Cholestatic Liver Disease

191 Pages·2008·10.66 MB·English

by  Velimir A. Luketic MD (auth.)

Cholestatic Liver Disease
CLINICAL GASTROENTEROOL G ~Y
George .Y WU, MD, PhD, SERIES EDrrOR
Nutrition and Gastrointestinal Disease, edited Inflammatory Bowel Disease: Diagnosis and
by Mark DeeL gge, 2008 Therapeutics, edited by Russe U D. Cohen, 2003
Cholestatic Uver Disease, edited by eK ith D. An Internist's mustrated Guide to Gastro-
iL ndor and aJ yant A. Talwalkar, 2008 intestinal Surgery, edited by George .Y Wu,
Portal yH pertension: Pathobiology, Evaluation, hK alid Aiz ,z iL ly .H iF duccia, and Giles .F
and Treatment, edited by Anm .J Sanyal Whalen, 2003
and Vijay .H Shah, 2005 Chronic V"a' U l Hepatitis: Diagnosis and
Pancreatltis and Its Complications, edited by Therapeutics, edited by Raymond S. Koff
Chris E. oF mnark, 2005 and George .Y Wu, 200 ]
Acute Gastrointestinal Bleeding: Diagnosis DiseuesoftbeM~ :_ The
and Treatment, edited by aK ren E. iK m, Add·Related DIsorders, edited by aJ mes W.
2003 rF eston, 200 ]
eLI N I CAL GAS T R () E N T E R 0 I, () G Y 1 1\
Cholestatic iL ver
Disease
Edited by
eK ith D. iL ndor, MD
Mayo Clinic, Rochester, MN
and
aJ yant A. Talwalkar, MD
Mayo Clinic, Rochester, MN
I~ I.
; J uH mana Press
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Preface
Over the past two decades, there has been a steady increase in the fund
of knowledge associated with the clinical manifestations of cholestatic
liver disease. In addition to a growing amount of information on the well-
studied disorders of primary biliary cirrhosis and primary sclerosing
cholangitis, there has also been a rapid accumulation of data on less well-
known but important topics such as overlap syndromes with autoimmune
hepatitis, cholestatic variants of alcohol and viral disease, and cholestasis
following liver transplantation. In tum, these emerging insights are being
complemented by further improvements regarding the diagnosis and
management of cholestasis.
Based on these clinical situations, we hope that Cholestatic iL ver
Disease will provide useful information for individuals who are involved
in the care of patients affected by various aspects of cholestatic liver
disease. The goal of this textbook is to provide scientific updates from
leading experts, which relate to the clinical evaluation and management
of cholestatic liver disorders. It is our hope that Cholestatic iL ver Disease
will be a useful reference for both learners and practitioners alike.
eK ith D. iL ndor, MD
aJ yant A. Talwalkar, MD
v
Contents
Preface ....................................... v
Contributors .................................. ix
1. Diagnosis of Cholestasis . . . . . . . . . . . . . . . . . . . . . . . . . 1
Velimir A. Luketk
2. Drug-Induced Cholestasis ....................... 21
JtmIa P. lbmlU ttm l11li1 J/letpl4liu M. Lturit
3. Primary Biliary Cirrhosis ....................... 45
Vu' pnia C a.rk l11li1 Cynthia Lwy
.4 Primary Sclerosing Cholangitis .................. 67
eK lly mtrren Burak
5. Overlap Syndrome with Autoimmune Hepatitis ..... 85
Altutair D. Smith
6. Rare Causes of Cholestasis ..................... 105
Aaron]. SnudlIl U tK nutantinO $ N. uL tr4 iiJ s
7. Cholestatic Variants of Viral Disease and Alcohol ... 119
Sakib hK IIli J l11li1 eJ fJ re:y S. Crippin
8. Cholestatic Liver Disease
Related to Systemic Disorders ................ 135
Kimberly oF rde II U DllviJ E. aK plAn
9. Complications of Cholestasis ................... 155
Abhitabh Plln/llu Mllrlyn]. MlI10
10. Cholestasis Post Liver Transplantation ............ 171
~K D. S. WIItt l11li1 TmwthyM . McCuhlmul
Index ....................................... 183
Vll
Contributors
EK yL L WARREN BRU A,K MD • nU iversity of Calgary Liver nU it, Calgary,
Alberta, Canada
VIRGINIA C. CLARK, MD • University of Florida, Gainesville, F L
EJ RF E Y S. CRIPPIN, MD • Washington University School of Medicine,
St. oL uis, MO
IK MBER YL FORDE, MD • University of Pennsylvania, Philadelphia, PA
AJ MES P. AH MITL ON, MD • University ofM aryland, School ofM edicine,
Baltimore, MD
DAVID E. KAPLAN, MD • University of Pennsylvania, Philadelphia, PA
SAIK B AHK IL D, MD • Washington nU iversity School ofM edicine, St. oL uis,
MO
AJ CQEU IL NE M. AL RU IN, MD· Georgetown nU iversity School ofM edicine,
Washington, DC
OK NSTANTINOS N. AL ZARIDIS, MD· Mayo Clinic, Rochester, MN
CYNTHIA LEVY, MD • University of Florida, Gainesville, FL
KEITH D. LINDOR, MD· Mayo Clinic, Rochester, MN
VELIMIR A. L U KETIc, MD • Virginia Commonwealth University Medical
Center, Richmond, VA
TIMOT YH M. MCCASHLAND, MD • University ofN ebraska, Omaha, NE
MARLYN .J MAYO, MD • University of Teax s Southwestern, Dallas, TX
ABIH TAB H PATI,L MD • University of Teax s Southwestern, Dallas, TX
AARON J. SMAL, MD· Mayo Clinic, Rochester, MN
AAL STAIR SMITH, MD • Duke University Medical Center, Durham, NC
AJ AY NT A. TAWL AAKL R, MD • Mayo Clinic, Rochester, MN
MYK BER YL D. S. WATT, MD· Mayo Clinic, Rochester, MN
ix
1 Diagnosis of Cholestasis
Velimir A. uL ketic
CONTENTS
INTRODUCTION
APPROACH TO DIAGNOSIS OF CHOLESTASIS
CHOLESTASIS - BIOCHEMICAL ABNORMALmES
INTRAEH PATIC V S. EXTRAHEPATIC CHOLESTASIS-
CROSS-SECTIONAL IMAGING STUDIES
IDENTIFYING THE CAUSE OF EXTRAHEPATIC
CHOLESTASIS -CHOLANGIOGRAPH Y
IDENTIFYING THE CAUSE OF INTRAEH PATIC
CHOLESTASIS - LABORATORY STUDIES
AND LIVER BIOPSY
SUMMARY AND RECOMMENDATIONS
REFERENCES
Abstract
An elevated serum alkaline phosphatase level is the hallmark of cholestasis.
An abnormal gamma glutamyl transferase, 5' n- ucleotidase, or liver alkaline phos-
phatase isoenyz me can confirm the source to be liver. lU trasound is the most
convenient way to differentiate between intrahepatic and etx rahepatic cholestasis.
Computed tomography or magnetic resonance imaging may be the initial test
depending on the clinical setting. The level of obstruction can be identified by
cholangiography: magnetic resonance cholangiography (or computed tomography
cholangiogram if there are contraindications) for diagnosis alone; endoscopic
retrograde cholangiography (or percutaneous transhepatic cholangiogram) if an
intervention is anticipated. Endoscopic ultrasound and intraductal ultrasound
may prove helpful in the evaluation of intraductal lesions. The choice of inves-
tigative test will depend on availability and local epx ertise in its use. Serologic
studies and other disease markers can help make the diagnosis in an appropriate
clinical setting or identify the netx best diagnostic step. iL ver biopsy often
rF om: Clinical Gastroenterology: Cholestatic Liver Disease
Edited by: .K D. iL ndor and 1. A. Talwalkar © uH mana Press Inc., Totowa, N J
1
2 uL ketic
remains the best way to make or confirm the diagnosis and to stage chronic
cholestatic disease.
eK y Words: Cholestasis; diagnosis.
1. INTRODUCTION
Cholestasis literally means "bile stoppage". The term was coined in
the 1930s and initially used as an adjective, "cholestatic", to describe
cirrhosis resulting from obstruction of the smallest biliary passages (if
inflammation was present the term used was "cholangiolitic") (1). It
was an attempt to develop a general term for disorders with histologic
findings of obstructive jaundice but normal extrahepatic bile ducts. It
took more than 20 year for the term "cholestasis" to include any liver
disorder characterized by impaired bile flow irrespective of the site-
both large (etx rahepatic cholestasis) and small, microscopic (intrahepatic
cholestasis) duct injuries ultimately became part of the definition. This
process was paralleled by the change from jaundice, a physical finding,
to abnormal serum alkaline phosphatase (AP), a laboratory test, as the
diagnostic hallmark for cholestasis. The association of high levels of
AP and jaundice because of biliary obstruction was first demonstrated
in 1933 (2). Development of a reproducible laboratory method to test
for AP (also in 1930s) extended these findings to show that chronic
cholestatic liver disease is mostly anicteric (1). Today, most patients
with cholestasis are identified when an abnormal serum AP level is
detected during routine blood testing or evaluation for an unrelated
medical problem.
2. APPROACH TO DIAGNOSIS OF COH EL STASIS
An approach to the diagnosis of cholestasis is outlined in Fig. 1.
It begins with the identification of an abnormal serum AP and confir-
mation that it is of liver origin. The netx step is to pinpoint the site of
interference with the flow of bile. The primary objective is to show
whether the ducts are or are not dilated thus differentiating between
intrahepatic and extrahepatic cholestasis. This is usually accomplished
radiologically with ultrasound (SU ), computed tomography (CT), or
magnetic resonance imaging (MRI). The last step is to determine the
cause of cholestasis and may include additional laboratory testing (sero-
logies), additional imaging (cholangiography), as well as liver biopsy
(with or without guidance).
The algorithm is not meant to be linear. The precise approach to an
individual patient will depend on the clinical setting including patient