Multiparametric liver assessment in patients successfully treated for hepatitis C: a 4-year follow-up.

BACKGROUND: Hepatitis C virus (HCV) is a major cause of chronic liver disease, in which liver stiffness increases. Liver stiffness measurements (LSM) are therefore essential in diagnosing liver diseases and predicting disease development. The study objective was to perform a comprehensive prospective assessment of the liver before, after and 4 years after treatment for HCV, including an assessment of the long-term outcome of fibrosis, steatosis and inflammation. METHODS AND FINDINGS: Patients eligible for HCV treatment were included prospectively in 2018 (n = 47). Liver stiffness was measured using transient elastography and 2D shear-wave elastography (SWE). Blood tests, B-mode ultrasound (US) and SWE, were performed before, after (end of treatment [EOT]), 3 months after (EOT3) and 4 years after treatment (4Y). At the final visit, we added attenuation imaging and shear-wave dispersion slope (SWDS) measurements to assess steatosis and inflammation. Three months after treatment, the sustained virologic response rate was 93%. The median liver stiffness for baseline, EOT, EOT3 and 4Y was 8.1, 5.9, 5.6 and 6.3 kPa, respectively. There was a significant reduction in liver stiffness from baseline to EOT, and from EOT to EOT3. After 4 years, the mean attenuation coefficient (AC) was 0.58 dB/cm/MHz, and the mean SWDS value was 14.3 (m/s)/kHz. CONCLUSION: The treatment for HCV was highly effective. Measurements of liver stiffness decreased significantly after treatment and remained low after 4 years. AC measurements indicated low levels of liver steatosis. Shear-wave dispersion values indicated inflammation of the liver, but the clinical implication is undetermined and should be explored in larger studies.Clinicaltrials.gov: NCT03434470. ABBREVIATIONS: AC: attenuation coefficient; APRI: aspartate aminotransferase to platelet ratio index; ATI: attenuation imaging; cACLD: compensated advanced chronic liver disease; CAP: controlled attenuation parameter; FIB-4: Fibrosis-4 Index for liver fibrosis; HCC: hepatocellular carcinoma; LSM: liver stiffness measurement; NAFLD: non-alcoholic fatty liver disease; NASH: non-alcoholic steatohepatitis; SWDS: shear-wave dispersion slope; SWE: shear-wave elastography; US: ultrasound.

Delivery of biannual ultrasound surveillance for individuals with cirrhosis and cured hepatitis C in the UK.

BACKGROUND: Previous studies show the uptake of biannual ultrasound (US) surveillance in patients with cirrhosis is suboptimal. Here, our goal was to understand in broader terms how surveillance is being delivered to cirrhosis patients with cured hepatitis C in the UK. METHODS: Hepatitis C cirrhosis patients achieving a sustained viral response (SVR) to antiviral therapies were identified from the national Hepatitis-C-Research-UK resource. Data on (i) liver/abdominal US examinations, (ii) HCC diagnoses, and (iii) HCC curative treatment were obtained through record-linkage to national health registries. The rate of US uptake was calculated by dividing the number of US episodes by follow-up time. RESULTS: A total of 1908 cirrhosis patients from 31 liver centres were followed for 3.8 (IQR: 3.4-4.9) years. Overall, 10 396 liver/abdominal USs were identified. The proportion with biannual US was 19% in the first 3 years after SVR and 9% for all follow-up years. Higher uptake of biannual US was associated with attending a liver transplant centre; older age and cirrhosis decompensation. Funnel plot analysis indicated significant inter-centre variability in biannual US uptake, with 6/29 centres outside control limits. Incident HCC occurred in 133 patients, of which 49/133 (37%) were treated with curative intent. The number of US episodes in the two years prior to HCC diagnosis was significantly associated with higher odds of curative-intent treatment (aOR: 1.53; 95% CI: 1.12-2,09; p = .007). CONCLUSIONS: This study provides novel data on the cascade of care for HCC in the UK. Our findings suggest biannual US is poorly targeted, inefficient and is not being delivered equitably to all patients.

Noninvasive Risk Stratification After HCV Eradication in Patients With Advanced Chronic Liver Disease.

BACKGROUND AND AIMS: Risk stratification after cure from hepatitis C virus (HCV) infection remains a clinical challenge. We investigated the predictive value of noninvasive surrogates of portal hypertension (liver stiffness measurement [LSM] by vibration-controlled transient elastography and von Willebrand factor/platelet count ratio [VITRO]) for development of hepatic decompensation and hepatocellular carcinoma in patients with pretreatment advanced chronic liver disease (ACLD) who achieved HCV cure. APPROACH AND RESULTS: A total of 276 patients with pretreatment ACLD and information on pretreatment and posttreatment follow-up (FU)-LSM and FU-VITRO were followed for a median of 36.6 months after the end of interferon-free therapy. FU-LSM (area under the receiver operating characteristic curve [AUROC]: 0.875 [95% confidence interval [CI]: 0.796-0.954]) and FU-VITRO (AUROC: 0.925 [95% CI: 0.874-0.977]) showed an excellent predictive performance for hepatic decompensation. Both parameters provided incremental information and were significantly associated with hepatic decompensation in adjusted models. A previously proposed combined approach (FU-LSM < 12.4 kPa and/or FU-VITRO < 0.95) to rule out clinically significant portal hypertension (CSPH, hepatic venous pressure gradient ≥10 mm Hg) at FU assigned most (57.3%) of the patients to the low-risk group; none of these patients developed hepatic decompensation. In contrast, in patients in whom FU-CSPH was ruled in (FU-LSM > 25.3 kPa and/or FU-VITRO > 3.3; 25.0% of patients), the risk of hepatic decompensation at 3 years following treatment was high (17.4%). Patients within the diagnostic gray-zone for FU-CSPH (17.8% of patients) had a very low risk of hepatic decompensation during FU (2.6%). The prognostic value of this algorithm was validated in an internal (n = 86) and external (n = 162) cohort. CONCLUSION: FU-LSM/FU-VITRO are strongly and independently predictive of posttreatment hepatic decompensation in HCV-induced ACLD. An algorithm combining these noninvasive markers not only rules in or rules out FU-CSPH, but also identifies populations at negligible versus high risk for hepatic decompensation. FU-LSM/FU-VITRO are readily accessible and enable risk stratification after sustained virological response, and thus facilitate personalized management.

Identification of the suitable candidates for EOB-MRI with the high risk of the presence of non-hypervascular hypointense nodules in patients with HCV infection.

OBJECTIVES: Non-hypervascular hypointense nodules (NHHNs) depicted by gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) have a high likelihood of progressing to hepatocellular carcinoma (HCC). The presence of NHHNs is a strong risk factor for HCC development in patients with chronic hepatitis C virus (HCV) infection after the achievement of sustained virologic response (SVR). However, it is difficult for all patients with HCV infection to undergo EOB-MRI for NHHN detection. We therefore explored serum markers that potentially indicate the presence of NHHNs. METHODS: Three serum markers, alpha-fetoprotein (AFP), FIB-4 index, and Wisteria floribunda agglutinin-positive Mac-2 binding protein glycan isomer (M2BPGi), were measured in 481 patients with HCV infection and no history of HCC who underwent EOB-MRI. The associations between these serum marker levels and the presence of NHHNs were investigated. RESULTS: All three markers were associated with the presence of NHHNs. M2BPGi predicted the presence of NHHNs more accurately than AFP and FBB-4 index; M2BPGi had the highest area under the receiver operating characteristic curve. Multivariate analysis identified male gender and high M2BPGi as factors associated with the presence of NHHNs. When patients were stratified by the degree of liver fibrosis, M2BPGi increased with the progression of fibrosis. In addition, NHHNs were more prevalently detected in patients with higher M2BPGi (COI > 3.46) in patients with similar fibrosis degree. CONCLUSIONS: M2BPGi is a serum marker that potentially identifies HCV patients with high risk of the presence of NHHNs, for whom EOB-MRI should be considered. KEY POINTS: • Non-hypervascular hypointense nodule on EOB-DTPA-enhanced MRI is pre-HCC nodule with high likelihood of progressing to HCC, which is a strong predictor for HCC that develops after the eradication of HCV in patients with HCV infection. • It is difficult for all patients with HCV infection to undergo EOB-MRI for NHHN detection due to limited access, limited availability of MRI equipment, and high costs. • Serum Wisteria floribunda agglutinin-positive Mac-2 binding protein glycan isomer (M2BPGi) levels effectively indicate the presence of NHHNs and can be used to identify patients with high risk of their presence, for whom EOB-DTPA-enhanced MRI should be considered.

Liver and Spleen Stiffness Surveillance Through Elastography During and After Direct-Acting Antiviral Therapy in Patients With Chronic Hepatitis C.

OBJECTIVES: Direct-acting antiviral agents achieve a high cure rate, resulting in early hepatic necroinflammatory resolution and sustained fibrosis regression. This study aimed to obtain longitudinal, concurrent within-subject measurements of liver stiffness (LS) and spleen stiffness (SS) and their correlates over time. METHODS: Participants with hepatitis C (n = 592) receiving direct-acting antiviral-based therapy were monitored through point shear-wave elastography from the treatment baseline (TW0) across follow-up visits in terms of LS and SS. RESULTS: Generalized linear mixed modeling indicated that all LS values (2301 visits) were negatively correlated with the follow-up times (all P < .05) from TW0 to 24 weeks (PW24) after the end of treatment (EOT) and positively correlated with baseline LS values (P < .001). The slopes of declines (preceding minus next) differed significantly (P < .001) between TW0-TW4 (treatment week 4) (0.060 [-0.050 to 0.225] meter/second/month [m/s/mo]) and TW4-EOT (0.010 [-0.030 to 0.075] m/s/mo). All SS values (1704 visits) were negatively correlated with time only at PW24 (P < .001) and positively correlated with baseline SS values (P < .001). The slopes of the SS values differed significantly (P < .001) only between EOT-PW12 (-0.010 [-0.110 to 0.083] m/s/mo) and PW12-PW24 (0.043 [-0.063 to 0.160] m/s/mo). CONCLUSIONS: The biphasic fast-to-slow decline in LS occurred early in the on-treatment phase, which is consistent with the resolution of hepatic necroinflammation. The slow-to-fast decline in SS occurred off treatment. Future studies should investigate the association with regressions in liver fibrosis and portal hypertension.

Changes in Liver Stiffness and Noninvasive Fibrosis Scores in Egyptian Adolescents Successfully Treated with Ledipasvir-Sofosbuvir for Chronic Hepatitis C Virus Infection.

OBJECTIVE: To assess changes in noninvasive liver fibrosis measurements after chronic hepatitis C eradication by direct-acting antivirals in Egyptian adolescents. STUDY DESIGN: Liver stiffness measurement (LSM), by vibration-controlled transient elastography and noninvasive fibrosis scores (Firbosis-4, aspartate aminotransferase-platelet ratio index), was obtained before and 12 months after eradication with ledipasvir-sofosbuvir. The primary outcome was a more than 30% decrease in LSM with resulting fibrosis stage regression for initial fibrosis of F2 or higher and nonprogression of F0-F1, using the Ishak score (F0-F6). The secondary outcome was change in noninvasive fibrosis scores after treatment. RESULTS: Analyzing 85 patients, the median baseline LSM was 5.8 (IQR, 4.2-6.5) and at follow-up 5.1 kPa (IQR, 4-6 kPa) (P = .045); 62 (73%) met the primary outcome, 16 patients (19%) experienced regression, and 46 (54%) nonprogression of LSM. Of 18 with initial fibrosis of F2 0r higher, 13 regressed to F0-F1 and 2 from F6 to F5, 1 unchanged at F3, and 1 increased to F3 and 1 to F4. Among 67 patients with a baseline fibrosis of F0-F1, 62 were unchanged and 5 increased-4 to F2 and 1 to F3. Although 23 (27%) had a more than 30% LSM increase, only 7 (8%), with associated comorbidities (4 ß-thalassemia, 3 hepatic steatosis), had increased fibrosis stage. The median baseline FIB-4 and aspartate aminotransferase-platelet ratio index scores were 0.34 (IQR, 0.22-0.47) and 0.35 (0.24-0.57), and at follow-up 0.3 (IQR, 0.22-0.34) and 0.2 (0.18-2.8) (P < .001, <.001), respectively. CONCLUSIONS: Chronic hepatitis C eradication by direct-acting antiviral agents in Egyptian adolescents was associated with nonprogression or regression of liver fibrosis, by noninvasive fibrosis measurements, at 12 months after treatment in the majority of cases.

Changes of liver stiffness measured by magnetic resonance elastography during direct-acting antivirals treatment in patients with chronic hepatitis C.

Almost all patients achieved sustained virological response (SVR) by direct-acting antivirals (DAA) therapy, but it is not clear as to what extent DAA therapy affects changes in liver fibrosis after achieving SVR. In this study, we investigated the changes of liver stiffness by magnetic resonance elastogaraphy (MRE) during DAA therapy. A total of 308 patients were enrolled in the study. Liver stiffness was measured twice before and after DAA treatment using MRE and time-course change of liver stiffness was investigated. The median (interquartile range) values for liver stiffness were 4.2 (3.2-6.1) kPa at baseline and 3.3 (2.6-4.8) kPa at SVR, demonstrating a significant improvement (p < .01). A total of 44% of patients had no improvement in liver stiffness despite achieving SVR. In patients with advanced fibrosis (lower level of albumin [Alb] or histological fibrosis stage F4), it was difficult to improve liver stiffness. Except for Alb, there were no blood tests associated with nonimprovement in liver stiffness, making these cases difficult to predict. In conclusion, despite obtaining SVR, improvement in liver stiffness could not be obtained in some cases, especially in patients with advanced fibrosis. In these patients, liver stiffness must be followed even if SVR is obtained.

Impact of liver-stiffness measurement on hepatocellular carcinoma development in chronic hepatitis C patients treated with direct-acting antivirals: A systematic review and time-to-event meta-analysis.

BACKGROUND AND AIM: Patients with chronic hepatitis C (CHC) treated with direct-acting antivirals (DAAs) are still at risk for developing hepatocellular carcinoma (HCC) even after achieving sustained virologic response (SVR). Liver-stiffness measurement (LSM) on imaging has been investigated as a predictor of HCC occurrence. OBJECTIVES: To provide systematic summary of the predictive value of LSM in predicting HCC occurrence in HCV patients treated with DAA. METHODS: A comprehensive literature search of the PubMed-MEDLINE and EMBASE databases was performed to identify studies that evaluated the predictive value of LSM in CHC patients treated with DAAs. Pooled hazard ratio (HR) comparing HCC occurrence between patients with positive and negative results on LSM was calculated for all studies and various subgroups. Subgroup analyses and meta-regression were performed. RESULTS: A review of 135 candidate articles identified eight eligible articles with a total of 3398patients for qualitative review and meta-analysis. The pooled HR for HCC occurrence determined by LSM was 3.43 (95% confidence interval [CI], 1.63-7.19) with heterogeneity (I2  = 81.87%, P < 0.001), thus indicating that LSM might be helpful for predicting HCC occurrence. In subgroup analyses, pooled HRs were different according to the study design (2.29; [95% CI, 0.96-5.45] for retrospective studies; 4.61 [95% CI, 2.44-8.71] for prospective studies), study population (4.00 [95% CI, 2.00-7.99] for CHC; 2.64 [0.99-7.00] for CHC with liver cirrhosis) and LSM parameter (3.17 [95% CI, 1.35-7.41] for baseline LSM; 4.19 [95% CI, 1.89-9.29] for others). In multivariate meta-regression, study design was the only influencing factor for pooled HR for HCC occurrence (P < 0.05). CONCLUSIONS: Consistent evidence demonstrated the predictive value of LSM for HCC occurrence in CHC patients treated with DAA. The significant influencing factor for risk of HCC occurrence indicated by LSM was study design.

Computed Tomography-Measured Liver Volume Predicts the Risk of Hepatocellular Carcinoma Development in Chronic Hepatitis C Patients.

AIM: In this retrospective cohort study, we evaluated the significance of liver volume in the prediction of hepatocellular carcinoma (HCC) in 277 chronic hepatitis C (CHC) patients who received dynamic computed tomography (CT) during surveillance. METHODS: Liver volumes were measured on portal venous phase of CT images by using ImageJ software. Liver volume index, a ratio of the standard liver volume expected by weight and height to the measured liver volume, was calculated to adjust for normal variations. The cohort was randomly divided to derivation (n = 100) and validation sets (n = 177) for the generation of a liver volume-based Cox prediction model and validation of a liver volume-based nomogram, respectively. RESULTS: The liver volume index was independent of weight or height, and it predicted further development of HCC (hazard ratio [HR] 16.30, 95% CI 6.70-39.62; p < 0.001). Liver cirrhosis, gamma-glutamyl transferase, and liver volume index were independent predictors of HCC, and nomogram-based prediction score from these three parameters identified high-risk patients at the cutoff of 110 in both derivation (p < 0.001) and validation cohort (p < 0.001). CONCLUSION: Liver volume-based prediction model stratifies the risk of developing HCC in CHC patients whose initial dynamic CT study gave negative results.

Reduction of Shear Wave Elastography but Not Shear Wave Dispersion After Successful Hepatitis C Treatment With Direct-Acting Antiviral Agents.

OBJECTIVES: Successful antiviral treatment in patients with hepatitis C can lead to reduced liver stiffness. In this study, we attempted to compare 2-dimensional (2D) shear wave elastography (SWE), shear wave dispersion (SWD), and attenuation imaging (ATI) with transient elastography (TE) and the controlled attenuation parameter (CAP) in patients under direct-acting antiviral (DAA) therapy. METHODS: Patients with chronic hepatitis C infection undergoing DAA therapy from January 2017 to June 2020 were retrospectively examined. The results of 2D SWE, SWD, ATI, TE, and CAP were recorded before and 12 weeks after the completion of DAA therapy. RESULTS: A total of 122 patients with a median age of 61 years were investigated; among them, 121 (99.2%) achieved a sustained virologic response at 12 weeks after DAA therapy. Fibrosis 4, the aspartate aminotransferase-to-platelet ratio index, 2D SWE, and TE were reduced after DAA therapy. The CAP was increased; however, SWD and ATI showed no statistically significant changes after DAA therapy. Two-dimensional SWE and TE were strongly correlated (r = 0.885-0.897; P < .001). Albumin and the baseline liver stiffness measurement were independent factors of liver stiffness measurement changes after DAA therapy. CONCLUSIONS: Direct-acting antiviral therapy can significantly decrease liver stiffness (using both 2D SWE and TE) but not SWD and ATI values in patients with hepatitis C. An increased CAP is also observed after DAA therapy.

Performance of Acoustic Radiation Force Impulse Elastography for Staging Liver Fibrosis in Patients With Chronic Hepatitis C After Viral Eradication.

BACKGROUND: Data on noninvasive liver fibrosis staging after viral eradication are unclear. This histology-based study validated the performance of liver stiffness (LS) measurements after viral eradication. METHODS: Consecutive participants with chronic hepatitis C (CHC) who received concomitant LS measurements through acoustic radiation force impulse (ARFI) elastography and percutaneous liver biopsy were prospectively screened and analyzed. RESULTS: Of the 644 patients, 521 (80.9%) underwent a biopsy at treatment baseline, and the remaining 123 (19.1%) underwent a biopsy at 3 years (median; interquartile range, 0.1) after the sustained virological response (SVR) to pegylated interferon-based and direct-acting antiviral treatments. The proportions of histological fibrosis stages did not differ significantly between the pretreatment and post-SVR groups (P = .0615). However, the LS values differed significantly (P < .0001). The median LS values (presented as shear wave velocities in meters per second) were 1.51 (0.92) for the pretreatment group and 1.22 (0.77) for the post-SVR group. The cutoffs (areas under the receiver operating characteristic curve, obtained using the bootstrap method) to dichotomize between METAVIR fibrosis stage F1 versus stages F2-F4, F1-F2 versus F3-F4, and F1-F3 versus F4 were 1.47 (0.8333, 95% confidence interval [CI] 0.7981-0.8663), 1.81 (0.8763, 95% CI 0.8376-0.9107), and 1.86 (0.8811, 95% CI 0.8378-0.9179) in the pretreatment group, respectively, and 1.22 (0.7872, 95% CI 0.7001-0.8624), 1.59 (0.8808, 95% CI 0.8034-0.9422), and 1.75 (0.9018, 95% CI 0.8201-0.9644) in the post-SVR group, respectively. CONCLUSIONS: The performance of LS measurements through ARFI elastography is promising to determine the liver fibrosis stage on necroinflammation-resolved histology in CHC after viral eradication.

Progressive multifocal leukoencephalopathy despite immune recovery in a HIV/HCV co-infected patient.

In HIV patients, HCV co-infection has been associated with an increased risk of progressive multifocal leukoencephalopathy (PML). Furthermore, PML has also been described in patients with cirrhosis, whether related to HCV infection or not. We describe here the case of a HIV/HCV co-infected patient with cirrhosis who developed PML despite HIV suppression and CD4 cell count above 250/mm3 for 2 years. Immunological studies performed at onset of PML and before HCV therapy showed a decrease in naïve CD4 cells (CD45RA+CCR7+CD27+ CD4+ T cells - 23% cells, i.e. 75/mm3) and NK lymphopenia with abnormal and activated NK cells (CD3- CD16+ and/or CD56+) (5% lymphocytes, i.e. 58/mm3, CD69 91%, NKp30 26%). This impaired immunity, possibly related to HIV infection, or HCV infection or cirrhosis, or a combination thereof, could have led to the development of PML.

Doppler ultrasonography: A non-invasive method used to diagnose and follow up patients with chronic hepatitis C.

BACKGROUND AND AIM: This study aimed to investigate the association between the findings of Doppler ultrasonography and transient elastography using FibroScan and to determine the cut-off points, sensitivity, and specificity of resistance indices, and pulsatility of the hepatic vessels to predict significant hepatic fibrosis. METHODS: This is a transversal, observational, and analytical study that includes 30 patients with chronic hepatitis C who were admitted at a public referral hospital. Transient elastography and ultrasonographic data were collected, and the linear association between these methods was evaluated using the Pearson test. Various Doppler velocimetric indices were compared according to the presence/absence of significant (≥ F2) fibrosis. RESULTS: There was a moderate-strong linear association between the FibroScan data and the Doppler velocimetric indices and splenic index in the hepatic vessels; the mean values of the indices differed between groups with absent/mild (F0/F1) and significant (≥ F2) hepatic fibrosis. There was an association between the monophasic and biphasic wave pattern of the suprahepatic veins and the stratification of hepatic fibrosis estimated by the values of kilopascal in FibroScan. CONCLUSION: Doppler ultrasonography is a non-invasive method used to evaluate liver fibrosis, and it presents acceptable sensitivity/specificity for the prediction of fibrosis ≥ F2 in patients with chronic hepatitis C.

Validation and Refinement of Noninvasive Methods to Assess Hepatic Fibrosis: Magnetic Resonance Elastography Versus Enhanced Liver Fibrosis Index.

BACKGROUND: Noninvasive fibrosis markers are routinely used in patients with liver disease. Magnetic resonance elastography (MRE) is recognized as a highly accurate methodology, but a reliable blood test for fibrosis would be useful. We examined performance characteristics of the Enhanced Liver Fibrosis (ELF) Index compared to MRE in a cohort including those with HCV, HIV, and HCV/HIV. METHODS: Subjects enrolled in the Miami Adult Studies on HIV (MASH) cohort underwent MRE and blood sampling. The ELF Index was scored and receiver-operator curves constructed to determine optimal cutoff levels relative to performance characteristics. Cytokine testing was performed to identify new markers to enhance noninvasive marker development. RESULTS: The ELF Index was determined in 459 subjects; more than half were male, non-white, and HIV-infected. MRE was obtained on a subset of 283 subjects and the group that had both studies served as the basis of the receiver-operator curve analysis. At an ELF Index of > 10.633, the area under the curve for cirrhosis (Metavir F4, MRE > 4.62 kPa) was 0.986 (95% CI 0.994-0.996; p < 0.001) with a specificity of 100%. For advanced fibrosis (Metavir F3/4), an ELF cutoff of 10 was associated with poor sensitivity but high specificity (98.9%, 95% CI 96.7-99.8%) with an AUC of 0.80 (95% CI 0.749-0.845). ELF Index performance characteristics exceeded FIB-4 performance. HCV and age were associated with increased fibrosis (p < 0.05) in a multivariable model. IP-10 was found to be a promising biomarker for improvement in noninvasive prediction algorithms. CONCLUSIONS: The ELF Index was a highly sensitive and specific marker of cirrhosis, even among HIV-infected individuals, when compared with MRE. IP-10 may be a biomarker that can enhance performance characteristics further, but additional validation is required.

Application of Baveno Criteria and Modified Baveno Criteria with Shear-wave Elastography in Compensated Advanced Chronic Liver Disease.

BACKGROUND: We aimed to validate Baveno VI and expanded Baveno VI criteria using two dimensional shear-wave elastography (2D-SWE) in compensated advanced chronic liver disease (cACLD) patients with alcohol as the main etiology. METHODS: Clinical data from 305 patients with cACLD who underwent a liver stiffness measurement (LSM) with 2D-SWE and endoscopy were consecutively collected. RESULTS: Among 305 patients, high-risk varix (HRV) was identified in 21.3% (n = 65). The main etiology was alcoholic liver disease (51.8%), followed by hepatitis B virus (29.8%) and hepatitis C virus (9.1%). Baveno VI criteria spared endoscopy in 118 of the 305 (38.7%) patients, and 7 (5.9%) were missed with HRV. Expanded Baveno VI criteria spared more endoscopies (60.0%), but missed more HRV (9.8%) compared with Baveno VI criteria. The other classification described as the modified Baveno VI criteria were LSM < 25 kPa and PLT ≥ 150 × 10³/mm³. In total, 131 of the 305 (43.0%) patients were within the modified Baveno VI criteria, of whom seven (5.3%) had missed HRV. After adding spleen diameter < 12 cm to the modified Baveno VI criteria, the number of spared endoscopies increased by 106/305 (34.8%), with three (2.8%) presenting with HRV, indicating a risk of missing HRV. CONCLUSION: Baveno VI and expanded Baveno VI criteria with 2D-SWE were insufficient with an HRV miss rate of over 5%. The modified Baveno VI criteria with spleen diameters < 12 cm with 2D-SWE spared more endoscopies with a minimal risk of missing HRV in cACLD patients with alcohol as the main etiology.

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

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 × 10 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.

Liver stiffness regression after successful Hepatitis C treatment is independent of HIV coinfection.

OBJECTIVES: The aim of the study was to assess the regression of liver stiffness after successful direct-acting antiviral (DAA) treatment in patients with hepatitis C virus (HCV) monoinfection and HCV/-HIV coinfection. In addition, we aimed to identify factors associated with liver stiffness regression. METHODS: We studied patients treated with interferon-free DAA regimens with a sustained virological response at week 12 (SVR12 ) or 24 (SVR24 ) post-treatment. Liver stiffness was assessed by transient elastography (TE) before the initiation and after the end of treatment (median 12 weeks). RESULTS: Of 214 enrolled patients, 85 (40%) were HCV monoinfected and 129 (60%) HCV/HIV coinfected. Baseline median TE values were 7.8 kPa [interquartile range (IQR) 5.9-12.0 kPa] in mono-infected patients and 10.7 kPa (IQR 7.8-17.0 kPa) in coinfected patients. Overall, the median TE value decreased from 10.1 to 6.8 kPa (n = 214; P < 0.0001). There was no difference between mono- and coinfected patients (-2.2 versus -3.3 kPa, respectively; P = 0.88), which was verified by an analysis of covariance (ANCOVA) adjusting for baseline TE values. Significant (≥ 30%) regression of liver stiffness was achieved by 45% of patients (54% with baseline TE ≥ 7.1 kPa). In multivariate analysis, a prior HCV treatment was a negative predictor of liver stiffness regression [odds ratio (OR) 0.31; P = 0.001]. A higher baseline TE value was positively associated with achieving a significant regression (OR 1.06; P = 0.02). HIV coinfection status, HCV genotype, age, sex, treatment duration, controlled attenuation parameter value, bilirubin concentration, platelet count and aspartate aminotransferase concentration were not associated with liver stiffness regression. CONCLUSIONS: Regression of liver stiffness after successful DAA treatment did not differ in patients with HCV monoinfection and those with HCV/HIV coinfection. Half of all patients achieved a significant (≥ 30%) regression. Prior treatment for HCV was a negative predictor for this endpoint, while a higher baseline TE value was positively associated with regression.

Interferon-free therapy as the cause of white matter tracts and cerebral perfusion recovery in patients with chronic hepatitis C.

The purpose of this study was to assess cerebral microstructural and perfusion changes in patients with chronic hepatitis C virus (HCV) infection before and after interferon-free therapy, using advanced magnetic resonance (MR) techniques. Eleven HCV-positive patients underwent diffusion tensor imaging (DTI) and perfusion-weighted imaging (PWI) using a 1.5T MR unit, before and 24 weeks after completion of interferon-free therapy. DTI fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were obtained from 14 white matter tracts. PWI values of relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) were assessed from 8 areas, including basal ganglia, and cortical and white matter locations. In HCV-positive patients therapy with ombitasvir, paritaprevir boosted with ritonavir and dasabuvir, with or without ribavirin, was scheduled. Cognitive tests were used to assess cognitive function. We found increased FA values after interferon-free therapy compared to values obtained before treatment in HCV patients in almost all white matter tracts. We also observed elevated rCBV values in basal ganglia after therapy. There were significant correlations between improvement in the score of cognitive tests and increased FA values in both inferior fronto-occipital fascicles and left posterior cingulum after treatment. Liver fibrosis regression in elastography, APRI and improvement in cognitive tests were observed. This is the first report of interferon-free therapy as the cause of white matter tracts recovery as well as cerebral perfusion improvement in HCV-infected patients, indicating better functioning of frontal lobes after interferon-free treatment.

Assessment of biopsy-proven liver fibrosis by two-dimensional shear wave elastography: An individual patient data-based meta-analysis.

Two-dimensional shear wave elastography (2D-SWE) has proven to be efficient for the evaluation of liver fibrosis in small to moderate-sized clinical trials. We aimed at running a larger-scale meta-analysis of individual data. Centers which have worked with Aixplorer ultrasound equipment were contacted to share their data. Retrospective statistical analysis used direct and paired receiver operating characteristic and area under the receiver operating characteristic curve (AUROC) analyses, accounting for random effects. Data on both 2D-SWE and liver biopsy were available for 1,134 patients from 13 sites, as well as on successful transient elastography in 665 patients. Most patients had chronic hepatitis C (n = 379), hepatitis B (n = 400), or nonalcoholic fatty liver disease (n = 156). AUROCs of 2D-SWE in patients with hepatitis C, hepatitis B, and nonalcoholic fatty liver disease were 86.3%, 90.6%, and 85.5% for diagnosing significant fibrosis and 92.9%, 95.5%, and 91.7% for diagnosing cirrhosis, respectively. The AUROC of 2D-SWE was 0.022-0.084 (95% confidence interval) larger than the AUROC of transient elastography for diagnosing significant fibrosis (P = 0.001) and 0.003-0.034 for diagnosing cirrhosis (P = 0.022) in all patients. This difference was strongest in hepatitis B patients. CONCLUSION: 2D-SWE has good to excellent performance for the noninvasive staging of liver fibrosis in patients with hepatitis B; further prospective studies are needed for head-to-head comparison between 2D-SWE and other imaging modalities to establish disease-specific appropriate cutoff points for assessment of fibrosis stage. (Hepatology 2018;67:260-272).

Cerebral patterns of neuropsychological disturbances in hepatitis C patients.

Neuropsychiatric symptoms and cognitive impairment have been consistently reported in patients with hepatitis C virus (HCV) infection. Since the mechanisms behind remain to be established, the present study attempted to assess whether neuropsychological impairments in HCV-infected patients are accompanied by structural alterations in the brain. Therefore, 19 anti-HCV-antibody-positive women with mild liver disease and 16 healthy controls underwent extensive neuropsychological testing and cranial magnetic resonance imaging (MRI) examination. Nine of the patients and five controls were followed up after 6-7 years. Voxel-based morphometry and magnetization transfer imaging were utilized to study HCV-associated structural gray and white matter changes. The HCV-infected patients had significantly worse fatigue and depression scores and significantly poorer performance on attention and memory tests than controls. The patients displayed gray matter (GM) atrophy in the bilateral insula and thalamus and a profound GM volume increases in the cerebellum. Microstructural GM changes in the insula were also evident by a reduced magnetization transfer ratio. Structural white matter changes were observed along several descending and crossing fiber tracts. Follow-up at 7 years revealed increased GM atrophy in the left amygdala and left parahippocampal regions over time. We conclude that our data provide evidence for structural alterations in the brains of patients with chronic HCV infection. Disturbances of cerebellothalamocortical regions and circuits, linking cerebellar projections to the prefrontal cortex through the thalamus, underpin the emotional and cognitive dysfunction characteristically observed in these patients.