Evaluating the Patient With Abnormal Liver Tests-2

פרופ' צבי אקרמן מבית חולים הדסה הר הצופים

Imaging studies

• Abdominal Ultrasound with Doppler of hepatic and portal veins

• Abdominal MRCP

• Upper endoscopy (EGD)

• Liver biopsy

• Non Invasive Tests for Fibrosis

Imaging studies-1

• Abdominal Ultrasound with Doppler of hepatic and portal veins-1

• Abdominal ultrasound is helpful in the evaluation of patients with cirrhosis.

• It may reveal a shrunken, nodular liver suggestive of cirrhosis.

Imaging studies-1a1a

• The liver may appear echogenic if excessive fat has infiltrated the liver as in NAFLD (nonalcoholic fatty liver disease).

• It is sensitive for the detection of small to moderate amounts of ascites.

• It can be used to screen for liver masses which may suggest the presence of hepatocellular carcinoma.

Imaging studies-2

• Abdominal Ultrasound with Doppler of hepatic and portal veins-2

• The use of Doppler ultrasonography can provide information about the hepatic and portal veins such as portal vein thrombosis.

• Because it is relatively inexpensive, and widely available, ultrasonography is the preferred initial imaging modality in patients with cirrhosis.

Imaging studies-3

• Abdominal MRCP

• MRI is not indicated in every evaluation of liver disease , only in cases where specific bile duct pathology is suspected.

• It is expensive and ‘simple”information can be obtained with ultrasonography.

Imaging studies-4

• Upper endoscopy (EGD)

• Upper endoscopy is useful in the diagnosis of esophageal varices, a finding seen with portal hypertension.

• In cirrhotic patients, it is useful to document the presence of varices so prophylactic measures can be instituted to decrease the risk of bleeding.

Imaging studies-3

Imaging studies-3

Imaging studies • Abdominal Ultrasound with Doppler of hepatic and

portal veins

• Abdominal MRCP

• Upper endoscopy (EGD)

• Liver fibrosis Assessment :Liver biopsy

• Liver fibrosis Assessment :Non Invasive Tests for Fibrosis

Liver Biopsy

Hepatic Injury : Hepatic Injury : necrotico-inflammatory activity, necrotico-inflammatory activity, fibrosis, fibrosis, steatosis, steatosis, biliary lesions, vascular lesionsbiliary lesions, vascular lesions

Fibrosis scores Fibrosis scores ( METAVIR, Knodell , Ishak,…)( METAVIR, Knodell , Ishak,…)

  Invasive procedure Invasive procedure  morbidity : 0.3 to 0.6% morbidity : 0.3 to 0.6% mortality : 0 to 0.05% mortality : 0 to 0.05%

Cost : approximately 4000 NIS ( without complications)Cost : approximately 4000 NIS ( without complications)

F1

F4

F2

F1

F4

Imaging studies

BioMarkers of liver injury

• Markers of Fibrosis

• Scores of Fibrosis

Hem orrhage Liver Failure Cancer

F4

F3

F2

F1

F0

Fibrotic LiverDisease

How must be an ideal marker of liver Fibrosis?

• Specific to the Liver

• Independant to metabolic dysfunction

• Easy to perform

• Sensitivity to detect the different stages of liver fibrosis

• Can reliably assess the efficacy of antifibrotic treatment

• Can be used whatever the etiology of chonic liver fibrosis

• Non influenced by extra-hepatic factors

Haptoglobin

Alpha2Macroglobulin

Apolipoprotein A1

Total Bilirubin

Gamma GT

In Situ In Serum: FibroTestIn Serum: FibroTest

Liver InjuryLiver Injury

Activated Stellate CellsActivated Stellate Cells

Fibrotic MatrixFibrotic Matrix

ALT

0.00

0.10

0.20

0.30

0.40

0.50

0.60

0.70

0.80

0.90

1.00

0 1 2 3 4

FibroTest

METAVIR Fibrosis Stage

Multicenter Independant ValidationHalfon, Am J Gastroenterol 2006

n=519

0.00

0.25

0.50

0.75

1.00

0 1 2 3 4

Fibrosis Stage

Fib

rote

stDisease

HBVHCVHCV_HIVNAFLDOH

Myers et al 2003

Poynard et al 2004

Myers et al 2003

Ratziu et al 2004

Naveau et al 2005

FibroFibroTestTest: fibrosis marker in other chronic : fibrosis marker in other chronic liver diseases (n=2,706)liver diseases (n=2,706)

LONGITUDINAL STUDIES

The Fibrotest was found to predict the evolution of HCV patients towards cirrhosis better than liver biopsy after 5 years of follow-upNgo Clin Chem 2006

Progression of liver fibrosis

0

1

2

3

4

0 10 20 30 40 50

F METAVIR

Duration in years

Rapid Intermediate

Slow fibroser

Poynard et al

Abnormal Liver Test Results: Points for Clinical Practice• Abnormal liver test results will be identified in 8%-20% of patients during

clinical care.

• Most patients with abnormal liver test results should have additional evaluation. A referral to the gastroenterologist may be needed.

• A careful history and physical examination frequently provide the diagnosis, obviating the need for invasive testing.

• If there are signs or symptoms of chronic liver disease, considering the patient's age may assist in the diagnosis.

• Isolated elevation of GGT occurs and a cause may not be identified.

CON-Abnormal Liver Test Results: Points for Clinical Practice

• The presence of multiple abnormal test results makes significant liver disease more likely.

• Aminotransferase, alkaline phosphatase, and GGT levels can be elevated from causes other than liver disease.

• Persisting abnormalities of aminotransferases or enzymes of cholestasis should be further evaluated because up to two thirds will have a diagnosis requiring follow-up or intervention.

• Supplemental testing with additional laboratory tests, ultrasonography, or magnetic resonance cholangiography should be considered when the diagnosis is unclear or confirmation of liver disease diagnosis is required.

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