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Review
. 2020 Aug 10;10(8):579.
doi: 10.3390/diagnostics10080579.

Surveillance of Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease

Yoshio Sumida  1 , Masashi Yoneda  1 , Yuya Seko  2 , Hiroshi Ishiba  3 , Tasuku Hara  4 , Hidenori Toyoda  5 , Satoshi Yasuda  5 , Takashi Kumada  5 , Hideki Hayashi  6 , Takashi Kobayashi  7 , Kento Imajo  7 , Masato Yoneda  7 , Toshifumi Tada  8 , Takumi Kawaguchi  9 , Yuichiro Eguchi  10 , Satoshi Oeda  11 , Hirokazu Takahashi  11 , Eiichi Tomita  6 , Takeshi Okanoue  12 , Atsushi Nakajima  7 , Japan Study Group Of Nafld Jsg-Nafld  13
Affiliations
Review

Surveillance of Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease

Yoshio Sumida et al. Diagnostics (Basel). .

Abstract

Nonalcoholic fatty liver disease (NAFLD) is becoming the leading cause of hepatocellular carcinoma (HCC), liver-related mortality, and liver transplantation. There is sufficient epidemiological cohort data to recommend the surveillance of patients with NAFLD based upon the incidence of HCC. The American Gastroenterology Association (AGA) expert review published in 2020 recommends that NAFLD patients with cirrhosis or advanced fibrosis estimated by non-invasive tests (NITs) consider HCC surveillance. NITs include the fibrosis-4 (FIB-4) index, the enhanced liver fibrosis (ELF) test, FibroScan, and MR elastography. The recommended surveillance modality is abdominal ultrasound (US), which is cost effective and noninvasive with good sensitivity. However, US is limited in obese patients and those with NAFLD. In NAFLD patients with a high likelihood of having an inadequate US, or if an US is attempted but inadequate, CT or MRI may be utilized. The GALAD score, consisting of age, gender, AFP, the lens culinaris-agglutinin-reactive fraction of AFP (AFP-L3), and the protein induced by the absence of vitamin K or antagonist-II (PIVKA-II), can help identify a high risk of HCC in NAFLD patients. Innovative parameters, including a Mac-2 binding protein glycated isomer, type IV collagen 7S, free apoptosis inhibitor of the macrophage, and a combination of single nucleoside polymorphisms, are expected to be established. Considering the large size of the NAFLD population, optimal screening tests must meet several criteria, including high sensitivity, cost effectiveness, and availability.

Keywords: Mac-2 binding protein glycated isomer; apoptosis inhibitor of macrophage; hepatic fibrosis; patatin-like phospholipase domain-containing protein 3; protein induced by vitamin K absence or antagonist-II; α-fetoprotein.

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Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
The 25% rule in nonalcoholic fatty liver disease (NAFLD) [10].
Figure 2
Figure 2
NITs for the surveillance of severe fibrosis and HCC in NAFLD. First, the NIT is used to determine advanced fibrosis (F3/4) from NAFLD. In cases of advanced fibrosis, regular image examinations are performed to detect HCC early. Then, strict surveillance is conducted among patients with a high GALAD score (>−0.63), high M2bpGi cases (>1.26), and PNPLA3 GG homozygous cases.
Figure 3
Figure 3
Algorithm for HCC surveillance in Nonalcoholic Fatty Liver Disease. NIT: noninvasive test, FIB-4: fibrosis-4, ELF: enhanced liver fibrosis, VCTE: vibration-controlled transient elastography, MRE: magnetic resonance elastography, HCC: hepatocellular carcinoma, US: ultrasonography, CT: computed tomography, MRI: magnetic resonance imaging, PIVKA-II: protein induced by vitamin K, AFP: α-fetoprotein, M2BPGi: Mac-2 binding protein glycosylated isomer. Mets: metabolic syndrome. The visualization score of the ultrasound for HCC screening is graded into the following categories: A—no or minimal limitations; B—moderate limitations, as the examination may obscure small masses; and C—severe limitation, as the examination may miss focal liver lesions [29].
See this image and copyright information in PMC

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