Defining the Minimum Acceptable Diagnostic Accuracy of Noninvasive Fibrosis Testing in Cirrhosis: A Decision Analytic Modeling Study

Abstract

No studies explore the clinical consequences of using noninvasive tests (NITs) compared to liver biopsy (LB) in diagnosing cirrhosis. Our aim was to combine two decision analytic models to determine the minimum diagnostic accuracy criteria for NITs to diagnose cirrhosis with equivalence to LB in terms of mortality. We further evaluated selected existing NITs used alone and sequentially. A decision tree was constructed with associated 2‐year mortality incorporating an LB or NIT strategy to diagnose cirrhosis in a hypothetical cohort of 1,000 asymptomatic patients. Cirrhosis prevalence was modeled at 5%, 20%, and 50%. Decision curve analyses were performed, expressing the net benefit of tests over a range of threshold probabilities (Pt). The NIT deriving from the two models that could diagnose cirrhosis with at least equal mortality to LB was termed “mNIT.” Existing NITs were then compared using both decision models. The combined mNIT minimum sensitivity and specificity to diagnose cirrhosis with equivalence to LB at 5%, 20% and 50% cirrhosis prevalence were; 89% and 88%, 94% and 85%, and 94% and 87%, respectively at Pt = 0.20. Sequential NITs performed better than single NITs at any prevalence. Combining both decision models, FibroTest plus vibration‐controlled transient elastography (VCTE) and VCTE alone were the only existing NITs that were better than or equal to LB at diagnosing cirrhosis at 5% prevalence. At 20% and 50% prevalence, only FibroTest high specificity cutoff plus VCTE was equivalent to or better than LB. Conclusion: Decision analytic models were used to determine the minimum acceptable diagnostic accuracy of NITs for diagnosing cirrhosis; we recommend that such models should be used as the standard in evaluating the diagnostic performance of NITs.

Collagen biology and non‐invasive biomarkers of liver fibrosis

“…Furthermore, direct biomarkers of fibrosis, such as ELF™ and PRO‐C3, have been demonstrated to be diagnostically superior to indirect indices such as APRI and FIB‐4 for the detection of advanced fibrosis . In a separate study, Majumdar et al concluded that APRI and FIB‐4 were unsuitable for the diagnosis of cirrhosis …”

Natural History of Nonalcoholic Fatty Liver Disease: Implications for Clinical Practice and an Individualized Approach

“…Patients in whom the second line of tests confirms advanced fibrosis should be referred to a hepatologist in order to reliably assess the presence of cirrhosis and portal hypertension, as these require further specific investigations that include screening for the presence of oesophageal varices and HCC [73]. Since noninvasive tests have a modest positive predictive value for cirrhosis (about 50 to 70%), patients who have been diagnosed with cirrhosis based on noninvasive tests usually need a liver biopsy to reliably determine the stage of fibrosis, as well as to assess the presence of other histological components [8,74]. As explained in the previous paragraph, it may be useful to quantify steatosis at baseline and during the follow-up period, although solid scientific evidence is still lacking.…”

Collagen proportionate area predicts clinical outcomes in patients with alcohol‐related liver disease

“…8 Several non-invasive methods are available for ruling out advanced fibrosis in ALD; however, a liver biopsy is still required to establish the diagnosis and assess the exact stage of disease in selected patients. 9,10 There is no histological scoring system developed specifically for ALD; however, liver fibrosis is routinely reported using the semiquantitative Brunt histological scoring system. 11 A recent study confirmed that advanced fibrosis is associated with liver-related mortality in patients with early/compensated ALD.…”