4/27/2018. Disclosures LIVER FUNCTION TESTS LIVER FUNCTION TESTS LIVER FUNCTION TESTS APPROACH TO THE PATIENT WITH ABNORMAL LIVER TESTS

Transcription

1 APPROACH TO THE PATIENT WITH ABNORMAL TESTS Kimberly A. Brown, M.D, FAST, FAASLD, AGAF Chief, Division of Gastroenterology and Hepatology Henry Ford Hospital Henry Ford Health System Detroit, Michigan FUNCTION TESTS Useful noninvasive screening tool for the presence of liver dysfunction Pattern recognition may be a clue to diagnosis Allow clinicians to assess the severity of liver dysfunction Useful in following patients with established liver disease to monitor for improvement, worsening or response to treatment Disclosures For the purposes of this presentation I have nothing to disclose FUNCTION TESTS Lack sensitivity: hepatitis C, cirrhosis, hepatocellular cancer Rarely provide a specific diagnosis Lack specificity: renal disease, cardiac or musculoskeletal disease No one LFT enables the clinician to accurately assess the total functional capacity of the liver INTERPRETING LFT S: IT S A LITTLE LIKE READING TEA LEAVES FUNCTION TESTS To increase both the sensitivity and specificity of laboratory tests in the detection of liver disease, it is essential to use them as a BATTERY 1

2 UTILITY OF TESTS IN ING FOR HEPATOCELLULAR DISEASE By definition chronic hepatitis is elevated ALT for greater than 6 months Minor elevations may occur in virtually all forms of liver disease and should be evaluated to exclude treatable forms of liver disease Typically ALT, AST, Bilirubin and Alkaline phosphatase most useful for screening with INR most useful to guide information on severity Back Tests to of the 3 Transport Questions: Acute and or Metabolic Chronic? Activity Serum Bilirubin Serum Bile Acids Breath Tests Sensitive Indicators of Hepatocyte Injury HYPERBILIRUBINEMIA Back Tests to of the 3 Hepatocellular Questions: Injury: Acute AST, or Chronic? ALT Most helpful in detecting acute hepatocellular disease May be useful in detecting chronic liver disease Height of elevation reflects degree of hepatocellular injury for most diseases except alcoholic liver disease, hepatitis C, fatty liver of pregnancy ALT found in highest concentration in liver AST may be found in liver, heart, skeletal muscle, kidneys, brain, pancreas, lung, leukocytes and erythrocytes HEPATOCYTE DUODENUM (Hydrolyzed to unconjugated bilirubin in distal ileum and colon (80% excreted feces, 20% absorbed, fraction filtered by kidney as urobilinogen) BILIRUBIN PRODUCTION (Breakdown Product of Heme) BILIRUBIN UPTAKE BILIRUBIN CONJUGATION BILIRUBIN EXCRETION (Bilirubin conjugates actively transported from hepatocyte into canalicular bile (rate limiting step in excretion) Various sources: liver, bone, intestine, lung, placenta HYPERBILIRUBINEMIA Alkaline Phosphatase Height of elevation does not distinguish intra vs extraheptic obstruction Less than 3X elevation may occur in most liver diseases an reflects indiscriminate injury Very low levels may be seen in Wilson s disease HEPATOCYTE Over Production(Hemolysis, Transfusion, Bleeding, Hematoma) Impaired Uptake (Gilbert s) Impaired Conjugation (Parenchymal disease, Passive congestion, Drugs) May be a clue to Primary Biliary Cholangitis Impaired Excretion(Sepsis, Extrahepatic obstruction Pancreatic disease, Cholecystitis 2

3 Albumin Synthesized exclusively by the liver Albumin less than 3 should raise the suspicion of chronic liver disease May be low in non-hepatic disease: protein-losing enteropathies, chronic infection, nephrotic syndrome Not useful as a single test to screen for liver disease Acute VS Chronic Hepatitis Acute Less than 6 months Consultation often inpatient Height of ALT reflects urgency What is new with the patient? ALT >1000 Ischemia Viral Autoimmune Drug/Medication Chronic Greater than 6 months Consultation often outpatient Differential Diagnosis ETOH Inherited (Wilson s, Hemochromatosis, A1AT) Immune (PBC, AIH, PSC) Viral (HBV, HCV) NAFLD Less common drug/medication Prolongation of prothrombin time is not specific for liver disease: coagulation factor deficiencies, medications, nutritional deficiency, consumption Obesity, Diabetes (NAFLD) Prothrombin Time Not a sensitive index of liver disease Patient History: Systemic Disease Immune Disease (Autoimmune Hepatitis) Cardiac Disease (Passive Congestion) Pancreatic Disease (Obstruction) Particularly important in monitoring short-term and long-term function of liver Fulminant hepatic Decompensation of failure chronic liver disease Malignancy (Metastatic or Obstructive) 3 Basic Questions Are the liver test abnormalities acute or chronic? What is the detailed patient and family history? What is the pattern and trend of abnormalities? Patient History: Exposure Needlesticks (Hepatitis B, C) Transfusion (risk of Hep C before 1992) Workplace: Institutions, Day care, Hospitals (Viral hepatitis) Prostitute use, sexual preference (Hep B, C) IVDA, snorting cocaine (Hep B, C) Travel (Hepatitis A, parasitic infection) Hobbies (chemical exposure) Ingestion (ETOH, medications, supplements) 3

4 Pattern of Abnormalities Patient History: Family History Obesity, DM, Hypertension, Hyperlipidemia (NAFLD) Thyroid Disease, Lupus, RA, IBD (Autoimmune Hepatitis, PSC, PBC) Viral Hepatitis (Transmission HBV, HCV) Liver Disease (Wilson s, Hemochromatosis, A1AT, Immune Disease) Hepatocellular AST and ALT primary Differential Diagnosis Viral hepatitis Drug-induced hepatitis Autoimmune hepatitis Inherited liver disease Fatty liver Ischemia Cholestatic Alk Phos and Bilirubin primary Differential Diagnosis Drug-induced Primary Biliary Cholangitis Primary Sclerosing Cholangitis Obstruction Patient History: Medications Prescription Over the Counter Antibiotics Statins Seizure Narcotics (Tylenol) Tylenol, NSAIDS Vitamins Supplements Drug Medications: Hepatocellular Induced Liver vs Cholestatic Injury Hepatocellular Cholestatic Mixed INH Green Tea Nitrofurantoin Methydopa Clindamycin Ketoconazole Amoxicillin/Clavulanate Ciprofloxacin Sulfonylureas Erythromycin Sulfonamides Phenytoin Enalopril Livertox.nih.gov Pattern Recognition Hepatocellular Cholestatic Elevations primarily of AST, ALT Alkaline Phosphatase mildly elevated Bilirubin elevation reflects disorganization, injury Primary elevations of Alkaline Phosphatase and/or Bilirubin Obstruction Both alkaline phosphatase and bilirubin elevated Production/Transport Issue Primary elevation is bilirubin UTILITY OF TESTS IN DIAGOSING SPECIFIC DISEASES Patient history is most important History of previous elevation, jaundice Family history Risk factors, exposures Medications, alcohol, drugs Symptom history, systemic illness Historical information of liver tests is critical Acute vs chronic Response to treatment, change in clinical condition or medication Pattern recognition is useful 4

5 CASE STUDY 1 32 year old woman presents to the ER with 2 days of nausea, vomiting and vague abdominal pain She denies IVDU but believes her partner used to use drugs She took Tylenol over the counter at home for her symptoms She is diagnosed with viral gastroenteritis and sent home She returns 1 day later with the same complaints Labs are checked and show AST 8753, ALT 7542, alk phos 173, bilirubin 2.1 She is admitted and you are consulted Case Study 1: Diagnosis Medication Tylenol undetected Tox screen negative No OTC, recent antibiotics, supplements or weight loss products Autoimmune No family history Autoimmune markers negative Ischemic Normal blood pressure, Doppler US normal VIRAL Diarrhea HAV IgM positive Case Study 1: Differential Diagnosis Viral Drug or Medication Ischemic Autoimmune Exposure through partner Community outbreaks (HAV) Tylenol amount and pattern Recent antibiotics, supplements, weight loss products Young age, absence of cardiac disease or hypotension points away Young age, female supports Most patients will present after symptoms ongoing for a time so bilirubin may be higher CASE STUDY 2 42 yo woman referred to you with 1 year hx fatigue. Noted to have ALT 53, AST 43, Alk Phos 89, Bilirubin 0.1, normal ultrasound Risk factors for viral hepatitis negative Medical history significant for thyroid disease on Synthroid for 7 years Recently started Zocor 3 weeks ago for 3 year history of hyperlipidemia BMI 28 History of elevated blood sugar on no meds Case Study 1: Work Up Case Study 2: Utility of History and Baseline Liver Tests Viral? Viral prodrome HAV IgM, HBsAg, HBcAb (IgM), HBsAb,HCVRNA,CMV IgM, CMVPCR,EBV (monospot), Herpes (think in pregnancy) Drug or Medication?History antibiotics, OTC, supplements, weight loss Tylenol level Tox screen (cocaine, narcotics containing acetominophen) Ischemic Presentation ( found down ) Ascites (Budd Chiari), Edema, Shortness of breath (Cardiac) Autoimmune Family History, personal history if immune disease? ANA, AMA, ASMA, IgG Differential Diagnosis Fatty Liver Autoimmune or other immune disease Inherited liver disease Drug or Medication Viral Hepatitis Baseline Liver Tests Elevated Normal 5

6 CASE STUDY 3 46 year old man hospitalized for 1 month Consulted for elevated liver tests: ALT 86 ALT73 Alkaline Phosphatase 180 Serum Bilirubin 6.7 (Direct 5.3) Albumin 3.1 Prothrombin time 14.2 seconds Ultrasound shows no biliary dilation Surgery consulted and request an ERCP CASE STUDY 4 33 YO woman admitted for chest pain MI ruled out, ECHO normal LV function ALT 853, AST 1475, Alk Phos 143, Bilirubin 1.2 Meds : recent use weight loss product Past history : Thyroid disease on Synthroid? INH hepatotoxicity 2004 with ALT 467 ALT ALT Family History Cousin lupus CASE STUDY 3: Differential Diagnosis Case Study 4: Differential Diagnosis Everything Drug or Medication Autoimmune Viral Ischemia CASE STUDY 3 Case Study 4: Clues 1/8 3/25 3/27 4/1 4/2 4/4 4/8 4/10 4/11 4/14 4/15 4/19 4/25 ALT AST ALK Phos BILI INR Cipro, Ceftaz Acute or Chronic? Previous ALT helpful History Previous history of similar episode Family history Personal history The Old Rule One diagnosis is better than two Diagnosis Autoimmune Hepatitis Young woman Prior elevations Positive personal and family history of immune disease 6

7 AUTOIMMUNE CHRONIC ACTIVE HEPATITIS Women Moderate elevations in transaminases Associated autoimmune disorders or family history Appropriate clinical symptoms in association with liver disease ANA, ASMA, Anti-LKM SPEP, Quantitative immunoglobulins DIAGNOSIS Response to steroids typically confirmatory ALPHA-1- ANTITRYPSIN DEFICIENCY Neonatal hepatitis Chronic active hepatitis Cirrhosis Precocious emphysema SPEP, alpha-1 level, Phenotype (ZZ) DIAGNOSIS Biopsy showing inclusion granules (PAS positive diastase resistant) HEMOCHROMATOSIS Liver disease in association with Skin bronzing Cardiomyopathy Conduction disturbances Diabetes Testicular atrophy Arthropathy Impotence Family History Iron, TIBC, Ferritin FATTY DISEASE Most common cause of chronic hepatitis in U.S. Associated with obesity, diabetes, hypertension, hyperlipidemia Likely affects up to 30% of American population Estimated 20-40% of patients with diagnosis of NASH will progress to cirrhosis Mild transaminase elevations occur and are often overlooked WILSON S DISEASE Liver disease in younger patients Liver disease with hemolysis Neuropsychiatric disease Kayser-Fleicher rings Family history Serum ceruloplasim INDIRECT BILIRUBIN R/O HEMOLYSIS (LDH/HAPTOGLOBIN Cholestasis: Work up CHOLESTASIS DIRECT BILIRUBIN _ ULTRASOUND + DIAGNOSIS 24 hour urinary copper, liver biopsy for quantitative copper GILBERT S AMA, ERCP R/O PBC, PSC ERCP, CT, PTC R/O STONES STRICTURES TUMOR 7

8 Primary Biliary Cholangitis Middle aged women Fatigue, puritus, jaundice may be common Elevated bilirubin and alkaline phosphatase Over 90% of patients will have alk phos > 2 fold elevated AMA positive in 90% Increased IgM DIAGNOSIS Biopsy showing granulomas, bile duct destruction Primary Sclerosing Cholangitis 50-75% will have associated inflammatory bowel disease Recurrent cholangitis MRCP ERCP Summary Liver function tests give us information about the liver and we should pay attention Function is best represented by changes in INR and Bilirubin Patient history is critical in establishing a differential diagnosis and work up plan Associated gender differences, co-morbidities, risk factors, exposures and family history can help to refine the differential diagnosis and treatment plan Liver tests outside the range of normal are NOT NORMAL and follow up or work up to ensure either resolution or diagnosis Pattern recognition is helpful to guide work up and decide on treatment 8