Noninvasive Diagnosis of Portal Hypertension in Patients With Compensated Advanced Chronic Liver Disease

Abstract

Objectives: We aimed to explore the prevalence of portal hypertension in the most common etiologies of patients with compensated advanced chronic liver disease (cACLD) and develop classification rules, based on liver stiffness measurement (LSM), that could be readily used to diagnose or exclude clinically significant portal hypertension (CSPH) in clinical practice. Methods: International cohort study including patients with paired LSM/hepatic venous pressure gradient (HVPG), LSM ≥10kPa and no prior decompensation. Portal hypertension was defined by an HVPG>5 mmHg. A positive predictive value (PPV) ≥90% was considered to validate LSM cut-offs for CSPH (HVPG≥10 mmHg), while a negative predictive value ≥90% ruled out CSPH. Results: 836 patients were evaluated: hepatitis C (HCV, n=358), non-alcoholic steatohepatitis (NASH, n=248), alcohol (ALD, n=203) and hepatitis B (HBV, n=27). Portal hypertension prevalence was >90% in all cACLD etiologies, except for NASH patients (60.9%), being even lower in NASH obese patients (53.3%); these lower prevalences of portal hypertension in NASH patients were maintained across different strata of LSM values. LSM≥25 kPa was the best cut-off to rule in CSPH in ALD, HBV, HCV and non-obese NASH patients, while in obese NASH patients the PPV was only 62.8%. A new model for NASH patients (ANTICIPATE-NASH model) to predict CSPH considering BMI, LSM and platelet count was developed and a nomogram constructed. LSM≤15 kPa plus platelets ≥150x10 9 /L ruled out CSPH in most etiologies. Conclusions: Patients with cACLD of NASH etiology, especially obese NASH patients, present lower prevalences of portal hypertension compared to other cACLD etiologies. LSM≥25 kPa is sufficient to rule in CSPH in most etiologies, including non-obese NASH patients, but not in obese NASH patients. Response to Reviewers:Point-by-point answers to reviewers' comments: Editor/Editorial Board Comments: Editors: After reviewing the manuscript and the comments from the peer reviewers, we would like to ask the authors to address the following issues raised by the editors:1. Was there any correlation of their findings with EGD, and specifically with the absence/presence of high-risk esophageal varices warranting prophylaxis with betablockers or endoscopic band ligation? This a very good point, but information regarding endoscopy was not requested to the participating centers (only LSM and HVPG were available) and it was not an objective of this study. Only the "ANTICIPATE" cohort had endoscopy data and this has been published in the "Anticipate" paper (Hepatology 2016; 64:2173-84) and the Expanded Baveno paper (Hepatology 2017; 66:1980-8).2. Can the authors please convert lab values in table 1 from SI to conventional units? Done.3. We request the authors provide clearer instructions on how to use the nomogram from figure 3. Maybe they can provide an example or improve the instructions, something similar to what was described for the nomogram in figure 4 of the Hepatology 2016 paper on the "Anticipate" study. Thank you for the...

Nonselective Beta-Blockers in Compensated Cirrhosis: Preventing Variceal Hemorrhage or Preventing Decompensation?

“…The ANTICIPATE study has recently provided a model to predict CSPH based on LS and platelet count. The model was developed 13 and subsequently validated 14 mainly in patients with hepatitis C and alcohol, although it requires a correction in patients with obesity and nonalcoholic steatohepatitis. 14 These predictive models can be simplified, and the finding of an LS >25 kPa has a very high positive predictive value for CSPH (Figure 1).…”

“…The model was developed 13 and subsequently validated 14 mainly in patients with hepatitis C and alcohol, although it requires a correction in patients with obesity and nonalcoholic steatohepatitis. 14 These predictive models can be simplified, and the finding of an LS >25 kPa has a very high positive predictive value for CSPH (Figure 1). In addition, as stated above, the presence of collaterals on ultrasound or of varices in a previous endoscopy also rule in CSPH.…”

EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis – 2021 update

“…The accuracy of LSM increases if this is combined with unrelated NITs, in particular platelet count and spleen size (liver stiffness-spleen diameter to platelet ratio score [LSPS]; 268 PH risk score 269,270 (see Table 4 for the most used formulas).…”

Cyclic GMP in Liver Cirrhosis—Role in Pathophysiology of Portal Hypertension and Therapeutic Implications

“…Several biochemical parameters in liver cirrhosis indicate hepatocyte damage or cholestasis, while others indicate stimulated synthesis of extracellular matrix proteins (laminin, hyaluronic acid, procollagen-III-peptide, Mac-2-binding protein glycosylation isomer) by stimulated HSCs (myofibroblasts), thus reflecting the degree of liver fibrosis. Various serum markers are suitable tools to detect clinically significant portal hypertension [ 119 , 120 , 121 , 122 , 123 ].…”