ORIGINAL ARTICLES LIVER, PANCREAS, AND BILIARY TRACT

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2010;8:703 708 ORIGINAL ARTICLES LIVER, PANCREAS, AND BILIARY TRACT Compliance With Practice Guidelines and Risk of a First Esophageal Variceal Hemorrhage in Patients With Cirrhosis JAYAVANI MOODLEY, ROCIO LOPEZ, and WILLIAM CAREY Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio See Editorial on page 649. BACKGROUND & AIMS: Esophageal variceal hemorrhage (EVH) is a serious complication of cirrhosis, with 20% mortality per episode. The 2007 American Association for the Study of Liver Disease and American College of Gastroenterology practice guidelines regarding esophageal varices in patients with cirrhosis recommend screening and intervention to prevent EVH. We assessed practice guideline compliance and its impact on the rate of first EVH. METHODS: An institutional review board-approved retrospective chart review was conducted on a random sample of adult patients newly evaluated for cirrhosis at the Cleveland Clinic from 2003 to 2006 (n 179). Exclusion criteria were a previous diagnosis of esophageal varices or EVH and/or treatment with -adrenergic antagonists. Patients were followed for 23 months (range, 9 38 months). Conformity with practice guidelines and subsequent bleeding rates were determined. Observed bleeding rates were compared to the North Italian Endoscopy Club (NIEC) model. RESULTS: Of the patients, 94% had a screening endoscopy, 80% within 6 months of the initial visit. Varices were present in 50% of the patients; 68% of all patients screened and 91% with large varices received a practice guideline-recommended treatment. Twelve patients (7%) had an episode of EVH; 82% of subjects without bleeding had their screening endoscopy within 6 months versus 50% of those with bleeding (P.016). Actuarial likelihood of bleeding at 2 years was 13% versus 27% predicted by the NIEC model (P.05). CONCLUSION: Compliance with practice guideline recommendations is associated with reduction in first EVH in the first 2 years. Keywords: Practice Guideline Compliance; Cirrhosis; Esophageal Varices; Hemorrhage. The risk of developing gastroesophageal varices in patients with cirrhosis is between 50% and 66% 1 and 30% 40% of patients with varices suffer a variceal hemorrhage. 2 Although the mortality rate associated with an episode of esophageal variceal hemorrhage (EVH) has decreased almost 3-fold in the past 2 decades owing to the combined use of endoscopic and pharmacological interventions, it is still high at 15% 20%. 3 4 If untreated, variceal hemorrhage portends a 70% risk of death within 1 year 2 ; this high mortality rate makes primary prevention of bleeding the best approach to improving outcomes for these patients. The American Association for the Study of Liver Disease (AASLD) jointly with the American College of Gastroenterology (ACG) recently published practice guidelines (PG) (Supplementary Appendix A) that recommend screening and intervention for high risk EV. 5 In 1988 the North Italian Endoscopy Club (NIEC) defined high risk varices as a composite measure of 3 variables: the severity of liver disease as determined by the Child Pugh Score (CPS); the size of varices, with large varices being the most ominous; and the presence and severity of red wale markings or red signs (longitudinal dilated venules on the varix, similar to whip marks) 6 (Supplementary Appendix B). In 2004 Zaman et al documented that self-reported PG compliance among gastroenterologists improved from 18% to 54% following the publication of the 1997 American College of Gastroenterology guidelines for the management of varices. 7 Four years later the compliance rate in the same population still sits at 54%. 8 There have been, however, no studies evaluating the impact improved compliance has on clinical outcomes such as rates of variceal hemorrhage or mortality among patients with cirrhosis. We undertook this study to assess actual compliance rates of gastroenterologists at a large tertiary institution with the current AASLD/ACG practice guidelines concerning EV screening and management. We also aimed to elucidate whether compliance resulted in improved patient outcomes, namely decreased risk of first variceal hemorrhage. Methods An institutional review board-approved retrospective chart review was conducted on 179 adult patients (age 18 years), selected by computerized randomization from 468 eligible patients, newly evaluated for cirrhosis at the Cleveland Clinic from 2003 2006. Exclusion criteria were a previous di- Abbreviations used in this paper: AASLD, American Association for the Study of Liver Disease; ACG, American College of Gastroenterology; BB, beta blocker; CPS, Child Pugh Score; EGD, endoscopy; EV, esophageal varices; EVH, esophageal variceal hemorrhage; EVL, esophageal variceal ligations; IGV, isolated gastric varices; NIEC, North Italian Endoscopy Club; PG, practice guideline. 2010 by the AGA Institute 1542-3565/$36.00 doi:10.1016/j.cgh.2010.02.022

704 MOODLEY ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 8, No. 8 agnosis of EV or EVH and/or treatment with -adrenergic antagonists. The diagnosis of cirrhosis was based on historical, clinical, and pathological data. The electronic database EPIC was used to retrieve relevant information spanning hepatology outpatient visits, hospital admissions, endoscopic procedures, and laboratory and other pathology-related data. Our analysis aimed to determine whether or not patients underwent timely screening for varices after initial evaluation by a hepatologist, follow-up surveillance endoscopies, and if found, were varices appropriately managed. Patients were followed for an average of 23.0 months (range, 9.2 37.8 months). Our endpoint was first EVH or last EPIC encounter. Information about bleeding episodes that occurred at the Cleveland Clinic was obtained directly from endoscopy reports, laboratory data, or hospital discharge summaries. If an episode of EVH occurred at another institution the data were documented by the hepatologist in the patient s outpatient record. The NIEC index was calculated for the patients who bled from EV, and the observed bleeding rates were compared with the NIEC predicted rates at 1 and 2 years. For the purpose of appropriate data collection the following variables were defined. Practice Guideline Recommended Management In compliance with the 2007 AASLD/ACG PG (Supplementary Appendix A), effective screening required that patients have their screening endoscopy within 6 months of their initial visit to a hepatologist; patients should be placed on a noncardioselective beta blocker (BB) or have esophageal variceal ligations (EVL) when needed; follow-up upper intestinal endoscopy (EGD) should be performed at appropriate intervals post esophageal variceal ligation (EVL); and for routine surveillance, BB should be titrated to the maximum tolerated dose. Clinically Significant Bleeding (Baveno IV Criteria) 9 Transfusion requirement 2 units of blood within 24 hours of time zero, and systolic blood pressure 100 mm Hg or postural systolic change 20 mm Hg, and/or heart rate 100 beats/minute. Endoscopic Findings and Description of Varices The presence or absence of esophageal varices was noted. Varices were classified as small, medium, or large. A5mmdiam- eter was used as the cutoff for designating small from medium and large varices. The presence or absence of gastric varices and red wale markings was also documented. Unlike in the NIEC study, red wale markings were not graded in the endoscopy records reviewed. For the purpose of calculating the NIEC index in patients who bled we assigned those with red wale markings to the mild category (Supplementary Appendix C). As such, patients with red wale markings may have been placed in a lower risk NIEC category. Length of Follow-Up Patients were followed until their first bleeding episode from EV or their last encounter in EPIC, with the average length of follow-up being 23.0 months (range, 9.2 37.8 months). Statistical Analysis Descriptive statistics were computed for all variables. These include median and percentiles for age and frequencies for categorical variables. Pearson s 2 tests were used to assess association between compliance to practice guidelines and factors such as presence of varices and CPS. The same was done to study factors associated with the presence and size of varices. Kaplan Meier estimates were used to study bleeding rates in patients with EV, and a log-rank test was used to compare NIEC groups. Time of follow-up was defined as months between EV diagnosis and either bleeding or last follow-up visit if no bleeding was observed. A P.05 was considered statistically significant. SAS version 9.2 software (The SAS Institute, Cary, NC) and R version 2.4.1 (The R Foundation for Statistical Computing, Vienna, Austria) were used for all analyses. Results Records of 562 cirrhotic patients presenting for the first time to a tertiary care liver clinic were screened. Ninety-four were excluded because of a previous diagnosis of EV, having suffered an EVH, or being recently (within the previous 12 months) or currently treated with beta blockers. Of the remaining eligible 468 patients, 179 were randomly selected for detailed analysis. Patient characteristics are shown in Table 1. Compliance With Practice Guidelines Screening for varices was accomplished in 169 cases (94%), although only 143 (80%) were screened within 6 months Table 1. Demographic Characteristics of Subjects Factor All (n 179) Male 107 (59.8) Age at the time of first visit, mean 52.9 (47.1 60.4) years (range) Race Caucasian 135 (76.3) Black 29 (16.4) Hispanic 6 (3.4) Asian 1 (0.6) Other 6 (3.4) CPS a A 121 (72.5) B 36 (21.6) C 10 (6.0) Etiology of cirrhosis Alcohol 39 (21.8) Autoimmune 10 (5.6) Cryptogenic 7 (3.9) Hep B 9 (5.0) Hep C 80 (44.7) NASH 21 (11.7) PBC 9 (5.0) PSC 3 (1.7) Wilson s 1 (0.6) NOTE. Unless otherwise noted, data are presented as n (%). Hep B, hepatitis B; Hep C, hepatitis C; NASH, nonalcoholic steatohepatitis; PBC, primary biliary cirrhosis; PSC, primary sclerosing cholangitis. a Two patients did not have required laboratory or clinical data to calculate the CPS.

August 2010 EXAMINING PRACTICES AT A LARGE TERTIARY INSTITUTION 705 Table 2. Findings at Initial Endoscopy Factor A a (n 120) B(n 36) C (n 10) EV found? b No varices 70 (58.3) 12 (33.3) 1 (10) Small 30 (25.0) 15 (41.7) 3 (30) Medium/large 20 (16.6) 9 (25.0) 6 (60) Description of EV Absent red signs 117 (97.5) 33 (91.6) 8 (80) Present red signs 3 (2.5) 3 (8.3) 2 (20) Appropriate advice given 85 (74.6) 20 (57.1) 8 (80) NOTE. Data are given as n (%). a One CPS A patient had incomplete data at endoscopy and was excluded. b CPS could not be calculated in 2 patients; 1 with no varices and 1 with small varices. of their first encounter with the hepatologist (Figure 1). Ten (6%) were never screened. Two thirds (68%) received PG recommended management after their screening endoscopy, 47 (28%) did not, and 7(4%) were lost to follow-up. PG compliance was found in 73.8% of patients with varices and 67.9% with no varices (P.41). Ninety-one percent of patients with medium and large varices received a PG recommended treatment compared with 60% with small varices (P.002). When stratified according to CPS, 75% of CPS A, 57% of CPS B, and 80% of CPS C received PG-recommended treatment (A vs B, P.048; C vs B, P.28). Failure of compliance to practice guidelines was noted in 57 patients. Reasons for fallout were due to physicianrelated factors in 47 patients (82%). Of these, 20 did not receive a follow-up surveillance endoscopy, 14 were not given BB (for CPS B/C with small varices), 10 did not have a screening EGD, and 3 did not receive either BB or EVL once diagnosed with varices. Eighteen percent (10 patients) had their subsequent EGD beyond the recommended interval due to nonphysician or indeterminate factors. Findings at Screening Endoscopy One hundred and sixty-nine patients had a screening EGD (Table 2). One was excluded because of incomplete records; there was no description of the size or appearance of varices in the endoscopy report. Eighty-four (50%) of the remaining 168 patients had varices. Seventy (58%) of CPS A had no varices while 6 (60%) of CPS C had medium/large varices. CPS A patients were more likely to have small varices than CPS B(P.002) and CPS C (P.003). The presence of red wale markings on varices was noted in 3 (2.5%) of CPS A patients and 2 (20%) of CPS C. Bleeding Twelve patients (7%) of the study population had an episode of clinically significant bleeding during the follow-up period. Nearly all (11/12) had either esophageal or gastric varices at the time of initial screening endoscopy. Thirteen percent (11/84) of those with varices at initial screening subsequently bled. Of the 9 patients with EV, 2 (17%) had small and 7 (58%) had medium or large varices. Eight subjects bled within 1 year, 3 in the second year, and 1 subject 2 years after their screening EGD. At screening, 6 (50%) patients with subsequent EVH were CPS A, 4 (33%) CPS B, and 2 (17%) CPS C. Six (50%) of the patients who bled had received a screening endoscopy within 6 months of initial diagnosis. Eighty-two percent (137/167) of subjects without bleeding had their screening EGD within 6 months of initial visit compared with 50% (6/12) of those with bleeding (P.016). Seventy-five percent (9/12) of patients with EVH did receive a PG-recommended treatment after their screening EGD. There were 52 patients with a NIEC score 26 and 32 with a NIEC 26 (Table 3). Three patients (5.8%) in the lower NIEC category bled compared with 6 (18.8%) in the group with a NIEC 26 (P.032), in conformity with previous predictions of increased bleeding risk with higher NIEC scores (Figure 2). 6 Eleven percent (9/84) of subjects with EV had EVH compared with 26.5% in the NIEC study (P.002). The cumulative actuarial likelihood of bleeding was 9.2% and 13.0% at 1 and 2 years respectively, significantly lower than predicted by the NIEC model namely 16% and 27% (P.05). As the NIEC index was developed for patients with EV, only the 9 patients with EV were used in comparison studies with the original NIEC. We observed no bleeding episodes attributable to band ligation. Eighteen percent of those with small varices were given beta blockers; eighty percent of those with medium/large varices were treated with EVL, indicating a preference in this facility for this management tool. Observed bleeding rates were not different between treatment groups. Discussion Our study confirms the high prevalence of esophageal varices (50%) in cirrhotic patients with no history of bleeding. Sixty-three percent of those with varices had features putting them at high risk for bleeding. These results are similar to Figure 1. Study population and screening endoscopy. *Reasons for exclusion: previous diagnosis of EV, EVH or already treated with beta blockers. CCF, Cleveland Clinic Foundation.

706 MOODLEY ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 8, No. 8 Figure 2. Kaplan Meier plot depicting bleeding rates for different NIEC indices. findings in other screening programs. 6 We further demonstrated that high compliance (80% 94%) with screening for esophageal varices among cirrhotic patients seen at a large tertiary care facility appears to translate into better patient outcomes. We are unaware of other published reports demonstrating actual compliance with esophageal varices screening practice guidelines. Two studies evaluating practice guideline compliance regionally and nationally among gastroenterologists found a low rate of reported adherence (54%). 7,8 These reports surveyed gastroenterologists (not hepatologists) from a variety of practice settings. Our study examined behavior of hepatologists in an academic center. Nearly all (94%) of newly diagnosed cirrhotic patients had a screening endoscopy, 80% within 6 months of being evaluated by a hepatologist. Endoscopic screening remains the gold standard for the diagnosis of varices. 5 The ACG/AASLD PG recommend a screening EGD to assess the presence of EV when the diagnosis of cirrhosis is made. Subsequent management depends on the nature of the varices, that being their size and appearance, and the patient s CPS. Both beta-blockers and EVL are advocated in the primary prophylaxis of first EVH, and use of these measures significantly reduces the risk of bleeding. 10 12 Of the 168 patients who received a screening endoscopy (regardless of when) 114 (68%) received PG-recommended management including either betablockers, EVL and/or timely follow-up. Significantly, 91% of patients with medium or large varices compared with 60% with small varices were treated in compliance with PG (P.002). This may reflect that practitioners consider small varices less threatening than larger ones and thus are less likely to treat them. However it is known that 4% 10% of small varices progress to large varices per year, and therefore appropriate and timely management is warranted. 2 Our center prefers EVL to beta blocker therapy, a choice influenced by 2 meta-analyses which indicate superiority of EVL in preventing initial bleeding. 12,13 Of our patients with medium or large varices, 80% were treated with EVL and only 11% by beta-blocker therapy. Concern about major hemorrhage caused by EVL was not realized in this study population. There was no significant difference in early bleeding (within 3 months of initiation of treatment) in those who received EVL and BB (10% and 3.7%, respectively, P.34) (Supplementary Table 4). We are aware of the recently published report of BB superiority compared with EVL in primary bleeding prophylaxis. 14 This finding, if verified, will likely alter our treatment strategy in the future. The most common reason for divergence from PG recommendations is lack of timely follow-up endoscopy for surveillance in patients with no or small esophageal varices, explained, in part, by the referral nature of this practice (Figure 3). Eighteen patients with Child Pugh B or C had small varices, a group for whom intervention with beta blocker therapy (with dose titration) is recommended. In this group only 22% were given beta blockers. Reasons for noncompliance have not been systematically determined, but may relate to many factors including the complexity of the management algorithm, or unfamiliarity or disagreement with individual PG recommendations. More emphasis may be needed in the specific care of this subset of patients. Bringing to light these areas of noncompliance can help physicians identify those patients who fall into potential gray areas where management may be unclear. The NIEC provides a rich and detailed prospective assessment of bleeding risk in cirrhotic patients with newly discovered varices. 6 Based on this, a scoring system of bleeding risk has been constructed and validated. 6,15 Recently suggestions have been made that the original NIEC assigns too much weight to the CPS limiting its prognostic efficiency and accuracy. 15,16 Zoli et al 16 propose that more leverage be assigned to the size and appearance of the varices instead and have proposed a revised NIEC index. The differences in predicted bleeding risk between the original and revised scoring systems seem small. Pending further studies, the original NIEC index remains the most widely used system and was selected for our analysis. This study suggests that the significant reduction in observed bleeding rates may be related to adherence to PG-recommended care. Patients who did not bleed were more likely to have received their screening EGD within the 6 month window as compared with those who bled (82% vs 50%, P.016), demonstrating the effectiveness of early variceal screening. Seventy-five percent of patients who bled (9/12) did actually receive PG-compliant management after their screening EGD. This finding underscores the fact that no currently available strategy will eliminate the risk of variceal hemorrhage. It is noteworthy that both patients found to have isolated gastric varices (IGV) suffered clinically significant bleeding from these culprit vessels. One patient was found to have bleeding from IGV at the time of initial EGD and subsequently underwent placement of a transjugular intrahepatic portosystemic shunt (Supplementary Table 4). Gastric varices are found in about 20% of patients with cirrhosis either alone as IGV or as gastroesophageal varices in direct continuity with their esophageal counterparts. IGV are less prevalent than gastroesophageal varices (10% versus 90%), but they have a greater propensity to bleed; bleeding is difficult to control and is associated with a high mortality rate. 2,17 Currently there is no consensus on optimum treatment of gastric varices, and therefore more studies are necessary to provide data for guidelines on appropriate prophylaxis. 9,17 In

August 2010 EXAMINING PRACTICES AT A LARGE TERTIARY INSTITUTION 707 Figure 3. Findings at screening endoscopy, management thereafter, and episodes of EV hemorrhage (EVH). 1 The report stated that varices were present but did not describe the size or appearance. This patient had EVL and was given BB and subsequently did not bleed. 2 Twenty patients had no follow-up EGD, 3 were not given BB, 3 had EGD overdue. 3 Three patients with medium/large varices had no EVL or BB. 4 Eleven patients were not given BB, 7 with follow-up EGD overdue. patients with IGV it is prudent to rule out the presence of splenic vein thrombosis. Our data need to be confirmed and validated. Of note, our endoscopists most often describe red wale markings as either present or absent (rather than following the NIEC protocol of mild-moderate-severe), making use of the NIEC scoring system difficult and subject to possible interpretive errors (Supplementary Appendix B). We also note a discrepancy between the higher rates of red signs in the NIEC data, namely 41% in Child s A and 39% in Child s C patients compared with 2.5% and 20%, respectively, in our study. This may represent the possibility of underreporting of red signs by our endoscopists and pose a potential limitation of our study. Retrospective studies sometimes lack granularity, ie, the ability to capture nuances such as reasons for clinical decisionmaking. Compliance depends on factors other than physician recommendations and includes patient understanding, motivation, family support, and logistical issues such as financial means. From our data set it is difficult to attribute definitively the cause of failure to the physician or patient. Nevertheless, the cumulative effect of physician recommendation plus patient factors has been shown in this population to be highly effective in achieving the goals of practice guideline compliance. A future study is planned to attempt to better understand the relative roles of patient, environment, and physician factors associated with noncompliance. In conclusion, this study confirms the high prevalence of esophageal varices in patients with cirrhosis and also finds high compliance rates with practice guidelines among hepatologists at a large tertiary institution regarding the prevention and management of EV. In our population, management according to principles endorsed by a recently published practice guideline was associated with a lower bleeding rate than that expected in untreated patients. It is Table 3. Bleeding Rates at 1 and 2 Years Rate of Bleeding (%) NIEC Index n Patients Who Bled (n) 1 Year 2 Years 26 52 3 6.6 6.6 26 32 6 13.5 26.8 NOTE. Three of 52 (5.8%) in the 26 group bled versus 6/32 (18.8%) in the 26 group (P.032). Kaplan Meier estimates were used to calculate bleeding rates.

708 MOODLEY ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 8, No. 8 recommended that efforts to promote increased awareness of and compliance to PG for the screening and management of EV are warranted. Supplementary Material Note: to access the supplementary material accompanying this article, visit the online version of Clinical Gastroenterology and Hepatology at www.cghjournal.org, and at doi: 10.1016/ j.cgh.2010.02.022. References 1. Jensen DM. Endoscopic screening for varices in cirrhosis: findings, implications, and outcomes. Gastroenterology 2002;122: 1620 1630. 2. Toubia N, Sanyal AJ. Portal hypertension and variceal hemorrhage. Med Clin North Am 2008;92:551 574. 3. Chalasani N, Kahi C, Francois F, et al. Improved patient survival after acute variceal bleeding: a multicenter, cohort study. Am J Gastroenterol 2003;98:653 659. 4. Carbonell N, Pauwels A, Serfaty L, et al. Improved survival after variceal bleeding in patients with cirrhosis over the past two decades. Hepatology 2004;40:652 659. 5. Garcia-Tsao G, Sanyal AJ, Grace ND, et al; Practice Guidelines Committee of the American Association for the Study of Liver Diseases; Practice Parameters Committee of the American College of Gastroenterology. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis [erratum in: 2007;46:2052]. Hepatology 2007;46:922 938. 6. North Italian Endoscopic Club for the Study and Treatment of Esophageal Varices. Prediction of the first variceal hemorrhage in patients with cirrhosis of the liver and esophageal varices. A prospective multicenter study. N Engl J Med 1988;319:983 989. 7. Zaman A, Hapke RJ, Flora K, et al. Changing compliance to the American College of Gastroenterology guidelines for the management of variceal hemorrhage: a regional study. Am J Gastroenterol 2004;99:645 649. 8. Carey E, Wakim-Fleming J, Lopez R, et al. National and regional conformity to the 2007 ACG/AASLD practice guidelines for prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Am J Gastroenterol 2008;103: S135. 9. de Franchis R. Evolving consensus in portal hypertension. Report of the Baveno IV consensus workshop on methodology of diagnosis and therapy in portal hypertension. J Hepatol 2005; 43:167 176. 10. Imperiale TF, Chalasani N. A meta-analysis of endoscopic variceal ligation for primary prophylaxis of esophageal variceal bleeding. Hepatology 2001;33:802 807. 11. D Amico G, Pagliaro L, Bosch J. Pharmacological treatment of portal hypertension: an evidence-based approach. Semin Liver Dis 1999;19:475 505. 12. Tripathi D, Graham C, Hayes PC. Variceal band ligation versus beta-blockers for primary prevention of variceal bleeding: a metaanalysis. Eur J Gastroenterol Hepatol 2007;19:835 845. 13. Gluud LL, Klingenberg S, Nikolova D, et al. Banding ligation versus beta-blockers as primary prophylaxis in esophageal varices: systematic review of randomized trials. Am J Gastroenterol 2007;102:2842 2848. 14. Tripathi D, Ferguson JW, Kochar N, et al. Randomized controlled trial of carvedilol versus band ligation for the prevention of first variceal bleed. Hepatology 2009;50:825 833. 15. Merkel C, Zoli M, Siringo S, et al. Prognostic indicators of risk for first variceal bleeding in cirrhosis: a multicenter study in 711 patients to validate and improve the North Italian Endoscopic Club (NIEC) index. Am J Gastroenterol 2000;95:2915 2920. 16. Zoli M, Merkel C, Magalotti D, et al. Evaluation of a new endoscopic index to predict first bleeding from the upper gastrointestinal tract in patients with cirrhosis. Hepatology 1996;24:1047 1052. 17. Ryan BM, Stockbrugger RW, Ryan JM. A pathophysiologic, gastroenterologic, and radiologic approach to the management of gastric varices. Gastroenterology 2004;126:1175 1189. Reprint requests Address requests for reprints to: Jayavani Moodley, MD, c/o William Carey, MD, Cleveland Clinic Foundation, Department of Gastroenterology and Hepatology, 9500 Euclid Avenue, Cleveland, Ohio 44195. e-mail: jayavani108@gmail.com; fax: (216) 445-5477. Conflicts of interest The authors disclose no conflicts.