Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) is a major cause of liver fibrosis and cirrhosis. Accurate assessment of liver fibrosis is important for predicting disease outcomes and assessing therapeutic response in clinical practice and clinical trials. Although noninvasive tests such as transient elastography and magnetic resonance elastography are preferred where possible, histological assessment of liver fibrosis via semiquantitative scoring systems remains the current gold standard. Collagen proportionate area provides more granularity by measuring the percentage of fibrosis on a continuous scale, but is limited by the absence of architectural input. Although not yet used in routine clinical practice, advances in second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) microscopy imaging show great promise in characterising architectural features of fibrosis at the individual collagen fiber level. Quantification and calculation of different detailed variables of collagen fibers can be used to establish algorithm-based quantitative fibrosis scores (e.g., qFibrosis, q-FPs), which have been validated against fibrosis stage in NAFLD. Artificial intelligence is being explored to further refine and develop quantitative fibrosis scoring methods. SHG-microscopy shows promise as the new gold standard for the quantitative measurement of liver fibrosis. This has reaffirmed the pivotal role of the liver biopsy in fibrosis assessment in NAFLD, at least for the near-future. The ability of SHG-derived algorithms to intuitively detect subtle nuances in liver fibrosis changes over a continuous scale should be employed to redress the efficacy endpoint for fibrosis in NASH clinical trials; this approach may improve the outcomes of the trials evaluating therapeutic response to antifibrotic drugs.
Keywords: Biopsy; Fibrosis; Nonalcoholic fatty liver disease.