Regression of Human Cirrhosis

Abstract Context.—Cirrhosis is widely regarded as being irreversible. Recent studies have demonstrated that fibrosis may decrease with time in humans and experimental animals if the disease activity becomes quiescent. The histologic appearance of regressing cirrhosis in the human has not been described in detail. Objectives.—To define histologic parameters that indicate regression of cirrhosis and to provide an interpretation of how regression occurs from a histologic point of view. Design.—A patient who underwent a series of biopsies that showed apparent regression of hepatitis B cirrhosis is presented. In addition, 52 livers removed at transplantation having cirrhosis or incomplete septal cirrhosis were graded for histologic parameters that suggest progression or regression of fibrosis. Progression parameters were steatohepatitis, inflammation, bridging necrosis, and piecemeal necrosis. The regression parameters (collectively called the hepatic repair complex) were delicate perforated septa, isolated thick collagen fibers, delicate periportal fibrous spikes, portal tract remnants, hepatic vein remnants with prolapsed hepatocytes, hepatocytes within portal tracts or splitting septa, minute regenerative nodules, and aberrant parenchymal veins. Results and Conclusions.—Regression parameters were found in all livers and were prominent in the majority. Livers with micronodular cirrhosis, macronodular cirrhosis, and incomplete septal cirrhosis demonstrate a histologic continuum. A continuum of regressive changes was also seen within individual livers. These appearances allow one to understand visually how fibrous regions of hepatic parenchyma can be returned toward a normal appearance. Many examples of incomplete septal cirrhosis could be the product of regressed cirrhosis.