Abstract
BackgroundAlcoholic liver disease (ALD) is a public health concern that is the cause of half of all cirrhosis‐related deaths. Early detection of fibrosis, ideally in the precirrhotic stage, is a key strategy for improving ALD outcomes and for preventing progression to cirrhosis. Previous studies identified the blood‐borne marker human microfibrillar‐associated protein 4 (MFAP4) as a biomarker for detection of hepatitis C virus (HCV)‐related fibrosis. Aim: To evaluate the diagnostic accuracy of MFAP4 to detect ALD‐induced fibrosis.MethodWe performed a prospective, liver biopsy‐controlled study involving 266 patients with prior or current alcohol overuse. Patients were split into a training and a validation cohort.ResultsMFAP4 was present in fibrotic hepatic tissue and serum MFAP4 levels increased with fibrosis grade. The area under the receiver operating characteristic curve (AUROC) for detection of cirrhosis was 0.91 (95% CI 0.85‐0.96) in the training cohort and 0.91 (95% CI 0.79‐1.00) in the validation cohort. For detection of advanced fibrosis, the AUROC was 0.88 (95% CI 0.81‐0.94) in the training cohort and 0.92 (95% CI 0.83‐1.00) in the validation cohort. The diagnostic accuracy did not differ between MFAP4 and the enhanced liver fibrosis (ELF) test or transient elastography (TE) in an intention‐to‐diagnose analysis. MFAP4 did not predict hepatic decompensation in a time‐to‐decompensation analysis in a subgroup of patients with cirrhosis.ConclusionMFAP4 is a novel biomarker that can detect ALD‐related fibrosis with high accuracy.
Highlights
Owing to the high prevalence of alcohol overuse there is a need for biomarkers that can penetrate into the primary care setting where the majority of patients with Alcoholic liver disease (ALD) are seen
We found that hepatic expression of microfibrillar-associated protein 4 (MFAP4) is upregulated in fibrotic tissue and that MFAP4 serum levels increase with the severity of fibrosis
We showed that serum MFAP4 has excellent diagnostic accuracy similar to that of enhanced liver fibrosis (ELF) and transient elastography (TE), which are the existing benchmarks for non-invasive detection of fibrosis in ALD.[14,15]
Summary
The majority of ALD patients are diagnosed in an advanced fibrotic stage for which the prognosis is poor even if abstinence is achieved and treatment guidelines are followed.[9] patients should ideally be identified before their disease progresses to advanced fibrosis, as this point marks the threshold for severely increased rates of liver- related mortality.[6] Such early diagnosis should be achievable as nearly half of ALD patients have interacted with the healthcare system for an alcohol-related purpose prior to developing alcoholic cirrhosis.[10,11]. The diagnostic accuracy did not differ between MFAP4 and the enhanced liver fibrosis (ELF) test or transient elastography (TE) in an intention-to-diagnose analysis. Conclusion: MFAP4 is a novel biomarker that can detect ALD-related fibrosis with high accuracy
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