Diagnosis of cirrhosis – Treatment of cirrhosis
Cirrhosis is defined histologically as the presence of fibrosis and regenerative nodules in the liver. It can be classified as micronodular, macronodular, or mixed; however, each form may be seen in the same patient at different stages of the disease. Cirrhosis manifests clinically with portal hypertension, hepatic encephalopathy, and variceal bleeding.
Diagnosis of cirrhosis
In addition to an assessment of liver function, the evaluation of patients with cirrhosis should also include an assessment of renal and circulatory function. Diagnostic workup is aimed primarily at identifying the most likely cause of cirrhosis. The history is extremely important:
• Alcohol abuse: alcoholic liver disease
• History of hepatitis B (chronic active hepatitis, primary hepatic neoplasm, or hepatitis C)
• History of IBD (primary sclerosing cholangitis)
• History of pruritus, hyperlipoproteinemia, and xanthomas in a middle-aged or elderly woman (primary biliary cirrhosis)
• Impotence, diabetes mellitus, hyperpigmentation, arthritis (hemochromatosis)
• Neurologic disturbances (Wilson’s disease, hepatolenticular degeneration)
• Family history of “liver disease” (hemochromatosis [positive family history in 25% of patients], alpha-1-antitrypsin deficiency)
• History of recurrent episodes of right upper quadrant pain (biliary tract disease)
• History of blood transfusions, IV drug abuse (hepatitis C)
• History of hepatotoxic drug exposure
• Coexistence of other diseases with immune or autoimmune features (immune thrombocytopenic purpura, myasthenia gravis, thyroiditis, autoimmune hepatitis)
• Decreased hemoglobin and hematocrit, elevated mean corpuscular volume, increased blood urea nitrogen (BUN) and creatinine (the BUN may also be “normal” or low if the patient has severely diminished liver function), decreased sodium (dilutional hyponatremia), and decreased potassium (as a result of secondary aldosteronism or urinary losses).
Evaluation of renal function should also include measurement of urinary sodium and urinary protein from 24-hr urine collection.
• Decreased glucose in a patient with liver disease, indicating severe liver damage.
• Other laboratory abnormalities:
1. Alcoholic hepatitis and cirrhosis: possible mild elevation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), usually <500 IU; AST >ALT (ratio >2:3).
2. Extrahepatic obstruction: possible moderate elevations of ALT and AST to levels <500 IU.
3. Viral, toxic, or ischemic hepatitis: extreme elevations (>500 IU) of ALT and AST.
4. Transaminases may be normal despite significant liver disease in patients with jejunoileal bypass operations or hemochromatosis or after methotrexate administration.
5. Alkaline phosphatase elevation can occur with extrahepatic obstruction, primary biliary cirrhosis, and primary sclerosing cholangitis.
6. Serum lactate dehydrogenase is significantly elevated in metastatic disease of the liver; lesser elevations are seen with hepatitis, cirrhosis, extrahepatic obstruction, and congestive hepatomegaly.
7. Serum gamma-glutamyl transpeptidase is elevated in alcoholic liver disease and may also be elevated with cholestatic disease (primary biliary cirrhosis, primary sclerosing cholangitis).
8. Serum bilirubin may be elevated; urinary bilirubin can be present in hepatitis, hepatocellular jaundice, and biliary obstruction.
9. Serum albumin: significant liver disease results in hypoalbuminemia.
10. Prothrombin time/INR: elevation in patients with liver disease indicates severe liver damage and poor prognosis.
11. Presence of hepatitis B surface antigen implies acute or chronic hepatitis B.
12. Presence of antimitochondrial antibody suggests primary biliary cirrhosis, chronic hepatitis.
13. Elevated serum copper, decreased serum ceruloplasmin, and elevated 24-hr urine may be diagnostic of Wilson’s disease.
14. Protein immunoelectrophoresis may reveal decreased α-1 globulins (alpha-1-antitrypsin deficiency), increased IgA (alcoholic cirrhosis), increased IgM (primary biliary cirrhosis), increased IgG (chronic hepatitis, cryptogenic cirrhosis).
15. An elevated serum ferritin and increased transferrin saturation are suggestive of hemochromatosis.
16. An elevated blood ammonia suggests hepatocellular dysfunction; serial values, however, are generally not useful in monitoring patients with hepatic encephalopathy because there is poor correlation between blood ammonia level and degree of hepatic encephalopathy.
17. Serum cholesterol is elevated in cholestatic disorders.
18. Antinuclear antibodies (ANA) may be found in autoimmune hepatitis.
19. Alpha fetoprotein: levels >1000 pg/ml are highly suggestive of primary liver cell carcinoma.
20. Hepatitis C viral testing identifies patients with chronic hepatitis C infection.
21. Elevated level of serum globulin (especially gamma-globulins) and positive ANA test may occur with autoimmune hepatitis.
22. End-stage liver disease is characterized by decreased levels of most procoagulant factors with the notable exceptions of factor VIII and von Willebrand factor, which are elevated.
• Ultrasonography is the procedure of choice for detecting gallstones and dilation of common bile ducts. The use of sonography on a periodic basis to screen for hepatocellular carcinoma in patients with cirrhosis has been questioned and should be avoided until additional data are available.
• CT scan is useful for detecting mass lesions in liver and pancreas, assessing hepatic fat content, identifying idiopathic hemochromatosis, diagnosing Budd-Chiari syndrome early, assessing dilation of intrahepatic bile ducts, and detecting varices and splenomegaly.
• MRI can be used to identify hemangiomas.
• Technetium-99m sulfur colloid scanning is rarely used but can be useful for diagnosing cirrhosis (there is a shift of colloid uptake to the spleen and bone marrow), identifying hepatic adenomas (cold defect is noted), and diagnosing Budd-Chiari syndrome (there is increased uptake by the caudate lobe).
• Endoscopic retrograde cholangiopancreatography can be used for diagnosing periampullary carcinoma and common duct stones; it is also useful in diagnosing primary sclerosing cholangitis.
• Percutaneous transhepatic cholangiography is useful when evaluating patients with cholestatic jaundice and dilated intrahepatic ducts by ultrasonography; presence of intrahepatic strictures and focal dilation is suggestive of primary sclerosing cholangitis.
• Percutaneous liver biopsy is useful in evaluating hepatic filling defects; diagnosing hepatocellular disease or hepatomegaly; evaluating persistently abnormal liver function tests; and diagnosing hemachromatosis, primary biliary cirrhosis, Wilson’s disease, glycogenstorage diseases, chronic hepatitis, autoimmune hepatitis, infiltrative diseases, alcoholic liver disease, drug-induced liver disease, and primary or secondary carcinoma.
Treatment of cirrhosis
• Avoid any hepatotoxins (e.g., ethanol, acetaminophen), improve nutritional status
• Transjugular intrahepatic portosystemic shunt (TIPS) in patients with recurrent variceal hemorrhage despite optical medical therapy. Early use of TIPS is associated with significant reductions in treatment failure and in mortality in patients with cirrhosis who are hospitalized for acute variceal bleeding and are at high risk for treatment failure.
• Beta-blockers with or without nitrates in patients with cirrhosis and variceal hemorrhage.
• Pruritus due to liver disease may be treated with cholestyramine 4 g/day initially. Dose can be increased to 24 g/day as needed.
• Remove excess body iron with phlebotomy and deferoxamine in patients with hemochromatosis.
• Remove copper deposits with d-penicillamine in patients with Wilson’s disease.
• Long-term ursodiol therapy will slow the progression of primary biliary cirrhosis. It is, however, ineffective in primary sclerosing cholangitis.
• Glucocorticoids (prednisone 20 to 30 mg/day initially or combination therapy or prednisone and azathioprine) are useful in autoimmune hepatitis.
• Liver transplantation may be indicated in otherwise healthy patients (age <65 yr) with sclerosing cholangitis, chronic hepatitis cirrhosis, or primary biliary cirrhosis with prognostic information suggesting <20% chance of survival without transplantation.
Contraindications to liver transplantation are AIDS, most metastatic malignancies, active substance abuse, uncontrolled sepsis, and uncontrolled cardiac or pulmonary disease.
• Treatment of complications of portal hypertension (ascites, esophagogastric varices, hepatic encephalopathy, and hepatorenal syndrome).
• Prognosis varies with the etiology of the patient’s cirrhosis and whether there is ongoing hepatic injury. Regression of cirrhosis has been demonstrated after antiviral therapy in some patients with chronic hepatitis C.
Regression is associated with decreased disease-related morbidity and improved survival. Mortality rate exceeds 80% in patients with hepatorenal syndrome.
• If advanced cirrhosis is present and transplantation is not feasible, survival is 1 to 2 yr.
• Cirrhosis is associated with an increased risk for hepatocellular carcinoma. However, the risk is low (1% 5-year cumulative risk in alcoholic cirrhosis).
Diagnosis of cirrhosis – Treatment of cirrhosis
FERRI’S CLINICAL ADVISOR, 2016