Non-invasive diagnosis of esophageal varices in chronic liver diseases

Current guidelines recommend esophagogastroduodenoscopy (EGD) in patients with cirrhosis to screen for gastroesophageal varices (GEV). Thrombocytopenia has been proposed as a noninvasive test to predict the presence of GEV. There is no agreement regarding a specific platelet count (PLT) that can reliably predict GEV. The present longitudinal study aims to (1) further investigate the relationship between varices and PLT at the time of endoscopy, (2) investigate whether changes in PLT from the baseline over time can predict the development of GEV, and (3) investigate whether changes in PLT correlate with the hepatic venous pressure gradient (HVPG). A secondary analysis was conducted for 213 subjects with compensated cirrhosis with portal hypertension but without GEV enrolled in a randomized, placebo-controlled, double-blind trial of a nonselective beta-blocker used to prevent GEV. PLTs were obtained every 3 months, and HVPG measurements and EGD were done annually. The PLTs were compared between subjects who did and did not develop GEV. In a median follow-up of 54.9 months, 84 patients developed GEV. PLT was greater than 150,000 in 15% of patients at the development of GEV. A receiver operating curve did not show any PLT with high sensitivity or specificity for the presence of GEV. Subjects with clinically insignificant portal hypertension (HVPG < 10 mm Hg) whose PLT remained greater than 100,000 had a 2-fold reduction in the occurrence of GEV (P ‫؍‬ 0.0374). A significant correlation was found between HVPG and PLT at the baseline, year 1, and year 5 (P < V ariceal hemorrhage is a leading cause of morbidity and mortality in cirrhosis. 1-3 Primary prophylaxis with nonselective beta-blockers and endoscopic therapy with band ligation are effective in preventing variceal hemorrhage in patients with large varices. 1 Current guidelines recommend screening for gastroesophageal varices (GEV) with esophagogastroduodenoscopy (EGD) in all patients with cirrhosis and starting prophylactic therapy in those with medium to large varices. [4][5][6][7] In patients without varices, EGD is repeated in 2-3 years, whereas in patients with small varices, the recommendation is to repeat EGD in 1-2 years. 2 Because of the cost and invasive nature of endoscopic screening, there is interest in developing a noninvasive predictor of the presence and development of GEV that would decrease the number of EGDs performed. The ideal noninvasive marker should be widely available at a reasonable cost, require minimal expertise, be reproducible, and be relatively unaffected by any other factors. A number of clinical, laboratory, and ultrasonographic variables have been considered. 8 However, the accuracy of these variables in predicting varices is currently inadequate to be recommended for clinical practice. 2 As varices are a direct consequence of portal hypertension, it is not surprising that the degree of portal hypertension determined by the hepatic venous pressure gradient (HVPG) has been found to be predictive of the

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“…[14][15][16][17][18] Three of the four studies with higher sensitivities had poor specificity. In a study by Madhotra et al, 17 Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Platelet counts (PLT) from 68,000 to 160,000 have shown sensitivities ranging from 71% to 88% for small varices. [14][15][16][17][18] The sensitivities for large varices are better but with unsatisfactory specificities. However, many of these studies were crosssectional and were limited by the variability and severity of the liver disease.…”

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confidence: 99%

Platelet count is not a predictor of the presence or development of gastroesophageal varices in cirrhosis

et al. 2007

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“…[24][25][26][27] All are time consuming and produce partially subjective fibrosis evaluations that are not very precise. 23 It has been shown that computerized imaging enables a precise quantification of fibrosis, and we have used this technique in a recent investigation of the effects of liver disease on cationic drug pharmacokinetics. 9 A number of studies have related MID estimated clearances in the fibrotic rat liver to changes in hepatic microcirculation.…”

Section: Discussionmentioning

confidence: 99%

Quantitative evaluation of altered hepatic spaces and membrane transport in fibrotic rat liver

et al. 2002

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Four animal models were used to quantitatively evaluate hepatic alterations in this study: (1) a carbon tetrachloride control group (phenobarbital treatment only), (2) a CCl 4 -treated group (phenobarbital with CCl 4 treatment), (3) an alcohol-treated group (liquid diet with alcohol treatment), and (4) a pair-fed alcohol control group (liquid diet only). At the end of induction, single-pass perfused livers were used to conduct multiple indicator dilution (MID) studies. Hepatic spaces (vascular space, extravascular albumin space, extravascular sucrose space, and cellular distribution volume) and water hepatocyte permeability/surface area product were estimated from nonlinear regression of outflow concentration versus time profile data. The hepatic extraction ratio of 3 H-taurocholate was determined by the nonparametric moments method. Livers were then dissected for histopathologic analyses (e.g., fibrosis index, number of fenestrae). In these 4 models, CCl 4 -treated rats were found to have the smallest vascular space, extravascular albumin space, 3 H-taurocholate extraction, and water hepatocyte permeability/surface area product but the largest extravascular sucrose space and cellular distribution volume. In addition, a linear relationship was found to exist between histopathologic analyses (fibrosis index or number of fenestrae) and hepatic spaces. The hepatic extraction ratio of 3 H-taurocholate and water hepatocyte permeability/surface area product also correlated to the severity of fibrosis as defined by the fibrosis index. In conclusion, the multiple indicator dilution data obtained from the in situ perfused rat liver can be directly related to histopathologic analyses. (HEPATOLOGY 2002;36:1180-1189 L iver fibrosis and cirrhosis represent a major worldwide health problem. In cirrhosis, the normal hepatic lobular architecture is replaced by interconnecting bands of fibrous tissue surrounding nodules of regenerating hepatocytes. The sinusoidal stellate cell is central to the fibrotic process. 1-4 Consequently, extravascular space accessible to macromolecules (e.g., albumin) decreases and the distribution of sucrose shows a barrierlimited pattern in the space of Disse instead of the normal flow-limited behavior due to 3 hepatic alterations: (1) collagenization of the space of Disse, (2) formation of a basement membrane of the sinusoid (capillarization), and (3) intrahepatic, portahepatic shunt formation. 5-8 A liver biopsy is currently mandatory to assess severity of fibrosis.We recently examined the drug structure/disposition kinetics of a series of cationic drugs in carbon tetrachloride-and alcohol-induced fibrosis in perfused rat livers. 9 In this case, cationic drug disposition in the fibrotic liver can be predicted from drug properties and liver histopathology. As a result, the question was raised of whether we could use histopathology from patient liver biopsy specimens to estimate changes in hepatic spaces and whether the active and passive transport of probes (e.g., 3 H-taurocholate, 3 H-water) across ...

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“…6,8,9,17 However, none of these methods were accurate enough when tested in independent validation series, 5,13 and some of them, such as a complete assessment of the portal vein system by ultrasound, were not easy to perform and required specific long-term training. 18 More recently, transient elastography, which estimates liver stiffness (LS), has been proposed as a new method to noninvasively diagnose CSPH and EVs in patients with cirrhosis.…”

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confidence: 99%

Elastography, Spleen Size, and Platelet Count Identify Portal Hypertension in Patients With Compensated Cirrhosis

et al. 2013

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BACKGROUND & AIMS:Noninvasive methods are needed to identify clinically significant portal hypertension (CSPH) and esophageal varices (EVs) in patients with compensated cirrhosis. We looked for markers of the presence of CSPH and EVs in patients with cirrhosis. METHODS: We performed a cross-sectional study that included a training set of 117 patients with compensated cirrhosis, confirmed by histology, from a tertiary referral center. Spleen diameter was measured by ultrasound and liver stiffness (LS) was measured by transient elastography; endoscopy was used as the standard for detection of EVs and measurements of hepatic venous pressure gradient were used as the standard for identifying CSPH. We assessed the ability of platelet count, spleen diameter, LS, and combinations of these factors (ie, ratio of platelet count to spleen size, and LS ϫ spleen size/platelet count [LSPS]) to identify patients with CSPH and EV. The analysis included 2 new statistical models: the PH risk score and the varices risk score. Results were validated using an independent series of 56 patients with compensated patients from another center. RESULTS: LS was the best single noninvasive variable for identifying patients with CSPH (area under the receiver operating characteristic, 0.883; 95% confidence interval [CI], 0.824 -0.943; P Ͻ .0001). The area under the receiver operating characteristic value increased when LS was combined with platelet count and spleen size, either as LSPS (0.918; 95% CI, 0.872Ϫ0.965; P Ͻ .0001) or PH risk score (0.935; 95% CI, 0.893-0.977; P Ͻ .0001). More than 80% of patients were accurately classified using LSPS and PH risk score. Analyses of the varices risk score and LSPS were superior to all other noninvasive tests for identifying patients with EVs (area under the receiver operating characteristic, 0.909; 95% CI, 0.841Ϫ0.954 and 0.882; 95% CI, 0.810 -0.935, respectively); they correctly classified 85% of patients in the training set and 75% in the validation set. CONCLUSIONS: Combined data on LS, spleen diameter, and platelet count can be used to identify patients with compensated cirrhosis most likely to have CSPH and EV.

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Non-invasive diagnosis of esophageal varices in chronic liver diseases

Cited by 156 publications

References 26 publications

Platelet count is not a predictor of the presence or development of gastroesophageal varices in cirrhosis

Platelet count is not a predictor of the presence or development of gastroesophageal varices in cirrhosis

Quantitative evaluation of altered hepatic spaces and membrane transport in fibrotic rat liver

Elastography, Spleen Size, and Platelet Count Identify Portal Hypertension in Patients With Compensated Cirrhosis

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