Median Transient Elastography Research Articles

Sustained virological response in chronic hepatitis C patients by direct-acting antiviral treatment significantly reduces liver stiffness over 24 weeks posttreatment.

To investigate whether direct-acting antiviral (DAA) treatment affected liver fibrosis testing, including transient elastography (TE), aspartate aminotransferase-to-platelet ratio index (APRI), and Fibrosis-4 (FIB-4) index, after establishing a sustained virological response for 24 weeks. This prospective cohort study was conducted between October 1, 2019, and September 30, 2020, at Rajavithi Hospital, Bangkok, Thailand. All the patients had significant liver fibrosis (TE ≥ 7.0 kPa) at baseline and completed 12 weeks of DAA therapy. After achieving SVR, liver stiffness measurements were repeated for at least 24 weeks. The primary outcome was a > 30% improvement in TE score at the end of the study compared to baseline. A multivariate logistic regression model was used to identify the parameters associated with the primary outcome. Temporal changes in APRI and FIB-4 indices from baseline to 24 weeks posttreatment were also examined. A total of 110 chronic HCV patients were included in our cohort, of which 57 (52.3%) achieved the primary outcome. The median TE decreased from 15.05 (8.76-23.68) kPa at pretreatment to 9.60 (6.50-14.40) kPa at 24 weeks posttreatment (P < .001). Those who had a baseline TE ≥ 9.5 kPa had higher odds of meeting the primary outcome, and this remained significant after adjusting for age, sex, baseline body mass index, underlying diabetes mellitus, HCV genotype 3, baseline laboratory levels, and treatment regimens (OR 3.04; 95% CI 1.22-7.60, P = .017). Similar to TE, the median APRI and FIB-4 index displayed a considerable reduction from baseline to 24 weeks after successful therapy. Modern DAA treatment has been associated with considerable improvement in liver stiffness measured by TE in chronic HCV patients who achieve SVR, with roughly 52% of patients experiencing a reduction of > 30% in TE over 24 weeks posttreatment compared to baseline. This probably indicates early fibrosis regression, although the effect of resolution of inflammation after treatment completion cannot be ruled out.

Correlation of Transient Elastography with Liver Iron Concentration and Serum Ferritin Levels in Patients with Transfusion-Dependent Thalassemia Major from Oman.

In a longitudinal study, we aimed to assess the correlation between ultrasound transient elastography (TE), serum ferritin (SF), liver iron content (LIC) by magnetic resonance imaging (MRI) T2* along with the fibrosis-4 (FIB-4) score as a screening tool to detect significant liver fibrosis among chronically transfusion-dependent beta-thalassemia (TDT) patients. The study was conducted at a tertiary health center treating TDT patients. Transient elastography was performed within 3 months of Liver MRI T2* examinations at the radiology department over a median of one-year duration. T-test for independent data or Mann-Whitney U test was used to analyze group differences. Spearman correlation with linear regression analysis was used to evaluate the correlation between TE liver stiffness measurements, Liver MRI T2* values, and SF levels. In this study on 91 patients, the median age (IQR) of the subjects was 33 (9) years, and the median (IQR) body mass index was 23.8 (6.1) kg/m2. Median (IQR) TE by fibroscan, MRI T2*(3T), Liver iron concentration (LIC) by MRI Liver T2*, and SF levels were 6.38 (2.6) kPa, 32.4 (18) milliseconds, 7(9) g/dry wt., and 1881 (2969) ng/mL, respectively. TE measurements correlated with LIC g/dry wt. (rS =0.39, p=0.0001) and with SF level (rS =0.43, P=0.001) but not with MRI T2* values (rS =-0.24; P=0.98). In TDT patients, liver stiffness measured as TE decreased significantly with improved iron overload measured as LIC by MRI and SF levels. However, there was no correlation of TE with the fibrosis-4 (FIB-4) score.

Use of a combined transient elastography and biochemical strategy to determine liver fibrosis in pediatric intestinal failure

Non-invasive monitoring of intestinal failure (IF) associated liver disease is an ongoing challenge in children with IF. Our objective was to develop a combined algorithm of clinical, transient elastography (TE) and biochemical parameters to identify liver fibrosis in this population. A retrospective cohort study of IF patients followed by our intestinal rehabilitation program between November 2015 to October 2019. Patients with a liver biopsy and TE were included. Demographic and liver function tests were collected. Fibrosis on liver biopsies was graded using the modified Scheuer score. Decision tree based algorithms classified low (F0-F1) versus high (F2-F4) fibrosis scores based on a combination of TE, biochemical and demographic parameters, using 6-fold classification error, sensitivity and specificity cross-validation (CV) scores. 42 patients (74% male, median age 7.6 (4.6; 42.7) months) were evaluated. Median length of PN therapy was 182 (121; 556) days. High fibrosis was present in 40.5% with a median TE of 12.1 (6.7; 12.9) kPa in high fibrosis children. An algorithm, based on cut-off values for TE of 11.3kPa and AST of 40 U/L, and grouping of the underlying etiology resulted in a correct classification of 88.1% of the pathology scores; with sensitivity 0.82 (95% CI 0.57; 0.96), specificity 0.92 (95% CI 0.74; 0.99), positive predictive value 0.88 (95% CI 0.64; 0.96) and negative predictive value 0.88 (95% CI 0.73; 0.96). The CV classification error was 28.6%, CV sensitivity 72.2% and CV specificity 75.5%. This algorithm shows promising results that could simplify non-invasive monitoring of liver fibrosis in children with IF. Validation in additional IF cohorts is needed.

Point Shear-Wave Elastography Using Acoustic Radiation Force Impulse Imaging for the Prediction of Liver-Related Events in Patients With Chronic Viral Hepatitis.

Chronic viral hepatitis is associated with substantial morbidity and mortality worldwide. The aim of our study was to assess the ability of point shear-wave elastography (pSWE) using acoustic radiation force impulse imaging for the prediction of the following liver-related events (LREs): new diagnosis of HCC, liver transplantation, or liver-related death (hepatic decompensation was not included as an LRE). pSWE was performed at study inclusion and compared with liver histology, transient elastography (TE), and serologic biomarkers (aspartate aminotransferase to platelet ratio index, Fibrosis-4, FibroTest). The performance of pSWE and TE to predict LREs was assessed by calculating the area under the receiver operating characteristic curve and a Cox proportional-hazards regression model. A total of 254 patients with a median follow-up of 78 months were included in the study. LRE occurred in 28 patients (11%) during follow-up. In both patients with hepatitis B virus and hepatitis C virus (HCV), pSWE showed significant correlations with noninvasive tests and TE, and median pSWE and TE values were significantly different between patients with LREs and patients without LREs (both P<0.0001). In patients with HCV, the area under the receiver operating characteristic curve for pSWE and TE to predict LREs were comparable: 0.859 (95% confidence interval [CI], 0.747-0.969) and 0.852 (95% CI, 0.737-0.967) (P=0.93). In Cox regression analysis, pSWE independently predicted LREs in all patients with HCV (hazard ratio, 17.9; 95% CI, 5.21-61-17; P<0.0001) and those who later received direct-acting antiviral therapy (hazard ratio, 17.11; 95% CI, 3.88-75.55; P=0.0002). Conclusion: Our study shows good comparability between pSWE and TE. pSWE is a promising tool for the prediction of LREs in patients with viral hepatitis, particularly those with chronic HCV. Further studies are needed to confirm our data and assess their prognostic value in other liver diseases.

Causative factors of liver fibrosis in HIV-infected patients. A single center study

BackgroundLiver disease is a leading cause of morbidity and mortality among Human Immunodeficiency virus (HIV) infected patients; however no consensus exists on HIV-related risk factors for it. The aim of this study was to identify risk factors for liver fibrosis/cirrhosis in a cohort of Greek HIV-infected patients.MethodsPatients attending the HIV outpatient clinic of Pathophysiology Department at «Laiko» General Hospital in Athens, Greece, between December 2014 and December 2017 were eligible for inclusion. Inclusion criteria were confirmed HIV infection and age > 18 years. Exclusion criteria were Body-Mass index (BMI) > 40, liver metastases of malignant diseases and concurrent or previous chemotherapy.Liver stiffness (LS) was measured using Vibration Controlled Transient Elastography (TE) and laboratory tests were acquired in all patients. Patients were classified in 2 groups: those with mild or no fibrosis (equivalent to Metavir score F0-F2) and those with significant fibrosis (equivalent to Metavir score F3-F4).ResultsA total of 187 consecutive patients were included in this study. Median TE value was 5.1 kilopascals (KPa) (range 2.8–26.3), with 92.5% (173/187) of the patients having no/mild fibrosis and 7.4% (14/187) significant fibrosis.On multivariate logistic regression analysis older patient’s age, abnormal serum aspartate aminotransferase (AST) value, Hepatitis C virus (HCV) infection, alcohol abuse, CD4/CD8 ratio and an increased number of liver related events (LREs) were significantly correlated with liver fibrosis/cirrhosis.ConclusionsIn our cohort of HIV-infected individuals HCV/HIV co-infection, older age, alcohol abuse and CD4/CD8 ratio seem to correlate with fibrogenesis in the liver.

P1.43: Use of transient elastography to determine liver fibrosis in pediatric intestinal failure

Introduction: Intestinal failure associated liver disease (IFALD) is a significant complication in pediatric intestinal failure. Liver fibrosis with or without cholestasis is a frequent occurrence in IFALD. However, the diagnosis of fibrosis in IFALD is challenging and currently limited to liver biopsy. Our objective was to evaluate the use of transient elastography (TE) in pediatric IF patients to determine its efficacy for monitoring liver fibrosis as an alternative to liver biopsy. Methods: A retrospective cohort study of IF patients between January 1, 2015 to December 31, 2017. The study cohort included a sample of patients who had a routine liver biopsy during an operative procedure and completed transient elastography at the same time. Liver biopsies were evaluated for stage of fibrosis using the modified Scheuer score. Statistical analysis included univariate analysis and Chi-square methods. High (grade 3–4) versus low (grade 0–2) fibrosis and TE scores were compared to determine sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Receiver operating characteristic (ROC) curves were also used to determine the ability of TE to discriminate various stages of fibrosis. Data is presented as medians with interquartile ranges and frequencies. Results: 30 patients (21 male [70%]) with a median age at biopsy of 320 days (154–1776) were evaluated. Majority of patients had an etiology of abdominal wall defects (12[40%]) and necrotizing enterocolitis (9[30%]). Median length of PN therapy was 190 days (120–789). All TE measurements were completed within a median of 8.5 days (5.0–13.3) of the liver biopsy. Individuals with histologic fibrosis scores of 0–1 (n=18) had a median TE score of 4.9 (3.9–7.1), fibrosis scores of 2 (n=5) had a median TE of 6.7 (4.4–11.4) and those with a fibrosis score of 3 (n=7) had a median TE of 12.1 (6.3–14.6). No patients had grade 4 fibrosis. Dichotomous evaluation of the fibrosis scores (low vs high grade) compared to the chronic cholestatic scale for Fibroscan demonstrated 95.7% sensitivity, 57.1% specificity, 88.0% PPV and 80.0% NPV for low grade fibrosis. The c-statistic for the ROC curve was 0.764. Conclusion: Fibrosis in patients with IF is often difficult to assess without liver biopsy. TE has only been evaluated in small cohorts but shows potential as a non-invasive method to monitor low vs high grade fibrosis in children with IF. Further studies in a larger cohort are required.

Vibration Controlled Transient Elastography (Fibroscan®) in sickle cell liver disease - could we strike while the liver is hard?

Vibration controlled transient elastography (VCTE) is validated for the evaluation of hepatic fibrosis in different liver diseases. Sickle cell liver disease (SCLD) results from a cumulative hepatic injury and its lifelong and progressive nature raises the need for a non-invasive tool for fibrosis evaluation. Fifty patients, aged between 23 and 59years with sickle cell disease and suspected SCLD underwent a VCTE followed by a liver biopsy. Biopsies were evaluated for various scores of liver disease that were then correlated to VCTE score. 90% of our patients had an Ishak Fibrosis (IF) score between 0-2 (Group A-minimal to no fibrosis) and 10% of the patients had IF score between 3-6 (Group B-advanced fibrosis). The median Transient Elastography (TE) for patients in Groups Aand B was 4·8 kilopascals (kPa) and 17·6kPa, respectively. A positive correlation was shown between TE and IF score, R=0·0·68 (P=<0·0001); a positivecorrelation was also shown with Histology Activity Index fibrosis score, R=0·64 (P=<0·0001). This study emphasises the need for further studies of non-invasive tools and their utility in liver fibrosis evaluation of patients with SCLD.

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

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. 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 12weeks). Of 214 enrolled patients, 85 (40%) were HCV monoinfected and 129 (60%) HCV/HIV coinfected. Baseline median TE values were 7.8kPa [interquartile range (IQR) 5.9-12.0 kPa] in mono-infected patients and 10.7kPa (IQR 7.8-17.0 kPa) in coinfected patients. Overall, the median TE value decreased from 10.1 to 6.8kPa (n=214; P<0.0001). There was no difference between mono- and coinfected patients (-2.2versus -3.3kPa, 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≥7.1kPa). 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. 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.

Abstract 5539: An integrated multidisciplinary approach for prediction of HCC development in patients with liver disease utilizing genomics, elastography, imaging and circulating tumor cells

Abstract Background: HCV induced HCC is higher in minority populations. To serve these communities, it is imperative that we understand the genetic and cellular based mechanisms underpinning the linkages between HCV and HCC. The aims of our study were to assess changes in transient elastography (TE) and fibrosis-4 (FIB-4) score in patients with chronic hepatitis C (CHC) in a large cohort of patients. Patients were also stratified for HCC risk based on genomic and imaging data with inclusion of screening for circulating tumor cells. Methods: Our cohort included 1,400 patients and approximately 500 had liver biopsies. Our retrospective prospective study included 60 patients with CHC and a baseline liver biopsy who achieved SVR after treatment with DAA regimens and had a pretreatment TE study and at least one follow up TE measurement at 24 weeks or later post end of treatment response (EOTR). The estimated stage of liver fibrosis based on TE was categorized as F0-F2 (&amp;lt;9.4kpa), or F3 (9.5 - 12.4 Kpa), or F4/cirrhotics (TE &amp;gt;12.5 kpa). Results: Approximately 1,400 patients were successfully assessed by fibroscan and comparisons made with clinical parameters of liver disease. The median baseline TE for the 60 patients who achieved SVR was 11.9 Kpa (range 3.8 to 65.2) and at follow up, TE decreased to 7.35 Kpa (range 2.9 to 34.8) with a median change in TE of -3.4 Kpa (range -35.3 to +1, p=7.355e- 11). Follow up median TE done in the cirrhotic population after median time of 39 weeks post EOTR decreased to 11.7 Kpa and FIB4 was 2.3. The median change of TE in cirrhotic patients was -6.5 kpa (range -35.3 to +1, p=1.043e-7) and for FIB4 was -1.97 (range -17.47 to -0.33, p=1.49e-8). Non-cirrhotic patients (TE&amp;lt;12.4) comprised 55% of the entire cohort and their median change of TE was -2.4 Kpa (range -6.4 to 0.7, p=1.539e-6) and FIB4 was -0.68 (range -2.8 to 0.41, p=2.987e-6). 48% of the entire cohort down-staged their liver fibrosis as determined by TE. In a multiple logistic regression analysis for factors associated with down-staging in liver fibrosis, we found that patients who were treatment naïve were more likely to improve their fibrosis stage (OR 5.73, p=0.033). Conclusions: Liver fibrosis stage, as determined by TE, improved after achieving SVR with DAA treatments in most patients. Although cirrhotic patients had a more significant drop in their median TE when compared to non-cirrhotic patients, they had a lower probability of improving their fibrosis stage and maintained a continued risk to develop HCC. In addition, we identified a group of patients whose TE score did not improve post SVR also representing a cohort of patients whose HCC risk remained. The patients who remain at risk for HCC will be further stratified for increased propensity to develop HCC utilizing genomics, advanced imaging and screening for circulating tumor cells. Citation Format: Emmanuel Thomas, Eugene Schiff, Deukwoo Kwon, Beatrice Madrazo. An integrated multidisciplinary approach for prediction of HCC development in patients with liver disease utilizing genomics, elastography, imaging and circulating tumor cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5539.

Sofosbuvir and Ribavirin for 24 Weeks Is An Effective Treatment Option for Recurrent Hepatitis C Infection After Living Donor Liver Transplantation

Recurrent hepatitis C virus (HCV) has been a serious problem after liver transplantation (LT). We report our experience of 24-week therapy with sofosbuvir (SOF) and ribavirin (RBV) in post-LT recurrent HCV in living donor liver transplantation (LDLT) setting in South Asia. Data from all patients treated for post-transplantation HCV recurrence in a single center were analyzed. Treatment regimen was 24 weeks of SOF 400mg daily and RBV (starting at 800mg daily, increased as tolerated). Sustained virological response (SVR) was assessed 12 weeks and 24 weeks after completion of treatment. 63 patients (median age 52 [range 30-69] years; 80% males) were treated. Most (76.2%) were treatment experienced and predominant HCV genotype was 3 (77.7%) followed by 1 (20.6%). Median transient elastography (Fibroscan) score was 7 (range 3-11) kPa and none of the patients had cirrhosis. SVR12 was achieved in 60 of 63 patients (95.2%) while SVR24 was noted in 59 (93.7%). SVR12 rates were as good in genotype-3 as in genotype-1. Older age, longer period after transplantation, higher Fibroscan value and higher need for erythropoietin were likely to be associated with relapse. Adverse effects were noted in 34 patients and weakness and fatigue were the commonest side effects. Significant drop in hemoglobin (<8g/dL) was seen in 6 patients. SOF+RBV combination therapy for 24 weeks was safe and effective in treatment of for post-LT recurrent HCV in a single LT center and remains relevant due to its low cost and lack of drug interactions.

Direct antiviral agent treatment of chronic hepatitis C results in rapid regression of transient elastography and fibrosis markers fibrosis-4 score and aspartate aminotransferase-platelet ratio index.

Novel direct antiviral agents (DAA) targeting hepatitis C virus (HCV) have revolutionized the treatment of chronic hepatitis C infection (CHC). Rates of sustained virological response (SVR) to treatment have drastically improved since introduction of DAA. Transient Elastography (TE) is an ultrasound based, non-invasive technique to assess liver stiffness (LS). We examined the changes in TE values and fibrosis scores FIB-4 and APRI after DAA treatment of CHC. 549 patients who received a DAA based treatment for CHC were screened and 392 were included. TE values recorded prior to therapy and within 18months after therapy were evaluated. In addition, FIB-4 and APRI scores were calculated and histopathological results were recorded if available. Median TE prior to DAA treatment was 12.65kPa (IQR 9.45-19.2kPa) and decreased to 8.55kPa (IQR 5.93-15.25) post-treatment. This finding is statistically significant (P<.001) and equals a TE regression of 32.4% after DAA treatment. Median FIB-4 and APRI values significantly decreased from 2.54 (IQR 1.65-4.43) and 1.10 (IQR 0.65-2.43) to 1.80 (IQR 1.23-2.84, P<.001) and 0.43 (IQR 0.3-0.79, P<.001) respectively. Patients with SVR after DAA therapy showed significant regression of TE values. Rapid decrease in TE was in concordance with regression of validated fibrosis scores FIB-4 and APRI. It remains to be examined whether this indicates a true regression of fibrosis or merely resolution of chronic liver inflammation with subsequent improvement of TE values and laboratory parameters.

Longitudinal Transient Elastography Measurements Used in Follow-up for Patients with Cystic Fibrosis

Cystic fibrosis–related liver disease (CFLD) is diagnosed using a combination of criteria. Transient elastography (TE), an ultrasonographic method to evaluate liver stiffness, can differentiate patients with and without liver disease. This retrospective study (2007–2013) aimed to detect developing CFLD using consequent TE measurements. All cystic fibrosis patients with TE measurements between 2007 and 2013 (n = 150, median age 17 (9–24) y) were included, of which 118 had a median of three (range, 2–4) measurements with an interval of 1 (1–2) y. Twenty (14%) had CFLD at the first TE measurement; five (3%) developed CFLD during follow-up. The median TE value in CFLD was 14 kPa (8.7–32.2) compared with 5.3 (4.9–5.7) in cystic fibrosis patients without liver disease (CFnoLD; p = 0.0001). In CFnoLD, TE was correlated with age (p = 0.031). A TE result >6.8 kPa had a sensitivity of 91.5% and a specificity of 91.7% in predicting CFLD, according to the receiver operating characteristics analysis. It also has a positive predictive value of 88.6% and a negative predictive value of 86.9%, increasing to 91.7% and 98%, respectively, in patients at risk (<14 y) for developing CFLD. Patients with developing CFLD had progressively increasing consecutive TE measurements.

PWE-194 The routine use of transient elastography to detect liver changes in chronic pancreatitis patients

Introduction Chronic Pancreatitis (CP) can cause obstruction of the common bile duct. Biliary drainage is often suboptimal due to coexistent CP complications. The effect of protracted biliary obstruction on liver fibrosis has not been assessed in CP patients. The aim of the study is to determine the usefulness of non-invasive transient elastography (TE) - FibroScan© in detecting changes to the liver in CP patients with and without biliary obstruction. Method 194 CP patients were identified from a prospectively maintained database from 2006 to 2012. 59 patients were scanned, including patients with normal liver function tests (LFTs) and those with abnormal LFTs +/- dilated common bile duct. FibroScan© readings were graded as absent/mild fibrosis (≤ 7.0 kPa), significant fibrosis (7.1–9.4 kPa), severe fibrosis (9.5–12.4 kPa), cirrhosis (≥12.5 kPa). Results The study group included 44 males and 15 females with CP. Median age was 69 yrs (37–88). The aetiological agent was alcohol in 43%. The median TE was 8.2 (2.5–34.3) kPa with 59.3% normal. Correlation for the whole group was found between pancreas atrophy (p = 0.017, median 7.7 kPa), Cambridge classification III (p = 0.010, median 10.7 kPa) and Creon® >80000 units tds (p = 0.010, median 7.8 kPa). For alcohol aetiology only, this was found with Creon® >80000 units tds (p = 0.018, median 11.2 kPa), abnormal bilirubin (p = 0.005, median 13.6 kPa) and intrahepatic duct dilatation (p = 0.027, median 12.0 kPa). 22% had significant fibrosis, 6.8% had severe fibrosis and 11.9% had values consistent with possible cirrhosis. The rate of fibrosis in this group was determined to be 28.8% with 47% (8/17) having normal serum LFTs. Conclusion This study suggests that even asymptomatic CP patients with normal liver function tests may have changes of their liver ranging from mild fibrosis to cirrhosis. Routine use of FibroScan© may be useful for the surveillance and detection of early liver disease in CP patients in the outpatient setting so that timely management can be initiated. Disclosure of interest None Declared. References Frossard JL, et al . The role of transient elastography in the detection of liver disease in patients with chronic pancreatitis. Liver Int. 2013;33(7):1121–1127 Fraquelli M, et al . Reproducibility of transient elastography in the evaluation of liver fibrosis in patients with chronic liver disease. Gut 2007;56(7):968–973 Braganza JM, et al . Chronic pancreatitis. Lancet 2011;377(9772): 1184–1197 Scobie BA, Summerskill WH. Hepatic Cirrhosis Secondary to Obstruction of the Biliary System. Am J Dig Dis. 1965;10:135–146

WS16.3 Consecutive transient elastography measurements to detect cystic fibrosis liver disease

Background Cystic fibrosis (CF) related liver disease (CFLD) is diagnosed using a combination of criteria. Transient elastography (TE) (ultrasonographic method evaluating liver stiffness) differentiates CF patients with and without liver disease (CFnoLD) and identifies patients with an increased risk for portal hypertension. Aim: Detect evolving CFLD using TE measurements. Method Retrospective study (2007–2013) including all patients with TE measurements, performed by the same operator. Measurement was correlated to the presence or development of CFLD based on the medical files. Results 150 CF patients [median age 17 (9–24) years] were included, 118 with repeated TE: 20 (14%) had CFLD at the first TE measurement, 4 (3%) developed CFLD during follow-up. The median TE value in CFLD was 14 (8.7–32.2) compared to 5.3 (4.9–5.7) in CFnoLD (P = 0.0001). The intra-individual differences between 2 consecutive measurements [median interval between measurements 1 yr (1–2)] was 0.05 (–1, 1.2) in CFnoLD and 0.55 (–1.68, 1.53) in the CFLD patients. The area under the receiver operating curve for TE predicting CFLD was 0.985. TE measurements above 6.55 kPa predicted CFLD with a sensitivity of 94.7% and a specificity of 90.8% according to the AUROC. In CF Conclusion TE measurements progressively increased in CF patients developing CFLD. A prospective study is needed to evaluate whether TE will be able to detect CFLD before it becomes clinically apparent.

Liver Fibrosis by Transient Elastography and Virologic Outcomes After Introduction of Tenofovir in Lamivudine-Experienced Adults With HIV and Hepatitis B Virus Coinfection in Ghana.

Antiretroviral treatment (ART) programs in sub-Saharan Africa have for many years included lamivudine as the sole hepatitis B virus (HBV) inhibitor. Long-term outcomes and the effects of introducing tenofovir as part of ART in these populations have not been characterized. The study comprised a cross-sectional analysis of 106 human immunodeficiency virus (HIV)/HBV-coinfected subjects maintained on lamivudine, as well as a prospective analysis of 76 lamivudine-experienced subjects who introduced tenofovir. Patients underwent assessment of liver fibrosis by transient elastography (TE) and testing to characterize HIV type 1 (HIV-1) and HBV replication. After a median of 45 months of lamivudine treatment, HIV-1 RNA and HBV DNA were detectable in 35 of 106 (33.0%) and 54 of 106 (50.9%) subjects, respectively, with corresponding drug resistance rates of 17 of 106 (16.0%) and 31 of 106 (29.2%), respectively. Median TE values were 5.7 kPa (interquartile range, 4.7-7.2 kPa) and independently associated with HBV DNA load, aspartate aminotransferase levels, and platelet counts; 13 of 106 (12.3%) subjects had TE measurements >9.4 kPa. Twelve months after the first assessment, and a median of 7.8 months after introducing tenofovir, HBV DNA levels declined by a mean of 1.5 log10 IU/mL (P < .001). TE values changed by a mean of -0.2 kPa (P = .097), and declined significantly in subjects who had pretenofovir HBV DNA levels >2000 IU/mL (mean, -0.8 kPa; P = .048) or TE values >7.6 kPa (mean, -1.2 kPa; P = .021). HIV-1 RNA detection rates remained unchanged. A proportion of HIV/HBV-coinfected patients on long-term lamivudine-containing ART had poor HIV and HBV suppression, drug resistance, and TE values indicative of advanced liver fibrosis. Tenofovir improved HBV control and reduced liver stiffness in subjects with high HBV DNA load and TE values.

Baseline prevalence and predictors of liver fibrosis among HIV-positive individuals: a substudy of the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial.

Liver disease is increasingly recognized in HIV-positive individuals, even among those without viral hepatitis, partly as a result of the recent availability of noninvasive methods of liver fibrosis assessment. The objective of this substudy is to compare the effects of early versus deferred antiretroviral therapy (ART) on liver fibrosis progression. Sites in the Strategic Timing of AntiRetroviral Treatment (START) study with access to FibroScan® were invited to participate in the Liver Fibrosis Progression Substudy. All substudy participants underwent FibroScan® at baseline, and two noninvasive serum algorithms, APRI and FIB-4, were calculated. Demographic and liver-related information was collected for all START participants at baseline. A total of 230 participants were enrolled in the substudy (11.5% with hepatitis B or C virus coinfection), of whom 221 had a valid transient elastography (TE) result. The median TE score was 4.9 kPa [interquartile range (IQR) 4.3-6.0 kPa]. Seventeen patients (7.8%) [95% confidence interval (CI) 5.1-12.1%] had a TE score of > 7.2 kPa, indicating significant liver fibrosis. Baseline factors associated with higher TE scores in multivariate analysis were higher alanine aminotransferase (ALT) per 10 U/L (P = 0.045), higher log10 HIV RNA (P < 0.001) and Hispanic/Latino ethnicity (P = 0.01). TE correlated weakly with noninvasive markers. At baseline, significant liver fibrosis was observed in approximately 8% of participants, with higher ALT and HIV RNA the only clinical factors associated with increasing TE score. TE will be used annually to monitor fibrosis and evaluate the role of ART in further fibrosis progression.

Liver stiffness measured by transient elastography in patients with acute pancreatitis

BackgroundAlcohol abuse constitutes a risk factor for acute pancreatitis and liver cirrhosis, and cirrhosis in turn may delay the recovery from pancreatitis. We evaluated the occurrence and significance of liver fibrosis or cirrhosis in patients with acute pancreatitis by applying transient elastography (TE). MethodsTE was carried out in 78 patients with acute pancreatitis. Comparisons were made to the severity and recurrence of pancreatitis, to biological markers for fibrosis (APRI test), alcohol intake (AST/ALT ratio, AUDIT), and prothrombin time (TT-SPA). A cut-off value of ≥7.5 kilopascals (kPa) was set for increased liver stiffness, and ≥10 kPa for significant fibrosis. ResultsThe aetiology of pancreatitis was alcohol intake in 62 patients, gallstones in 11, idiopathic in 3, tumour in 1 and medication in 1. TE was successful in 64 out of 78 patients. The median TE value was 6.5 kPa (range 2.5–61.1); 22 (35%) had values ≥7.5 kPa and 7 (11%) ≥10 kPa. Values ≥7.5 were associated with older age, higher APRI ratio, and lower TT-SPA. It did not predict the length of hospitalization or the recurrence of pancreatitis. Increased AST/ALT ratio was associated with high TE values, whereas AUDIT values were not. Values ≥10 kPa seemed to indicate manifest cirrhosis, hepatitis or subsequent development of diabetes. ConclusionsTE values ≥7.5 kPa did not predict the length of hospital stay or recurrence of pancreatitis but there were some findings of impaired liver function. Values ≥10 kPa may indicate subsequent development of diabetes and a more severe course of acute pancreatitis.

Identification of Combined Genetic Determinants of Liver Stiffness within the SREBP1c-PNPLA3 Pathway

The common PNPLA3 (adiponutrin) variant, p.I148M, was identified as a genetic determinant of liver fibrosis. Since the expression of PNPLA3 is induced by sterol regulatory element binding protein 1c (SREBP1c), we investigate two common SREBP1c variants (rs2297508 and rs11868035) for their association with liver stiffness. In 899 individuals (aged 17–83 years, 547 males) with chronic liver diseases, hepatic fibrosis was non-invasively phenotyped by transient elastography (TE). The SREBP1c single nucleotide polymorphisms (SNPs) were genotyped using PCR-based assays with 5′-nuclease and fluorescence detection. The SREBP1c rs11868035 variant affected liver fibrosis significantly (p = 0.029): median TE levels were 7.2, 6.6 and 6.0 kPa in carriers of (TT) (n = 421), (CT) (n = 384) and (CC) (n = 87) genotypes, respectively. Overall, the SREBP1c SNP was associated with low TE levels (5.0–8.0 kPa). Carriers of both PNPLA3 and SREBP1c risk genotypes displayed significantly (p = 0.005) higher median liver stiffness, as compared to patients carrying none of these variants. The common SREBP1c variant may affect early stages of liver fibrosis. Our study supports a role of the SREBP1c-PNPLA3 pathway as a “disease module” that promotes hepatic fibrogenesis.

The diagnostic accuracy of Fibroscan® for cirrhosis is influenced by liver morphometry in HCV patients with a sustained virological response

Transient elastography (TE) is a validated non-invasive tool to evaluate hepatic fibrosis in patients with hepatitis C virus (HCV) infection. Whether TE may sense changes of liver fibrosis following therapeutic HCV eradication has never been evaluated. 37 HCV cirrhotics with paired pre- and post-sustained virological response (SVR) liver biopsies (LB) underwent TE at the time of post-SVR LB. Liver fibrosis was staged with the METAVIR scoring system and the area of fibrosis (%) was assessed morphometrically. Thirty-three patients had valid TE measurements after 61 (48-104) months from an SVR, and 20 (61%) of them had cirrhosis regression. On post-SVR LB, the median area of fibrosis was 2.3%, being significantly reduced from baseline (p<0.0001). Median TE value was 9.8 kPa being lower in regressed vs. not regressed patients (9.1 kPa vs. 12.9 kPa, p=0.01). TE was <12 kPa in 5 (38%) F4 patients and in 19 (95%) ≤F3 patients (p=0.0007). The diagnostic accuracy of TE for diagnosing F4 after treatment was 61% sensitivity, 95% specificity, 12.3 LR+, 0.4 LR-, and AUROC 0.77. A significant correlation was found between TE and both fibrosis stage (r=0.56; p=0.001) and morphometry (r=0.56, p=0.001) as well as between fibrosis stage and area of fibrosis (r=0.72, p=0001). Following therapeutic eradication of HCV, the predictive power of the viremic cut-off of 12 kPa was low as a consequence of liver remodelling and fibrosis reabsorption. LB still remains the only reliable approach to stage liver fibrosis following an SVR.

The effect of hemodialysis on liver stiffness measurement

The noninvasive measurement of liver stiffness using transient elastography (TE) is increasingly being used alongside liver biopsy. However, several conditions may lead to higher liver stiffness values without reflecting more fibrosis. Such conditions (e.g. hepatitis, cholestasis, heart failure, mechanical ventilation) limit the interpretation of liver stiffness measurements. The influence of hemodialysis on the measurement of liver stiffness has not been investigated to date. Here, we analyzed liver stiffness assessed by fibroscan in 17 patients directly before and after a hemodialysis session. Measurement of hepatic stiffness by TE was carried out using the Fibroscan device with the 'M probe' directly before and directly after one session of hemodialysis. Each measurement consisted of at least 10 individual and valid measurements, with a success rate of at least 60%, and an interquartile range of less than 25%. All measurements were carried out by one investigator not involved in patient management. Before dialysis, the median TE was 5.1 kPa (2.8-17 kPa). Ten patients had values below the threshold of 7.1 kPa and seven patients had TE>7.1 kPa. The median net fluid withdrawal by hemodialysis was 2.5 l (0.4-3.1 l) and did not differ between patients. After dialysis, the TE median was 7.4 kPa (3.5-12.5 kPa) and had changed in all patients except one. Liver stiffness increased significantly when the initial TE was lower than 7.1 kPa (P=0.05), but not when the initial TE was higher than 7.1 kPa. Furthermore, the magnitude of the change in TE after hemodialysis correlated inversely with the liver stiffness before hemodialysis (P=0.03) and with spleen length measured by ultrasound (P=0.03). This study is the first to report on the influence of hemodialysis on liver stiffness measurement. In contrast to previous reports, liver stiffness might increase after fluid withdrawal if patients do not show significant fibrosis. We conclude that before dialysis, TE possibly better differentiates between patients with or without significant fibrosis.