CIRRHOSIS/ HEPATIC CIRRHOSIS

†††† Hepatic cirrhosis is the end stage of a continuum of liver injury which can result from a number of hepatic insults (excessive alcohol consumption, viral hepatitis, autoimmune hepatitis, hemochromatosis, Wilsonís disease, alpha-1 antitrypsin deficiency, drug or toxin cellular injury, nonalcoholic steatohepatitis, primary biliary cirrhosis, etc.).† When no cause can be identified after a thorough evaluation, the cirrhosis is termed cryptogenic.† As hepatic parenchymal damage progresses there is the development of diffuse fibrosis and abnormal nodules, which mark the histologic findings of cirrhosis.† As the liver is progressively damaged, there is diminished hepatocellular function and increased vascular resistance to hepatic blood flow with resultant accumulation of toxic metabolic wastes in the systemic circulation, impaired hepatic protein synthesis, elevated portal venous pressure, and potentially portosystemic shunting of blood.† These complications manifest clinically as ascites, encephalopathy, and gastroesophageal variceal formation with the potential for life-threatening hemorrhage.† Other clinical manifestations of cirrhosis include jaundice, digital clubbing, scleral icteris, spider angiomata, palmar erythema, dilated abdominal veins, splenomegaly and the development of hepatocellular carcinoma (HCC). Cirrhosis is considered decompensated when there is concomitant variceal hemorrhage, encephalopathy, ascites, or jaundice. Conversely, the lack of these complications indicates compensated disease.

Liver biopsy is a direct way to assess the hepatic parenchyma. The limitations of needle biopsy are the potential complications (pneumothorax, hemorrhage, or biliary tree damage) and the small sample size obtained with needle biopsy. Since liver disease progresses in a heterogenous fashion and needle biopsy retrieves an extremely small percentage of the liver to evaluate, the potential to miss underlying fibrosis or cirrhosis is great. Wedge resections allow for a larger sample size but requires a surgical procedure. The various stages of liver damage are staged accordingly:

          STAGE 0: normal liver histology.

          STAGE 1: only the portal triads are surrounded by fibrous connective tissue.

          STAGE 2: fibrous connective tissue surrounds the portal triads and extends into the periportal space without connecting portal triads.

          STAGE 3: fibrous connective tissue surrounds the portal triads and extends into the periportal space connecting adjacent triads.

          STAGE 4: cirrhosis.            

†††† Transaminasemia may be noted when there is hepatocellular injury; whereas, an elevated alkaline phosphatase may be noted with infiltrative diseases or cholestasis.† Tests of liver function are often used to determine the extent of liver damage to include serum bilirubin, serum albumin, and prothrombin time and are parameters of the Child-Pugh classification of severity of liver disease. Transaminase levels, which reflect underlying hepatocyte injury are inaccurate. Levels may be normal despite severe underlying cirrhosis, and the degree of transaminasemia does not correlate with the stage of underlying liver disease. The AST/ALT ratio is often used to follow patients with an underlying chronic liver disease. When the ratio is greater then 1.3, this is consistent with underlying fibrosis and/or cirrhosis. The above-mentioned symptoms do not appear until late in the progression of liver damage. Likewise, laboratory abnormalities associated with cirrhosis (hyperbilirubinemia, hypoalbuminemia, transminasemia, and the dilutional hyponatremia seen with ascites) are late findings (when portal hypertension causes resultant splenomegaly with hypersplenism, leukopenia and thrombocytopenia are observed). Even radiographic analysis of the liver with ultrasound or CT scanning is inaccurate. Regardless, the Child-Pugh classification is often used to stratify the level of liver damage when making treatment decisions.

†††† When possible, treatment of the underlying disease process is the first step in therapy.† Abstinence from alcohol consumption, drug abuse, and excessive use of NSAIDs or acetaminophen should be strongly encouraged.† Screening and surveillance for hepatocellular carcinoma  and esophageal varices should be instituted in all patients with cirrhosis.† Immunization status should be maintained (pneumovac, influenza vaccine, and especially hepatitis A and B vaccines).† If cirrhosis progresses, patients should be considered for liver transplantation.