Updates in the quantitative assessment of liver fibrosis for nonalcoholic fatty liver disease: Histological perspective

Abstract

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. Clin Mol Hepatol 2020 Nov 19.

Maternal Western diet exposure increases periportal fibrosis beginning in utero in nonhuman primate offspring

“…Fetuses exposed to maternal WSD had increased periportal collagen deposition. We used SHG/2-photon excitation fluorescence microscopy imaging, a highly sensitive technique used to detect collagen deposition in pediatric patients with NAFLD (24,25), to quantify fibrillar collagen deposition directly without staining. WSD-exposed fetuses, compared with CD-exposed fetuses, had a 22% (P < 0.0005) increase in SHG signal intensity in the portal triad region of the liver (Figure 1, A and F) and a 43% (P < 0.005) increase in SHG signal area around the portal triads (Figure 1, B and F).…”

Dietary Polyphenols and Non-Alcoholic Fatty Liver Disease

“…Liver steatosis is the biochemical result of an imbalance between fatty acid uptake and synthesis in the hepatocytes, and their discharge from the cell through beta-oxidation and secretion by Very Low-Density Lipoproteins (VLDLs). In greater detail, the metabolic steps that lead to the accumulation of triglycerides in the hepatocytes are fatty acid uptake, de novolipidogenesis, fat oxidation, and VLDL export into the blood [ 18 , 20 ]. Several enzymes are responsible for lipid metabolism processes—the rate of de novolipidogenesis depends on the activity of mitochondrial Citrate Carrier (CiC), Acetyl-CoA Carboxylase (ACC), Fatty Acid Synthase (FAS), Diacylglycerol Acyltransferase (DGAT).It also depends on transcriptional factors, namely, the Steroid Regulatory Element Binding Proteins (SREBPs), Carbohydrate Element Response Binding Protein (ChREBP), Liver X receptor alfa (LXR-α), Farnesoid X Receptor (FXR), and Peroxisome Proliferator-Activated Receptors (PPARs) [ 21 ].…”

The Need for Alternatives to Liver Biopsies: Non-Invasive Analytics and Diagnostics

“… 74 Techniques such as second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) microscopy imaging are showing great promise in characterizing architectural features of fibrosis at the individual collagen fiber level. 75 Detailed spatial profiling of lymphocyte subsets within parenchymal liver disease is now possible using multiplex immunostaining and digital analysis, massively enriching the depth of information available from the biopsy. 76 Indeed, digital pathology is likely to dramatically enhance the value of the liver biopsy in the coming years.…”