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Evaluating the Patient With Abnormal Liver Tests-1. פרופ' צבי אקרמן מבית חולים הדסה הר הצופים. צורות של פרזנטציה בקליניקה של רופא המשפחה. A 20 years old women with severe hepatitis[an aspartate (AST ,GOT)or alanine aminotransferase (ALT ,GPT) levels of >x 10 ULN .
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Evaluating the Patient With Abnormal Liver Tests-1 פרופ' צבי אקרמן מבית חולים הדסה הר הצופים
צורות של פרזנטציה בקליניקה של רופא המשפחה • A 20 years old women with severe hepatitis[an aspartate (AST ,GOT)or alanine aminotransferase (ALT ,GPT) levels of >x 10ULN. • A 42-year-old asymptomatic man with AST or GPT levels of x 2-5ULN. • A 35-year-old woman with itching and an alkaline phosphatase level of x 2-4ULN. • A obese woman with right-upper-quadrant pain and minimal aminotransferase elevation.
שכיחות ההפרעות באנזימי כבד-1 • Abnormal liver test results are a common problem in clinical practice. • Patients with abnormal liver tests pose clinical challenges in diagnosis. • Aminotransferase elevation occurs in approximately 8% of Americans, with men (9.3%) more likely to have abnormalities than women (6.6%). • Not all who have abnormal liver test results will be found to significant acute or chronic liver diseases.
Upper Limit of Normal ALT Levels • Updated upper limits • Males: 30 U/L (-25% from previous ULN) • Females: 19 U/L (-37% from previous ULN) • Based on retrospective cohort study • 6835 first time blood donors 1995-1999 • Anti-HCV negative and no contraindication to donation • ALT activity independently related to • BMI • Abnormal lipid or carbohydrate metabolism Keeffe EB, et al. Clin Gastroenterol Hepatol. 2008;6:1315-1341. Prati D, et al. Ann Intern Med. 2002;137:1-9.
שכיחות ההפרעות באנזימי כבד-2 • Men are also more likely to have underlying chronic liver disease, including: • Nonalcoholic fatty liver disease (NAFLD). • Hepatitis B. • Hepatitis C with or without alcoholic liver disease. • Alcoholic liver disease. • NAFLD is often the most likely diagnosis when abnormal liver tests are encountered in adults in the absence of overt signs of advanced liver disease.
הגישה ההתחלתית להפרעות באנזימי כבד-1 • The presence of elevated aminotransferase and gamma glutamyltranspeptidase (GGT) serum levels can indicate a greater likelihood of finding a cause for the liver injury. • Additional factors that may cause abnormal liver tests in adults in the absence of overt signs of advanced liver disease are: • Ethanol. • Medications.
הגישה ההתחלתית להפרעות באנזימי כבד-2 • If there are no physical signs of chronic liver disease in patients with mild increases of aminotransferase or alkaline phosphatase, it may be best to simply retest the patient in 3-5 months. • If more than 1 liver test result is abnormal or test values are moderately or markedly elevated, the patient should be evaluated immediately. • A careful history and physical examination coupled with a thoughtful laboratory and radiologic evaluation will often provide a likely diagnosis.
אנמנזה-1 • The symptoms of liver disease are nonspecific. • Anorexia, nausea and vomiting, fever and chills, right-upper-quadrant pain, dark urine and light-colored stools, or alteration of taste for cigarettes (suggesting acute hepatitis) may be present. • Dry mouth and dry eyes are associated with autoimmune disorders such as primary biliary cirrhosis. • Pruritus develops with intrahepatic cholestasis or extrahepatic biliary blockage.
אנמנזה-2 • In advanced liver disease, symptoms of confusion and disorientation may indicate hepatic encephalopathy. • A history of illicit or prescribed medications, ethanol use, tattoos (especially self-administered), multiple sexual partners, and travel to endemic areas can raise questions of drug-induced or chronic viral hepatitis. • The presence of type 2 diabetes mellitus, hypertension, or hyperlipidemia can suggest NAFLD
Signs of congestive heart failure: jugular venous distention, right pleural -effusion, S3 gallop- Cardiac cirrhosis
Arterial bruit heard over the liver- Hepatocellular carcinoma, alcoholic hepatitis, arteriovenous malformation (rare)
גיל ומחלת כבד-1 • Chronic liver disorders tend to group within specific age ranges. • In the teenage years, Wilson's disease and autoimmune hepatitis are the most prevalent chronic liver diseases. • During the twenties, Wilson's disease continues to present as liver disease up to the age of 25 years, and autoimmune hepatitis and chronic viral hepatitis also occur. • In the 30-year age group, chronic viral hepatitis and primary biliary cirrhosis (90% are women) are likely.
גיל ומחלת כבד-2 • During the forties and fifties, primary biliary cirrhosis remains prevalent in women and alcoholic hepatitis, chronic viral hepatitis occur in men. • Drug-induced liver disease can be found at any age, although it is more common in older adults. • Primary sclerosing cholangitis may also occur at any age, although it tends to occur in men in their twenties and thirties. • NAFLD coupled with metabolic syndrome occurs at any age.
Abnormal Liver Test Results-1 • Most laboratory liver tests are not actual tests of liver function, although hepatic function can be inferred from: • Prothrombin times (international normalized ratio). • Albumin levels. • Bilirubinlevels.
INR-international normalized ratio • Impaired synthesis of vitamin K-dependent coagulation factors
Albumin • Cirrhosis, severe hepatocellular injury. • Other causes for low albumin?
Bilirubin • Any acute or chronic liver disease. • Congenital disorders of bilirubin metabolism.
Causes for Hyperbilirubinemia: • Increased bilirubin production • Reduced bilirubin uptake by hepatic cells • Disrupted intracellular conjugation • Disrupted secretion of bilirubin into bile canaliculi • Intra/extra-hepatic bile duct obstruction Lead to increase in free (unconj.) bilirubin Result in rise in conj.bilirubin levels
+ GST B :GST B DISRUPTED INTRACELLULAR CONJUGATION(unconj. Hyperbilirubinemia) • Gilbert’s Syndrome :glucuronosyltransferase activity reduced to 10-30% of normal; also accompanied by defective bilirubin uptake mechanism Plasma Hepatic cell Bile Alb B MRP2 B CB + UDPGA UGT1A1 Alb sER
Additional points -Hyperbilirubinemia • In acute and chronic liver diseases every point in the metabolism of bilirubin may be defected.
Abnormal Liver Test Results • Aminotransferases, alkaline phosphatase, and GGT are enzymes that are released during injury to liver cells or bile ducts.
Aminotransferases (AST, ALT) • Hepatocellular injury Acute or Chronic : • Ethanol. • Drug-induced hepatitis. • Hepatitis A or B or C. • Ischemic injury. • Chronic liver disease. • NAFLD. • Acute biliary obstruction. • Hyperthyroidism (rarely ). • Celiac disease. • skeletal muscle disease.
Aminotransferases-Heightof enzymes • Marked elevations of aminotransferases occur from viral infection, ischemic liver injury, and drug-induced liver disease. • Moderate elevations occur in patients with autoimmune hepatitis and some patients with cirrhosis. • Minimal elevations of aminotransferases are more frequent in NAFLD, chronic viral hepatitis, alcoholism, nonspecific viral injury, and cholestatic liver disease.
Aminotransferases • The ratio of AST to ALT may indicate alcoholic liver disease when greater than 2:1.
Alkaline phosphatase • Cholestasis (Canalicular injury ,intrahepatic and extra hepatic bile duct obstruction). • Hepatocellular damage. • Children during bone growth. • Bone disease. • Pregnancy (placenta origin).
GGT - gamma glutamyltransferase • Cholestasis (Canalicular injury ,intrahepatic and extra hepatic bile duct obstruction). • Medications. • Ethanol
Abnormal Liver Test Results-1 • Liver tests can be used to: • Screen for liver disease. • Confirm suspected liver disease. • Assist in differential diagnosis of liver disease. • Monitor the progression of liver disease. • Monitor the progress of specific therapies.
Lactate dehydrogenase • Lactate dehydrogenase (LDH) is not a reliable liver test but can be significantly elevated during: • Ischemic injury. • Liver disease associated with hemolysis. • Solid tumors or rapidly growing lymphomas.
MCV • Alcohol consumption, folic acid and B12 deficiency
ADDITIONAL HEMATOLOGICAL PARAMETERS MAY BE HELPFUL IN LIVER PATEINT EVALUATION • Leukopenia. • Thrombocytopenia . • These may result from hypersplenism associated with portal hypertension.
Cholestasis • Laboratory tests for cholestasis include GGT and alkaline phosphatase. • These enzymes are elevated in hepatobiliary diseases, including abnormalities of either the canaliculus or the intrahepatic and extrahepatic bile ducts and in replacement disease from hepatic tumors or granulomas. • Hepatobiliary diseases include: • partial biliary tract obstruction from stones. • pancreatitis. • parasitic disease. • acute cholecystitis. • papillary dysfunction. • With biliary disorders, the tests may fluctuate in value, suggesting intermittent or partial blockage.