Validation of the Baveno VI criteria to rule out high-risk varices using hepatic shear-wave elastography.

INTRODUCTION AND OBJECTIVES: Liver stiffness measurement (LSM) by transient elastography has been validated to predict high-risk varices (HRV). We aimed to evaluate the accuracy of shear-wave elastography (SWE) and platelet count (Baveno VI criteria) to rule out HRV in patients with compensated advanced chronic liver disease (c-ACLD). METHODS: This retrospective study analyzed data of patients with c-ACLD (transient elastography ≥ 10 kPa) submitted to two-dimensional SWE (2D-SWE) (GE-LOGIQ-S8) and/or point SWE (p-SWE) (ElastPQ) who had a gastrointestinal endoscopy within 24 months. HRV definition was a large size and presence of red wale marks or sequelae from previous treatment. Optimal thresholds of SWE systems for HRV were identified. The proportion of spared gastrointestinal endoscopies and missing HRV considering a favorable SWE Baveno VI criteria were assessed. RESULTS: Eighty patients [36% male, median age = 63 (interquartile range, 57-69) years] were included. The prevalence of HRV was 34% ( n  = 27/80). The optimal thresholds to predict HRV were 10 kPa and 12 kPa for 2D-SWE and p-SWE, respectively. A favorable 2D-SWE Baveno VI criteria (LSM < 10 kPa and platelets count > 150 × 10 9 /mm 3 ) avoided 19% of gastrointestinal endoscopies without missing HRVs. A favorable p-SWE Baveno VI criteria (LSM < 12 kPa and platelets count > 150 × 10 9 /mm 3 ) spared 20% of gastrointestinal endoscopy without missing HRVs. Using a lower threshold of platelet count (<110 × 10 9 /mm 3 , expanded Baveno VI), 2D-SWE (<10 kPa) avoided 33% of gastrointestinal endoscopy with 8% of missing HRVs, while p-SWE (<12 kPa) avoided 36% of gastrointestinal endoscopy with 5% of missing HRVs. CONCLUSION: LSM by p-SWE or 2D-SWE combined with platelet count (Baveno VI criteria) can spare a considerable number of gastrointestinal endoscopies missing a negligible proportion of HRV.

Natural History of Hepatosplenic Schistosomiasis (HSS) Non-Cirrhotic Portal Hypertension (NCPH): Influence of Gastrointestinal Bleeding and Decompensation in Prognosis.

BACKGROUND: Hepatosplenic schistosomiasis (HSS) is a peculiar form of non-cirrhotic portal hypertension (NCPH). Although HSS patients present normal hepatic function, some evolve signs of hepatocellular failure and features of decompensated cirrhosis. The natural history of HSS-NCPH is unknown. METHODS: A retrospective study was conducted that evaluated patients who fulfilled clinical-laboratorial criteria for HSS. RESULTS: A total of 105 patients were included. Eleven patients already presented with decompensated disease and had lower transplant-free survival at 5 years than those without (61% vs. 95%, p = 0.015). Among 94 patients without prior decompensation, the median follow-up was 62 months and 44% of them had varicose bleeding (two or more episodes in 27%). Twenty-one patients presented at least one episode of decompensation (10-year probability 38%). Upon multivariate analysis, varicose bleeding and higher bilirubin levels were associated with decompensation. The 10-year probability of survival was 87%. Development of decompensation and age were predictive of mortality. CONCLUSION: HSS is characterized by multiple episodes of GI bleeding, a high probability of decompensation and reduced survival at the end of the first decade. Decompensation is more common in patients with varicose esophageal bleeding and is associated with lower survival.

2-D Shear Wave Elastography for the Evaluation of Liver Fibrosis in Hepatosplenic Schistosomiasis: Reliability of a Single Measurement and Inter-Hepatic Lobe Variability.

Data on liver and spleen stiffness by 2-D shear wave elastography (2-D SWE) in hepatosplenic schistosomiasis (HES) remain scarce. We aimed to assess the correlation between single to multiple measurements of liver and spleen stiffness and to evaluate inter-hepatic lobe variability of liver stiffness measurement (LSM) using 2-D SWE in HES patients. Liver and spleen elastography were performed in HES patients in this cross-sectional study. A total of four stiffness measurements were performed in the right lobe (RL), left lobe (LL), and spleen. The correlation between the first measurement and the median of four measurements was assessed. Liver stiffness measurement of both hepatic lobes was compared. Twenty-six HES patients were included. Liver stiffness measurement was higher in the left than in the right hepatic lobe (17.9 kPa [11.3-92.0] versus 14.9 kPa [5.6-44.4]; P = 0.019). The first measurement was similar to the median of the four measurements for the RL (14.6 [5.6-60.8] versus 14.9 kPa [5.6-44.4]; P = 0.87), LL (17.4 [8.0-128.1] versus 17.9 kPa [11.3-92.0]; P = 0.54), and spleen (50.5 [10.0-157.0] versus 55.7 kPa [19.1-119.4]; P = 0.48). An excellent correlation between the first measurement and the median of four measurements for the RL (r = 0.93; P < 0.001), LL (r = 0.88; P < 0.001), and spleen (r = 0.89; P < 0.001) was observed. In HES, LSM of the LL seems to be higher than that of the right hepatic lobe. Considering the excellent correlation between the first measurement and the median of four measurements in both hepatic lobes and spleen, a single measurement would be sufficient to evaluate liver and splenic stiffness in patients with HES.

Effectiveness of direct-acting agents for hepatitis C and liver stiffness changing after sustained virological response.

BACKGROUND AND AIM: Few studies have evaluated sustained virological response (SVR) rates by direct-acting agents (DAAs) and liver stiffness measurement (LSM) changing post-SVR in limited-resource settings. We aimed to describe the effectiveness of DAAs for hepatitis C virus treatment and to assess the changing of LSM post-SVR. METHODS: This retrospective study analyzed data of consecutive hepatitis C virus-infected patients treated by DAAs from 2015 to 2017 in two tertiary centers in Brazil. SVR rates were reported by intention-to-treat and per-protocol analyses. LSM by transient elastography performed before treatment and post-SVR was compared, and logistic regression models were performed. RESULTS: Six hundred seventy-one patients (63% female, 62 years [55-68], 89% genotype 1, 8% HIV co-infected, and 64% with cirrhosis) were included. Most patients were treated by sofosbuvir/daclatasvir ± ribavirin (74%) and sofosbuvir/simeprevir ± ribavirin (21%). SVR rates (95% confidence interval [CI]) were 94.6% (92.7-96.1) and 97.8% (96.4-98.7) for intention-to-treat and per-protocol analyses, respectively. The leading adverse event was anemia (9.6% [95% CI 7.6-12.1]). Pretreatment and post-SVR12 LSM were available in 400 patients. LSM had significantly decreased after SVR (13.6 kPa [interquartile range, 10.0-21.6] vs 10.2 kPa [7.0-17.6], P < 0.001). A total of 167 patients (42%) decreased at least 30% of LSM post-SVR. The absence of type 2 diabetes (odds ratio = 1.52 [95% CI 1.05-2.21], P = 0.028) and presence of platelet count ≥ 150 × 109 /mm3 (odds ratio = 1.75 [1.23-2.50], P = 0.002) were independently associated with a significant LSM regression (≥ 30%) post-SVR. CONCLUSION: DAAs were highly effective and safe, and LSM significantly decreased after SVR in a real-life cohort in Brazil. The absence of type 2 diabetes and presence of high platelet count were independently associated with LSM decrease post-SVR.

Reliability and safety of transnasal compared to conventional endoscopy for detecting oesophageal varices in cirrhotic patients.

BACKGROUND & AIMS: Unsedated transnasal endoscopy may be used for detecting oesophageal varices. However, few studies evaluated feasibility and accuracy of this technique. We aimed to evaluate accuracy, interobserver agreement and safety of the transnasal ultrathin compared to conventional endoscopy in patients with cirrhosis. METHODS: This cross-sectional study included consecutive patients referred for screening or surveillance of oesophageal varices. Patients underwent unsedated transnasal and sedated conventional endoscopies at the same day, which were recorded in a digital video file and randomly analysed by two double-blinded endoscopists. High-risk varices were defined by the presence of large calibre or red wale marks. Accuracy, interobserver agreement and safety of transnasal were compared to conventional endoscopy. RESULTS: One hundred and thirty-three cirrhotic patients (48% male, aged of 60 ± 5, 34% Child-Pugh B/C and 71% of cases for variceal screening) were included in the study. The prevalence of oesophageal varices and high-risk oesophageal varices were 59% (n = 79) and 29% (n = 39) respectively. For the presence of oesophageal varices, transnasal GIE yielded sensitivity of 94% [95% Confidence Interval, CI 88-99], specificity of 89% [81-97] as well as positive and negative predictive value of 93% and 91% respectively. A satisfactory interobserver agreement was observed for the presence of oesophageal varices (κ = 0.89) and high-risk varices (κ = 0.65). No serious adverse events were recorded; transnasal GIE was safe and significantly associated with lower rates of hypoxaemia (P < .0001) and hypotension (P < .0001) compared to conventional endoscopy. CONCLUSIONS: Unsedated transnasal endoscopy was safe and had an excellent accuracy and high interobserver agreement for detecting oesophageal varices and for identifying high-risk varices in cirrhotic patients.

Latent Class Analysis of Noninvasive Methods and Liver Biopsy in Chronic Hepatitis C: An Approach without a Gold Standard.

AIMS: To evaluate the applicability of the Latent Class Analysis (LCA) and accuracy of transient elastography (TE), aspartate-to-platelet-ratio-index (APRI), enhanced liver fibrosis (ELF), and liver biopsy (LB) for liver fibrosis assessment in a model without a gold standard. METHODS: Significant fibrosis was defined as TE ≥ 7.1 kPa, APRI ≥ 1.5, ELF ≥ 9.37, or LB METAVIR F ≥ 2. Cirrhosis was defined as TE ≥ 12.5 kPa, APRI ≥ 2.0, ELF ≥ 10.31, or LB as METAVIR F = 4. RESULTS: 117 patients with chronic hepatitis C were included. In the LCA, for significant fibrosis the sensitivities and specificities (95% CI) were 0.92 (0.86-0.98) and 0.79 (0.72-0.86) for TE; 0.47 (0.40-0.54) and 0.99 (0.95-1.00) for APRI; 0.81 (0.74-0.88) and 0.78 (0.71-0.85) for ELF; and 0.86 (0.68-1.00) and 0.91 (0.79-1.00) for LB. For cirrhosis, the sensitivities and specificities were 0.92 (0.76-1.00) and 0.94 (0.91-0.97) for TE; 0.57 (0.37-0.77) and 0.97 (0.93-1.00) for APRI; 0.94 (0.84-1.00) and 0.88 (0.82-0.94) for ELF; and 0.30 (0.12-0.48) and 1.00 for LB. CONCLUSION: LCA was useful to evaluate accuracy of methods for liver fibrosis staging. Sensitivities and specificities of noninvasive methods were increased in LCA compared to the use of LB as the gold standard.

Transient elastography evaluation of hepatic and spleen stiffness in patients with hepatosplenic schistosomiasis.

BACKGROUND: Hepatosplenic schistosomiasis (HES) has not been evaluated by transient elastography so far and its correlation with ultrasound variables remains to be defined. AIMS: The aim of this study was to describe the parameters of liver and spleen stiffness in HES assessed by transient elastography in comparison with cirrhotics and controls evaluating its correlation with ultrasonographic data. PATIENTS AND METHODS: HES, hepatitis C virus-cirrhotic, and control patients were included in this sectional study. Liver and spleen stiffness were compared among the three groups. The ultrasonographic parameters were compared with transient elastography in HES patients. RESULTS: Thirty HES, 30 hepatitis C virus-cirrhotic patients, and 17 controls were included. Those with HES presented liver stiffness that was significantly higher than the controls and lower than the cirrhotics: 9.7 (3.6-75.0) versus 3.7 (2.8-5.4) versus 27.0 (14.7-61.5) kPa (P<0.001). Spleen stiffness values were comparable between hepatosplenic and cirrhotics: 66.4 (25.7-75.0) versus 69.1 (18.0-75.0) kPa (P=0.78) and were significantly higher than the controls 16.5 kPa (6.3-34.3) (P<0.001). In patients with HES, high spleen stiffness was associated with right liver lobe diameter (P=0.015), splenic artery resistance index (P=0.002), portal vein diameter (P=0.021), portal vein area (P=0.008), portal vein congestion index (P=0.035), splenic vein diameter (P=0.013), and spleen diameter (P=0.021). CONCLUSION: Liver stiffness may be a useful tool to differentiate portal hypertension related to cirrhosis from that of HES. High spleen stiffness is a potential surrogate marker of portal hypertension in this population.

Learning curve and intra/interobserver agreement of transient elastography in chronic hepatitis C patients with or without HIV co-infection.

BACKGROUND AND OBJECTIVES: Liver stiffness measurement (LSM) by transient elastography has been validated as a noninvasive method to stage liver fibrosis. Few studies have evaluated the learning curve of this method and its reproducibility has led to controversy results. We aimed to evaluate the intra- and interobserver agreement of transient elastography as well as its learning curve for definition of an experimented operator. METHODS: We retrospectively analyzed 922 examinations performed in 544 patients during a training program of transient elastography. Patients with chronic hepatitis C with or without HIV co-infection that had two examinations by the training operator (intraobserver analysis; n=125) or examination by both training and experimented operators (interobserver analysis; n=151) in the same day were included. LSM was converted to METAVIR score: <7.1 as F0F1, 7.1-9.4 as F2, 9.5-12.4, as F3 and >12.4 kPa as F4. RESULTS: The overall intra- and interobserver intraclass correlation coefficient [ICC 95% CI] were 0.926 (0.901-0.951) and 0.912 (0.885-0.939), respectively. Measurements were correlated [Spearman's] in intra- [0.906, P<0.0001] and interobserver [0.907, P<0.0001] analysis. Reliability values [kappa (SE)] were k=0.74 (0.09) and k=0.85 (0.08) for fibrosis stages F ≥ 2 and k=0.77 (0.09) and k=0.75 (0.08) for cirrhosis in intra- and interobserver analysis, respectively. Agreement was improved when operator's experience was higher than 100 exams. However, it was observed discordance for fibrosis staging between examinations in a quarter of patients. CONCLUSION: Although there was a considerable discrepancy on fibrosis staging between examinations and a small power, transient elastography had an acceptable reproducibility in our population. Performance of at least 100 examinations should be used to define an experimented operator.

Interobserver variability in transient elastography analysis of patients with chronic hepatitis C.

BACKGROUND & AIMS: Transient elastography based on liver stiffness measurement is a non-invasive method to assess hepatic fibrosis. However, interobserver variability has led to controversy over its use in fibrosis evaluation. To evaluate the interobserver variation in transient elastography in chronic hepatitis C. METHODS: We performed a cross-sectional study, analysing findings from two experienced operators who each assessed 195 patients by transient elastography on the same day. Liver stiffness measurement used to define fibrosis stages, based on METAVIR score, was: <7.1 as F0F1, 7.1-9.4 as F2, 9.5-12.4, as F3 and >12.4 kPa as F4. We also assessed interobserver variation in identification of potential oesophageal varices screening based on transient elastography. RESULTS: The interobserver intraclass correlation coefficient was 0.940 (95% CI 0.863-0.967) and measurements made by operators correlated [Spearman's ρ = 0.924; P < 0.001]. However, the median liver stiffness measurement assessed by first operators was higher (11.5 vs 9.8 kPa; P < 0.001). The discordance between operators was 35% for at least one stage of fibrosis and 5% for two or more stages. Interobserver reliability values were κ = 0.61 for fibrosis stages F ≥ 2 and κ = 0.80 for cirrhosis. Among the 74 patients determined to have cirrhosis by at least one operator, there was considerable discordance in identification of those with indication for oesophageal varices screening (κ values from 0.13 to 0.61) according to several cut-offs. CONCLUSION: Although a high correlation of liver stiffness measurement between operators, interobserver variability in transient elastography was not negligible. This method should not be used as the only screening tool for oesophageal varices in chronic hepatitis C.

Enhanced liver fibrosis panel as a predictor of liver fibrosis in chronic hepatitis C patients.

BACKGROUND: Evaluation of fibrosis is crucial in the assessment of chronic hepatitis C (CHC). The enhanced liver fibrosis (ELF) is a serological panel including hyaluronic acid (HA), tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), and amino-terminal propeptide of type III procollagen (PIIINP) that has shown good results in predicting liver fibrosis in distinct scenarios of chronic liver diseases. AIMS: We aimed to assess the performance of ELF on the detection of fibrosis and cirrhosis in a CHC patient cohort and to compare the results of ELF and transient elastography (TE-Fibroscan) using liver biopsy as reference. PATIENTS AND METHODS: One hundred twenty patients were prospectively evaluated by TE and ELF using an ADVIA Centaur automated system. The ELF score was calculated using the manufacturer's algorithm. Biopsies were classified according to the METAVIR score. Receiver operator characteristic curve analyses were performed to evaluate the accuracy of ELF and TE. RESULTS: The area under the receiver operator characteristic curve (AUROC) of ELF for the diagnosis of significant fibrosis was 0.81 [95% confidence interval (CI), 0.73-0.87], for advanced fibrosis was 0.82 (95% CI, 0.74-0.88), and for cirrhosis was 0.78 (95% CI, 0.70-0.85). Using the proposed cutoffs, ELF overestimated fibrosis in 66% (81/120) of cases and underestimated in 3% (3/120). We found no statistically significant difference when comparing the AUROC of ELF and TE for diagnosing fibrosis or cirrhosis. CONCLUSIONS: ELF panel is a good noninvasive fibrosis marker and showed similar results to TE in CHC patients. However, new cutoff points need to be established to improve its performance on patients with CHC.