunkusumo Hospital 2017.

REFERENCES

1. Merli M, Nicolini G, Angeloni S, Rinaldi V, De Santis A, Merkel C, Attili AF, Riggio O. Incidence and natural history of small esophageal varices in cirrhotic patients. Journal of hepatology. 2003; 38(3): 266-72. [DOI: 10.1016/s0168-8278(02)00420-8].

2. D’Amico G, Pasta L, Madonia S, Tarantino IG, Mancuso A, Malizia G, Giannuoli GC, Pagliaro L. The incidence of esophageal varices in cirrhosis. Gastroenterology. 2001; 120(5): A2.

3. de Franchis R, Primignani M. Natural history of portal hypertension in patients with cirrhosis. Clinics in liver disease. 2001; 5(3): 645-63. [DOI: 10.1016/s1089-3261(05)70186-0].

4. Kovalak M, Lake J, Mattek N, Eisen G, Lieberman D, Zaman A. Endoscopic screening for varices in cirrhotic patients: data from a national endoscopic database. Gastrointestinal endoscopy. 2007; 65(1): 82-8. [PMID: 17185084]. [DOI: 10.1016/j.gie.2006.08.023].

5. Prediction of the first variceal hemorrhage in patients with cirrhosis of the liver and esophageal varices. A prospective multicenter study. The New England journal of medicine. 1988; 319(15): 983-9. [PMID: 3262200]. [DOI: 10.1056/nejm198810133191505].

6. Fortune BE, Garcia-Tsao G, Ciarleglio M, Deng Y, Fallon MB, Sigal S, Chalasani NP, Lim JK, Reuben A, Vargas HE, Abrams G, Lewis MD, Hassanein T, Trotter JF, Sanyal AJ, Beavers KL, Ganger D, Thuluvath PJ, Grace ND, Groszmann RJ. Child-Turcotte-Pugh Class is Best at Stratifying Risk in Variceal Hemorrhage: Analysis of a US Multicenter Prospective Study. Journal of clinical gastroenterology. 2017; 51(5): 446-53. [PMID: PMC5403609]. [DOI: 10.1097/mcg.0000000000000733].

7. Garcia-Tsao G, Abraldes JG, Berzigotti A, Bosch J. Portal hypertensive bleeding in cirrhosis: Risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the study of liver diseases. Hepatology (Baltimore, Md). 2017; 65(1): 310-35. [PMID: 27786365]. [DOI: 10.1002/hep.28906].

8. LaBrecque D, Khan AG, Sarin SK, Le Mair AW. World Gastroenterology Organisation Global Guidelines: Esophageal Varices Milwaukee: World Gastroenterology Organisation; 2014 [Available from: https: //www.worldgastroenterology.org/guidelines/global-guidelines/esophageal-varices/esophageal-varices-english.

9. Schepis F, Cammà C, Niceforo D, Magnano A, Pallio S, Cinquegrani M, D’Amico G, Pasta L, Craxì A, Saitta A, Raimondo G. Which patients with cirrhosis should undergo endoscopic screening for esophageal varices detection? Hepatology (Baltimore, Md). 2001; 33(2): 333-8. [PMID: 11172334]. [DOI: 10.1053/jhep.2001.21410].

10. Austin PC, Steyerberg EW. The number of subjects per variable required in linear regression analyses. J Clin Epidemiol. 2015; 68(6): 627-36. [PMID: 25704724]. [DOI: 10.1016/j.jclinepi.2014.12.014].

11. D’Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J Hepatol. 2006; 44(1): 217-31. [PMID: 16298014]. [DOI: 10.1016/j.jhep.2005.10.013].

12. Durand F, Valla D. Assessment of the prognosis of cirrhosis: Child-Pugh versus MELD. J Hepatol. 2005; 42 Suppl(1): S100-7. [PMID: 15777564]. [DOI: 10.1016/j.jhep.2004.11.015].

13. Sumon SM, Sutradhar SR, Chowdhury M, Khan NA, Uddin MZ, Hasan MI, Rozana FK, Haque MF, Barman TK, Ferdous J. Relation of different grades of esophageal varices with Child-Pugh classes in cirrhosis of liver. Mymensingh Med J. 2013; 22(1): 37-41. [PMID: 23416806].

14. Thapa P, Maharjan D, Tamang T, Shrestha S. Clinical correlation between Child Pugh’s score and oesophageal varices in upper gastrointestinal endoscopy in cirrhotic patient. J Kathmandu Med Coll. 2017; 4(4): 135-9.

15. Ashraf D, El-Sayed I. Esophageal varices predictive score in liver cirrhosis. The Egyptian Journal of Internal Medicine. 2018; 30(2): 72-7. [DOI: 10.4103/ejim.ejim_85_17].

16. Sharma SK, Aggarwal R. Prediction of large esophageal varices in patients with cirrhosis of the liver using clinical, laboratory and imaging parameters. J Gastroenterol Hepatol. 2007; 22(11): 1909-15. [PMID: 17914969]. [10.1111/j.1440-1746.2006.04501.x].

17. Qamar AA, Grace ND, Groszmann RJ, Garcia-Tsao G, Bosch J, Burroughs AK, Maurer R, Planas R, Escorsell A, Garcia-Pagan JC, Patch D, Matloff DS, Makuch R. Platelet count is not a predictor of the presence or development of gastroesophageal varices in cirrhosis. Hepatology (Baltimore, Md). 2008; 47(1): 153-9. [PMID: 18161700]. [DOI: 10.1002/hep.21941].

18. Afdhal N, McHutchison J, Brown R, Jacobson I, Manns M, Poordad F, Weksler B, Esteban R. Thrombocytopenia associated with chronic liver disease. J Hepatol. 2008; 48(6): 1000-7. [PMID: 18433919]. [DOI: 10.1016/j.jhep.2008.03.009].

19. Mitchell O, Feldman DM, Diakow M, Sigal SH. The pathophysiology of thrombocytopenia in chronic liver disease. Hepat Med. 2016; 8: 39-50. [PMID: PMC4847598]. [DOI: 10.2147/hmer.S74612].

20. Berzigotti A, Zappoli P, Magalotti D, Tiani C, Rossi V, Zoli M. Spleen enlargement on follow-up evaluation: a noninvasive predictor of complications of portal hypertension in cirrhosis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2008; 6(10): 1129-34. [PMID: 18619917]. [DOI: 10.1016/j.cgh.2008.05.004].

21. Binţinţan A, Chira RI, Mircea PA. Non-invasive ultrasound-based diagnosis and staging of esophageal varices in liver cirrhosis. A systematic review of the literature published in the third millenium. Med Ultrason. 2013; 15(2): 116-24. [PMID: 23702501]. [DOI: 10.11152/mu.2013.2066.152.ab1ric2].

22. Bolognesi M, Merkel C, Sacerdoti D, Nava V, Gatta A. Role of spleen enlargement in cirrhosis with portal hypertension. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2002; 34(2): 144-50. [PMID: 11926560]. [DOI: 10.1016/s1590-8658(02)80246-8].

23. Giannini E, Botta F, Borro P, Risso D, Romagnoli P, Fasoli A, Mele MR, Testa E, Mansi C, Savarino V, Testa R. Platelet count/spleen diameter ratio: proposal and validation of a non-invasive parameter to predict the presence of oesophageal varices in patients with liver cirrhosis. Gut. 2003; 52(8): 1200-5. [PMID: PMC1773759].

24. Chen R, Deng H, Ding X, Xie C, Wang W, Shen Q. Platelet Count to Spleen Diameter Ratio for the Diagnosis of Gastroesophageal Varices in Liver Cirrhosis: A Systematic Review and Meta-Analysis. 2017; 2017: 7407506. [DOI: 10.1155/2017/7407506].

25. Abu El Makarem MA, Shatat ME, Shaker Y, Abdel Aleem AA, El Sherif AM, Moaty MA, Abdel Ghany HS, Elakad A, Kamal Eldeen AM. Platelet count/bipolar spleen diameter ratio for the prediction of esophageal varices: The special Egyptian situation: Noninvasive prediction of esophageal varices. Hepatitis Monthly. 2011; 11(4): 278-84. [PMID: PMC3206702].

26. Baig WW, Nagaraja MV, Varma M, Prabhu R. Platelet count to spleen diameter ratio for the diagnosis of esophageal varices: Is it feasible? Can J Gastroenterol. 2008; 22(10): 825-8. [PMID: PMC2661302]. [DOI: 10.1155/2008/287274].

Refbacks

  • There are currently no refbacks.


Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.