Role of noninvasive tests on the prediction of... : European Journal of Gastroenterology & Hepatology (original) (raw)

Original articles: Hepatology

Role of noninvasive tests on the prediction of hepatocellular carcinoma in nonalcoholic fatty liver disease patients without cirrhosis: a systematic review and meta-analysis of aggregate and individual patient data

Siriwong, Nanichaa,*; Sriphoosanaphan, Supachayaa,*; Decharatanachart, Pakanatb,*; Yongpisarn, Tanata; Kerr, Stephen J.c; Treeprasertsuk, Sombata; Tiyarattanachai, Thodsawitd; Apiparakoon, Terapapa; Hagström, Hannese,f; Akbari, Camillae; Ekstedt, Mattiasg; Yip, Terry Cheuk-Fungh,i,j; Wong, Grace Lai-Hungh,i,j; Ito, Takanorik; Ishigami, Masatoshik; Toyoda, Hidenoril; Peleg, Noamm; Shlomai, Amirn; Seko, Yuyao; Sumida, Yoshiop; Kawanaka, Miwaq; Hino, Keisuker; Chaiteerakij, Roongruedeea,s

aDivision of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, and King Chulalongkorn Memorial Hospital, Thai Red Cross Society

bDivision of Academic Affairs, Faculty of Medicine, Chulalongkorn University

cBiostatistics Excellence Centre, Faculty of Medicine, Chulalongkorn University

dDepartment of Medicine, Faculty of Medicine, Chulalongkorn University, and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand

eDepartment of Medicine, Huddinge, Karolinska Institutet

fDivision of Hepatology, Department of Upper GI, Karolinska University Hospital, Stockholm

gDivision of Diagnostics and Specialist Medicine, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden

hDepartment of Medicine and Therapeutics

iMedical Data Analytics Centre

jState Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong

kDepartment of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya

lDepartment of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Gifu, Japan

mDepartment of Gastroenterology and Hepatology, Rabin Medical Center, Beilinson Hospital, Petach-Tikva

nDepartment of Medicine D, Beilinson Hospital, Rabin Medical Center and the Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel

oDepartment of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto

pDivision of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University, Nagakute, Aichi

qDepartment of General Internal Medicine, Kawasaki Medical Center, Kawasaki Medical School, Okayama

rDepartment of Hepatology and Pancreatology, Kawasaki Medical School, Kurashiki, Japan

sCenter of Excellence for Innovation and Endoscopy in Gastrointestinal Oncology, Division of Gastroenterology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

*Nanicha Siriwong, Supachaya Sriphoosanaphan, and Pakanat Decharatanachart contributed equally to the writing of this article.

Received 10 February 2024 Accepted 9 September 2024.

Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website, www.eurojgh.com.

Correspondence to Roongruedee Chaiteerakij, MD, PhD, Center of Excellence for Innovation and Endoscopy in Gastrointestinal Oncology, Division of Gastroenterology, Faculty of Medicine, Chulalongkorn University, 1873 Rama IV Road, Patumwan, Bangkok 10330, Thailand, Tel: +66 2 256 4265; fax: +66 2 256 4356; e-mail: [email protected]

European Journal of Gastroenterology & Hepatology 37(3):p 358-369, March 2025. | DOI: 10.1097/MEG.0000000000002912

Abstract

Background

Nonalcoholic fatty liver disease (NAFLD) has been identified as an emerging risk factor for hepatocellular carcinoma (HCC). Identifying non-cirrhotic NAFLD patients at risk for HCC is crucial. We aimed to investigate the utility of noninvasive tests (NITs) as predictors for HCC and to determine optimal and cost-effective NIT cutoffs for HCC surveillance in non-cirrhotic NAFLD patients.

Methods

Medline, EMBASE, and Scopus databases were searched for studies evaluating the relationship between NITs and HCC in this population. Random-effects models were used to estimate hazard ratios or risk ratios and 95% confidence interval (95% CI). Cutoffs of NITs for identifying high-risk patients for HCC were determined.

Results

This systematic review comprised 20 studies. A meta-analysis of 379 194 patients was conducted using six studies with individual patient data and five studies with aggregate data. Among NITs studied, fibrosis-4 index (FIB-4), aspartate aminotransferase to platelet ratio index (APRI), and NAFLD fibrosis score (NFS) were significantly associated with HCC, with pooled risk ratio (95% CI) of 9.21 (5.79–14.64), pooled hazard ratio of 12.53 (6.57–23.90), and 13.32 (6.48–27.37), respectively. FIB-4, APRI, and NFS of more than 2.06, 0.65, and 0.51 resulted in the highest area under the receiver operating characteristics of 0.83, 0.80, and 0.85, respectively. Surveillance in patients with FIB-4 ≥ 5.91 and NFS ≥ 2.85 would be cost-effective with an annual HCC incidence of ≥15 per 1000 patient-years.

Conclusion

FIB-4, APRI, and NFS are associated with HCC development in non-cirrhotic NAFLD patients. Different NIT cutoffs may be used to enroll high-risk NAFLD patients for HCC surveillance, according to resource availability in different settings.