Noninvasive fibrosis test for chronic liver diseases: Which tools, and how often?

According to data presented at HKMF 2023, transient elastography (TE) is preferred for noninvasive assessment of fibrosis for patients with chronic liver diseases (CLDs) in Hong Kong. Liver stiffness measurement (LSM) using noninvasive tests (NITs) can be repeated annually to monitor disease progression in patients with compensated advanced CLDs (cACLDs).

“NITs have become standard of care for assessing liver fibrosis in CLD patients,” said Dr Loey Mak of Department of Medicine, the University of Hong Kong. These tests enable prediction of clinical outcomes in patients with common CLDs, such as chronic hepatitis B (CHB) and nonalcoholic fatty liver disease (NAFLD). [Clin Infect Dis 2022;75:2257-2259; Hepatology 2023;77:606-618; Ther Adv Gastroenterol 2022;15:1-13; Nutrients 2023;15:66]

Which noninvasive tools?

“TE stands out not only for its good diagnostic performance, but also for its widespread availability in most hospitals in Hong Kong. This makes TE a preferred NIT for assessing liver fibrosis,” highlighted Mak.

TE is an ultrasound-based imaging approach that measures liver stiffness based on the viscoelasticity of liver tissue. It has demonstrated high diagnostic accuracy for staging fibrosis ≥F2 in CHB patients, with sensitivity of 80 percent, specificity of 82 percent, and an area under the receiver operator characteristic curve (AUROC) of 0.88. [Ann Transl Med 2017;5:40] However, its accuracy may be diminished in patients with elevated alanine transaminase (ALT; >5x upper limit of normal), cholestatic liver diseases, ascites, or cardiac failure. [World J Gastrointest Pharmacol Ther 2016;7:91-106]

“When TE is not available, serum markers such as the Fibrosis-4 [FIB-4] index can be employed instead,” suggested Mak.

FIB-4 is a serum biomarker–based index that generates a score using readily available parameters, namely, age, aspartate transaminase (AST), ALT and platelet count. A higher FIB-4 score indicates a higher degree of fibrosis. However, the FIB-4 index (low cut-off) showed a lower sensitivity of 65 percent and lower specificity of 77 percent for staging fibrosis ≥F2, with an AUROC of 0.78. [Ann Transl Med 2017;5:40] Additionally, specificity of the FIB-4 score may decline with patients’ age (>65 years), leading to increased false positive rates. [Am J Gasteoenterol 2017;112:740-751]

How often?

“A single measurement of liver fibrosis may not be sufficient, due to the dynamic nature of CLDs. Over the past decade, clinical evidence has shown a possibility of fibrosis regression in some patients with CLDs, such as CHB patients who receive long-term antiviral therapy and NAFLD patients who undergo bariatric surgery,” Mak pointed out. [Hepatology 2010;52:886-893; Lancet 2013;381:468-475; Gastroenterology 2020;159:1290-1301.e5]

The Baveno VII consensus recommends annual LSM for cACLD patients (level of evidence, II; grade of recommendation, B). For those with LSM ≥20 kPa, screening endoscopy for varices can be considered (level of evidence, I; grade of recommendation, D). A clinically significant reduction in LSM can be defined as a decrease in LSM of ≥20 percent associated with LSM <20 kPa, or any decrease to LSM <10 kPa (level of evidence, II; grade of recommendation, C). [J Hepatol 2022;76:959-974]

“[In my clinical experience,] the baseline LSM value is a reference to guide varices endoscopy,” advised Mak. “For the significance of LSM reduction, the Baveno VII recommendations are based on early or small-scale studies. Further research is needed to determine the LSM [cut-offs for liver fibrosis] to guide follow-up strategies in CLD management.”