A Pratical Approach to Abnormal LFTs: Acute vs Chronic Brenda Appolo PAC, MHS University of Pennsylvania, Perelman School of Medicine Objectives • Discuss history, physical and diagnostic work up of patients with acute and chronic liver test abnormalities • Discussion of patient cases and practical ddx Approach to the Liver Patient Acute vs Chronic • Acute Liver Failiure (ALF) - Accepted definition: INR > 1.5 and any degree of mental alteration (HE) in a patient without pre existing cirrhosis - illness up to 26 weeks duration -Most common: Viral, Drug -Patients w/ Wilson Disease, vertically acquired HBV or AIH may be included in spite of possibility of cirrhosis if their disease has only been recognized for 26 weeks or less • “Acute on Chronic” Liver Failure -Acute-on-chronic liver failure (ACLF) is an increasingly recognized entity encompassing an acute deterioration of liver function in patients with cirrhosis, which is usually associated with a precipitating event leading to liver or multi organ failure Approach to the Liver Patient Acute vs Chronic • Acute Hepatitis -Time limited injury to the liver -Often does not lead to hepatic fibrosis -Not a diagnosis rendered on liver biopsy alone -Viral most common HAV, HBV, EBV, HSV • Chronic Hepatitis -Inflammatory state with propensity to cause liver fibrosis -Histological hallmark includes influx of chronic inflammatory cells, lymphocytes and plasma cells -“LFT elevations for > 6 months” -Chronic hepatitis does NOT denote a specific etiology Chronic hepatitis does not always signify chronic liver / intrinsic disease! (i.e.: celiac disease is a reactive hepatopathy) Approach to the Patient History is paramount • Sx onset; many patients asx though • Sx – anorexia, weight change, fever, malaise, GI sx, rash, pruritus, lymphadenopathy • Family History • Medications / Herbal therapies • Social History blood transfusions; IVDU; intranasal drugs; anabolic steroids; tattoos; incarceration, EtOH, travel, occupational exposures Approach to the patient Physical Examination • Nutritional Status Proximal muscle wasting • Neuro – Psych Asterixis; Mini mental exam (serial 7s) • Scleral icterus Detectable typically if t bili > 3.0 mg/dL • Skin Ecchymosis; Petechia; Spider angiomata; Jaundice • Abdominal Exam Abdominal bruits; Caput Medusa Hepatomegaly; Hepatic mass Pulsatile Liver (tricuspid regurgitation) Ascites (fluid wave; shifting dullness; tense abdomen) RUQ pain Splenomegaly Approach to the patient Laboratory Testing • Liver Function Tests (cholestasis / transaminitis / mix) AST; AST; Alkaline Phosphatase Total bilirubin – direct / indirect GGT Albumin • CBC Platelets; H/H; MCV; WBC • • PT / INR Basic Metabolic Panel Serum Sodium Potassium Creatinine / BUN Approach to the patient Laboratory Testing • Viral serologies HAV; HBV; HCV; EBV • Iron panel Total iron, Ferriten, T Sat, Transferriten • Autoimmune panel Anti-LKM Ab, ASMA • • • • • • Ceruloplasmin Serum Copper A1 Antitrypsin AMA ANA Quantitative Immunoglobulins IgM, IgG, IgA Approach to Liver Patient ALF – Initial Laboratory Assessment • • • • • • • • • • • • • Prothrombin time/INR Chemistries sodium, potassium, chloride, bicarbonate, calcium, magnesium, phosphate glucose AST, ALT, alkaline phosphatase, GGT, total bilirubin, albumin creatinine, blood urea nitrogen Acetaminophen level Toxicology screen Viral hepatitis serologies anti-HAV IgM, HBSAg, anti-HBc IgM, antiHEV§, anti-HCV* Ceruloplasmin Level / Copper * Autoimmune markers ANA, ASMA, Immunoglobulin levels • • • • • • • • Arterial blood gas Arterial lactate Complete blood count Blood type and screen Pregnancy test (females) Ammonia (arterial if possible) HIV status (if txp potential) Amylase and lipase *Done only if Wilson disease is a consideration e.g., in patients less than 40years without another obvious explanation for ALF); in this case uric acid level and bilirubin to alkaline phosphatase ratio may be helpful as well. Approach to patient: staging injury • • • • • Percutaneous Needle Liver Biopsy Transjugular Liver Biopsy (TJLB / portal pressures) Noninvansive Markers Fibroscan MR Elastography Liver Diseases: Overview - DDx • Viral HAV HBV HCV Other – EBV, CMV, HSV • Steatohepatitis (Fatty Liver) Alcohol Non alcohol (metabolic syndrome) Pregnancy (microvesicular fatty droplet formation) Drug • Autoimmune Hepatitis Liver Diseases: Overview - DDx • Metabolic Wilson’s Disease – copper overload Alpha 1 Antitrypsin Disease Hereditary Hemochromatosis – iron overload • Drug Toxicity Antibiotics Statins Herbal / Other • Vascular injury Veno-occlusive Disease Budd Chiari Syndrome • Congenital Congenital Hepatic Fibrosis Polycystic Liver Disease Caroli’s Disease Alagille’s Syndrome Case #1 • • • • • 18 male presents with general malaise x 2 m, 10lb weight loss to his primary care office Student health records 6 m prior with normal LFTs AST 901; ALT 848; AlkPhos 343; T bil 5.4; WBC 8.6; Hg 14.7; MCV 92; Plt 201; INR 1.2 U/s Abd: borderline hepato-splenomegaly; otherwise normal appearing liver; normal gb Does this patient have acute liver failure or acute hepatitis? What is your differential diagnosis? What other information is helpful to you at this point? Should we do a liver biopsy? Does this patient have portal hypertension? Case #2 • • • • • • • • 59 black male presents for yearly check up to primary care Primary care opts to start a statin for hyperlipidemia; obtains pre treatment labs No other sig PMHx FHx – CAD, DM, Hyperlipidemia SHx – alcohol rare; never smoker; no illicit drug hx ; no transfusions AST 64; ALT 84 ; AlkPhos 200; T bil 1.3; Albumin 3.2 WBC 6.2; Hg 16.7; MCV 98; Plt 117K RUQ (limited) U/s Abd: Increased echogenicity of liver, no obvious cirrhosis; no liver mass; no ascites; top normal spleen What is your differential diagnosis? What other information is helpful to you at this point? Do you want a liver biopsy? Is a statin contradindicated? Case #3 • 67 yr old female presents with malaise, jaundice to primary care • PMHx – hypothyroidism • T bil 6.5; AST 590; ALT 463; Alb 3.4; AlkPhos 300 • WBC 6.5; Hg 12.3; MCV 91; Plt 215k • Cr 1.2; INR 1.3; AFP 3 What is your differential diagnosis? What other information are helpful to you at this point? Case #4 • • • 53 F presents to GI office post hospitalization for jaundice, ascites and abdominal pain Discharge labs: Cr 1.4; Na 131; K 3.3; T bil 8.5; AST 75; ALT 32; AP 212; Alb 2.6; Hg 9.4; WBC 13; Plt 90k; MCV 103; Fluid analysis 314 PMN; culture negative; high SAAG U/s Abd: hepatomegaly; mass can not be rule out based on limited exam; distended gallbladder; no acute cholecystitis; moderate ascites; enlarged spleen; PV patent What is your differential diagnosis? What other information are helpful to you at this point? Surgery consult?