Regression of fibrosis andevenoffullyestablishedcirrhosismayfollowdiseaseremissionorcure.Scarsbecomethinner,moredenselycompacted,andeventuallystarttofragment(see
Fig.16.6,B ).Asfibrousseptabreakapart,adjacentnodulesofregeneratingparenchymacoalesceintolargerislands.Allcirrhoticliversshowelementsofbothprogressionandregression,withthebalancebeingdictatedbytheseverityandpersistenceoftheunderlyingdisease.
About 40% of individuals with cirrhosis are asymptomatic until the most advanced stages of the disease. Even at late stages, they present with nonspecific clinical manifestations, such as anorexia, weight loss, weakness, and, eventually signs and symptoms of liver failure discussed earlier. Jaundice, encephalopathy, and coagulopathy may result from chronic liver disease, much the same as in acute liver failure. However, there are some significant additional features:
Chronic severe jaundice can lead to pruritus (itching), the intensity of which may be so profound that patients scratch their skin raw and risk repeated bouts of potentially life-threatening infection. In some patients, severe pruritus is the primary indication for liver transplantation. Pruritus also is frequently seen in other disorders associated with cholestasis, suggesting that it is somehow related to the build up of bile salts in the body, but its precise pathogenesis is unknown.
Portal hypertension is more frequent and manifests in more complex ways in chronic liver failure than in acute liver failure (
Fig. 16.7 ). Portosystemic shunts develop when blood flow is reversed from the portal to systemic circulation. These shunts are principally produced by dilation of collateral vessels. Most notably, venous bypasses develop wherever the systemic and the portal circulations share common capillary beds, the most clinically important of which are esophagogastric varices, which appear in about 40% of individuals with advanced-stage liver disease. These often cause massive, frequently fatal hematemesis, particularly when there is compounding coagulopathy. Portal hypertension often occurs and may lead to congestive splenomegaly, which can lower the platelet count due to sequestration of these elements in the expanded red pulp.
Hyperestrogenemia due to impaired estrogen metabolism in male patients with chronic liver failure can give rise to palmar erythema (a reflection of local vasodilatation) and spider angiomas of the skin. Such male hyperestrogenemia also leads to hypogonadism and gynecomastia. Hypogonadism also may occur in women from disruption of hypothalamic-pituitary axis functioning.
Most chronic liver diseases predispose to development of hepatocellular carcinoma (HCC, discussed later).
The course and severity of chronic liver disease with cirrhosis vary widely from patient to patient. Even in instances in which cirrhosis regresses following disease remission or cure, portal hypertension may persist due to the presence of irreversible shunts. The causes of death are
Fig. 16.6 Alcoholiccirrhosisinanactivedrinker(A)andfollowinglong-termabstinence(B).A, Thickbandsofcollagenseparateroundedcirrhoticnodules.B, After1yearofabstinence,mostscarsaregone(Massontrichromestain).(Courtesy of Drs. Hongfa Zhu and Isabel Fiel, Mount Sinai School of Medicine, New York, New York.) http://ebooksmedicine.net
Fig. 16.7 Major clinical consequences of portal hypertension in the setting of cirrhosis, shown for the male. In females, oligomenorrhea, amenorrhea, and sterility are frequent as a result of hypogonadism.