Laurent Castera

Noninvasive Methods to Assess Liver Disease in Patients With Hepatitis B or C

The prognosis and management of patients with chronic viral hepatitis B and C depend on the amount and progression of liver fibrosis and the risk for cirrhosis. Liver biopsy, traditionally considered to be the reference standard for staging of fibrosis, has been challenged over the past decade by the development of noninvasive methodologies. These methods rely on distinct but complementary approaches: a biologic approach, which quantifies serum levels of biomarkers of fibrosis, and a physical approach, which measures liver stiffness by ultrasound or magnetic resonance elastography. Noninvasive methods were initially studied and validated in patients with chronic hepatitis C but are now used increasingly for patients with hepatitis B, reducing the need for liver biopsy analysis. We review the advantages and limitations of the noninvasive methods used to manage patients with chronic viral hepatitis B or C infection.

WFUMB Guidelines and Recommendations for Clinical Use of Ultrasound Elastography: Part 2: Breast

The World Federation for Ultrasound in Medicine and Biology (WFUMB) has produced these guidelines for the use of elastography techniques in liver disease. For each available technique, the reproducibility, results, and limitations are analyzed, and recommendations are given. Finally, recommendations based on the international literature and the findings of the WFUMB expert group are established as answers to common questions. The document has a clinical perspective and is aimed at assessing the usefulness of elastography in the management of liver diseases.

Non invasive evaluation of portal hypertension using transient elastography

The development of portal hypertension is a common consequence of chronic liver diseases leading to the formation of esophageal and gastric varices responsible for variceal bleeding, associated with a high mortality rate, as well as other severe complications such as portosystemic encephalopathy and sepsis. Measurement of hepatic venous pressure gradient (HVPG) and upper GI endoscopy are considered the gold standards for portal hypertension assessment in patients with cirrhosis. However, both types of investigation are invasive and HVPG measurement is routinely available and/or performed with adequate standards only in expert centres. There is thus a need for non invasive methods able to predict, with acceptable diagnostic accuracy, the progression of portal hypertension toward the levels of clinically significant (i.e. HVPG ≥ 10 mmHg) and severe (HVPG ≥ 12 mmHg) as well as the presence and the size of oesophageal varices. Transient elastography (TE) is a novel non invasive technology that allows measuring liver stiffness and that has gained popularity over the past few years. Although TE has been initially proposed to assess liver fibrosis, a good correlation has been reported between liver stiffness values and HVPG as well as the presence of oesophageal varices, suggesting that it could be an interesting tool for the non invasive evaluation of portal hypertension. This review is aimed at discussing the advantages and limits of TE and the perspectives for its rationale use in clinical practice for the management of patients with portal hypertension.

The new paradigm of hepatitis C therapy: integration of oral therapies into best practices

Emerging data indicate that all‐oral antiviral treatments for chronic hepatitis C virus (HCV) will become a reality in the near future. In replacing interferon‐based therapies, all‐oral regimens are expected to be more tolerable, more effective, shorter in duration and simpler to administer. Coinciding with new treatment options are novel methodologies for disease screening and staging, which create the possibility of more timely care and treatment. Assessments of histologic damage typically are performed using liver biopsy, yet noninvasive assessments of histologic damage have become the norm in some European countries and are becoming more widespread in the United States. Also in place are new Centers for Disease Control and Prevention (CDC) initiatives to simplify testing, improve provider and patient awareness and expand recommendations for HCV screening beyond risk‐based strategies. Issued in 2012, the CDC recommendations aim to increase HCV testing among those with the greatest HCV burden in the United States by recommending one‐time testing for all persons born during 1945–1965. In 2013, the United States Preventive Services Task Force adopted similar recommendations for risk‐based and birth‐cohort‐based testing. Taken together, the developments in screening, diagnosis and treatment will likely increase demand for therapy and stimulate a shift in delivery of care related to chronic HCV, with increased involvement of primary care and infectious disease specialists. Yet even in this new era of therapy, barriers to curing patients of HCV will exist. Overcoming such barriers will require novel, integrative strategies and investment of resources at local, regional and national levels.

FibroScan (Vibration-Controlled Transient Elastography): Where Does It Stand in the United States Practice

With widespread screening and increasingly effective treatments for patients with viral hepatitis as well as the increasing prevalence of nonalcoholic fatty liver disease, the population presenting to the care of gastroenterologists and hepatologists is certain to increase. Assessment of advanced liver disease is traditionally invasive and expensive. Vibration-controlled transient elastography, commonly delivered by the FibroScan device, is an option recently approved by the Food and Drug Administration for the noninvasive assessment of liver disease at the point of care. Herein, we review the promise and pitfalls of vibration-controlled transient elastography with the aim of providing clinicians with a framework to interpret its results and apply this technology to the changing needs of our patients.

EFSUMB Guidelines and Recommendations on the Clinical Use of Liver Ultrasound Elastography, Update 2017 (Long Version)

We present here the first update of the 2013 EFSUMB (European Federation of Societies for Ultrasound in Medicine and Biology) Guidelines and Recommendations on the clinical use of elastography with a focus on the assessment of diffuse liver disease. The short version provides clinical information about the practical use of elastography equipment and interpretation of results in the assessment of diffuse liver disease and analyzes the main findings based on published studies, stressing the evidence from meta-analyses. The role of elastography in different etiologies of liver disease and in several clinical scenarios is also discussed. All of the recommendations are judged with regard to their evidence-based strength according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. This updated document is intended to act as a reference and to provide a practical guide for both beginners and advanced clinical users.

Non-invasive assessment of liver fibrosis in chronic hepatitis C

Quantification of hepatic fibrosis is of critical importance in chronic hepatitis C not only for prognosis, but also for antiviral treatment indication. Two end points are clinically relevant: detection of significant fibrosis (indication for antiviral treatment) and detection of cirrhosis (screening for eosphageal varices and hepatocellular carcinoma). Until recently, liver biopsy was considered the reference method for the evaluation of liver fibrosis. Limitations of liver biopsy (invasiveness, sampling error, and inter-observer variability) have led to the development of non-invasive methods. Currently available methods rely on two different approaches: a “biological” approach based on the dosage of serum fibrosis biomarkers; and a “physical” approach based on the measurement of liver stiffness, using transient elastography (TE). This review is aimed at discussing the advantages and limits of non-invasive methods and liver biopsy and the perspectives for their rational use in clinical practice in the management of patients with chronic hepatitis C.

Noninvasive Evaluation of Nonalcoholic Fatty Liver Disease.

Key issues in patients with nonalcoholic fatty liver disease (NAFLD) are the differentiation of nonalcoholic steatohepatitis (NASH) from simple steatosis and staging of liver fibrosis, as patients with NASH/advanced fibrosis are at greatest risk of developing complications of end-stage liver disease. The controlled attenuation parameter is the most promising noninvasive technique for detecting and quantifying hepatic steatosis, but needs to be implemented with the XL probe and compared with ultrasound that, despite its limitations, remains the most widely used method. Cytokeratin-18 is currently the most extensively validated serum marker of NASH as a stand-alone test or as part of prediction models. However, it is not widely available and thus has not been introduced yet into practice. Transient elastography, as well as FIB-4 and NAFLD fibrosis scores are the best methods to rule out severe fibrosis and cirrhosis. However, the high rate of unreliable results with transient elastography remains a challenge, which is not completely addressed by the use of the XL probe. Given the high prevalence of NAFLD in the general population, these noninvasive methods could be used in clinical practice as first-line tools to screen patients with NAFLD to help determine those who may still require a liver biopsy.

Hepatitis B: are non‐invasive markers of liver fibrosis reliable?

Liver biopsy, which was traditionally considered to be the gold standard for the staging of fibrosis, has been challenged in the past decade by non‐invasive techniques. These techniques rely on two distinct but complementary approaches: a ‘biological’ approach, based on the quantification of biomarkers of fibrosis in serum, and a ‘physical’ approach, based on the measurement of liver stiffness using elastography‐based technologies. Advantages of serum biomarkers include their high applicability (>95%) and good reproducibility. However, as none are liver specific their results can be influenced by comorbid conditions (risk of false positive results with FibroTest® in patients with Gilberts syndrome or with APRI in case of acute hepatitis). Transient elastograpy has the advantages of being a users friendly procedure that can be performed at the bedside or in an outpatient clinic with high performance for detecting cirrhosis. However, its applicability is lower (80%) than that of serum biomarker (particularly in case of ascites, obesity and limited operator experience) with the risk of false positive results in case of ALT flares. Although these non‐invasive methods were initially developed and validated in patients with chronic hepatitis C, they are now increasingly used in patients with hepatitis B, reducing the need for liver biopsy.

Screening for liver fibrosis in the general population: a call for action

Liver cirrhosis is one of the main causes of death and disability-adjusted life-years worldwide. Generally, cirrhosis develops after a long period of liver-cell injury that leads to the deposition of collagen, leading to progressive fibrosis and nodule formation in the liver tissue. Most patients are diagnosed in late stages when liver decompensation or liver cancer develops. The diagnosis is rarely made in early stages-when liver fibrosis is mild to moderate but cirrhosis is not yet established-because the disease is asymptomatic. No strategies for detection of liver fibrosis at these early stages have been developed, but therapies are more effective in early stages than late stages of chronic liver diseases, so enabling early detection is an important research topic. Non-invasive methods for assessing liver fibrosis have been developed, of which the most commonly used are transient elastography-which estimates liver fibrosis by measuring liver stiffness-and serum biomarkers of fibrosis. Studies have shown that 6-7% of the adult population without known liver disease have liver fibrosis, mostly associated with non-alcoholic fatty liver disease. These data suggest that programmes of screening for liver fibrosis in the general population should be assessed.