Impact of statin treatment on non-invasive tests based prediction of fibrosis

Abstract

Background and Rationale The degree of fibrosis in nonalcoholic fatty liver disease (NAFLD) determines the risk of liver complications. Non-invasive tests (NITs) such as FIB-4, NFS and Hepamet, have been proposed to triage patients in primary care (PC) for further assessment due to their high negative predictive values (NPVs) for advanced fibrosis. These tests include AST±ALT in their calculations. Many patients with NAFLD take statins, and although these tests are used in the calculation of these NITs, it is unknown if NITs’ performance is affected by statin use. Purpose and Hypothesis The purpose of this study was to determine whether statins modify NITs predictions of fibrosis as assessed by vibration controlled transient elastography (VCTE) in patients referred from PC for NAFLD. Methods We assessed 934 patients with suspected NAFLD from PC referred to a hepatology triage clinic and included those with a final NAFLD diagnosis (n=856). In this pilot pathway, all patients underwent VCTE, 832 with reliable measurements. We assessed with logistic regression the effects of being on a statin on the association between NITs and VCTE at different thresholds (8,10,12 and 16 kPa). Results 129 patients were on a statin, and 138 additional patients fulfilled Canadian criteria for statin use but were not on a statin. Patients on a statin were older, more frequently diabetic and had higher BMI than patients not on a statin. In patients on a statin 25,16,13, and 7% had VCTE >=8,10,12 and 16 kPa respectively, while these figures were lower for patients not on a statin (10,7,4 and 2% respectively). For any given FIB-4 value, patients on a statin had higher probabilities of high VCTE than patients not on a statin. Adjusting for BMI, diabetes and age almost completely abrogated these differences, suggesting that these were related to patients’ profile rather to a specific effect of statins. NPVs of a FIB-4 <1.3 for a VCTE >8,10,12 and 16 were, respectively, 89, 94, 96 and 100% in patients on a statin, and 92,95,98 and 99% in patients not on a statin. Statins’ impact on the association between Hepamet and VCTE was similar to that for FIB-4, while statins did not affect NFS predictions of VCTE. Conclusion In patients with NAFLD referred from PC, those on statins had higher chances of a high VCTE for a given FIB-4 value. This was explained, in most part, by a different clinical profile of these patients and had a negligible impact on the NPV of the commonly used FIB-4 threshold (<1.3). A similar effect of statins was observed with Hepamet, but not with NFS. More than half of the patients with indications were not on a statin at the time of referral.