Approach to the Patient with

Liver Disease

Diagnosis of liver disease

Careful history taking

Physical examination

Laboratory tests

Radiologic examination and imaging studies

Liver biopsy

Liver diseases

Inherited hyperbilirubinemia→ Gilbert disease← 5% of the

population

Viral hepatitis→ A, B, C, D, E

Immune and autoimmune liver diseases→ Primary biliary cirrhosis,

Autoimmune hepatitis, Sclerosing cholangitis

Genetic liver diseases→

Hemochromatosis, Wilson disease

Liver diseases 2

Alcoholic liver disease→ Acute fatty liver,

Acute alcoholic hepatitis, Laennec cirrhosis

Nonalcoholic fatty liver→ Steatosis,

Steatohepatitis

Liver involvement in systemic diseases→

Sarcoidosis, Tuberculosis

Cholestatic syndromes→ Cholangitis and

cholecystitis, Extrahepatic biliary obstruction (stone, stricture,cancer)

Liver diseases 3

Drug-induced liver disease→ Isoniazid,

Acetaminophen, Methotrexate

Vascular injury→ Venoocclusive disease,

Budd-Chiary syndrome, Portal vein thrombosis

Mass lesions→ Hepatocellular carcinoma,

Cholangiocarcinoma, Adenoma, Metastatic tumors, Focal nodular hyperplasia, Abscess, Cysts, Hemangioma

Liver diseases

Hepatocellular diseases

Cholestatic diseases→ gall stone,

malignant obstruction

Symptoms

Jaundice→ scleral icterus

Dark urine

Light stools

Nausea

Fatigue

Itching

Right upper quadrant pain

Abdominal bloating

GI bleeding

Physical examination Icterus Hepatomegaly Hepatic tenderness Liver edge Irregularity of the surface Splenomegaly Spider angiomata Palmar erythema Ascites Edema Hepatic fetor Gynecomastia Hepatic encephalopahy

Laboratory Testing

ALT = serum alanine aminotransferase

AST = serum aspartate aminotransferase

Alkaline phosphatase

GGT = gamma-glutamyl transpeptidase

Total and direct serum bilirubin

Prothrombin time

Evaluation of Liver Function

Serum Bilirubin (indirect, direct) normal: <17 μmol/L

Urine Bilirubin→ liver disease

Blood Ammonia→ hepatic

encephalopathy, hepatic failure

Serum albumin→ hypoalbuminemia

Serum Globulins: gamma globulins

Diagnostic Tests

Hepatitis A→ Anti-HAV IgM Hepatis B→ HBsAg, anti-HBc IgM, HBV DNA Hepatitis C→ Anti-HCV, HCV RNA Autoimmune hepatitis→ ANA, SMA Primary biliary cirrhosis→ AMA Primary sclerosing cholangitis→ P-ANCA Wilson disease→ serum ceruolplasmin↓,copper↑ Hemochromatosis→ iron saturation↑,serum ferritin↑ Hepatocellular cancer→ AFP↑

Diagnostic Imaging

Ultrasound

CT

MRI

ERCP (endoscopic retrograde cholangiopancreatography)→

sphincterotomy, stone extraction, placement of biliary stent

Doppler ultrasound

Liver Biopsy

Gold standard

Hepatocellular disease of uncertain cause

Unexplained hepatomegaly

FUO (fever of unknown origin)

Gilbert´s Syndrome

Mild unconjugated indirect hyperbilirubinemia

Normal values for standard hepatic biochemical tests

Normal hepatic histology

Serum bilirubin <51 μmol/L

Provocation test→ 48 h of fasting

Prevalence ≥8 %

Males predominate over females

Gilbert´s Syndrome 2

Autosomal dominant inheritance

Jaundice

Icterus

Yellowish discoloration← deposition

of bilirubin

Sclerae→ scleral icterus

Darkening of the urine← conjugated bilirubin→ urine as tea or cola

colored

Measurement of serum Bilirubin

Van den Bergh reaction→ direct- and indirect-reacting bilirubin

Normal: 17 μmol/L

Unconjugated Hyperbilirubinemia→ hemolytic disorders→spherocytosis, sickle cell anemia, thalassemia, hemolytic-uremic syndrome, PNH, immune hemolysis, Gilbert´s syndrome

Elevation of serum Bilirubin with

other liver test

Conjugated hyperbilirubinemia

Hepatocellular process

Intra- or extrahepatic cholestasis

Hepatocellular conditions with

jaundice

Hepatitis A,B,C,D and E

EBV, CMV, Herpes simplex

Alcohol

Drug toxicity→ Acetaminophen, Isoniazid

Environmental toxins→ wild mushrooms

Amanita phalloides

Wilson´s disease

Autoimmune hepatitis

Cholestatic conditions with jaundice

I. Intrahepatic

II. Extrahepatic

Intrahepatic cholestatic conditions

Viral hepatitis

Alcoholic hepatitis

Drug toxicity→ anabolic steroids,

contraceptive pills,

PBC

Primary sclerosing cholangitis

Infiltrative disease→ TB, lymphoma,

amyloid

Extrahepatic cholestatic conditions

Cholangiocarcinoma

Pancreatic cancer

Gallbladder cancer

Malignant involvement of the porta hepatis lymph nodes

Choledocholithiasis

Chronic pancreatitis