Noninvasive Assessment of Liver Disease in Patients With Nonalcoholic Fatty Liver Disease

Abstract

Nonalcoholic fatty liver disease (NAFLD) is estimated to afflict approximately 1 billion individuals worldwide. In a subset of NAFLD patients, who have the progressive form of NAFLD termed nonalcoholic steatohepatitis (NASH), it can progress to advanced fibrosis, cirrhosis, hepatocellular carcinoma, and liver-related morbidity and mortality. NASH is typically characterized by a specific pattern on liver histology, including steatosis, lobular inflammation, and ballooning with or without peri-sinusoidal fibrosis. Thus, key issues in NAFLD patients are the differentiation of NASH from simple steatosis and identification of advanced hepatic fibrosis. Until now, liver biopsy has been the gold standard for identifying these 2 critical end points, but has well-known limitations, including invasiveness; rare but potentially life-threatening complications; poor acceptability; sampling variability; and cost. Furthermore, due to the epidemic proportion of individuals with NAFLD worldwide, liver biopsy evaluation is impractical, and noninvasive assessment for the diagnosis of NASH and fibrosis is needed. Although much of the work remains to be done in establishing cost-effective strategies for screening for NASH, advanced fibrosis, and cirrhosis, in this review, we summarize the current state of the noninvasive assessment of liver disease in NAFLD, and we provide an expert synthesis of how these noninvasive tools could be utilized in clinical practice. Finally, we also list the key areas of research priorities in this area to move forward clinical practice.

Keywords: ARFI; CAP; Fibrosis; MRE; MRI-PDFF; NAFLD; NASH; Noninvasive; SWE; Serum Biomarkers; Steatosis; VCTE.

Conflict of interest statement

Conflicts of interest

The authors disclose the following: Laurent Castera: speaker bureau of AbbVie, Echosens, Intercept, Gilead, and Sirtex. Advisory boards for Allergan, Gilead, MSD, Pfizer, and Servier. Mireen Friedrich-Rust: speaker honorarium from Echosens, Siemens. Advisory board for Toshiba. Research support for Echosens, Supersonic, and Siemens. Rohit Loomba: grants from Allergan, BMS, Boehringer Ingleheim, Eli Lily, Galectin, Galmed, GE, Genfit, Gilead, Intercept, Janssen, Madrigal, NGM, Prometheus, Siemens, Shire, Pfizer, advisory committees for Arrowhead Research, Conatus, Galmed, Gemphire, Gilead, Intercept, NGM, and Cirius. Consultant for Bird Rock Bio, BMS, Coh Bar, Celgene, Civi Bio, Conatus, Enanta, Gilead, GRI Bio, Ionis, Metacrine, NGM, Receptos, Sanofi, Salix, Kowa, and Median technologies. Co-founder of Liponexus Inc.

Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1.

A suggested algorithm for the use of noninvasive tests for risk stratification of patients with suspected NAFLD in clinical practice. *Suspicion of NAFLD is based on the presence of steatosis on ultrasound or abnormal liver tests (transaminases/γ-glutamyltransferase) in patients with risk factors (obesity, type 2 diabetes, or metabolic syndrome). Significant alcohol consumption and secondary causes of steatosis should be excluded. The proposed algorithm is based on expert opinion. The choice of noninvasive tools should be sequential, guided by local availability and the context of use: in primary health care setting, simple inexpensive and widely available serum biomarkers, such as FIB-4 or NFS, with high negative predictive value (88%−95%) for ruling out advanced fibrosis should be used as first-line. Patients with low risk (FIB-4 <1.3 or NAFLD Fibrosis score < −1.455; 55 to 58% of cases) do not need further assessment. They should be offered lifestyle modifications and exercise. Those with intermediate (FIB-4 = 1.3 to 3.25 or NFS = −1.455 to 0.672; 30% of cases) and high risk (FIB-4 >3.25 or NFS >0.672; 12%–15% of cases, positive predictive value 75%–90%) of having advanced fibrosis should be addressed to a referral center for LSM, using TE, in fasting condition, using M-probe for patients with skin-liver capsule distance <25 mm otherwise with the XL-probe. Patients at low risk of having advanced fibrosis (LSM <8 kPa; NPV 94%–100%) should be considered for a repeat evaluation within 1 year. Those with intermediate (LSM = 8–10 kPa) or high risk (LSM ≥10 kPa, PPV 47%–70%) of having advanced fibrosis should be considered for liver biopsy. However, confounders for liver stiffness should be carefully excluded to minimize the risk of false positive results. **Also patented serum biomarkers (FibroTest, Fibrometer, or ELF) could be considered in patients with intermediate risk according to local availability. In case of TE failure, alternative such as SWE/ARFI, MRE (particularly when BMI >35 kg/m2) may be considered according to local availability. In any case, all patients should be offered lifestyle modifications and exercise. As recommended by recent European Association for the Study of the Liver or American Association for the Study of Liver Diseases clinical practice guidelines, vitamin E (in non-diabetics) and pioglitazone may be considered in these patients. Also patients with cirrhosis should be screened for esophageal varices (OV) and hepatocellular carcinoma (HCC). In those with a liver biopsy, follow-up during treatment of LSM, using MRE, is the most promising noninvasive approach but requires further validation. NPV, negative predictive value; PPV, positive predictive value.