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Is Transient Elastography Needed for Noninvasive Assessment of High-Risk Varices? The REAL Experience

Calvaruso, Vincenza MD, PhD1; Cacciola, Irene MD2; Licata, Anna MD3; Madonia, Salvatore MD4; Benigno, Rosa MD5; Petta, Salvatore MD, PhD1; Bronte, Fabrizio MD, PhD1; Conte, Elisabetta MD1; Malizia, Giuseppe MD6; Bertino, Gaetano MD7; Distefano, Marco MD8; Montineri, Arturo MD9; Digiacomo, Antonio MD10; Alaimo, Giuseppe MD11; Cacopardo, Bruno MD12; Davì, Antonio MD13; Guarneri, Luigi MD14; Scalisi, Ignazio MD15; Colletti, Pietro MD16; Cartabellotta, Fabio MD17; Portelli, Vincenzo MD18; Prestileo, Tullio MD19; Averna, Alfonso MD20; Iacobello, Carmelo MD21; Mondello, Lorenzo MD22; Scifo, Gaetano MD8; Russello, Maurizio MD5; Squadrito, Giovanni MD2; Raimondo, Giovanni MD2; Cammà, Calogero MD1; Craxì, Antonio MD1; Di Marco, Vito MD1 on behalf of RESIST-HCV (Rete Sicilia Selezione Terapia–HCV)

American Journal of Gastroenterology: August 2019 - Volume 114 - Issue 8 - p 1275–1282
doi: 10.14309/ajg.0000000000000266
ARTICLE
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INTRODUCTION: The Baveno VI consensus guidelines and an expanded algorithm suggest that transient elastography (TE) and platelet (PLT) count can be used to identify patients with cirrhosis who can avoid esophagogastroduodenoscopy (EGD). The primary aims of this study were to assess the ability of a simple algorithm, which uses only laboratory parameters, to predict medium/large esophageal varices (EV) in patients with hepatitis C virus (HCV) and cirrhosis from the Rete Sicilia Selezione Terapia–HCV (RESIST-HCV) cohort and to compare the performance of the algorithm with Baveno VI and Expanded Baveno VI criteria. The secondary aim was to assess the role of TE in ruling out large EV.

METHODS: In total, 1,381 patients with HCV-associated cirrhosis who had EGD and TE within 1 year of starting treatment with direct-acting antivirals were evaluated. Using multivariate logistic analysis, laboratory variables were selected to determine which were independently associated with medium/large EV to create the RESIST-HCV criteria. These criteria were tested in a training cohort with patients from a single center (Palermo) and validated with patients from the 21 other centers of the RESIST-HCV program (validation cohort).

RESULTS: In the entire cohort, medium/large EV were identified in 5 of 216 patients (2.3%) using the Baveno VI criteria and 13 of 497 patients (2.6%) using the Expanded Baveno VI criteria. PLT count and albumin level were independently associated with medium/large EV. The best cut-off values were a PLT count greater than 120 × 109 cells/μL and serum albumin level greater than 3.6 g/dL; negative predictive values (NPVs) were 97.2% and 94.7%, respectively. In the training cohort of 326 patients, 119 (36.5%) met the RESIST-HCV criteria and the NPV was 99.2%. Among 1,055 patients in the validation cohort, 315 (30%) met the RESIST-HCV criteria and the NPV was 98.1%. Adding TE to the RESIST-HCV criteria reduced the avoided EGDs for approximately 25% of patients and the NPV was 98.2%.

DISCUSSION: The “easy-to-use” RESIST-HCV algorithm avoids EGD for high-risk EV screening for more than 30% of patients and has the same performance criteria as TE. Using these criteria simplifies the diagnosis of portal hypertension.

1Sezione di Gastroenterologia e Epatologia, Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S.), University of Palermo, Palermo, Italy;

2UOC Epatologia Clinica e Biomolecolare and AOUP G Martino, Dipartimento di Medicina Interna e Sperimentale, University of Messina, Messina, Italy;

3UOC Medicina Interna, AOUP Paolo Giaccone, Palermo, Italy;

4UOC Medicina Interna, AO Villa Sofia-Cervello, Palermo, Italy;

5UOS Epatologia, ARNAS Garibaldi-Nesima, Catania, Italy;

6UOC Gastroenterologia, AO Villa Sofia-Cervello, Palermo, Italy;

7UOC Medicina Interna, AOUP G Rodolico, Catania, Italy;

8UOC Malattie Infettive, Ospedale Vittorio Emanuele di Siracusa, ASP Siracusa, Siracusa, Italy;

9UOC Malattie Infettive, Presidio Ospedaliero Ferrarotto, Catania, Italy;

10UOC Medicina Interna, Ospedale di Comiso, ASP Ragusa, Ragusa, Italy;

11UOC Medicina Interna, Ospedale di Agrigento, ASP Agrigento, Agrigento, Italy;

12UOC Malattie Infettive, ARNAS Garibaldi-Nesima, Catania, Italy;

13UOC Malattie Infettive, Ospedale di Modica, ASP Ragusa, Ragusa, Italy;

14UOC Malattie Infettive, Ospedale di Enna, ASP Enna, Enna, Italy;

15UOC Medicina Interna, Ospedale di Mazzara Del Vallo, ASP, Trapani, Italy;

16UOC Malattie Infettive, Azienda Ospedaliera Universitaria Paolo Giaccone, Palermo, Italy;

17UOC Medicina Interna, Ospedale Buccheri La Ferla, Palermo, Italy;

18UOC Malattie Infettive, Ospedale di Trapani, ASP Trapani, Trapani, Italy;

19UOC Malattie Infettive, ARNAS Civico-Di Cristina-Benefratelli, Palermo, Italy;

20UOC Malattie Infettive, Ospedale di Caltanissetta, ASP Caltanissetta, Italy;

21UOC Malattie Infettive, AO Cannizzaro, Catania, Italy;

22UOC Malattie Infettive, AO Papardo e Piemonte, Messina, Italy.

Correspondence: Vincenza Calvaruso, MD, PhD. E-mail: vincenza.calvaruso@unipa.it.

SUPPLEMENTARY MATERIAL accompanies this paper at http://links.lww.com/AJG/A183, http://links.lww.com/AJG/A184, and http://links.lww.com/AJG/A185

Received October 07, 2018

Accepted March 04, 2019

Online date: May 24, 2019

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INTRODUCTION

The development of portal hypertension is a key event in the progression of chronic liver disease (1). In patients with compensated cirrhosis, varices develop at a rate of 7%–8% per year (2). The presence of esophageal varices (EV) indicates a clinical stage of compensated cirrhosis with a different prognosis (3). Small EV progress to medium/large EV in 10%–12% of cases after 1 year, and variceal size is the main predictor of bleeding (2).

For the past few years, international guidelines have recommended that all patients with newly diagnosed cirrhosis should undergo esophagogastroduodenoscopy (EGD) to screen for the presence of EV; if present, patients should be evaluated for the need for primary prophylaxis against variceal bleeding (4). The recommended intervals for follow-up EGD are 2–3 years for patients without EV and 1–2 years for patients with small EV.

However, EGD screening, as with all invasive procedures, is not well-accepted by patients; hence, the adherence to screening recommendations is suboptimal. Additionally, an endoscopic surveillance program for patients with cirrhosis requires considerable organizational effort and resources at liver centers. Consequently, the development of a simple alternative screening method that is reproducible and accurate has become a priority of scientific research (5).

In 2015, experts at the Baveno VI Consensus Workshop suggested that liver stiffness, as measured by transient elastography (TE) with a cut-off value of less than 20 kPa, and a platelet (PLT) count greater than 150 × 109 cells/μL be used to identify patients with compensated liver cirrhosis of any etiology who could avoid EGD screening to identify medium/large EV (6). The Baveno VI criteria were met with great enthusiasm by the hepatologic community, and the criteria are used currently to guide screening.

Although the Baveno VI criteria have been validated by other studies (7,8), the rate of endoscopy avoidance has been unsatisfactory (9). Therefore, the Expanded Baveno VI criteria were proposed to include a PLT count greater than 110 × 109 cells/μL and a TE pressure result of less than 25 kPa; the use of these guidelines would avoid 40% of endoscopies and miss less than 5% of varices needing treatment (9). However, both criteria have been validated in multietiological cohorts of patients who have a low prevalence of high-risk EV (7–9) and require TE.

The primary aims of this study were to validate an “easy-to-use” algorithm for ruling out the presence of EV requiring prophylactic therapy in patients with cirrhosis by identifying biohumoral baseline predictors of large EV and to compare the “easy-to-use” algorithm with Baveno VI and Expanded Baveno VI criteria. The secondary aim was to identify the role of TE in the evaluation of portal hypertension in this patient group.

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METHODS

Patient selection

Rete Sicilia Selezione Terapia–hepatitis C virus (RESIST-HCV) is a regional network, acknowledged by the Regional Health Authority, which is used to register all patients with chronic hepatitis C virus (HCV) infection who are assessed for direct-acting antiviral treatment. The network encompasses 22 public hospitals and academic centers throughout Sicily. Recording of all patients in the RESIST-HCV database has been mandatory since the introduction of direct-acting antivirals in Italy (February 2015); the network is used to determine whether treatment is provided according to the Italian Medicines Agency criteria. The RESIST-HCV database registers individual disease features and staging information: liver biopsy results, liver stiffness (as measured by TE), PLT count, EGD results, liver ultrasonography findings, liver function tests, and baseline virologic evaluation (HCV genotype, viral load, hepatitis B virus status, and HIV status). A diagnosis of cirrhosis is established if at least one of the following is present: previous liver biopsy showing stage 4 fibrosis by METAVIR score, evidence of esophageal or gastric EV on EGD, or liver stiffness greater than 12 kPa on TE (10). Cirrhosis functional class was determined by Child-Pugh scoring.

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Exclusion criteria

The exclusion criteria included the absence of a cirrhosis diagnosis according to previously defined criteria (10), a history of liver transplantation, EV banding, portal or splenic vein thrombosis and splenectomy, baseline liver stiffness measurement (LSM) not evaluable (because TE was not performed or LSM values were uninterpretable), or nonavailability of baseline EGD. Patients were excluded from this study if there had been 1 year or more between TE and EGD evaluations.

This study was approved by the Ethics Committee. All patients included in the RESIST-HCV study provided informed consent.

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Patient evaluation

Laboratory parameters of albumin, bilirubin, international normalized ratio (INR), creatinine, hemoglobin, and PLT count were requested for all patients registered in the RESIST-HCV network.

Upper abdominal ultrasound was performed in all patients with cirrhosis for the surveillance of hepatocellular carcinoma and signs of portal hypertension (based on the measurements of the spleen and portal vein diameters). LSM by TE was performed by experienced operators who had performed more than 250 procedures at each of the 12 liver units where the equipment was available. Patients fasted for at least 6 hours before the procedure. All patients were examined in the standard fashion, with the right lobe of the liver accessed with the patient lying in the dorsal cubitus position with maximal abduction of the right arm. TEs were considered valid if they had 10 valid measurements (more than 60% of the total measurements), with an interquartile range less than 0.3. Medium/large varices (i.e., those requiring prophylactic therapy) were assessed using the North Italian Endoscopic Club criteria (11). All consecutive patients with HCV-associated cirrhosis and an endoscopy performed within the 1 year preceding the TE and who had laboratory analyses were included in the RESIST-HCV cohort.

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Study design

A sequential analysis plan was designed to achieve the study aims.

  1. The entire RESIST-HCV cohort was used to validate the performance of the Baveno VI criteria (4).
  2. The entire RESIST-HCV cohort was used to explore the Expanded Baveno VI criteria (9).
  3. Patients enrolled in the RESIST-HCV cohort by the Gastrointestinal & Liver Unit of the University of Palermo comprised the training cohort. This cohort was used to identify the biohumoral parameters associated with medium/large EV and to establish the best cut-off values and test the RESIST-HCV criteria.
  4. The RESIST-HCV criteria were validated in a validation cohort composed of all patients enrolled at the other 21 Sicilian centers involved in the RESIST-HCV.
  5. To assess the role of TE in predicting medium/large EV, a TE cut-off value of less than 25 kPa (9) was added to the RESIST-HCV criteria and the performance of this algorithm was evaluated in both training and validation cohorts.
  6. Last, the rates for endoscopies avoided and false-negative for the various criteria were evaluated for the entire RESIST-HCV cohort.

Flowchart of the study is shown in Figure 1.

Figure 1

Figure 1

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Statistical analysis

Data were collected using a standardized form. Clinical, biochemical, ultrasonographic, and endoscopic results for each patient were entered into a computerized database. Based on variables described in the literature (12), we selected age, sex, PLT count, serum albumin, bilirubin, INR, Child-Pugh score, ultrasonographic longitudinal spleen axis, portal vein diameter, and liver stiffness (measured by TE) as candidate predictors of the endoscopic presence of medium/large EV.

Comparisons between the groups were performed using Mann-Whitney U tests for nonparametric tests and χ2 tests for proportions. Variables found to be significant in the univariate analysis (P < 0.05) were included in a multivariate stepwise logistic regression model.

For laboratory variables independently associated with medium/large EV, the area under the receiver operating characteristic (AUROC) curves were constructed to obtain the best cut-off values and calculate sensitivity and negative predictive value (NPV) for the prediction of EV requiring prophylactic therapy. Patients were classified according to the categories defined by the laboratory variables significantly associated with medium/large EV, and the number of endoscopies that could have been avoided was calculated and compared with the number avoided by the Baveno VI criteria, Expanded VI criteria, and RESIST-HCV plus TE.

The analysis was performed using SPSS package v.20 (SPSS, Chicago, IL).

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RESULTS

Validation of the Baveno VI and Expanded Baveno VI criteria

Both Baveno VI and Expanded Baveno VI criteria were validated with the entire cohort of patients enrolled in the RESIST-HCV Assessment of Medium/Large Varices (REAL) study at the 22 centers of the RESIST-HCV network. Patient characteristics are presented in Table 1.

Table 1

Table 1

Only 216 of the 1,381 patients (15.6%) met the Baveno VI criteria for EV. Of these 216 patients, 71 (32.9%) had small EV and 5 (2.3%) had large EV (Figure 2). As expected, 497 of the 1,381 patients (36%) met the Expanded Baveno VI criteria; among them, 170 patients (34.2%) had small EV and 13 (2.6%) had large EV (Figure 2).

Figure 2

Figure 2

Figure 3

Figure 3

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Analysis of variables related to large EV using the proposed algorithm

The training cohort was composed of 326 patients with HCV-associated cirrhosis who were enrolled in the RESIST-HCV network at the Gastrointestinal & Liver Unit of the University of Palermo. Patient characteristics are presented in Supplementary Table 1 (see Supplementary Digital Content 1, http://links.lww.com/AJG/A183).

Using univariate logistic regression analysis, variables related to the presence of large EV were identified in 326 patients from the training cohort. The logistic model was built using the variables age, sex, bilirubin, albumin, INR, PLT count, portal vein diameter, spleen diameter, and TE.

In multivariable analysis, the variables that were independently associated with the presence of large EV were albumin (odds ratio [OR], 0.54; 95% confidence interval [CI], 0.34–0.85; P = 0.008), PLT count (OR, 0.99; 95% CI, 0.98–0.99; P < 0.001), spleen diameter (OR, 1.16; 95% CI, 1.05–1.28; P = 0.003), and liver stiffness by TE (OR, 1.02; 95% CI, 1.01–1.03; P = 0.042) (Table 2). To create an “easy-to-use” algorithm using values from tests routinely performed for patients with cirrhosis, serum albumin level and PLT count were selected. Both values were independently associated with large EV; the best cut-off values were obtained by AUROC analysis.

Table 2

Table 2

Pairwise comparison of AUROCs for PLT count and serum albumin level showed no difference in the ability to predict large EV (AUROC PLT count = 0.77; AUROC serum albumin level = 0.72; P = 0.307). The optimal threshold for ruling out large EV was with a PLT count greater than 120 × 109 cells/μL and a serum albumin level greater than 3.6 g/dL (Figure 4). A combination of these 2 parameters comprised the RESIST-HCV criteria. In the training cohort, these criteria were met in 119 patients (36.5%). Large EV were present in only 1 patient (0.8%), whereas small EV were identified in 58% of patients (Figure 5). A single patient met the RESIST-HCV criteria despite the diagnosis of grade 2 EV; this man had Child-Pugh A cirrhosis, a PLT count of 154 × 109 cell/L, and a serum albumin level of 4.1 g/dL.

Figure 4

Figure 4

Figure 5

Figure 5

The validation cohort was composed of 1,055 patients with HCV-associated cirrhosis from the other 21 centers involved in the RESIST-HCV network.

There were no differences with respect to patient characteristics between the training and validation cohorts, except for the percentage of patients with EV (see Table 1, Supplementary Digital Content 1, http://links.lww.com/AJG/A183). The overall EV prevalence in the validation cohort was lower than that in the training cohort (42.4% vs 71.5%; P < 0.001), but the rates of large EV were similar between the groups (9.5% and 8.9%; P = 0.88).

In the validation cohort, the RESIST-HCV criteria were met by 315 patients (30%); among them, 75 (23.8%) had grade 1 varices and 6 (1.9%) had grade 2 or 3 EV (Figure 5).

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Assessment of TE utility in the algorithm for noninvasive prediction of large varices

To assess the role of TE in predicting large EV, we first performed a pairwise comparison of AUROC for the 2 parameters of PLT count and serum albumin level included in the Baveno VI and Expanded Baveno VI criteria. We found that PLT count had superior performance in predicting large EV compared with TE (AUROC PLT = 0.77 vs AUROC LSM = 0.61; P = .0132; see Figure 1, Supplementary Digital Content 2, http://links.lww.com/AJG/A184). Indeed, on attempting to verify the ability of a single PLT count to predict large EV, we found that 83 of 326 patients (25.5%) had PLT counts higher than 150 × 109 cell/L. Results were similar to those found with the Baveno VI and Expanded Baveno VI criteria, as 45 patients (54.2%) had small EV and only 2 patients (2.4%) had large EV (see Figure 2, Supplementary Digital Content 3, http://links.lww.com/AJG/A185). For these 2 cases, the TE showed pressures of 21.2 and 16.0 kPa, whereas PLT counts were 173 × 109 cell/L and 194 × 109 cell/L. Both cases had grade 2 EV and compensated cirrhosis. To the PLT count and serum albumin level validated in our validation cohort, we added a TE cut-off of 25 kPa, as proposed by the Expanded Baveno VI criteria.

The percentage of cases that met the RESIST-HCV criteria plus TE (27.6% and 22.7% among training and validation cohorts, respectively) was lower than the percentage that met the RESIST-HCV criteria. As with the RESIST-HCV criteria without TE, 1 of 90 patients (1.1%) from the training cohort and 5 of 240 patients (2.1%) from the validation cohort had large EV who met the RESIST-HCV criteria with TE (Figure 5).

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Analysis of the avoidance of endoscopy based on the Baveno VI, Expanded Baveno VI, and RESIST-HCV criteria in the entire RESIST cohort

Overall, 15.6% of patients met criteria for Baveno VI, 36% for Expanded Baveno VI, and 31.4% for RESIST-HCV. False-negative rates and NPVs for the entire RESIST-HCV cohort, the training cohort, and the validation cohort are shown in Table 3 and Supplementary Table 2 (Supplementary Digital Content 1, http://links.lww.com/AJG/A183).

Table 3

Table 3

The rates of endoscopy avoidance were similar using the RESIST-HCV and Expanded Baveno VI criteria; the NPVs were also similar (98.4% and 97.4%). Adding TE to the RESIST-HCV algorithm reduced the number of EGDs that would have been performed without increasing the NPV (98.2%). Moreover, the RESIST-HCV criteria do not include the liver stiffness evaluation, so they may be used in centers that lack this capability. Further diagnostic performance characteristics of noninvasive criteria used to rule out medium/large EV are shown in Supplementary Table 3 (Supplementary Digital Content 1, http://links.lww.com/AJG/A183).

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DISCUSSION

In this study, we have shown that the original Baveno VI criteria (6) and the Expanded Baveno VI criteria (9) to screen for EV requiring prophylactic therapy in patients with cirrhosis can be simplified and safely replaced with the RESIST-HCV algorithm that includes only serum albumin level and PLT count. The use of the RESIST-HCV criteria can reduce the number of endoscopies needed by more than 30% while minimizing the risk of missing varices needing treatment.

We have also validated in our cohort both the Baveno VI and the Expanded Baveno VI recommendations. In contrast to previous studies (7–9), however, our study also aimed to validate the criteria using a large cohort of patients with a single etiology and included patients with Child-Pugh B cirrhosis. This approach was informed by the issues highlighted in the meta-analysis of Marot and colleagues (13), who stated that these validations have relevant bias related to the stage of advanced liver disease, EV prevalence, and cirrhosis etiology. Previously, Maurice et al. (7) analyzed data for 310 patients with cirrhosis (any etiology) who had TE measurements of 10 kPa or greater and had non-decompensated disease. A TE cut-off value of 10 kPa is associated with a high rate of patient misclassification, with a large portion of patients not having a clear diagnosis of cirrhosis and portal hypertension (14). Despite selection rules, the Baveno VI criteria incorrectly classified 2% of patients in an English cohort (7). A study by Ding et al. (15) excluded patients with a history of decompensation and analyzed 2 cohorts of less than 100 patients with any cirrhosis etiology.

The Expanded Baveno VI criteria (9) were met by 36% of patients in our cohort who would have been able to forego EGD. This reduction in invasive testing occurred without an increase in the false-negative results. It should be noted that using these criteria, 13 patients had medium/large EV for whom it would have been unsafe to forego EGD.

The main objectives of our study were to simplify the assessment of portal hypertension in patients with HCV and advanced liver disease and to identify the role of TE in predicting the presence of EV requiring prophylactic therapy to assess the advantage of using a noninvasive algorithm including TE in this setting. Although TE has now been adopted broadly by hepatology centers, it is not immediately available in all liver units. Thus, hepatologists have asked patients to go to other centers if TE is needed to establish the diagnosis of cirrhosis.

Among the 22 centers in the RESIST-HCV network, TE was available in 12. All 12 of these facilities offered TE for patients referred from outside centers that lacked access to that testing. However, the main limitation of TE unavailability is in the need for an annual re-screening, as suggested by the Baveno VI criteria, to determine whether there are TE changes that would prompt an EGD evaluation. An even greater challenge is the use of TE for at-risk persons with poor adherence who have a history of drug use, HIV, or incarceration, who may not have access to TE.

To simplify the criteria for the diagnosis of medium/large EV, we have proposed an alternative, noninvasive algorithm using only routinely performed laboratory tests. Indeed, multivariate logistic analysis showed that PLT count and serum albumin level were independently associated with medium/large EV and that a PLT count cut-off of greater than 120,000 cells/μL and a serum albumin level greater than 3.6 g/dL were able to identify patients without medium/large EV with an NPV slightly higher than that for the Baveno VI and Expanded Baveno VI criteria. Nevertheless, the great advantage of the RESIST-HCV criteria was the ability to identify more than 30% of cases for which EGD could be avoided. Adding TE to the RESIST-HCV algorithm did not further improve the performance of the criteria.

Our study has some limitations that deserve mention. First, the data analysis was retrospective. Second, a minority of patients with decompensated cirrhosis was included; for these patients, the EV size is less applicable as a predictor of bleeding. Third, the evaluation of EV size was performed by several endoscopists, as cohorts composed of patients from more than 20 liver centers throughout Sicily. To investigate the possibility of bias, we selected patients attending a referral liver centre for the training cohort and included all other patients attending other centers in the validation cohort. Our data show the cohorts to have similar prevalences of EV requiring prophylaxis and similar diagnostic results for the Baveno VI, Expanded Baveno VI, and RESIST-HCV criteria.

Another relevant point that needs to be addressed is that the AUROC curves for all noninvasive tools analyzed were low. This phenomenon reflects the fact that for all noninvasive criteria used to diagnose medium/large EV, researchers have given priority to sensitivity over specificity. Therefore, the AUROCs are often suboptimal.

We maintain that at least 3 issues still need to be addressed. First, noninvasive testing does not allow for the detection of small EV, which are used to define the cirrhosis stage and have prognostic relevance after sustained virological response achievement (1–3). Second, for patients with HCV, modifications induced by sustained virological response in liver stiffness and in blood tests may hamper the ability of noninvasive strategies in the setting of long-term follow-up of patients with cirrhosis (16,17). Third, further studies are needed to validate our new criteria in the growing population of patients with cirrhosis caused by alcoholic and nonalcoholic steatohepatitis.

In conclusion, the use of our new noninvasive strategy can avoid more than 30% of EGDs by using only routine blood test results (PLT count and serum albumin level) while maintaining a very high NPV and low false-negative rate. A noninvasive strategy is needed to rule out also the presence of small EV, and the RESIST-HCV criteria require validation in other larger cohorts of persons with cirrhosis of different etiologies.

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CONFLICTS OF INTEREST

Guarantor of the article: Vincenza Calvaruso, MD, PhD.

Specific author contributions: V.C.: analysis and interpretation of data, drafting of the manuscript, statistical analysis, critical revision of the manuscript for important intellectual content. I.C., A.L., S.M., R.B.: acquisition of data. S.P.: acquisition of data, critical revision of the manuscript for important intellectual content. F.B., E.C., G.M., G.B., M.D., A.M., A.D., G.A., B.C., A.D., L.G., I.S., P.C., F.C., V.P., T.P., A.A., C.I., L.M., G. Scifo, M.R., G. Squadrito: acquisition of data. G.R.: study concept and design, critical revision of the manuscript for important intellectual content. C.C.: study concept and design, analysis and interpretation of data, statistical analysis, critical revision of the manuscript for important intellectual content. A.C.: study concept and design, analysis and interpretation of data, critical revision of the manuscript for important intellectual content. V.D.M.: study concept and design, analysis and interpretation of data, drafting of the manuscript, study supervision. All authors approved the final version of the manuscript.

Financial support: No financial support was received in relation to this manuscript. The RESIST-HCV is funded by unrestricted grants from Gilead, MSD, Abbvie, and BMS.

Potential competing interests: V.C., S.P., M.D., G. Scifo: participated in the advisory board for Abbvie. G.R.: Participated in the advisory boards for Abbvie, BMS, Gilead, MSD/Merck. C.C.: participated in the advisory board for MSD/Merck. A.C.: research support from Abbvie, BMS, Gilead, Merck/MSD, Intercept; provided consultancy, speakers bureau, and participated in the advisory boards for Abbvie, BMS, Gilead, MSD/Merck. V.D.M.: research support from Abbvie, BMS, Gilead, Merck/MSD; participated in the advisory boards for Abbvie, BMS, MSD/Merck. The other authors have no disclosures to declare.

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Study Highlights

WHAT IS KNOWN

  • ✓ Patients with cirrhosis should undergo EGD to screen for the presence of EV.
  • ✓ The Baveno VI consensus and an expanded algorithm use TE and PLT count to identify patients with cirrhosis who can avoid EGD.
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WHAT IS NEW HERE

  • ✓ RESIST-HCV criteria using only routine blood tests (PLTs, albumin) can avoid more than 30% of EGDs used to screen for EV.
  • ✓ The use of RESIST-HCV criteria simplifies the diagnosis of portal hypertension.
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