lecture 2 may

8/6/2019 Lecture 2 May

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New Onset Jaundice Viral hepatitis

Autoimmune hepatitis

Medication-induced liver disease

Common bile duct stones

Pancreatic cancer

Primary Biliary Cirrhosis (PBC)

Primary Sclerosing Cholangitis (PSC)


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Jaundice Unrelated to

Intrinsic Liver Disease Hemolysis (usually T. bili < 4)

Massive Transfusion

Resorption of Hematoma Ineffective Erythropoesis

Disorders of Conjugation

y Gilberts syndrome

Intrahepatic Cholestasis

y Sepsis, TPN, Post-operation


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Pancreatic cancer



Alcoholic liver disease


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HBV Serology

HBSA

g

HBcA

b

IgM

HBcA

b

IgG

HBSA

b

Acute HBV + + - -Resolved HBV

- - + +Chronic HBV + - + -HBV

vaccinated - - - +


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Acute Hepatitis C

From DL Thomas

HCV

RNAAnti-HCV

0 10 20 30 40 50 60 70 80 90 100

Infection Day 0

HCV RNA Day 12

HCV Antibody Day 70

Plateau phase = 57 days


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Pancreatic cancer




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Pancreatic cancer




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Autoimmune Hepatitis Widely variable clinical presentations

yAsymptomatic LFT abnormality (ALT and AST)

y Severe hepatitis with jaundice

y Cirrhosis and complications of portal HTN Often associated with other autoimmune dz

Diagnosis:

y Compatible clinical presentation

yANA or ASMA with titer 1:80 or greater

y IgG > 1.5 upper limits of normal

y Liver biopsy: portal lymphocytes + plasma cells


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New Onset JaundiceViral hepatitis


Medication-induced liver diseaseCommon bile duct stones

Pancreatic cancer




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Drug-induced Liver Disease

Hepatocellulary acetaminophen, INH, methyldopa, MTX

Cholestatic

y

chlorpromazine, estradiol, antibiotics Chronic Hepatitis

y methyldopa, phenytoin, macrodantin, PTU

Hypersensitivity Reaction

y Phenytoin, Augmentin, allopurinol

Microvesicular Steatosis

y amiodarone, IV tetracycline, AZT, ddI, stavudine


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Fulminant Hepatic Failure

Definition:yRapid development of hepatic dysfunction

yHepatic encephalopathy

yNo prior history of liver diseaseMost common causes:yAcetaminophen

yUnknowny Idiosyncratic drug reaction

yAcute HAV or HBV (or HDV or HEV)


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Fulminant Hepatic Failure

Close glucose monitoring IV glucose

Avoid sedatives - give PO lactulose

Avoid nephrotoxins and hypovolemiaVitamin K SQ

yDo not give FFP unless active bleeding,since INR is an important prognostic factor

GI bleed prophylaxis with PPI

Transfer all patients with FHF who arecandidates to a liver transplant center


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5,6741 Liver Transplants in 2003

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%


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Liver Transplantation:

ContraindicationsABSOLUTEy active alcohol or drug abuse

y HIV positivity

y extrahepatic malignancy

y uncontrolled extrahepatic infection

y advanced cardiopulmonary disease RELATIVE

y Age over 65

y poor social supporty poorly controlled mental illness


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Pancreatic cancer




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Obstructive JaundiceCBD stones (choledocholithiasis) vs. tumor

Clinical features favoring CBD stones:

yAge < 45

y Biliary colic

y Fevery Transient spike in AST or amylase

Clinical features favoring cancer:

y

Painless jaundicey Weight loss

y Palpable gallbladder

y Bilirubin > 10


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Ascending Cholangitis Pus under pressure

Charcots triad: fever, jaundice, RUQ painyAll 3 present in 70% of patients, but fever > 95%

yMay also present as confusion or hypotension

Most frequent causative organisms:y E. Coli, Klebsiella, Enterobacter, Enterococcus

y anaerobes are rare and usually post-surgical

Treatment:yAntibiotics: Levaquin, Zosyn, meropenem

y ERCP with biliary drainage


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Ascending Cholangitis

Indications for Urgent ERCP

Persistent abdominal pain

Hypotension despite adequate IVF

Fever > 102

Mental confusionFailure to improve after 12 hours of

antibiotics and supportive care


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Obstructive JaundiceMalignant Causes

Cancer of the Pancreas

Cancer of the Bile Ducts

(Cholangiocarcinoma)

Ampullary TumorsPortal Lymphadenopathy


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Pancreatic cancer




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Primary Biliary Cirrhosis

Cholestatic liver disease (ALP)y Most common symptoms: pruritus and fatigue

y Many patients asx, and dx by abnormal LFT

Female:male ratio 9:1

Diagnosis:

y Compatible clinical presentation

yAMA titer 1:80 or greater (95% sens/spec)

y IgM > 1.5 upper limits of normaly Liver biopsy: bile duct destruction

Treatment: Ursodeoxycholic acid 15 mg/kg


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Primary Sclerosing Cholangitis

Cholestatic liver disease (ALP) Inflammation of large bile ducts

90% associated with IBD

y but only 5% of IBD patients get PSC Diagnosis: ERCP (now MRCP)

y No autoantibodies, no elevated globulins

yBiopsy: concentric fibrosis around bile ducts

Cholangiocarcinoma: 10-15% lifetime risk

Treatment: Liver Transplantation


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Diagnosis of

Immune-Mediated Liver Disease

LFT Serology QuantitativeImmunoglobulins

Biopsy

AIH ALT ANAASMA

IgG PortalinflammationPlasmacytes

Piecemeal

necrosis

PBC ALP AMA IgMBile duct

destruction

granulomas

PSC ALP none normalPeriductal

concentric

fibrosis


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Unusual Causes of Jaundice

Ischemic hepatitis Congestive hepatopathy

Wilsons disease

AIDS cholangiopathy

Amanita phalloides (mushrooms)

Jamaican bush tea

Infiltrative diseases of the liver

yAmyloidosis

y Sarcoidosis

y Malignancy: lymphoma, metastatic dz


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Wilsons Disease

Autosomal recessive copper metabolism

Chronic hepatitis or fulminant hepatitis

Associated clinical features:y Neuropsychiatric disease

y Hemolytic anemia

Physical exam: Kayser-Fleischer rings

Diagnosis: ceruloplasmin, urinary Cu

Treatment: d-penicillamine


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Critical Questions in the Evaluation

of the Jaundiced Patient

Acute vs. Chronic Liver Disease

Hepatocellular vs. Cholestaticy Biliary Obstruction vs. Intrahepatic Cholestasis

Fevery Could the patient have ascending cholangitis?

Encephalopathyy Could the patient have fulminant hepatic failure?


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Evaluation of the Jaundiced Patient

HISTORY

Pain

Fever

Confusion

Weight loss

Drugs, R&RAlcohol

Medications

pruritus

malaise, myalgias

dark urine

abdominal girth

edema

other autoimmune dz

HIV status prior biliary surgery

family history liver dz


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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 (Virchowsnode)


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LAB EVALUATION

AST-ALT-ALP

Bilirubin total/indirect

Albumin

INR

Glucose

Na-K-PO4, acid-base

CBC/plt

Ammonia

Viral serologies

ANA-ASMA-AMA Quantitative Ig

Ceruloplasmin

Iron profile

Blood cultures


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Ultrasound:y More sensitive than CT for gallbladder stones

y Equally sensitive for dilated ducts

y Portable, cheap, no radiation, no IV contrast

CT:y Better imaging of the pancreas and abdomen

MRCP:y Imaging of biliary tree comparable to ERCP

ERCP:y Therapeutic intervention for stones

y Brushing and biopsy for malignancy


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YesYes

Treat


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Unknown Case #1

59 year old male lawyery Nausea, vomiting, lethargy, chronic back pain

y PMH: HTN, hypercholesterolemia

y Meds: Prinivil, Lipitor, Vicodin

VSS afebrile, jaundice, no stigmata cirrhosisyA/O, no asterixis no edema, no ascites

y sl RUQ tender, liver span 18 cm, no palp spleen

AST 3246, ALT 4620, ALP 105, bili 5.2


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Unknown Case #2

38 year old female managery 3 days of episodic severe RUQ pain

y 2 days of fever/chills/rigors

y Daughter noticed yellow eyes today

y PMH: DM, HTN

y Meds: glipizide, HCTZ

BP 110/64 HR 112, temp 101.8

y Jaundice, no stigmata of cirrhosis

y RUQ tender to palp, no spleen, no ascites

AST 602, ALT 654, ALP 256, bili 5.2


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YesYes

Treat


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Thanks

lecture 2 may

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