1 Zhejiang-California International Nanosystems Institute (ZCNI), Proprium Research Center, Zhejiang University, Hangzhou, China.
2 Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.
3 Department of Urology, University of Washington School of Medicine, Seattle, Washington.
4 School of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China.
5 Department of Liver Diseases, The Second Hospital of Yunnan Province, Kunming, China.
6 The Third People's Hospital of Changzhou, Changzhou, China.
7 State Key Laboratory for Diagnosis and Treatment of Infectious Disease, The Research Center for Clinical Pharmacy, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.
Nonalcoholic fatty liver disease (NAFLD) is a growing global public health concern and becoming the leading cause of liver disease worldwide. The estimated global prevalence of NAFLD is ∼25% depending on the country and the assessment method used to establish the diagnosis. Meta-analyses suggest that the highest prevalence is in the Middle East (31.8%) and South America (30.4%), and the lowest in Africa (13.5%). In the United States, between 75 and 100 million individuals were estimated to have NAFLD. This important disease is associated with increased incidence of liver-related deaths, hepatocarcinoma, and overall mortality. Fibrosis stage, among other histological characteristics, is the most critical factor in predicting all-cause and disease-specific mortality in NAFLD. The ability to detect fibrosis early in NAFLD patients is critical in controlling mortality associated with this highly prevalent disease. We present here an expert review on recent advances in novel blood biomarkers, for example, the Wisteria floribunda agglutinin-positive mac-2 binding protein (WFA+-M2BP), type IV collagen 7S, chitinase 3 like 1 (CHI3L1; YKL-40), and insulin-like growth factor-1 (IGF-1). Algorithms using multiple biomarkers such as alpha-2-macroglobulin, mir34a, YKL-40, and hemoglobin A1c (HbA1c; NIS4), enhanced liver fibrosis (ELF), Hepascore, FibroMeter, FibroTest, FIBROSpect, FIB-C3, and ADPAPT are highlighted. Novel technologies such as tandem mass spectrometry to directly measure protein turnover rate of the key proteins involved in hepatic fibrosis, as an indicator of fibrogenesis, are also discussed. In conclusion, NAFLD is a growing global health problem that warrants long-term funding, research, and training of scholars across the fields of public health diagnostics, systems sciences, nutrition, hepatology, and clinical oncology.