Approach to the Jaundiced Patient

Approach to the Jaundiced Patient
Internal Medicine Survivor Series
By:Joel Bruggen, MD

New Onset Jaundice
* Viral hepatitis
* Alcoholic liver disease
* Autoimmune hepatitis
* Medication-induced liver disease
* Common bile duct stones
* Pancreatic cancer
* Primary Biliary Cirrhosis (PBC)
* Primary Sclerosing Cholangitis (PSC)

Jaundiced Emergencies
* Acetaminophen Toxicity
* Fulminant Hepatic Failure
* Ascending Cholangitis

Jaundice Unrelated to Intrinsic Liver Disease
* Hemolysis (usually T. bili < 4)
* Massive Transfusion
* Resorption of Hematoma
* Ineffective Erythropoesis
* Disorders of Conjugation
o Gilbert’s syndrome
* Intrahepatic Cholestasis
o Sepsis, TPN, Post-operation

New Onset Jaundice
* Viral hepatitis
* Alcoholic liver disease
* Autoimmune hepatitis
* Medication-induced liver disease
* Common bile duct stones
* Pancreatic cancer
* Primary Biliary Cirrhosis (PBC)
* Primary Sclerosing Cholangitis (PSC)

HBV Serology
Resolved HBV
HBV vaccinated
Chronic HBV
Acute HBV
HBSAb
HBcAb
IgG
HBcAb
IgM
Acute Hepatitis C
HCV RNA
Anti-HCV
Infection Day 0
HCV RNA Day 12
HCV Antibody Day 70
Plateau phase = 57 days

Alcoholic Liver Disease
* The history is the key – 60 grams/day
* Gynecomastia, parotids, Dupuytren’s
* Lab clues: AST/ALT > 2, MCV > 94

AST < 300
* Alcoholic hepatitis:
o Anorexia, fever, jaundice, hepatomegaly
o Treatment:
+ Abstinence
+ Nutrition
+ Consider prednisolone or pentoxifylline

Alcoholic Liver Disease
Discriminant Function Formula:
DF = [4.6 x (PT – control)] + bilirubin
Consider treatment for DF > 32
* Prednisolone 40 mg/day x 28 days
o contraindications: infection, renal failure, GIB
* Pentoxifylline 400 mg PO tid x 28 days

Autoimmune Hepatitis
* Widely variable clinical presentations
o Asymptomatic LFT abnormality (ALT and AST)
o Severe hepatitis with jaundice
o Cirrhosis and complications of portal HTN
* Often associated with other autoimmune dz
* Diagnosis:
o Compatible clinical presentation
o ANA or ASMA with titer 1:80 or greater
o IgG > 1.5 upper limits of normal
o Liver biopsy: portal lymphocytes + plasma cells

Drug-induced Liver Disease
* Hepatocellular
o acetaminophen, INH, methyldopa, MTX
* Cholestatic
o chlorpromazine, estradiol, antibiotics
* Chronic Hepatitis
o methyldopa, phenytoin, macrodantin, PTU
* Hypersensitivity Reaction
o Phenytoin, Augmentin, allopurinol
* Microvesicular Steatosis
o amiodarone, IV tetracycline, AZT, ddI, stavudine

Acetaminophen Toxicity
* Danger dosages (70 kg patient)
o Toxicity possible > 10 gm
o Severe toxicity certain > 25 gm
o Lower doses potentially hepatotoxic in:
+ Chronic alcoholics
+ Malnutrition or fasting
+ Dilantin, Tegretol, phenobarbital, INH, rifampin
+ NOT in acute EtOH ingestion
+ NOT in non-alcoholic chronic liver disease

Acetaminophen Toxicity
* Day 1:
o Nausea, vomiting, malaise, or asymptomatic
* Day 2 – 3:
o Initial symptoms resolve
o AST and ALT begin to rise by 36 hours
o RUQ pain, tender enlarged liver on exam
* Day 4
o AST and ALT peak > 3000
o Liver dysfunction: PT, encephalopathy, jaundice
o Acute renal failure (ATN)

Acetaminophen Toxicity Treatment
Indications for NAC therapy:
Fulminant Hepatic Failure
* Definition:
o Rapid development of hepatic dysfunction
o Hepatic encephalopathy
o No prior history of liver disease
* Most common causes:
o Acetaminophen
o Unknown
o Idiosyncratic drug reaction
o Acute HAV or HBV (or HDV or HEV)

Fulminant Hepatic Failure
* Close glucose monitoring IV glucose
* Avoid sedatives - give PO lactulose
* Avoid nephrotoxins and hypovolemia
* Vitamin K SQ
o Do not give FFP unless active bleeding, since INR is an important prognostic factor
* GI bleed prophylaxis with PPI
* Transfer all patients with FHF who are candidates to a liver transplant center

Indications:
* Hepatitis C 29%
* Alcoholic Liver Disease 15%
* Cirrhosis of unknown etiology 8%
* Hepatocellular Carcinoma 7%
* Fulminant Hepatic Failure 6%
* Primary Sclerosing Cholangitis 5%
* Primary Biliary Cirrhosis 4%
* Metabolic Liver Disease 4%
* Autoimmune Hepatitis 3%
* Hepatitis B 3%

Liver Transplantation:
Contraindications
* ABSOLUTE
o active alcohol or drug abuse
o HIV positivity
o extrahepatic malignancy
o uncontrolled extrahepatic infection
o advanced cardiopulmonary disease
* RELATIVE
o Age over 65
o poor social support
o poorly controlled mental illness

Obstructive Jaundice
CBD stones (choledocholithiasis) vs. tumor
* Clinical features favoring CBD stones:
o Age < 45
o Biliary colic
o Fever
o Transient spike in AST or amylase
* Clinical features favoring cancer:
o Painless jaundice
o Weight loss
o Palpable gallbladder
o Bilirubin > 10

Ascending Cholangitis
* Pus under pressure
* Charcot’s triad: fever, jaundice, RUQ pain
o All 3 present in 70% of patients, but fever > 95%
o May also present as confusion or hypotension
* Most frequent causative organisms:
o E. Coli, Klebsiella, Enterobacter, Enterococcus
o anaerobes are rare and usually post-surgical
* Treatment:
o Antibiotics: Levaquin, Zosyn, meropenem
o ERCP with biliary drainage

Ascending Cholangitis
Indications for Urgent ERCP
* Persistent abdominal pain
* Hypotension despite adequate IVF
* Fever > 102
* Mental confusion
* Failure to improve after 12 hours of antibiotics and supportive care

Obstructive Jaundice Malignant Causes
* Cancer of the Pancreas
* Cancer of the Bile Ducts (Cholangiocarcinoma)
* Ampullary Tumors
* Portal Lymphadenopathy

Primary Biliary Cirrhosis
* Cholestatic liver disease (ALP)
o Most common symptoms: pruritus and fatigue
o Many patients asx, and dx by abnormal LFT
* Female:male ratio 9:1
* Diagnosis:
o Compatible clinical presentation
o AMA titer 1:80 or greater (95% sens/spec)
o IgM > 1.5 upper limits of normal
o Liver biopsy: bile duct destruction
* Treatment: Ursodeoxycholic acid 15 mg/kg

Primary Sclerosing Cholangitis
* Cholestatic liver disease (ALP)
* Inflammation of large bile ducts
* 90% associated with IBD
o but only 5% of IBD patients get PSC
* Diagnosis: ERCP (now MRCP)
o No autoantibodies, no elevated globulins
o Biopsy: concentric fibrosis around bile ducts
* Cholangiocarcinoma: 10-15% lifetime risk
* Treatment: Liver Transplantation

Diagnosis of Immune-Mediated Liver Disease
Periductal concentric fibrosis
Unusual Causes of Jaundice
* Ischemic hepatitis
* Congestive hepatopathy
* Wilson’s disease
* AIDS cholangiopathy
* Amanita phalloides (mushrooms)
* Jamaican bush tea
* Infiltrative diseases of the liver
o Amyloidosis
o Sarcoidosis
o Malignancy: lymphoma, metastatic dz

Wilson’s Disease
* Autosomal recessive – copper metabolism
* Chronic hepatitis or fulminant hepatitis
* Associated clinical features:
o Neuropsychiatric disease
o Hemolytic anemia
* Physical exam: Kayser-Fleischer rings
* Diagnosis: ceruloplasmin, urinary Cu
* Treatment: d-penicillamine

Critical Questions in the Evaluation of the Jaundiced Patient
* Acute vs. Chronic Liver Disease
* Hepatocellular vs. Cholestatic
o Biliary Obstruction vs. Intrahepatic Cholestasis
* Fever
o Could the patient have ascending cholangitis?
* Encephalopathy
o Could the patient have fulminant hepatic failure?

Evaluation of the Jaundiced Patient HISTORY

* Pain
* Fever
* Confusion
* Weight loss
* Sex, drugs, R&R
* Alcohol
* Medications
* pruritus
* malaise, myalgias
* dark urine
* abdominal girth
* edema
* other autoimmune dz
* HIV status
* prior biliary surgery
* family history liver dz

Evaluation of the Jaundiced Patient PHYSICAL EXAM
* BP/HR/Temp
* Mental status
* Asterixis
* Abd tenderness
* Liver size
* Splenomegaly
* Ascites
* Edema
* Spider angiomata
* Hyperpigmentation
* Kayser-Fleischer rings
* Xanthomas
* Gynecomastia
* Left supraclavicular adenopathy (Virchow’s node)

Evaluation of the Jaundiced Patient LAB EVALUATION
* AST-ALT-ALP
* Bilirubin – total/indirect
* Albumin
* INR
* Glucose
* Na-K-PO4, acid-base
* Acetaminophen level
* CBC/plt
* Ammonia
* Viral serologies
* ANA-ASMA-AMA
* Quantitative Ig
* Ceruloplasmin
* Iron profile
* Blood cultures

Evaluation of the Jaundiced Patient
* Ultrasound:
o More sensitive than CT for gallbladder stones
o Equally sensitive for dilated ducts
o Portable, cheap, no radiation, no IV contrast
* CT:
o Better imaging of the pancreas and abdomen
* MRCP:
o Imaging of biliary tree comparable to ERCP
* ERCP:
o Therapeutic intervention for stones
o Brushing and biopsy for malignancy

Case studies

Approach to the Jaundiced Patient.ppt