Risk stratification of decompensation using liver stiffness and platelet counts in compensated advanced chronic liver disease (CHESS2102)

The latest EASL guidelines on non-invasive tests for the evaluation of liver disease severity and prognosis proposed an algorithm for risk stratification in compensated chronic liver disease (CLD) using non-invasive tools.[1]Berzigotti A. Boursier J. Castera L. Cazzagon N. Friedrich-Rust M. Petta S. et al.European Association for the Study of the Liver; List of panel members (alphabetical order)Easl clinical practice guidelines (Cpgs) on non-invasive tests for evaluation of liver disease severity and prognosis – 2021 update.J Hepatol. 2021; 75: 659-689Abstract Full Text Full Text PDF PubMed Scopus (129) Google Scholar Patients with liver stiffness measurement (LSM) <20 kPa and platelet counts (PLT) >150 ×109/L are very unlikely to have varices needing treatment, while those not meeting this criteria are at an increased risk of clinical decompensation.[1]Berzigotti A. Boursier J. Castera L. Cazzagon N. Friedrich-Rust M. Petta S. et al.European Association for the Study of the Liver; List of panel members (alphabetical order)Easl clinical practice guidelines (Cpgs) on non-invasive tests for evaluation of liver disease severity and prognosis – 2021 update.J Hepatol. 2021; 75: 659-689Abstract Full Text Full Text PDF PubMed Scopus (129) Google Scholar LSM is the most validated non-invasive tool for risk stratification in CLD and a cut-off >20-25 kPa could be used to identify patients with clinically significant portal hypertension,[2]You M.W. Kim K.W. Pyo J. Huh J. Kim H.J. Lee S.J. et al.A meta-analysis for the diagnostic performance of transient elastography for clinically significant portal hypertension.Ultrasound Med Biol. 2017; 43: 59-68Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar,[3]Qi X. Berzigotti A. Cardenas A. Sarin S.K. Emerging non-invasive approaches for diagnosis and monitoring of portal hypertension.Lancet Gastroenterol Hepatol. 2018; 3: 708-719Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar which is closely associated with decompensation in patients with CLD.[4]Ripoll C. Groszmann R. Garcia-Tsao G. Grace N. Burroughs A. Planas R. et al.Hepatic venous pressure gradient predicts clinical decompensation in patients with compensated cirrhosis.Gastroenterology. 2007; 133: 481-488Abstract Full Text Full Text PDF PubMed Scopus (718) Google Scholar,[5]Albillos A. Bañares R. González M. Ripoll C. Gonzalez R. Catalina M.V. et al.Value of the hepatic venous pressure gradient to monitor drug therapy for portal hypertension: a meta-analysis.Am J Gastroenterol. 2007; 102: 1116-1126Crossref PubMed Scopus (113) Google Scholar However, in the latest EASL and AASLD guidelines on portal hypertension, no clear recommendation was given on whether 20 kPa or 25 kPa is better to differentiate patients at risk of clinical decompensation.[6]Garcia-Tsao G. Abraldes J.G. 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. 2017; 65: 310-335Crossref PubMed Scopus (920) Google Scholar,[7]de Franchis R. Baveno VI facultyExpanding consensus in portal hypertension: report of the Baveno VI Consensus Workshop: stratifying risk and individualizing care for portal hypertension.J Hepatol. 2015; 63: 743-752Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar This study aimed to further stratify patients at risk of clinical decompensation using LSM cut-offs of 20 kPa and 25 kPa. We retrospectively included adult patients diagnosed with compensated advanced chronic liver disease (cACLD) in the study initiated by Chinese Portal Hypertension Alliance (CHESS) from China, Japan, and South Korea between January 2009 and June 2018. Decompensation events, defined as ascites, variceal hemorrhage, or hepatic encephalopathy were reviewed from the follow-up data. As a result, 661 eligible patients with cACLD (male/female, 405/256) with a mean age of 53 years (standard deviation, 12) were included. The median length of follow-up was 41.2 months (interquartile range, 28.2-60.5). The overall decompensation rate was 10.7% (71/661). Details for the baseline characteristics were summarized in Table S1. Based on LSM by transient elastography (FibroScan, Echosens, France) and PLT, patients were divided into 4 grades, Grade 0 (LSM <20 kPa and PLT >150 ×109/L) (n = 223), Grade 1 (LSM <20 kPa and PLT <150 ×109/L) (n = 238), Grade 2 (20 kPa≤ LSM <25 kPa) (n = 66), and Grade 3 (LSM ≥25 kPa) (n = 134), respectively (Fig. 1A). Ascites remained the most common decompensation event in patients of each grade. As shown in Fig. 1B, the sub-distribution hazard ratios of reaching decompensation between Grade 0 and 1, 2, 3 were 9.8 (95% CI 2.3-42.1), 16.8 (95% CI 3.7-76.7), and 38.0 (95% CI 9.2-158.0), respectively. The cumulative incidence curves revealed a trend of increasing incidence of decompensation from patients with Grade 0 to Grade 3 (Fig. 1B). Pairwise comparisons using log-rank test in 4 groups showed significant differences in incidence of decompensation (all p adjust <0.001) except for the comparison between Grade 1 and Grade 2 (p adjust = 0.148). LSM <20 kPa and PLT >150 ×109/L, known as the Baveno VI criteria, has been well validated for the identification of patients with cACLD who are unlikely to have varices needing treatment and can safely avoid variceal screening endoscopy.6Garcia-Tsao G. Abraldes J.G. 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. 2017; 65: 310-335Crossref PubMed Scopus (920) Google Scholar, 7de Franchis R. Baveno VI facultyExpanding consensus in portal hypertension: report of the Baveno VI Consensus Workshop: stratifying risk and individualizing care for portal hypertension.J Hepatol. 2015; 63: 743-752Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar, 8Thabut D. Bureau C. Layese R. Bourcier V. Hammouche M. Cagnot C. et al.Validation of Baveno VI criteria for screening and surveillance of esophageal varices in patients with compensated cirrhosis and a sustained response to antiviral therapy.Gastroenterology. 2019; 156: 997-1009.e5Abstract Full Text Full Text PDF PubMed Scopus (68) Google Scholar, 9Stafylidou M. Paschos P. Katsoula A. Malandris K. Ioakim K. Bekiari E. et al.Performance of Baveno VI and expanded Baveno VI criteria for excluding high-risk varices in patients with chronic liver diseases: a systematic review and meta-analysis.Clin Gastroenterol Hepatol. 2019; 17: 1744-1755.e11Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar Our results demonstrated that patients not meeting the Baveno VI criteria were indeed at a significantly higher risk of liver decompensation compared to those meeting the criteria. More importantly, the results of the present study showed a similar cumulative incidence of decompensation between patients with Grade 1 (LSM <20 kPa and PLT <150 ×109/L) and Grade 2 (20 kPa≤ LSM <25 kPa, regardless of PLT). These patients might be classified as patients with medium risk of clinical decompensation. Besides, patients with an LSM ≥25 kPa had a significantly higher rate of reaching decompensation than patients with Grade 0, 1, and 2; therefore, they could be classified as patients with a high risk of clinical decompensation. A risk stratification algorithm of decompensation based on LSM and PLT in patients with cACLD was summarized in Fig. 1C. As etiology of cACLD should be considered when applying non-invasive tools,[10]Qi X. Liu F. Li Z. Chen S. Liu Y. Yang Y. et al.Insufficient accuracy of computed tomography-based portal pressure assessment in hepatitis B virus-related cirrhosis: an analysis of data from CHESS-1601 trial.J Hepatol. 2017; 5 (S0168–8278(17)32277–8)Google Scholar the hepatitis B or C virus-dominant etiology and retrospective nature of our study may bring bias to the study; thus, prospective studies with different etiological spectrums are needed to validate our results. To conclude, this international study further stratifies patients at risk of clinical decompensation and could be a supplement to the proposed algorithm in the latest EASL guidelines on non-invasive risk stratification of patients with cACLD. This study was supported by Gansu Science Foundation for Distinguished Young Scholars ( 20JR10RA713 ). Study design and concept: Qi X; Acquisition of data: Li J, Kim TH, Enomoto H; Statistical analysis and interpretation of data: Liu C, Liu Y; Drafting of the manuscript: Liu Y, Liu C; Critical revision of the manuscript: Qi X, Li J, Kim TH, Enomoto H. All authors have approved the final version of the article. The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details. We thank Prof. Hiroko Iijima and Dr. Takashi Nishimura (Hyogo College of Medicine Hospital, Nishinomiya, Japan); Prof. Young Kul Jung and Prof. Hyung Joon Yim (Korea University Ansan Hospital, Ansan-si, Gyeonggi-do, Republic of Korea); and Prof. Zhongfang Yan, Xin Li, and Dr. Lili Zhao (Tianjin Second People's Hospital, Tianjin, China) for their support in acquisition of data in this study. The following is the supplementary data to this article: Download .pdf (.18 MB) Help with pdf files Multimedia component 1 Download .pdf (.19 MB) Help with pdf files Multimedia component 2 EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis – 2021 updateJournal of HepatologyVol. 75Issue 3PreviewNon-invasive tests are increasingly being used to improve the diagnosis and prognostication of chronic liver diseases across aetiologies. Herein, we provide the latest update to the EASL Clinical Practice Guidelines on the use of non-invasive tests for the evaluation of liver disease severity and prognosis, focusing on the topics for which relevant evidence has been published in the last 5 years. Full-Text PDF Reply to: Correspondence on "EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis – 2021 update"Journal of HepatologyVol. 76Issue 1PreviewWe thank Loosen et al.,1 van Kleef et al.2 and Liu et al.3 for their interest in our work.4 The observation of Loosen et al. that fibrosis-4 (FIB-4) ≥1.3 is associated with an over 12-fold increase in the risk of hepatocellular carcinoma in a large cohort of 29,999 patients with non-alcoholic fatty liver disease (NAFLD) in Germany followed-up between 2005 and 2019 is very important, and confirms previous observations in the Asian population with NAFLD.5 This data underlines that patients with FIB-4 >1.3 should be referred for further evaluation and surveillance, as suggested by our CPGs. Full-Text PDF