Format

Send to

Choose Destination
Lancet Gastroenterol Hepatol. 2019 Jul;4(7):538-544. doi: 10.1016/S2468-1253(19)30087-1. Epub 2019 Apr 9.

Optimisation of the use of APRI and FIB-4 to rule out cirrhosis in patients with chronic hepatitis B: results from the SONIC-B study.

Author information

1
Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, Netherlands.
2
Department of Medicine and Therapeutics and Institute of Digestive Disease, the Chinese University of Hong Kong, Hong Kong SAR, China.
3
NKC Institute of Gastroenterology and Hepatology, Songklanagarind Hospital, Prince of Songkla University, Hat Yai, Thailand.
4
Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
5
Medical Clinic 1, Johann Wolfgang Goethe University Medical Center, Frankfurt, Germany.
6
Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan.
7
Toronto Centre for Liver Disease, University Health Network, Toronto, Canada; IHPME, University of Toronto, Toronto, Canada.
8
Toronto Centre for Liver Disease, University Health Network, Toronto, Canada.
9
Roche Products Ltd, Welwyn Garden City, UK.
10
Gilead Sciences, Foster City, CA, USA.
11
Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
12
Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron and Universitat Autònoma de Barcelona Liver Unit, Hospital Universitari Vall d'Hebron and CIBEHED del Instituto Carlos III, Barcelona, Spain.
13
Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, Netherlands; Toronto Centre for Liver Disease, University Health Network, Toronto, Canada. Electronic address: harry.janssen@uhn.ca.

Abstract

BACKGROUND:

Ruling out the presence of cirrhosis is important for the management of chronic hepatitis B. We aimed to study and optimise the performance of two non-invasive indices for ruling out cirrhosis: the aspartate aminotransferase-platelet ratio index (APRI) and fibrosis score based on four factors (FIB-4).

METHODS:

We applied established cutoffs to rule in (APRI >2·00; FIB-4 >3·25) or rule out (APRI <1·00; FIB-4 <1·45) cirrhosis to data from eight global randomised trials that required baseline biopsy, and identified new cutoffs aiming for a sensitivity for detection of cirrhosis greater than 90% and a negative predictive value (NPV) of greater than 95% in the same dataset. We externally validated the new cutoffs using data from all consecutive biopsied patients from two tertiary referral hospitals in the Netherlands and Canada.

FINDINGS:

In the derivation dataset (n=2926; of whom 1750 were Asian); 340 (12%) individuals had cirrhosis. The validation cohort consisted of 1034 individuals (of whom 575 were Asian), with 155 (15%) individuals with cirrhosis. Application of conventional cutoffs for FIB-4 in the derivation dataset yielded unclassifiable results in 686 (23%) individuals, and 139 (41%) of the 340 patients with cirrhosis were misclassified as having no cirrhosis. Similarly, conventional cutoffs for APRI in the derivation dataset yielded unclassifiable results in 706 (24%) individuals, and 153 (45%) were misclassified as having no cirrhosis. An APRI of 0·45 or less had sensitivity of 91·5%, an NPV of 95·4%, and misclassified 29 (9%) of 340 individuals with cirrhosis in the derivation dataset, but performance was reduced in the validation set (22 [14%] of 155 individuals with cirrhosis misclassified). A FIB-4 score of 0·70 had a sensitivity of 90·9%, an NPV of 96·6%, and misclassified 31 (9%) of individuals with cirrhosis in the derivation dataset. In the validation cohort, the same score gave a sensitivity of 94·2%, an NPV of 97·3%, and misclassified nine (6%) of the individuals with cirrhosis. Subgroup analysis indicated that the new FIB-4 cutoff performed acceptably in all subgroups except for individuals aged 30 years or younger.

INTERPRETATION:

Conventional cutoffs for APRI and FIB-4 should not be used to guide management of patients with chronic hepatitis B due to high rates of misclassification. A newly identified and externally validated cutoff for FIB-4 (≤0·70) can be used to exclude cirrhosis in patients over 30 years of age.

FUNDING:

Foundation for Liver and Gastrointestinal Research, Rotterdam, Netherlands.

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center