Cirrhosis: The end-stage outcome

The canalicular bile plugs result from cessation of the contractile activity of the hepatocyte pericanalicular actin microfilament web. Two patterns of hepatocyte cell death are seen. In the

first, rupture of cell membranes leads to cytolysis and focal loss of hepatocytes. The sinusoidal collagen reticulin framework collapses where the cells have disappeared, and scavenger

macrophage aggregatesmark sites of hepatocyte loss. The second pattern of cell death, apoptosis, is more conspicuous. It is caused by anti-viral cytotoxic T cells. Apoptotic hepatocytes

shrink, become intensely eosinophilic, and have fragmented nuclei; effector T cells may still be present in the immediate vicinity. Apoptotic cells also are phagocytosed within hours by

macrophages and hence might be difficult to find despite a brisk rate of hepatocyte injury. In severe cases of acute hepatitis (not depicted in Fig. 18-17A ), confluent necrosis of hepatocytes

may lead to bridging necrosisconnecting portal-to-portal, central-to-central, or portal-to-central regions of adjacent lobules. Hepatocyte swelling and regeneration compress sinusoids, and

the more or less radial array of the parenchyma is lost.

Inflammation is a characteristic and usually prominent feature of acute hepatitis. Kupffer cells undergo hypertrophy and hyperplasiaand are often laden with lipofuscin pigment due to

phagocytosis of hepatocellular debris. The portal tracts are usually infiltrated with a mixture of inflammatory cells.The inflammatory infiltrate may spill over into the adjacent

parenchyma to cause necrosis of periportal hepatocytes; this "interface hepatitis"can occur in both acute and chronic hepatitis. Finally, bile duct epithelia may become reactive and even

proliferate to form poorly defined ductular structures (ductular reaction), particularly in cases of HCV hepatitis.

Chronic Hepatitis.

The histologic features of chronic hepatitis ( Fig. 18-17B and Fig. 18-20 ) range from exceedingly mild to severe. In the mildest forms, significant inflammation is limited to portal tracts

and consists of lymphocytes, macrophages, occasional plasma cells, and rare neutrophils or eosinophils. Liver architecture is usually well preserved, but smoldering hepatocyte necrosis

throughout the lobule may occur in all forms of chronic hepatitis. Even in mild chronic hepatitis due to HCV infection, common findings are lymphoid aggregatesand bile duct damage

in the portal tracts and focally mild to moderate macrovesicular steatosis. In all forms of chronic hepatitis, continued interface hepatitisand bridging necrosisare harbingers of

progressive liver damage. The hallmark of irreversible liver damage is the deposition of fibrous tissue.At first, only portal tracts exhibit increased fibrosis, but with time, periportal

septal fibrosisoccurs, followed by linking of fibrous septa between lobules (bridging fibrosis).

Continued loss of hepatocytes and fibrosis results in cirrhosis, with fibrous septae and hepatocyte regenerative nodules.This pattern of cirrhosis is characterized by irregularly sized

nodules separated by variable but mostly broad scars ( Fig. 18-21 ). Historically, this pattern of cirrhosis has been termed postnecrotic cirrhosis, but it should be noted that the term

"postnecrotic cirrhosis" has been applied to all forms of cirrhosis in which the liver shows large, irregular-sized nodules with broad scars, regardless of etiology. Autoimmune hepatitis,

hepatotoxins (carbon tetrachloride, mushroom poisoning), pharmaceutical drugs (acetaminophen, a-methyldopa), and even alcohol (discussed later) may give rise to a cirrhotic liver with

irregular-sized large nodules. In some cases that come to autopsy, the inciting cause of the so-called postnecrotic cirrhosis cannot be determined at all ("cryptogenic cirrhosis"). In essence,

the morphology of the end-stage cirrhotic liver is neither helpful in determining the basis of the liver injury, nor can it be easily related to any specific set of clinical circumstances.

The clinical course of viral hepatitis is unpredictable. Patients may experience spontaneous remission or may have indolent disease without progression for many years. Conversely, some

patients have rapidly progressive disease and develop cirrhosis within a few years. The major causes of death are cirrhosis, with liver failure and hepatic encephalopathy or massive

hematemesis from esophageal varices, and hepatocellular carcinoma in those with long-standing HBV (particularly neonatal) or HCV infection.

Date: 2016-04-22; view: 714