Laboratory Tests in Liver Diseases

Laboratory Tests in Liver Diseases 인하의대 소화기내과 이진우    LFT provide only indirect evidence of hepatic integrity. Depending on the disease process, some of these functions may be highly compromised while others remain nearly normal. In assessing the severity & course of liver disease, the practical principle for physician is; the test selected should 1. 2. 3. Assess different parameters of liver function Be used serially in order to evaluate the evolution or course of the disease Be interpreted within the total clinical context Enzyme Assay Markers of Hepatocellular Necrosis  Aminotransferases – AST/ALT Ratio     in normal; < 1 Viral hepatitis, NASH; < 1 Alcoholic hepatitis; > 2 LC, acute fatty liver of preganacy; >1 – AST and ALT Levels  Lactate Dehydrogenase – Nonspecific, but often  in liver ds Aminotransferase (Transaminase) AST & ALT; most useful indicators of hepatocellular damage  ALT; in the liver (cytosol) more specific indicator of liver function  AST; in the liver (mitochondria & cytosol), heart, skeletal muscle, kidney & brain Highest level  – extensive hepatic necrosis such as viral hepatitis, toxininduced liver injury or prolonged circulatory collapse Lesser elevation – mild acute viral hepatitis, diffuse and/or focal chronic liver disease, biliary tract obstruction, cholecystitis Continued  Asolute level of aminotransferases correlate poorly with severity of liver injury or prognosis. – – severe alcoholic hepatitis; usually <300 IU/L AST/ALT > 2  Clinical role – – Screening test for hepatobiliary ds Monitoring of clinical course  Serial determinations are usually most helpful. In general AST & ALT levels parallel each other.  Plasma membrane-derived enzyme of uncertain physiologic function ; hydrolyze synthetic phosphate esters at alkaline pH Alkaline Phosphatase (ALP)  Several forms – Bone, intestine, liver, kidney, placenta, leukocyte – In the absence of bone disease or pregnancy, elevated levels of ALP activity reflect impaired biliary tract functon. Slight & moderate elevation (1 to 2 times normal) – in parenchimal liver disorders such as hepatitis, cirrhosis High elevation (3 to 10 times) – in extrahepatic biliary tract obstruction – intrahepatic cholestasis (drug induced or PBC) – more sensitive marker than bilirubin in biliary tract obstruction  To diffentiate hepatic origin from nonhepatic origin – parellel determination of 5’-nucleotidase or g-glutamyltrasnspeptidase (GGT) – isoenzyme assay; not practical Causes of isolated serum ALP increase Other hepatic enzymes    5’-nucleotidase (5’-NT) – Elevation are generally associated with hepatobiliary ds. Leucine aminopeptidase (LAP) – Significantly increased in hepatobiliary & pancreas ds GGT – In hepatobiliary system as well as in other tissues ; pancreatic, cardiac, renal, pulmonarydisorder as well as DM & alcoholics – The most sensitive indicator of biliary tract ds – However, nonspecific – Lack of specificity has limited its clinical usefulness.  Lactate dehydrogenase (LDH) – Often elevated in liver ds Causes of increase plasma GGT Clearance of Metabolites & Drugs Metabolites clearance  Ammonia (NH3) – Clear ammonia from blood by converting it to urea via Krebs-Henseleit cycle for excretion by kidney – Elevation of ammonia reflects disruption of this pathway in sever hepatic dysfunction such as fulminant hepatic failure or portosystemic shunt. – Serum level is used to confirm the diagnosis of hepatic encephalopathy & to monitor the success of therapy   Bilirubin Bile acids – Enterohepatic recycling in normal – Impaired hepatic uptake or bile duct ostruction can lead to high plasma elevation & result in pruritus. Drug clearance  Quantitative liver function test – Clearance of certain drugs, which are excreted by liver cells, has been used such as indocyanine green (ICG), sulfobromophthalein (BSP), antipyrene, caffeine & rose bengal.  ICG test – Useful estimate of hepatic blood flow as exclusively taken by hepatocytes & its hepatic excretion – Hepatic clearance = hepatic BF x hepatic extraction – Advantage; relatively preserved hepatic uptake, less toxic – Disadvantage; nonsensitive, expensive Continued Synthetic Functions Prothrombin time (PT)  Depend on the plasma concentration of clotting factors synthesized in the liver – Can represent liver function  Plasma half-life of these factors – Less than 1 hr – Respond rapidly to changes in hepatic synthetic function   Useful for following the course of active liver ds – Significant PT prologation indicates an poor prognosis Cause of PT prologation – Reduced synthesis; liver failure, vitamin K defeciency – Increased consumption; DIC Continued  Causes of PT prolongation Albumin    Synthesized in the liver at a rate of 100 to 200 mg of BW/day Long half-life in plasma; 2 to 3 weeks – Less than 5% turn over daily Cause of loss – Nephrotic syndrome, protein-losing enteropathy, severe burns, exfoliative dermatitis, & GI bleeding  Hypoalbuminemia – important indicator of CLD when other factor can be excluded – Adequate synthesis may continue until extensive liver injury Cause of low plasma albumin Serum lipids & lipoproteins  Parenchymal liver ds & bile duct obstruction may produce significant abnormalities – Sensitive ,but nonspecific indicator   In cholestasis –  unesterified cholesterol & phopholipids Hypercholesterolemia, hypertriglyceridemia Immunologic Tests Globulins Limited diagnostic utility in hepatobiliary ds  Hyperglobulinemia in chronic liver ds  – may reflect  stimulation of antibody production due to shunting of antigen & impaired clearance by Kupffer cells –  IgM in PBC  Anti-mitochondrial Ab (AMA) – in PBC; 90% – CAH & LC, postnecrotic; 25% Anti-nuclear Ab (ANA)  Anti-smooth muscle Ab (ASMA)  Hematologic Tests Hematologic abnormalities  Coagulopathy – in severe hepatic failure  Pancytopenia – due to portal HT with secondary hypersplenism  In chronic liver ds – Erythrocytic target cells – acanthosis (spur cell) Biochemical Liver Tests General Patterns of Biochemical Liver Tests Diagnostic algorithm in liver ds Diagnostic algorithm in liver ds Diagnostic algorithm in liver ds Liver Biopsy Methods  US-guided percutaneous biopsy  Peritoneosopy – Gross appearance – Ascites of unknown origin – Peritoneal disease  Transjugular biopsy Indication      Hepatocellular ds of uncertain cause Prolonged hepatitis with the possibility of CAH Unexplained hepatomegaly or splenomegaly Hepatic filling defects by radiologic imaging Systemic or infiltrating ds with the possibility of liver involvement – Amyloidosis, miliary tuberculosis   FUO Staging of malignant lymphoma Contraindication 환자  PT 연장 > 3 sec thrombocytopenia < 80,000/mm3  우측 늑막염, 담도염  심한 복수  담도폐색  혈관성 질환이 의심  비협조적인 LIVER ABSCESS 인하의대 소화기내과 이진우 Pyogenic Liver Abscess Pathogenesis 1. local spread from contigious infection – biliary tract disease ; m/c cause 2. hematogenous spread – intraabdominal infection ; through portal vein – septicemia ; through hepatic artery Continued  Organisms 1. from the biliary tree – enteric gram(-) aerobic bacilli & enterococci (E. coli – 2/3) 2. from pelvic & other intraperitoneal sources – mixed flora including aerobic & anaerobic species (esp. B. fragilis) 3. hematogenous – usually single organisms (S. aureus or streptococcal species) 4. folowing fungemia in pts receiving chemotherapy for cancer – candida species Continued Symptom & Sign 1. 2. 3. 4. 5. 6. fever; most common pain; guarding, direct & rebound tenderness on RUQ nonspecific Sx; chills, anorexia, weight loss, N/V cough, pleutic pain; 10-25% localizing sign; hepatomegaly or jaundice – 50% FUO may be the only Sx in the eldely. Continued Diagnosis Laboratory finding 1.  alkaline phosphatase (90%) 2. leukocytosis (77%) 3.  bilirubin (50%) 4.  AST (48%) 5. anemia (50%) 6. hypoalbuminemia (33%) 7. bacteremia (1/3)  Continued  Imaging diagnosis ; most common methods for Dx 1. 2. 3. 4. 5. Chest X-ray (1/2); elevation of right hemidiaphragm, right basilar infiltrates & pleural effusion US CT gallium- or indium-labeled WBC scan MRI Continued Continued Continued  1. Diagnostic aspiration creamed colored, light tan, or green-tinged, and often putrid odor of anaerobes positive culture in 73-100% 2. Complications 1. Pleuropulmonary involvement ; Most common complication (15-20%) ; pleuritis, empyema 2. peritonitis Drainage mainstay of therapy Tx without drainage generally require longer course of antibiotic therapy  Treatment PCD Hospital stay Time required for fever to resolve Mortality > = = Surgery Continued ContraIx of PCD 1. ascites 2. cogulopathy Cx of PCD 1. perforation of other abdominal organ 2. Pneumothorax 3. Hemorrhage 4. Peritoneal leakage of abscess content Ix of open surgical drainage 1. multiple, sizable abscess 2. viscous abscess contents which tend to plug the catheter 3. associated disease (e.g., of biliary tract) that require surgery 4. lack of clinical response to PCD in 4 to 7 days Continued Continued  Antibiotics – Emperical therapy with broad spectrum antibiotics including anaerobic coverage   Confirm culture Specific therapy – 10~14 days of parenteral therapy  Prolonged course of oral therapy  total duration may be guided by imaging. Prognosis  Mortality – 15% (despite treatment) – high in case of multiple abscess Amebic Liver Abscess Life cycle & Transmission  Ingestion of cyst – from fecally contaminated water, food, or hands  Motile trophozoits – released from cysts in the small intestine  Encystation  Infectious cysts are shed in the stool Continued  In some patients, trophozoits invade – bowel mucosa; symptomatic colitis – bloodstream; distant abscess of liver, lungs, or brain  Trophozoits – not infectious – rapidly killed by exposure to air or gastric acid Continued Pathogenesis & Pathology  Intestinal colonization (may be asymptomatic) – Trophozoits invade veins – Reach the liver through the portal vein – Acute cellular infiltrate consisting predominantly of neutrophils – Abscess formation (usually solitary & affect right lobe in 80% of cases) Ameba, if seen, tend to be found only near the capsular of the abscess.  Clinical infection does not induce immunity  – Antibody is not protective Clinical Manifestations  Symptoms 1. pain (90%); mainly RUQ 2. past Hx of dysentery (20%) 3. diarrhea or dysentery (10%)  Signs 1. tenderness of RUQ (85%) 2. palpable, tender liver (80%) 3. fever (75%) ; fever only (10-15%) – amebic liver abscess must be considered in case of FUO 4. signs of right lung base Diagnosis  Routine hematologic & biochemical test 1. of little use 2. leukocytosis (>10,000); 3/4 3. anemia 4. ALP; most often elevated  Stool examination for E. histolytica – Positive in 25% Trophozoite of E. histolytica Single nucleus with a central, dot-like karyosome (trichrome stain) Cyst of E. histolytica Three of the four nuclei (trichrome stain) Continued  Serology 1. counterimmunodiffusion, agar gel diffusion, & ELISA (most sensitive)    Sensitivity; >90% Serologies usually revert to negative within 6 to 12 months. Misleading in endemic area d/t previous infection 2. indirect hemagglutination (IHA)  may remain positive for as long as 10 yrs Continued  Radiographic studies 1. Chest X-ray ; elevated right Diaphragm (50-55%) atelectasis, pleural effusion 2. Liver scans; filling defect 3. US; imaging method of choice 4. CT 5. MRI Continued Continued Continued  Diagnostic aspiration No longer required – – high sensitivity & accuracy of serologic tests high rate of response to medical therapy Aspirate – non-odorous, reddish-brown in color (anchovy paste) Differential Diagnosis  The most important differential is between amebic & pyogenic abscess Amebic serology is helpful, but aspiration of the abscess, with Gram stains & cultures may be required. Pts with pyogenic abscess typically older & have a history of underlying bowel ds or recent surgery. Complications 1. Pleuropulmonary involvement (20-30%) – – – – most frequent Cx sterile effusions, contigious spread; usually resolve with medical therapy rupture into the pleural space; requires drainage hepatobronchial fistula; expectoration of amebic pus, give chance of spontaneous cure of abscess sudden severe pain with sign of acute abdomen 2. Rupture into the peritoneum – 3. Rupture into the pericardium – – in case of left lobe lesion gravest prognosis Full course of therapy  Metronidazole – 750mg tid, 10 days – does not eradicate cyst   Idoquinol (intestinal amebicide) - 650mg tid, 20 days Continued Continued  Indication of aspiration 1. need to rule out a pyogenic abscess, particularly in pts with multiple lesion 2. failure to respond clinically in 3 to 5 days 3. treatment of imminent rupture 4. prevention of rupture of the left lobe abscesses into pericardium 5. negative serology or large abscess (> 10 cm) There is no evidence that aspiration, even of large abscess (upto 10cm), leads to more rapid healing. Prognosis  Complete resolution within 6 months ; 2/3  Mortality from uncomplicated amebic abscess; < 1% Comparison of pyogenic & amebic liver abscess  Age Sex Epidemiology Pyogenic any; most older equal none Ass. Medical conditions common - surgery,biliary ds diverticulitis, tumor Significant jaundice common rare Multiple abscess common rare Complication rupture rupture extension, sepsis Amebic serology negative positive Blood culture frequently (+) negative Abscess contents pus thick fluid - creamy yellow, foul odor - anchovy paste, non-odorous Medical therapy often almost always PCD often vary rarely Surgery required sometimes almost never Mortality appreciable very low Amebic any; mostly younger male more than female endemic area poor hygiene, poverty rare