Non-invasive Measures Of Fibrosis Research Articles

Shear wave elastography: How well does it perform in chronic hepatitis D virus infection?

Hepatitis delta virus (HDV) infection is associated with accelerated progression of liver disease to cirrhosis. Shear wave elastography (SWE) is a non-invasive evaluation method of liver fibrosis. Its performance in accurately characterizing HDV fibrosis compared to other noninvasive markers remains unknown. We assessed the performance of SWE in patients with chronic HDV, Hepatitis B (HBV) and Hepatitis C (HCV) infection. Cirrhosis was determined by histology or clinical data. Area under receiver operator characteristics (AUROC) was used to assess diagnostic performance in identifying cirrhosis by SWE in comparison with Fibroscan® (VCTE) and serologic tests of fibrosis. 158 patients with chronic hepatitis (HDV:44%, HBV: 46% and HCV: 29%) were evaluated. Cirrhosis was diagnosed in 28 (17.7%) patients. Mean noninvasive fibrosis measurements for the HBV/HCV and HDV groups, respectively, were as follows: APRI: 0.73 ± 1.08 and 1.3 ± 1.38; FIB-4: 1.90 ± 2.24 and 2.33 ± 2.24; VCTE: 8.9 ± 6.7kPa vs 10.4 ± 5.3kPa; SWE: 1.5 ± 0.2m/s and 1.6 ± 0.2m/s. The performance of SWE in detecting HDV-induced cirrhosis (AUROC 0.84, 95% CI 0.71-0.97) was slightly lower than in HBV/HCV induced disease (AUROC 0.88, 95% CI 0.81-0.96). For HDV patients, the performance of SWE was comparable to VCTE and slightly better than APRI and FIB-4 especially in APRI and FIB-4 indeterminate zones. The overall less accurate performance of noninvasive markers in HDV in comparison with HBV and HCV may be a result of significant hepatic inflammation in HDV.

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

To assess changes in noninvasive liver fibrosis measurements after chronic hepatitis C eradication by direct-acting antivirals in Egyptian adolescents. Liver stiffness measurement (LSM), by vibration-controlled transient elastography and noninvasive fibrosis scores (Firbosis-4, aspartate aminotransferase-platelet ratio index), was obtained before and 12months 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. Analyzing 85 patients, the median baseline LSM was 5.8 (IQR, 4.2-6.5) and at follow-up 5.1kPa (IQR, 4-6kPa)(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 β-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. 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 12months after treatment in the majority of cases.

S3265 Assessment of the Likelihood of Hepatic Decompensation and Portal Hypertension Using Noninvasive Techniques in NAFLD-Cirrhotic Patients

INTRODUCTION: Nonalcoholic Fatty Liver Disease (NAFLD) can culminate in liver cirrhosis with the potential complication of portal hypertension. Among patients with cirrhosis, prognosis of their condition has been demonstrated through the use of the Model for End-Stage Liver Disease (MELD)-Na. Other methods of assessing a patient with cirrhosis’s prognosis is through measuring their hepatic venous pressure gradient (HVPG). The HVPG has been shown in previous studies to correlate with a patient’s MELD-Na score. The aim of this study was to determine the relationship between non-invasive measures of fibrosis with invasive HVPG measurements in a NAFLD-cirrhotic population. The MELD-Na scores were then calculated to assess their correlation with these noninvasive and invasive measures of clinical prognosis. METHODS: A retrospective study was done on a cohort of NAFLD-cirrhosis patients seen at Liver Associates of Texas in Houston, TX from 1/18 – 5/20. Patients’ portal hypertension was assessed using the HVPG calculated from transjugular pressure measurements. Fibrosis measurements were measured through liver stiffness readings through transient elastography. A multivariate linear regression was performed using fibrosis on elastography as the outcome variable to assess factors independently associated with fibrosis progression: gender, ethnicity, HPVG measurements, AST, ALT, and MELD-Na. Then a linear regression was performed between the MELD-Na and kilopascal (kPa) score to assess the correlation between these two values. RESULTS: 99 patients were included in the study, 38 had transjugular liver biopsies, and 49 had fibrosis measurements. 69% were females. 43% were Caucasian, 5% African American, 20% Hispanic, 4% Asian, and 27% were other. 29.05 (± 17.81) and 10.20 (±4.3) were the mean kPa and MELD-Na scores respectively. No significant finding was seen between HVPG and kPa measurements. Elastography and MELD-Na score were significantly correlated (P = 0.03) as well as elastography with AST (P = 0.034). CONCLUSION: This study demonstrated a significant correlation between elastography and the MELD-Na score in patients with NAFLD-cirrhosis. AST was also identified as a possible surrogate marker of fibrosis while HVPG was not. This gives more credence to the idea that NAFLD patients with cirrhosis could be better prognosticated through noninvasive studies such as the use of elastography or serum AST levels rather than more invasive methods such as HVPG measurements.Table 1.: Linear Regression on Selected Variables Compared to Fibrosis Measured on Elastography

Liver fibrosis improvement in chronic hepatitis C after direct acting-antivirals is accompanied by reduced profibrogenic biomarkers–a role for MMP-9/TIMP-1

Background and aimsDisturbances in matrix metalloproteinases (MMPs) and corresponding tissue inhibitors (TIMPs) contribute to hepatitis C virus (HCV)-induced fibrosis. This study aimed to determine MMP-9/TIMP-1 levels in addition to MMP-2 and -9 activities; correlating with the improvement of liver fibrosis in patients under direct-acting antiviral (DAA) therapy. MethodsClinical and laboratory follow-up were performed before treatment and after 12 weeks post-treatment, referred as sustained viral response (SVR). We evaluated liver function including non-invasive fibrosis measurements; MMP activity by zymography; and MMP-9/TIMP-1 complex, inflammatory and pro-fibrogenic mediators by immunoenzymatic assays. ResultsCohort included 33 patients (59.5 ± 9.3 years, 60.6% females) whose reached SVR and 11 control-paired subjects (42.5 ± 15 years, 54.5% females). Before treatment, HCV patients presented higher MMP-9/TIMP-1 levels (P < 0.05) when compared to controls, and the highest values were observed in patients with fibrosis (P < 0.05). In addition, MMP-9/TIMP-1 levels were significantly reduced after DAA therapy (P < 0.0001) and were associated with profibrogenic biomarkers. No differences were observed for MMP-2 and -9 activities; however, these biomarkers were significantly associated with inflammatory mediators. ConclusionOur data suggest that MMP-9/TIMP-1 complex can be a promising biomarker of active fibrogenesis, being able to identify the interruption of fibrosis progression after HCV eradication.

Fibrosis stage is an independent predictor of outcome in primary biliary cholangitis despite biochemical treatment response.

Fibrosis stage predicts prognosis in patients with chronic liver disease independent of aetiology, although its precise role in risk stratification in patients with primary biliary cholangitis (PBC) remains undefined. To assess the utility of baseline fibrosis stage in predicting long-term outcomes in the context of biochemical risk stratification METHODS: In a large and globally representative cohort of patients with PBC, liver biopsies performed from 1980 to 2014 were evaluated. The predictive ability of histologic fibrosis stage in addition to treatment response at 1year (Toronto/Paris-II criteria), as well as non-invasive markers of fibrosis (AST/ALT ratio [AAR], AST to platelet ratio index [APRI], FIB-4), for transplant-free survival was assessed with Cox proportional-hazards models. There were 1828 patients with baseline liver biopsy. Advanced histologic fibrosis (stage 3/4) was an independent predictor of survival in addition to non-invasive measures of fibrosis with the hazard ratios ranging from 1.59 to 2.73 (P<.001). Patients with advanced histologic fibrosis stage had worse survival despite biochemical treatment response, with a 10-year survival of 76.0%-86.6% compared to 94.5%-95.1% depending on the treatment response criteria used. Poor correlations were observed between non-invasive measures of fibrosis and histologic fibrosis stage. Assessment of fibrosis stage grants prognostic value beyond biochemical treatment response at 1year. This highlights the need to incorporate fibrosis stage in individual risk stratification in patients with PBC, partly to identify those that may derive benefit from novel therapies.

Applying Non-Invasive Fibrosis Measurements in NAFLD/NASH: Progress to Date.

Nonalcoholic fatty liver disease (NAFLD) has now become a worldwide health issue due to the obesity epidemic, affecting approximately 90% of the obese population and 15-40% of the general population. It is the most common form of chronic liver disease in the United States. NAFLD constitutes a spectrum of diseases ranging in severity from mild, such as fatty liver, progressing into nonalcoholic steatohepatitis (NASH), then fibrosis, and ending with cirrhosis. NASH and increasing fibrosis stage are associated with increased morbidity and mortality; the fibrosis stage is therefore a critical element of risk stratification needed to determine therapeutic approach and also the response to treatment. Liver biopsy is considered the 'gold standard' in the diagnosis of NAFLD. However, it is not practical for widespread clinical use because it is invasive, costly, and associated with complications including occasional death. These limitations have driven the development of noninvasive tests that can accurately predict the fibrosis stage in those with NAFLD. In this review, we provide a concise overview of different non-invasive measurements used for NAFLD/NASH.

PS-012-Validation of histologic and non-invasive measures of fibrosis as surrogate end points of disease progression in patients with primary sclerosing cholangitis

PS-012-Validation of histologic and non-invasive measures of fibrosis as surrogate end points of disease progression in patients with primary sclerosing cholangitis

Prognostic durability of liver fibrosis tests and improvement in predictive performance for mortality by combining tests.

There is currently no recommended time interval between noninvasive fibrosis measurements for monitoring chronic liver diseases. We determined how long a single liver fibrosis evaluation may accurately predict mortality, and assessed whether combining tests improves prognostic performance. We included 1559 patients with chronic liver disease and available baseline liver stiffness measurement (LSM) by Fibroscan, aspartate aminotransferase to platelet ratio index (APRI), FIB-4, Hepascore, and FibroMeterV2G . Median follow-up was 2.8years during which 262 (16.8%) patients died, with 115 liver-related deaths. All fibrosis tests were able to predict mortality, although APRI (and FIB-4 for liver-related mortality) showed lower overall discriminative ability than the other tests (differences in Harrell's C-index: P<0.050). According to time-dependent AUROCs, the time period with optimal predictive performance was 2-3years in patients with no/mild fibrosis, 1year in patients with significant fibrosis, and <6months in cirrhotic patients even in those with a model of end-stage liver disease (MELD) score <15. Patients were then randomly split in training/testing sets. In the training set, blood tests and LSM were independent predictors of all-cause mortality. The best-fit multivariate model included age, sex, LSM, and FibroMeterV2G with C-index=0.834 (95% confidence interval, 0.803-0.862). The prognostic model for liver-related mortality included the same covariates with C-index=0.868 (0.831-0.902). In the testing set, the multivariate models had higher prognostic accuracy than FibroMeterV2G or LSM alone for all-cause mortality and FibroMeterV2G alone for liver-related mortality. The prognostic durability of a single baseline fibrosis evaluation depends on the liver fibrosis level. Combining LSM with a blood fibrosis test improves mortality risk assessment.

PTU-086 Suboptimal Performance of Shearwave Elastography (ElastPQ) for Predicting Advanced Fibrosis in a Nafld Enriched Cohort: Abstract PTU-086 Table 1

Introduction It is important to identify those at risk of advanced liver fibrosis in order to stratify care. Histological assessment by liver biopsy (LBx) is the gold standard for staging liver fibrosis, but is impractical for widespread use. Several non-invasive measures of fibrosis, such as transient elastography and simple markers (FIB4 score and AST/ALT ratio (AAR)) have shown promise as alternatives to LBx. Shearwave elastography (SWE), assessed using acoustic radiation force impulses (ARFI), offers a potential alternative technique that can be performed on a conventional ultrasound machine. To date, few studies have evaluated the Phillips ElastPQ system, particularly in patients with non-alcoholic fatty liver disease (NAFLD). Our aim was to evaluate the accuracy of SWE using ElastPQ compared with liver biopsy in a “real world” cohort. Methods Patients undergoing LBx between Sept 2014-Dec 2015 who had SWE conducted at the time of LBx were included. Clinical and demographic data were collected from the time of LBx. The AAR and FIB4 scores were calculated. Liver fibrosis was staged from 0–4; stage 3–4 was considered advanced fibrosis. SWE was conducted by experienced sonographers. SWE values (m/s) were defined as normal ( 1.55). Results 92 patients were identified (52% male; median age 51 yrs, range 20–90). LBx diagnoses were: 57 NAFLD, 10 AIH, 9 PBC, 6 HBV/HCV and 10 other. Median biopsy size was 20 mm (IQR 16.2–24). Overall, there was significant correlation between SWE and fibrosis stage (r = 0.44 p Conclusion In this real world cohort, SWE using ElastPq had suboptimal performance and missed clinically significant advanced fibrosis in 24% of cases. It appears that this technique does not perform as well in patients with NAFLD as other liver diseases, such as viral hepatitis. Disclosure of Interest None Declared

Predictive value of FIB-4 and APRI versus METAVIR on sustained virologic response in genotype 1 hepatitis C patients.

Advanced liver fibrosis is a negative predictor of virologic response in genotype 1 chronic hepatitis C (CHC) patients. Biopsy, however, is invasive, costly, and carries some risk of complications. Using data from the prospective, international cohort study PROPHESYS, we assessed two alternative noninvasive measures of fibrosis, the FIB-4 and AST-to-platelet ratio index (APRI), to predict virologic response in CHC patients. CHC genotype 1, monoinfected, treatment-naive patients prescribed peginterferon alfa-2a (40KD)/ribavirin in accordance with country-specific legal and regulatory requirements and who had baseline METAVIR, FIB-4, and APRI scores (N=1,592) were included in this analysis. Patients were stratified according to the baseline METAVIR, FIB-4, or APRI score to assess virologic response [hepatitis C virus (HCV) RNA <50IU/mL] by week 4 of treatment (rapid virologic response) and 24weeks after untreated follow-up ]sustained virologic response (SVR)]. Baseline predictors of SVR were explored by multiple logistic regression, and the strength of the association between each fibrosis measure and SVR was evaluated. Both FIB-4 and APRI scores increased with increasing levels of biopsy-assessed fibrosis. The association between FIB-4 and SVR (p<0.1×10(-30)) was stronger than that between METAVIR (p=3.86×10(-13)) or APRI (p=5.48×10(-6)) and SVR. Baseline factors significantly associated with SVR included male gender, lower HCV RNA, lower FIB-4 score, no steatosis, and higher alanine aminotransferase ratio. The FIB-4 index provides a valuable, noninvasive measure of fibrosis and can be used to predict virologic response in patients treated with peginterferon alfa-2a (40KD)/ribavirin.

Biochemical assessment of myocardial fibrosis in hypertensive heart disease.

Fibrous tissue accumulation is an integral feature of the adverse structural remodeling of cardiac tissue seen with hypertensive heart disease. Given the importance of fibrous tissue in leading to myocardial dysfunction and failure, noninvasive monitoring of myocardial fibrosis by use of serological markers of collagen turnover could prove a clinically useful tool, particularly given the potential for cardioprotective and cardioreparative pharmacological strategies. An emerging experimental and clinical experience holds promise for the use of radioimmunoassays of various serological markers of fibrillar collagen type I and type III turnover in arterial hypertension. More specifically, the measurement of serum concentrations of procollagen type I C-terminal propeptide (a peptide that is cleaved from procollagen type I during the synthesis of fibril-forming collagen type I) may provide indirect diagnostic information on both the extent of myocardial fibrosis and the ability of antihypertensive treatment to diminish collagen type I synthesis and reduce myocardial fibrosis. This approach represents an exciting and innovative strategy, and available data set the stage for larger trials, in which noninvasive measures of fibrosis in hypertensive heart disease could prove useful.