Nonalcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease worldwide, and the progressive form of this condition, nonalcoholic steatohepatitis (NASH), has ...become one of the leading indications for liver transplantation. Despite intensive investigations, there are currently no United States Food and Drug Administration–approved therapies for treating NASH. A major barrier for drug development in NASH is that treatment response assessment continues to require liver biopsy, which is invasive and interpreted subjectively. Therefore, there is a major unmet need for developing noninvasive, objective, and quantitative biomarkers for diagnosis and assessment of treatment response. Emerging data support the use of magnetic resonance imaging–derived proton density fat fraction (MRI‐PDFF) as a noninvasive, quantitative, and accurate measure of liver fat content to assess treatment response in early‐phase NASH trials. In this review, we discuss the role and utility, including potential sample size reduction, of MRI‐PDFF as a quantitative and noninvasive imaging‐based biomarker in early‐phase NASH trials.
Nonalcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease worldwide.() NAFLD can be broadly classified into two categories: nonalcoholic fatty liver, which has a minimal risk of progression to cirrhosis, and nonalcoholic steatohepatitis (NASH), the more progressive form of NAFLD, which has a significantly increased risk of progression to cirrhosis.() Over the past two decades, NASH‐related cirrhosis has become the second leading indication for liver transplantation in the United States.() For these reasons, pharmacological therapy for NASH is needed urgently. Despite intensive investigations, there are currently no therapies for treating NASH that have been approved by the United States Food and Drug Administration.()
Abstract Nonalcoholic fatty liver disease (NAFLD) represents one of the most common causes of chronic liver disease, and its prevalence is rising worldwide. The occurrence of nonalcoholic ...steatohepatitis (NASH) is associated with a substantial increase in disease related morbidity and mortality. Accordingly, there has been a surge of innovation surrounding drug development in an effort to off-set the natural progression and long-term risks of this disease. Disease assessment within clinical trials and clinical practice for NAFLD is currently done with liver biopsies. Liver biopsy-based assessments, however, remain imprecise and are not without cost or risk. This carries significant implications for the feasibility and costs of bringing therapeutic interventions to market. A need therefore arises for reliable and highly accurate surrogate end-points that can be used in phase 2 and 3 clinical trials to reduce trial size requirements and costs, while improving feasibility and ease of implementation in clinical practice. Significant advances have now been made in magnetic resonance technology, and magnetic resonance imaging (MRI) and elastrography (MRE) have been demonstrated to be highly accurate diagnostic tools for the detection of hepatic steatosis and fibrosis. In this review article, we will summarize the currently available evidence regarding the use of MRI and MRE among NAFLD patients, and the evolving role these surrogate biomarkers will play in the rapidly advancing arena of clinical trials in NASH and hepatic fibrosis. Furthermore, we will highlight how these tools can be readily applied to routine clinical practice, where the growing burden of NAFLD will need to be met with enhanced monitoring algorithms.
Hepatocellular carcinoma (HCC) is the sixth most common cancer and the second leading cause of cancer mortality worldwide. Incidence rates of liver cancer vary widely between geographic regions and ...are highest in Eastern Asia and sub-Saharan Africa. In the United States, the incidence of HCC has increased since the 1980s. HCC detection at an early stage through surveillance and curative therapy has considerably improved the 5-year survival. Therefore, medical societies advocate systematic screening and surveillance of target populations at particularly high risk for developing HCC to facilitate early-stage detection. Risk factors for HCC include cirrhosis, chronic infection with hepatitis B virus (HBV), hepatitis C virus (HCV), excess alcohol consumption, non-alcoholic fatty liver disease, family history of HCC, obesity, type 2 diabetes mellitus, and smoking. Medical societies utilize risk estimates to define target patient populations in which imaging surveillance is recommended (risk above threshold) or in which the benefits of surveillance are uncertain (risk unknown or below threshold). All medical societies currently recommend screening and surveillance in patients with cirrhosis and subsets of patients with chronic HBV; some societies also include patients with stage 3 fibrosis due to HCV as well as additional groups. Thus, target population definitions vary between regions, reflecting cultural, demographic, economic, healthcare priority, and biological differences. The Liver Imaging Reporting and Data System (LI-RADS) defines different patient populations for surveillance and for diagnosis and staging. We also discuss general trends pertaining to geographic region, age, gender, ethnicity, impact of surveillance on survival, mortality, and future trends.
To improve standardization and consensus regarding performance, interpreting, and reporting computed tomography (CT) and magnetic resonance imaging (MRI) examinations of the liver in patients at risk ...for hepatocellular carcinoma (HCC), LI‐RADS (Liver Imaging Reporting and Data System) was launched in March 2011 and adopted by many clinical practices throughout the world. LI‐RADS categorizes nodules recognized at CT or MRI, in patients at high risk of HCC, as definitively benign, probably benign, intermediate probability of being HCC, probably HCC, and definitively HCC (corresponding to LI‐RADS categories 1‐5). The LI‐RADS Management Working Group, consisting of internationally recognized medical and surgical experts on HCC management, as well as radiologists involved in the development of LI‐RADS, was convened to evaluate management implications related to radiological categorization of the estimated probability that a lesion will be ultimately diagnosed as HCC. In this commentary, we briefly review LI‐RADS and the initial consensus of the LI‐RADS Management Working Group reached during its deliberations in 2013. We then focus on initial discordance of LI‐RADS with American Association for the Study of Liver Diseases and Organ Procurement Transplant Network guidelines, the basis for these differences, and how they are being addressed going forward to optimize reporting of CT and MRI findings in patients at risk for HCC and to increase consensus throughout the international community of physicians involved in the diagnosis and treatment of HCC. (Hepatology 2015;61:1056–1065)
Computed tomography (CT) and magnetic resonance (MR) imaging play critical roles in the diagnosis and staging of hepatocellular carcinoma (HCC). The second article of this two-part review discusses ...basic concepts of diagnosis and staging, reviews the diagnostic performance of CT and MR imaging with extracellular contrast agents and of MR imaging with hepatobiliary contrast agents, and examines in depth the major and ancillary imaging features used in the diagnosis and characterization of HCC.
Computed tomography (CT) and magnetic resonance (MR) imaging play critical roles in the diagnosis and staging of hepatocellular carcinoma (HCC). The first article of this two-part review discusses ...key concepts of HCC development, growth, and spread, emphasizing those features with imaging correlates and hence most relevant to radiologists; state-of-the-art CT and MR imaging technique with extracellular and hepatobiliary contrast agents; and the imaging appearance of precursor nodules that eventually may transform into overt HCC.
The presence of advanced fibrosis in nonalcoholic fatty liver disease (NAFLD) is the most important predictor of liver mortality. There are limited data on the diagnostic accuracy of gut ...microbiota-derived signature for predicting the presence of advanced fibrosis. In this prospective study, we characterized the gut microbiome compositions using whole-genome shotgun sequencing of DNA extracted from stool samples. This study included 86 uniquely well-characterized patients with biopsy-proven NAFLD, of which 72 had mild/moderate (stage 0–2 fibrosis) NAFLD, and 14 had advanced fibrosis (stage 3 or 4 fibrosis). We identified a set of 40 features (p < 0.006), which included 37 bacterial species that were used to construct a Random Forest classifier model to distinguish mild/moderate NAFLD from advanced fibrosis. The model had a robust diagnostic accuracy (AUC 0.936) for detecting advanced fibrosis. This study provides preliminary evidence for a fecal-microbiome-derived metagenomic signature to detect advanced fibrosis in NAFLD.
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•Gut microbiota is associated with advanced fibrosis in human NAFLD•Metagenome-based gut microbiome panel can accurately diagnose advanced fibrosis
Loomba et al. reveal how a panel of gut microbiome biomarkers can be used as a non-invasive test to accurately diagnose advanced fibrosis in patients with non-alcoholic fatty liver disease.
Objectives
The 8th International Forum for Liver Magnetic Resonance Imaging (MRI), held in Basel, Switzerland, in October 2017, brought together clinical and academic radiologists from around the ...world to discuss developments in and reach consensus on key issues in the field of gadoxetic acid–enhanced liver MRI since the previous Forum held in 2013.
Methods
Two main themes in liver MRI were considered in detail at the Forum: the use of gadoxetic acid for contrast-enhanced MRI in patients with liver cirrhosis and the technical performance of gadoxetic acid–enhanced liver MRI, both opportunities and challenges. This article summarises the expert presentations and the delegate voting on consensus statements discussed at the Forum.
Results and conclusions
It was concluded that gadoxetic acid–enhanced MRI has higher sensitivity for the diagnosis of hepatocellular carcinoma (HCC), when compared with multidetector CT, by utilising features of hyperenhancement in the arterial phase and hypointensity in the hepatobiliary phase (HBP). Recent HCC management guidelines recognise an increasing role for gadoxetic acid–enhanced MRI in early diagnosis and monitoring post-resection. Additional research is needed to define the role of HBP in predicting microvascular invasion, to better define washout during the transitional phase in gadoxetic acid–enhanced MRI for HCC diagnosis, and to reduce the artefacts encountered in the arterial phase. Technical developments are being directed to shortening the MRI protocol for reducing time and patient discomfort and toward utilising faster imaging and non-Cartesian free-breathing approaches that have the potential to improve multiphasic dynamic imaging.
Key Points
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Gadoxetic acid–enhanced MRI provides higher diagnostic sensitivity than CT for diagnosing HCC.
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Gadoxetic acid–enhanced MRI has roles in early-HCC diagnosis and monitoring post-resection response.
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Faster imaging and free-breathing approaches have potential to improve multiphasic dynamic imaging.
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