Non-invasive tests for clinically significant portal hypertension after HCV cure

• DOI: 10.1016/j.jhep.2022.08.025
• Publication Date: 2022-09-05T17:33:48Z
• Authors: Georg Semmler; Sabela Lens; Elias L. Meyer; Anna Baiges; Edilmar Alvardo-T...; Elba Llop; Luis Tellez; Philipp Schwabl; Ezequiel Mauro; Laia Escudé; Cristina Díez; Luis Ibañez-Saman...; Ángela Puente; José Ignacio Fortea; Marta Abadía; Alberto Zanetto; Andrés Conthe; Helena Hernandez-...; Irina Sofia Luzko...; Jidong Jia; Hitoshi Yoshiji; Sven M. Francque; Emmanuel A. Tsoch...; Francesco Paolo R...; Gonzalo Crespo; Xavier Forns; Rafael Bañares; Càndid Villanueva; Virginia Hernánde...; Thomas Reiberger; Jaume Bosch; Juan Carlos Garcí...; Mattias Mandorfer
• Keywords: CSPH; HVPG; LSM; NIT; SVR; aetiological cure; chronic hepatitis C; hepatic venous pressure gradient; liver stiffness measurement; platelet count; sustained virologic response; transient elastography; liver cell carcinoma; Sustained Virologic Response; prevalence; portal vein blood pressure; 610 Medicine & health; Hepacivirus; Article; compensated liver cirrhosis; Hypertension, Portal; follow up; Humans; controlled study; diagnostic test accuracy study; human; sustained virologic response; chronic liver disease; portal hypertension; interferon; platelet count; cohort analysis; major clinical study; transient elastography; Hepatitis C; Portal Pressure; 3. Good health; hepatic venous pressure gradient; liver stiffness; sensitivity and specificity; diagnostic accuracy; Human medicine; diagnostic value; hepatitis C; non invasive measurement; clinically significant portal hypertension; decompensated liver cirrhosis

Non-invasive tests (NITs) for clinically significant portal hypertension (CSPH; hepatic venous pressure gradient [HVPG] ≥10 mmHg) have predominantly been studied in patients with active HCV infection. Investigations after HCV cure are limited and have yielded conflicting results. We conducted a pooled analysis to determine the diagnostic/prognostic utility of liver stiffness measurement (LSM)/platelet count (PLT) in this setting.A total of 418 patients with pre-treatment HVPG ≥6 mmHg who achieved sustained virological response (SVR) and underwent post-treatment HVPG measurement were assessed, of whom 324 (HVPG/NIT-cohort) also had paired data on pre-/post-treatment LSM/PLT. The derived LSM/PLT criteria were then validated against the direct endpoint decompensation in 755 patients with compensated advanced chronic liver disease (cACLD) with SVR (cACLD-validation-cohort).HVPG/NIT-cohort: Among patients with cACLD, the pre-/post-treatment prevalence of CSPH was 80%/54%. The correlation between LSM/HVPG increased from pre- to post-treatment (r = 0.45 vs. 0.60), while that of PLT/HVPG remained unchanged. For given LSM/PLT values, HVPG tended to be lower post- vs. pre-treatment, indicating the need for dedicated algorithms. Combining post-treatment LSM/PLT yielded a high diagnostic accuracy for post-treatment CSPH in cACLD (AUC 0.884; 95% CI 0.843-0.926). Post-treatment LSM <12 kPa & PLT >150 G/L excluded CSPH (sensitivity: 99.2%), while LSM ≥25 kPa was highly specific for CSPH (93.6%). cACLD-validation-cohort: the 3-year decompensation risk was 0% in the 42.5% of patients who met the LSM <12 kPa & PLT >150 G/L criteria. In patients with post-treatment LSM ≥25 kPa (prevalence: 16.8%), the 3-year decompensation risk was 9.6%, while it was 1.3% in those meeting none of the above criteria (prevalence: 40.7%).NITs can estimate the probability of CSPH after HCV cure and predict clinical outcomes. Patients with cACLD but LSM <12 kPa & PLT>150 G/L may be discharged from portal hypertension surveillance if no co-factors are present, while patients with LSM ≥25 kPa require surveillance/treatment.Measurement of liver stiffness by a specific ultrasound device and platelet count (a simple blood test) are broadly used for the non-invasive diagnosis of increased blood pressure in the veins leading to the liver, which drives the development of complications in patients with advanced liver disease. The results of our pooled analysis refute previous concerns that these tests are less accurate after the cure of hepatitis C virus (HCV) infection. We have developed diagnostic criteria that facilitate personalized management after HCV cure and allow for a de-escalation of care in a high proportion of patients, thereby decreasing disease burden.