Audio-Digest GASTROENTEROLOGY
®
Volume 28, Issue 16
August 21, 2014
SURGICAL CONSIDERATIONS FOR PATIENTS WITH LIVER DISEASE
Highlights from the 8th Annual Advanced Liver Disease and Liver Transplantation
Update, sponsored by the University of Michigan Transplant Center
Pancreaticobiliary Endoscopy in
Patients with Liver Disease
B. Joseph Elmunzer, MD, Assistant Professor, Department of Internal Medicine, University of Michigan Medical
School, Ann Arbor
Endoscopic Retrograde Cholangiopancreatography (ERCP)
Preprocedural considerations: sedation — ERCPs now generally
performed with support of anesthesiologist; those still using
conscious sedation or endoscopist-assisted propofol should be
aware that metabolism of fentanyl and propofol not affected
by liver disease; midazolam (Versed) preferred benzodiazepine
in liver disease, except in patients on triple therapy (metabolism of drug slowed); antibiotics — because contrast catheter
usually contaminated, administration recommended for all
patients in whom contrast delivered and any segment of bile
duct not subsequently drained (due to presence of strictures in
medium-sized bile ducts secondary to, eg, primary sclerosing
cholangitis [PSC], IgG4 cholangiopathy, presence of hilar cholangiocarcinoma in which one or both sides of liver opacified);
starting antibiotics empirically in all patients with liver transplantation (LT) before ERCP remains controversial (supported
by large study showing that LT independent predictor for systemic infection after ERCP); ascites — not relevant if ERCP
performed in left lateral decubitus or supine position; prone
position difficult in patient with massive ascites and uncomfortable in ERCP with conscious sedation; preprocedural paracentesis reasonable for patient with large-volume ascites
Coagulopathy: presence and how to address preprocedurally most
important considerations in patients with liver disease; American Society for Gastrointestinal Endoscopy (ASGE) separates
endoscopies into low- and high-risk procedures; ERCP with
low bleeding risk — diagnostic only (cholangiography); performed for stent placement or with extraction of stone through
preexisting sphincterotomy; no specific adjustment or correction of coagulopathies recommended; ERCP with high bleeding risk — procedures with biliary sphincterotomy or dilation of
intraductal stricture; recommendation states that platelets should
be >50,000/μL; International Normalized Ratio (INR) not reliable predictor of bleeding in patients with advanced liver disease;
speaker attempts to decrease INR to ≤1.5 before ERCP with high
bleeding risk, but would not delay urgent procedure to do so; no
data support use of novel prothrombotic agents (eg, recombinant
factor VIIa) before ERCP; in patient with choledocholithiasis
and coagulopathy, consider balloon dilation instead of biliary
Educational Objectives
The goals of this program are to improve the management of
liver disease and the outcomes of liver transplantation. After
hearing and assimilating this program, the clinician will be better able to:
1. Recognize the indications for administration of antibiotics before endoscopic retrograde cholangiopancreatography (ERCP).
2. Manage coagulopathy in patients who require ERCP.
3. Recommend appropriate testing for the diagnosis of primary sclerosing cholangitis.
4. Use morphometric measures of frailty to predict outcomes of liver transplantation.
sphincterotomy to extract stone; balloon dilation has lower risk
for bleeding, but has higher risk for post-ERCP pancreatitis
Choledocholithiasis and Biliary Pancreatitis
Spontaneous passage of stone: occurs in >80% of cases
ASGE guidelines: noncirrhotic patients — perform preoperative
risk stratification based on clinical, laboratory, and radiographic
parameters to determine likelihood of ongoing choledocholithiasis; ERCP not indicated in patients at intermediate risk
for ongoing choledocholithiasis, but should be performed for
extraction of stone in high-risk patients; for intermediate-risk
patient (eg, with improving pain and decreasing liver function
tests [LFTs]), perform endoscopic ultrasonography (EUS) or
magnetic resonance cholangiopancreatography (MRCP) to
definitively exclude bile duct stone (ie, clear duct), and follow up with cholecystectomy to prevent recurrence of gallstone pancreatitis or choledocholithiasis and cholangitis; EUS
and MRCP more accurate than cholangiography for bile duct
stones, with none of risks associated with ERCP; cirrhotic
patients — not candidates for cholecystectomy due to risk for
decompensation or portal hypertension; clearing duct does not
prevent recurrence in future; ERCP, extraction of stone, and
performance of biliary sphincterotomy recommended to prevent recurrence of choledocholithiasis and biliary pancreatitis
Sphincterotomy: prevents recurrence by expanding biliary orifice (so stones can easily pass through); also separates biliary
orifice from pancreatic orifice, and bile duct from pancreatic
duct, thus eliminating common channel (ie, mechanism of gallstone pancreatitis is obstruction of common channel by stone
in bile duct); retrospective cohort study — looked at patients
admitted to hospital for gallstone pancreatitis; found that in
patients discharged without definitive treatment (ie, no cholecystectomy or endoscopic sphincterotomy), risk for recurrence ≈13%; with cholecystectomy, risk <2%; with endoscopic
sphincterotomy, risk 5%; outcomes influenced by adequacy or
completeness of sphincterotomy; other data — suggest that risk
for recurrent gallstone pancreatitis after endoscopic sphincterotomy 0% to 5% (closer to 1%-2% with complete sphincterotomy); viable option in patients with problems related to stones
in bile duct who cannot undergo cholecystectomy (usually
those with advanced liver disease)
Recurrent symptomatic gallstones and acute cholecystitis:
common in patients with gallstones who cannot undergo
cholecystectomy (mechanism is obstruction of cystic duct
by stone); if obstruction transient and stone spontaneously
dislodges, symptoms improve (biliary-type colic); if stone
5. Empower patients awaiting liver transplantation to
improve their health and chances for good outcomes.
Faculty Disclosure
In adherence to ACCME Standards for Commercial Support,
Audio-Digest requires all faculty and members of the planning
committee to disclose relevant financial relationships within
the past 12 months that might create any personal conflicts of
interest. Any identified conflicts were resolved to ensure that
this educational activity promotes quality in health care and
not a proprietary business or commercial interest. For this program, members of the faculty and planning committee reported
nothing to disclose. In his lecture, Dr. Elmunzer presents information that is related to the off-label or investigational use of a
therapy, product, or device.
AUDIO-DIGEST GASTROENTEROLOGY 28:16
impacted, pressure within gallbladder increases and gallbladder wall becomes inflamed (acute cholecystitis)
Placement of thin-caliber gallbladder stent: endoscopic
approach for patients unable to undergo cholecystectomy
due to Child-Pugh class C cirrhosis; stent runs through cystic
duct, with one pigtail in gallbladder and another in duodenum; occludes after 2 wk, but prevents stones from completely obstructing duct by occupying space within cystic
duct; technical success rate high; highly clinically effective;
originally developed as bridge to LT in patients with cirrhosis; unlike bile duct stents, routine replacement unnecessary;
if difficulty encountered in inserting wire selectively into
gallbladder, introduce scope directly into bile duct (cholangioscopy) and directly visualize bifurcation of bile duct, then
explore bile duct endoscopically to find opening of cystic
duct; under direct visualization, wire advanced selectively
into cystic take-off; rendezvous procedure — recommended
for selective cannulation of cystic duct (with help of interventional radiologist) when advancement of wire into gallbladder fails
Primary Sclerosing Cholangitis
Diagnosis: meta-analysis looked at diagnostic accuracy of
MRCP; using ERCP as gold standard, found sensitivity of
MRCP ≈86% and specificity 94% (ie, in patient with high
pretest probability of having PSC, positive MRCP highly suggestive of diagnosis; in patient with low pretest probability,
negative MRCP excludes diagnosis); MRCP found to be diagnostic even in patients with medium probability; based on data,
American Association for the Study of Liver Diseases (AASLD)
recommended MRCP as first step in diagnosis of PSC; AASLD
algorithm — MRCP next step after laboratory evaluation and
clinical assessment; ERCP reserved only for situations in
which MRCP not helpful; indications for ERCP — diagnosis in
question after MRCP; diagnostic certainty has implications in
treating other disorders; patient requires therapeutic intervention (in context of new hyperbilirubinemia or new cholestatic
LFTs); patient has symptoms suggestive of biliary obstruction;
diagnostic sampling of dominant strictures needed
Endotherapy: sphincterotomy — main intervention; previously
avoided in PSC because of concerns that procedure provides conduit for intestinal bacteria to reach biliary system and cause cholangitis; presently, risk for cholangitis believed to be low; biliary
sphincter may be involved in sclerotic process and contribute to
symptoms and abnormal LFTs (sphincterotomy beneficial); balloon dilation of dominant strictures — alternative intervention;
strictures due to PSC respond to balloon dilation significantly
better than do other types of strictures; stents — small ducts
common in PSC (require small stents); due to significant amount
of sludge produced, stent occlusion and cholangitis common;
therefore, stents avoided in PSC, except for refractory strictures
(risk for malignancy high); benefits of endotherapy — improves
symptoms; based on observational data, appears to improve survival, compared with expectations; benefits must be weighed
against risk for complications (rate ≤20%; majority infectious)
Other Applications of Endoscopy in Liver Disease
Biliary complications: most common type of complication in
LT recipients; cause ≤10% to die or require retransplantation;
bile leak — occurs in ≤20 of cases; strictures — anastomotic
(account for 80% that occur after LT); nonanastomotic (more
difficult to treat endoscopically); others — eg, stones or blood
clots in duct, sphincter of Oddi dysfunction
Diagnostic ERCP: almost never done in patients with low probability of requiring endoscopic intervention because of accuracy and lack of risk associated with EUS and MRCP; in
speaker’s institution, threshold for diagnostic ERCP much
lower in patients who have had LT
Study: compared clinical yield and complications of diagnostic vs therapeutic ERCP; therapeutic ERCP defined as clear
evidence on noninvasive testing of indication that would
unquestionably justify ERCP in clinical practice (all others
considered diagnostic ERCP); outcome measure high-yield
cholangiography (defined as ERCP that provided clinically
important intervention, found on follow-up to modify disease
course); findings — in therapeutic ERCP group, >90% of procedures high-yield cholangiography; >66% of cases in diagnostic ERCP group also high-yield cholangiography; overall
complications infrequent; conclusions — diagnostic ERCP
reasonable clinical approach in LT recipients with suspected
biliary complications, based on high likelihood of high-yield
study and low rate of complications; decision to proceed with
ERCP in LT recipients should not be taken lightly because of
small but real risk for life-threatening complications; in LT
recipients, proceeding to ERCP reasonable even if probability of intervention moderate or low; MRCP — appropriate in
lower-urgency, lower-probability situations
Post-ERCP pancreatitis: infrequently seen in patients with liver
disease and those with LT; prevented with prophylactic placement of pancreatic stent or prophylactic rectal indomethacin;
speaker’s study of high-risk patients undergoing ERCP found
that indomethacin appeared to reduce risk for overall pancreatitis by 50% and moderate to severe pancreatitis by 50%; adverse
events same in each group
Recognition and Treatment of Frailty Among
Candidates for Liver Transplantation
Christopher J. Sonnenday, MD, MHS, Associate Professor of Surgery, Surgical Director of Liver Transplantation,
University of Michigan Health System, Ann Arbor
Liver transplantation: solid organ transplantation faces persistent
disparity between supply and demand; average age of patients on
waiting lists, and proportion with nonalcoholic fatty liver disease
and metabolic syndrome, increasing (patient population “sicker
and older”); current method of allocation for LT based on Model
for End-stage Liver Disease (MELD) score; among factors in
MELD score, creatinine level weighted most strongly; posttransplantation 1-yr survival rate stagnant (85%-90%); need-based
system of allocation for LT does not consider difference between
predictors of mortality while waiting for LT and those that predict
outcome after LT (MELD score poor predictor of posttransplantation survival); speaker advocates allocation based on benefit
of receiving LT (ie, potential increase in life expectancy), which
would require metrics for prediction (other than age)
Frailty: progressive loss of muscle mass (sarcopenia), associated with decreased strength, metabolic rate, activity or walking speed, and energy expenditure, which can result in chronic
malnutrition and further muscle loss; Fried metrics — 5 measurable elements, consisting of 3 objective elements (unintentional weight loss, grip strength, and walking speed) and
2 subjective elements (self-reported exhaustion and physical
activity); 0 or 1 pt assigned for each element; Cardiovascular
Health Study (Fried) — found that high (>3 pt) frailty score
associated with increased risk for hospital admissions and falls,
and decreased independent living and survival over relatively
long periods; also found that frailty score remains fairly consistent over time
Study of frailty in chronic liver disease: found that frailty
relatively uncommon in patients seen in hepatology clinics,
including those with well-compensated cirrhosis; however,
differences in frailty measureable among patients being considered for LT (frailty scores found to follow normal distribution in this population [appropriate as diagnostic test or tool
for risk stratification]); highly frail patients not necessarily
older or have more severe liver disease; highly frail patients
have higher rates of depression and reported decreased quality of life; MELD score and frailty weakly correlated; frailty
distinct from other factors used to risk-stratify patients for
AUDIO-DIGEST GASTROENTEROLOGY 28:16
LT; high MELD score plus high frailty score predicts poor
survival (may identify patients for whom LT futile)
Frailty and outcomes of LT: highly frail patients had longer
hospital stays, higher rates of biliary complications and renal
failure, higher rate of discharge to skilled nursing facilities,
and higher readmission rates after LT; 1-yr mortality rates
similar in patients with low vs high frailty scores; higher
rates of reoperation seen in highly frail patients
Morphometric measures of frailty: computed tomography can
be used to measure physical characteristics of patients and
to create volume measures of particular structures (eg, psoas
muscle); 1-yr survival after LT linearly related to psoas area;
distribution of subcutaneous vs visceral fat (described in other
studies as marker of health) and vascular calcification additional morphometric measures; speaker measured these characteristics in control group to calculate morphometric age; in LT
recipients, morphometric age did not show direct relationship
with chronologic age; survival of those chronologically oldest
in age, not significantly different from those younger in age;
morphometrically older age found to be predictive of poor outcomes; when outcomes followed in patients in middle of age
group (ie, 50 yr); survival found to be significantly reduced in
those whose morphometric age increased, while those whose
morphometric age decreased had excellent 1-yr survival; conclusion — frailty may predict wait list and LT outcomes better
than does severity of liver disease
“Prehabilitation” for LT: includes nutritional assessment,
exercise instruction, incentive spirometry, tobacco cessation
resources, and stress relief and relaxation techniques; aimed
at potentially preventing or improving frailty and other factors
that drive adverse outcomes after LT; takes advantage of waiting time for LT; empowers patients to take control of own health
Acknowledgements
Drs. Elmunzer and Sonnenday were recorded at the 8th Annual Advanced Liver Disease and Liver Transplantation Update, held May 3,
2013, in Novi, MI, and sponsored by the University of Michigan Transplant Center. For future CME activities from this sponsor, please
visit www.med.umich.edu/intmed/cme/calendar.htm. The Audio-Digest Foundation thanks the speakers and the sponsor for their cooperation in the production of this program.
Suggested Reading
Cameron ID et al: A multifactorial interdisciplinary intervention
reduces frailty in older people: randomized trial. BMC Med, 2013
Mar 11;11:65; De Lisi S et al: Endoscopic ultrasonography versus
endoscopic retrograde cholangiopancreatography in acute biliary
pancreatitis: a systematic review. Eur J Gastroenterol Hepatol,
2011 May;23(5):367-74; Draganov PV et al: Large size balloon
dilation of the ampulla after biliary sphincterotomy can facilitate
endoscopic extraction of difficult bile duct stones. J Clin Gastroenterol, 2009 Sep;43(8):782-6; Horiuchi A et al: Biliary stenting
in the management of large or multiple common bile duct stones.
Gastrointest Endosc, 2010 Jun;71(7):1200-1203.e2; Iorgulescu
A et al: Post-ERCP acute pancreatitis and its risk factors. J Med
Life, 2013 Mar 15;6(1):109-13; Iqbal J et al: Frailty assessment
in elderly people. Lancet, 2013 Jun 8;381(9882):1985-6; Kawaguchi Y et al: Randomized controlled trial of pancreatic stenting
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to prevent pancreatitis after endoscopic retrograde cholangiopancreatography. World J Gastroenterol, 2012 Apr 14;18(14):163541; Khandelwal D et al: Frailty is associated with longer hospital
stay and increased mortality in hospitalized older patients. J Nutr
Health Aging, 2012 Aug;16(8):732-5; Lynn AP et al: Endoscopic
retrograde cholangiopancreatography in the treatment of intraoperatively demonstrated choledocholithiasis. Ann R Coll Surg Engl,
2014 Jan;96(1):45-8; Peterlejtner T et al: Endoscopic treatment
of the choledocholithiasis — effectiveness, safety and limitations
of the method. Pol Przegl Chir, 2012 Jul;84(7):333-40; Swahn
F et al: Rendezvous cannulation technique reduces post-ERCP
pancreatitis: a prospective nationwide study of 12,718 ERCP procedures. Am J Gastroenterol, 2013 Apr;108(4):552-9; Theou O
et al: Operationalization of frailty using eight commonly used
scales and comparison of their ability to predict all-cause mortality. J Am Geriatr Soc, 2013 Sep;61(9):1537-51.
(AANP Approved Provider number 030904). Audio-Digest designates
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Estimated time to complete the educational process:
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AUDIO-DIGEST GASTROENTEROLOGY 28:16
SURGICAL CONSIDERATIONS FOR PATIENTS WITH LIVER DISEASE
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To submit a test form by mail or fax, complete Pretest section before listening and Posttest section after listening.
1. Antibiotics are required before endoscopic retrograde cholangiopancreatography (ERCP) in patients with:
(A) Primary sclerosing cholangitis (PSC)
(B) IgG4 cholangiopathy
(C) Hilar cholangiocarcinoma when one or both sides of liver opacified
(D) All the above**
2. ERCP is associated with high risk for bleeding when it is performed with which of the following?
1.
2.
3.
4.
Stent placement
Biliary sphincterotomy
Extraction of stone through preexisting sphincterotomy
Dilation of intraductal stricture
(A) 1,3
(B) 2,4**
(C) 1,2,3
(D) 2,3,4
3. International Normalized Ratio (INR) is a reliable predictor of bleeding in patients with advanced liver disease.
(A) True
(B) False**
4. According to an algorithm for diagnosing PSC from the American Association for the Study of Liver Diseases, which of
the following is the next step after laboratory evaluation and clinical assessment?
(A) Endoscopic ultrasonography
(B) ERCP
(C) Magnetic resonance cholangiopancreatography**
(D) Computed tomography
5. Bile leaks occur in _______ of patients who receive liver transplantation (LT). _______ strictures are more difficult to treat
endoscopically.
(A) ≤20; anastomotic
(C) ≤5; anastomotic
(B) ≤20; nonanastomotic **
(D) ≤5; nonanastomotic
6. Which of the following factors in the Model for End-stage Liver Disease (MELD) score is most strongly weighted?
(A) INR
(B) Bilirubin
(C) Creatinine**
(D) Albumin
7. The MELD score is an excellent predictor of posttransplantation survival.
(A) True
(B) False**
8. All the following statements about frailty among patients with liver disease are true, except:
(A) Highly frail patients are usually older and have more severe disease**
(B) Highly frail patients have higher rates of depression and report decreased quality of life
(C) There is a weak relationship between frailty and MELD score
(D) High MELD score plus high frailty score predicts poor survival after LT
9. In LT recipients, morphometric age _______ directly related to chronologic age; survival was found to be _______ by a
decrease in morphometric age over time.
(A) Is; unaffected
(C) Is; improved
(B) Is not; unaffected
(D) Is not; improved **
10. Choose the incorrect statement about “prehabilitation” for LT candidates.
(A) Aimed at preventing or improving frailty and other factors that drive adverse outcomes after LT
(B) Takes advantage of patient’s waiting time for LT
(C) Empowers patients to take control of own health
(D) Refusal to participate used as grounds for denial of LT **
Answers to Audio-Digest Gastroenterology Volume 28, Issue 15: 1-B, 2-C, 3-D, 4-D, 5-A, 6-A, 7-C, 8-A, 9-D, 10-B
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