The modern era of fibrosis research was initiated by pathologists who, through careful study of histological sections, were able to relate excess connective tissue in the liver (fibrosis) to clinical disease. They pointed out that not only is the amount of fibrosis important, but also its localization. This was useful for prognosis and led to formal systems for fibrosis staging. A subject of debate was the way in which the observed fibrous strands or bands formed. Some argued that the process was a passive result of hepatocyte dropout and apposition of preexisting layers of extracellular matrix (ECM, or "ground substance"). Others believed that fibrogenesis was an active process involving the elaboration of scar by specialized fibrogenic cells from within or outside the liver.
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